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U. 8. DEPARTMENT OF HéALTH, EDUCATION. AND WELFARE Z I
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Health Servlcee and Mental Health Admlnletratlon fl.

 

POISONING AND INTOXICATION
BY TRACE ELEMENTS
IN CHILDREN

an abstract review of
the worldwide

medical lite ratu re 1966-1971

DHEW Publication No. (HSM) 73-10005

U.$. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE
Public Health Service
Health Services and Mental Health Administration
Bureau of Community Environmental Management

.II Division of Community Iniury Control

 

For sale by the Superintendent of Documents, U.S. Government
Printing Office, Washington, D.C. 20402

PREPARED BY

EXCERPTA MEDICA

THE INTERNATIONAL MEDICAL
ABSTRACTING SERVICE

 

 

Acknowledgement

The Proiect upon which this publication is based was performed
pursuant to Contract no. HSM 99-72-79 with the Health Services
and Mental Health Administration, Department of Health,

Education, and Welfare.

 

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4

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Contents

General aspects and reviews ..................

Sources of poisoning, epidemiology and pica studies ' ° '

CIinico-pathological studies ----- - . .............

Diagonosis and screening --------------------

Laboratory methods ........................

Treatment and prevention -----------

Subject index .............................

Index of OUi’hOl’S ................ . . . .

000.000

20

4]

54

61

76

85

97

General aspects and reviews

1. Plumbism exists today—Reddick L.P., Bowman Gray Sch. of Med., Wake Forrest Univ.,
Winston—Salem, N.Car.—STH MED. J. (BGHAM, ALA.) 1971, 64/4 (446-450)

Although lead poisoning accounts for only a small proportion of cases of accidental poi-
soning, the high mortality associated with the condition makes it by far the most common
cause of death due to accidental poisoning. Most cases of lead poisoning are due to pica
in children who ingest old house paint from the structure and furniture of their housing.
Less common sources reported include the application of an eye cosmetic containing lead
sulphide to the eyelids and conjunctivae of a 3 year old boy and the swallowing of a lead
button by a 2 year old child who subsequently died. In adults illegally distilled whisky,
home brewed alcoholic drinks in lead-lined containers and soft or acid drinking water in
lead pipes are important sources as well as industrial exposure. Smokers have slightly but
consistently higher concentrations of serum lead than non-smokers due to lead arsenate
spraying of the soil in which tobacco is grown.

2. Asymptomatic lead poisoning in 85 Chicago children. Some diagnostic, therapeutic, prog-
nostic and sociologic considerations—Rennen O.M., Weiner P. and Madden 1., Dept. of
Fed, Univ. of Florida Coll. of Med, Gainesville, Fla.—CLIN. PEDIAT. 1970, 9/1 (9-13)

Eighty-five children with blood lead levels higher than 60 lug./ 100 ml. were found as the
result of a door-to—door survey in high-risk neighborhoods of almost all children under
7 years. The children were aged from 1 1 months to 7 years with 35% being 2 years old. Ninety
per cent of the children were asymptomatic but 10% had significant coproporphyrinuria
and 6% had significant anemia. All patients were give a course of intramuscular chelation
therapy with dimercaprol and EDTA. Those with blood lead levels greater than 150
,ug./ 100 ml. were hospitalized for treatment. There were wide discrepancies between blood
lead values reported by different laboratories. This posed a problem both in diagnosis and
evaluation of the results of chelation therapy. Since none of the children had any symp-
toms before therapy, the overall effects of treatment were not clearly demonstrated. To
eliminate childhood plumbism requires massive rebuilding of slums. However emotional
factors may also be involved aside from the availability of paint chips and plaster. Usu-
ally only one child in a family, most often the youngest, is affected and it is possible that
pica may be an indicator of emotional deprivation.

3. Lead poisoning in children - a disease of the environment—Roffman H. and Finberg L.—
HLTH NEWS 1969, 46/7 (3-5)

The high risk of lead poisoning in children which exists in the ghetto districts of large cit-
ies has clearly been demonstrated. This risk mainly affects the children between the ages of
l and 3 due to the pica common to 20-30% of children in this age group. The lead is absorbed
and distributed in soluble form through the soft tissues and later deposited in the bone as
an insoluble phosphate compound. The toxic effect of lead, which predominantly affects

l

the nervous system, blood, kidneys and gastrointestinal tract, is produced by the soluble
form and the amount of damage done therefore depends on the level of lead in the soft
tissues, which may vary according to intake and mobilization from the bones. Seasonal
variations, probably caused by variations in the absorption from the intestinal tract, have
thus been observed. The symptomatology of lead poisoning may vary and individual symp-
toms produced also by other diseases. However, the diagnosis can be confirmed by deter—
mination of urinary coproporphyrin and d-aminolevulinic acid of blood, blood and urinary
levels of lead, morphological examination of red cells and X-rays of bones and abdomen.
Two agents, which form a complex with soluble lead and thereby give rise to a precipitate
excretion, are widely used in the treatment of lead poisoning. Lead poisoning is a recurrent
disease by the nature of the social and economic conditions which foster its existence.
Mass investigations with screening tests such as urinary coproporphyrin levels and blood
levels, as well as the newer inexpensive techniques such as urinary 6-aminolevu1inic acid
determinations serve to detect and should ultimately eradicate this preventable disease.

. Iron poisoning—J. AMER. MED. ASS. I966, 198/ 12 (165-166)

Acute iron intoxication is one of the most common lethal childhood poisonings in the US.
It almost invariably occurs in the pediatric age group, and the poison is usually in the
form of ferrous sulfate tablets prescribed for a pregnant woman in the household of the
poisoned child. Ingestion of as few as 10 to 15 5-grain tablets has been lethal. Typically, in
the child who has ingested ferrous sulfate, symptoms develop within 30 to 90 minutes,
with signs of shock, coma, acidosis, vomiting, diarrhea, and melena. The child may sub-
sequently appear to improve somewhat, but within 10 to 14 hours further acidosis and
coma, bleeding, and irreversible shock develop, and the child dies. Autopsy reveals no
anatomic cause of death. The pathophysiology remains obscure. The iron chelater, defer-
oxamine, promises to reduce substantially the mortality of acute iron intoxication. It is
most effective when given relatively early. Moreover, some question has arisen as to the
occasional toxicity (principally hypotension) of deferoxamine or the iron-deferoxamine
complex. A delineation of the mechanisms of iron toxicity is, therefore, considered im-
portant in order to improve the management and therapy of the poisoned individual, es-
pecially the patient who is not seen soon after iron ingestion, or in whom deferoxamine
therapy fails. Animal experiments have shown that acute iron overload results in hyper-
ventilation, profound acidosis with lactic and citric acidemia, and death. These findings
suggest that a disturbance in oxidative metabolism is rapidly created by iron overload.
Massive intravenous iron overloading of rabbits results in the development of hepatic
necrosis. A study of the enzyme histochemical changes induced in the livers of acutely
iron—overloaded rabbits has shown alterations in several enzymes involved in oxidative
metabolism. Electron-microscopic studies of animals exposed to the same experimental pro-
cedures show early and severe mitochondrial injury, indicating that these organelles may be
the site of the observed disturbances. The mechanism of this injury is not yet evident,
but the experimental protocol provides a potential means of further acute iron poisoning.

. More leads on lead—FD. COSMET. TOXICOL. 1967, 5 (414-418)

Lesions in chronic lead poisoning include kidney damage and cardiovascular disease. There
is evidence that chronic lead poisoning during childhood can produce renal failure in later
life. There is a significant increase in deaths from cardiovascular disease in retired lead
workers which is related to vascular damage rather than hypertension. Blood hemoglobin
levels are of little value in detecting incipient lead poisoning. Blood lead levels and urine
excretion levels of 6-aminolevulinic acid (ALA) are the only valuable indicators of lead
exposure. The cause of the anemia of lead poisoning is not known but it may be related to

the effect of lead on the enzymes responsible for hemosynthesis and red cell glycolysis.
Lead poisoning among storage battery workers has been found to be more common in
those drinking more than 0.75 l. of strong liquor monthly. Children are particularly
vulnerable to the domestic hazards of lead with paint presenting the most serious prob-
lems. Mental retardation and recurrent seizures are the most common long-term effects.
A recent problem is environmental exposure to lead due to atmospheric pollution, water
pollution and possibly also the high lead content of some fish from polluted water in small
localized areas.

6. Prevention, diagnosis, and treatment of lead poisoning in childhood—Alpert 1.]. et al.—
PEDIATRICS 1969, 44/ 2 (291-298)

The causative factors in childhood lead poisoning include pica, which is often associated
with difficulties in the relationship between the child and its mother, and poor housing
conditions with window frames, plaster and walls painted with lead pigment paints. The
biosynthesis of heme is very sensitive to the toxic effects of lead. This is the basis of one
emergency test for lead poisoning — the qualitative detection of urinary coproporphyrin.
Other emergency tests are X-rays of the abdomen to detect radiopaque material and X-rays
of the wrists and knees for lead lines. Specific tests are estimation of whole blood and urine
lead levels and the determination of 6-aminolevulinic acid in urine. Early diagnosis de-
pends on early identification of the high-risk child since early symptoms and signs are
non-specific. Treatment includes permanent separation of the child from his source of lead,
chelation therapy with dimercaprol and EDTA and long-term after care. No child must
ever be allowed to return to a leaded house.

7. 0n lead lines—Leone Jr A.J., Dept. of Radiol., Johns Hopkins Hosp., Baltimore, Md.—
AMER. J. ROENTGENOL. 1968, 103/1 (165-167)

In lead poisoning in children at the time of initial calcification of the cartilage matrix there
is in addition a laying down of lead in the same cartilage. The area of preference for lead
deposition is the zone of calcified cartilage in the epiphysis. The next stage in normal epi-
physeal plate growth would be osteoclastic resorption of the calcified and leadified cartil-
aginous trabeculae. The presence of lead in these trabeculae makes them resistant to re-
sorption by the osteoclasts. The lead has no effect on osteoblasts and new bone is laid
down on these persistent trabeculae. The result is an increase in the number and thickness
of trabeculae at the metaphysis. Although lead is deposited here it is in very small amounts
relative to calcium and it is the calcium that is principally responsible for the increased
radiodensity.

8. Lead poisoning in children—Lin-Fu J .S., Div. of Hlth Serv., US Dept. of Hlth, Educ. and
Welf., Bethesda, Md.—U.S. PUBL. HLTH SERV. PUBL. NO. 2108, 1970, 25 pages

The main cause of this condition is the ingestion of flakes of lead-containing paint from
the walls and woodwork of dilapidated houses. Many cases are attributable to pica. The
highest incidence is between 1 and 3 years with over 50% occurring in 2-year-olds. Mor-
tality and morbidity are higher than is generally appreciated. From 1959 to 1961 lead poi-
soning accounted for 4.7% of 9853 cases of accidental childhood poisoning reported to
the Chicago Board of Health, but it was the cause of 79% of the total deaths due to acciden-
tal poisoning in this period. A Chicago study of 425 children followed up for 6 months to
10 years after treatment for lead poisoning revealed that 39% had some form of neurolog-
ical sequelae. The condition is often asymptomatic or manifested by symptoms commonly
seen in other childhood illnesses. Confirmation of the condition requires a blood lead

3

estimation. A level of 0.06 mg. / 100 ml. or higher is generally accepted as a positive finding.
Treatment must not be delayed while waiting for full continuation of the diagnosis. Pre-
vention should be concentrated on the following: (1) education of doctors and other
health workers many of whom are unaware of the extent and seriousness of the condition;
(2) informing the public of the risks of paint ingestion in old houses and also of the danger
from fumes produced by burning battery cases; (3) case finding programs; (4) follow-up
of discharged cases and their siblings in view of the high rate of recurrence; (5) legislation
directed at notification of cases, prohibition of use of paint containing lead for indoor
use and removal of the danger from old housing.

9. Selected bibliography on lead poisoning in children—Lin-Fu J .S., US Dept. of Hlth, Educ.
and Welf., Rockville, Md.—U.S. PUBL. HLTH SERV., NO. 72—5105, 1971, 30 pages

This bibliography covering the problem of childhood poisoning includes only literature
published in English. Most of the papers are from the pediatric literature, but topics
covered more thoroughly in relation to adults than children, e.g. metabolism, chronic renal
complication, are also included. A limited number of papers on experiments in laboratory
animals are cited.

10. Childhood lead poisoning an eradicable disease—Lin-Fu 1.8., US Dept. of Hlth,
Educ. and Welf., Soc. and Rehab. Serv., Child. Bur., Washington, D.C.—CHILDREN 1970,
17/1 (2-9)

Childhood lead poisoning is still epidemic in many US cities, despite full descriptions and
knowledge of its prevention. It still takes a high toll among children, particularly Negros
and Puerto Ricans. In 1960 there were 30.6 million houses in the US built in or before 1939,
when lead paint had not been replaced by titanium in interior decoration. Until chelating
agents were available, two-thirds of children with lead encephalopathy died. With dimer-
caprol combined with EDTA the mortality is less than 5%, but many of the survivors are
left severely handicapped. Chronic renal lesions may lead to hypertension, gout and further
mental impairment. Lower exposure to the poison may later result in chronic debilitation.
Social, cultural and political factors are important in prevention. The mandatory use of
lead-free paint for toys and furniture has not eliminated the problem, and routine medical
checks are essential. The public and the courts should recognize that violations of housing
codes are true crimes, as distinct from the ‘social welfare offenses’ which mainly carry
only minimal penalties. Slum clearance should be accelerated, and here voluntary helpers
have been active. It should be more widely known that the price of treating, to the age of
60, a person who incurs severe lead poisoning in childhood is about $220,000, whereas the
cost of removing old lead paint from an average rowhouse is $250,300.

11. Undue absorption of lead among children - a new look at an old problem—Lin-Fu J .5.—
NEW ENGL. J. MED. 1972, 286/ 13 (702-710)

The shifting of focus from treatment to prevention through early detection and termina-
tion of undue exposure has put childhood lead poisoning in its proper perspective. Many
biological indices have been used to measure lead absorption and toxicity, but blood lead
determination, even with its limitations, is generally accepted as the most valid and reliable
indicator of recent excessive lead absorption. ‘Normal’ levels of blood lead have been the
subject of varying assessments, but in general it may be stated that the mean blood
lead level of the urban population without undue intake, expressed in micrograms per 100
ml., falls between the teens and lower twenties with an upper limit at or below 40 ,ug. / 100 ml.,
while that of children with few exceptions is somewhat higher. Large-scale screening pro-

grams in US cities have indicated that the problem of undue absorption of lead is enorm-
ous among young children living in old, dilapidated neighborhoods, as shown by figures
from Chicago and New York City, where 20% or more of the children in the age group
1-6 years had blood lead levels of 40 or more ,ug./ 100 ml. Three to 6 months of fairly steady
ingestion of lead generally precedes the development of lead poisoning in children and
detection at this early stage and prompt termination of such ingestion will therefore pre-
vent almost all cases of lead poisoning. Metabolic disturbances at low blood lead levels
have been demonstrated in vitro and, although far from conclusive, findings have been
reported which suggest that lead may cause serious damage, particularly to the nervous
system in children who appear to be ‘asymptomatic’ and also that young children may be
particularly vulnerable to the toxic effect of lead. Undue absorption of lead in children
from deprived environments is therefore to be considered a health problem of alarming
proportion, and early detection and termination of exposure are regarded as essential steps
in the prevention of lead poxsonjng in children.

12. Two health problems: one solution—McLaughlin M.C.—BULL. N.Y. ACAD. MED.
1970, 46 (454-456)

In New York City there are 450,000 or more units of dilapidated housing in which old
paint can be peeled off and eaten by toddlers. This paint was applied before lead-based
interior paint was outlawed and can cause lead poisoning when ingested. A crash pro-
gram of prevention and detection was instituted on a budget of $150,000 which was only
sufficient to provide stop—gap measures. The City’s Health Department has been working
to overcome the difficulties involved in complex municipal administration — housing
agencies, invisible and absentee landlords, court battles — and in the technical problems of
removing and covering the dangerous paint. The Department is also working on the prob-
lem of interim rehousing and fostering to avoid sending a child back to the same conditions;
but wherever possible keeping the child with his family. The development of a portable
detection instrument has been of great assistance. It can detect as little as 1% of lead in old
paint even under 10 coats of lead-free paint. It is to be hoped this problem will be tackled
and solved with results as satisfactory as have been achieved by the recent anti-rubella
vaccination program.

13. Lead and 6-aminolaevulinic acid dehydratase levels in mentally retarded children and in
lead-poisoned suckling rats—Millar J.A., Cumming R.L.C., Battistini V., Carswell F. and
Goldberg A., Med. Res. Counc. Res. Group in Iron and Porphyrin Metab., Univ. Dept. of
Med., Western Infirm., Glasgow—LANCET 1970, 2 (695-698)

There has been controversy over an association between elevated blood-lead levels in
children and mental deficiency. This study has revealed a negative correlation (r = -0.81)
between blood-lead levels and 6-aminolevulinic acid dehydratase (ALA-dehydratase) ac-
tivity in children. Significant decreases in enzyme activity occurred at lead levels con-
sidered to be in the upper range of normal (20-40 ,ug. / 100 ml.). When lead was fed to lactat-
ing rats there was a significant and commensurate reduction in both blood and brain
ALA-dehydratase activity in the suckling rat. These results suggest that even modest eleva-
tions of blood-lead may be associated with biochemical abnormalities in the child brain.

14. Community aspects of childhood lead poisoning—Moore J .E.—AMER. J. PUBL. HLTH
1970, 60/8 (1430-1434)

The existence of lead poisoning in the US is one of the many manifestations of society‘s
lack of concern for the impoverished and badly housed. Departments concerned with

5

health and housing are often ineffectual because of compartmental alignments and poor
liaison. Attempts to deal with housing which is unfit and in violation of local codes often
end in court hearings resulting in inadequate penalties. Rehousing when it is effected is
often undertaken without adequate screening of the unit which the family has been allo-
cated. After more than 30 years of piecemeal and poorly financed housing programs,
decent housing is still lacking for disadvantaged urban dwellers. Non-white families are the
worst victims, 56% of them living in areas of substandard housing and urban blight. In
discussing the social aspects of lead poisoning we must give first consideration to measures
of detection and treatment and to immediate stop-gap measures. But we must not forget
the larger social factors that are operating and by which underprivileged families are
inescapably confined to poisoned housing.

15. Umbilical cord blood lead concentration. Relationship to urban or suburban residency
during gestation—Scanlon J., Dept. of Neonat. Res., Boston Hosp. for Women, Boston,
Mass—AMER. J. DIS. CHILD. 1971, 121 (325-326)

No statistically significant relationship was shown for umbiliml cord blood levels of lead
and residency during gestation in either city or suburbs. The role of smoking cigarettes was
also not significantly related. These values for cord blood lead are the first noted in the
literature. If atmospheric contamination with lead continues at its present rate, further
studies of cord blood lead concentration should be undertaken.

16. Lead poisoning - the silent epidemic—Rothschild E.O.—NEW ENGL. J. MED. I970,
283/ 13 (704-705)

A review of the problem of lead poisoning in ghetto children is presented. This is a well
known intoxication in the US, being associated almost exclusively with deteriorated hous-
ing, the defective walls, and woodwork of which provide a limitless source of ingestible old
lead paint. The great bulk of affected children are poor and nonwhite. The charge of genoc-
ide by neglect has already been leveled against the health profession regarding this situation.
This charge cannot be readily dismissed. The problem of lead poisoning in ghetto children
will not be solved until a truly comprehensive family care is provided with an emphasis
on preventive medicine for all citizens. Another problem mentioned is the potential hazard
of lead poisoning from ceramic glazes. The question is raised of who has the responsibility
to test and certify earthenware as safe for use with food.

17. Lead poisoning—Chisolm Jr J. J.—SCIENT. AMER. 1971, 224/2 (15-23)

It is possible that an amount of lead in the body insufficient to cause symptoms may never-
theless produce chronic adverse effects. There is evidence that lead waste has been accu-
mulating in urban areas during the past century. Post mortem findings show a higher lead
content in individuals from industrial societies than in those from primitive populations.
There is a need therefore to try to control the dissemination of lead into the environment
but a more pressing need is to control the exposure to lead of certain at-risk groups: young
children from dilapidated houses where they can ingest pieces of lead paint, consumers of
illicit (moonshine) whiskey, people who eat and drink from lead-glazed earthenware and
workers in certain small industrial concerns where exposure to lead is not controlled. Some
of the biochemical effects of lead have been biochemically investigated. One is the inhibito-
ry effect on the enzymes which depend on the presence of sulfhydryl. This interferes with the
biosynthesis of the iron-containing substance heme which, combined with protein, forms
hemoglobin. Lead inhibits at least 2 of the 6’steps in the synthetic pathway. This results
in the accumulation of coproporphyrin in the urine and red cells, and use can be made of

this as a presymptomatic diagnostic test. The toxic effects of lead on the CNS are not fully
understood. Two mechanisms seem to be at work: increased capillary permeability leading
to edema, and a direct effect on the structure and functions of the brain cells.

18. History and epidemiology of lead poisoning—Ascher S.F., Office of Prod. Safety, US
Food and Drug Admin, New York, N.Y.——PUBL. HLTH NEWS 1970, 51/7 (151-152)

Lead poisoning in children has come to be recognized over the last 40 years for the
insidious disease resulting almost exclusively from ingestion of flaking and peeling lead
containing paints in old dilapidated housing and on old furniture. Historically, the 4 major
factors contributing to childhood lead poisoning were not interrelated in the traditional
epidemiological approach. Dilapidated housing, lack of awareness of the problem among
physicians and other health workers, lack of information on the part of the public, and
lack of or inadequate prevention of reexposure to lead all worked together to perpetuate
the problem. High risk areas for lead poisoning are almost synonymous with the slums or
lead belts, where old, deteriorating housing prevails. Over 50% of all deaths from lead
poisoning occur in 2 year olds. Some epidemiological facts pertaining to childhood lead
poisoning are discussed.

19. Lead poisoning—Barltrop D., St Mary’s Hosp. Med. Sch., London—ARCH. DIS.
CHILDH. 1971, 46 (233-235)

British pediatricians diagnose fewer cases of lead poisoning, compared with the Americans.
In England it has been suggested that 200 to 2000 cases were diagnosed per year. Wrist-
drop and the Burtonian gingival blue line seldom if ever occur in children. Those affected
tend to be 1-5 years old, have anorexia, irritability, anemia and later convulsions. Lead
hazards are numerous, apart from defective housepaint. Metallic lead was found in an
intragastn'c foreign body, lead nipple shields were used for nursing mothers, fall-out
from factories can be toxic, and lead-glazed pottery is potentially dangerous. Buming—
battery cases may cause inhalation of toxic amounts of lead. Lead is a cumulative poison
and the ingestion of paint flakes containing 1-2 mg. lead may continue for 5-6 months
before symptoms occur. X-ray changes may take 3 months to develop. Profound disturb-
ances in the alpha/ beta globulin synthesis were recently noted. The domestic environment
should be screened to detect lead if an improvement is to be made.

20. Lead poisoning—Barltrop D., St Mary’s Hosp. Med. Sch., London—J. HOSP. MED.
1969, 2/9 (1567-1573)

Lead is a widely distributed contaminant of air, water and foodstuffs, so that most adults
have a daily intake of about 0.3 mg. Domestic water may contain lead dissolved from
pipes; and children, particularly those with pica, may obtain lead from painted surfaces.
Lead is a cumulative poison and its effects usually result from repeated ingestion of very
small quantities over a long period. Ingestion of lead causes an immediate rise in the lead
content of the soft tissues for which it has a special affinity, such as the erythrocytes, liver
and kidneys. Ultimately, the soft tissue lead is transferred to the skeleton. The metabolic
processes blocked by lead are still imperfectly understood but they depend on interference
by lead with enzyme-controlled processes. The symptoms of lead poisoning are non-specif-
ic. The early manifestations include pallor, constipation, lassitude and anorexia. General-
ized intestinal colic is also an early feature and muscular spasm occurs in adults. In more
severe cases there are headaches and irritability, associated with vomiting and ketosis. In
the late stages consciousness is impaired and convulsions and bulbar involvement
precede death. The only characteristic physical sign is Burton’s blue line at the gingival

7

margin. Stippled pigmentation of the retina has been reported but is not generally accepted
as a reliable sign. Children have few symptoms other than pallor or irritability before the
onset of encephalopathy. Diagnostic tests include testing for microcytic hypochromic
anemia. A blood-film should be examined for basophil stippling of the erythrocytes. Urine
tests will show interference with renal tubular absorptive function and an excess of normal
metabolites such as the porphyrin precursors. In children with pica, lead-containing paint
flakes in the bowel may be detectable by X—rays. Treatment consists of removal from the
source of lead and chelation with one or more of the 3 drugs: penicillamine, EDTA and
dirnercaprol. Severe cases bordering on encephalopathy should receive immediate treat-
ment with paraldehyde and phenobarbital to control the seizures and with dexamethasone
or intravenous hypertonic solutions of dextrose or urea to limit the cerebral edema. The
deposition of lead in bone cannot yet be enhanced, and giving calcium and vitamin D is
likely to do more harm than good. The prognosis depends on the presence of encephal-
opathy. Deaths from this cause are commoner in children than adults, and a mortality of
up to 24% has been reported in children. Neurological damage is likely to be permanent,
and survivors from lead poisoning may show an increased liability to chronic nephritis.

21. Lead poisoning in childhood—Barltrop D., Paed. Unit, St Mary's Hosp. Med. Sch.,
London—POSTGRAD. MED. J. 1968, 44/513 (537-548)

The prevalence of lead poisoning in children has yet to be determined because only
severe cases are recognized. Since lead poisoning may cause cerebral damage and death it
is important that children exposed to lead should be identified and if necessary treated.
The most common source is flaking paint in old dwellings, and lead poisoning is commonly
associated with pica. Children about 2 years old are chiefly affected. There are no symp-
toms up to a blood level of about 60 g. / 100 g., but above that there may be irritability,
anorexia and vomiting, constipation, pallor, and coproporphyrinuria. When the blood
level is over 80 ,ug./ 100 g. there may be impaired consciousness, with convulsions, coma and
vomiting. The CSF protein and pressure are raised. Cessation of exposure and active
treatment may reverse the progress but encephalopathy cannot always be prevented. The
most reliable test for lead poisoning is determination of the blood-lead level. Values above
36 ,ug./ 100 g. are abnormal. Fecal lead is indicative only of current lead ingestion and
determinations of urinary lead have no advantage over those of blood lead. Abnormal
amounts of soft-tissue lead may be inferred from abnormalities of porphyrin metabolism.
The reabsorptive mechanisms of the renal tubules are impaired in lead poisoning and
glycosuria with a normal blood sugar is suggestive. Radiology is of only limited value in
detecting ingested lead paint. As soon as lead poisoning is diagnosed, the affected child
should be removed from the source of the lead. Unabsorbed lead in the intestine is re-
moved by a saline purge. Oral EDTA should not be given as it may enhance absorption
of lead from the intestine and precipitate encephalopathy. The 3 drugs used to remove
soft-tissue lead are: EDTA (calcium verSenate) administered as calcium disodium chelate,
D-penicillamine hydrochloride, Which may be given simultaneously with EDTA, and
dirnercaprol. Treatment is usually continued for 2-6 weeks. The possible value of a high
calcium diet to increase the deposition of lead in bone has not yet been confirmed. It is
agreed that vitamin D and agents to promote bone reabsorption, such as parathormone,
should not be given. When lead encephalopathy occurs the treatment is to control the
cerebral edema with 1.0 mg. of dexamethasone per kg. bodyweight daily intravenously,
restrict the fluid intake to maintenance levels for 24 hours, and give dehydrating agents,
such as l g. of 30% urea or 2 g. of mannitol per kg. bodyweight. Surgical decompression
has been attended by a high mortality and is not recommended. The prognosis for chil-
dren with encephalopathy is poor. Permanent cerebral damage is a common sequel to lead
poisoning, 30% of the survivors being affected.

22. Disturbances of metabolic regulation in acute intermittent porphyria and lead poisoning
/ Regulationssttirungen bei akuter intermittierender Porphyrie und Bleivergiftung—Goreczky
L. and Roth 1., Zentrallab., MAV Krankenh., Budapest—Z. KLIN. CHEM. KLIN. BIO-
CHEM. 1969, 7/4 (333-338)

The symptoms of acute intermittent porphyria and lead poisoning were compared and
found to be similar. In disturbances of porphyrin metabolism there is evidence of enzyme
induction or enzyme inhibition. In both cases, however, the clinical diagnosis is based on
an increase of metabolites. In lead poisoning, practically every stage of heme synthesis
is affected. Too little attention is paid to the increase of uroporphyrinogen observed by
Brugsch in lead poisoning; the urinary porphobilinogen value remains normal. Uropor-.
phyrin is not formed in the urine during storage. In both conditions there are disturbances
in the mineral and water balance. This is due to an increased secretion of antidiuretic hor-
mone. There is also an increased secretion of melanophoric, somatotropic and thyrotropic
hormones by the hypophysis. The increased secretion of hormones by the hypophysis is
correlated with anatomical changes in the hypothalamus, which can be demonstrated both
in porphyric patients and in experimental animals.

23. Lead absorption in children—Gordon N., King E. and Mackay R.I., Serv. for the Handi-
capped Child, Roy. Manchester Child. Hosp., Manchester—BRIT. MED. J. 1967, 2 (480-
482)

It has been claimed that a raised blood-lead level is a common finding among mentally
retarded children and that this is of etiological significance. 123 mentally handicapped
children of uncertain etiology, 24 with mongolism, and 73 controls have been examined
for lead intoxication. The results indicate that the 3 groups do not differ significantly as
regards blood lead levels and no definite evidence of either acute or chronic lead poisoning
has been obtained. This study does not suggest that these mentally backward children
have been particularly at risk from lead poisoning, and emphasizes the limited value of an
isolated estimation of the blood lead level. These conclusions do not depend on whether
36 or 50 pg. of lead per 100 ml. of blood is regarded as the upper limit of normal. However,
if a value is found which is above the accepted level for the population in a particular area,
this is an indication for further investigation, but not necessarily for treatment.

24. Lead poisoning as a disorder of heme synthesis—Goldberg A., Univ. Dept. of Med.,
Gardiner Inst., Western Infirm, Glasgow—SEMIN. HEMAT. 1968, 5/4 (424-433)

Despite their diverse etiology, lead poisoning bears some clinical similarity to acute inter-
mittent porphyria, both producing abdominal pain, constipation and vomiting. Abdom-
inal rigidity is more common in lead poisoning, and neuropsychiatric manifestations in
acute porphyria. Paresthesia occurs in both. Epilepsy is more common in porphyria but
has been observed in lead poisoning. Cardiovascular anomalies may be associated with
porphyria and also with lead poisoning, but whereas 94% of patients with lead poisoning
were found to be anemic, anemia was found in only one patient with acute intermittent
porphyria. The cause of the anemia in lead poisoning is probably a combination of hemol-
ysis and direct inhibition of hemoglobin formation. The main clinical effect of both lead
poisoning and acute porphyria is on the nervous system. There is demyelination and axon
degeneration and the diseases cause similar damage to the anterior horn cells of the spinal
cord and the medulla. Porphyria and inorganic lead poisoning both cause changes in the
urinary and blood porphyrins, but in organic lead poisoning the urinary excretion of
aminolevulinic acid (ALA) and the protoporphyrin content of the erythrocytes are normal.
In children, as distinct from adults, with lead poisoning, there is a poor correlation between

9

25

moderate levels of blood lead and urinary excretion of coproporphyrin and ALA. The cor-
relation is better between blood lead and raised erythrocyte protoporphyrin levels. A block
at the stage of the incorporation of iron into protoporphyrin inhibits the formation of
heme, causing an accumulation of porphyrin and porphyrin precursors. There is also evi-
dence of an inhibition of ALA dehydrase in the erythrocytes and of heme synthetase in
bone-marrow erythroid cells. The neurological complications of lead poisoning may ap-
parently be caused by the direct action of lead on the nervous system. This would explain
most of the clinical signs, but not the anemia which results from the action of lead on the
bone-marrow. The abnormalities of porphyrin metabolism in human lead poisoning are
similar to those produced in experimental animals. In porphyria, however, the clinical
neurological manifestations found in man have not been reproduced in animals. In acute
intermittent porphyria there is no evidence of a disorder of heme synthesis in the nervous
system, and the defects in the brain and nervous system seem to be only indirectly asso-
ciated with the disorder of pyrrole pigment metabolism in the liver.

. A short history of Minamata disease research and the present situation of mercury pol-

lution in Japan—Ui .1., Dept. of Sanit. Engin., Univ. of Tokyo—NORD. HYG. TIDSKR.

19

26

69, 50/2(l39—146)

The Minamata disease is a severe intoxication of the central nervous system caused by
low molecular normal alkyl mercury compound in fish and shellfish. It was discovered
in 1956 by Dr. Hosokawa, Director of the Minamata Factory Hospital. The first case
had appeared in 1953 and by 1956 the disease had reached epidemic proportions in pa—
tients who had been eating large quantities of fish from Minamata Bay. In most of a group
of 41 patients, movement and speech were impaired, about half were affected in sensation
and vision, and a fifth suffered difficulties in hearing and swallowing. Mental disturbances
occurred in 20%, convulsions in 14%, paralysis in 12%, salivation troubles in 10%, and
muscular rigidity in 10%. Methyl mercury was discovered in the factory waste and in 1965
there was a second outbreak of the disease in villages along the Anago river, arising from
waste discharged from a factory using an acetaldehyde synthesis process. Phenyl mercury
compounds used as fungicides in rice fields have also been a source of pollution and their
use has been stopped. The author considers that unpolluted fish from rivers in Japan
have a mercury concentration of about 0.02 mg. /kg. and that values above 0.1 mg. / kg.
indicate pollution. Various factors, however, have to be considered, including the species of
fish, ecological conditions, food-chains, the quantity of the water flow, and the discharge
of synthetic substances in waste. These may account for pollution values being much lower
in Japan than in Sweden, where methyl mercury pollution has also been reported.

. Lead poisoning remains health hazard—Waite R.—J. ENVIRONM. HLTH 1968, 31/3

(274—275)

10

lead has 2 properties which contribute to its wide usage: it does not readily oxidize and
it has a low melting point, making it easily fashioned into dishes and utensils. The Romans
already used it in their aqueducts. In the 16th and 17th centuries the toxicity of lead was
recognized and its use forbidden. But in the US the control of lead was only established
after about 1920. In 1965, 1 billion tons of lead were processed in the US. The principal
uses are automobile batteries, petroleum industry, in manufacture of anti-knock gasoline,
and manufacture of paints. Lead is absorbed in the human body by ingestion (pica), inha-
lation of fume or dust (shipbreakers, miners) and skin absorption (painters, battery-wor-
kers). The gastrointestinal absorption of lead is enhanced by high intake of vitamin D,
the amount of absorption is in the order of 1-5%. Cattle may eat greasy residue carelessly
dumped by service stations. Waterfowl may ingest pellets from hunt‘ers‘ shot guns in heavy

hunting areas. The toxicity of lead to animals and man poses a health problem, especially
with the growing use of leaded gasoline. There is no immediate danger for the general
population, but smoking city dwellers, a police officer directing traffic and a garage
mechanic are examples of those exposed to greater amounts of lead.

27. Acrodym'a - postmortem of a disease—Warkany J., Child. Hosp. Res. Found., Cincin-
nati, Ohio—AMER. J. DIS. CHILD. I966, 112 (147-156)

This article reviews the history of acrodynia (pink disease) in children, its early descrip-
tion, international incidence, causation and gradual virtual elimination. A detailed des-
cription given in 1920 is compared with the known, though unrecognized because un-
suspected, picture of mercury poisoning. Affected children had taken mercury in calomel
(‘mild' mercurous chloride) as a laxative, in anthelmintics, and for any febrile disease; un-
known ingestion of mercury in teething powders, from ammoniated mercury ointment,
and bichloride of mercury as a diaper rinse, also occurred and made establishment of
cause and effect difficult. Accidental exposure to sealing wax (mercuric sulfide), felt hats,
batteries and several other miscellaneous articles also explains why history did not al-
ways indicate ingestion of mercury. Laboratory determination of urinary mercury however
cleared up some of the confusion. However, acrodynia only occurs in a small minority
of children exposed to mercury, and the adverse reaction may occur months after expo-
sure when mercury that has been stored in a harmless insoluble form becomes, for some
unknown reason, soluble and toxic. Eradication of mercury from teething powders and
worm medicines, either by compulsion or by voluntary action, has almost eliminated
acrodynia.

28. Acute and chronic childhood lead poisoning—Wehrle P.F. et al.—PEDIATRICS 1971,
47/5 (950-951)

According to this report virtually all cases of childhood lead poisoning occur in children
who live in old, deteriorated houses built and painted when the use of lead-based paints
on housing surfaces was widespread. Eighty-five per cent of recognized cases occur in
children in the l- to 3~year age range in which pica is prevalent. Consequently, the disease
results from the interaction between hazardous housing and the child with pica. Early
diagnosis of plumbism on clinical grounds alone is exceedingly difficult, and often im-
possible. Furthermore, by the time the clinical diagnosis is obvious, permanent brain dam-
age which cannot be modified by therapy may already have taken place. Surveys have
revealed that 10 to 25% of young children who live in deteriorated urban slum housing
show evidence of increased absorption of lead and that 2 to 5% show evidence of poison-
ing. While recent therapeutic advances have reduced the mortality of acute lead encephalo-
pathy, it is now apparent that at least one-third of the survivors of encephalopathy sustain
pennant irreversible damage to the brain. Significant reduction in the risk of permanent
brain damage, therefore, requires identification of the child with increased body lead bur-
den prior to the onset of poisoning. The following recommendations have been made: (1)
The major emphasis of programs designed to prevent adverse health effects in children
from lead be placed on the testing of dwellings for lead-pigment paints on housing sur-
faces, both interior and exterior, in order to identify high-risk areas within the community.
(2) As a policy, determine lead in blood of all 12- to lS-month-old children living in poorly
maintained dwellings in identified high-risk areas and wherever other special local situa-
tions expose children to lead hazards. A subsequent sample of blood should be obtained
during the following spring or summer. Those children with levels of blood lead greater
than 50 ,ug./ 100 ml. whole blood should be referred immediately for definitive medical
evaluation and a repeat blood lead determination. All children having 2 blood samples

11

with a concentration greater than 50 ,ug./ 100 ml. whole blood should be reported to the
responsible local government agency by appropriate officials and action taken to eliminate
the hazard.

29. Epidemiological and experimental aspects of lead and mercury contamination of food—
Clarkson T.W., Dept. of Radiat. Biol. and Biophys., Univ. of Rochester, Rochester, NY.—
FD. COSMET. TOXICOL. 1971, 9 (229-243)

There is now an increasing release of lead and mercury into the environment, with in-
creasing levels occurring in human food. The author discussed the ways in which heavy
metals enter human food and the chemical state of heavy metals in food. Hitherto esti-
mates of the allowable quantities have been assessed too crudely, with insufficient regard
to the form taken by the metal. It has been found that the toxic effects of mercury differ
according to its chemical form, and the rate of absorption in the gastrointestinal tract is
influenced by it. In the normal population the average blood level of lead is considered
to be 17 ,ug./ 100 ml., as compared with a no-effect level of 50-80 lug./ 100 ml. Most nor-
mal subjects have mercury blood levels below 4 ,ug./ 100 ml. and the no-effect level is
believed to be 60 yg./ 100 ml. Data are not available for the no-effect level for chronic
ingestion of lead but it is calculated as being 1-8 mg. / day; the allowable daily intake should
therefore not exceed 100-800 ,ug./ day. The estimation of no-effect levels of mercury is even
more difficult as the interaction of alkylmercury compounds with drugs is not known but
the no-effect threshold may be about 0.7 mg./day. The antidotes proposed for heavy met-
al poisoning are mostly complexing or chelating agents. Dimercaprol and EDTA have
been used for lead poisoning but EDTA is useless in mercury poisoning. Both dirnercaprol
and EDTA are ineffective in cases of alkylmercury poisoning, to which no antidote has
yet been found. It has, however, been reported that D-penicillamine may be able to in-
crease the excretion of mercury. Any antidote to alkylmercury would have to be given
early to prevent damage to the central nervous system. More needs to be known about the
mechanism of urinary and fecal excretion of heavy metals. Fecal excretion of mercury
could be greatly increased if the rapid absorption of methylmercury-cysteine secreted in
bile could be prevented, perhaps by oral doses of mercury-binding agents; Research is
needed to increase the sensitivity of analytical methods, to find a sensitive biochemical
test for mercury poisoning, and to find an antidote for alkylmercury poisoning.

30. Methyl mercury poisoning in fish and human beings—Eyl T.B.—MOD. MED. (MIN-
NEAP.) 1970, 38/23 (127, 136-7, 141)

The relatively inoffensive metal is converted, before entering the algae-fish-human food
chain, into methyl mercury. This biological methylation is accomplished by bacteria
walled Methanobacterium omelanskii living in the bottom mud. These bacteria are then
eaten by plankton, which in turn are eaten by fish. The symptoms and signs of methyl
mercury poisoning are briefly reviewed, as well as the possible fetal and genetic effects.
The problems of pollution control are discussed.

31. Lead poisoning: biochemical lesions and biological semeiology / Le satumisme: lesions
biochimiques et séméiologie biologique———Delwaide P., Heusghem C. and Noirfalise A., Lab.
de Chim. Med, Toxicol. et Hyg., Univ. de Liege—ANN. BIOL. CLIN. 1968, 26/7-9 (987-
1001)

The laboratory can give direct and indirect evidence of tissue impregnation by lead and
diagnose early manifestations of toxicity in the hemopoietic organs. It is thus possible to
make a diagnosis before any clinical manifestations of symptoms develop in chronic lead

12

poisoning. Provided that it is thorough and that it is accurately discerned, the biochem-
ical investigation is the basis for a diagnosis of lead poisoning.

32. Certain biological effects of lead upon the animal organism~De Bruin A., Coronel Lab.
for Occupat. Med. and Environm. Hlth, Univ. of Amsterdam—ARCH. ENVIRONM.
HLTH 1971, 23/4 (249-264)

In a comprehensive review of the scientific literature, all of the biological, for the most
part biochemical, phenomena which are known to result from the absorption of lead in
measurable quantities into the bodies of animals and men have been assembled. An at-
tempt has been made to indicate the extent to which the quantitative measurement of
certain of these reactions to the absorption of lead might be employed, or developed to
the point of employment, in order to recognize the likelihood of the occurrence of clinical
lead poisoning in time to prevent its occurrence. 0f greater import is the demonstration
of the multiplicity of effects which sufficient concentrations of lead may induce in the
biochemistry and physiology of animals.

33. Lead poisoning: a preventable childhood disease of the slums—Oberle M.W.—SCIENCE
I969, 165 (991-992)

The classical signs and symptoms of lead poisoning include convulsions, vomiting, anemia,
cramps and a high blood content of lead. Since the metal often accumulates slowly over
a period of months a child may reach a dangerously high tissue concentration without
showing any of the external signs. Since 1940 in the US leaded paint has been sup-
planted by titanium-dioxide—based paints and many authorities have banned the use of
leaded paint for interior surfaces. However, the poorer areas of many cities have many
old properties with peeling coats of leaded paint and it has been estimated that 5-10% of
children between the ages of l and 6 years have an abnormally high content of lead in their
blood. When a child is found to be suffering from lead poisoning he is usually treated in
hospital with chelating agents, including dimercaprol and EDTA. It is estimated that early
detection and treatment have reduced the mortality of severe lead poisoning from 66% to
less than 5%. However, 25% of the survivors still suffer from brain damage. Also, after re-
turning home the survivors often resume their paint-eating habits and if they have a second
attack brain damage is almost certain to occur. Dissatisfaction with the apparent lack of
concern about this danger on the part of the authorities has led to rent strikes and the
formation of community action groups. Three bills proposing federal aid for testing pro-
grams and house decontamination have been submitted by 19 Congressmen but have
received little support.

34. Lead poisoning—Danovitch S. and Gruver C.—MED. ANN. DC. 1970, 39/10 (583-
589)

; In Washington, DC. and other major metropolitan areas of the US lead poisoning in
children is reaching near-epidemic proportions. A pilot screening of children between 18
months and 4 years showed that 8% had levels of 40 ,ug./ 100 ml. Children under 6 years
living in poor housing are the most susceptible. Physicians are warned to be alert to
symptoms of irritability, fatigue, central nervous-system dysfunction and neurological
syndromes including convulsions, particularly if the child engages in pica and ingestion of
paint. Lead concentrations of over 60 ,ug./ 100 ml. can be considered definitely abnormal,
while 40-60 lug./ 100 ml. are borderline cases. Patients with over 100 ,ug./ 100 ml. may still
be asymptomatic but are at risk of lead encephalopathy, with an attendant mortality
of 5-lO% and permanent chronic disability of 25-50%. Urinary 6-aminolevulinic acid

13

(ALA) concentrations in excess of 1 mg. / 100 m1. correlate well with blood lead concen-
trations in excess of 60 ,ug./ 100 ml. and with the presence of symptoms, and urinary ALA
may therefore be used as a screening device when blood testing is not feasible. Other
tests are not recommended as they are not sufficiently specific or sensitive. When a blood
concentration of about 60 fig./ 100 ml. is found, chelation therapy with dimercaprol and /or
EDTA should be promptly initiated, and the source of the intoxication removed. Cases
in Washington, DC, must now be reported to the Department of Public Health as a case
of a notifiable disease.

35. Metabolism of aminoacetone and lead poisoning / Metabolismo dell’aminoacetone e
intossicazione saturnina—Pisani W., Bonzanino A. and Lacquaniti A., Ist. di Clin. Med.
eTer. Gen., Univ. di Torino—MED. D. LAVORO 1967, 58/4 (279-285)

The metabolic cycle of aminoacetone, an aminoketone derived, as the d-aminolevulinic
acid (ALA), from the condensation of glycine with an acyl derivative, is described and the
experiments are reported, by which such cycle could be suggested. The plasma level and the
urinary excretion of the 2 aminoketones were determined by a technique of chromatograph-
ic separation, in subjects exposed to the risk, with clinical findings of lead poisoning. Both
the blood level and the urinary excretion of the 2 aminoketones resulted to be increased,
although much less than those of ALA. The hypothesis is suggested that such an increase
might be due to an enzymatic blockage by lead on the oxidative deamination of amino-
ketones.

36. Lead poisoning in children—Standard R.L., Hlth Serv. Adm., Washington D.C.—MED.
ANN. DC. 1970, 39/7 (399-340)

In Washington DC lead poisoning is now included in the health regulations as a reportable
disease. It is also forbidden by law to use paint containing more than 1% lead on toys,
furniture and interior surfaces of any dwelling. In 1968 there were 45 cases of plumbism
diagnosed at Children’s Hospital. It has been estimated that more than 500 children in
Washington DC. are stricken with lead poisoning each year and that about 5000 children
have significant amounts of lead in their system. Lead poisoning seems to be related to
22,000 substandard dwellings in the city, which were painted with lead-base paint prior
to World War II. A prevention program was begun with the screening of 900 children,
aged 18 months to 4 years, in cooperation with the Health Service, the United Flaming
Organization and the Medical Committee for Human Rights. It was their intention to
find and treat all children with lead poisoning.

37. Lead poisoning—Harrison H.E., Baltimore City Hosp., Baltimore, Md.—US PUBL.
HLTH. SERV. N0. 1791 1968, (245-253)

In discussing lead poisoning in children, the author first summarizes the mechanism of
its action, by interference with heme synthesis, and the significance of the raised blood-
levels of porphyrin precursors. His studies with Chisolm indicate that slum children may
swallow as much as 5-100 mg. of lead daily through chewing painted surfaces, which is
far more than the intake from industrial exposure. The lead levels in the blood of healthy
subjects under normal exposure at various ages are set out in a table. The median and
range, in ,ug. / 100 g., at 0-6 months were 15 and 5-31; at from 6 months to 8 years they were
27 and 15—40; at from 4 months to 14 years they were 24 and 14-42; and in adults they were
27 and 15—40. There is a table of mortality-rates and the incidence of permanent neurologic
residua, summarized from the literature, and another showing the relation between the
incidence of severe CNS sequelae and re-exposure to lead after recovery from a first attack

14

of acute lead encephalopathy. In children the disease is a chronic one with high lead levels
in the soft tissues and a liability to acute exacerbations, mostly either in the summer as
a result of exposure to the sun or following febrile infections. Measles has been an impor-
tant precipitating cause in many of the acute attacks. Children with lead poisoning who
are subjected to chronic exposure and have multiple acute exacerbations finally develop
severe brain damage with serious mental deterioration. The treatment methods used in-
cluded dimercaprol, CaEDTA and penicillamine.

38. Lead poisoning in children—Lin-Fu J.S., Div. of Hlth Serv., US Dept. of Hlth, Educ.
and Welf., Washington, D.C.—US DEPT. OF HEW PUBL. NO. 452 1967, 25 pages

A review is presented of the incidence of lead poisoning in a number of US cities, covering
mortality and morbidity, epidemiology, diagnosis and screening, and factors contributing
to lead poisoning. The ways to control and prevention include: professional and public
education, case finding, follow up of cases, legislative measures, research, and improved
housing.

39. Clinical toxicology—Poison C.J. and Tattersall R.N.—J.B. LIPPINCOTT CO, PHILA-
DELPHIA, PA. 1969, 655 pages

Poisoning from the domestic rather than the industrial standpoint is considered in this
book on clinical toxicology. Part 1 deals with diagnosis, treatment, accidental poisoning
in childhood and the doctor’s procedure when poisoning is suspected and part 2 with
individual poisons. In part I the diagnosis of lead poisoning is based on convulsions
associated with the onset of coma, as possible symptom of lead encephalopathy; cerebral
convulsions in adults may be produced by lead in addition to other poisons; peripheral
muscular weakness, often associated with wasting and sometimes with gastrointestinal
disturbances may possibly be due to lead poisoning. The chapter on lead in part 2 briefly
reviews domestic lead poisoning and discusses this form of poisoning from the standpoint
of incidence, absorption, distribution, excretion, normal intake of lead, the lethal dose,
clinical manifestations, diagnosis, lead poisoning in children and treatment. Seventeen
cases are reported.

40. Drugs and poisons in relation to the developing nervous system. Proceedings of the
conference on drugs and poisons as etiological agents in mental retardation—US PUBL.
HLTH SERV. PUBL. NO. 1791 1968, 276 pages

The main subjects covered at the conference of drugs and poisons as etiological agents in
mental retardation were: parameters of the developing nervous system, role of a regulatory
agency, epidemiology approaches, and specific model systems. Although here the problem
is known it is difficult to get improved action. Is it cheaper to let things go on happening
at the cost of lead encephalopathy and its consequences than to do something about it?
Even if a case of mental retardation were regarded as an accident, in the way that every
aircraft crash is recognized as an accident, a better system of surveillance and investiga-
tions could be evolved.

41. Self-poisoning and accidental poisoning—Hyman S. and Greengard J., Cook County
Hosp, Chicago, Ill—POSTGRAD. MED. J. 1967, 41 (578-584)

A series of 468 cases of self-poisoning in teenagers and adults and 1645 cases of accidental
poisoning in children are reviewed. The most common causes of poisoning in the teenagers
and adults were barbiturates, aspirin and tranquillizers. In the children 35% of poisonings

15

were due to medicines, 25% to corrosives, 22% to lead paint or plaster and the remainder to
household chemicals. Poison control centers established under departments of public
health can provide information concerning toxic ingredients in commercial products and
medicaments. The physician is a key person in poisoning prevention, especially in the
education of parents and in not prescribing excessive amounts of medication. Of 221
children with lead encephalopathy 61 (27%) died.

42. What is the statm of knowledge of the toxic effect of lead on identifiable groups in the
population?—Hardy H.L., Occupat. Med. Serv., Massachusetts Inst. of Technol., Cambridge,
Mass—CLIN. PHARMACOL. THER. 1966, 7/6 (713-722)

The wrist-drop occurring in painters is the only specific symptom in lead poisoning. Lead
affects many biological systems and chronic poisoning may alter cells at the molecular
level. It has injurious effects on the germ cells of both sexes, and it has been used as an
abortifacient agent. Enzyme systems in the brain may be disturbed in lead encephalopathy,
and in acute cases, renal function can be impaired. Growing tissue is probably more
vulnerable than adult tissue — accounting for the difficulty of diagnosis in industrial wor-
kers. The possibility of illness, indirectly caused by lead, should be carefully considered,
e.g., peptic ulceration and jaundice. Even cigarette smoking and alcohol may contribute
to the hazard. Well-designed prospective studies of special populations are needed to safe-
guard the extra burden of lead in the air, water, soil and food.

43. Lead poisoning in childhood: signs, symptoms, current therapy, clinical expressions—
Greengard J ., Cook County Child. Hosp., Chicago, Ill.—CLIN. PEDIAT. 1966, 5 (269-276)

Early symptoms of lead poisoning are vague and non-specific and the physician some-
times fails to consider the possibility that they are caused by lead. Pica in children in slum
housing is the most common case. Seasonal factors are of great importance in the overt
manifestations of lead intoxication. Children with high blood lead concentrations may be
Symptom-free in winter and develop serious disorder with the advent of warm, sunny
weather. Basophilic stippling of erythrocytes is only seen in 30-40% of children with lead
poisoning. The urine contains large excesses of coproporphyrin and 6-aminolevulinic
acid. Tests for lead in blood and urine are time consuming and cannot be performed in
most hospital laboratories. Blood lead levels are useful but urinary lead determinations are
much less reliable. Radiology of the abdomen for radiopaque lead-containing plaster
and of the bones for lead lines is valuable. The definitive clinical diagnosis of lead
encephalopathy is based on spinal fluid findings but lumbar puncture itself may precipitate
fatal complications due to release of fluid under increased pressure with herniation of the
cerebellar tonsils or temporal lobes. Paraldehyde is a safe drug for the treatment of con-
vulsions but if it proves ineffective a general anesthetic may be used. Chelation of lead
with EDTA and dimercaprol in combination may be effective in encephalopathy and is
of considerable importance in early cases. Respiratory arrest, anemia, gastrointestinal
bleeding, shock and nephritis are frequent complications of lead intoxication. The prob-
lem of removal of the child from the source of lead is difficult, involving the cooperation
of many agencies.

44. Varying psychological sequelae of lead ingestion in children—Wiener G., Div. of Matem.
and Child Hlth, Dept. of Populat. and Pam. Hlth, Johns Hopkins Univ., Baltimore, Md.—
PUBL. HLTH REP. 1970, 85/ 1 (19-24)

Pica is a predisposing factor to lead poisoning in children over 18 months of age and may
therefore be a cause of mental retardation. Blood and urine tests for lead do not correlate

l6

perfectly with each other or with severe encephalopathy. The inner city metropolitan areas
in the US termed the ‘lead belt’ are characterized by old and neglected dwellings with a
poor, mainly Negro, population. Many of the older buildings have outside and inside
paintwork containing lead pigments which may poison children with pica who chew it.
In one study of low-income families in the US, mainly Negro, 33% of the 604 children
under 5 years of age showed coproporphyrinuria, indicating chronic lead poisoning, and
in another study of 333 children brought for medical examination, 44% had abnormally
high blood-lead levels (over 0.05 mg./ 100 ml.). Age and duration of exposure to lead were
the most critical factors. Young children may be neurologically affected by excessive lead
absorption because their brain enzymes are poisoned during development, but in asymp-
tomatic cases of lead poisoning there may be intellectual improvement. Of 10 cases surviv-
ing in 1964 who had had convulsions and had blood-lead levels over 0.04 mg. / 100 ml.,
only 2 had IQs over 90. All but 2 of the studies reviewed here reported some mental impair-
ment in children with lead poisoning, but the controls were not rigid enough to prove that
lead caused the changes. The necessity for controlling the subjects’ sociocultural back-
ground, age, nutritional and emotional state, and intellectual level while varying the lead
intake poses diffith research problems, and though animal experiment can avoid many
of these difficulties, generalizations from comparative research, though often fruitful, are
also tenuous. But, despite the lack of definite research, undiagnosed and therefore un-
treated lead poisoning is certainly a cause for concern.

45. The biochemistry of lead: review of the body distribution and methods of lead deter-
mination—Berman E., Dept. of Toxicol., Hektoen Inst. of Cook County Hosp., Chicago,
Ill—CLIN. PEDIAT. 1966, 5/5 (287-291)

The gastrointestinal and the respiratory tract are the 2 major routes of absorption of lead
salts. Most cases of lead intoxication in children result from lead ingestion while the
majority of industrial cases follow inhalation of lead dust or fumes. Significant amounts of
lead can be absorbed from a shot wound. Organic lead compounds rapidly penetrate
the intact skin. Following absorption, lead is distributed to various tissues. Highest initial
soft tissue concentration is in the liver and kidney from where, however, lead quickly
disappears for deposition in bone. A comparison is made between the previously reported
lead levels in tissues and new findings based on autopsy reports. Skeletal lead is fairly
inert but under certain metabolic conditions lead may suddenly be mobilized from bones
and an acute lead intoxication may ensue. Lead is excreted in feces, urine and sweat. Fecal
lead mostly represents lead that was ingested but not absorbed. Urinary lead indicates
the degree of lead absorption. Blood lead levels are of value only in acute cases since the
blood is rapidly cleared of lead. Blood levels in chronic cases are not remarkable. It is
recommended that a blood level of 0—21 ,ug.% be considered as negative, 21-60 ,ug.% as
evidence of increased lead exposure, and above 60 ,ug.% as dangerous. There is a discussion
of procedures for lead analysis (spectrography, polarography, calorimetry). Recently,
atomic absorption flame spectrophotometry has proved to be more sensitive and specific
than the older procedures.

46. Childhood lead intoxication. Diagnosis, management and prevention—Chisolm Jr J. J .,
Dept. of Fed, Johns Hopkins Univ. Sch. of Med., Baltimore, Md.—MED. TMS (N.Y.)
1970, 98/9 (92-106)

Acute lead poisoning in the US occurs mostly in young children who live in deteriorated
houses. Of preschool children in selected slum areas, 2-5% show evidence of lead intoxi-
cation. Among causative factors listed are: pica, normal mouthing of children and in-
creased oral activity in an emotional state. The peeling paint and crumbling painted

l7

plaster in older houses constitute the main hazard to the small child. Other sources of lead
are tabulated. Repetitive ingestion of small amounts of lead is usually more dangerous
than a single massive exposure. The symptoms of plumbism are protean in character. Initial
manifestations include vomiting, anorexia, apathy, hyperirritability, incoordination, de-
lay in the normal development of speech and behavior disorders. The symptoms increase
with each toxic episode. Acute encephalopathy is most common in children 15 to 30
months of age. Peripheral neuropathy or cramp-like abdominal pain are mostly seen only
in the older child. In early childhood special laboratory tests (whole blood lead, urine lead
output) are required to establish the diagnosis of plumbism so that the diagnosis must be
tabulated. As to the treatment of symptomatic plumbism, chelation therapy is of primary
and the high-risk dwelling. These factors are firm clinical indications for blood lead and
other laboratory examinations. The presumptive tests include the qualitative copropor-
phyrin test, the serum 6-aminolevulinic test, lead in hair, X-rays, blood study and urin-
analysis. The clinical significance of various concentrations of lead in whole blood are
shown in a table. The clinical classification of the severity of plumbism in children is also
tabulated. As to the treatment of symptomatic plumbism, chelation therapy is of primary
importance. Appropriate supportive therapy is just as vital to survival as is the selection
and correct administration of chelating agents. Control of seizures comes in the first place.
The indications for chelation therapy in asymptomatic children are listed. After com-
pletion of active therapy the child is hospitalized in a convalescent clinic until a safe dwel-
ling is obtained. Adequate information of the parents and education of the child are an
important part of the after-care.

47. Poisoning due to heavy metals—Chisolm Jr J. J., Dept. of Fed, Johns Hopkins Univ.
Sch. of Med., Baltimore, Md.—PEDIAT. CLIN. N. AMER. 1970, 17/3 (591-615)

Poisoning due to lead, mercury, arsenic, thallium, cadmium, iron, gold, and copper is
discussed. Both acute and chronic poisoning due to these heavy metals cause a variable
pattern of multiorgan injury and so should be considered in the differential diagnosis
whenever the clinical picture indicates simultaneous involvement of two or more organ
systems. Accurate diagnosis depends upon identification by chemical tests of the heavy
metal in blood, urine, and sometimes hair and fingernails. Chelating agents (calcium diso-
dium edetate, dimercaprol, D-penicillamine, and deferoxamine) are important and some-
times life—saving adjuncts in the treatment of heavy metal poisonings. Since the chelating
agents of choice vary from metal to metal, accurate chemical identification of the heavy
metal responsible for the poisoning is also essential for proper therapy. Similarly, accurate
chemical identification of the environmental source of the patient’s toxic exposure is
essential if recurrences of toxic exposure are to be prevented. Dosage and choice of chel-
ating agent vary with the severity of the intoxication. An important principle of chelation
therapy is the principle that an adequate molar excess of Chelating agent over toxic
heavy metal must be provided. Use of insufficient dosage may intensify the intoxication.
In some instances, careful supportive therapy is also of vital importance in determining
the over-all therapeutic result.

48. Lead poisoning in childhood - comprehensive management and prevention—Chisolm
Jr J. J. and Kaplan E., Dept. of Fed, Johns Hopkins Med. Sch., Baltimore, Md.—J.
PEDIAT. 1968, 73/ 6 (942-950)

Attention is draw to the need for a cooperative community approach to the social, environ-
mental, and psychological aspects of the problems of children with lead intoxication.
Comprehensive care is just as urgent for the asymptomatic child with an increased body
burden of lead as it is for the child with manifest acute plumbism. While chelation therapy

18

for the acute toxic episodes of chronic lead poisoning is deservedly emphasized, hospitali-
zation in a chronic disease facility which has a positive program of child and family re-
habilitation serves an important role in the total care of the affected child. Experience
in Baltimore and other large cities has shown that coordinated and sustained efforts by
health departments, pediatricians, medical social workers, and child guidance workers are
essential for an effective program for the prevention and treatment of childhood lead
intoxication.

49. Trace metals of the brain and their importance in human disease—Cumings J .N., Dept.
of Chem. Pathol, Inst. of Neurol, Nat. Hosp., London~CHEM. WEEKBL. 1967, 63/42
(473-479)

Many trace metals have been found in the cerebral tissues and it is likely that each metal
plays some part in various enzyme mechanisms. When the metal is in excess due to poison-
ing it acts as a cell poison, possibly by direct action on certain enzyme system. The present
discussion is limited to manganese, zinc, mercury, lead, and copper. Manganese appears
to be an essential element for nutrition. The occipital lobe of the brain contains more
manganese than other parts. Manganese in vitro will activate certain enzymes. In animals
there is a lowered threshold for seizures in manganese deficiency. Men working in manga-
nese mines developed a Parkinsonian-like condition. There is a daily intake of about 10-15
mg. of zinc, practically all of which is excreted in the feces. A low urinary excretion occurs
in kwashiorkor and a raised output is found in some forms of acute porphyn'a and in
certain types of cirrhosis of the liver. The zinc content of hair is a guide to zinc deficiency
in man. Parts of the hippocampus in guinea pigs contain large amounts of zinc. A small
amount of mercury circulates in the blood. It has been shown that following administra-
tion of organic compounds of mercury to animals the calcarine area of the brain contained
the largest amounts of mercury. Enzyme activity is inhibited by mercury. Inorganic mer-
cury poisoning is largely an industrial hazard. Intoxication following organic mercury
occurs in industry or after accidental ingestion. There is a normal intake of copper between
2 and 5 mg. a day. Almost all of it is excreted in the feces. Copper is present in almost all
tissues and in the body fluids. Special attention is paid to the copper proteins ceruloplasm-
in, cerebrocuprein, tyrosinase, monoamine oxidase and hepatocuprein. Copper is toxic to
many enzyme systems. Wilson’s disease is characterized by a deposition of copper in many
tissues, especially in the brain and the liver. The clinical and biochemical features of Wil-
sons’s disease are discussed at length. It has been suggested that in this disease there is a
failure in ceruloplasmin synthesis. Recently, isotope studies have facilitated the diagnosis.
Treatment of the condition is based on removal of excess copper by chelating agents.

19

Sources of poisoning, epidemiology and pica studies

50. Accidental poisoning in childhood / Vergiftigungsunl'alle im Kindesalter—Reddemann
H. and Amendt P., Kinderklin., Ernst-Moritz-Arndt-Univ., Greifswald—ARCH. KINDER-
HEILK. I968, 177 (284—295)

The incidence of accidental poisoning in childhood has increased in recent years in all
countries. Over a 12 year period 356 infants and children were treated for accidental poison-
ing. The incidence was highest in the second and third years of life and fell off sharply by
7 years. Over 95% of poisonings occurred in the home. Wrong prescriptions given by
doctors accounted for 6.5%. The most frequent form of poisoning was with drugs (39%),
with household chemicals next (25%). Other causes were insecticides, rat poison, poison-
ous plants, gases, alcohol and mercury. Most cases were due to parental carelessness. Pre-
vention of this form of poisoning requires the cooperation of many different sectors, es-
pecially the parents.

51. Absorption and excretion of mercury in man. Xl. Mercury content of ‘normal’ human
tissues—Joselow M.M., Goldwater LJ. and Weinberg S.B., Div. of Occupat. Med., Sch. of
Pub]. Hlth and Admin. Med., Columbia Univ., New York, N.Y.—ARCH. ENVIRONM.
HLTH 1967, 15 (64-66)

Mercury analyses were performed on 236 samples of tissues removed at autopsy from 39
‘normal’ human subjects. The samples represented 12 different tissues or organs. The
highest values were found in the kidneys. Age did not appear to be a factor in the mercury
levels.

52. Pink disease (correspondence)—Stephenson J.B.P., Rayner P.H.W. and Kesaree N.,
Roy. Hosp. for Sick Child., Glasgow (Stephenson); Child. Hosp., Birmingham (Rayner);
Oldchurch Hosp., Romford (Kesaree)—BRIT. MED. J. 1966, l (l l 10-] l l 1)

Dr. Stephenson reports 3 cases of pink disease caused by teething or worm powders. All
3 children excreted large quantities of mercury and were treated with N~acetyl-D-penicill-
amine. He gives a warning that ointments and powders are not the only source of mercury
— mercury seed dressing are available and in the US mercury vapor from wall-paint has
been known to cause pink disease. Not all cases of the disease are classically pink, and may
therefore be overlooked unless accurate urine mercury estimations are carried out on clin-
ical suspicion. Dr. Rayner recalls a case of pink disease which he saw in 1964, which was
due to a mercury-containing dusting powder used for diaper rash. There was some evi-
dence that mercury had played a part in the etiology of primary renal tubular acidosis in
an elder sibling. Mercury can be absorbed through even intact skin in potentially toxic
amounts and absorption would be enhanced in inflamed skin areas. The toxic effects are
not entirely dose-dependent but depend partly on individual sensitivity. He expresses
concern that mercury-containing ointment has been reintroduced for diaper rash, which
requires only treatment by simple nursing measures. Dr. Kesaree reports a case of a 2

20

year old girl referred for conjunctivitis resistant to treatment. She was irritable, photo-
phobic, and had the typical appearance and behavior of pink disease. The extremities
were unusually pink, but cold and she had an erythematous rash. The mother had been
treating a diaper rash with ung. hydrarg. ammon. dil. at intervals over a 5-month period.

53. Mercury poisoning from application to omphalocele—Stanley-Brown EC. and Frank J.
E.—J. AMER. MED. ASS. 1971, 216/ 13 (2144-2145)

The case is reported of a newborn child who died of mercury poisoning following the
painting of a giant omphalocele with merbromin. The child, weighing 5 lbs. 8 02., was
born at 36 weeks’ gestation. A giant omphalocele was present with an intact sac, and the
base measured 5 x 6 cm. The distance from the xiphoid process to the pubic symphysis
was 9 x 6 cm. The liver and most of the intestines were within the omphalocele. Initial
treatment included intravenous fluid, penicillin, kanamycin sulphate and, through mis-
understanding, the exposed sac was painted with 1% merbromin every 3 hours for a total
of 3 treatments. This was changed to 2% merbromin every '12 hours on the following
day, when oral feedings were started and intravenous fluids discontinued. Oliguria on the
second day of life led to anuria on the third day and there was an episode of pink urine.
Diffuse sclerema began on the third day. Mercury poisoning was considered and an ex-
change transfusion carried out. The omphalocele sac was painted with tincture of ben-
zalkonium chloride and hydrocortisone and dimercaprol were administered. On the fourth
day of life the sclerema seemed diminished and the infant was more active. Urinary output
increased slightly. However, on the fifth day of life, respiratory arrest occurred and the in-
fant died. The blood mercury level in this patient was 30,ug./deciliter. Normal patients
not exposed to mercury vapor have been found to have levels between 0.6 and 1.2 ,ug./
deciliter.

54. Congenital mercury poisoning—Snyder R.D., Dept. of Fed, Univ. of New Mexico Sch.
of Med., Albuquerque, N.M.—NEW ENGL. J. MED. 1971, 284/ 18 (1014-1016)

A case is reported of congenital mercury poisoning in a family with several cases of mer-
cury poisoning acquired by eating pork from pigs fed on seed grain treated with a methyl
mercury fungicide. The 40-year-old mother ate pork containing mercury between the 3rd
and 6th months of pregnancy, and her urinary mercury levels were markedly elevated in the
7th and 8th months. A 3062 g. male infant was born at term and at 1 minute of life he be-
came dusky and intermittent gross tremulous movements of the extremities developed, but
the EEG and EMG were normal; mercury could no longer be detected in the urine. At
3 months the EEG was abnormal with widespread occurrence of spike activity more
abundant in the left central and parietal regions. By 6 months generalized myoclonic
jerks developed and the EEG was markedly abnormal, with paroxysmal high-voltage
spike, polyspike and spike and slow wave patterns. At 8 months the patient was hypotonic
and irritable and had nystagmoid eye movements, without evidence of visual fixation. The
child was never breast-fed, so he had no opportunity of ingesting food poisoned with
mercury. His clinical state was therefore presumably due to transplacental poisoning. His
symptomatology was in striking contrast to an absence of symptoms in the mother. This
may reflect a special susceptibility of the developing nervous system to damage from
mercury. The tremors and EEG abnormalities recall the clinical signs of mercury poison-
ing in Japan (Minamata disease). Cases of mercury poisoning from misuse of mercury-
treated seed grain have been reported in Iraq, West Pakistan and Guatemala. The wide-
spread use of mercury in agricultural and industrial use renders it very liable to enter

21

the food chain. An asymptomatic woman who ingests organic mercury compounds during
pregnancy may produce a neurologically defective infant with cerebral palsy, mental re-
tardation, convulsions, involuntary movements or defective vision.

55. The human body burden of lead—Schroeder HA. and Tipton I.H., Dept. of Physiol.
Dartmouth Med. Sch., Hanover, NIL—ARCH. ENVIRONM. HLTH 1968, 17(965—978)

Concentrations of lead in human tissues from 33 cities of the US and foreign countries
were determined. Differences from place to place were observed, median values generally
being higher in US subjects than in those from Africa, the Middle East, and in a few tis—
sues, the Far East. In the US mean values of lead increased with age in the aorta, kidney,
bone, liver, lung, spleen, and pancreas; in foreign tissues only aortic lead increased with
age. Smooth, striated, and heart muscles and brain had little lead. Bone lead was higher
in US subjects than in Far Easterners. Bone contained 91% of the total body lead. At the
time these samples were collected (1952-1957) the exposure of US subjects to lead from all
sources was apparently large enough to cause accumulation with age, whereas in most for-
eign areas it was not. It is likely that atmospheric lead from motor vehicle exhausts largely
accounts for increased exposures, and that inspired lead may make up a sizable portion
of the total amount absorbed by the body. Although experimental toxicity of lead in
animals with tissue concentrations similar to those of human beings has been demonstrated,
no clinical evidence of bizarre innate toxicity was discovered in these human subjects.
In human soft tissues, mean concentrations of lead were not found to displace any of the
essential trace elements of low concentration: chromium, manganese, cobalt, copper, or
molybdenum. In view of the steadily increasing annual pollution of air and soils with
lead from motor vehicle exhausts, innate toxicity in exposed human beings may appear.

56. Plumb unexpected: new source of lead poisoning—DELAWARE MED. J. 1971, 43/1,
(19-21)

57

22

This editorial discussed the occurrence of lead poisoning following the use of earthenware
pottery. In investigation of a recent outbreak, 264 earthenware glazed cups and pitchers,
collected in Canada, were tested. It was found that one quarter of these released enough
lead to cause severe poisoning, and that half released enough lead to be unsafe for every-
day use. Earthenware may be glazed with a frit containing lead not chemically bound
and prone to leach into liquids contained in the pottery, especially if these are warm and /
or acidic. Handcrafting of pottery is increasing, and only an expert can distinguish easily
between earthenware and stoneware; the latter is never made with lead frits. There is no
legal requirement for labeling when lead is used in glazing. Cases of lead poisoning follow-
ing drinking of warm apple juice and of Coke from earthenware containers were mention-
ed. Use of pewter is also potentially dangerous, though this substance is used less widely.

. The ubiquity of lead—FD. AND COSMET. TOXICOL. 1966, 4 (532-535)

The ubiquity of lead in the human environment exposes everyone to some extent to this
toxic metal. Despite effective control of the industrial environment, shipbreaking, where
fumes from anticorrosive paints are produwd in small spaces, still presents a considerable
hazard. Attention is therefore being focused on the detection of incipient lead poisoning
in the subclinical stages. Various parameters have been studied in order to establish the
diagnostically most reliable test for this condition. It has been shown that the symptoms
correlate most closely with the excretion of the porphyrin precursor 6-aminolevulinic acid
(ALA) whereas correlation with urinary lead and coproporphyn'n was poor. Urinary ALA
was also found to be the most useful diagnostic parameter following penicillamine treat-

ment, thus suggesting that the initial excretion of ALA indicates the size of the metabol-
ically active lead pool. Attention has been drawn to the similarity between lead poisoning
and acute intermittent porphyria, although the sites of action differ in the 2 conditions,
the liver being the site of deranged porphyrin metabolism, while the bone marrow is the
main site of attack in lead poisoning, which in addition may have a direct neurotoxic
effect and induce a hematolytic process. Sources of lead intoxication, apart from ship-
breaking, are mainly lead-containing paint from old buildings ingested by children and the
burning of old battery cases as domestic fuel. Another source of lead poisoning in the
home is the use of tinned-steel cooking utensils. A warning against purchase of these
utensils has been issued. General atmospheric pollution with lead is mainly attributed to
the use of leaded petrol in motor vehicles, but no conclusive connection between chronic
subtoxic lead exposure and any specific disorder has as yet been established.

58. Apple-juice colic—LANCET 1971, 1 (278)

Although now controlled in Britain by statutory regulations, the lead content of pottery
glazes is not controlled by legislation in many countries. In a report from Canada, lead-
poisoning in 2 young brothers is described, one of whom died after apple-juice had been
stored in a lead-glazed earthenware jug. The authors obtained 117 samples of Canadian-
produced and imported earthenware vessels and prepared an additional 147 pieces of
glazed pottery with glazes used by amateur und professional pottcrs. Half of all the
glaze-surfaces tested contained sufficient lead to cause chronic poisoning (yielding more
than 7 mg. / 1. lead in 4% acetic acid stored in the vessel for 18 hours). A quarter of all
homemade handcraft and a tenth of imported and commercial earthenware were more
dangerous, yielding a concentration greater than 100 mg./l. in their standard test, a con-
centration sufficiently high to cause severe acute poisoning in small children if an acidic
fluid was stored in it.

59. Child lead paint poisoning still prevalent—MARYLAND MED. J. 1968, 17 (137-138)

Child lead poisoning from ingested lead paint is still prevalent in Baltimore City as shown
by the number of cases recorded since 1931. The drop in the number of cases observed in
1967 is ascribed to the relatively cool summer of that year since it is known that the risk of
lead encephalopathy is much greater during warm summer months. It is pointed out that
every child showing initial symptoms such as anorexia, apathy, hyperirritability, inco-
ordination and loss of recently acquired skills should be considered suspect for lead poi-
soning. Appropriate kits are made available by the local health authorities on request. If
lead ingestion continues the symptoms intensify and the classic signs of increased intra-
cranial pressure appear. The age distribution of the 1111 cases of lead poisoning recorded
since 1931 shows that a large majority of cases fall within the age group 1-3. Warnings to the
public have been issued through the mass media and physicians who deal with young
children are in a strategic position to warn high risk families of the lead danger and to take
appropriate steps if symptoms appear.

60. Effects of particular pollutants. Mercury pollution in Sweden with special reference to
conditions in the water habitat—Ackefors H., Inst. of Mar. Res., S-453 00 Lysekil—PROC.
ROY. SOC. LOND. 1971, 177 (365-387)

During the 1950s and 1960s, great attention was paid to the Hg problem in Japan and
Sweden. In Sweden the whole environment was contaminated due to the widespread use
of Hg in agriculture and industry. The organic Hg compounds of alkyl-type and aryl-
type, which were used for 10 to 20 years as fungicides in agriculture and in the pulp industry,

23

have had serious effects on animals in both terrestrial and aquatic environments. These
two types of Hg compounds are now forbidden in Sweden. However, a new type of com-
pound, alkoxyalkyl-type, may now be used as a fungicide in agriculture. Much Hg is
discharged into the air and water due to industrial activities, e.g., the chlorine-alkali indus-
try and many other activities such as the burning of waste products containing small
amounts of Hg. Although most Hg is inorganic or organic in the form of phenyl-Hg (aryl-
type) (discharged as industrial wastes), most of the Hg in fish from lakes and the Baltic in
Sweden is present as methyl-Hg (alkyl-type). It has been demonstrated that methylation
of Hg takes place due to bacterial and enzymic activity. High Hg contents in the wild
fauna, grain-eating birds and their predators, gave the first scientific evidence that the
terrestrial environment was contaminated. Since the ban on alkyl-Hg in agriculture was
introduced the Hg concentrations in birds living in the terrestrial environment and of food
such as eggs, pork, etc, produced on land, have dropped. Unfortunately this is not the
case in the aquatic habitat. Although the discharge of Hg to water and air has been
restricted in Sweden, the whole environment is so heavily contaminated that it will take a
long time for the Hg concentrations to decrease. The most serious Hg problem in Sweden
today is the high Hg concentration in fish. Fish from a certain number of lakes and from
extensive coastal areas on the Swedish east and west coasts are now forbidden for sale in
Sweden. In general, water organisms or birds feeding in the water habitat have higher
‘natural’ contents of Hg than terrestrial wildlife. Pike has been chosen as an indicator
organism of Hg contamination. Levels higher than 200 ng.Hg/ g. are considered abnormal.
Most of the investigated fishes from freshwater and coastal areas have concentrations in
the range of 200 to 1000 ng.Hg/ g. Fish with more than 1000 ng.Hg/ g. exceed the tem-
porary limit of l mg.Hg/ kg. (1000 ng./ g.) now valid in Sweden. Earlier, FAQ/WHO pro-
posed a practical residue limit up to 0.05 mg.Hg/kg. (50 ng. / g.) for terrestrial food. The
effects of Hg intake in man were first observed in Japan. During the years 1953 to 1960, 111
persons living around Minimata Bay, were killed or seriously disabled. They were poisoned
by fish and shellfish with elevated Hg concentrations. In Sweden elevated Hg concen-
trations have been observed in blood corpuscles, blood plasma and hair of people eating
very much freshwater fish, but also the people eating saltwater fish.

61. Conservative treatment of umbilical hernia with mercurochrome / Breitag zur konserva-
tiven Nabelschnurbruch-Behandlung mit Mercurochrom—Schippa R. and Wehran H.J.,
Klin. und Poliklin. filr Kinderchir., Karl-Marx—Univ., Leipzig—KINDERCHIR. 1968, 6/3
(319-326)

Thirteen cases of large exomphalos seen between 1963 and 1966 who were treated with
mercurochrome are reported. In at least 5 children there were clinical symptoms of mercuro-
chrome absorption, which caused death with symptoms and signs of intoxication. The
estimation of mercury in the urine and the organs of 6 fatal cases and of 2 survivors
showed a high mercury concentration. It is likely that mercurochrome itself or one of its
decomposition products are toxic. There was no conclusive evidence of a mercury poison-
ing. Treatment with mercurochrome can therefore no longer be considered the treatment
of choice as a conservative means of managing large exomphalos.

62. Mercury poisoning through eating fish? / Metyllrvicksilverfbrgifming genom fdrt‘a‘ring
av flslr2—Birke G., Johnels A.G., Plantin L.0., Sjostrand B. and Westerrnark T., Konung
Gustav V’s Forskningsinst., Stockholm—LAKARTIDNINGEN 1967, 64/37 (3628-3637)

Previous research on the concentration of mercury in nature is surveyed. In recent years
there has been a striking increase in the mercury content of the fish in many Swedish

24

lakes. People who eat unusual quantities of fish have therefore been examined, and
several have shown high concentrations of mercury in the blood, which, however, slowly
declined after a change of diet. No reliable cases of serious clinical symptoms caused by
the high content have yet been recorded, but the concentration in these people is of an
order of magnitude such that they should avoid a large consumption of fish with
clearly increased contents of mercury. The reorganization of the emission of mercury—
containing substances in natural surroundings should also be intensified.

63. Pica and poisoning—Laurie R.S., Child. Hosp., Washington, D.C.—AMER. J. ORTHO-
PSYCHIAT. 1971, 141 (697-699)

Some children suffering from plumbism were found to have ingested not paint but news-
paper. Pica may result not only in lead intoxication but also, for example, methemo-
globinemia from the ingestion of crayons. Severe anemias resulting from persistent pica
were observed as far back as 1865. The most consistent factor found in pica is unavailable
mothering. For various reasons ranging from overwork to alcoholism, mothers are not
available to stop the child's habit. Pica has been found to disappear when the mother
became more available to the child. It is only in the most resistant cases that psychotherapy
has been found necessary. The program of action started in Washington provides for every
child with pica to be screened as a presumptive lead poisoning case and the incidence of
lead poisoning cases detected, mostly preclinical, has risen by more than 300%. The re-
moval of all lead from the child’s environment is obviously an important preventive mea-
sure but it is over-simplifying the question to explain pica as resulting from an unstimul-
ating environment. Removing the sources of lead will not correct the conditions facing the
mothers of children who would not have pica if the mothers were available to stop them.

64. Epidemiology of lead poisoning in New Haven children - operational factors—Meigs
J.W. and Whitmire 13., Dept. of Epidemiol. and Publ. Hlth, Yale Univ. Sch. of Med., New
Haven, Conn—CONN. MED. 1971, 35/ 6 (363-369)

Childhood lead poisoning in New Haven was studied from the standpoint of operational
characteristics of families whose children had the condition. A sample of families with lead
poisoned children was matched by age and sex against families with children with 2
other conditions: inguinal hernia treated surgically, and pneumonia. Families with lead
poisoned children were significantly more likely than the matched controls to: be black;
have marital separation; have a father unemployed; have a mother employed or at school;
have more children in the family; have the index child supervised by someone other than
the mother; live in poor housing; be a recipient of public assistance; have serious family
problems. A second sample, drawn from all children hospitalized from April to September
1969 was studied similarly. Black families in general differed from white families with res-
pect to the foregoing variables. Within the group of 58 black families, those with lead
poisoned children differed significantly from all other black families and in the directions
previously described. It is concluded that black families generally are coping with opera-
tional problems that are significantly less prevalent among white families. When the over-
load becomes too great childhood lead poisoning is likely if children have access to lead.
Control of this syndrome will require attention to family operation as well as improve-
ment of the physical environment.

65. Lead poisoning in blind children—Ames A.C. and Swift P.N., Dept. of Chem. Pathol.,
Lewisham Hosp., London—BRIT. MED. J. 1968, 3/5611 (152-153)

Many partially sighted children use the mouth, lips, and tongue as an aid in identifying
objects — this has been termed discriminatory pica. Investigation of a case of lead poison-

25

ing in a pupil at a residential school for the blind led to the discovery of others with asympto-
matic lead poisoning, all of whom had the same habit. All the children recovered with-
out treatment when they abandoned their habit of discrimination by use of the mouth.
Authorities responsible for schools for the blind should be aware of this risk.

66. Factors influencing exposure of children to lead—Barltrop D. and Killala N.J.P., Paed.
Unit, St Mary’s Hosp. Med. Sch., London—ARCH. DIS. CHILDH. 1969, 44/ 236 (476-479)

Paint samples from 56 homes of 103 children aged l-l4 years were obtained. The lead
content of the samples was related to the age of the building and to the social class of the
family; 53% of the samples contained more than 1% of lead. Old houses, and families
of low social class, were frequently associated with indoor paints of high lead content.
Lead paint applied several decades ago, even if infrequently covered by other paint, may
still continue to provide a potential hazard. Detection and removal of lead paint already
in situ should therefore be the aim in preventing lead poisoning of children from this
source.

67. Environmental lead and its paediatric slgnificance——Barltrop D., Dept. of Clin. Sci.,
Paed. Unit, St Mary’s Hosp. Med. Sch., London—POSTGRAD. MED. J. 1969, 45/520 (129-
134)

There is evidence that appreciable body burdens of stable and radioactive lead may be
acquired by children and also that part of the maternal intake of lead may influence the
fetus. The rapid growth rate, immature metabolic apparatus and varying dietary patterns
which characterize the pediatric age groups suggest that standards for adult males might
not be applicable. Numerous environmental sources may contribute to the lead intake of
children but the metabolism of lead in this group is not well understood and deserves
further study.

68. The prevalence of pica—Barltrop D., Dept. of Fed, Harvard Med. Sch., Child Hlth Div.,
Child’s Hosp. Med. Cent, Boston, Mass—AMER. J. DIS. CHILD. 1966, 112/2 (116-
123)

The prevalence of pica in random samples of children, selected for age and color, was
determined from parental observations. Information was obtained by interview concerning
439 children and by mailed questionnaire concerning 277 children. The prevalence of pica
and the range of articles ingested decreased with increasing age over the age range studied
(1-6 years). The siblings of white children with pica were more likely to have pica than
the siblings of unaffected white children. The occurrence of pica was related neither to
the sex, race, family rank, place of birth of the parents, nor to the size or social position
of the family. The prevalence of mouthing and several other age-dependent activities,
simultaneously determined using the same techniques, showed characteristic variations
with age. Pica is not uncommon in children 1 to 6 years of age.

69. Respiratory exposure to lead: epidemiological and experimental dose-response relation-
ships—Goldsmith J.R. and Hexter A.C., California State Dept. of Publ. Hlth, Berkeley,
Calif—SCIENCE 1967, 158/3797 (132-134)

Epidemiologic studies of blood lead levels in general and occupational groups show a
logarithmic regression on estimated atmospheric exposure. Experimental results at the
same and higher levels show a dose-response relationship which fits the same regression.
The data imply that long-term increases in atmospheric lead will result in predictably
higher blood lead levels in the exposed populations.

26

70. Chronic lead poisoning in children: a review of 90 children diagnosed in Sydney, 1948-
l967—Freeman R., Dept. of Paed., Prince of Wales Hosp., Sydney—AUST. PAEDIAT. J.
1969, 5/1 (27-35)

In the past 20 years, 90 children with chronic lead poisoning, mostly due to the ingestion
of peeling paint, have been diagnosed in Sydney. Eleven of the children died and at least
30% have serious neurological or renal sequelae. The aim of this brief review is to renew
interest among the medical profession in this hazard, for only by early diagnosis and
appropriate treatment will this sad picture be improved. It is also hoped to stimulate
measures to rid our society of a preventable disease.

71. Chronic lead poisoning in children: a review of 90 children diagnosed in Sydney, 1948-
1967. I. Epidemiological aspects—Freeman R., Dept. of Paed., Prince of Wales Hosp., Syd-
ney—MED. J. AUST. 1970, I (II) (640-647)

Chronic lead poisoning in children was prevalent in Queensland, Australia, in the early
part of the century, but legislation restricting the lead content of paint has practically
eliminated the hazard in that state. There have been few reports of childhood plumbism
from the other states, where it has not been considered a problem. However, 90 children
diagnosed in Sydney between 1948 and 1967 show that it is a common hazard in New
South Wales. Most of the children were poisoned after ingesting lead-based paint peeling
off the walls of their homes. The incidence was highest in 3 of the older municipalities,
but individual cases came from many other parts of Sydney, which suggests that the
hazard is widespread. In a few cases, the only source of lead was from toys, which are
available today in toy shops. It is hoped that this and subsequent reports will stimulate
measures to eradicate a serious and preventable disease from our community.

72. Lead in environments (Japanese)—Tada 0., Div. of Hyg., Inst. for Sci. of Labour, Tokyo
—J. SCI. LABOUR (TOKYO) 1970, 46/ 10 (577-583)

Reports of studies on lead in environments of living, in atmospheric air and in working
environments are discussed. Lead occasionally causes intoxications in workshops where
the fume and dust control is insufficient. The air pollution by automotive emissions over
the city streets has become a serious problem of public health with the increase in traffic.
Polluted air contains lead from the emissions of automobiles, and attention should be
paid to the accumulation of lead in the bodies of city dwellers due to the rise in concen-
tration of atmospheric lead. The effect of lead absorption on human health depends on
the quantity and duration of lead-absorption from the air. The possibility of lead being
absorbed by the body through food and beverage should not be ignored.

73. Lead poisoning at Bradford—Tumer W., Bamford F.N. and Dodge J.S., I-Ilth Dept.,
Bradford—BRIT. MED. J. 1967, 3 (56)

The presentation of 2 young children with convulsions, in the absence of a history of
epilepsy, and the deaths of several animals with convulsions in the same neighborhood,
caused the local Medical Officer of Health to investigate the home and surroundings of
these children. It was found that battery cases had been burnt in their house and in others
nearby, the casings being obtained from scrapyards. The 2 children whose illness had
prompted investigation died despite calcium disodium versenate treatment. Five other
children and 2 adults found in the initial examination of residents in houses where battery
cases had been used for fuel were thought to have lead poisoning and were hospitalized.
The plastic battery case is probably non-toxic but substantial quantities of lead adhere to

27

it. Toxic ash remains after burning, is probably ingested and possibly inhaled. Indiscrimi-
nate dumping of these cases should be prevented by legislation.

74. An outbreak of lead poisoning of bread in Malta—Vassallo L.—J. ROY. NAV. MED.
SERV. 1971, 57 (37-40)

An usual outbreak of lead poisoning occurred in Malta in 1903 and 1904 due to wide-
spread contamination of Maltese bread by lead salts. Varying degrees of poisoning occurred
among the population. Most people were treated at home but 9 patients were admitted
to hospital staying for an average time of 2 weeks. There were no deaths. The source of
the lead was lead painted wood burned directly on the floors of the ovens to heat them.
The contaminated ashes were then swept away and the loaves put on the heated floor for
baking. The painted wood used came from a naval ship which had been sold for scrap.

75. Pink disease from cutaneous absorption of mercury—Ward CC. and Hingerty D.—J.
IRISH MED. ASS. 1967, 60/357 (94-95, 98)

A case report of mercury intoxication due to cutaneous absorption in an ll-month-old
child is presented, and the symptomatology, etiology and possible mechanisms of pink
disease (erythredema polyneuropathy) are discussed. After all other possibilities (including
the child‘s playthings) had been ruled out, it was concluded that inorganic mercury had
been absorbed from a 2% ammoniated mercury ointment (2 ounces used over 2 periods
of 7-10 days with a 1-month interval) prescribed for seborreic dermatitis. A 24-hour urine
specimen was found to contain 40 ,ug. of mercury (60 ,ug./ 100 ml.). After 6 weeks’ treat-
ment with 750 mg. of penicillamine daily, the patient was fully recovered clinically. The
mechanism by which mercury produces the clinical picture of pink disease remains ob-
scure. Mercury is taken up especially by the kidney, has a marked diuretic effect, acts as
a general protoplasmic poison by combining with the sulfhydryl groups of proteins, and at
low concentrations can inhibit many enzyme systems. Potentiation of catecholamine activ-
ity, especially of the effects of a normal circulating blood catecholamine level, seem a
plausible explanation of many of the symptoms. The diuretic action may be an important
factor. Since many enzymes are sulfhydryl—dependent, it is unlikely that the varied symp-
toms of pink disease could be explained on the basis of a single inhibitory action of mer-
cury.

76. Lead poisoning from eye cosmetic—Warley M.A., Blackledge P. and O’Gorman P.,
Brook Gen. Hosp, London—BRIT. MED. J. 1968, l (117)

The authors report lead poisoning in 3 members of an Indian family resident in England;
1 adult and 2 children were involved; the interesting feature of the case was the difficulty
with which the source of lead was identified. Investigation of paintwork, water supply,
cooking utensils, food etc, were negative. It was eventually found that the 3 affected people
all used a mascara-like substance applied to eyelids and conjunctivae, for cosmetic or
‘health’ reasons. This powder contained 80% lead sulphide. Treatment has been successful
in deleading these patients, though the child whose admission with lead encephalopathy
sparked off the investigation was gravely ill and the prognosis for his mental develop-
ment is uncertain. Use of powders originating from India and Pakistan for the above pur-
poses is not rare and the implications are serious. Some Indians and Pakistanis resident in
England use a home-made carbon paste instead.

77. An outbreak of lead poisoning~Fernandes M.T., London Borough of Redbridge, Lon-
don—MED. OFFR 1969, 122/6 (88)

28

In this outbreak of lead poisoning there were 4 people at risk: the father, the mother, and
2 sons aged 41/2 and 11/2 years. Another son, aged 3‘/2 years, had already been admitted
to hospital with a suspected case of gastroenteritis. After further examination it was con-
firmed and proved to be a case of severe lead poisoning with lead encephalopathy. The
boy was seriously ill, lying in a coma, and X-rays of the abdomen showed a heavy opaque
shadow presumably due to the heavy lead content. 0n notification steps were taken
to investigate the whole family, as well as to take other preventive measures in the borough.
Lead estimations of the 2 other children showed lead contents of 53 and 46 ug.%. whereas
that of the father and mother were within normal limits. Samples of paint revealed 3.2%

W/ W of lead, which was above the permissible limit of lead, the normal being 1.6%.
Analysis of the plaster, putty, and water were normal for lead. The 2 children were ad-
mitted to hospital, being at risk, for further treatment. The original case (the boy of 31/,
years) improved more slowly and was discharged 3' / 2 months after admission. Investiga-
tions revealed that a cosmetic was being used, called ‘Surma’. Analysis of this sample
showed it contained 88% lead sulphide. The sample was removed from the house and all
Indian grocers in the borough were approached and asked not to sell any more of this
eye cosmetic.

78. Pink disease—Feldman G.V. and Harris P.F., Duchess of York Hosp. for Babies,
Manchester (Feldman); Child. Hosp, Sheffield—BRIT. MED. J. 1966, I (977)

In letters to the editor 3 cases of pink disease are mentioned. In 2 cases mercurial oint-
ments were applied to a diaper rash. The third, a 21 months old boy, was referred to an
outpatient department on account of weight loss. On examination he looked as if he had
lost weight; he was pulling his hair out, and scratching his wrists and feet. His hands and
feet were unusually pink, and he was perspiring. There were no other abnormal physical
signs. The urine mercury was 56 ,ug./ 100 ml. The mother stated that she had been ad-
ministering teething powders intermittently since the age of 8 months. The powders were
Steedman’s, and they contained 26.7% of hydrargsubchlor.

79. Soil lead and pediatric lead poisoning in Charleston, S.C.—Fairly PS. and Gray III J .W.
—.I.S. CAR. MED. ASS. 1970. 66 (79-82)

bead levels of the soil of the peninsular city of Charleston, S.C. were very high. Although
the source of the soil lead has not been determined, city-wide fires, pesticides, automobile
exhausts and native lead have been eliminated as reasonable sources for the high soil lead
content. Pica is common among children under 6, and soil lead levels are sufficient to
cause chronic pediatric lead poisoning.'Furthermore, the yards of houses where pediatric
lead poisoning has occurred contain large amounts of lead, and most cases of pediatric
lead poisoning occur in an area of high soil lead values.

80. Pink disease - ten years after (The epilogue)—Dathan J.G. and Harvey C.C.—BRIT.
MED. J. 1965,1/5443(118l-1182)

The incidence and mortality rate of pink disease have fallen dramatically since teething
powders containing mercury were withdrawn from the market in 1954. In one pediatric
practice in South Yorkshire, England, an average of 9 new cases had been seen annually
during the period l94&1954, whereas only 4 cases have occurred since. The national death-
rate from pink disease shows a similar decline, from 57 in 1950 to 7 in I955, and to none in
1961 and 1962. A fatal case occurring in 1963 is described where out-of-date mercury—
containing teething powders, bought from a village shop in Oxfordshire, had been ad-
ministered. The divergent views on the causation of pink disease are discussed, and the

29

results of this survey interpreted as conclusive evidence that this disease is caused by the
ingestion of mercury.

81. The lead content of breast milk and its substitutes / Teneur en plomb du lait humain et
de ses produits de substitution—Noirfalise A., Heusghem C. and Legros J ., Lab. de Toxicol.,
Fae. de Méd., Univ. de Liege—ARCH. BELGES MED. SOC. 1967, 25/2 (73-79)

Seventy-six samples of breast milk were studied from women without manifestations of
lead poisoning, all of whom lived in the area of Liege. Also studied was the lead content
of 10 samples of milk substitutes, 25 samples of cow’s milk from the Liege area, and
10 samples of bottled cow‘s milk. The technical details of qualitative and quantitative
determination of lead are briefly described. Results showed that 96.05% of the samples of
breast milk contained less than 100 ,ug.% lead; 84.21% contained less than 50 ,ug.%; 2.63%
contained less than 10 Mg.% lead. The samples of powdered dry milk had a mean content
of 19.8 1 3.4 lug.% lead. When diluted, the mean lead content was reduced to 2.6 1 0.4 ,ug.%
lead. Cow’s milk collected in the dairy had a mean lead content of 8.2 d: 2.5 pg.%. In bottled
milk, the mean lead content was 13.6 :t 4.8 ,ug.%. A number of general data on the metab-
olism of lead are given. In a previous study the authors had found a mean value of 40-50
,ug.% lead in blood. There seems to be a certain parallel between the lead contents of blood
and those of breast milk. The possible metabolic disorders caused by the ingestion of lead
in breast milk have not yet been determined.

82. Lead poisoning: risks for pencil chewers?—Pichirallo J .—SCIENCE 1971, 173 (509-510)

In the 16th century graphite replaced metallic lead as the main ingredient in pencil points,
but the term lead pencil has persisted. Recent studies confirm, however, that this term is
perhaps not a misnomer. The paint covering most pencils contains lead. Though 1% lead
in paints is considered safe, the percentage in paints on pencils was found to be greater.
In a report of the Department of Health, Education, and Welfare’s Bureau of Community
Environmental Management the weight of lead in some wooden pencils ranged from
0.1146 to 1.037 mg. This amount is high enough to make them harmful for a pencil-
chewing child. Similar studies were done in New York City and in Washington, DC.
It was found that the paint on 51 of 138 pencils contained more than the approved 1%
level of lead. Leaded paints were detected in 17 different brands of pencils manufactured
by 6 different companies. The safety of the 1% level of lead is also disputed by some ex-
perts. In Washington DC. pencils painted yellow or green had a high lead content.
Samples of the large round pencils used in the primary grades in public schools also con-
tained excessive lead. In the US the responsibility for the removal of hazardous pencils
from the market rests with the Food and Drug Administration, but at the moment they
believe there is insufficient evidence to take any action.

83. Untaxed whiskey and fetal lead exposure—Palmisano P.A., Sneed RC. and Cassady 6.,
Dept. of Pharmacol, Univ. of Alabama Med. Cent., Birmingham, Ala—J. PEDIAT. 1969,
75/ 5 (869-871)

A lO—week-old infant with evidence of neurologic defects, intrauterine growth retardation,
and postnatal failure to thrive was studied for abnormal lead accumulation because of a
maternal history of long-term ingestion of untaxed whiskey. After challenge doses of
CaEDTA, the infant and the mother each excreted an abnormally large amount of lead
in the urine. These data provide suggestive evidence of transmission of lead transplacental-
1y. Because of the widespread ingestion of untaxed whiskey in the southeastern US, in-
trauterine lead exposure may be a cause of fetal and neonatal disease.

30

84. Epidemiological study of a disease in the Guatemalan Highlands believed to be encephal-
itis / Estudio epidemiologico de um enfermedad considerada como encefalitis en la region
de los altos de Guatemala—0rdénez J.V., Carrilo J.A., Miranda M. and Gale J.L., Dept.
de Microbiol, Fac. de Cienc. Méd., Univ. de San Carlos de Guatemala, Guatemala—30L.
OFIC. SANIT. PANAMER. 1966, 60/6 (510-519)

In 1965 an epidemiological study was made in an agricultural area of Guatemala to
establish the etiology of a disease affecting certain families. The involvement of the central
nervous system gave the impression that the disease was an encephalitis of undetermined
etiology. The persons afflicted were Indians living in the mountains and cultivating corn
and wheat. Except for small wooded areas, most of the land is cultivated; part of the crop
is sold and the remainder kept for food. The water they drink comes from mountain
springs, and there is no system of excreta or garbage disposal. Insects are not plentiful in
the area. During a 4—month period 45 cases occurred and of these 20 died. Only 12 families
were affected. Over 50% of the cases occurred among children under 10 years of age, and
75% among those under 20 years of age. There was no case among children under one
year of age. The death rates were similar for all age groups. The predominant symptoms
of the disease were: loss of the use of extremities; blindness; deafness; and loss of conscious-
ness. Among significant laboratory findings mention should be made of the absence of
changes in the spinal fluid and high levels of albumin (0.5-2 g. / liter) in the urine. It was
discovered that the solution with which the wheat used for sowing had been treated had
a high mercury content, and investigation showed that the families in which the disease
occurred had used part of this seeding wheat for food, despite the clear warning printed on
the wrapping. A toxicological examination of a mixture of organs taken from a dead
patient revealed the presence of 15 ug. of mercury. An examination of other samples of
post mortem material, as well as wheat seeds, was also positive for mercury. The con-
clusion reached was that the cause of the disease was mercury poisoning resulting from
the ingestion of wheat treated with that substance.

85. Pica and blood lead in psychotic children—Oliver BE. and O’Gorman G., Smith Hosp.,
Henley-on—Thames—DEVELOP. MED. CHILD NEUROL. 1966, 8 (704-707)

Of 40 children aged 3-13 years resident in a long-stay unit for severely disturbed and
psychotic children, 17 (43%) showed frequent pica and 9 (22%) occasional pica. Twenty-
three (58%) had blood lead levels of over 36 ,ug./ 100 ml. and the high blood lead levels
were associated with frequent pica except in 2 cases in which it was entirely absent. Two
patients with ‘intermediate’ lead levels also showed no pica. Of a total of 26 patients with
pica, blood lead levels within the normal range were found in 7 (2 with frequent pica
and 5 with occasional pica). Thus 26.9% showed no rise in blood lead above normal as
a result of the pica habit. It was not found possible to discover why 2 patients with frequent
pica had normal blood lead levels. Possibly there are causes other than pica for raised
blood lead levels. Possibly the 2 children with frequent pica fortuitously chose lead-free
objects. Some patients in whom pica was not observed may have indulged in it surrepti-
tiously or had had periods of pica which had ceased. The main sources of lead appear to
have been paint work, toys and rubbish, but children exhibiting pica chewed a wide
variety of materials. The authors suggest further lines of research, including the time-
factor between the onset of pica and the elevation of blood values and the effect of various
chelating agents. The planning of a lead-free environment could affect the planning of
long-stay care units for children.

86. Lead and the legislature - l97l—Oliver R.G.—CONN. MED. 1971, 35 (498-500)

31

In spite of the existing legislation designed to minimize the risk of lead poisoning the
danger still exists. The 1971 legislative package prepared by the Connecticut Governor's
Lead Task Force aimed at furthering the reinforcement of the existing laws and at attempt-
ing to attack the main source of lead poisoning in the interiors of dilapidated houses.
One Bill will require notification of the name and address of any person found to have
a level of blood lead equal to or greater than 0.04 mg./ 100 g. of blood or any other abnormal
body burden of lead. The local Director of Health will then be required to investigate
the source of the lead and report to the local building official who will, in turn, be re-
quired to take action to prevent further exposure. If necessary, this may include rehousing
of the family. Other Bills in the package are designed to secure adequate screening and
diagnostic facilities, to set up Citizens Advisory Committees and to create housing divi-
sions in the Circuit Courts. Specially assigned judges and prosecutors in these Circuit
Courts would have jurisdiction over matters relating to housing code violation and hous-
ing discrimination offenses.

87. Mercury poisoning——Swales J.D., Dept. of Med., Univ. of Manchester—NURSING
TIMES 1971, 47 (409-410)

The various sources of mercury poisoning are described. Besides the occupational hazards
of working with mercury and the problem of high concentrations of methyl mercury in
sea fish, the effect of mercury poisoning in children is discussed. Mercury poisoning in
children produces 2 diseases that were not uncommon in the post-war years: pink disease
and infantile renal tubular acidosis. Infants with pink disease show mysterious failure to
thrive, excessive sweating and dilated peripheral blood vessels, which give the flushed ap-
pearance. The child is also fretful- and irritable. In infantile renal tubular acidosis fail-
ure to thrive is associated with a failure to acidify the urine, resulting in acidosis. In 1954
the decline in the incidence of renal tubular acidosis was ascribed to the withdrawal of
mercury compounds of teething powders. Likewise the incidence of pink disease declined,
which seemed associated with the elimination of dusting powders containing calomel.

88. Lead poisoning from an unusual source—Srivastava RC. and Varadi 8., Dept. of
Haematol., Northern Gen. Hosp, SheffieldfiBRIT. MED. J. 1968, l (578)

Hemolytic anemia due almost certainly to lead poisoning was diagnosed in a 15 year old
girl. Both blood and bone marrow findings confirmed the clinical diagnosis, and urinary
lead was high. However the source of the lead was unidentifiable. It was then noticed
that the patient wore an unusual bright salmon-pink lipstick, which turned out to be
ointment which her grandmother used for skin blemishes and bunions; this proprietary
preparation, sold without prescription, had been used by the patient, who was a lip biter,
as lipsalve/ lipstick. It was calculated that she had ingested about 45 g. of elemental lead
in the course of her use of this ointment which contains 67% basic lead carbonate. The
ointment jar was labeled for outward use only but possibly this warning is insufficient.
The patient is now well both clinically and hematologically. Reference is made to an-
other cosmetic, surma, a mascara-like substance used by women from India, which has
also been responsible for lead poisoning and has proved to be a source which may be
missed in history-taking.

89. Short and long-term effects of acute poisoning—Done A., Univ. of Utah, Salt Lake
City, Utah—US PUBL. HLTl-I SERV. PUBL. NO. 1791 1968 (155-163)

Of the accidental poisonings each year about 500 occur in children 5 years or under. In
this group lead poisoning is the 3rd most common cause of death and it is the main cause

32

of mental retardation. Up to 10 severe cases of lead poisoning occur for each fatal case.
Data available relating brain damage to poisoning and use of drugs show that there is
mental deterioration. Inadequacy of the measuring techniques used may be the reason
for brain damage not being detected.

90. Lead poisoning in childhood: epidemiology, manifestations and prevention—Jacobziner
H.—CLIN. PEDIAT. 1966, 5 (277-286)

Lead poisoning in children is a major health problem in big cities. It is fatal in 15-20% of
uses and the encephalopathy leaves neurological and mental sequelae in over 25% of the
survivors. It used to be recognized only when there were clinical signs of CNS irritation,
and little was known of the subclinical cases. The toxic agent is usually house-paint con-
taining lead. Poisoning may arise from inhaling lead fumes, or by absorption through the
skin, but usually the lead is ingested, and pica is a valuable clue to the occurrence. In a
New York City study, over 30% of children with pica had lead poisoning (shown by a
blood-lead level over 0.06 mg./ 100 ml.). Symptoms may be absent but they may include
anorexia (18%), vomiting (9%), abdominal pain or constipation, hypochromic anemia,
encephalopathy (12%), stupor, lethargy or convulsions, and X~ray signs of increased den-
sity in the long bones (24%), or opacities representing lead flakes in the abdomen (2%).
Over half the deaths from lead poisoning are in 2-year-olds. The incidence is highest in
slum areas here the houses are dilapidated. Asymptomatic lead poisoning occurs all
through the year but lead encephalopathy is commoner in the summer, when stored
and ingested lead is more easily absorbed and distributed to the tissues because of greater
ultra-violet ray exposure, and the nerve cells are more susceptible to lead poisoning. It
is important for doctors to be on the alert for cases of lead poisoning. When such cases
are reported in New York, the home is inspected. The mother is questioned about pica
in children under 7 years, their urine is tested and possible sources of lead are investigated.
Landlords are required to comply with the health code in repainting. The most reliable
procedure for identifying lead intoxication in asymptomatic cases is to determine the
blood-lead level. This gives positive results in 37% of suspected cases, against 5.5% for
raised urinary coproporphyrin levels. Other possible diagnostic tests include lead excretion
after an intramuscular dose of sodium calcium EDTA, red fluorescence of the erythrocytes,
and pigmentation of the retina. Lead poisoning is preventable and strenuous efforts should
be made to eliminate it, including improvements in the physical environment and health
education to demonstrate the harmful effects of pica.

91. Mercury poisoning in infancy—Egan B. and McNicholl B., Reg. Hosp., Galway—BRIT.
MED. J. 1966, 1(1482)

The case is presented of an ll-month-old boy admitted to hospital with anorexia, ir-
ritability, weight loss and intermittent constipation. There was pyrexia, gingivitis and
cervical adenitis. In the following 5 weeks the clinical features of pink disease devel-
oped and a 10-day course of dimercaprol was given. It was thought that the child had
ingested ointment used for a facial rash. The ointment was tested and found to have a
high mercury content. Some improvement followed the course of dimercaprol but the
infant died in the 11th week of his hospital stay, following fulminating bronchopneumonia.
Organ and urine analysis then failed to demonstrate mercury; bone was not analyzed.

92. Mercury poisoning in infancy (correspondence)—Hunt G.M.—BRIT. MED. J. 1966,
1(1482)

33

A case is reported in which a breast-fed baby’s stools became pea green on the second day
of life. Her diarrhea improved when bottle-feeding was substituted but returned with
further breast-feeding. The mother developed an erythematous rash on her breasts and
the child a rash on chin, forehead and neck. The mother had been using lotio hydrargyri
perchloridi 1 : 2000 (in water) for cracked nipples and the amount used between the
second and tenth day from the baby’s birth contained about 100 mg. mercuric chloride.
Eleven days after discontinuing the lotion the mother’s urine contained only 13 mg. / 100
ml. of mercury and the baby’s 2 mg./ 100 ml. The baby at no time developed any signs
of pink disease.

93. Hair trace metal levels and environmental exposure—Hammer D.I., F inklea J. F ., Hen-
dricks R.H., Shy CM. and Horton R.J.M., Div. of Hlth Effects Res., Dept. of Hlth, Educ.
and Welf., Durham, N.C.—AMER. J. EPIDEMIOL. 1971, 93/2 (84-92)

Hair trace metal levels were related to environmental exposure in a study of fourth-grade
boys in cities representing exposure dose gradients for arsenic (As), cadmium (Cd), copper
(Cu), lead (Pb), and zinc (Zn). Hair samples were carefully and stringently washed before
analysis for As by spectrophotometry and for Cd, Cu, Pb, and Zn by atomic absorption
spectroscopy. Hair trace metal distributions for As, Cd, Cu, and Pb were positively skewed
while those for Zn were symmetrical. Means were in accord with exposure rankings for As,
Cd, and Pb but not for Cu and Zn. When grouped across a ranking gradient, differences
among the means for As, Cd, and Pb were statistically significant while those of Cu and
Zn were not. The present study minimized possible effects of age, sex, hair color, varying
hair length, and chemical treatments. Despite the problems of exogenous deposition,
endogenous absorption routes, and relationships of hair metal to body burden, mean hair
metals levels for As, Cd, and Pb accurately reflected community exposures.

94. Epidemiology of increased lead exposure among 954 one-five year old Hartford, Con-
necticut, children-1970—Hale M. and Lepow M.L., Univ. of Connecticut Sch. of Med.,
Hartford, Conn—CONN. MED. 1971, 35/8 (492-497)

In a survey of 954 small children for lead poisoning, 60 were found to have increased
urinary 6-aminolevulinie acid (ALA) levels. Nine received treatment for elevated lead levels.
Poor housing and pica characterized over half of the population surveyed. Children with
+ALA levels generally lived in poor housing, had a higher prevalence of pica and a higher
prevalence of pica for paint than the general population. Black children had a higher pre-
valence of +ALA tests, histories of pica, and histories of pica for paint than other ethnic
groups by their life-time exposure to poorer housing and its attendant hazards. Finally,
the survey team found extremely widespread sale and use of lead based paint, indicating
that the current state and local laws are ineffectual in restricting the use of this paint.

95. Pica and lead poisoning—Guinee V.F., Bur. of Lead Poisoning Control, New York
City Dept. of Hlth, New York, N.Y.~NUTR. REV. I971, 29/ 12 (267-269)

Lead poisoning is most prevalent among black children in older cities in the US. At least
100,000 children are affected and pica is an important factor in the cause. Paint put on 50
years ago remains toxic even though 20 new coats have been applied. In 3 or 4 months a
steady diet of 3 mg. of lead can raise the serum level significantly. In young children, the
habit of eating paper, paint and dirt seems to amount to the earliest addiction. The prob-
lem in New York is enormous so that house repair, venous blood screening and health
education were started in 1970. The ‘pica balloon’, a 30 second spot TV announcement,
has been broadcast hundreds of times on television in New York. Three per cent of the

34

children city-wide had lead levels in the serum of 60 ,ug. or higher. Substandard housing
is the main fault and eradication of this will solve the problem.

96. Controlling pica via an environmental-psychobehavioral strategy: with special reference
to lead poisoning—Woody R.H., Psychobehavioral Inst. for Hum. Resources, Grandville,
Mich.—J. SCH. HLTH 1971, 41 (548-549, 552-555)

Existing theories of pica, namely that pica is due to a nutritional deficit or a psycho-
sexual emotional conflict, have not been validated, and there is reason to believe that a
third etiological theory, aligned with behaviorism, might be equally justifiable. Treatment
of the pica child and especially children who have ingested significant amounts of lead-
based materials have been relatively ineffective. Moreover, certain elements of the crisis-
on'ented approach to the treatment, from the exaggerated effect of both parents and profes-
sionals to the physical rennovation of the child’s home environment (supposedly to elimin-
ate the possibility of further lead poisoning), could serve to reinforce the pica behavior
(particularly if the hypothesized psychosexual elements are present) and thus might actual-
ly be deleterious actions. It would appear that behavioral modification techniques have
been too long bypassed in the treatment of pica, and that the most appropriate treatment
would be an integrated environmental-psychobehavioral approach.

97. Absorption and excretion of lead in gasoline burns—Wood McD., Price W.R., Childers
D. and Cook F., Dept. of Surg., Maricopa County Gen. Hosp., Phoenix, Adz—AMER.
J. SURG. 1968, 116/5 (622-626)

Of 163 persons burned by flame, there was a greater mortality when injury was by gasoline
flames (29%) than by nongasoline flames (16%). Urinary lead and coproporphyrins were
measured in 18 persons thermally burned by gasoline. The levels were elevated above the
normal or safe limits in 14. Gasoline, with tetracthyllead and tetramethyllead, contains a
significant amount of lead. Absorption of lead is unlikely through the intestinal tract,
possibly through the respiratory tract from combustion products, but most probably
through the burned surface. Biopsy of the eschar indicated persistence of lead in the
burned surface. This is a possible continuing source of absorption long after the initial
exposure. In the treatment of gasoline burns it is suggested that, with the finding of lead
within the burn eschar initially and for many days after the burn occurred, early’removal
of the eschar would reduce the source of lead. The detriment of extensive debridement
must be weighed against the potential hazard of lead, and excision will require sound
clinical judgment. An increased lead excretion was observed when an increase in urinary
volume occurred. It would be logical to assume that maintaining an adequate urinary
output would provide improved lead excretion. Although acute lead absorption, poison-
ing, and encephalopathy are difficult to define, it is speculated that levels of lead higher
than normal in the tissues and in the urine of a burned person may contribute to the
morbidity and mortality.

98. Earthenware containers as a source of fatal lead poisoning. Case study and public-health
considerations—Klein M., Namer R., Harpur E. and Corbin R., Dept. of Fed, McGill Univ.,
Quebec—NEW ENGL. J. MED. 1970, 283/ 13(669-672)

Two young children suffered lead poisoning as a result of drinking juice stored in a modern
handmade earthenware jug. One of the children died. Subsequent testing of 264 contempo-
rary earthenware glaze surfaces revealed that 50% released sufficient lead to make them
unsafe for culinary use. Between 10 and 25% of the pieces tested would have been capable of
causing severe lead poisoning. Compounding of safe earthenware glazes is essential.

35

99. Mercury in the marine environment—Klein DH. and Goldberg E.D., Scripps Inst. of
Oceanography, La Jolla, Calif.—ENVIRONM. SCI. TECHNOL. 1970, 4/9 (765-768)

A survey of the literature in respect to the production, consumption, release and dispersion
of mercury shows that these factors are influenced not only by humans, but also by other
members of the biosphere. Mercury is concentrated more highly in marine organisms than
in seawater, thereby causing increasing levels with depth in the water column, a situation
also known for other elements involved in biological cycles. To extend the present know-
ledge about mercury in the marine environment a study was undertaken in which analyses
were carried out on the soft parts of 81 marine organisms, most of which were epibenthic
fauna, and on 16 samples of marine sediments collected at varying distances from a sewer
outfall. The following findings were recorded: Mercury levels in sea animals appear to be
500 or more times greater than those in comparable volumes of sea-water, assuming the
living organisms contain 90% water by weight. The differences within the same species were
the same as or greater than differences in content between different organisms. The mercury
level in the organisms near the sewer outfall were comparable to those far removed. How-
ever, near the outfall the mercury content of sediments was as much as 50-fold higher than
presumably uncontaminated sediments further away, thereby implying the human influence
on the marine environment. It is therefore concluded that industrial and agricultural
dispersion of mercury compounds involves organisms by their ingestion of compounds of
this element or of the element itself. Pollution studies involving mercury may benefit from
the identification of indicator organisms in diagnosing the human influence on the environ-
ment.

100. Maximum daily intake of lead without excessive body lead-burden in children—King
B.G., Bur. of Commun. Environm. Management, Publ. Hlth Serv., Cincinnati, O.—AMER.
.I. DIS. CHILD. 1971, 122 (337-340)

Three hundred micrograms of elemental lead is considered to be the maximum daily per-
missible intake (DPI) from all sources for children. As the average intake increases above
this value, the entire amount cannot be excreted and accumulation in the body begins.
This will increase progressively as long as undue ingestion continues. The DPI has been
established on the basis of levels of lead in the blood of nonexposed and exposed children
including those with frank lead poisoning; results of experimental lead ingestion by adults;
fecal lead output in children; initial biologic effects of increased lead intake; rates of in-
crease in lead in the blood of exposed children; and sequelae of lead poisoning. The aim
of the DPI is prevention of disease and preservation of health in children.

101. Pink disease—Jenner G.G.—N.Z. MED. J. 1966, 65/ 411 (802-803)

A case of pink disease in a baby of 38 weeks who presented with extreme crossness, poor
appetite and failure to gain weight is described. He had had eczema of the scalp for 2 months
which was being treated with an ointment containing 3% ammoniated mercury. He was
found to have a fine rash on his body with red, cold, peeling hands and feet and photopho-
bia. He responded slowly to general care.

102. Minamoto disease / Minamata—sjukan—Berglund F.—LAKARTIDN. 1967, 64/36
(3531-3539)

Between 1953 and 1960 a number of cases of poisoning with methyl mercury was observed
in the region of the Minamata Bay of Japan. It was found that the poisoning was caused by
consumption of fish and shellfish contaminated by chemical waste. All age groups, par-

36

ticularly children under 10 years, were affected. The Minamata disease gave rise to a variety
of CNS symptoms depending on the severity of the intoxication, which in the acute form
proved fatal within about 2 months. Autopsy showed the pathological changes to be local-
ized exclusively in the brain, particularly the cerebellum, but also the occipital and temporal
lobes. No specific changes were observed in the spinal marrow or peripheral nerves, and no
changes in the optic nerve or retina were observed even in cases with severe visual disturb-
ances. The mercury content of liver, kidney and brain were markedly elevated in these
patients, but considerably lower levels were observed in cases of intrauterine methyl mer-
cury poisoning. Cases of this nature had occurred even when the mother was only slightly
affected or symptom-free. High mercury content was demonstrated in the wash of the
Minamata Bay near the industrial outlet and, in experimental animals, shellfish from this
site gave rise to a symptomatology similar to that observed in humans. Data from animal
experiments have shown the similarity between the symptoms of experimental alkyl mer-
cury poisoning and the Minamata disease. Certain differences were observed however
between the clinical manifestations of this disease and those of 331 cases of alkyl mercury
poisoning observed in Iraq within the period 1956-1960, possibly because of a different body
distribution of the 2 mercury derivatives involved. The mercury content in fish from various
parts of Sweden has in some cases been found to be high. Since Sweden, like Japan, has
families with a seasonal daily consumption of fish, there could also be a certain minimal
risk of methyl mercury poisoning. Warning against consumption of fish with a mercury
content about 1 mg/kg., particularly by pregnant women and young children, has been
issued by the Swedish public health authorities.

103. The effects of heavy metals (other than mercury) on marine and estuarine organisms—
Bryan G.W., The Lab., Citadel Hill, Plymouth—PROC. ROY. SOC. LOND. l77/B
(389—410)

Heavy metals such as copper, zinc and lead are normal constituents of marine and estuarine
environments. When additional quantities are introduced from industrial wastes or sewage
they enter the biogeochemical cycle and, as a result of being potentially toxic, may interfere
with the ecology of a particular environment. In different marine organisms, the behavior
of heavy metals is described in terms of their absorption, storage, excretion and regulation
when different concentrations are available in the environment. At higher concentrations,
the detrimental effects of heavy metals become apparent and their different toxic effects and
factors affecting them are also described.

104. Lead concentrations in human tissues~—Barry RS]. and Mossman D.B., The Associated
Octel Co. Ltd., London—BRIT. J. IN DUSTR. MED. 1970, 27/4 (339-351)

A study of 69 subjects at post-mortem, 4 of whom had histories of occupational exposure
to lead, demonstrated a marked difference in the lead concentrations between bones and
soft tissues. The soft tissues of infants and young children contained low concentrations of
lead, varying from 0-01 ppm in muscle to 0-46 ppm in liver. By the end of the second decade
of life the concentrations of lead in most of the soft tissues showed values varying between
0-06 ppm in muscle and 1-35 ppm in liver and thereafter did not increase with advancing age.
The concentrations of lead in bone were considerably greater than those in the soft tissues,
being about 1 ppm in infants and young children and increasing to more than 40 ppm in
persons over the age of 50 years. Adult male bones contained more lead than adult females
by a ratio of 3 to 2, and in both sexes the long bone contained concentrations of lead two and
a half times that observed in the flat bone. No marked difference was noted in lead concen-
trations between the corresponding soft tissues of the 2 sexes. From the findings it appeared
that in adults the total body burden varied widely from subject to subject. Nearly 95% was

37

represented by the lead content in bone, of which more than 70% was in dense bone. A far
lower concentration of lead was found in the bones of children than in those of adults, but
there was less divergence in the lead concentrations in the soft tissues. The total lead
content in the soft tissues of the majority of the subjects investigated appeared to be rela-
tively stable and did not correlate with levels in bone. The 4 men with known occupational
exposure to lead had greater concentrations of lead in bone than those with no known
occupational exposure, but no difference was noted in the soft tissues between the 2 groups,
with the exception of the most heavily exposed subject in whom concentrations of lead in
the brain were over 4 ppm and in the aorta 28 ppm. Hair and nails were found to contain
relatively high concentrations of lead, approximately 20 ppm; some signifimnce may be
attached to this finding in a medico—legal context. The findings of this study would suggest
that the present intake of lead among the general population is no greater than in the past.

105. Copper, zinc, cadmium, and lead in human blood from 19 locations in the United States
—I(ubota J., Lazar V.A. and Losee F., Soil Conserv. Serv. and US Plant, Soil and Nutrit.
Lab., Agricult. Res. Serv., Ithaca, N.Y.—ARCH. ENVIRONM. HLTH 1968, 16/6 (788-793)

Copper, zinc, cadmium, and lead were determined in 243 blood samples of male residents
of 19 cities in the continental US. The mean copper and zinc concentrations of all samples
agreed closely with values reported by other investigators. The means among the 19
locations, however, differed by 3-fold in copper and 5-fold in zinc. The levels of cop-
per and zinc in blood in 17 locations were normally distributed about their means except in
2 locations. Unlike copper and zinc, the concentrations of cadmium and lead varied widely
among samples from a given location.

106. The hygienic evaluation of baby powders / Ocena higieniczna zasypek dla dzieci—
Krechniak A., Kat. iZakl. Hig. AM, Gdansk—PEDIAT. POL. 1969, 44/ 3 (325-328)

A hygienic evaluation of baby powders produced in Poland was made. The evaluation was
based on determination of the content of arsenic, copper, lead, starch, stearates and on
determination of the degree of dispersion. In all powders the test for stearates was negative,
starch was present in one powder only. The contents of arsenic, copper and lead were within
admissible limits. The determination of the degree of dispersion showed that the amount of
powder remaining on a normalized sieve did not exceed the accepted normal value.

107. Community aspects of lead intoxication in children—Charest S., Cohen G.J., Lourie
R.S. and Anderson D., Comprehensive Hlth Care Clin., Child. Hosp., Washington, DC.
CLIN. PROC. CHILD. HOSP. (WASH) 1969, 25 (308-319)

Cultural problems rather than malnutrition accounts for pica and also the risk of lead
poisoning. Discipline from the mother is bound to be inadequate in this respect. It is easy
in 3 months for a 30 lb. child to ingest a lethal amount of lead from paint flakes containing
lead. In addition to the blood, bone, brain and kidney toxicity, arrhythmias may result -
suggesting myocardial change. The arbitrary blood lead level of 60 ,ug./ 100 ml. is an indi-
cation for treatment at a lower level. A 24-hour urine level of 80 pg. is suspicious, and a 10-
fold increase after one dose of EDTA confirms this. X-rays may show opaque paint-chips in
the intestine and transverse lines of increased density in the ends of the long bones. Social
workers reinforce the prophylactic message: pica does not usually continue after the age of
5 years and when associated with lead poisoning, it is a man-made illness.

108. Chronic lead intoxication mimicking motor neuron disease—Campbell A.M.G. and
Williams E.R., Bristol United Hosps, Bristol—BRIT. MED. .I. 1968 (582)

38

The authors report that a survey of cases of motor neuron disease in Britain showed that
17% had a history of known contact with lead. The motor neuron system disease, however,
shows itself long after actual exposure to the lead. A woman who had handled lead 10
years previously presented with motor neuron weakness but improved considerably on
treatment with calcium versenate. The improvement had continued but she still shows
some motor disability. A severe case of motor neuron disturbance occurred in a farmer
who had been treated 25 years earlier for acute lead poisoning from contaminated cider,
and a clergyman developed the disease 10 years after painting his church with white lead.
The final cause of motor neuron disease remains unknown but genetic, viral, deficiency and
toxic factors may all play a part in disturbing enzyme function at a cellular level. An in-
vestigation is being made into the etiological factors in motor neuron disease.

109. Lead in mentally retarded chlldren—Bicknell J ., Clayton B.E. and Delves H.T., Queen
Mary’s Hosp. for Children, Carshalton, Surrey—J. MENT. DEFIC. RES. 1968, 12/4
(282-293)

From a population of hospitalized severely subnorrnal children in long-term care, 3 groups
were selected: (a) with pica, (b) physically handicapped without pica and (c) mobile chil-
dren without pica. Excessive ingestion of lead by approximately 70% of subjects in the
‘pica’ group was shown from a study of blood lead levels and the urinary lead excretion
in response to oral calcium EDTA. There was no evidence that moderately raised blood
lead levels had any relationship to the original cause of the mental retardation. Pita ap-
pears to be more common in the disturbed retarded child and may be both selective and
highly motivated even with a low mental age. The oral calcium EDTA-lead excretion test
with random specimens of urine appears to be safe and free from unpleasant side effects.
It may be a useful supplement to blood and urine lead levels when equivocal results have
been previously obtained.

110. Childhood lead poisoning: a major urban health problem—Christian J.R.—NEB.
MED. J. 1969, 54 (677-682)

A review of lead poisoning in children is presented, covering historical, experimental,
epidemiological, diagnostic and therapeutic aspects. It has been suggested that lead poison-
ing was a major factor in the degeneration, decay and fall of Rome. There are indications
that residents of the US are undergoing severe chronic lead insult. Excessive lead absorp-
tion in childhood has been suggested as the nephrotoxic agent which was responsible for
deaths from chronic nephritis in Queensland between 1870 and 1920. Experimental studies
have shown lead to cause neoplasia in the rat, severe renal damage in the rat deficient in
magnesium, and severe retinopathy and an interruption of the formation of osteoid and
collagenous matrices in the rabbit. Diagnostic signs, symptoms and laboratory evidence of
lead intoxication are listed. Epidemiological data collected by the Poison Control Center
of the Chicago Board of Health in 1959-1964 show 926 cases of lead intoxication (4% of the
total cases of accidental poisoning), 116 of them fatal (71% of the total mortality); pica
was responsible for 62% of the reported cases; the highest incidence was characteristically
higher during June-September; and the sex distribution was not significant. Observations
on the 582 children treated for lead poisoning in 1967-1968 showed no significant changes
in distribution compared to 1959-1964. The general plan for the management of children
with lead intoxication, which was successful during the past 3 years in Chicago, is outlined.
Each suspected patient is screened by urinary coproporphyrin and serum lead determina-
tions: serum lead levels above 50 ag.% are considered significant, but the patient may or
may not have symptoms. Evaluation of asymptomatic children includes complete history,
physical examination and laboratory studies: if serum lead, on respected determination, is

39

below 50 ,ug.% only follow-up is instituted, if it is 50-100 yg.%, treatment is probably
indicated, and if it is above 100 ug.%, treatment is definitely indicated. The 5-day therapy
includes administration of sodium calcium edetate or penicillamine; if the lst course of
edetate is ineffective, addition of dimercaprol may be indicated. Follow-up should in-
clude, in addition to a narrative description of clinical course, instructions to the parents
and repeated blood lead determinations, inspection for possible building-code violations.

1]]. Lead in drinking water—Crawford MD. and Morris J.N., MRC Soc. Med. Res. Unit,
London Sch. of Hyg. and Trop. Med., London—LANCET 1967, 2 (1087-1088)

Preliminary reports on 2 studies undertaken to investigate the association between mortality
from cardiovascular disease and softness of drinking water in Britain showed that there
was no indication of an important excess of any likely metal contamination in any of
the waters examined. Lead concentration was less than 0.1 ppm in all the samples except
in one from a hard-water town, which had 0.1-0.2 ppm. The nature of the piping was not
taken into account in these studies. Metal contamination from pipes at this level did not
seem to be significantly involved in the association between cardiovascular mortality and
softness of drinking water. It has, however, been suggested that the plumbosolvency may
still be a problem in Britain and that the lead content of water lying in pipes overnight or
longer might be dangerously high in some soft-water areas. A study was therefore under-
taken in which overnight water samples were collected from 5-6 inhabited houses with lead
piping in each of 18 large boroughs, 9 with soft and 9 with hard water, and analyzed for
lead. The findings of this study indicated that there still is a plumbosolvency problem in
Britain in water lying in contact with lead piping for some hours. The highest concentra-
tion of lead was in fact found in soft water, but lead value above the conventional safety
standard (0.1 ppm) were observed also in hard waters. The possible variation in the lead
content of tap water from house to house and from day to day should therefore be in-
vestigated and the facilities for the testing for plumbosolvency extended in some areas. Soft
acid waters are potentially more dangerous, but the study demonstrated that certain hard
waters may be plumbosolvent. The possible health implications of these findings should
therefore be the subject of further consideration.

Clinico—pathological studies

112. A case of acute iron poisoning. Case report and contribution to the therapy of acute
iron poisoning with the iron chelator deieroxamine B / Ein Fall von akuter Eisenvergiftung.
Zugleicb ein Beitrag zrn Tberapie der alruten Eisenvergiftung mit dem Eisen-Komplexbildner
Desferrioxamin B.—Scherzinger F., Harrisburg Hosp., Harrisburg, Pa.—MSCHR. KIN-
DERHEILK. 1966, 114/ 12(596-597)

A l6-month-old girl ingested approximately 50 tablets of a commercial iron preparation
containing 39 mg. per tablet of elemental iron. Initial examination revealed no remarkable
findings. Vomiting was induced by syrup of ipecac. Subsequent gastric lavage produced
only small fragments of tablets. Shortly afterward the child became confused and apathetic.
Several thin tarry stools were passed. Serum iron values were 375’}%. An intravenous drip
with 5% glucose and I/,N saline was started. Deferoxamine 5000 mg. was given by
gastric tube. Every 4 hours 500 mg. of the same drug was administered injected intra-
muscularly. Within 12 hours the cardiocirculatory collapse improved to the point that the
child was able to ingest liquid food. On the fourth hospital day the patient was discharged
in normal clinical conditions. The clinical picture of acute iron poisoning is discussed. The
main features are vomiting, diarrhea with tarry stools and ensuing hypovolemic shock.
Confusion is an early symptom and may be followed by unconsciousness. Convulsions
have been observed. Serum iron levels are closely linked to the severity of the clinical con-
dition. Deferoxamine is the drug of choice. One gram is mpable of binding 85 mg. of iron.
Immediate administration of 8000 mg. should be given orally, followed by 2000 mg. by
intramuscular or intravenous injection. Subsequent doses depend on the clinical condition
of the patient.

113. Pink disease in Eastern Anatolia. A study of 15 cases of chronic mercury poisoning—
Aksungur L. and Ozcan N., Dept. of Dermatol., Ataturk Univ. Med. Sch., Erzurum—
TURK. J. PEDIAT. 1969, 11/1 (18-27)

Twenty patients were examined who became ill from eating wheat seed which had been
treated by fungicides containing mercury. Fifteen showed the presence of mercury in their
urine. They were selected for a more complete study and were divided into 3 groups ac-
cording to their symptoms. The symptoms and their implications for each group were
discussed. It is believed that the symptoms of mercury poisoning depend upon the amount
of mercury in the tissues, the age and the constitution of the individual. It was also found
that acrodynia may occur in persons aged up to 18 years, and that hypertension is not
commonly seen in this disease. One must be alert to the possibility of chronic mercury
poisoning in Turkey, especially in areas where the population is forced to eat wheat seed
because of a shortage of flour during the winter.

114. Embryopathy induced by aminopterin, kwashiorkor, ill treated child, congenital lis-
teriosis and lead poisoning, leptospiral jaundice / Embryopatbie de l'aminoptérine, Irwas-
hiorlror, enfant maltraité, listériose congénitale et satumisme, maladie de Wail—Gautier
E., Serv. de Péd., Hép. Cant. Univ., Lausanne—SCHWEIZ. MED. WSCHR. 1969, 99
(33-40)

41

Among the unusual clinical pictures presented in the paper there is an interesting case
concerning a child with congenital listeriosis which subsequently developed chronic plumb-
ism. At birth, the child exhibited symptoms of congenital listeriosis. This diagnosis was
corroborated by laboratory studies. Treatment with antibiotics and sulfonamides had a
beneficial effect on the general physical condition but subsequently there developed marked
psychomotor retardation. At the age of 43/, years the child was hospitalized because of
pain and swelling of several joints. Neurological examination was unremarkable, except
psychomotor retardation and impairment of hearing. The EEG was normal. X-ray exami-
nation showed an abnormal density of the epiphyseal lines. Hemoglobin was 9.6 g.%.
Obstinate constipation was present and flat films of the abdomen showed radiopaque
metal fragments. These features should have raised the suspicion of plumbism. At the age
of 51/2 years the child was again admitted to hospital with fever, arthritis in the lower
limbs, anorexia and constipation. The density of the epiphyseal lines and the number of
metal fragments in the bowel had considerably increased. Then the diagnosis of plumbism
was entertained. On close questioning the parents stated that the child used to play with lead
fragments in the workshop of his father and to mouth them. The family did not stop this
habit as they were not conversant with the hazards involved. Additional examinations
showed a moderate elevation of blood lead. Spinal fluid pressure was normal. No stippled
basophil erythrocytes were found but belated search for these cells in the blood smears
taken 9 months previously gave a positive result. Urinary lead levels were increased only
in one sample. The remaining lead fragments were evacuated and a combined treatment
with EDTA and dimercaprol was instituted. Side effects consisted of fever, vomiting and
hypertension. After three cycles the blood lead levels returned to normal and there was
considerable improvement in the general physical condition of the child. Measures were
taken to avoid further exposure to lead.

115. A case of mercury poisoning: acrodynia in a child of 8—Alexander J .F . and Rosario R.,
Dept. of Gen. Pract., Regina Gen. Hosp., Regina—CANAD. MED. ASS. J. 1971, 104/10
(929-930)

A case of mercury poisoning in a girl of 8 years is described. She presented with a 4 weeks‘
history of irritability, sweating, generalized pains and an erythematous rash which had
faded but was followed by an itchy vesicular eruption of the hands and feet. On admission
she was very distressed, assumed the fetal position with limbs rigidly flexed and sweated
profusely although her temperature was normal. Photophobia was not marked. Her serum
and urine mercury levels were found to be raised. She responded rapidly to treatment with
intramuscular dimercaprol. Her mother, father and 5 sisters were all found to have raised
urinary mercury excretion but none of them showed symptoms of mercury poisoning. The
source of the mercury was found to be a can of mercury taken home from school by one
of the children of the family with which all the children had played daily.

116. The pathological picture of acrodynia / Zum Krankheitsbild der Akrodynie (Syndrom
von Feer)—Sch6ne D., Wasser St. and Polster H., Kinderklin., Karl-Marx-Univ., Leipzig—-
KINDERARZTL. PRAX. 1970, 38/ 9 (390-397)

A variety of symptoms characterizes acrodynia. The disease is now rare and the diagnosis
can be made only if the clinical picture is beyond doubt. The etiopathology, management
and prognosis are discussed. A girl, aged 7, is described in whom acrodynia was compli-
cated by rectal prolapse, attacks of apnea, extensive trophic disturbances (ulcerations,
spontaneous fractures) and secondary infective lesions. Mercury from a defective dental
filling was considered to have been the causative agent.

42

117. Damage from chronic mercury poisoning. A new variety / Uber cine bisher nicht be-
achtete Miiglichkeit chronischer Quecksilberschiiden—Giideke R., Univ.~Kinderklin., Frei-
burg i. Br.—ARCH. KINDERHEILK. 1966, 174/2 (107-1 1 1)

Chronic mercury intoxication in an 11 year old girl is reported. A striking 10ml alopecia
of the eyelashes and eyebrows was one of the main symptoms. The mercury originated
from wooden masts serving as holders of electrical lines and drenched in sublimate. This
child played among such masts. The wood was also used as heating material in her home.

118. Lead poisoning in children / Intossicazione dn piombo nel bambino—Gelli G., Div.
Ped., Osp. Civ., La Spezia—MINERVA PEDIAT. 1967, 19/33 (1570-1573)

A case of lead poisoning is described in a 2' /2 year old girl who absorbed the poison
through her lungs. The symptoms were not very severe and were partly revealed by an
upper respiratory infection. The results obtained in this case combined the therapeutic
effectiveness of not very large doses of EDTA and of the accessory use of prednisolone.
A survey of the literature is presented.

119. Lead poisoning from home remedies—McNiel J .R. and Reinhard M.C., Dept. of Fed,
Arabian Amer. Oil Co.,' Ras Tanura—CLIN. PEDIAT. 1967, 6/3 (150456)

Ten cases of lead poisoning in children with lead-containing home remedies are reported
from the hospital of an oil company in Saudi Arabia and 5 of the most instructive case
histories are presented. In each case the source of lead was identified as a home remedy
with a content of 90-98% of lead oxide. Since lead contaminated remedies may be used as
treatment for other illnesses, the symptoms of these may obscure the diagnosis of lead
poisoning. It is therefore advised that all children with unexplained convulsions should
undergo a spinal fluid examination. In lead poisoning with encephalopathy spinal fluid
protein as well as fluid pressure are usually elevated. The cell count is generally below
20 white cells per cu.mm with a predominance of lymphocytes, but may be higher and
have more polymorphonuclear cells. Since viral meningoencephalitis presents similar find-
ings, the possibility of lead encephalopathy should be ruled out in children with suspected
viral encephalitis. Specific changes in blood, urine and long bones are observed in cases of
lead poisoning. When available, blood lead level determinations are especially valuable.
The current therapeutic recommendations are outlined as follows: Initially dimercaprol
only in a dose of 4 mg / kg. body weight intramuscularly, followed after 4 hours and sub-
sequently every 4 hours for 5 days by a combination of dimercaprol and CaEDTA given
intramuscularly at different sites in the following doses: dimercaprol 4 mg./kg. body
weight/dose and CaEdTA 12.5 mg. / kg. body weight/ dose. For a newborn the dose of
CaEDTA may be reduced to 10 mg. /kg. body weight. In some cases it may be advan-
tageous simultaneously to clear the bowel of lead with saline enemas.

1211. Lead poisoning in childhood in Ceylon—Miranda EB. and Gomez M., Lady Ridge-
way Child’s Hosp., Colombo—ARCH. DIS. CHILDH. 1967, 42/226 (579-582)

A series of 12 cases of lead poisoning in children in Colombo is reported. In addition to
the sources of lead which are generally recognized, in 6 cases the source was traced to the
fact that the children were living in premises where small—scale gold recovery from jew-
eller’s wastes was carried out. Inhalation of lead-containing fumes was a feature in many
of the cases.

43

121. Lead encephalopathy in children. Uncommon clinical aspects—Mirando E.H. and Ra-
nasinghe L., Lady Ridgeway Hosp. for Children, Colombo—MED. J. AUST. 1970, 57 (ID/21
(966—968)

Three cases of lead encephalopathy (from a series of 24) are reported in order to draw
attention to the unusual features: acute communicating hydrocephalus, tremors and
visual failure. Views on the pathogenesis of hydrocephalus in lead poisoning are discussed.
Emphasis is laid on the need for recognizing the uncommon manifestations for early
diagnosis of childhood plumbism.

122. Erythrocyte hypoplasia due to lead poisoning. A devastating, yet curable disease—Moo-
sa A. and Harris F., Dept. of Child Hlth, Univ. of Sheffield—CLIN. PEDIAT. 1969, 8/7
(400—402)

Heavy-metal intoxication in children still occurs as illustrated by the case history of a 3-
year-old boy who was admitted with an unusually severe anemia. The diagnosis of lead
poisoning suggested by pallor and abdominal pain was confirmed by both increased blood
lead levels and the increased urinary lead excretion following a CaEDTA diagnostic test.
The absence in this case of diagnostic criteria such as basophilic stippling, ‘lead lines' on
X-rays of long bones and coproporphyrinuria has also been reported elsewhere. However,
the unusual and significant feature of this patient was his severe anemia and erythrocyte
hypoplasia of the bone marrow, which differed from the usual description in standard
textbooks. This finding may have been the result of a nonregenerative phase following
hemolysis and both anomalies due to the toxic agent. The absence of basophilic stippling
may have been due to erythrocyte hypoplasia. Since it has been suggested that stippled cells
are reticulocytes in which basophilic material is altered by lead, the presence of stippled
cells may be a measure of erythroid regeneration. In the patient in question, stippled cells
were only observed after therapy with CaEDTA when marrow regeneration had occurred.
Erythrocyte hypoplasia is a serious condition in childhood with poor prognosis and the
possibility of lead intoxication should therefore always be considered in the differential
diagnosis of cases of this nature. Blood lead level determination will establish the diagnosis
and adequate treatment with chelating agents usually resolves the erythrocyte hypoplasia
of the bone marrow.

123. Lead hazard in artisans and their families with the description of chronic lead poisoning
in a child / Narazenie na dzialanie olowiu rzemieslnikdw i ich rodzin z opisem przewleklej
olowicy u dziecka—Salwa S. and wojcik T., Wojewodzk. Spec. Szpit. Dziec., Kieleach—
MED. PRACY 1966, 17/ 1 (57—63)

A case of chronic lead poisoning is described in a child whose family had a pottery work-
shop in the home. Symptoms of lead poisoning were also found in the parents. The authors
determined the number of erythrocytes with basophilous granulations, as well as copro-
porphyrin and lead levels in the urine of 13 other persons employed in making earthen-
ware. As the examinations gave evidence of the considerable occupational hazard in home
production of pots, sanitary supervision and medical protection of all pottery workshops,
as well as the family members is considered a necessity. Glazes containing boron com-
pounds are recommended as a substitute for lead glazes.

124. Chronic encephalopathy in lead poisoning / L’encefalopatie cronica da piombo—Ro-
mm C., Tortorolo G., Grossi-Bianchi ML. and Verde 1., Clin. Ped. ‘G. Gaslini', Univ. di
Genova—MINERVA PEDIAT. 1966, 18/8 (416-425)

44

The aim of this paper is to show that lead poisoning in children produces a chronic disorder
characterized by regression and mental retardation rather than acute hypertensive encephal-
opathy. In 1960, White and Fowler in the US described 2 cases with psychomotor distur-
bances and severe behavioral disorders. The present authors suggest that a new syndrome
can be described on the basis of these 2 cases and a third that they have themselves observed,
comprising aphasia, peculiar character changes, and psychomotor regression. The boy was
first seen at the age of 15 months for ‘toxic symptoms’ (dyspepsia and urticaria) which
the mother attributed to eating paint. At 18 months he was again seen with similar symp-
toms, and at 2 years 11 months, the mother reported regression in his psychomotor devel—
opment, disturbances in his character and behavior, and temper tantrums. In the previous
fortnight he had vomited, with slight fever, loss of appetite, abdominal pain and enuresis;
he had also had attacks of falling or throwing himself on the ground. The child made
neurological examination difficult. He was given a detailed physiological examination and
was tested for general mental and speech development. The tests showed sensory aphasia
with severe amnesia. His spontaneous speech was a year behind the average. His IQ was 74.
The boy’s mental deficiency was ascribed to encephalopathy of an unspecified nature, but
X-rays of the joints demonstrated signs of lead poisoning. There was no sign of acute
hypertensive encephalopathy and chelators led to a striking improvement, with a rise in
his IQ to within normal limits. In this case there was no microcytic anemia or glycosuria
with a normal blood-sugar, which are the usual diagnostic criteria of lead encephalopathy.
The diagnosis was based on the history, the transverse bands of metaphysial bone thicken-
ing in the X-rays, the high blood-lead level, and the above-average urinary coproporphyrin.
The diagnosis was confirmed by the success of treatment with the chelators, calcium-EDTA
or sodium-EDTA, given intravenously every 2 hours for 4 days, with 4 days’ interval be-
tween courses. In a case where chelators were not given, progress was much slower.

125. Aphasla and dementia in childhood chronic lead encephalopathy: a curable form of
acquired mental impairment—Romano C. and Grossi-Bianchi M.L., Dept. of Ped., Univ. of
Genoa—PANMINERVA MED. 1968, 10(448-450)

A 3-year-old child with chronic lead encephalopathy presenting as mental deficiency
and speech delay is discussed. A diagnosis of lead poisoning was made on a history of
exposure, recurrent gastroenteritis and skin eruptions, and confirmed radiologically and
by estimations of_ blood lead, urinary coproporphyrins, and the EDTA test. There was
neither basophilic stippling nor lead line. There had been language delay, recent mental
deterioration, and behavior changes. Neurological examination was normal; there were
slight abnormalities in the EEG with irregular slowing and spiking in temporal areas.
Psychometric examination gave a diagnosis of aphasia, mainly receptive, and dementia.
EDTA treatment was begun, 4 courses being given. Subsequent examination showed re-
sumption of mental development with diminution of aphasia and behavior disorders.
EEG returned to normal. By 1 year after treatment, IQ, language and behavior were all
within normal limits. The sparse literature on chronic lead encephalopathy without signs
of increased intracranial pressure and with essentially psychological symptoms is reviewed.
The importance of recognition of the syndrome emphasized.

126. Uncommon differential diagnoses from suspected tuberculous spondylitis in early child-
hood / Seltene Diffential diagnosen zum Spondylitis-tbc.-Verdacht im Kleinkindesalter—
Tietz H., Orthop. Abt., Univ. Kinderklin., Greifswald—Z. ORTHOP. 1966, 101 (514—517)

Two cases are reported where the suspected diagnosis of spondylitis tuberculosa seemed
to be confirmed. During the course of observation the 14 month old girl was found to have
an intramedullar tumor (oligodendroglioma-spongioblastoma). The second case, a 2'/2
year old boy, was found to have Feer’s disease (infantile encephalopathy), induced by

45

mercury intoxication. In both children, the immediate ‘classical’ therapy of spondylitis,
Le. rest in a long cast-bed, positively influenced the algesic symptoms. According to the
basic disease, the girl with the inoperable glioma died after 16 months (from the manifes-
tations of the first symptoms), while the boy with Feer's disease was cured within 6 months.

127. Encephalopathy in chronic lead poisoning (Greek)——Anastassea-Vlachou P., Benetou S.
and Mandalenaki-Asfi E.—DELT. PAIDET. KLIN. PANEP. ATHIN. 1968, 15/3 (250—267)

Encephalopathy due to chronic lead poisoning is described in a 9 month old girl. A short
review of the pertinent literature is given.

128. Lead poisoning in children—Bapat V.R.—HARPER HOSP. BULL. 1968, 26/ 1 (34-39)

This paper reviews the cause, diagnosis, and treatment of lead poisoning, and includes an
illustrative case report. Early diagnosis is necessary in order to lessen danger of mental
defect or death. Most frequent clues to this malady are stippling of the erythrocytes and
hypochromic microcytic anemia. Blood lead levels range from 0.04 to 0.06 mg.%. Removal
of lead from soft tissues may be effected by treatment with Ca-EDTA. Paraldehyde is use-
ful for convulsions, with sodium amytal reserved for intractable cases.

129. Neurological symptomatology in cases of chronic mercury poisoning in children /
Symptomatologia neurologiczm w przypadkach przewleklego zatrucia rtecia u dzieci—
Gosciriska Z., Bartoszewicz B. and Piasecka M., Inst. Ped., II Klin. Choréb Dzieci, Kra-
kéw-Prokocim—PEDIAT. POL. 1967, 42/ 3 (297-303)

Three cases of chronic poisoning with mercury compounds in children with predominating
neurological symptoms are described. In a 4l/z-year-old boy signs of cerebral and cere-
bellar cortical damage (typical for Minamata's disease) were observed after poisoning with
a fungicide used in agriculture called Fungitoks. In a girl aged 21/2, in whom a mercury
skin ointment was used for a long time, acrodynia was diagnosed together with poly-
radiculoneuritis with cell-protein divergence in the cerebrospinal fluid. In a 3' / 2-year-old
girl there were slight skin changes and severe neurological changes; tremor, muscle hypo-
tonia, lack of reflexes and mental disturbances. Only after giving dimercaprol was excess
mercury excretion in urine noted. The girl had previously used a mercury ointment and
had contact with Fungitoks.

130. Acute iron poisoning. Clinical and laboratory observations with deferoxamine—Ge-
virtz NR. and Rausen A.R., Dept. of Hematol, City Hosp. at Elmhurst, Mt Sinai Hosp.,
New York, N.Y.——J. MT SINAI HOSP. 1966, 53/ 1 (64-68)

A child with acute iron toxicity, due to the ingestion of 1.26 to 2.10 g. of iron as ferrous
sulfate, had a rapid and favorable response to deferoxamine therapy. The rapidity of the
response can be explained by deferoxamine’s high stability constant for iron, by the rapid
in vivo distribution of deferoxamine, and by low toxicity of iron which is bound to
deferoxamine. A method for the determination of the total iron in serum containing
deferoxamine is described.

131. Chronic lead poisoning in children: A review of 90 children diagnosed in Sydney, 1948~
1967. 2. Clinical featues and investigations—Freeman R., Dept. of Paed., Prince of Wales
Hosp., Sydney—MED. J. AUST. 1970, 1 (648-651)

46

The distribution of lead in the body and the disturbance in porphyrin metabolism in lead
intoxication are described. The clinical features of 90 children with chronic lead poisoning
diagnosed in Sydney between 1948 and 1967 are discovered. Early symptoms were vague
and mainly gastro-enterological or neurological. Anemia was frequent, but often absent
early on. Encephalopathy, the most serious result of chronic lead poisoning, occurred in
more than half of the children. It was often the mode of presentation, sometimes pre-
cipitated by an infection, but minor symptoms tended to precede encephalopathy for
months in some cases. The investigations of these children are described, and it was notable
that many of the accepted diagnostic tests gave negative results. The urinary lead excretion
was found to be more reliable than the blood lead level as a parameter of lead intoxication.
In a number of doubtful cases, the increased excretion of lead after administration of
calcium EDTA was valuable in establishing the diagnosis.

132. Acute, lethal poisoning after ingestion of metallic lead—Forsby N., Fristedt B. and
Kjellman 3., Dept. of Occupat. Med., Univ. Hosp., Lund—ACTA PAEDIAT. SCAND.
1967, Suppl. 177 (107)

A previously healthy 2-year-old girl was admitted to hospital with vomiting of 10 days’
duration. She had normal stools, normal temperature and no catarrhal symptoms. She
was pale and lethargic. The muscle tone was slightly increased and her neck stiff. She had
spontaneous vertical nystagmus and normal optic disks. Hemoglobin was 9.4 g./ 100 ml.
Stippling of the red cells was noted (299/ 10,000 counted cells). White cells were 15,600
cmm. with a normal distribution. Serum electrolytes and glucose were normal. There was
no albuminuria and urinary sediment was normal. Analyses of cerebrospinal fluid dis-
closed 0 red cells, 7 white cells, 73 mg./100 ml. protein and 83 mg./100 ml. glucose.
EEG showed a slow background activity, but no focal abnormalities. Inquiries about
medicines and poisons were negative. The girl died 24 hours after admission. At postmor-
tem examination a lead button with a diameter of 22 mm. was found lying free in the
stomach. The brain showed edema with signs of increased intracranial pressure and hemia-
tion. There were multiple subependymal petechial hemorrhages in the third ventricle.
Microscopic examination revealed tiny cortical micro-infarcts with disappearance of some
neurons and glial proliferation. The parenchymatous organs showed toxic changes. No
‘lead line’ was found in the gingivae. X-ray of the femur revealed no deposits in the
epiphyses. The following tissue concentrations of lead were found; brain: 0.69 mg. / 100 g.,
liver: 5.4 mg. / 100 g. and kidney: 3.0 mg. / 100 g. In relation to corresponding figures in the
literature these values are extremely high. The button was of a type used as curtain weights
in the girl’s home and still available in the ‘shops. Children can easily swallow them and
if caught in the gastrointestinal canal they can cause severe lead poisoning.

133. Acute basophil myelocytic leukemia with skin and bone signs resembling lead poisoning
in a young child / Leucémie aigué i basophlles avee signes cutanés associée in des signes
osseux évoquant un saturnisme chez un jeune enfant—Teillet F., Weisgerber C., Meyer B.
and Vialatte 1., Inst. de Rech. sur les Maladies du Sang, Hep. Saint-Louis, Paris—ANN.
PEDIAT. (PARIS) 1970, 17/ 8-9 (543-550)

The authors report the case of a 5 year old boy with acute myelocytic leukemia, prolifera-
tion and maturation of basophil polymorphs, the granules being present not only in the
latter but also in the eosinophil and neutrophil polymorphs. This leukemia is accompanied
by a skin rash resembling erythema multiforme and coinciding with the multiplication of
basophil cells. The course lasted 2 years without any of the various treatments causing a true
remission. The disease ended in acute undifferentiated leukemia with disappearance of the
skin signs. The probable relationship between the basophils and the skin lesions was diffi—

47

cult to prove. Finally the presence of skeletal abnormalities very different from the usual
bony lesions in leukemia but resembling lead poisoning suggested the chance association
of chronic lead poisoning.

134. Congenital and familial iron overload—Vitale L., Opitz J.M. and Shahidi N.T., Dept.
of Fed, Univ. of Wisconsin Med. Sch., Madison, Wisc.—NEW ENGL. J. MED. 1969, 280/
12 (642-645)

Two infants with hypotonia and minor congenital anomalies were found to have a striking
increase in the total body iron in the absence of any hemolysis or unusual iron intake. The in-
crease in iron was demonstrated histochemically and also by direct tissue iron determina-
tion. The absence of hemolysis and exogenous iron intake suggested a disturbance of
iron transfer in utero. The presence of iron overload in both infants with similar clinical
and pathological findings indicated that this condition is probably genetically determined.

135. The Children’s Hospital Medical Center, Boston, Mass.—Farber S. and Vawler G.F.——
J. PEDIAT. 1968, 68/ 3 (480-487)

A lS-month-old boy was admitted to hospital because of increasing weakness and a
morbilliform rash. He had episodes of sweating and examination showed proteinuria and
hematuria. Given prophylactic doses of oxytetracycline and a diet with added salt, he
improved slightly. Further improvement followed the administration of 0.6 g. Versene
intravenously for 3 days. When irritability, lethargy and hyporeflexia increased he was
given a second course of Versene but this failed to produce further improvement. On the
13th day he had a temperature of 102°F and signs of shock. In spite of salt administered
intravenously and 250 cc. whole blood, he died 9 hours later. The child presented a clear
symptomatological study of acrodynia (pink disease) with characteristic skin changes, al-
though erythema was absent. The morbilliform rash and autonomic nervous system in-
volvement found were typical. Excessive water loss made an important contribution to the
death. Renal changes of a salt-losing type were part of the picture. Urine examination on
the third day in hospital showed a mercury level of 334 g. / 1., suggesting mercury poisoning
but no source of mercury could be traced. In the course of discussion attention was called
to the similarity of the clinical picture in this case to adrenal overfunctioning of the medulla
and cortex. Comments were also made on possible sources of mercury, including oint-
ments, toys, teething powders, and water-based paints.

136. Neurologic sequelae of plumbism in children—Perlstein MA. and Attala R., Child’s
Neurol. Serv., Cook County Hosp, Chicago, Ill.—-CLIN. PEDIAT. 1966, 5/5 (292—298)

Among 425 children with plumbism, 39% had neurologic sequelae. Mental retardation and
recurrent seizures are most common and persist in approximately 1 out of 5 patients.
Cerebral palsy and optic atrophy occur less frequently and are limited to those who pre-
sent with either encephalopathic or ataxic syndromes. Cerebral palsy is usually of the
spastic hemiplegic type. A patient who developed dystonia musculorum deformans is
unique in the authors‘ experience. The younger the child and the more fulminating the on-
set, the greater the incidence of sequelae. In children presenting with severe encephalopathy,
sequelae persist in over 4 out of 5. In those who present with seizures without increased
intracranial pressure, sequelae occur in 2 out of 3. When ataxia is the only neurologic pre-
senting symptom, sequelae occur in 3 out of 5. In those in whom the presenting symptoms
are gastrointestinal, sequelae occur in less than 1 out of 3. When the onset is with a
fever only, or asymptomatic, the incidence of sequelae is 1 out of 5 to 10. The nature
and incidence of sequelae seem to be unrelated to the type of treatment employed.

48

{—

 

137. Aspects of lead absorption in hospitalised psychotic children—Oliver B.E., Chelrnsley
Hosp., Marston Green, Birmingham—J. MENT. DEFIC. RES. 1967, 11 (132-142)

This is a report of 2 years of observations on aspects of lead metabolism of children show-
ing psychotic features, in long term hospital care. The following observations were made.
Sunny and/ or warm and/ or dry weather appears to be associated with a rise in blood
lead. An attempt to reduce the amount of environmental lead produced an apparent
reduction in the incidence of raised blood lead, although there are considerable reserva-
tions to this observation. There was a general lowering of hemoglobin level in relation to
raised but still relatively low blood lead levels. Basophilic stippling was rare and lead lines
in gums and paresis were not observed. Those children prone to have raised blood leads
required about 3 to 4 months for their blood leads to rise 3040 ,ug./ 100 ml. after they had
been reduced by treatment. Penicillamine was effective in reducing blood lead in most
cases. Toxic effects on the kidney from the raised blood leads or penicillamine were not
observed. There was an overall reduction in the incidence of radiological evidence of lead
deposition within the period of the study. However, abdominal X—rays continued to show
evidence of ingestion of lead-containing substances.

138. Fine structural changes in human lead encephalopathy—Raimondi A.J., Beckman
F. and Evans J.P.—TRANS. AMER. NEUROL. ASS. 1966, 91 (322—323)

Biopsy specimens from white matter and gray matter were removed from 6 children suffer-
ing from proven lead encephalopathy. Their clinical status varied from status epilepticus to
deep coma with episodes of respiratory arrest. In the gray matter the most obvious changes
were in the neurons with distension of the lamellar components of the granular ergasto-
plasm. There were changes compatible with swelling in the glial elements. The capillary
endothelium of the gray matter showed the most obvious changes. The changes in the
capillary endothelium in the white matter were insignificant. The most prominent changes
in the white matter were in the extracellular space with extensive opening in correspondence
to the pericapillary area and the area intervening between glial cells, cell processes and
myelinated axons. There was swelling of the glial cells. The granular ergastoplasm disten-
sion was more obvious than that noted in the Golgi apparatus. Exhaustion phenomenon
of the nuclei of the glial cells was common. There was splitting and delamination at the
level of the intraperiod line within the myelin sheaths. The axonal changes consisted of
a loss of neurofrlaments and their replacement by diffuse granular looking material.

139. Lead poisoning from drinking soft water—Bacon A.P.C., Froome K., Gent A.E., Cooke
T.K. and Sowerby P.-—LANCET 1967, 1 (264-266)

Three cases of lead poisoning are described, in one of which the diagnosis had been missed
for 12 years. In each instance the cause was long-term ingestion of soft water which had
eroded lead from the inside of lead pipes bringing water to their houses.

140. Acute iron poisoning: assessment of severity and prognosis—James J.A., Children’s
Div., Los Angeles County-Univ. of Southern California Med. Cent., Los Angeles, Calif.—
J. PEDIAT. 1970, 77/ I (118-119)

Sixty-six children with iron poisoning were studied. They were admitted to a pediatric in-
patient service from 1965 to 1968. Seven children did not develop symptoms. Eighteen pa-
tients were considered mildly poisoned with vomiting and l or 2 loose stools. Those with
vomiting and loose stools but without lethargy or shock were considered moderately
poisoned (12 patients); and those with symptoms of vomiting, diarrhea, and lethargy, with

49

or without shock, were considered severely poisoned (29 patients). Of 17 patients who were
believed to have ingested fewer than 10 tablets of ferrous sulphate only 3 were considered
severely poisoned; of 17 patients who had ingested 20 or more tablets all were symptomatic
and 15 were moderately or severely poisoned. Fifteen of 20 patients with admission serum
iron concentration in excess of 500 pg./ 100 ml. were considered moderately or severely
poisoned. Only 4 of 13 patients with concentrations below 300 ,ug./ 100 m1. showed a
definite poisoning. When the serum iron concentrations exceeded 500 [Ag/100 ml. a
leukocytosis of more than 15,000 cells / ml. was found in 11 of 16 instances. Blood glucose
concentrations were usually high. In a scout film of the abdomen radiopaque foreign
material in tablet or granular form was visualized in 16 (29%) of 56 patients. Although pre-
and post-gastric lavage films were not obtained, the impression was that lavage often
fails to remove particulate material completely from the stomach. There were no deaths
in this series. Thirty-eight children were treated with the intramuscular or intravenous
administration of deferoxamine, 2 critically ill children received the drug by nasogastric
tube and intravenously. No toxic effects of deferoxamine were noted.

141. Infantile renal tubular acidosis due to mercury poisoning—Husband P. and McKellar
W.J.D., Dept of Paed., Charing Cross Group of Hosps, London—ARCH. DIS. CHILDH.
1970, 45 (264-268)

A 9-month-old infant with renal tubular acidosis is reported. This illness followed the use
of ammoniated mercury ointment for a diaper rash. Raised levels of inorganic mercury
were found in the urine. The patient was treated with alkalis, dimercaprol, and penicill-
amine. After 5 months, all therapy was discontinued and she has remained well.

142. Electroencephalographic studies of Minamata disease in children—Harada Y., Miya-
moto Y., Nonaka I., Ohta S. and Ninomiya T.—DEVELOP. MED. CHILD NEUROL.
1968, 10(257-256)

The EEGs of 32 patients with Minamata disease, a neurological disorder due to poisoning
with organic mercury compounds, were examined in 1965 and 1966. Of the 19 congenital
cases, 7 showed normal E1365, 2 were borderline and 10 were abnormal (6 with epileptic
discharges); of the 13 acquired cases, in 4 the EEGs were normal, one was borderline and
8 were abnormal (one with epileptic discharges). Specific abnormal patterns in the back-
ground activity, with diffuse and slow wave dysrhythmia, appeared in 18 of the 32 cases
(56%). No focal abnormalities were seen. The findings suggested that diffuse brain damage
is present in Minamata disease.

143. Acute iron intoxication. A case treated by chelation—Whelan G., Fazic V. and Biggs
.I.C., Dept. of Med., St. Vincent’s Hosp., Sidney—AMER. J. MED. 1966, 41 (626628)

A description is given of a 2 year old child who ingested an ordinarily fatal dose of ferrous
sulfate (20 g.). The early oral and parenteral administration of deferoxamine undoubtedly
had a favorable influence on the ultimate outcome, which was early and complete recovery.

144. Ferrous sulphate poisoning (Russian)—Kleut, Jelié R., Sovljanski M., Sovljanski R. and
Obradovié D., Inst. for Mother and Child Hlth Care, Novi Sad—MED. PREGL. 1971,
24 (383-386)

Two cases of ferrous sulphate. poisoning are described: the one, a child of 21 months,
ended fatally; the other, a child of 20 months with pronounced indications of poisoning,
recovered successfully. In the first case the lethal dose was 466 mg./ kg. bodyweight while

50

H

 

in the second case the toxic effect was manifested even with only 66 mg. / kg. bodyweight.
The clinical, pathoanatomical, histological, chemical-toxicological and laboratory findings
show that ferrous sulphate poisoning involves a local reaction on the mucous membrane
of the stomach and the upper part of the small intestine as well as toxic damage to the liver,
the spleen, the brain and other parenchymatous organs during the reabsorption and com-
pounding of iron. Judging from the circumstances under which this poisoning occurred it
is worth pointing both to the large and more than lethal dose of poison in individual packets
of ferrous sulphate intended for use by adults, and also to the fact that parents are ill-
informed concerning its toxic effects.

145. Accidental ferrous sulfate poisoning in a 3-year-old child/ Uber eine akzidentelle Eisen-
sulfat-Vergiftung bei einem 3 Jahre alten Kind——Keller P. and Schneider V., Christophorus-
Kinderkrankenh., Berlin-Lichtenrade—MSCHR. KINDERHEILK. 1968, 116/8 (476-478)

A 3-year-old child was admitted to hospital because of acute abdominal manifestations,
dyspnea and marked abdominal distension. A plain radiogram revealed the signs of mas-
sive pneumoperitoneum with marked elevation of the diaphragm. A tentative diagnosis of
gastric perforation was made. The child died before an emergency operation could be
performed. Autopsy revealed a coin-sized perforation of the posterior gastric wall. The per—
foration was surrounded by grayish-brown exudate. Hemorrhagic inflammation was pres-
ent in the area of the perforation. The abdominal cavity contained 100 ml. of a grayish-
brown liquid. Histologic study of the liver showed punched-out nuclei in the liver cells
such as have been reported in several morbid conditions. The findings suggested the local
effect of a corrosive substance. Questioning of the parents revealed a possibility that the
child had swallowed a whitish substance present on the terminals of an automobile bat-
tery. This substance was shown to be anhydrous ferrous sulfate. Chemical study of the
contents of stomach and abdominal cavity revealed a quantity of 6.7 mg. ferrous sulfate.
This compound is a dangerous corrosive. The lethal dose for children is from 2 to 10 g. Ferrous
sulfate produces severe corrosive injury of the gastrointestinal tract and lesions of the nerv-
ous system and liver.

146. Acute iron intoxication. Case report - treatment—Katman EC. and Burke W.A.——
DELAWARE MED. J. 1967, 39 (317-320, 324)

A l9-month-old boy was admitted to hospital about 11/2-2 hours after ingesting an estimated
45-50 ferrous sulphate tablets. He had vomited and had become lethargic and tachypneic,
with diarrhea. On arrival at the hospital he was in a state of stupor. He was given intravenous
fluids and 5 g. of deferoxamine were placed in the stomach via nasogastric tube following
gastric lavage. Additional deferoxamine was given an hour later and 2 hours afterwards.
The urine was then deep red. By the following morning the child was more responsive but
his respiratory rate increased, with costal retractions and coarse rales becoming audible.
Ampicillin therapy was started and further deferoxamine was given, but deterioration con-
tinued and grand mal seizures occurred. An exchange blood transfusion was given which
was followed by remarkable clinical improvement with cessation of the convulsions. The
patient made a gradual uneventful recovery. After 8 weeks there had been no vomiting or
other signs of gastrointestinal obstruction and the hemoglobin had remained stable. There
was no evidence of pyloric stenosis or scarring elsewhere in the intestinal tract. The authors
make recommendations for the treatment of children with acute iron intoxication. As no
definite criteria have been established for determining before treatment whether circulatory
collapse or CNS depression will occur, they recommend that specific and supportive treat-
ment should be instituted without awaiting the results of serum iron level testing. Deferox-
amine has been found to be well tolerated and delay may be costly in terms of increased iron

51

absorption. After the induction of vomiting and the performance of gastric lavage, 4000-
8000 mg. of deferoxarnine should be instilled into the stomach and 2 g. of deferoxamine in
500 ml. dextrose solution given intravenously over 6 hours. If the urine turns reddish a sec-
ond course should be given using 1 g. in 250 ml. over 2-3 hours or 1/2 to l g. intramuscularly.
Acidosis and dehydration should be corrected and treatment given for shock. If renal
function is inadequate, exchange transfusion should be carried out. Serum iron level
should be determined before treatment and every 6 hours until it is below 200 mg. An upper
gastrointestinal series should'be carried out in 3 to 6 weeks (for pyloric stenosis).

147. Lead poisoning in a family of 18 members in Vellore Town—Joshua G.E., Ratnaike N.
and Benjamin V., Dept. of Child Hlth, Christian Med. C011,, Vellore—INDIAN J. MED.
RES. 1971, 59/9(l496—l507)

This paper reports chronic lead poisoning in all members of a family consisting of 9 adults
and 9 children. The source of poisoning was traced to lead fumes and lead oxide dust
emanating during the process of extraction of gold and silver from jewellers’ waste. In this
study the younger children, aged 3 years and less, were more severely affected than the older
members of the family. Children suffered from gastrointestinal disturbances, recurrent
respiratory infections and with encephalopathy in the advanced cases. Fatality was con-
fined to the younger age group. On the other hand, adults suffered chiefly from a general
intoxication with weakness, lassitude and asthenia. Gastrointestinal disturbances and neuro-
muscular symptoms were also prominent features. Urine was positive for coproporphyrin
intermittently in all members of the family. Blood lead levels in most members during qui-
escent periods ranged between 50 and 60 ,ug./ 100 ml. All members up to the age of 19 years,
showed radiological evidence of lead deposit in the bone. Interesting features in these were
generalized sclerosis of bone of varying density in the younger members of the family and
transient appearance of dense miliary shadows in the lungs of 2 children under 3 years of age.

148. Chronic lead poisoning: recurrent encephalopathy in a child—Joshua G.E., Dept. of
Paed., Christian Med. Coll., Vellore—INDIAN PEDIAT. 1969, 6/ 5 (329-337)

A case of chronic lead toxicity, resulting in recurrent encephalopathy in a child aged 14
months is reported from the town of Vellore in Madras State, South India. This is be-
lieved to be the first report in Indian medical literature on lead encephalopathy in chil-
dren. The parents of this child are engaged in gold and silver recovery process from jeweller’s
wastes. Inhalation of lead containing fumes and lead oxide laden dust was the main mode
of intoxication. Diagnosis was based on the evidence available in the patient’s history,
family history, father‘s occupation, clinical signs, laboratory evidence of anemia, increased
reticulocyte count, basophilic stippling, elevated urinary coproporphyrin and X-ray evi-
dence consistent with lead deposits in the bones. The findings of lead lines in the gums of
parent and elder sibling was further collaborative evidence. The diagnosis was continued
by identifying the source of lead. Generalized sclerosis of all the bones and the transient
appearance of dense miliary shadows in lung were the 2 interesting, unusual features of
the case. It is important to bear in mind that undetected lead toxicity may be an etiological
factor in some cases of mental deficiency in Indian children.

149. Aerodynia treated with d-penieillamine—Javett SN. and Kaplan 13., Transvaal Mem.
Hosp. for Children, Johannesburg—AMER. J. DIS. CHILD. 1968, 115/ 1 (71-73)

A case of acrodynia in an 8 month old girl treated with d-penicillamine is described. The
dosage was 150 mg. 3 times daily for 2 weeks. Clinical improvement was prompt and
marked. Over a 3 week period, the patient’s urinary excretion of mercury decreased from
1100 ,ug./l. to nil.

52

150. Selective pica and lead poisoning in a severely subnormal child—Bicknell J., Queen
Mary’s Hosp. for Children, Carshalton—J. MENT. DEFIC. RES. 1967, 11/4 (278-28l)

A mentally subnormal child with a behavior disturbance who developed pica for wood
is described. He showed persistently raised blood lead levels which failed to respond to
repeated courses of penicillamine. During this period, no signs of mental deterioration or
neurological abnormalities were found.

151. Hyperprolinuria and lead inloxication——Kushnick T., Bilenker KM. and Sadaty M.,
Dept. of Fed, New Jersey Coll. of Med. and Dent., Jersey City, N.J.—J. MED. SOC.
NEW JERSEY 1967, 64 (262-263)

A study was carried out to determine if there is any relationship between the findings of
hyperprolinuria and lead lines in the bones in patients with lead intoxication. Of 16
patients with diagnosed lead poisoning, 9 were found to have hyperaminoaciduria and
hyperprolinuria. Five of these had definite lead-lines and 2 had questionable lead lines;
2 had no X—ray findings of lead intoxication. Five additional patients had lead lines but
4 of these had no hyperaminoaciduria or hyperprolinuria. One patient had only hyper-
aminoaciduria. Two other patients with lead intoxication had no lead lines and only one
had increased urinary amino acids without hyperprolinuria. In lead poisoning the lead
lines are considered to represent growth retardation due to various factors including in-
hibition of osteoblastic building activity, inhibition of osteoclasts, and phosphate diuresis
due to renal tubular disease. It therefore seemed possible that one mechanism whereby
proline might appear in the urine would be its reduced utilization for the formation of
hydroxyproline which could then be used for collagen formation. Renal tubular poisoning
by lead could also contribute to proline excretion in the urine. The data obtained in this
study indicated no relationship between the presence of lead lines in the bones of patients
with lead intoxication and their excretion of proline and other amino acids in the urine.
Not all patients with lead poisoning and hyperaminoaciduria excrete proline and this
variance remains unexplained.

152. Chronic lead poisoning in children: a case report and review of the literature—Cohen
B.L., Harper D.L. and Neal W., Div. of Fed, Doctors Hosp., Columbus, 0—]. AMER.
OSTEOPATH. ASS. 1968, 67/ 10 (72-73, 82-84)

The rise in the number of cases of lead poisoning is a source of growing alarm in many
major metropolitan centers. However, plumbism is still a rarity in many large communities
and poses diagnostic problems. A case in a l9-month-old child is reported in which the
diagnosis was obscured by overlying physical findings. It appeared to be a routine case of
febrile seizures in overt bronchopneumonia with anemia due to iron deficiency. Only
when basophilic stippling appeared was the diagnosis of lead poisoning considered. This
case shows that when anemia is present, the history of pica should be sought. When this
history is positive, additional studies as outlined herein, should be performed.

53

Diagnosis and screening

153. Diagnosis of inorganic lead poisoning: a statement—BRIT. MED. J. 1968, 4/ 5629 (501)

The diagnosis of lead poisoning should be based on clinical findings, biochemical evidence
of excessive lead absorption and if possible should be supported by evidence of unusual
exposure. Lead absorption can be divided into 4 arbitrary categories which are: (1) Ab-
sorption found in the normal population without occupational or abnormal exposure.
(2) Increased absorption resulting from occupational exposure which is occupationally
acceptable and with no symptoms attributable to it. (3) Increased absorption from ex-
cessive occupational or other exposure with mild or severe symptoms or signs, which is
unacceptable. (4) Dangerous absorption in which symptoms and long-term sequelac are
increasingly probable. Mild symptoms and signs of lead poisoning are non-specific with
the exception of a blue lead line in the gums and a metallic taste. Severe symptoms and
signs include severe colic, neuropathy and encephalopathy. The incidence of sequelae in-
creases not only with increased absorption but with the length of time that excessive ab-
sorption continues.

154. Plumbism—Dept. of Radiol., Maine Med. Cent., Portland, Me.—J. MAINE MED.
ASS. 1970. 61 (18)

Although the incidence of lead poisoning has greatly decreased in recent years, the clinici-
an is still faced an occasion with a chronically ill child presenting with a history and
symptomatology highly suspicious of lead toxication. The case is described of a 17-month-
old girl, admitted to hospital because of persistent vomiting of one week’s duration. Of
considerable importance in this child’s history was his fondness for the paint on the win-
dowsills. The importance of a roentgenographic evaluation is stressed in the diagnosis of
lead intoxication. A routine radiologic work-up of such a patient should include single
projections of the abdomen and extremities. The plain film of the abdomen will often
demonstrate the opaque lead particles within the gastrointestinal tract. However, the most
valuable information is often obtained from radiographs of the extremities and pelvis
where dense transverse metaphyseal bands are seen just under the epiphyseal plates. The
width of the ‘lead lines’ varies and depends upon the amount of lead ingested and the
length of time it has been taken. In the case presented, the lead particles were clearly visu-
alized within the abdomen. The lead lines of the metaphyses are also well seen.

155. Use of the values of ALA dehydratases and eoproporphyrinuria in screening for lead
poisoning / Utililzazione dei valori di ALA-deidratasi e coproporfirinuria per la selezione
dei soggetti saturnini—Agnese G. and Bonsignore D., Catt. di Statist. Med. e Biomet.,
Univ. di Genova—-—FOLIA MED. (N APOLI) 1968, 51/8 (580-587)

A study was carried out on the usefulness of contemporary determination of values of ery-
throcytic ALA dehydratases and coproporphyrin urine levels for the purpose of a more
efficient differentiation between healthy and satumine patients. The method of multi-

54

varied test is used. By the contemporary determination of the above mentioned values it
will be possible to obtain a particularly reliable differentiation.

156. Comparison of delta-aminolevulinic acid levels in urine and blood lead levels for screen-
ing children for lead poisoning—Murphy T. and Lepow M.L., Univ. of Connecticut Sch.
of Med., Storrs, Conn—CONN. MED. 1971, 35 (488-492)

As part of a screening program urinary 6-aminolevulinic (ALA) levels and blood lead
levels were measured in 76 children from ‘high risk’ areas. Forty-eight children had normal
blood lead and urinary ALA levels, 18 had elevated ALA levels with normal blood lead
levels, 5 had elevated blood lead levels with normal urinary ALA and 5 had elevated levels
of both blood lead and urinary ALA. Of the 5 children with elevated blood lead levels
and normal urinary ALA, 3 had had an elevated ALA test 1-4 months previously. False
negative ALA levels may reflect variable urinary ALA output or destruction of the ALA
present in the urine when passed before testing. It is suggested that abnormal ALA excre-
tion with normal blood lead levels may be due to sequestration of the lead in body tissues.
The measurement of urinary ALA levels in random urine samples alone will fail to
identify a significant number of children with elevated blood lead levels who may require
treatment. It is also suggested that both tests should be used together.

157. Screening for lead poisoning—Lin—Fu J.S., Matern. and Child Hlth Serv., US Dept.
of Hlth, Educ. and Welf., Washington, D.C.——PEDIATRICS I970, 45 (720-722)

Screening for lead poisoning has 2 aspects, firstly for evidence of increased lead absorption
and secondly for evidence of lead toxicity. A mass screening program should be designed
to detect the child with asymptomatic increased lead absorption prior to the appearance
of actual lead poisoning. Lead in the hair appears to be related to increased exposure and
absorption. The lead level in capillary blood obtained by a finger prick may be practical
approach but there are problems in the present methods of blood lead determinations.
Increased aminolevulinic acid (ALA) in blood or urine is a biochemical manifestation of
lead poisoning at the metabolic level. Recent investigations indicate that urine ALA
determinations have their limitations. The sensitivity of the test as an early indicator of
increased exposure to lead has been questioned. The validity of random samples of urine
for ALA determinations is also in doubt.

158. Lead poisoning - children at risk—NATURE 1970, 228 (1253)

The New York City Bureau of Lead Poisoning Control has been conducting a screening
program for children and endeavoring to provide preventive care. It is estimated that
between 6000 and 8000 children in the city have pathologically significant blood lead levels.
The number of deaths has dropped sharply because of improved testing but for the same
reason the number of known non-fatal cases has risen from 151 in 1959 to nearly 2500 in
1970. The main source of poisoning is the ingestion by children of chipping paint in old
apartments. The Bureau screened more than 79,000 children in 1970 and found that 2500
had a blood lead level of at least 60 ,ug. / 100 ml. — the accepted definition of a positive case.
The apartments where these 2500 children lived were inspected by the Bureau. If any
painted wall was found to have more than 1% of lead the area was required to be repaired
and painted, either by the landlord or by the Bureau at his expense. Because of limited
staff and budget it was not possible to test the homes of 31,000 children who had lesser
amounts of lead in their blood nor to investigate the other 400,000 odd apartments that
are probably also contaminated.

55

159. The excretion of delta-aminolaevulinic acid by children—Barltrop D., Paed. Unit,
St Mary’s Hosp. Med. Sch., London—ACTA PAEDIAT. SCAND. 1967, 56 (265-268)

Twenty-four-hour urine specimens were collected from 339 children aged 0—l2 years ad-
mitted to hospital over an 11-month period. The mean excretion of 6-aminolevulinic
acid (ALA) per 24 hours was 1.61 mg. with a range of 0.0-6.5 mg. Ninety-five percent of
the values were in the range 0.08—4.39 mg./24 hours. The mean excretion of ALA per unit
bodyweight was 0.08 mg. /kg. bodyweight/ 24 hours and this value did not vary with age.
A seasonal variation in the mean excretion of ALA per unit bodyweight was found with
maximum values in the winter months and minimum values in the summer.

160. Faecal excretion of lead by children—Barltrop D. and Killala N.J.P., Paed. Unit, St
Mary’s Hosp. Med. Sch., London—LANCET 1967, 2 (1017-1019)

Fecal lead is a sensitive index of ingested lead. Normal values for children aged 2 years
have been determined and contrasted with the findings in 3 cases of lead poisoning. Fecal
lead determinations have a place in population screening programs and in the interpreta-
tion of blood-lead values in children.

161. Lead intoxication in children. Diagnosis and treatment—Grad J .W., Kopito L. and
Schwachman H., Child. Hosp. Med. Cent., Boston, Mass.—POSTGRAD. MED. l97l, 50
(133-138)

In the diagnosis of lead overload the most important and practical evidence is provided
by a lead mobilization test. Urinary lead excretion in the 24 hours after the administra-
tion of a single dose of a chelating agent EDTA (50 mg./kg. bodyweight) of over 500 ,ug.
indicates excessive lead burden. In a series of 184 children with lead intoxication, over a
third had blood lead levels below 50 ,ug./ 100 g., but more than half of these had a positive
lead mobilization test.

162. Blood lead levels in normal and mentally deficient children—Gibson S.L.M., Lam C.N.,
McCrae W.M. and Goldberg A., Dept. of Med., Univ. of Glasgow—ARCH. DIS.
CHILDI-I. 1967, 42/ 226 (573-578)

A series of prepubertal children were investigated for evidence of exposure to lead. The
series comprised 20 children of normal intelligence (group A), 20 with mental deficiency
of known etiology (group B), and 20 who were mentally deficient from unknown etiology
(group C). Three children in group A and 6 in group C were found to have blood lead
levels greater than 40 ,ug. 100 g. blood. In these the urinary lead excretion was normal
but was increased significantly after an oral dose of 300 mg. penicillamine. This test (the
penicillamine-lead excretion test) and the blood lead levels are shown to be the most help-
ful procedures in the diagnosis of lead exposure in childhood. The presence of a raised
erythrocyte protoporphyrin level is suggestive of lead exposure, but in contrast to adult
lead poisoning urinary coproporphyrin and d-aminolevulinic acid estimations are of no
value in the detection of this state. All of the 9 children with raised blood lead levels had a
history of pica and with one exception lived in old houses. Furthermore, there were no
children with raised blood lead levels in group B which contained children with organic
brain damage some of whom were severely immobilized and consequently were more
closely supervised than those in the other 2 groups. This emphasizes the importance of
pica and of access to environmental lead in the development of lead intoxication. There
is evidence that lead inhibits an important heme enzyme in the brain (ALA dehydrase)
and that acute lead intoxication leads in some cases to mental deficiency or aggravates a

56

pre—existent mentally deficient state. The growing brain of young animals is more sus-
ceptible to damage by lead than that of adult animals. These considerations acid weight
to the suggestion that previously undetected lead poisoning may be a factor in the devel-
opment of some cases of mental deficiency, but the problem requires further investigation.

163. The resolution on childhood lead poisoning~Blanksma L.A., 2951 King Drive, Chicago,
Ill—AMER. J. PUBL. HLTH 1970, 60/7 (1191-1193)

The resolution on childhood lead poisoning reported in the American Journal of Public
Health in 1970 is criticized in this article. The present author agrees with the call for
prompt treatment and comprehensive follow-up of all detected cases, and feels this to be
the most important part of the resolution. He disagrees with the resolution on the question
of mass urine testing for excessive lead content, which it advocates. Urine lead analysis
has no diagnostic screening value, urinary concentrations not always being high when
blood lead is high, excretion of lead in urine being variable, and specimens being difficult
to obtain. Blood lead analysis is the only sage method for screening children. Testing and
treatment of ghetto housing is also recommended in the resolution. The present author
feels however that so many of these houses are at fault that identification is hardly nec-
essary and anyway could follow testing of children, and that even if all paint in these
buildings were rendered inaccessible the effect which would result on the incidence of child—
hood poisoning is unknown, the buildings containing numerous other hazards.

164. Serum (5-minolevulinic acid in plumbism—Feldman F., Lichtman H.C., Oransky
S., Sta Ana E. and Reiser L., Dept. of Fed, Coney Island Hosp., Brooklyn, N.Y.—J.
PEDIAT. 1969, 74/6 (917-923)

Blood lead and serum 6-aminolevulinic acid (ALA) levels were determined in groups of
children with increased lead absorption, lead intoxication, and lead encephalopathy. Al-
though blood lead values tended to be higher in children with intoxication, they tended to
overlap those of patients with increased absorption but without intoxication. Serum ALA
was consistently higher in patients with overt toxicity, with almost no overlapping of
values. Blood lead and serum ALA levels were both markedly elevated in patients with
encephalopathy. Lead and ALA values failed to correlate well. Cerebrospinal fluid ALA
values were consistently lower than serum values. It is concluded that serum ALA determi-
nations are valuable in selecting infants who are intoxicated from those exposed to in-
creased amounts of lead.

165. Use of urinary ALA levels as a large-scale screening technique for the detection of early
lead exposure in children—Davis .1.R., Abrahams R.H., Andelman S.L. and Fabrega E.A.,
Loyola Univ. Stritch Sch. of Med., Hines, Ill—FED. PROC. 1968, 27 (466)

The use of disposable ion-exchange chromatography columns prefilled with resin has
markedly simplified the analysis of urinary d-aminolevulinic acid (ALA). Urinary ALA-
levels were determined in 3510 children residing in high-incidence areas of lead poisoning in
Chicago, employing 0.5 ml. of a random urine sample. A total of 216 children (6.1%) were
found to have elevated urinary ALA values greater than 1.00 mg.%, with 188 values
between 1.00-1.49 mg.%, 15 values between 1.50-1.99 mg.%, 11 values between 2.00-2.99
mg.% and 2 values between 3.00-5.99 mg.%. The correlation of urinary ALA values with
the clinical diagnosis of lead exposure was investigated in an additional series of 250 chil-
dren suspected of lead ingestion because of an initially elevated blood level value. Following
clinical examination, the incidence of a correct correlation between urinary ALA and the
diagnosis of lead exposure was 91%. These data indicate that urinary ALA testing em-

57

ploying easily obtainable random urine samples constitutes a practical and accurate large-
scale screening technique for the detection of early lead exposure in asymptomatic children.

166. Reliability of urinary delta-aminolevulinic acid as a mass screening teehnic for childhood
exposure to lead—Davis J .R., Loyola Univ. Stritch Sch. of Med., Maywood, Ill.—
AMER. J. CLIN. PATHOL. 1970, 53 (967-969)

The author reports laboratory experience in using urinary 6-aminolevulinic acid (ALA)
levels to detect exposure to lead in children. The laboratory modified the determination of
urinary ALA by introducing dual disposable chromatographic column units prefilled with
resin that could be conveniently held in a support rack over a drain tray, and a kit is now
available commercially. A table is given showing statistical comparison of urinary ALA and
blood lead values and a comparison of urinary ALA levels with chelation therapy in 233
children with elevated ALA (over 1.00 mg. / 100 ml.). The data indicate a positive corre-
lation between elevated urinary ALA levels and increased exposure to lead in children.
A second study to find the incidence of possible false-negative values of urinary ALA was
made of 3068 children with normal levels of urinary ALA below 1.00 mg./ 100 ml., basing
the incidence of false-negatives on a determination of blood lead by atomic absorption
spectrometry. Only 1.1% of these children had possible false-negative urinary ALA values
in terms of blood lead levels greater than 60 ,ug./ 100 ml. and only 0.14% had possible false-
negative urinary ALA values in terms of blood lead levels greater than 80 ,ug./ 100 ml. The
proper preservation and storage of the urine sample is important. In view of the possibility
of evaporation of the small quantity of acetic acid used, it is recommended that tartaric
acid-coated vials should be used or citric acid dried in the vials. The use of urinary ALA was
never intended to replace the determination of blood lead levels but it remains the only
practical large-scale screening technique for the detection of increased exposure to lead in
small children which is available at present.

167. Lead poisoning in children: detection by ion-selective electrode—Rechnitz G. A., Dept.
of Chem., State Univ. of New York, Buffalo, N.Y.—SCIENCE 1969, 166 (532)

Attention has been drawn to the need for more rapid and sensitive detection methods of
lead poisoning in children caused by the ingestion of lead-based paints, which can be used
for the diagnostic screening of large numbers of children. An analytical. device is a solid-
state ion—selective membrane electrode selective for lead ions in solution. This electrode
seems to have the appropriate characteristics of sensitivity (to as low as 10‘7M Pb") and
selectivity (normal ionic constituents of body fluids should not interfere) to warrant
further exploration of its use as a diagnostic tool. Similar electrodes, selective for Cl‘, are
being used for the detection of cystic fibrosis in children.

168. Bismuth ingestion simulating acute plumbism on abdominal roentgenogram—Heller
R.H. and Waitsman E.S.—J. PEDIAT. 1970, 70/4 (637-638)

A case report is presented of a 3 year old child seen for evaluation of pyrexia of 3 weeks’
duration without other symptoms except occasional mild diarrhea. He was known to ingest
dirt. Besides pyrexia the only other abnormal finding on examination was equivocal left
lower quadrant tenderness. Blood count, electrolytes, urine, marrow and chest X-ray were
normal. Abdominal film showed numerous scattered radiopaque flecks suggestive of paint-
chip ingestion. Urinary test for coproporphyrin was negative: blood lead was 0.013 mg./ 100
ml. Stool inspection revealed chunks of material shown chemically to contain large
amounts of bismuth which might have come from a proprietary bismuth mixture kept in
the home. Stool culture was positive for Salmonella typhimurium; blood titer for this

58

organism was 1 : 128. Ampicillin was given orally for 14 days; the child rapidly became
afebrile.

169. Enzyme inhibition by lead under normal urban conditions—Hernberg S. and Nikkanen
J., Inst. of Occupational Hlth, Helsinki—LANCET 1970, 1 (63-64)

A close negative correlation was found between the concentration of lead in blood and the
activity of erythrocyte d-aminolevulinic acid dehydrogenase in 26 healthy individuals, never
exposed occupationally to lead. The results indicate that present levels of environmental
contamination with lead can produce a measurable biochemical alteration in man.

170. Effects of abnormal lead content of water supplies on maternity patients. The use of a
simple industrial screening test in ante—natal care in general practice—Wilson A.T.—SCOT.
MED. J. 1966, 11/3 (73-82)

In a small town and rural practice it was found that the water supplies intermittently ex-
ceeded the present WHO standard limit for lead content of 0.05 mg./l. owing to their
agglessive action on lead pipes. All the routine urine samples of all the maternity patients
were used for a study over a 2—year period. A simple industrial screening test for increased
urine coproporphyrin showed differences, of statistical significance, in results before and
after restriction of intake of water. There were also differences on less detailed comparison
of groups of patients in other practices on hard and soft water supplies. Only 2% of 404
hospital antenatal patients showed urine coproporphyrin results in the range 100 to 200
,ug./l. or higher. Eleven of 35 patients in the practice (3l%) subject to no water restriction
reached this level at some stage during their antenatal supervision. One stillbirth from a
series of 75 pregnancies studied gave evidence of abnormal exposure to lead, having in-
creased fetal kidney and maternal blood lead levels. On one very unsatisfactory water
supply a patient had a history of miscarriage or antepartum hemorrhage in 7 of 8 pregnan-
cies. A patient with a raised antenatal urine coproporphyrin output had a baby with con-
genital nystagmus and partial albinism. In some instances blood lead estimations were
extraordinarily low. Difficulties in the interpretation of blood lead levels have been related
to certain alterations in the blood chemistry in pregnancy.

171. Chronic plumbism in children. Diagnosis by hair analysis—Kopito L., Briley A.M. and
Shwachman H., Div. of Clin. Labs, Dept. of Med., Child’s Hosp. Med. Cent., Boston, Mass.
—J. AMER. MED. ASS. 1969, 209/ 2 (243-248)

The determination of lead in scalp hair is a valuable diagnostic aid in chronic of mild lead
intoxication particularly when the other clinical or laboratory evidence is of questionable
diagnostic quality. This continuously growing tissue accumulates and stores lead for long
periods and may be used for estimating the time and duration of the exposure. Hair is
easy to obtain, store, transport, and analyze and may provide a practical means for finding
little children who may have been exposed to lead.

172. Lead ingestion in New Orleans children—Blumenthal D., Dept. of Fed, Tulane Med.
Sch., Charity Hosp, New Orleans, La.—STH. MED. J. (BGHAM, ALA.) 1971, 64/3 (364-
365)

The use of a simple screening procedure is described to detect increased body burdens of
lead in asymptomatic children. One hundred children, aged 1-5, from low income families
were selected at random. Urine samples were collected and qualitative coproporphyrin tests
were performed using the de Langen and ten Berg method as modified by McCord.

59

17
M
19

Asymptomatic children with positive urine coproporphyrin were studied further by means
of blood lead determinations, radiographs of the abdomen and long bones, hemoglobin
determinations, and inquiries as to possible sources of lead. Four children were found to
have coproporphyrin in the urine. Of these, one child had a normal blood lead level and no
other evidence of lead poisoning. The other 3 exhibited evidence of increased lead exposure.
Two of the children had been observed to ingest paint and plaster fragments. Neither had
significant anemia nor radiologic evidence of lead poisoning. Both children were clinically
asymptomatic. The housing conditions of the children were not investigated. A sample
limited to children living in deteriorating houses may yield a higher percentage of subclinic-
a1 lead poisoning. Comparison of the present report with other studies of increased body
burden of lead in asymptomatic children indicates that in susceptible population groups 3-
8% of preschool children show elevated body burdens of lead. The use of a simple screening
test may prove to be useful in the control of lead poisoning.

3. Incidence of high blood lead levels in Chicago children—Blanksma L.A., Sachs H.K.,
urray BF. and O’Connell M.J., Chicago Board of Hlth, Chicago, Ill—PEDIATRICS
69, 44/ 5 (I) (661-667)

The Chicago Board of Health in October 1966 began a mass-screening program using a
blood lead test to detect lead poisoning in children. Atomic absorption spectroscopy made
it possible to screen 5000 specimens in 1 month and to test a total of 68,744 children in 2 years.
The incidence of high blood lead values was variable and seasonal; it was lowest in Novem—
ber through January and highest in June. Control children exhibited the same seasonal
variation in lead levels as did the children at-risk for lead poisoning. As a result of this
program, 1154 children were treated with chelates for lead poisoning in 1967 and 1968 at
the Lead Poisoning Clinic, and the incidence of high blood lead levels among children
living in the same areas declined from 8.5% in 1967 to 3.8% in 1968.

174. D.C. mounts unfunded program of screening for lead poisoning—Conn R.H. and
Anderson D., D.C. Dept. of Hum. Resources, Commun. Hlth Serv. Administ., Washing-
ton, D.C.—-HSMA REP. 1971, 86/5 (409-413)

60

A nonfunded screening program for lead poisoning was launched in 1970 by the Health
Services Administration of the District of Columbia’s Department of Human Resources.
The organization and the results of the screening program are summarized. Blood samples
were taken from 808 children ranging in age from 1-8 and over. 165 children (20.4%) had
pica. Of this group, 47 children (5.8%) had elevated blood-lead levels of at least 40 ,ug./
100 ml. In these children pica was reported in 44.7%. For the 476 children under age 5
(58.9% of the total who were tested), the mean blood-lead level was 26.4 ,ug. as compared
with a mean blood lead level of 25.0 for all children tested. It is well known that children
in this age group are more likely to have a higher level because of the tendency to pica. No
child living in more recently built projects had a blood lead level above 39.9 ,ug. In fact,
all but 1 of these children had levels below 34.9 Mg. In the areas of deteriorating houses in
the District of Columbia, 11.2% of the children under 5 years had elevated blood-lead
levels. Referrals to Children’s Hospital for additional diagnosis and treatment were made
for 47 children with levels of 40 lug. or higher. Of these,5 children (10.6%) were admitted
to the hospital for treatment.

Laboratory methods

175. The unsuitsbillty of random urinary delta aminolevulinic acid samples as a screening
test for lead poisoning—Specter M.J., Guinee V.F. and Davidow 8., Cent. for Dis. Control,
US Dept. of Hlth, Educ. and Welf., New York, N.Y.—J. PEDIAT. 1971, 79/5 (799-804)

Lead poisoning in childhood is a significant health problem which has prompted the initia-
tion of mass screening programs to detect children in danger of developing this disease. In
this study, multiple urine specimens were collected on consecutive days and tested for the
presence of d-aminolevulinic acid (ALA) in a group of children who were living 1n a ‘lead-
free’ environment and in another group with evidence of significant lead ingestion. No
single value for ALA was found which separates the normal children from those with an
increased body burden of lead. In random, untirned samples of urine the presence of
‘abnormal’ ALA values in normal children and ‘normal’ values in children with lead
poisoning makes such testing unsuitable for screening purposes.

176. Determination of lead in blood by atomic absorption spectrophotometry—Selander
S. and Cramér K., Med. Serv. I, Dept. of Hyg., Univ. of Goteborg—BRIT. J. INDUSTR.
MED. 1968, 25 (209-213)

Lead in blood was determined by atomic absorption spectrophotometry, using a wet ashing
procedure and a procedure in which the proteins were precipitated with trichloroacetic acid.
In both methods the lead was extracted into isobutylmethylketone before measurement,
using ammonium pyrrolidine dithiocarbamate as chelator. The simpler precipitation proce-
dure was shown to give results identical with those obtained with the ashing technique. In
addition, blood specimens were examined by the precipitation method and by spectral
analysis, which method includes wet ashing of the samples, with good agreement. All
analyses were done on blood samples from ‘normal’ persons or from lead-exposed workers,
and no additions of inorganic lead were made. The relatively simple protein precipitation
technique gave accurate results and is suitable for the large-scale control of lead-exposed
workers.

177. The level 01' lead in the blood and the excretion of S-aminolevulinic acid / Bleigehalt
lm Blut and 5-Aminolivulinsiiure—Ausscheidung—Baumler J., Gerichtl.-med. Inst., Univ.
Basel—Z. PRAV. MED. 1966, 11/3 (265-275)

The micro-determination of lead in blood is mentioned and the excretion of 5-aminolevu-
linic acid in urine is discussed. For the clarification of the influence of lead on a larger col—
lection it is proposed to determine the amount of 5-aminolevulinic acid in the first sample
of urine in the morning. Detailed instruction for this procedure is given. Based on the
results of a great number of experiments the level of lead in blood and the excretion of
aminolevulinic acid in urine are compared. It is found that concentrations below 600 mg.%
5-aminolevulinic acid in morning urine are normal.

61

178. Quantitative coproporphyrin determinations / Zur Praxis der quantitativen Kopro-
porphyrinbestimmung im Ham—Kisser W., Inst. fur Gerichtl. Med., Univ. Wien—ZBL.
ARBEITSMED. 1968, 18/ 12 (368-371)

Side by side with coproporphyrin, its biogenetic precursor, coproporphyrinogen, is also
excreted with the urine in variable quantities. It can be transformed into copropor-
phyrin by oxidation, preferably by exposure to light of the solution in ether. Since there is
no fixed ratio of the coproporphyrin and coproporphyrinogen levels, the quantitative
determination of the total porphyrin excretion always requires the transformation of
coproporphyrinogen into coproporphyrin. If samples of urine are kept at room tempera-
ture for periods of up to 24 hours, a considerable loss of porphyrin occurs, so that the results
are no longer suitable for diagnostic purposes. Consequently, if it is not possible to analyze
the urine within 4 to 5 hours after micturition, the samples should be kept in the refrigerator
(for not longer than 24 hours). If longer storage at room temperature is unavoidable (e.g.
if the sample is to be dispatched by post), preservation of the urine should be carried out
immediately after micturition; the method is described. However, even if this treatment
is applied, a significant loss of porphyrin must be taken into account. In any case, the
urine should be kept in absolute darkness during storage.

179. The effect of lead and ferrous and ferric iron on d-aminolaevulie acid synthetase—Mor-
row 11, Urata G. and Goldberg A., Univ. Dept. of Med., Western Infirm., Glasgow—
CLIN. SCI. 1969, 37 (533-538)

Properties of the enzymes d-aminolevulic acid synthetase were studied using particles of
chicken cell hemolysate as the source of enzyme, glycine and a-ketoglutarate as substrates,
and optimal concentrations of pyridoxal phosphate, coenzyme A, EDTA and MgClz.
Ferrous iron in concentrations of 10'6M increased the activity of the enzyme by 12%
and at 10‘3M depressed activity by 56%. Ferric iron had no stimulating action but de-
pressed activity by 12% at 10‘3M. Lead caused progressive depression of activity with
increasing concentration.

180. Procedure for the determination of lead-210 and total lead in biological samples—

Langford J.C., Batelle Mem. Inst, Pacific Northwest Lab., Richland, Wash.—ANALYT.
CHEM. 1969, 41 (1716)

An improved method was described for the preparation of stable lead extracts from
biological samples for assay by atomic absorption spectrometry. Samples were ashed at
under 500°C, although urine was acidified with nitric acid, dried under a lamp and wet-
ashed with nitric acid and perchloric acid. The ash was dissolved in 50 ml. of hot 0.6 M
hydrochloric acid, with the addition of 100 ,ug. of bismuth carrier and a specially prepared
me sample. The cooled solution was extracted twice with 20 ml. of 1% diethylammo-
nium-diethyl—dithiomrbamate in chloroform. The organic phase was evaporated after acid-
ification with nitric acid, and any charred organic matter was destroyed with nitric acid, hy-
drogen peroxide and perchloric acid. The acidic residue was taken up in water and diluted
to 8 m1. A further 2 ml. of 9 M sodium iodide was added, and the mixture was extracted
twice with 10 ml. of hexone (isobutyl-methyl-ketone) pre—treatcd with 1 M hydrochloric
acid. Yields were determined by measurements of the MN} radioactivity. A 2 ml. aliquot
of the hexone phase was used to determine total lead by atomic absorption analysis. The
remaining hexone phase was evaporated, treated with nitric acid and stored for 5 days.
The 2”Bi beta particle emission was then counted in order to determine 2"le levels.
With this procedure, the extraction gave 70.5 x 11% yields from biological samples, and
5 ,ug. of lead could be measured with t 20% accuracy.

62

181. X-ray fluorescence: detection of lead in wall paint—Laurer G.R., Kneip T.J., Albert
KB. and Kent F.S., Inst. of Environm. Med., New YOrk Univ. Med. Cent._. New York, NY.
—SCIENCE 1971, 172 (466-468)

An instrument has been developed for the in situ determination of lead on painted sur-
faces. It utilizes, as a source of gamma rays, radioactive cadmium-109 and its daughter
silver-109 (metastable) to excite the K series X-rays of lead, and a solid-state, lithium-
drifted germanium detector. The device, which is capable of detecting 0.26 mg. of lead per
square centimeter of paint (approximately 3% (by weight) of lead in a single coat) beneath
10 layers of lead-free paint, has been tested in a preliminary survey of several tenement
apartments in New York City.

182. A reliable and rapid method for the determination of lead in small quantities of blood /
Eine zuverlissige Schnellmethode zur Bleibestimmung in kleinen Blutmengen—Lehnert G.,
Schaller K.-H. and Szadkowski D., Inst. fur Arbeits— und Sozialmed., Univ. Erlangen-
Numberg—Z. KLIN. CHEM. KLIN. BIOCHEM. 1969, 7/3 (310)

The conventional techniques for the determination of blood lead levels are not entirely
conclusive and require experience on the side of the analyst. In previous publications the
authors described a technique using atomic absorption spectrophotometry which has
proved its value in 6000 analyses. An improved modification is described: 0.1 ml. of a 50%
aqueous solution of crude agal and 1 ml. of a 5% aqueous solution of ammonium-
pyrrolidine-dithiocarbamate are added to 2 ml. of whole blood. The mixture is homo-
genized by centrifugation. Following addition of 1 ml. of methylisobutylketone the mix-
ture is shaken for 2 minutes and the organic portion is removed by centrifugation. This
portion is used for determination of lead by atomic absorption spectrophotometry. The
method has proved accurate and specific. It can be carried out in less than 10 minutes,
it requires a small volume of blood, and the hazards of lead loss or contamination are
reduced. This technique is suitable for routine blood checks for lead in the surveillance
of lead exposed workers.

183. A simplified screening test for exposure to lead—Morgan J.M., Ren. Res. Lab., V.
A. Hosp., Birmingham, Ala—8TH. MED. J. (BGHAM, ALA.) 1967, 60/4(435-438)

EDTA may be used orally to demonstrate excessive absorption of lead in the past. The
test is simple, safe and effective in detecting persons who have been subjected to excessive
storage of lead. A very significant proportion of men over 35 years of age in the South,
particularly among Negroes, demonstrate excessive storage of lead as a result of previous
regular use of illegally produced alcohol. Most of these persons do not have clinically
recognized evidence of lead toxicity. Further studies are needed to elucidate the longterm
consequences of this excess.

184. Changes of the isoenzymatic fractions of the erythrocytic lactodehydrogenase in satur-
nine anemia - Modificazioni delle frazlonl lsoenzimatische della lattato-deldrogenase (LDH)
eritrocitaria nell’anemia saturnina—Secchi G.C. and Alessio L., Clin. del Lav. ‘L. Devoto’,
Univ. di Milano—MED. D. LAVORO 1968, 59/ 12 (784-792)

The changes of the isoenzymatic fractions of the erythrocytic lacticodehydrogenase (LDH)
were studied in 11 workers engaged in the production of electric accumulators, who pre-
sented clinical hematological and biochemical signs of lead poisoning. The characteriza-
tion of LDH isoenzymes was obtained by Cellogel electrophoresis; the fractions were
demonstrated by a method based on the reduction of tetrazolium salts. In the satumine

63

subjects a significant increase of the cathodic isoenzymatic fractions (LDH IV and V)
was demonstrated. On the basis of the known data of the literature on the localization
of LDH V in the nuclear structures, this finding can be attributed to the persistence in the
red blood cells of saturnine subjects of enzymatic proteins derived from the nucleus. The
high values of the cathodic fractions of LDH in the saturnine anemia might indicate the
existence of a red blood cell population with at least partial characters of immaturity.

185. A spot test for detection of lead in paint—Sayre J .W. and Wilson D.J., Dept. of Ped.,
Univ. of Rochester Sch. of Dent., Rochester, N.Y.—PEDIATRICS 1970, 46/5 (783-785)

A method of testing is proposed which is simple, inexpensive, and specific, and can be
performed in the patients home. It involves the precipitation of lead as an insoluble black
sulfide through the following reaction: Pb + Nags PbS. The specificity and sensitivity of
this method are briefly discussed.

186. Inverse voltammetric determination of lead in small blood samples. I. Determination
after dry-ashing / Inversvoltammetrische Bestimmung von Blei in kleinen Blutrnengen. I.
Bestimmung nach Trackenverrschung—Roschig M. and Matschiner H., Anorgan. Chem.
Inst., Martin-Luther—Univ., Halle Wittenberg—Z. MED. LABORT. 1970, 11/1 (7-16)

A micromethod for the determination of the lead concentration in capillary blood taken
from the ear is described. The volume of blood required is 0.2 ml. and the method is able
to detect a concentration of 0.1 parts per million. After dry incineration and disintegration
of the ash with hydrochloric acid, the lead content of the sample is determined by anodic
stripping in the presence of ascorbic acid. The relative standard deviation of the method
was found to be 12%. One worker can perform about 20 determinations in one working
day.

187. Toxicology. Technique of emission spectrographic demonstration of heavy metals in
biologic material / Toxikologie. Zur Technik des emissionspektrographischen Nach-
weise von Schwcrmetallen in biologischem Material—Geldmacher—v. Mailinckrodt M., Inst.
flir Gerichtl. Med. und Kriminalist., Univ. Erlangen-Nllmberg—DTSCH. Z. GES. GE-
RICHTL. MED. 1967, 59 (280-286)

For the detection of heavy metals of forensic importance in organs and body fluids it is
useful to extract them with diethylammonia-diethyldithiocarbamate in chloroform after
mineralization and to analyze the residue of the organic phase after absorption to carbon
powder spectrographically. Thus it is possible, for example, to detect even such small
amounts as 1 ,ug. of lead, mercury and thallium and 5 gig. of arsenic in 100 ml. of urine or
10 g. of liver.

188. Large lymphocytes in the peripheral blood in cases of satumism / Sui grandi linfociti
del sangue dei saturnini—Ambrosi LL, Vimercati F. and Di Nunno C., Ist. di Med. Leg. e
delle Assicur., Univ. di Bari—MED. D. LAVORO 1968, 59/2 (125-135)

High percentages of large lymphocytes were found in the peripheral blood of 20 patients
with satumism. These cells, stained by the method of Unna-Pappenheim, showed an in-
tense cytoplasmic basophilia. In the peripheral blood of 20 subjects not exposed to lead,
the percentage of large lymphocytes was within normal limits. The results are discussed
on the basis of bibliographic data on the significance of the large lymphocytes and of
changes of Coombs’ test in saturnism. The usefulness of the determination of large lym-
phocytes in saturnism is stressed.

64

189. Simple methods for the determination of 6-aminolevulinic acid in the urine / Die ein-
fachen Bestimmungsmethoden der 6-Aminolivulinsa'ure im Ham—Grabecki J., Haduch
T. and Urbanowicz H., Toxikol. Abt., Inst. fiir Arbeitsmed., Zabrze—INT. ARCH. GE—
WERBEPATHOL. GEWERBEHYG. 1967, 23 (226-240)

A comparison was made of several simple methods for the determination of d-amino-
levulinic acid (ALA). The best method was found to be that of Mauzerall and Granick
but the length of time required for its completion is a drawback in routine work. A modifi-
cation is described which reduces the time for performance of the analysis to 20 minutes.
The principle of the method is the condensation of the ALA in the urine with acetylacetol
to a pyrrole which is estimated spectrophotometn'cally by the formation of a color com~
plex with p-dimethylaminobenzaldehyde in acid solution. The precision and accuracy
were found to be satisfactory, and there was good agreement between the results ob-
tained by the modified and unmodified methods. This modification should have wide
application in the routine diagnosis of lead poisoning.

190. Application of the polarograph by anodic redissolution in biochemistry. 1. Estimation
of lead in the urine / Application de la polarographie par redissolution anodique en blochi-
mie. I. Dosage du plomh urinaire—Girard M.-L., Dreux C., Paolaggi F. and Delattre J .,
Chaire de Biochim. App]. et CES d’Electrochim. Appl. a l‘Analyse, Fae. de Pharrn., Paris—
ANN. BIOL. CLIN. 1968, 26/ 3-4 (401-415)

The application of polarography by anodic redissolution while avoiding mineralization
of the samples, allows the rapid and accurate estimation of very small quantities of lead
in the urine of the order of 0.01 pg. /m1. even in the presence of a complex agent like
EDTA. A certain number of conditions are indispensible to obtain quantitative and re-
producible results, either by the electrochemical method (temperature, time of electrolysis,
surface of the droplet) or by the nature of the metach element as well as the complexity of
the biological medium. These conditions were determined during a systematic analytical
study. The values of lead in the urine obtained by this method in normal subjects were
between 0 and 28 ,ug./1., slightly less than those obtained by classical methods.

191. Dry destruction technique for the identification of trace elements in biological milieu.
Application to the urinary excretion of lead / Méthode de destruction par voie seche pour
la recherche dos traces d’éléments dans les milieux biologiques. Application a la déter-
mination de la plomburie—Truffert L. and Girard-Wallon C., Inst. d'Hyg. Industr. et de
Med. du Travail, Paris—ARCH. MAL. PROF. 1968, 29/ 1-2 (23-28)

The technique of dry mineralization allows simultaneous processing of numerous urine
specimens without special surveillance. An original apparatus consisting entirely of quartz
and Pyrex glass was designed to obtain the mineralization of the specimen. A number of
technical details are given. The percentages of recovery for contents of 0.5 mg. /l. to 1.0
mg./l. lead varied from 90 to 100. The results of square wave polarography of different
elements studied in mineralized human urines are tabulated. It was shown that the lead
contents calculated corresponded fairly well to the quantities of this element introduced
into the specimens.

192. New screening test for stippled red cells. Confirmation by this test of the identity of the
reticulocyte, the stipped red cell and the red cell with diffuse polychromasia / Nouvelle mé-
thode de recherche des hématies ponctuées. Confirmation, grace a elle, de l’identité du
rétlculocyte avec l'hématie ponctuée et l’hématie a polychromasie difl'use—Van Houte
G. and Cocle P., Serv. Méd. des Tréfrleries Léon Bekaert, Zwevegem—ARCH. MAL.
PROF. 1968, 29 /7-8 (403—410)

65

A number of workers have advanced the theory that stippled red cells, erythrocytes with
diffuse polychromasia and reticulocytes are only different forms of a single cell type, the
young or immature erythrocyte (proerythrocyte). The blood of 65 individuals exposed to
lead but without clinical signs of lead poisoning was studied. The following techniques
were employed: (1) An original method of fluorescent microscopy using an orange acridine
stain; (2) other types of stains (cresyl blue, Manson-Schwarz, and Wright). The technical
details are presented. The comparative results are tabulated. It was shown by painstaking
enumeration that stippled red cells, polychromatophil erythrocytes and reticulocytes
indeed are only different types of the young erythrocyte. Their different morphology is the
result of varying laboratory manipulations. In another small series comprising normal
individuals or patients with diseases other than lead poisoning the numbers of reticulocytes
and stippled red cells were also comparable. The somewhat particular appearance of
basophilic stippling in the red cells of individuals exposed to lead is considered to be due
to the inhibitory effect of lead on the enzymatic processes of cell wtabolism. Specialists
in industrial medicine are advised to enumerate all proerythrocytes by the conventional
cresyl blue technique or preferably by fluorescent microscopy of specimens stained with
orange acridine instead of the Manson-Schwarz count of stippled red cells.

193. The measurement of urinary delta-aminolevulinic acid in detection of childhood lead
poisoning—Vincent W.F., Ullmann W.W. and Weidner G.L., Connecticut State Dept. of
Hlth, Hartfold, Conn—AMER. J. CLIN. PATHOL. 1970, 53 (963-966)

Different opinions of the test for increased urinary d-aminolevulinic acid (ALA) as an in-
dication of early asymptomatic lead poisoning in children are presented. One series shows
that there is a complete lack of correlation between urinary ALA levels and blood lead
in several thousand children. Up to 75% false negative ALA tests were obtained in another
series of 250 children, though the incidence of false negatives falls to 31% when blood
lead increases to the range 60-200 ,ug./ 100 ml. whole blood. Other authors, however, report
positive correlations between ALA and blood levels in more than 1000 children. Of those
with elevated ALA, 48% had elevated blood lead, and there were no false negatives on
the ALA test. The latter authors also describe a second series of 500 children in which
results apparently confirm the correlation between urinary ALA and blood lead. Technical
details in handling of specimens might have affected some results and are discussed.

194. Critique of interlaboratory evaluation of the reliability of blood-lead analyses—Weil
C.S., Carnegie-Mellon Univ., Mellon Inst., Pittsburgh, Pa.——AMER. INDUSTR. HYG.
ASS. J. 1971, 32 (304-312)

Interlaboratory comparison of the results of analytical procedures is important to deline-
ate the presence or absence of accuracy and precision. As part of laboratory accreditation
must depend on accurate analysis of the results of such interlaboratory trials, a reanalysis
of the blood-lead values (Keppler et al., Amer. Industr. Hyg. Ass. J. 1970, 31, 412) deter-
mined by 60 laboratories is presented. In the nonparametric procedures used, the outlying
laboratories (those whose central tendency and those whose variability were abnormal) are
clearly delineated. These outlying laboratories can, therefore, more easily attempt to cor-
rect their method of analysis, knowing how they compare with the majority of other
laboratories.

195. d-aminolevulinic acid debydratase activity in circulating blood cells. A sensitive labora-
tory test for the detection of childhood lead polsoning—Weissberg J.B., Lipschutz F. and
Oski F.A., Dept. of Fed, Univ. of Pennsylvania Sch. of Med., Philadelphia, Pa.—NEW
ENGL. J. MED. 1971, 284/ 11 (565-569)

66

An inverse correlation was demonstrated between erythrocyte 6-aminolevulinic acid (ALA)
dehydratase activity and blood lead levels. ALA-dehydratase activity was shown to be a
sensitive index of subclinical lead poisoning, more so than either urinary coproporphyrin or
urinary ALA. Enzyme levels were lower in children living in deteriorated slum housing
of the inner city than in those living in better housing in urban and suburban areas. It is
suggested that assays for this enzyme will serve both as a practical screening test for un-
recognized plumbism among suspect populations and as an adjunct to the rapid diagnosis
of acute lead intoxication.

196. Measurement of lead in blood and urine by atomic absorption spectrophotometry—
Farrelly RD. and Pybus 1., Dept. of Chem. Pathol., Auckland Hosp., Auckland—CLIN.
CHEM. 1969, 15/7(566-574)

An extraction method for the estimation of lead in red cells is given. The method avoids
both acid digestion and/ or protein precipitation. It is extremely simple and reliable, and
can easily be performed by technicians. A technical error of 4.5 ug. lead per 100 ml. of red
cells has been obtained. The use of red cells instead of whole blood provides a more accurate
measure of exposure to lead as the lead is concentrated within the red cells. Normal and
toxic ranges are given. As it is frequently required to monitor the lead excretion of pa-
tients receiving chelates for thereapy, a method for the analysis of urine specimens from
patients on this therapy is given.

197. Blood lead estimations—Edwards R.G., Berriman H. and Geary T.D., Inst. of Med.
and Veter. Sci., Adelaide—PATHOLOGY (SYDNEY) 1970, 2/ I (75-76)

Whole blood or red cell lead content estimations are known to be the best indications of
exposure to lead, but these measurements are not used as frequently as is desirable in
Australia apparently because of the supposed technical difficulty of the laboratory methods.
A simple method of estimating blood lead is presented. This can be established in any good
laboratory and is based on lysis of an aliquot of blood, chelation of the lead, concentra-
tion of the complex in an organic phase and the spraying of this extract into an atomic
absorption spectrophotometer. Values obtained from a group of 40 adults not exposed
to a lead hazard ranged from 5—20 ,ug. of lead 100 ml. of whole blood with a median value
of 15 lug. As lead is bound to red cells it has been recommended that results be expressed
as micrograms of lead ml. of erythrocytes (mean erythrocyte lead concentration or
MELC). The normal MELC range is then 0.15-0.50 Mg. with a median value of 0.30 ,ug.
Five hundred estimations on industrial workers engaged in the manufacture of car bodies
and batteries gave a range of values from 5130 ,ug./ 100 ml. and demonstrated, as would
be expected, that certain activities involved more exposure to lead than others. However,
some which were previously thought to have a low risk of exposure were shown in fact to
have quite a high risk. Several workers had values which were regarded as dangerously
high. It was also clear from discussions with the workers themselves that these values
had probably been present for several years. Measurements on some workers have dem-
onstrated the value of blood lead estimations in the rapid detection of changes in indus-
trial exposure. The effects of blood lead levels in excess of 70 ,ug. on adult tissue and, in
particular the nephron, has yet to be elucidated.

198. Detection by X-ray fluorescence of metals and metalloids contained in histological
sections / Detection par la fluorescence X des métaux et métalloi‘des contenus dans les
coupes histologiques—Duprez A., Wittmann A., Rauber G. and Florentin P., Lab. d’Anat.
Pathol., CHU., Nancy—CR. SOC. BIOL. (PARIS) [967, 161 (871-874)

67

X-ray fluorescence allows specific identification of the substances searched for without
interfering with morphological and other studies of the histological sections. Sections
5.5.,uthick are embedded in paraffin, spread and fixed onto a mylar foil of 6,uthickness.
Following extraction of the paraffin the sections are soaked in water and subsequently
dried. Then they are mounted on a support and are introduced into the X-ray fluorescence
apparatus. If the presence of a certain atom is suspected, the apparatus is set for the
principal rays of the corresponding atom and its presence is investigated. Following this,
water is added again to the preparations which then are stained and placed between a slide
and a cover glass to be studied under the light microscope. Using this method, iron was
detected in the liver tissue of a patient with hemochromatosis. Copper was identified in
spleen and liver of a patient with Wilson’s disease. Silicon was encountered in the lung
tissue of a miner with silico-asbestosis. Lead was found in the gingival mucosa of a patient
with plumbism. Next to calcium and sulfur, potassium was present in all tissues analyzed
of a young individual with an osteochondroma. Iodine, antimony, calcium and potassium
were found in a simple goiter. This method allows the detection of all atoms whose atomic
number is higher than 12. The multiple possibilities of practical application are briefly dis-
cussed.

199. A method for the determination of lead in blood by atomic-absorption spectrophoto-
metry—Donovan RP. and Feeley D.T., Publ. Anal. Lab., Galway Reg. Hosp., Galway—
ANALYST 1969, 94 (879-883)

A method for the determination of trace amounts of lead in blood is described. The organic
material in the blood is oxidized by dry ashing at 500°C and a solution of the ash in dilute
hydrochloric acid prepared. The lead in the ash solution is determined by atomic ab-
sorption at 217 nm. in an air-propane flame after isolation by a double-extraction
procedure with dithizone and ammonium tetramethylenedithiocarbamate as complexing
agents. Recovery tests are carried out and the lead content of the blood of workers from
a lead mine, determined by this method, is compared with results obtained by using the
mixed color method of the Analytical Methods Committee. Comparative tests will wet-
oxidation and dry-ashing techniques are made on samples of blood to which known
amounts of lead have been added. The interference caused by bismuth is also investigated.

200. Tests for lead poisoning—Deutsch R.H., New York Univ. Sch. of Med., New York,
N.Y.—NEW ENGL. J. MED. 1971, 285/27 (1541)

The author reports a comparison of a microfluorimetrix protoporphyrin test with micro-
aminolevulinic acid dehydratase (ALAD) assay in detection of lead exposure. The subjects
were baboons. Animals not poisoned with lead had blood lead, ALAD and protoporphy-
rin levels not appreciably different from those in humans with no detectable symptoms of
lead poisoning. In 3 experimental animals, the high blood level (which would indicate
lead poisoning in man) did not produce overt symptoms, and ALAD activity and proto-
porphyrin concentration remained within normal limits. High blood lead in baboons does
not, therefore, necessarily indicate lead poisoning. ALAD assay and fluorimetric proto-
porphyrin tests were shown to be positively correlated with one another. The latter test
is quicker than the former and further research to test its suitability for use in a mass
screening program to detect lead exposure in disadvantaged areas is suggested.

201. Significant decrease of stippled red ceels in plumbism under the influence of certain anti-
coagulants / Raréfaction importante des hérnatiee ponctuées du satumisme du fait de
certain: anticoagulants—Desoille H., Philbert M., Marin E., Rosignoli H. and Albahary
C., Inst. d’Hyg. Indust. et de Méd. du Travail, Paris—ARCH. MWL. PROF. 1970, 31/4-5
(230-236)

68

It has been observed that the enumeration of stippled red cells is more difficult in hepar-
inized smears than in smears of blood collected without the use of this anticoagulant. The
aim of the present study was to ascertain whether anticoagulants other than heparin would
have the same effect. Control studies were carried out on reticulocytes (proerythrocytes).
Lead poisoning was induced in 80 male albino guinea pigs orally administered neutral
lead acetate. Parallel studies were made of untreated blood and blood treated with: hepa-
rin; sequestrene-potassium; Wintrobe’s mixture; sodium fluoride-potassium oxalate; and
sodium citrate. The results are shown in 7 tables. A significant fall in the number of stippled
red cells was noted under the influence of sequestrene—potassium, Wintrobe’s mixture
and sodium fluoride—potassium oxalate. No modification was found with the use of hepa-
rin or sodium citrate. The influence of the concentration of the anticoagulant was studied
for sequestrene and Wintrobe’s mixture. The diminution in stippled red cells paralleled
the increase in concentration. In contrast to the stippled red cells, the number of reticulo-
cytes was uninfluenced by addition of the different anticoagulants. The exact mechanism
of the phenomenon remains obscure. Since sequestrene and Wintrobe’s mixture are being
used routinely in laboratory studies, their influence in the detection of plumbism is of
practical importance.

202. Semi-automatic determination of lead in whole blood—Delves HT. and Vinter P.,
Inst. of Child Hlth, Hosp. for Sick Children, London—J. CLIN. PATH. 1966, 19(504-509)

The procedure developed by Browett and Moss for the semi-automatic determination of
the lead content of urine has been adapted for the determination of lead in blood. Deter-
minations are normally carried out in duplicate on 2.0 ml. samples of whole blood and
the minimum sample size is 0.5 ml. The organic substances present in blood are destroyed
by a manual wet-oxidation procedure and the lead is determined colorimetrically as lead
dithizonate using a Technicon Autoanalyzer. The lower limit of detection, expressed as
3 times the standard deviation of the blank value, is 5 ,ug. lead/ 100 ml. blood. The standard
deviation of the method in the upper range of normal blood lead level of 30 ug. lead/
100 ml. blood, is :i: 3 ,ug. lead/ 100 ml. blood. Ten samples per hour may be estimated in
duplicate.

203. A micro-sampling method for the rapid determination of lead in blood by atomic-
absorption spectrophotometry—Delves H.T., Dept. of Chem. Pathol., Hosp. for Sick
Children, London—ANALYST 1970, 95 (431-438)

The concentrations of lead in 10-,ul. samples of whole blood are accurately determined
in less than 5 minutes by atomic-absorption spectrophotometry. After partial oxidation
with hydrogen peroxide in micro crucibles made from nickel foil, the samples are volatil-
ized, by using an air-acetylene flame, into a nickel absorption tube situated in the flame.
The sensitivity of the method is l x 10"°g. of lead per 1% absorption at 283.3 nm., and
the standard deviation if :t 4% at the 3 ng. level. Thirty-nine blood samples with lead
concentrations ranging from 19 to 245 ,ug./100 ml. were analyzed by the method de-
scribed and by automated colorimetry involving the use of dithiozone. The correlation
coefficient between the results of both methods was 0.989.

204. Urinary delta-aminolevulinic acid (ALA) levels in lead poisoning. II. Correlation of
ALA values with clinical findings in 250 children with suspected lead ingestion—Davis J .R.,
Abrahams R.H., Fishbein W.I. and Fabrega E.A., Dept. of Pharmacol. and Therapeut.,
Loyola Univ. Stritch Sch. of Med., Hines, [IL—ARCH. ENVIRONM. HLTH 1968, 17/2
(164-171)

69

The method for the determination of urinary d-aminolevulinic acid (ALA) from random
urine samples has been modified utilizing a dual disposable chromatographic column unit
prefilled with resin that can be conveniently held in a support rack over a drain tray.
The present procedure now permits one individual to perform as many as 1000 analyses
of urinary ALA in a normal working week. A single-blind evaluation was made of the
laboratory findings and clinical impression of increased lead exposure versus the urinary
ALA levels obtained in each of 250 children suspected of lead ingestion. It was found that
the incidence of a correct correlation between urinary ALA and the clinical diagnosis of
increased urinary ALA and the clinical diagnosis of increased lead exposure was 91%.
None of the other laboratory tests studied had a comparable degree of accuracy for the
detection of early lead exposure.

205. A simple rapid test for lead poisoning—Qazi Q.H. and Madahar D.P., State Univ.
of New York, Downstate Med. Cent., Brooklyn, N.Y.—J. PEDIAT. 1971, 79/ 5 (805-808)

The test described in this communication utilizes the phenomenon of osmotic resistance
of erythrocytes in lead poisoning and could be used for detection of children with an
increased lead burden. Preliminary observations suggested that it can identify more than
85% of children with blood lead levels of 0.06 mg. / 100 ml. or higher, and a higher percentage
of children with blood lead levels of 0.09 mg./ 100 ml. and higher. The test is rapid, simple
to perform, requires only 0.04 ml. of blood, and utilizes reagents and equipment available
in almost any laboratory.

206. A microquantitative method for determining mercury in the urine by means of im-
pregnated chromatographic paper (Bulgarian)—Nikolcheva Ya.——HIG. ZDRAVEOP.
(SOFIA) 1966, 9/ 6 (591-594)

A method for determining mercury in the urine is presented. The organic substances
are decomposed using a mixture of HZSOZ and HNC3, both in concentrated form.
Ditizone is used for extraction of the mercury. The quantity of mercury can then be deter-
mined with Whatman paper No. l impregnated in molybdenylferrocyanide. The methods
for the preparation of the paper and for the quantitative determination are discussed.

207. Fluorescence of erythrocytes in relation to erythrocyte protoporphyrin and to urinary
lead excretion—Nelson J.D., Dorn P., Rogers LE. and Sartain P., Dept. of Fed, Univ. of

Texas Southwestern Med. Sch., Dallas. Tex.~AMER. J. CLIN. PATHOL. 1968, 50 (297-
301)

Estimation of the percentage of erythrocytes which fluoresce when stimulated with near
ultraviolet light was made in 927 patients. Increased fluorescytosis was found in 97%
of patients with proved lead poisoning and in only 1.8% of patients without other historical
or laboratory evidence of lead poisoning. Comparison of the percentage of fluorescytes and
the urinary lead excretion after stimulation with calcium disodium EDTA in 89 specimens
revealed that only one patient with increased lead excretion failed to show increased fluor-
escytosis. Quantitative erythrocyte protoporphyrin determinations were performed in 35
patients. Of 23 patients with normal values( § 50 ,ug./ 100 m1. of packed red blood cells), 21
had 1% or fewer fluorescytes and two had 2 to 5% fluorescytes. In 6 specimens with slightly
elevated values (60-223 Mg/ 100 ml. of packed RBC), there were fewer than 10% fluorescytes.
All 6 patients with the markedly increased erythrocyte protoporphyrin (570-2416 ,ug./ 100
ml. of packed RBC) of lead poisoning lead over 50% fluorescing erythrocytes. These obser-
vations confirm the assumption that increased erythrocyte protoporphyrin is responsible
for the fluorescence of peripheral red blood cells.

70

208. Enhanced potassium loss in blood cells from men exposed to lead—Hasan J ., Hemberg
S., Metsala P. and Vihko V., Inst. of Occupational Hlth, Helsinki—ARCH. ENVIRONM.
HLTH 1967, 14(309—312)

Blood samples were collected from 7 shipyard workers exposed to lead oxide paint and
from 7 nonexposed control subjects. No signs or symptoms of lead poisoning could be
detected in the exposed men, and the concentration of lead in their blood did not exceed
0.07 mg./ 100 ml. During incubation in a heparinized glass tube at 37C for 2 hours, the
concentration of potassium in the plasma of blood samples from the control group con-
sistently decreased by 019-0. 62 mEq./l.; it decreased in the blood sample of one exposed
worker by 0.17 mEq./l. In the blood samples of 7 of the exposed workers, the concentra-
tions of potassium, under identical conditions, increased by 0.34-1.38 mEq./l. No dif-
ferences could be demonstrated between the mean potassium concentrations in the red
cells samples from the 2 groups. Essentially similar results were obtained in samples from
7 control subjects and 7 of the same exposed workers after an interval of 4 months. No
systematic differences were observed between the changes in sodium concentration in the
blood samples from exposed and nonexposed workers. The results are interpreted as re-
flecting a deficiency in the functional capacity of erythrocytes of men exposed to inorganic
lead, revealed by the load imposed on the cells by the incubation in vitro.

209. A simple rapid method of determining the approximate serum iron level in acute iron
poisoning—Hosking C.S., Dept. of Pathol., Univ. of Queensland—MED. J. AUST. 1969,
1 (981-982)

A simple method is described to determine whether or not the serum iron level is significant-
ly raised in acute iron poisoning. The method depends on the fact that trivalent iron is
bound by desfern'oxamine and the resultant compound, ferioxamine, is colored.

210. Determination of lead in hair by atomic absorption spectroscopy for simple screening
of lead intoxication—Hasegawa N., Hirai A., Shibata T., Sugino H. and Kashiwagi T., Res.
Inst. of Environm. Med., Nagoya Univ., Nagoya—ANN. REP. RES. INST. ENVIRONM.
MED. (NAGOYA UNIV.) 1971, 18 (1-5)

The analysis of lead in hair segments was described. In most cases a good correlation was
observed among clinical and laboratory findings and the occupational history of the pa-
tient. This analysis may provide a simple screening method in health control in the case
of lead workers who are exposed to possible lead poisoning. The time exposure to lead
was calculated.

211. Evaluation of two methods for measuring 6—aminolaevulinic acid in urine—Haeger-
Aronsen B., Dept. of Med., Malmo—SCAND. J. CLIN. LAB. INVEST. 1970, 25 (19-23)

The concentration of 6-aminolevulinic acid in the urine is known to be a good measure
of the degree of lead intoxication. The first methods for quantitative determination of the
acid were laborious but have since been simplified. One of these modifications, the one
described by Grabccki er al. was compared with the technique originally elaborated by
Mauzerall & Granick. It was found that the former procedure was as reliable as the latter,
and both quicker and cheaper. The modification by Grabccki et al. is therefore recom-
mended in the control of lead workers.

212. 6-aminolevulinic acid determination in urine by continuous flow and sequential auto-
matic analyzers / Determinazione dell’ALA nelle orine mediante analizzatori automatici a
llusso continuo e sequenziali—Grisler R., Genchi M. and Perini M., Clin. del Lav. ‘Luigi
Devoto’, Univ. di Milano—MED. D. LAVORO 1967, 60/ 11 (678-686)

71

d—aminolevulinic acid determinations in urine were carried out according to the method
of Grabecki et al. both by the Technicon Autoanalyzer, a representative of the ‘flow
system‘, and by the Clino-Mak Analyzer, a representative of the ‘discrete system‘. Both
automatic analyzers can perform 35 analyses in 1 hour and 90 in 2; moreover by the
Technicon Autoanalyzer 155 analyses can be done in 3 hours and 275 analyses in 5 hours.
The results are satisfactorily reproducible. The sensitivity, lower than 0.5 mg./ 100 ml.
allows to make determinations also on urine of normal subjects. Therefore the automatic
determination of the urinary 6-aminolevulinic acid can be largely used in industrial pre-
ventive medicine, as a quick and reliable test for the control of the degree of exposure to
lead adsorption.

213. Clinical validity for the diagnosis of lead poisoning of a new hematologic index: the
average red blood cell concentration of lead / Validita’ clinica per la diagnosi di satumismo
di un nuovo indice ematologico: 1a concentrazione eritrocitaria media del piombo—Grisler
R. and Farina 6., Clin. del Lav. ‘Luigi Devoto’, Univ. di Milano—MED. D. LAVORO 1967,
60/ 5 (360-365)

The average red blood cell concentration of lead, that is the average amount of lead pres-
ent in the single erythrocyte, calculated by the ratio between the blood lead value and the
hematocn't, was studied with the aim of evaluating its usefulness for the diagnosis of
saturnism. The values of such concentration in normal subjects of the Italian population
are lower than 1.30 with a probability of 95.45%; the maximum normal value of the con-
centration is 1.66. When compared with the blood lead levels, the values of the average
erythrocyte lead concentration in 98 saturnine patients showed a higher agreement, statis-
tically significant, with the urinary lead values in basal conditions and after administra-
tion, with the presence of basophilic stippling and of the erythrocyte protoporphyrin
IX. The authors propose to calculate the average erythrocyte concentration of lead at the
same time of the blood lead determination, and to consider the values higher than 1.30
as highly suspicious for an abnormal lead absorption; this pathologic condition would
be certain for values higher than 1.66.

214. Analysis of human hair by spark source mass spectrometry—Yurachek J.P., Glemena
GO. and Harrison W.W., Dept. of Chem., Univ. of Virginia, Charlottesville, Va.—ANALYT.
CHEM. 1969, 41 (1666-1668)

An A.E.1. MS 702 spark source mass spectrometer was used to analyze the contents of a
number of elements in human hair, including lead, iron, copper, zinc, arsenic, magnesium
and silver. Hair samples of about 100-1000 mg. were ashed at 450°C and mixed with very
high purity silver powder and graphite to produce an electrode source. Yttrium oxide was
also added as an internal standard. Very small samples of hair, in the order of 10-100 mg.,
were wet-ashed with nitric acid and with the subsequent addition of perchloric acid. This
wet-ashed material was dried and used to prepare and electrode source. With some reser-
vations, the technique appeared to give reasonably reproducible results. Thus the lead
content in, 3 aliquots of one hair sample was assayed at 52, 47 and 45 ,ug./ g. dry weight,
respectively. Some of this variation may have been due to a variation of the lead content
in the hair itself, but some of it was due to experimental error. The method is therefore
suitable for the determination of elements in hair, which may reflect the long-term status
of some trace elements in the body, and is especially significant in detecting excesses of
toxic metals such as lead.

215. Determination of lead in urine by atomic absorption spectroscopy using coprecipitation
with bismuth—Kopito L. and Shwachman H., Child. Cancer Res. Found, Boston, Mass.—
J. LAB. CLIN. MED. 1967, 70/2 (326-332)

72

Lead is separated from urine by coprecipitation with bismuth nitrate preparatory to analy-
sis by atomic absorption spectroscopy. The procedure may be used in determining lead in
freshly voided specimens and also in partially decomposed urines. The presence of bismuth
in the analyte is compatible with the analysis and suppresses interferences from sodium,
potassium, calcium, magnesium, and phosphates. This determination is relatively simple,
rapid, and may be performed in a routine clinical laboratory. Single determinations can be
done in about 15 minutes and a run of 10 determinations per hour. Lead, added to urine in
quantities of up to 100 lug. /l. is recovered with a precision of 99% and a standard deviation
of 4.5%. In patients with lead poisoning undergoing therapy with chelating agents, this
procedure is not suitable nor is it necessary since the urine contains sufficient lead to be
determined directly without prior concentration. Since the summer of 1964, this method
has been used in confirming the diagnosis of plumbism in 24 children. Over 100 urine
specimens obtained from patients with other diseases and healthy individuals served as
controls.

216. Lead in hair of children with chronic lead poisoning—Kopito L., Byers R.K. and
Shwachman H., Dept. of Clin. Pathol, Child. Cancer Res. Found., Boston, Mass—NEW
ENGL. J. MED. 1967, 276/ 17 (949-953)

A procedure for the analysis of lead in hair is described. The results, based on differences
in the lead levels of adjacent hair segments or considerably elevated concentrations, or both,
provide an additional means for confirming the diagnosis of chronic plumbism in children.
Good correlation is observed with the major clinical and laboratory findings. This method
is most useful when used in conjunction with the radiographic observations and other
laboratory data, particularly when these are equivocal and of nondiagnostic quality. Be-
cause hair is readily available and easy to obtain, this measurement may provide a simple
means for screening children exposed to possible lead intoxication. The procedure described
is not suitable for establishing the diagnosis of acute lead intoxication.

217. A polarographic method for the simultaneous determination of lead and cadmium in
urine—Knockaert O.E., Macs G.L. and Faes M.H., Dept. of Indust. Med., Cent. for Study
of Nucl. Energy, Mel—AMER. IN DUSTR. HYG. ASS. J. 1967, 28 (595-598)

This polarographic method for simultaneous determination of urinary lead and cadmium
employs one container for ashing, chemical separation, centrifugation and polarographic
recording. It covers a range from ~ 10 ,ug./l. to high concentrations. Full details are given.
Ashing is effected with a mixture of sulfuric and perchloric acids. Most satisfactory results
are obtained by ashing in the presence of nitric and perchloric acids with perchloric acid
used in quantities sufficient to minimize the explosion hazard. Residue is purified by
precipitation reactions. The best results were obtained with precipitates of mixed crystals of
Sr and Pb sulfates. The disadvantages are that several centrifugations and large amounts
of ethanol are needed. This can be avoided by using phosphate precipitations although
recoveries thus obtained are less. Presence of iron at concentrations of l mg./l. makes
analysis of microgram quantities of lead and cadmium difficult. Urine never normally
contains this amount of iron, though blood does. Acidification at the precipitation step
eliminates all elements but lead, but gives low recoveries. Details of possible interference by
copper, bismuth and thallium are given, with methods of preventing this interference.
Results of testing of I ll] urines of workers occupationally exposed to lead and 175 urines
of workers occupationally exposed to cadmium are given.

73

218. Determination of lead chelated with ethylenediaminetetra-acetie acid in blood after
precipitation of protein with perchloric aeid—Cernik A.A., Med. Branch, H.M. Fact. In-
spectorate, Dept. of Employm. and Productivity, London—BRIT. J. INDUSTR. MED.
1970, 27 (40-42)

A method is described for the determination of lead in whole blood containing ethylene—
diaminetetra-aectic acid. Proteins were precipitated by 2-0 M perchloric acid. The ionized
lead in the supernatant was chelated with ammonium pyrrolidine dithicarbamate and was
extracted with xylene. The method agreed well with a dry ashing technique (30 samples,
correlation coefficient 0-985). Perchloric acid gave consistently good recoveries, unlike
trichloroacetic acid, which frequently produced losses of up to 15%.

219. Fast hemoglobin in lead poisoning—Charaehe S. and Weatherall D.J., Dept. of Med.,
Johns Hopkins Univ. Sch. of Med., Baltimore, Md.-—BLOOD 1966, 28/ 3 (377-386)

An electrophoretically fast hemoglobin was found in approximately 40% of preschool
children with elevated blood lead levels. Fast hemoglobin was found more often in lead-
poisoned patients with hypochromic anemia than in patients with normochromic red cells.
It differed from hemoglobins produced in virro by incubation with chromate or oxidized
glutathione. It had electrophoretic properties similar to that found in a few patients re-
ceiving tolbutamide. A differentiation could not be made between fast hemoglobin and
normal hemoglobin A3 by any technic utilized. Both lead and A3 hemoglobins were
heterogeneous molecular species. The mechanism leading to the production of hemoglobin
A3 and lead hemoglobin remain unknown.

220. Determination of 6-amlnolevulinic acid in plasma—Chisolm Jr J. J ., Dept. of Fed,
Johns Hopkins Univ. Sch. of Med., Baltimore, Md.—ANALYT. BIOCHEM. 1968, 22
(54-64)

A method for determination of 6-aminolevulinic acid (ALA) in plasma is reported. The
procedure is adapted from an ion-exchange resin chromatography procedure for deter-
mination of ALA in urine. Normal fasting children and fasted patients with symptomatic
lead intoxication and acute intermittent porphyria were studied. The mean normal value
found in healthy subjects is 0.056 ,ug./ ml. This method is best suited to the study of acutely
ill patients in whom the concentration of ALA in plasma is increased by 4- to 40-fold.

221. A screening method for copper and lead in urine—Chiu 0., Ma L. and Chang H.M.,
Dept. of Chem., United Coll., Chinese Univ. of Hong Kong—MIKROCHIM. ACT. (WIEN)
1968, 6 (1224—1228)

A method for screening copper and lead in urine is described. The heavy metals are extracted
from urine using a chelating ion exchange resin, and subsequently separated by paper
chromatography. By comparing the color intensities of the metal dithizonates developed
from the standards and the samples, a semiquantitative measurement can be made.

222. Emergency semiquantitative estimation of plasma iron concentration—Cooper H.A.,
Ekblad MD. and Fairbanks V.F., Mayo Grad. Sch. of Med., Univ. of Minnesota, Roches-
ter, Minn. AMER. J. DIS. CHILD 1971, 122 (19-21)

A rapid semiquantitative method for early diagnosis of iron poisoning is described using
iron-free glassware, one drop each of tripyridyltriazine and thioglycolic acid are added to
one ml. of citrated plasma and the resultant color is compared with a graded color chart.

74

The method takes only 10 minutes to complete and the results correlate well with con-
ventional spectrophotometric methods for plasma iron levels of less than 500 ,ug./ 100 m1.
Since plasma iron levels of 300 ,ug. / 100 ml. in young children indimte the need for vigorous
therapy this estimation permits the rapid institution of such therapy. The method can also
be used to test gastric aspirates to confirm suspected iron ingestion.

Treatment and prevention

223. Treatment of acute iron poisoning—Robertson W.O., Univ. Hosp., Seattle, Wash.—
MOD. TREATM. 1967, 4 (671-678)

Acute iron poisoning is one of the most common lethal poisonings today due to the wide-
spread prescription of iron preparations for real or imagined anemia. It occurs exclusively
in children, no case having yet been reported in an adult. Overdosage of iron exerts both
local and systemic effects. There is rapid necrosis of the mucosa of the gastrointestinal
tract and subsequent severe hemorrhage. At the same time absorbed iron soon exceeds
binding capacity and it is sequestered in the liver and spleen where it is a potent proto-
plasmic poison. A severe metabolic acidosis develops rapidly. The elevated serum iron
interferes with clotting and augments the hemorrhagic process. Typically symptoms begin
with vomiting followed by lethargy, shock, metabolic acidosis with its respiratory
consequences, liver failure and deepening coma. Treatment is directed towards removal of
iron from the gastrointestinal tract, from the plasma and from intracellular locations. The
chelating agent deferoxamine has strong selective affinity for ferric iron with any affinity
for calcium. In addition general supportive therapy is necessary. Exchange transfusion has
been performed for acute iron intoxication but its value remains in doubt.

224. Treatment of lead poisoning—Chisolm Jr 1]., Dept. of Fed, Johns Hopkins Univ.
Sch. of Med., Baltimore, Md.—MOD. TREATM. 1967, 4 (710-727)

Following a number of general remarks on plumbism, the author discusses childhood
lead poisoning. Effective therapy depends on early diagnosis and treatment of acute epi-
sodes, permanent separation of the child from environmental lead sources, and prevention
of pica. Since acute encephalopathy can develop with unpredictable rapidity, any child
with symptoms suggestive of plumbism should be hospitalized immediately. Early diag-
nosis is dependent upon a high index of suspicion, a knowledge of the epidemiology of
plumbism and interpretation of specific laboratory tests. These 3 items are discussed at
length and the laboratory determinations required for diagnosis are tabulated. Treatment
comprises supportive measures and chelation therapy with dimercaprol, EDTA and
penicillamine. Dosage schedules are given, possible side effects are described and the neces—
sary precautions are listed. Convalescent and long-term care are gone into. The second part
of the paper deals with adult lead intoxication. Here, industrial exposure is the chief
hazard. Nonindustrial types of exposure are listed in a table. The laboratory parameters
used in industry for medical supervision are summarized. Principles for the use of chelating
agents are essentially the same as in the child. Indications for chelation therapy and dosage
are presented. In the author’s opinion combined dimercaprol—EDTA followed by penicil-
larnine is indicated whenever blood lead exceeds 100 ,ug./ 100 g. whole blood even in the
absence of clinical symptoms. Intoxication due to organic lead compounds (tetraethyl
lead and tetramethyl lead) occurs in the petroleum industry. Illness begins acutely with
psychotic symptoms. Urinary lead excretion is very elevated but blood lead is only slightly
high. No specific therapy is available and the mortality rate is approximately 20%.

76

225. Medical aspects of childhood lead poisoning—HSMHA HLTH REP. 1971, 86/2 (140-
143)

The US Public Health Service recommends a screening program for lead poisoning in
children aged 1-6 years living in poorly maintained houses. Lead paint was often used for
interior decoration up to 1940 and is still used externally. Plumbism can be prevented by
early detection of the risk The range of blood-leads found in the US urban population
is 15-40 pg./ 100 ml. All children with levels of 50-79 ,ug./ 100 ml. who are not diagnosed as
having lead poisoning should be closely followed and supervised, and also children under
3 years of age with levels of 40—49 lug./ 100 ml. Children with levels of 80 lug. or more per
100 ml. should be treated as emergencies, whether or not they have any signs or symptoms
of poisoning. Chelating agents should be used because 40% of such children will sustain
permanent brain damage if they develop encephalopathy. When anorexia, constipation
and cholic occurs without obvious cause, lead poisoning should be considered. Additional
evidence is: (l) a 24-hour urinary excretion of more than 1 yg./ ml. lead of Ca-EDTA
given intramuscularly at a dosage of 50 ml. /kg. bodyweight; (2) a serum 6-aminolevulinic
acid level over 20 ,ug./ 100 ml.; (3) a 24-hour urinary coproporphyrin output of over 150
,ug.; (4) a 24-hour urinary output of d—aminolevulinic acid over 5 mg.; and (5) basophil
stippling of the red cells and radiological evidence of ‘lead lines‘ in the long bones, or a
strongly positive urine spot test for coproporphyrin. When lead poisoning is suspected or
discovered, the source of lead exposure should be removed and the child followed up for
at least 6 years. Confirmed cases must also be reported to the local health authority.

226. Lead poisoning in children—J. ARKANSAS MED. SOC. 1970, 56 (290)

The hazard to man’s health from the use of lead in industry has been recognized for several
generations. Only in the last 2 decades have health workers begun to realize that lead
poisoning of children in cities is a problem of great magnitude. The widespread lead pois-
oning in children basically involves toddlers who have abnormal appetites, leading them
to act numerous nonfood items. Pica forms an essential linkage in making lead poisoning
the problem that it is. Access to crumbling lead paint is most common in older, usually
rundown housing. Lead poisoning is a preventable disease requiring a joint effort among
health workers, physicians, social workers, housing authorities and parents. One of the
first preventive measures sought was elimination of lead-based paints in housing interiors.
Since 1955, the American Standards Association has recommended that only paint with
1% of lead content or less be considered for safe use on children‘s toys, furniture and
housing interiors. Builders of modern structures have generally followed this recommenda-
tion for interiors. Hence the problem is minimal in modern homes, while it remains a
threat in older, dilapidated houses. Housing authorities can enforce housing codes to spur
repair or elimination of undesirable housing. Parents need to see that chipping and peeling
paint is removed from all interior surfaces, and that they are repainted with a safe non-
lead-based paint. Children should also be prevented from chewing or eating foreign ob-
jects. Finally, providing the child with safe, interesting toys as well as the parental attention
that all younger children require can do a great deal to prevent this disease.

227. Treatment of toxic and drug induced neuropathies—Afifi A.K. and Sabra F.A., Dept.
of Int. Med., Div. of Neurol., Sch. of Med., Amer. Univ. of Beirut—MOD. TREATM.
(N.Y.) 1968, 5/6 (1236-1248)

General treatment of toxic polyneuropathy includes removal of the toxin and treatment
of the neuritis as well as symptomatic therapy. Arsenic neuropathy may follow acute or
chronic poisoning. Arsenic is thought to react with an essential thiol group thereby in-
activating one of the components of the pyruvate and a-ketoglutarate oxidase enzyme

77

system. Treatment with dimercaprol is required for at least 10 days and generally the course
of the disability is a long one with permanent crippling in the most severe cases. Lead
neuropathy is much commoner in adults than in children. Dimercaprol is of no value in
its treatment but calcium disodium EDTA and penicillamine are more effective. Mercury
neuropathy is most commonly due to ingestion of mercury in teething powder, calomel
anthelmintics or absorption from ammoniated mercury ointment and mercury bichloride
diaper rinse. Dimercaprol in large doses as soon as possible after ingestion is effective in
acute poisoning. Thaliium neuropathy results either from accidental ingestion of rodenti—
cides or insecticides or industrially in the manufacture of sulphuric acid from iron pyrites.
Treatment is general.

228. Chelation therapy in acute iron poisoning—Leikin S., Vossough P. and Mochir-
Fatemi F., Dept. of Ped., George Washington Univ. Sch. of Med., Washington, DC.—
J. PEDIAT. 1967, 71/ 3 (425-430)

Deferoxamine, a highly specific iron chelating agent, was used in association with sup-
portive therapy in 14 children with acute iron intoxication of mild to moderate severity.
The serum iron levels and iron excretion of these patients were compared with those of 8
patients who received only supportive therapy. A rapid drop in serum iron levels occurred
in both groups. Increased urinary excretion of iron occurred in patients receiving deferox-
amine. All of the children recovered. It is recommended that this chelating agent not be
used routinely in mild cases of iron intoxication.

229. Treatment of acute iron ingestion with deferoxamine in 20 children~McEnery J .T.
and Greengard J., Hektoen Res. Inst., Dept. of Ped., Cook County Hosp., Chicago, Ill.—
.l. PEDIAT. 1966, 68/ 5 (773-779)

The use of deferoxamine in acute iron poisoning is discussed and details are given for the
management of cases of such poisoning with this drug.

230. Deferoxamine as a chelating agent—McEnery J.T., Dept. of Ped., Cook County Child.
Hosp, Chicago, Ill—J. PEDIAT. 1968, 72/ 1 (147-148)

Deferoxamine has been recommended as a chelating agent only in severe cases of iron
poisoning. It is usually not possible to accurately determine how much iron has been
ingested but most cases treated involve mildly to moderately sick children. Some of_ these
children might have died if the iron in excess of the binding capacity of the iron-binding
protein had not been chelated. No toxic effects have been observed with oral deferox-
amine, although used intravenously it has produced shock when administered rapidly. The
rate of 15 mg. /kg. / hour now recommended appears to be safe. Depending on their size
and degree of pre-existing anemia, children can tolerate serum iron levels of 500y%, but
the higher the initial serum iron level, the more likely the child is to be lethargic or in
shock. It is these patients who excrete pink colored urine while receiving 90 mg./ kg. of
deferoxamine in a continuous intravenous drip. This test has helped in the evaluation of
the need for additional chelating therapy before serum iron results are available. The child
who is not too sick initially may be the one who dies during the later phase of acute iron
overload of the liver enzyme systems. This should be preventable by the use of chelating
agents, of which the best available is deferoxamine. A table is given to show the level of
iron in 24—hour urine collection in relation to the pre-treatment serum iron levels in 38
children treated with chelating agent. It demonstrated a correlation between pink—colored
urine and high pre—treatment serum iron levels.

78

23]. Prevention of childhood poisoning. A community project—Scherz R.G., Madigan
Gen. Hosp., Tacoma, Wash.—PEDIAT. CLIN. N.-AMER. 1970, 17/3 (713—727)

The approach to the problem of accidental poisoning should be a community one with
close collaboration between the poison control center, local health department, communi—
cations media, schools, doctors, pharmacists, public health nurses, social workers and
family units. Poison control centers can supply vital information about the types of
poisonings occurring, to whom and how frequently. The doctor, in addition to treating the
patient, should be aware of the risks of repetition and caution the child’s parents, arrang-
ing, if necessary, for them to be visited by a public health worker. He should also see that
his prescriptions are properly labeled. The pharmacist, by insisting on safety precautions
and spreading information, is in a position to prevent many cases of childhood poisoning.
Nurses and social workers also have an educative role in prevention. In the US the mass
media have been used in public education programs designed to create an awareness of the
dangers of accidental poisoning. It is the pre—school child who is at greatest risk, so educa-
tional programs for the child of school age will be informational rather than preventive,
a way of reaching parents and pro-school siblings. Some community programs have been
concerned with specific poisoning problems, particularly lead poisoning from paint in old
housing. Safety packaging has helped to reduce poisoning from prescription medications
and there is a growing use of child-resistant containers (CRCs). There is evidence to show
that the rate of poisoning from substances packed in CRCs is lower than the general
average and two-thirds of the cases which did occur were due to a misuse of the CRCs.
Safer packaging is not, however, a substitute for parental vigilance, child guidance or safe
storage principles.

232. Ambulatory treatment of lead poisoning: report of 1155 cases—Sachs H.K., Blanksma
L.A., Murray E.F. and O’Connell M.J., Lead Poisoning Clin., Chicago Board of Hlth,
Chicago, Ill—PEDIATRICS 1970, 46/ 3 (389-396)

Subjects with lead concentrations greater than 50 ,ug./ 100 ml. whole blood were referred to
a municipal lead poisoning clinic for evaluation. Chelating agents were administered when
2 blood-lead levels were more than 50 ,ug. or EDTA provocative test yielded over 1000
lug/l. of lead in the urine in the succeeding 8 hours. Therapy was on an ambulatory basis.
Patients with moderate encephalopathy were hospitalized. Intramuscular EDTA, oral
penicillamine, or the 2 drugs in sequence were given to 582 patients in 1967 and to 573
patients in 1968. Clinical evidence of lead intoxication was present in 103 or 8.9% of the
1155 patients. Several drug reactions to penicillamine were observed, but none to EDTA,
and mortality dropped due to early detection and detoxification of subcliniml cases of
lead poisoning.

233. Acute iron poisoning—Bachman D.S., Nat. Inst. of Hlth, Bethesda, Md.—J. PEDIAT.
1971, 78/2 (367-368)

Treatment of acute iron poisoning is discussed. It is pointed out that gastric lavage often
fails to remove particulate matter from the stomach. The relative merits of ipecac-induced
emesis are then considered. It is felt that the latter is more effective in producing the
prompt emptying of the stomach which is the first priority in treatment. And for iron
poisoning specifically induced emesis is preferable to lavage.

234. Acute iron poisoning in children: role of chelating agents—Barr D.G.D. and Fraser
D.K.B., Dept. of Med. Paed., Roy. Hosp. for Sick Child, Edinburgh—BRIT. MED. .1.
1968, 1/5594 (737-741)

79

Sixteen cases of accidental iron ingestion treated with diethylenetriamine penta-acetic acid
(DTPA) or deferoxamine are described in detail. One fatality was associated with delay
in the onset of specific chelation therapy. In 3 severe cases recovery was associated with
large excretions of iron. Chelation data in apparently mild poisoning showed that 2 out of
12 cases excreted large amounts of iron, suggesting that potentially more severe intoxica-
tion had been averted. No toxic effects attributable to DTPA or deferoxamine occurred.
At follow-up one severe case had possible neurological sequelae. There were no instances
of gastrointestinal stenosis. From these results and a review of the literature it can be con-
cluded that these drugs are biochemically effective, are largely free of side effects, and have
probably improved the prognosis for survival and morbidity. Further evidence is needed
from cases of severe iron intoxication. ‘

235. Chelating agents in treatment of lead intoxication—Freeman R., Dept. of Paed., Prince
of Wales Hosp, Sydney—J. PEDIAT. 1969, 74/ 2 (322-324)

Lead poisoning in children in Australia is discussed in two letters. In Queensland there is
no legislation restricting the use of lead paint and the number of children affected is in-
creasing, there having been 42 cases in the last 5 years. For the last 18 months all have
received long-term treatment with d-penicillamine. Possibly this treatment of children or
young adults may avoid chronic lead nephropathy later in life. Criteria for termination of
this therapy are not yet established. Chronic renal disease may follow childhood plumbism
in Queensland, though apparently not elsewhere. This difference may be related to climate
and/or nature and duration of exposure, or to the duration of follow up. Use of blood
lead concentration, endogenous urinary lead excretion and the EDTA mobilization test is
discussed. The latter is probably the most reliable index of increased body burden of
lead. Data are presented showing that in patients with impaired renal function the EDTA
test should include a 4-day collection period but that 24 hours suffices where renal function
is normal. The test needs standardization, for results are affected by dose, rate and route
of administration. It is not known what proportion of lead excreted in this test is mobil-
ized from storage depots and what from transient recently increased absorption.

236. Experiments with different antidotes in acute poisoning by different mercury com-
pounds. Effects on survival and on distribution and excretion of mercury——Swensson A.
and Ulfvarson U., Clin. of Occupat. Med., Karolinska Sjukh., Stockholm—INT. ARCH.
GEWERBEPATH. GEWERBEHYG. 1967, 24/1 (12—50)

In these investigations, the treatment of acute poisoning with mercury compounds of
different types, with dimermprol, d—penicillamine, Rongalite C, and thioctic acid, pro-
duced an increase in the survival rate. The effect of PAS in one case may have been due
to a chance variation, and needs to be checked before it can be accepted as definitely estab-
lished. The other antidotes studied had no life saving effect. The therapeutic effect of an
antidote varied, and depended upon the type of mercury compound that had caused the
poisoning. There were also great differences between the various antidotes used with regard
to their influence on the excretion of mercury and its distribution between the different
organs. As a general assessment, it might probably be stated that, on the whole, ascorbic
acid had no essential effect. When dimercaprol and thiomalic acid were used, all the
mercury compounds studied showed an increased excretion, which corresponded to certain
similar decreases in the content of the organs. For the other antidotes, the results varied
more. It is important to point out that treatment with dirnercaprol, thioctic acid, Rongalite
C, and thioacetamide caused, in several cases, an increase in the mercury content of the
brain, even in cases in which there was increased mercury excretion as a result of treatment.
In view of the sensitivity of the CNS to mercury, this is a very important observation in

80

regard to practical therapy. With certain antidotes, for example, thioctic acid, thioacet-
amide, and PAS, a diametrically opposed effect on excretion was observed in the case of
mercuric nitrate and phenyl mercury hydroxide. This may probably be interpreted as
indicating that these compounds behave in an entirely different way in the body, and that
the phenyl mercury compound, at any rate during the short duration of the experiment,
remained mainly intact. A persistent characteristic throughout was that the methyl mercury
compound was less affected by the administration of the antidotes than were the rest of
the mercury compounds studied. In this case, the strongest effect was produced by thio-
malic acid. It is apparent that an increase in the survival rate need not be tied to an in-
crease in the excretion of mercury or even to an increase or decrease in the mercury content
in a certain organ. When a therapeutic effect occurs, it is probable that the mercury ion
or mercury complex is detached from its cellular bond and, instead becomes bound to the
antidote, as a basis for the therapeutic effect. This new compound, however, does not
necessarily have to be conveyed away. Conversely, it is conceivable that some mercury is
removed from an organ, but at the same time there is a redisposition in the cells, which
may cause a more injurious condition in the organ than when the content was greater,
and thereby increase mortality despite the decrease in the mercury content in the organs,
especially when it is in a critical organ.

237. Philadelphia combats ‘silent epidemic’ in the ghetto. Lead poisoning control—Tyler
R.L., Dept. of Publ. Hlth, Accident Control Sect., Philadelphia, Pa.—~J. ENVIRONM.
HLTH 1970, 33/1 (64—71)

The fight to prevent lead poisoning in children living in the ‘lead belt‘ of Philadelphia is
described. Substantial numbers of children still sustain brain damage in this way. Lead
poisoning has been reportable in Philadelphia since 1950. A program designed to control
lead poisoning has been set up, and in 1966 an ordinance was passed declaring lead paint
to be a health hazard and prohibiting its use where this could be a danger to children. The
source of lead is investigated in each case where blood lead exceeds .04 mg./ 100 g. blood,
and children with pica are followed up. Details of legislation, system of reporting and
investigations are given. Issuing orders for removal of hazardous paint, with court action
where necessary, have achieved a compliance rate of 79%, and damage to children has been
substantially reduced. From 1964-1968, there was an average of 155 cases and 2 deaths
annually; from 1956-1960, corresponding figures were 45 cases annually, with 7 deaths over
the whole 5-year period. In 1969 a comprehensive plan to eradicate lead poisoning in
Philadelphia, based on a resolution passed by the American Public Health Association,
involving citizen groups and a preventive program, was discussed. Details of this prospec-
tive scheme are given.

238. Ten years penicillamine / Zehn Jahre Penicillamin—Wemer T. and Weinmann H.M.,
Kreiskrankenh., Landau/Isar—MED. KLIN. 1966, 61/46 (1827-1831)

The amino acid penicillamine was detected in 1953 by Walshe in the urine of patients with
hepatic disease who had received penicillin. The free SH group present in this substance
prompted Walshe to try the use of penicillamine in heavy metal poisoning and in Wilson’s
disease with the intention of binding the free metal and eliminating it from the system.
The trial was successful. A critical review is presented of the experience gained with the use
of penicillamine during the past decade. There are 2 isomers of penicillamine. The L-form
is extremely toxic while the D-form is almost nontoxic. Its great affinity to heavy metals
endows it with important therapeutic properties. In Wilson's disease penicillamine is
capable of eliminating large quantities of the abnormal copper deposits. The practical
application of the drug is discussed in detail. Chronic lead poisoning is favorably influ-

81

enced by penicillamine. The same applies to gold intoxication. In cystinura, penicillamine
enhances the solubility and elimination of cystine. Penicillamine therapy in other diseases
like macroglobulinemia, rheumatoid arthritis, melanosis and schizophrenia is still in the
experimental stage. Side effects observed so far consist of skin eruptions, febrile reactions,
nephrotic symptoms, leukopenia, thrombocytopenia and vitamin B6 deficiency. All these
side effects occur infrequently.

239. Code of safety requirements of children’s toys and playthings—BRIT. STDS. INST.
N0. BS 3443 1968, 13 pages

The scope of the 88] code covers general safety requirements for children’s toys and play-
things but does not include items such as table-tennis balls, air guns or fireworks, which
involve risks inherent in themselves. The requirements cover provide inflammable and
extractable materials, metal edges, other construction materials for toys, and other things,
and the obligation of manufacturers to instruction, for use and packaging materials.
Among the extractable materials, prescribed in the Safety Regulations 1967, the require-
ment for lead states that a toy shall not have any coating of paint which contains lead, or
any compound of lead, in a proportion (by weight) of lead, calculated as the element,
exceeding 11,000 parts (or, after 3lst October 1968, 5000 parts) in 1,000,000 parts of the
dry paint film.

240. Acute iron poisoning. Reply—James J.A., Los Angeles County-Univ. of Southern
California Med. Cent., Los Angeles, Calif—J. PEDIAT. 1971, 78/ 2 (367-368)

A case is described of a 9 months old infant who died in shock with profuse gastrointestinal
hemorrhage about 2 hours after ingesting 11 or 12 ferrous sulfate tablets. Serum iron con-
centration was 38,000 ,ug./ 100 ml. Prompt emptying of the stomach is considered to the
first priority of treatment. The use of ipecac is favored over gastric lavage for inducing
emesrs.

241. Medical progress in the prevention of childhood lead intoxication—Greengard J.,
Zollar L. and Sharifi M., Dept. of Fed, Loma Linda Univ., Chicago, Ill.—ILLINOIS
MED. J. 1968, 133/5 (615-618 and 650)

A case finding survey aimed at detecting children in the 1-5 year age group at risk from
lead intoxication is described. Of 812 such children referred to the Cook County Hospital,
Chicago, 111., 288 or a little over one-third were considered to have body burdens of lead
high enough to be benefited by therapy. Qualitative determination of coproporphyrin III
in the urine as a screening test in case finding is extremely inefficient. A history of pica in
such children residing in deteriorated housing in the lead belt is more rewarding. In the 8
year period immediately preceding the year of this neighborhood survey, 160 children were
treated for lead encephalopathy with 6] deaths, a case fatality rate of 38.1%. During the
survey year, there were 22 admissions for lead encephalopathy with 3 deaths, a fatality
rate of 13.6%. 164 children were treated as outpatients with a daily intramuscular injection
of mlcium disodium edetate in a 5-day course. The risk of this procedure was recognized.
No instance of aggravated lead intoxication in this group was documented. Some method
of separation of such children from their source of lead is recommended.

242. Deferoxamine in the treatment of acute iron poisoning. Clinical experiences with 172
children—~-Westlin W.F., Res. Dept, CIBA Pharmaceut. Co., Summit, N.J.—CLIN.
PEDIAT. (PHILAD) 1966, 5 (531-535)

82

Deferoxamine is a potent specific iron-chelating agent whose use in treatment of acute iron
poisoning in 172 patients is described. 2000 cases of acute iron poisoning occur in the US
annually; 45% may be fatal. All the 172 patients except 1 were young children. In 36% the
amount ingested was unknown; 50% had taken more than 3 g. Overall mortality was only
1.7%. Serum iron levels appeared to be of prognostic significance, in contradiction to
results reported elsewhere. Incidence of shock or coma was greater with higher levels.
Deferoxamine forms an adjunct to standard methods of treatment. When given orally, it
will remove ingested iron from the gut but is only absorbed to a small extent, so intra-
muscular or intravenous administration is necessary to chelate absorbed iron. Intramuscu-
lar administration is preferable because it avoids the potential hazard of drug-induced
hypotension; however where the patient is comatose or collapsed with severe poisoning
deferoxamine should be given by slow intravenous administration. Details of dosage and
administration techniques are given. Deferoxamine and the complex which it forms with
iron are excreted almost entirely by the kidney, so treatment is contraindicated where renal
function is impaired unless dialysis is used.

243. The treatment of poisonings - aggressive or conservative?—James J.A.—J. PEDIAT.
1970, 76/4 (651-652)

Should treatment of poisoning be aggressive or conservative? A good example for the
answer to this question is given in the treatment of iron poisoning. When dogs are given a
lethal dose of ferrous sulfate, an exchange transfusion with an infusion of deferoxamine,
in most cases, proved effective. Can these data be extrapolated to the clinical situation of
poisoned children? In infants the mortality rate of iron poisoning is small: in a recent
series of 66 consecutive children admitted to the Los Angeles County-University of Southern
California Medical Center there were no deaths. In 172 cases from several medical centers
there were only 3 deaths (1.7%). Most of these patients received only deferoxamine with
supportive therapy. The value of exchange transfusions will be most difficult to define in
these circumstances in clinical medicine. Better means will be necessary for the early recog-
nition of a child who has ingested a lethal or probably lethal dose of iron.

244. Clinical uses of metal-binding drugs—Chenoweth M.B., Biochem. Res. Lab., Dow
Chem. Co., Midland, Mich.—CLIN. PHARMACOL. THER. 1968, 9/3 (365-387)

Arsenic and mercury poisonings call for immediate systematic treatment with dimercaprol;
symptoms of chronic lead poisoning respond well to systemic calcium disodium edetate;
Wilson’s disease is ameliorated by oral d-penicillamine; and all the other situations dis-
cussed are still experimental and sub judice. Many of the observations reported on the
effects of these drugs do not seem to be clearly related to metal binding. Certain toxic
metals such as cadmium, thallium, beryllium, and manganese have as yet no notably effec-
tive antidotes.

245. The use of chelating agents in the treatment of acute and chronic lead intoxication in
childhood—Chisolm Jr 1]., Dept. of Fed, Johns Hopkins Univ. Sch. of Med., Baltimore,
Md.—J. PEDIAT. 1968, 73/1 (1-38)

The toxicologic studies reported here provide supportive evidence that prompt institution
of chelation therapy with the combination of dimercaprol and CaEDTA together with
appropriate supportive therapy can reduce substantially the mortality rate of acute ence-
phalopathy in children with lead intoxication. Treatment of acute encephalopathy with
EDTA alone is associated with a mortality rate of 25% or greater. The author reported no
deaths in 24 cases of acute encephalopathy treated with dimercaprol and EDTA. Bio-

83

chemical data also indicate that the dimercaprol-EDTA combination is superior to EDTA
alone in the treatment of severe acute toxic episodes of plumbism. Evidence presented also
suggests that long-term oral administration of d-penicillamine is safe and may be effica-
cious in the management of the chronic phase of lead poisoning. The rationale for the use
of each of these 3 Chelating agents is discussed.

246. Treatment of acute iron intoxication with deferoxamine: a report of six cases. Chelating
agent proves effective in management of acute iron poisoning—Coli R.D., Leone LA. and
Albala M.M., Dept. of Oncol., Rhode Island Hosp., Providence, R.I.—R.I. MED. J. 1967,
56/8 (549-553, 578—579)

The iron chelating agent, deferoxamine, has given promising results in the treatment of
acute iron poisoning in children. In 172 cases of various degrees of severity, it reduced the
mortality to 1.7% (3 deaths). This is a report on 6 children who accidentally ingested toxic
doses of ferrous sulfate. The first child took 6.0 g. and vomited repeatedly but was never
severely ill and rapidly recovered after gastric lavage and 3 g. of deferoxamine methane-
sulfate orally with l g. intramuscularly. The second child became lethargic and incontinent
after 5.9 g. His clinical course was that of acute iron poisoning, initial improvement being
followed by a relapse ending in coma, convulsions and death. The third child took a much
larger amount (19.5 g.) and had a higher serum-iron content than the child who died but
recovered uneventfully. The management of acute iron intoxication includes gastric lavage,
correction of acidosis and electrolyte abnormalities, and vigorous treatment of cardio-
vascular collapse. Chelating agents, of which deferoxamine is the most potent, are impor-
tant adjuncts. Deferoxamine has a high affinity for plasma iron in vitro, but in vivo it
removes only insignificant amounts of iron from transferrin and does not remove iron
from the bone marrow or from hemoglobin. Given parenterally, it competes with trans-
ferrin for plasma iron and forms a complex with excess ferric ions, rendering them non-
toxic. Chelating agents have strikingly reduced the mortality from iron poisoning, and
deferoxamine has proved the most potent and specific and also the safest of them. After
parenteral deferoxamine, the serum-iron levels return to normal or subnormal in 12-36
hours. This is a more rapid fall than is obtainable with EDTA, and deferoxamine does
not increase the excretion of sodium, potassium, calcium, magnesium, or any of the impor-
tant trace metals, such as copper and zinc. No toxic effects have been reported. Large oral
doses may slightly aggravate the diarrhea by causing additional intestinal irritation, but
this effect may be actually helpful in promoting the elimination of deferoxamine-bound
iron. Rapid intravenous injections sometimes produce a rash, transient tachycardia and
hypotension, and they should therefore be reserved for patients who are already in coma
or shock. The initial dose of deferoxamine recommended for norrnotensive patients with
suspected iron intoxication is 5-10 g., given after gastric lavage, followed by 1-2 g. intra-
muscularly every 12 hours for 1-2 days. Intramuscular injection seems to be an acceptable
alternative to intravenous infusion, which has been used in most of the reported cases.

247. Treatment of lead encephalopathy in children—Coffin R., Phillips J.L., Staples W.I.
and Spector 8., Dept. of Fed, Western Reserve Univ. Sch. of Med., Cleveland, 0—].
PEDIAT. 1966, 69/2 (198-206)

A method for the treatment of severe lead encephalopathy using the combination of
calcium EDTA and dimercaprol is presented. Twenty-two patients have been treated be-
tween 1954 and 1965 with only 1 death. The rationale for the use of this treatment is
discussed, as well as measures intended to reduce cerebral edema.

84

Subject Index

Prepared by N. van Strijthem, M.D.

acridine orange staining
lead poisoning, 192
acrodynia
27,113,115,116,129,135,149
acute basophilic myelocytic leukemia
133
acute intermittent porphyria
lead poisoning similarity, 22, 24, 57
acute iron poisoning
4, 47, 112, 130, 140, 143-146, 223, 228,
233, 234, 240, 242, 243, 246
autopsy, 145
diagnostic test, 209, 222, 230
fatality, 144, 145, 234, 242, 246
gastric lavage, 112, 140, 146, 233, 240,
246
pathology, 4, 144, 145
pneumoperitoneum, 145
serum iron level, 140, 240, 242
therapy, 112, 140, 143, 146, 223, 228-
230, 233, 234, 240, 242, 243, 246
acute leukemia
133
age
hair trace metal level, 93
ALA
see delta aminolevulinic acid
ALA dehydrase
see delta aminolevulinase
albinism
lead exposure, 170
alkoxyalkyl mercury fungicide
60
alkylmercury
25, 29
alkylmercury fungicide
25, 60
alkylmercury fungicide poisoning
25, 29, 102
alopecia
eyelashes, eyebrows, 117
mercury poisoning, 117

alpha globulin synthesis
lead poisoning disturbance, l9
aminoacetone
metabolic cycle, 35
aminoaciduria
lead poisoning, 151
delta aminolevulinase
13, 24, 155, 162, 169, 195, 200
delta aminolevulinic acid
cerebrospinal fluid, 164
plasma determination, 220
delta aminolevulinic acid blood level
determination method, 220
lead poisoning diagnosis, 3, 46, 157,
164, 225
delta aminolevulinase brain level
lead poisoning, 13, 162
delta aminolevulinic acid dehydrase
see delta aminolevulinase
delta aminolevulinic acid synthetase
ferric iron influence, 179
ferrous iron influence, 179
delta aminolevulinic acid urine level
automatic analysis, 212
blood lead level, comparison, 166, 177
determination method, 189, 204, 212
diagnostic value, 157, 162, 165, 166,
193, 211
lead poisoning diagnosis, 3, 5, 24, 34, 43,
57, 94, 156, 165, 204, 225
mean excretion, 159
organic lead poisoning, 24
screening test, 157, 175, 193
seasonal variation, 159
amnesia
124
amytal sodium
lead encephalopathy treatment, 128
anemia
absence, lead poisoning, 124, 131, 172
lead poisoning, 2, 5, 19, 20, 24, 63, 88,
90,122,128,131,148,152, 219

85

antepartum hemorrhage
lead exposure, 170
anterior horn nerve cell
lead poisoning damage, 24
anthelmintic agent
mercury poisoning source, 27
anticoagulant agent
erythrocyte basophilic stippling, 201
reticulocyte, 201
antidiuretic hormone
22
aphasia
lead poisoning, 124, 125
apple juice colic
fatality, 58, 98
arsenic
baby powder, 106
environmental exposure, 93
hair, 93
arsenic detection
biologic material, 187
arylmercury fungicide
60
ascorbic acid
186
mercury poisoning, 236
ataxia
136
atomic absorption spectrophotometry
lead determination, 45, 173, 176, 182,
197, 199, 203
automatic analysis
blood lead determination, 202
urinary delta aminolevulinic acid, 212
axon degeneration
24

baby powder

hygienic evaluation, 106

lead concentration, 106
BAL therapy

see dimercaprol therapy
basophilic stippling, erythrocyte

see erythrocyte basophilic stippling
battery case

lead poisoning source, 19, 73
behavior

pica, 96
behavior disorder

lead poisoning, 124, 125, 150
beta globan synthesis

86

lead poisoning disturbance, l9
bismuth
lead determination interference, 199,
217
simulating lead poisoning, 168
urinary lead determination, 215
blood glucose
see glucose blood level
bone disorder
differential radiodiagnosis, 133
bone growth
lead poisoning, 7, 110
bone lead line
6, 7,107,124,151,154
absence, 132, 137, 151
hyperprolinuria, 151
pathogenesis, 7, 151
bone marrow
lead poisoning, 24, 57
unusual finding, 122
bone metaphysis
lead poisoning, 7
bone sclerosis
generalized, lead poisoning, 147, 148
brain
see also nerve cell and brain damage
biochemical abnormality, 13, 49, 162
iron toxicity, 144
lead concentration, 132
mercury concentration, 236
methylmercury poisoning, 49, 102
trace elements, 49
brain edema
lead encephalopathy therapy, 21, 247
lead poisoning, autopsy, 132
brain damage
see also brain, lead encephalopathy and
mental retardation
electron microscopy, 138
lead poisoning, 20, 28, 33, 37, 89, 132,
237
Minamata disease, 102, 142
breast feeding
lead concentration, 81
mercury poisoning source, 92
Burton’s blue line
19, 20, 132, 137, 148, 153

cadmium

environmental exposure, 93
cadmium 109

181
cadmium blood level
105
cadmium hair level
93
cadmium urine level
polarographic detemiination method, 217
Ca-EDTA
see ethylenediamine tetra-acetic acid
calcium
lead poisoning therapy, 20, 21
calcium excretion
dcferoxamine therapy, 246
calcium sodium edetate
see ethylenediamine tetra-acetic acid
calcium versenate therapy
see ethylenediamine tetra-acetic acid
therapy
calomel
mercury poisoning source, 27, 87
capillary permeability
lead poisoning, l7
cardiovascular disease
water lead concentration, 1 1 l
cartilage
lead poisoning, 7
catecholamine
mercury influence, 75
central nervous system
lead toxic effect, 17
methylmercury poisoning, 102
cerebellum
methylmercury poisoning, 102
cerebral palsy
lead encephalopathy, 136
cerebrospinal fluid
delta aminolevulinic acid, 164
lead poisoning, 21, 43, 119, 132
mercury poisoning, 129
chelation therapy
see also deferoxamine-, dimercaprol-,
ethylenediamine tetra-acetic acid- and
penicillamine therapy
2, 6, 29, 43, 46-48, 112, 122, 124, 140,
143, 166, 173, 196, 215, 224, 225,
228-230, 232, 234, 235, 244-246
chronic lead poisoning
see also lead poisoning
23, 28, 31, 42, 44-47, 58, 70, 71, 79, 110,
124, 131
case report, 108, 123-125, 127, 147, 148,
152

diagnosis, 5, 152, 216
lead hair concentration, 216
mimicking motoneuron disease, 108
penicillamine therapy, 238
therapy, 238, 244
chronic mercury poisoning
47, 113, 117
case study, 117, 129
neurological symptomatology, 129
congenital iron overload
case report, 134
familial iron transfer disturbance, 134
congenital lead poisoning
83
congenital listeriosis
114
congenital mercury poisoning
54
congenital nystagmus
lead exposure, 170
Coombs test
lead poisoning, 188
copper
environment, 93, 103
lead determination interference, 217
copper blood level
105
copper concentration
baby powder, 106
copper hair level
93
copper urine level
screening method, 221
coproporphyrinogen
178
coproporphyrin urine level
determination, 178
gasoline lead poisoning, 97
lead poisoning diagnosis, 2, 3, 6, 1'7, 24,
43, 44, 46, 90, 124, 147, 155, 162, 170,
172, 178, 225
lead poisoning screening, 110, 241
lead poisoning therapy, 45
cosmetics
eye cosmetic, Surma, 77, 88
lead poisoning source, 77, 88
lipstick, 77, 88
cow milk
lead concentration, 81
cresyl blue staining
proerythrocyte, 192

87

D-penicillamine
see penicillamine
deferoxamine
sodium excretion, 246
toxicity, 4
deferoxamine test
acute iron poisoning, 230
deferoxamine therapy
see also chelation therapy
acute iron poisoning, 4, 112, 130, 140,
143, 146, 223, 228-230, 234, 242, 243,
246
dementia
125
demyelination
24
dental filling
mercury poisoning source, 116
dexamethasone
20, 21
dextrose
hypertonic solution, 20
therapeutic use, 20
diarrhea
neonatal mercury poisoning, 92
diethylenetriamine penta—acetic acid
234
dimercaprol
ethylenediamine tetra-acetic acid
combination therapy, 245, 247
mercury poisoning diagnosis, 129
dimercaprol therapy
see also chelation therapy
lead poisoning, 2, 6, 10, 20, 21, 29, 37,
43, 91,110,114,115,119,141,224,
227, 236, 244, 245, 247
down syndrome
see mongolism
drinking water
see water

earthenware
lead poisoning source, 16, 17, 56, 58, 98,
123
EDTA
see ethylenediamine tetra-acetic acid
EEG
lead poisoning, 114, 125, 132
mercury poisoning, 54, 142
Minamata disease, 142
electroencephalography
see EEG

88

electromyography
see EMG
EMG
mercury poisoning, 54
epilewy
24
epiphyseal cartilage
lead poisoning, 7
epiphyseal plate
lead poisoning, 7
ergastoplasm
lead encephalopathy, 138
erythrocyte basophilic stippling
20, 43, 114, 128, 132, 137, 152, 192,
213. 225
absence, 122, 124
anticoagulant agent, 201
heparin, 201
potassium oxalate, 201
reticulocyte, 192
sequestrene-potassium, 201
sodium citrate, 201
sodium fluoride, 20]
Wintrobe’s mixture, 201
erythrocyte fluorescence
lead poisoning, 90, 192, 207
erythrocyte hypoplasia
122
erythrocyte osmotic resistance
lead poisoning, 205
ethylenediamine tetra-acetic acid
lead mobilization test, 90, 107, 109, 122,
131,161,183, 235
urinary lead estimation, 190
ethylenediamine tetra-acetic acid therapy
see also chelation therapy
acute iron intoxication, 246
chronic lead encephalopathy, 125
lead neuropathy, 227
lead poisoning, 2, 6, 10, 20, 21, 29, 37,
43, 45, 73,110, “4,118,119,124,
128, 224, 232, 244, 245, 247
exchange transfusion
acute iron poisoning therapy, 223, 243
exornphalos
see omphalocele
eyebrow alopecia
mercury poisoning, 117
eyelash alopecia
mercury poisoning, 117

fast hemoglobin

hypochromic anemia, 219
lead poisoning, 219
Feer’s disease
differential diagnosis, 126
spondylitis symptomatology, 126
ferric iron
delta aminolevulinic acid synthetase,
179
deferoxamine, 223
ferrous iron
delta aminolevulinic acid synthetase,
179
ferrous sulfate poisoning
see acute iron poisoning
fetal death
see stillbirth
fish
lead content, 5, 103
mercury concentration, 25, 94
mercury poisoning source, 60, 62, 87,
102
fluorescytosis
lead poisoning, 90, 192, 207
fungicide
mercury poisoning source, 25, 113, 129

gasoline burn

lead absorption, 97

skin biopsy, 97
gastrointestinal stenosis

prevention, 234
gestation

lead exposure, 15, 83
gingival lead line

see Burton’s blue line
glia cell

lead encephalopathy, 138
globulin synthesis

lead poisoning disturbance, 19
glucose blood level

acute iron poisoning, 140

lead encephalopathy, 124
glycoslu'ia

absence, lead encephalopathy, 124

lead encephalopathy, 124

lead poisoning diagnosis, 21
Golgi apparatus

lead encephalopathy, 138
granular ergastoplasm

see ergastoplasm
growth hormone

22

growth retardation
intrauterine, 83

heart arrhythmia

107
heme synthesis

see also porphyrin metabolism

lead poisoning, 5, 6, 17, 22, 24, 31, 37,

162

heme synthetase

24
hemoglobin

blood lead level, 5, 137

lead poisoning, 24, 219
hemoglobin A,

fast hemoglobin, 219
heparin

erythrocyte basophilic stippling, 201
hydrocephalus

acute communicating, 121

lead poisoning, pathogenesis, 121
hydroxyproline

lead poisoning, 151
hyperaminoaciduria

lead poisoning, 151
hyperprolinuria

lead poisoning, 151
hypochromic anemia

fast hemoglobin, 219
hypophysis

lead poisoning, 22
hypothalamus

lead poisoning, 22

infection
lead encephalopathy, 131
intelligence quotient
44, 124, 125
intestine
acute iron poisoning, 144
ipecac
acute iron poisoning therapy, 112, 233,
240
iron
urinary lead determination, 217
iron blood level
acute iron poisoning, 112, 140, 228, 230,
242
determination method, 130, 209
emergency semiquantitative
method, 222
prognostic value, 242

89

iron detection

histological sections, 198

X-ray fluorescence, 198
iron overload

congenital, familial, 134
iron poisoning, acute

see acute iron poisoning

kidney
lead concentration, 20, 45, 132
mercury concentration, 51
methylmercury poisoning, 102
kidney disease
lead poisoning, 5, 9, 10, 20, 21, 42, 70,
110, 151, 235
mercury poisoning, 52, 87, 141

lactodehydrogenase erythrocyte level
isoenzymatic fraction changes, 184
lead poisoning, 184
lactodehydrogenase IV
lead poisoning, 184
lactodehydrogenase V
lead poisoning, 184
LDH
see lactodehydrogenase IV and V
lead
biochemistry, 17, 31, 32, 35, 37, 45
body distribution, 3, 39, 45, 55, 67, 100,
104, 131
daily permissible intake, 29, 39, 100
environmental aspects, 1, 5, 15, 20, 26,
55, 57, 67, 69, 72, 79, 93, 94, 103, 105,
169
fecal, see lead feces level
lethal dose, 39
in situ determination, 181
skin biopsy, 97
urine, see lead urine level
lead absorption
3, 11, 32, 39, 45, 153
gasoline burn, 97
maximum daily intake, 39, 100
psychotic children. 137
lead blood level
2, 3, 5, 6, 8,11,13,15, 21, 23, 24, 29,
34, 37, 43-46, 69, 81, 85, 90, 95, 110,
147, 150, 173, 174, 200
delta aminolevulinic acid dehydrase, l3
capillary blood, 157
coproporphyrinun'a, 172
environmental lead, 15, 55, 137, 169

hematocrit, 213
hemoglobin level, 137
lead exposure, 208
lead poisoning diagnosis, 21, 124, 128,
l31,147,150,163,164,174, 200, 225
mental retardation, 13, 23, 109, 162
mongolism, 7.3
pregnancy, 170
seasonal influence, 137, 173
umbilical cord, 15
urinary delta aminolevulinic acid, 166,
177, 193
19 US-cities, 105
lead blood level determination
ethylenediamine tetra-acetic acid, 218
interlaboratory evaluation critique, 194
method, 173, 176, 182, 196, 197, 199,
218
micromethod, 177, 186, 203
semiautomatic method, 202
lead bone level
104
lead poisoning, 45, 55
lead brain level
132
lead button
fatal lead poisoning source, 1, 132
lead determination
45, 180, 182, 190, 199
biological material, 187
histological sections, 198
instrument, 12, 181, 191
micromethod, 186
screening, 181
spot test, 185
lead 210 determination
biological sample, 180
lead encephalopathy
see also brain damage,
and mental retardation
10, 20, 21, 28, 34, 37, 39-44, 45, 46, 59,
76, 77, 90, 97,121,124,127,131,136,
147, 148,164, 241
brain biopsy, 138
chronic case, 124, 125, 131
electron microscopy, 138
therapy, 21, 128, 245, 247
lead erythrocyte level
concentration, 213
determination, 196
lead poisoning diagnosis, 213
mean, 197

lead exposure
see also lead
antepartum hemorrhage, 170
epidemiology, 94
hair lead level, 93
miscarriage, 170
screening, 162, 164, 165, 170, 183, 200,
204
lead feces level
21, 29, 45,100,160
lead hair level
concentration, 93, 104
determination method, 210, 214, 216
lead poisoning diagnosis, 46, 157, 171,
216
lead inhalation
120, 148
lead intoxication
see lead poisoning
lead kidney level
20, 45, 132
lead line, bone
see bone lead linc
lead line, gingiva
see Burton’s blue line
lead liver level
45, 104, 132
lead milk level
81
lead mobilization test
see also penicillamine-lead excretion
test
109,131,161,162, 207, 235
lead muscle level
104
lead nail level
104
lead neuropathy
46
therapy, 227
lead paint
see also lead paint poisoning
33, 66, 226
legal aspect, 36, 94
safety requirement, 239
in situ detection test, 185
X-ray fluorescence detection, 181
lead paint poisoning
see also lead paint
1, 3, 8,10-12,14,16-19, 28, 33, 36, 39,

41, 44, 46, 57, 59, 66, 70, 71, 82, 85, 86.

90. 94, 95, 107, 158, 163, 174, 226

lead poisoning

see also chronic lead poisoning

1-3, 5-10, 19, 20, 22-24, 26, 28, 31, 33,
36—43, 45—48, 56-59, 63-65, 71-74, 76,
77, 79, 82, 83, 85, 88-90, 95, 97, 98,
107,108,110,118-123,127,128,131,
132, 139, 147, 148, 150-155, 172, 225,
226, 235

acute intermittent p01 phyria, comparison
24

bibliography, 9

biochemical aspect, 9, 17, 22, 31, 32, 37,
45, 162

blind children, 65

brain biochemical lesion, 13, 49

case reports, 39, 114, 118-120, 122-125,
128,132,139,147,154

climate, 235

congenital, 83

congenital listeriosis, 1 14

detection program, 12

diagnosis, 3, 6, 20, 21, 31, 32, 38, 39, 45,
46, 57, 90, 107, 110,114, 122,124,
125,128,131,133,148,153,154,161,
164,167,168,I7l,188,189,195, 200,
201, 213, 214, 225

discriminatory pica, 65

environmental aspects, 3, 17, 20, 26, 48,
57, 72, 79, 96, 1 18

epidemiological aspects, 18, 29, 34, 38,
64, 71, 90, 94,110

experimental aspects, 29, 110

fast hemoglobin, 219

fluorescent microscopy, 90, 192, 207

gasoline burn, 97

history, 18, 26, 74, 110

hydrocephalus, 121

hyperprolinuria, 151

incidence, 8, 36, 39, 41, 59, 89, 110

legal aspect, 8, 33, 34, 36, 38, 71, 86.
225, 235, 237

lymphocyte, 188

magnesium deficiency, 110

mortality, 10, 33, 37, 38, 97

neurologic sequela, 8, 11, 24, 70, 90, 136

pregnancy, 83

prevention, 6, 8, 10-12, 16, 28, 33, 36,
38, 46, 48, 90, 95, 225, 226, 231, 237,
241

protoporphyrin test, 200

psychological aspects, 44, 48, 96

radiodiagnosis, 6, 19, 21, 43, 46, 107,

s

91

114,124,147,148,151,154,l68
renal aspects, 5, 9, 10, 20, 21, 42, 70,
110, 151, 235
review, 21, 26, 28, 33, 37-39, 43, 44, 46,
47, 110
screening, 2, 3, 6, 11, 34, 36, 38, 110,
155-158,160,162,163,165,167,172-
175, 183, 193, 195, 205, 210, 225
seasonal influence, 3, 37, 43, 59, 90,
110, 137, 159
sex, 110
social aspect, 2, 10, 14, 16, 18, 33, 36,
43, 44, 46, 48, 64, 66, 86, 94-96, 107,
163, 174, 226, 231, 237
source, 1, 6, 8, 16,17,19, 21, 26, 39, 45,
46, 56-59, 71, 72, 74, 76-79, 82, 83, 85,
88, 90, 95, 98, 108, 114, 118-120, 123,
139,147,148,154
symptomatology, 3, 19-21, 34, 39, 43, 46,
90, 153
therapy, 6, 20, 21, 45, 46-48, 110, 128,
137, I61, 224, 225, 227, 232, 235, 241,
247
transplacental, 83
water, 139, 170
lead poisoning, chronic
see chronic lead poisoning
lead sweat level
45
lead toxicity
11, 31, 42, 67,107
marine organism, 103
lead urine level
determination method, 190, 191, 196,
215, 217, 221
gasoline burn, 97
lead poisoning, 3, 21, 43-45, 97, 107,
109, 131,161, 163, 207, 225
lead water level
111
leukemia
unusual skeletal abnormality, 133
leukocytosis
acute iron poisoning, 140
leukopenia
penicillamine therapy side effect, 238
listeriosis, congenital
see congenital listeriosis
liver
see also liver cell
20
iron toxicity, 144, 145

92

lead concentration, 45, 104, 132
lead detection, 187
mercury detection, 187
methylmercury poisoning, 102
liver cell
acute iron poisoning, 145
liver necrosis
rabbit, 4
lung
miliary shadows, 147, 148
lymphocyte
lead poisoning, 188

magnesium deficiency
lead poisoning, 110
magnesium urine level
246
mannitol
therapeutic use, 21
Manson-Schwarz stain
192
mass screening
lead poisoning mass detection, 167
measles
37
melanophoric hormone
22
MELC
see lead erythrocyte level
mental retardation
see also brain damage and lead
encephalopathy
5, 10, 13, 23, 25, 37, 40, 44, 89, 109,
114,124,125,129,136,150,162
mercurous chloride
see calomel
mercury
absorption, 52
age difference, 51
autopsy material, 51, 84
biochemical aspects, 75
biological methylation, 30, 60
brain damage, 49
detection, 187
environmental aspects, 25, 27, 30, 54, 60,
62, 99, 102
fecal excretion, 29
kidney concentration, 51
tissue concentration, 51, 61, 84
urine, see mercury urine level
mercury blood level
29, 53, 62,115,135

mercury brain level
236
mercury encephalopathy
see Feer’s disease
mercury intoxication
see mercury poisoning
merclu'y kidney level
51
merclu'y neuropathy
therapy, 227
mercury ointment
poisoning source, 52, 75, 78, 91, 92, 101,
129, 141
mercury poisoning
see also acrodynia, chronic mercury
poisoning, F eer’s disease and Pink
disease
47, 53, 61, 80, 92, 102, 236
acute, 47
alopecia, 117
case reports, 92,115,116,129,135,l41,
149
congenital, 54
cutaneous absorption, 75
during pregnancy, 54
eczema treatment, 101
EEG, 142
environment, 25
enzyme activity inhibition, 49
epidemiological aspect, 29, 84
etiopathology, 116
experimental aspect, 29
fatality, 53, 80, 84, 91, 135
food contamination, 29
incidence, 50, 80
mortality, 80
neonatal period, 54
neonatus, 92
neurological sequela, 54
neurological symptomatology, 129
pathogenesis, 75
presenting as encephalitis, 84
prognosis, 116
renal tubular acidosis, 141
review, 47, 80
source, 27, 50, 52-54, 62, 75, 78, 80,
84, 87, 91, 92,101,102,113,115,117,
129, 135, 141
symptomatology, 87, 91, 113, 116
therapy, 47, 149, 227, 236, 244
transplacental, 54
merclu'y poisoning, chronic

see chronic mercury poisoning
mercury pollution
see mercury
mercury urine level
determination method, 206
mercury poisoning, 61, 75, 78, 129, 135,
141, 149
Methanobacterium omelanskii
30
methylmercury
see also methylmercury poisoning
25, 30, 87, 236
methylmercury poisoning
see also methylmercury and Minamata
disease
autopsy finding, 102
EEG, 142
fetal effect, 30
genetic effect, 30
intrauterine poisoning, 102
occurrence, 30
review, 30
source, 54, 102
symptomatology, 30, 102
milk
lead concentration, 81
Minamata disease
see also methylmercury poisoning
25, 54, 60, 102, 129
EEG study, 142
history, 25, 102
miscarriage
lead exposure, 170
mongolism
blood lead level, 23
motoneuron disease
chronic lead poisoning, 108
muscle
. lead concentration, 104
myelin sheath
lead encephalopathy, 138

nerve
methylmercury poisoning, 102
nerve cell
see also brain
lead effect, 17, 49
lead encephalopathy, electron
microscopy, 138
neurological complication
acute iron poisoning. 234
lead poisoning, 8, 11, 20, 24, 37, 46, 57,

93

83, 90, 136
mercury poisoning, 75, 129
news paper
pica, lead poisoning, 63
nystagmus V
132
congenital, 170

old house paint

see lead paint poisoning
omphalocele

merbromin treatment, mercury poisoning

source, 53, 61

optic atrophy

136

orange acridine staining, 192
osmotic resistance, erythrocyte

see erythrocyte osmotic resistance
osteoblast

7, 151
osteoclast

7, 151
oxidative metabolism

iron overload disturbance, 4

paint poisoning
see lead paint poisoning
paraldehyde
lead encephalopathy treatment, 20, 43,
128
parathormone
21
PAS
236
pencil paint
lead poisoning source, 82
penicillamine
drug reaction, 232, 238
penicillamine-lead excretion test
see also lead mobilization test
162
penicillamine therapy
see also chelation therapy
review, 238
therapeutic use, 20, 21, 29, 37, 52, 75,
110, 135, 141, 149, 150, 224, 227, 234,
235, 236, 244
treatment control, 57
phenobarbital
lead encephalopathy treatment, 20
phenylmereury
25

94

phenylmercury hydroxide
236
pica
1-3, 8, 12, 20, 28, 33, 37, 43, 44, 46, 63,
68, 70, 71, 79, 85, 90, 94-96, 107, 109,
110, 150, 162, 172, 174, 226, 241
behaviorism, 96
discriminatory, 65
Pink disease
52, 75, 78, 80, 87, 91,101,113,135
placenta transport
poisoning, 54, 67, 83, 102
plumbism
see lead poisoning
pneumoperitoneum
acute iron poisoning, 145
poison control center
41, 231
poisoning
incidence, 50, 89
prevention, 50, 231
review, 39, 41, 47
source, 50
polyradiculoneuropathy
129
pork
methylmercury poisoning source, 54, 60
porphobilinogen
urine, 22
porphyria
acute, intermittent, 22, 24
porphyrin metabolism
see also heme biosynthesis
disturbance, 22, 24, 131
potassium blood level
lead exposure, 208
potassium erythrocyte level
lead exposure, 208
potassium oxalate
erythrocyte basophilic stippling, 201
potassium urine level
246
prednisolone
therapeutic use, 118
pregnancy
lead exposure, 170
lead poisoning, l3
methylmercury poisoning, 102
transplacental lead poisoning, 83
transplacental methylmercury poisoning,
54
proerythrocyte

see reticulocyte
prollnuria

lead poisoning, 151
protoporphyrin

24

diagnostic value, 162
protoporphyrln erythrocyte level

24, 207, 213

diagnostic value, 24, 162

erythrocyte fluorescence, 207

organic lead poisoning, 24

quantitative determination, 207
protoporphyrin test

delta aminolevulinic acid dehydratase,

200

lead poisoning, 200
psychornotor retardation

see mental retardation
psychosis

lead absorption, 137

pica and lead poisoning, 85
pylorus stenosis

iron poisoning, 146

radiodlagnosis
acute iron poisoning, 143
lead detection, 181
lead poisoning, 6, 19, 21, 43, 46, 107,
114,124,133,147,148,151,154,l68
metal and metalloid detection, 198
reticulocyte
122
anticoagulant influence, 201
cresyl blue staining, 192
erythrocyte basophilic stippling, 192
retina pigmentation
20, 90
Roentgen fluorescence
see radiodiagnosis
Rongalite C
mercury poisoning therapy, 236

sequestrene-potassium
erythrocyte basophilic stippling, 201
sex
hair trace metal level, 93
silver 109
181
snoking
lead poisoning, l, 15, 42
sodium blood level
lead exposure, 208

sodium calcium EDTA
see ethylenediamine tetra-acetic acid
sodium calcium ethylenediamine tetra-
acetic acid
see ethylenediamine tetra-acetic acid
sodium citrate
erythrocyte basophilic stippling, 201
sodium EDTA
see ethylenediamine tetra-acetic acid
sodium ethylenediamine tetra-acetic acid
see ethylenediamine tetra—acetic acid
sodium fluoride
erythrocyte basophilic stippling, 201
sodium urine level
deferoxamine therapy, 246
soft tissue
lead concentration, 20, 37, 45, 104
somatotropic hormone
see growth hormone
speech disorder
chronic lead encephalopathy, 124, 125
spinal cord
lead poisoning, 24
spinal fluid
see cerebrospinal fluid
spleen
iron toxicity, 144
stillbirth
lead exposure, 170
stomach aspirate
iron poisoning diagnosis, 222
stomach lavage
acute iron poisoning, 112, 140, 146, 233,
240, 246
stomach mucosa
acute iron poisoning, 144
stomach perforation
145
sun exposure
lead poisoning, 3, 37, 43, 59, 90, 110,
137, 159
sweat
lead concentration, 45

“teething powder

mercury poisoning source, 27, 78, 80, 87
tetraethyl lead

gasoline burn, 97
tetramethyl lead

gasoline burn, 97
thallium

lead determination interference, 217

95

thallium detection

biologic material, 187
thioacetamide

mercury poisoning treatment, 236
thioctic acid

mercury poisoning therapy, 236
thiomalic acid

mercury poisoning treatment, 236
thrombocytopenia

penicillamine therapy side effect, 238
thyrotropin

lead poisoning, 22
tobacco

see smoking
toys

lead poisoning source, 71, 85

safety requirement, 239
trace elements

55, 103,105, 187,191

brain, 49

hair concentration, 93
transferrin

deferoxamine, 246

ultraviolet radiation
see sun exposure
umbilical hernia
see omphalocele
Unna-Pappenheim stain
large lymphocyte, lead poisoning, 188
urea
hypertonic, lead poisoning therapy, 20,
21
urine
deferoxamine treatment, 146
lead detection, 188
mercury detection, 188
uroporphyrin

96

22
uroporphyrinogen
22
versenate therapy
see ethylenediamine tetra-acetic acid
therapy
visual impairment
lead encephalopathy, 121
vitamin Ba deficiency
penicillamine therapy side effect, 238
vitamin D
20, 21, 26

water

lead concentration, 11]

lead poisoning source, 20, 139, 170
wheat seed

mercury poisoning source, 84, 113
whiskey

transplacental lead poisoning source, 83
Wilson's disease

49, 244
Wintrobe mixture

erythrocyte basophilic stippling, 201
Wright stain

lead poisoning, 192
wrist-drop

19, 41

X-ray diagnosis
see radiodiagnosis

n'nc
environment, 93, 103
hair, 93
zinc blood level
105
zinc urine level
246

Index of authors

Abrahams, R. H., 165, 204
Ackefors, H., 60

Afifi, A. K., 227

Agnese, G., 155

Aksungur, L., 113
Albahary, C., 201

Albala, M. M., 246
Albert, R. 13., 181

Alessio, L., 184
Alexander, J. F., 115
Alpert, J. J., 6

Ambrosi, L., 188

Amendt, P., 50

Ames, A. C., 65
Anastassea-Vlachou, P., 127
Andelman, S. L., 165
A'ndersson, D., 107, 174
Ascher, S. F., 18

Attala, R., 136

Bachman, D. S., 233
Bacon, A. P. C., 139
Bamford, F. N., 73
Bapat, V. R., 128
Barltrop, D., 19, 20, 21, 66, 67, 68, 159
Barr, D. G. D., 234
Barry, P. S. 1., 104
Bartoszewicz, B., 129
Battistini, V., 13
Baumler, J., 177
Beckman, F., 138
Benetou, S., 127
Benjamin, V., 147
Berglund, F ., 102
Berman, E., 45
Berriman, H., 197
Bicknell, J., 109, 150
Biggs, J. C., 143
Bilenker, R. M., 151
Birke, G., 62
Blackledge, P., 76
Blanksma, L. A., 163, 173, 232

Blumenthal, D., 172
Bonsignore, D., 155
Bonzanino, A., 35
Briley, A. M., 171
Bryan, G. W., 103
Burke, W. A., 146
Byers, R. K., 216

Campell, A. M. G., 108
Carrillo, J. A., 84
Carswell, F., 13
Cassady, G., 83
Cernik, A. A., 218
Chang, H. M., 221
Charache, S., 219
Charest, S., 107
Chenoweth, M. B., 244
Childers, D., 97
Chisolm Jr J. J ., 17, 46, 47, 48, 220, 224, 245
Chiu, G., 221
Christian, J. R., 110
Clarkson, T. W., 29
Clayton, B. E., 109
Clemena, G. G., 214
Cocle, P., 192

Coffin, R., 247

Cohn, B. L., 152
Cohn, G. J., 107

Coli, R. D., 246

Conn, R. H., 174
Cook, F., 97

Cooke, T. K., 139
Cooper, H. A., 222
Corbin, R., 98

Cramér, K., 176
Crawford, M. D., 111
Cumings, J. N., 49
Cumming, R. L. C., 13

Danovitch, S., 34
Dathan, J-. G., 80
Davidow, B., 175

97

Davis, J. R., 165, 166, 204
De Bruin, A., 32

Delattre, J ., 190

Delves, H. T., 109, 202, 203
Delwaide, P., 31

Desoillc, H., 201

Deutsch, R. A., 200
DiNunno, C., 188
Dodge, J. S., 73

Done, A., 89

Donovan, P. P., 199
Dorn, P., 207

Dreux, C., 190

Duprez, A., 198

Edwards, R. G., 197
Egan, B., 91
Ekblad, M. D., 222
Evans, J. P., [38
Eyl, T. B., 30

Fabrega, E. A., 165, 204
Faes, M. H., 217
Fairbanks, V. F., 222
Fairey, F. S., 79
Farber, S., 135
Farina, G., 213
Farrelly, R. 0., 196
Fazio, V., 143
Feeley, D. T., 199
Feldman, F., 164
Feldman, G. V., 78
Fernandes, M. T., 77
Finberg, L., 3
Finklea, J. F., 93
Fishbein, W. 1., 204
Florentin, P., 198
Forsby, N., 132
Frank, J. E., 53
Fraser, D. K. B., 234
Freeman, R., 70, 71, 131, 235
Fristedt, B., 132
Froome, K., 139

Gadeke, R., 117

Gale, J. L., 84

Gautier, E., 114

Geary, T. D., 197

Geldmacher v. Mallinckrodt, M., 187
Gelli, G., 118

Genchi, M., 212

Gent, A. E., 139

98

Gevirtz, N. R., 130

Gibson, S. L. M., 162

Girard, M. L., 190
Girard-Wallon, C., 191
Goldberg, A., 13, 24, 162, 179
Goldberg, E. D., 99
Goldsmith, J. R., 69
Goldwater, L. J ., 51

Gomez, M., 120

Gordon, N., 23

Goreczky, L., 22

Géscinska, Z., 129

Grabecki, J ., 189

Graef, J. W., 161

Gray 111, J. W., 79
Greengard, J., 41, 43, 224, 241
Grisler, R., 212, 213
Grossi-Bianchi, M. L., 124, 125
Gruver, C., 34

Guinee, V. F., 95, 175

Haduch, T., 189
Haeger- Aronson, B., 211
Hale, M., 94
Hammer, D. 1., 93
Harada, Y., 142
Hardy, H. L., 42
Harper, D. L., 152
Harpur, E., 98
Harris, F., 122
Harris, P. F., 78
Harrison, H. E., 37
Harrison, W. W., 214
Harvey, C. C., 80
Hasan, J., 208
Hasegawa, N., 210
Heller, R. H., 168
Hendricks, R. H., 93
Hernberg, S., 168, 169, 208
Heusghem, C., 31, 81
Hexter, A. C., 69
Hingerty, D., 75
Hirai, A., 210
Horton, R. J. M., 93
Hosking, C. S., 209
Hunt, G. M., 92
Husband, P., 141
Hyman, S., 41

Jacobziner, H., 90
James, J. A., 140, 240, 243
Javett, S. N., 149

Jenner, G. G., 101
Johnels, A. G., 62
Joselow, M. M., 51
Joshua, G. E., 147, 148

Kaplan, B., 149
Kaplan, E., 48
Kashiwagi, T., 210
Katzman, E. C., 146
Keller, P., 145

Kent, F. S., 181
Kesaree, N., 52
Killala, N. J. P., 66, 160
King, B. G., 100
King, 13., 23

Kisser, W., 178
Kjellman, B., 132
Klein, D. H., 99
Klein, M., 98
Kleut-Jclié, R., 144
Kneip, T. J., 181
Knockaert, O. E., 217
Kopito, L, 161, 171, 215, 216
Krechniak, A., 106
Kubota, J., 105
Kushnick, T., 151

Lacquaniti, A., 35
Lam, C. N., 162
Langford, J. C., 180
Laurer, G. R., 181
Lazar, V. A., 105
Legros, J., 81
Lehnert, G., 182
Leiking, S., 228
Leone Jr, A. J., 7
Leone, L. A., 246
Lepow, M. L., 94, 156
Lichtman, H. C., 164
Lin-Fu, J. S., 8, 9,10, 11, 38,157
Lipschutz, F., 195
Losee, F., 105

Lourie, R. S., 63, 107

Ma, L., 221

Mackay, R. I., 23
Madahar, D. B., 206
Madden, J., 2

Macs, G. L., 217
Mandalenaki-Asfi, E., 127
Marin, E., 201
Matschiner, H., 186

McCrae, W. M., 162
McEnery, J. T., 229, 230
McKellar, W. J. D., 141
McLaughlin, M. C., 12
McNicholl, B., 91
McNiel, J. R., 119
Meigs, J. W., 64
Metséila‘, P., 208

Meyer, B., 133

Millar, J. A., 13
Miranda, M., 84
Mirando, E. H., 120, 121
Miyamoto, Y., 142
Mochir-Fatemi, F., 228
Moore, J. E., 14
Moosa, A., 122
Morgan, J. M., 183
Morris, J. N., 111
Morrow, J. J., 179
Mossman, D. B., 104
Murphy, T., 156
Murray, E. F., 173, 232

Namer, R., 98

Neal, W., 152
Nelson, J. D., 207
Nikkanen, J., 169
Nikolcheva, Ya., 206
Ninomiya, T., 142
Noirfalise, A., 31, 81
Nonaka, 1., 142

Oberle, M. W., 33
Obradovié, D., 144
O’Connell, M. J., 132, 173
O‘Gorman, G., 85
O’Gorman, P., 76
Ohta, S., 142
Oliver, B. E., 85, 137
Oliver, R. G., 86
Opitz, J. M., 134
Oransky, S., 164
Ordonez, J. V., 84
Oski, F. A., 195
Ozcan, N., 113

Palmisano, P. A., 83
Paolaggi, F., 190
Perini, M., 212
Perlstein, M. A., 136
Philbert, M., 201
Phillips, J. L., 247

99

Piasecka, M., 129
Pichirallo, J., 82
Pisani, W., 35
Plantin, L.—O., 62
Polson, C. J., 39
Polster, H., 116
Price, W. R., 97
Pybus, J., 196

Qazi, Q. H., 205

Raimondi, A. J., 138
Ranasinghe, L., 121
Ratnaike, N., 147
Rauber, G., 198
Rausen, A. R., 130
Rayner, P. H. W., 52
Rechnitz, G. A., 167
Reddemann, H., 50
Reddick, L. P., 1
Reinhard, M. C., 119
Reiser, L., 164
Rennert, O. M., 2
Robertson, W. 0., 223
Roffman, H., 3
Rogers, L. E., 207
Romano, C., 124, 125
Rosario, R., 115
Roschig, M., 186
Rosignoli, H., 201
Roth, 1., 22
Rothschild, E. 0., 16

Sabra, F. A., 227
Sachs, H. K., 173, 232
Sadaty, M., 151
Salwa, S., 123
Sanain, P., 207
Sayre, J. W., 185
Scanlon, J., 15
Secchi, G. C., 184
Selander, S., 176
Schaller, K.-H., 182
Scherz, R. G., 231
Scherzinger, F., 112
Schippa, R., 61
Schneider, V., 145
Schone, D., 116
Schroeder, H. A., 55
Shahidi, N. T., 134
Sharifi, M., 241
Shibata, T., 210

100

Shwachman, H.,l61, 171, 215, 216
Shy, C. M., 93
Sjostrand, B., 62
Sneed, R. C., 83
Snyder, R. D., 54
Sovljanski, M, 144
Sovljanski, R., 144
Sowerby, P., 139
Specter, M. J., 175
Spector, S., 247
Srivastava, P. C., 88
Sta Ana, E., 164
Standard, R. L., 36
Stanley-Brown, E. G., 53
Staples, W. 1., 247
Stephenson, J. B. P., 52
Sugino, H., 210

Swales, J. D., 87
Swensson, A., 236
Swift, P. N., 65
Szadkowski, D., 182

Tada, 0., 72
Tattersall, R. N., 39
Teillet, F., 133
Tietz, H., 126
Tipton, I. H., 55
Tortorolo, G., 124
Truffert, L., 191
Turner, W., 73
Tyler, R. L., 237

Ui, J ., 25

Ulfvarson, U., 236
Ullmann, W. W., 193
Urbanowicz, H., 189
Urata, G., 179

Van Houte, G., 192
Varadi, S., 88
Vassallo, L., 74
Vawler, G. F., 135
Verde, J., 124
Vialatte, J., 133
Vihko, V., 208
Vincent, W. F., 193
Vinter, P., 202
Vimercati, F., 188
Vitale, L., 134
Vossough, P., 228

Waite, R., 26

Waitsman, E. S., 168
Ward, 0. C., 75
Warkany, J ., 27
Warley, M. A., 76
Wisser, St., 116
Weatherall, D. J., 219
Wehran, H.-J., 61
Wehrle, P. F., 28
Weidner, G. L., 193
Wei], C. S., 193
Weinberg, S. B., 51
Weiner, P., 2
Weinmann, H. M., 238
Weisgerber, C., 133
Weissberg, J. B., 195
Werner, T., 238

Westermark, T., 62
Westhin, W. F., 242
Whelan, G., 143
Whitmire, E., 64
Wiener, G., 44
Williams, E. R., 108
Wilson, A. T., 170
Wilson, D. J., 185
Wittmann, A., 198
Wéjcik, T., 123
Wood, MacD., 97
Woody, R. H., 96

Yurachek, J. P., 214

Zollar, L., 241

fiU.S.Government Printlng Office: 1973 — 759-953/1171 Region 5-H

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DHEW Publication No. (HSM) 73-10005

 

 

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