Environmental Health Perspectives Volume
103, Supplement 6, September 1995
[Citation
in PubMed]
Environmental Poisoning of Children -- Lessons from the Past
Walter J. Rogan
National Institute of Environmental Health Sciences, Research Triangle
Park, North Carolina
Abstract
Children have physiologic and behavioral characteristics that make them
vulnerable to damage from environmental chemicals. In the past, there have
been episodes in which children became ill or died from environmental exposures
that spared adults or affected them less severely. Among the characteristics
leading to children's sensitivity are their limited diets, dividing cells,
differentiating organs and organ systems, slow or absent detoxification
mechanisms, long life expectancy with the resulting ability to express damage
with delayed consequences, and the severe metabolic demands of growth. There
have been large outbreaks of poisonings involving children in Asia and Turkey,
and some of the less obvious effects of chemicals have appeared in children
in the United States. Although the United States has been spared a widespread
outbreak of severe poisoning, such an incident is possible and would likely
have greater consequences for children than adults. -- Environ Health
Perspect 103(Suppl 6):19-23 (1995)
Key words: polychlorinated biphenyls (PCBs), chloracne, mother's
milk, dichlorodiphenyl trichloroethane (DDT), polybrominated biphenyls (PBBs),
hexachlorobenzene, endrin, lead, mercury, asbestos
This paper was presented at the symposium on Preventing
Child Exposures to Environmental Hazards: Research and Policy Issues held
18-19 March 1993 in Washington, DC.
Address correspondence to Dr. Walter J. Rogan, Acting
Clinical Director, National Institute of Environmental Health Sciences,
P. O. Box 12233, Research Triangle Park, NC 27709. Telephone (919) 541-4578.
Fax (919) 541-7640.
Introduction
This article is a compilation of incidents in which children have been
affected by exposure to environmental chemicals. The results range from
subtle developmental delay to death. They illustrate the ways in which differences
between children and adults can make exposures that are safe or produce
minimal toxicity in adults lead to detectable damage in children.
PCBs
In 1968, an epidemic of severe acne among residents of Kyushu province
in Japan was traced to use of cooking oil that had been contaminated by
PCBs during processing (1). Over 1000 people were eventually diagnosed
as having "Yusho" (oil disease) by the local health authorities.
Yusho was essentially chloracne, familiar to occupational physicians as
"cable handler's itch," from the linear pruritic bands it produced
at points of contact with insulated or impregnated cable. Chloracne was
not specific to PCBs; in fact, it was produced by chlorinated naphthalenes,
furans, or dioxins, all of which shared the substituted double-ring structure.
Chloracne is similar to acne vulgaris except that cysts tend to be more
severe and inflammation relatively less prominent. Healing is quite prolonged,
and Yusho cases remained active for several years after exposure ceased,
with, ultimately, substantial scarring among those that did resolve.
There are reports of 13 women who were pregnant at the time of exposure.
One of the children was stillborn and was deeply and diffusely pigmented
(2). Of the remaining children, 4 were small for dates, 8 had hyperbilirubinemia,
4 had pigmented gums, 9 had conjunctivitis with dilatation of the sebaceous
glands of the eyelid, and 10 had diffuse skin pigmentation. PCBs appeared
in the breast milk of cases, although levels were not remarkably different
from those of controls. Breast-fed children had higher levels in their serum
than bottle-fed children. Follow-up of children up to 9 years later, including
some cases that were reported to have been produced by breast-milk transmission
alone, showed apathy, lethargy, and soft neurological signs (3).
The growth deficit apparent at birth resolved by about 4 years of age.
In 1979, there was an outbreak of acne among school children near a food-processing
plant in Taichung province of Taiwan (4). Investigation proceeded
much more rapidly than had been the case in Japan 11 years earlier, and
contaminated rice oil was again the vector. Although the specific machine
was not identified, residue under the site of a scrapped machine showed
PCB-contaminated cooking oil. At this time, over 2000 patients are being
followed by health authorities. The symptoms, signs, and laboratory findings
are roughly similar to the Japanese outbreak, except that some of the milder
cases have diffuse skin pigmentation without acne. Babies born to affected
mothers show the same syndrome as in Japan, including several with natal
teeth. We examined 117 such children in 1985 (5) and have followed
them since. They have a variety of ectodermal defects, such as excess pigmentation,
carious teeth, poor nail formation, and short stature. They also have a
developmental delay, on the average of about 5 to 8 points on standard IQ
scales, which hasboth persisted as they have gotten older and is no better
in children born up to 6 years after exposure than it is in those born in
1979 (6). The children also score higher on tests measuring poor
conduct and hyperactive behavior (7).
Since PCBs accumulate in human beings, since they are of known toxic
potential, and since they are present in a wide variety of goods and products,
strict regulations concerning their disposal were developed as part of the
Toxic Substances Control Act (TOSCA) of 1976. PCBs are no longer produced
in the United States; however, large amounts have yet to be dealt with as
the large transformers and other heavy machinery of which they are a part
wear out and must be discarded. Under TOSCA, wastes with greater than 50
ppm PCBs must be handled as hazardous substances and be disposed of in special
landfills or subjected to high-temperature incineration. Both of these options
are expensive. In addition, there are many old dump sites and abandoned
factories that afford poorly controlled or uncontrollable access to PCBs.
Finally, there is a substantial fear that illegal dumping of substances
will become more common as regulations are enforced. The experience of North
Carolina, where about 200 miles of roadside were contaminated by dumped
PCBs, would seem to bear this out (8). We had access to breast-milk
samples of 11 women who told us that they lived on or near or had contact
with this spill. We found that while their levels were no higher than expected,
the heavily chlorinated congeners of the kind found in the spill occurred
more frequently in the chromatograms of their milk. This indicated that
absorption had likely taken place, but that the amount was small in relation
to the existing body burden.
Hexachlorobenzene
A dermatologist at the government hospital at Diyarbakir in southeastern
Turkey described an outbreak of porphyria cutanea tarda in 1957. The cause
was the ingestion during periods of famine of seed wheat that had been treated
with hexachlorobenzene as a fungicide. Until the government ban of treated
wheat seed in 1959, almost 3000 cases were reported. The attack rate was
highest among children 5 to 15 years of age. Patients had photosensitivity,
skin pigmentation, bullae, hypertrichosis, and bright red urine. There was
about a 10% case fatality rate (9).
Younger children tended not to develop porphyria. Rather, breast-fed
children of cases had pembe yara (pink sore), which included weakness, convulsions,
and an annular papular rash. This condition carried about a 95% case fatality
rate, and cohorts of children died in some of the villages. The chemical
was shown to be present in breast milk. Cripps and colleagues have followed
32 cases of porphyria turcica for 20 years (10) and still find elevated
porphyrin excretion in urine among some and hexachlorobenzene still detectable
in breast milk of one case. Attempts have been made to treat patients with
chelating agents, with mixed success.
In the United States, there have been several accidental exposures, but
no porphyria. Although residues have been reported in fat samples from those
not occupationally exposed in Europe, Japan, and Canada, fat samples in
the United States have not been shown to be generally contaminated (11).
The major use of hexachlorobenzene is as a seed treatment to control wheat
bunt; however, the chemical is a byproduct of several industrial synthetic
processes and appears as a contaminant in waste flows. The chance for population
exposure in the United States to treated seed is nil; exposure during transport
or disposal of waste is a possibility.
Endrin
Endrin is a cyclodiene that was used in the United States only for control
of birds in airplane hangars. Transport of endrin in the same trucks used
for sugar transport was incriminated circumstantially in an outbreak in
Pakistan (12). Nineteen of 194 affected persons died, most of an
acute seizure disorder and respiratory arrest. Seventy percent of cases
were children. Epidemiologic investigation showed that consumption of sugar
that had been transported in trucks contaminated by the pesticide was associated
with the illness, and the sugar was found to be contaminated with endrin.
The authors stated that the levels found in the sugar were not high enough
to be the obvious cause, but that there may have been foods high in sugar
that children ate preferentially.
Lead
For a history of lead poisoning, see Lin-Fu (13). For a review
of the effects of low-level exposure on cognition, see Needleman (14).
White lead paint, which was an equal mixture of lead oxide and linseed oil,
produced a durable, washable, white finish. It was used in the United States
for interior surfaces in expensive housing and in high moisture or high
abrasion areas, such as doors, windows, kitchens, and bathrooms, in all
kinds of housing through the 1960s and 1970s. Lead had been known to be
toxic from antiquity, and lead colic and wrist drop were known among painters
and smelter workers. As the inner-city housing stock began to deteriorate
in the 1940s and the process accelerated in the 1950s, interiors of homes
painted with the expensive lead paints were not maintained, since families
were unable or landlords were unwilling to do so. Lead paint chips, containing
about 50% lead by weight, were ingested by children. Chips are poorly absorbed,
but lead is poorly excreted, and children who had the habit of mouthing
or swallowing paint chips could develop a cumulative dose leading to lead
poisoning. Lead inhibits the formation of heme, the pigment in red blood
cells that carries oxygen, and such children were anemic. They were constipated,
further slowing the elimination of chips, which were visible in the intestines
on X-ray. They stored lead in the metabolically active areas of their long
bones, leading to lead lines visible on X-ray. In severe cases, they became
unable to regulate the volume and pressure of the fluid surrounding their
brains, leading to lead encephalopathy, with coma, convulsions, and often
death. Early clinicians believed that a child who recovered from a bout
of lead encephalopathy did so without sequelae, but with improving medical
supportive care and the introduction of chelating drugs that promoted the
excretion of lead, more children survived, and follow-up showed that they
were frequently mentally retarded or had disorders of behavior and conduct.
Clinicians were familiar with the idea that a disaster of the central
nervous system, such as trauma or infection, could permanently compromise
brain function; and the idea that lead encephalopathy could have that effect
was accepted. However, lead encephalopathy was rare, and mental retardation
and behavior disorders were common. Thus the question arose as to whether
exposure to lead insufficient to produce encephalopathy might be sufficient
to affect behavior and intelligence. These problems, when studied by finding
children with retardation or disordered behavior and comparing their lead
exposure with that of controls, were confounded by two questions. First,
since lead exposure through deteriorated housing occurred in disadvantaged
families, and since there appeared to be an independent effect of social
class on IQ and behavior, might it be that the circumstances of the children's
lives produced both the effects on their brains and their lead exposure?
Second, since children got their lead from eating paint, and more active,
less intelligent children were thought to exhibit more frequent and promiscuous
mouthing behavior, might not the behavior have produced the lead exposure
rather than the lead exposure the behavior?
Only in the 1980s, following studies in which children were identified
at birth and followed, did the idea that lead exposure preceded and produced
disordered behavior and deficits in intelligence achieve acceptance. In
addition, the levels at which such effects were detectable turned out to
be much lower than expected, and the duration of the effect, now documented
to be well into school age, longer than expected. Children are now thought
to be lead poisoned at levels that, a decade ago, were thought to be safe,
and millions of children in the United States have what public health authorities
have declared to be unacceptable lead exposure.
Lead paint was not meant to poison children, and it is easy to imagine
that no one thought children would be exposed to it or that they would be
as sensitive to it as they are. No amount of experience with adult toxicology
would allow prediction of the young child's response to lead. Perversely,
two of the three major industrial uses of lead, in paint and in gasoline,
inadvertently insured the widest possible exposure for children; in fact,
it is difficult to think of two methods better suited to saturation exposure
than putting it on the walls and vaporizing it into the air. Lead is now
gone from gasoline, but another generation of children will grow up in housing
painted with lead oxide and linseed oil. Advertisements from before World
War II extol the extreme durability of the paint, and the copy was right.
Mercury Poisoning in Minamata, Japan
Minamata is a fishing village in Japan and also the home, since 1907,
of the Chisso chemical corporation. By tradition, the fisherman sold their
best fish, took the second best for their families, and gave the worst fish
to the cats. In 1952, the cats began walking stiff-legged about the docks
and were reported to be "committing suicide"; in 1956, the first
cases of disturbed speech, gait, and loss of fine motor skills occurred
in the fishermen's families. The cause was determined to be a heavy-metal
poisoning in October of that year; however, controversy over the source
remained. Chisso Corporation produced acetaldehyde by a process involving
mercury, which was then discharged into the bay. Chisso, however, denied
that the illness was due to the mercury from their plant. It was not until
1968 that the Japanese government declared that Chisso's discharges were
the cause of the illness. By January of 1975, about 800 patients were confirmed,
with another 2800 seeking indemnification (3).
Not all of the families who made their living from the bay were affected.
However, by 1962, 17 cases of a cerebral palsylike illness developed in
the children of women thought to be healthy but who had consumed fish. Some
of these children died, and autopsy showed widespread lesions of the cerebral
cortex attributable to mercury poisoning.
The Minamata episode led to the founding, in 1970, of the Central Pollution
Board in Japan. The episode illustrates several aspects that have recurred
at other times and places. First, a chemical etiology was not thought of
or sought for the illness, and the victims were feared because they appeared
to have a contagious disease. Second, children and fetuses were more susceptible
because of their developmental stage, in the sense that doses that were
insufficient to produce obvious illness in the pregnant women were sufficient
to cripple the children.
Organic mercury remains a worldwide pollution problem, especially for
cultures that depend on ocean fish for most of their protein. Mercury is
still widely used in the photographic and battery industry and is a significant
part of the waste stream. There is no evidence that the levels of either
organic or inorganic mercury that occur commonly in the United States produce
illness, but the margin of safety is likely not large. About half of the
mercury exposure is organic, and probably comes from low-level food contamination.
The other half is from metallic mercury used in restorative dentistry (15).
DDT
Dichlorodiphenyl trichloroethane (DDT) enjoyed extremely widespread use
from its introduction in the 1930s to the withdrawal of its registration
by the EPA in 1972. It is stable in the environment and remains active long
after initial application. It was this stability, in fact, that led to its
role as a widespread environmental pollutant. Once in the food chain, it
resisted ultimate metabolism and was bioconcentrated in predators (16).
Among those predators was man, and during the 1960s evidence accrued that
residue levels of DDT or its metabolites were detectable with very high
prevalence in human fat tissue (as a consequence of their fat solubility)
and human milk (as a consequence of its fat content).
Certain of the DDT family have some hormonal activity and are inducers
of the mixed function oxidase system of enzymes. It was some combination
of these properties that is hypothesized to have been the mechanism for
the effect on sea bird reproduction (17) of DDT. o,p-DDET
is a weak estrogen (18), and the metabolism of estrogens is accomplished
in part by the P-450 system. Thus, an estrogen imbalance is thought to have
resulted in the thin shells and decreased hatching that was reported. DDT
is a carcinogen in mice (19).
As part of a project in which we were looking for morbidity in children
exposed to DDT (and PCBs) in breast milk, we collected breast-milk samples
from about 800 women in North Carolina and followed their children. We had
hypothesized that, rather than seeing a strong increase in illnesses in
breast-fed children if DDT were toxic, we would see at most a mild increase
and that women would then wean their children earlier, since it is clinical
practice in the United States to provide supplemental feedings to children
who are breast-fed but not doing well. As it turned out, we saw no evidence
of increased illnesses among children even at the highest levels of DDT
contamination. We did, however, see an unexpectedly large difference in
lactation performance between women at the extremes of the DDET distribution;
the women with the highest levels breast fed less than 40% as long as women
with the lowest levels (20). We have preliminary data from a study
we did in Mexico, where levels are higher, of a similar effect (21).
Breast feeding is the optimum way to feed a baby. Although there is at
most a small difference in mortality between breast- and bottle-fed children
in the United States, the differences in countries where there is not clean
water or money for enough formula are huge. If this relationship between
a broadcast pesticide and lactation performance is causal, it has implications
for infant mortality. Further, if the mechanism is through the estrogenicity
of DDT, then the problem is even greater. DDT use is declining throughout
the world, but many pesticides have estrogenlike properties. To initiate
lactation, women need a very low level of estrogen so that prolactin can
act unopposed. This is another example of the vulnerability of children
to physiologic disruption, this time because of their unique food supply,
from levels of chemicals that result in no morbidity to adults.
Asbestos
Men who worked around uncontrolled asbestos dust developed severe pulmonary
fibrosis and died young of right heart failure or pulmonary failure. As
levels of exposure diminished, the workers lived longer, only to die of
lung cancer, especially if they smoked cigarettes. As levels came down even
more, workers who lived long enough developed mesothelioma, a tumor of the
lining of the lung cavity or the abdominal cavity. Mesothelioma is uncommon,
even among asbestos workers. It has a very long latency period, that is,
the time between exposure and the development of illness can be decades.
Many more workers might develop mesothelioma if they lived long enough,
but the tumor's latency is longer than their life span. Asbestos dust, however,
is tenacious. Anderson et al. (22) reported several cases of mesothelioma
arising in the children of asbestos workers. Their source of exposure was
dust brought home on their fathers' work clothes. Although this exposure
was low, it took place very early in life, and the children had a long time
during which to express disease. These tumors showed up when the offspring
were in their 30s and 40s.
The first report of mesothelioma in association with asbestos exposure
also resulted from an exposure that is peculiar to childhood. Wagner et
al. (23) reported that children who played around the mine tailings
in an asbestos-rich area of Cape Province in South Africa developed mesothelioma
later in life.
Asbestos exposure is common, even though asbestos is now banned, and
mesothelioma incidence has been rising. Some of this is due to the large
number of workers who were employed short-term in shipyards during World
War II (24). So far, disease in their offspring, who would now be
in their 40s and 50s, has not been reported.
Polybrominated Biphenyls
In 1973, the Michigan Chemical Company was marketing two compounds with
similar names and packaging--Nutrimaster, a magnesium oxide supplement for
dairy cows, and Firemaster, a polybrominated biphenyl mixture used as a
flame retardant. A mix-up occurred in shipment, and an unknown amount of
PBB was mixed with feed. Cows developed a toxic syndrome, the cause of which
was not readily apparent, since PBBs are not detected in routine analysis
for pesticide residues; and other tests gave confusing or negative results.
Eventually, a USDA chemist observed a very late-emerging peak on a feed
sample chromatogram that had been left running inadvertently and identified
the unusual pattern as PBB. By that time, however, cows, swine, and chickens
that had eaten the food had been marketed.
Chemically, PBBs are similar to PCBs; they differ only in the halogen
substitution. Since they were not intended as food additives or drugs, there
had been very little toxicologic information gathered on them prior to marketing.
There was no reason to believe that they would be any less toxic than PCBs,
however, and a series of quarantines went into effect, resulting in the
slaughter of thousands of livestock over the next few years. Little of the
contaminated meat and dairy products made its way out of state. However,
farm families both consumed their own goods and sold locally, and those
who ate the food absorbed and stored the chemical. Like PCBs, PBBs are fat
soluble and resist metabolism or excretion. By 1978, Michigan public health
officials were able to show that more than 90% of a random sample of lower
peninsula nursing women had PBBs in their milk; by inference, 90% of the
population was detectably contaminated (25). The state eventually
offered to test breast milk for PBBs and adopted advisory levels above which
breast feeding was discouraged. In general, these were calculated to allow
for the fact that the infant's mass was increasing, and that intake below
a certain level would still allow a net decrease in concentration. The impact
of these programs is difficult to measure. There has not been a report of
any specific illness occurring in a child attributable to PBB in his milk;
thus, whether any morbidity was prevented by advisory activity is conjectural.
A variety of illnesses were ascribed by residents to the toxic effects
of PBBs; and several state and federally sponsored surveys attempted to
relate morbidity, mortality, or outcome of pregnancy to the degree of contamination.
The "PBB syndrome"--asthenia, fatigue, short-term memory loss,
dermatitis, and hypersomnia--did not seem to appear more frequently in those
with higher blood levels of chemical, nor at all in Michigan Chemical Company
workers, who had the highest levels. However, there were reports of T cell
abnormalities (26), hepatosplenomegaly, and nonspecific liver function
changes. No teratologic syndrome was reported in children born to farm families,
and several studies of childhood morbidity did not show any consistent syndrome
(27,28). However, when farm children were arrayed by their level
of PBB as determined by analysis of fat biopsy specimens, there was a consistent
tendency for those above the median to show lower developmental scores,
as measured by the McCarthy Scales of Children's Abilities (29).
Overall, most children were in the normal range.
The long-term consequences, if any, for the health of Michigan children
are unclear, although the passage of time has provided some reassurance.
A cohort of over 4000 people, including children and reproductive-age women,
is under prospective surveillance by the state. Conditions that have long
latency periods may only develop after ten or more years of observation,
but thus far no striking patterns of illness have emerged. Body burdens
of the chemical, as measured by periodic screens and rescreens of serum
samples, have remained remarkably stable, although there is some suggestion
of a downward secular trend.
Discussion
It is intuitively plausible that children are more vulnerable to their
environment than adults. Children are less able to identify substances as
toxic; they are curious; they have a fascination with the beautiful, such
as liquid mercury, and the gross, such as the slime on a waste site pool.
They have higher intakes (per kilo) and metabolic rates than adults; the
demands on their metabolism for growth are much higher; their detoxification
systems are not mature. Diseases that take a long time to appear can result
from exposures in childhood, while the consequences of the same exposure
later in life might have appeared if death from some other cause had not
supervened. Examples of environmental chemical exposures leading to greater
morbidity in children illustrate this vulnerability. The selection of examples
here is highly arbitrary and not exhaustive, and tends to be international.
The United States has thus far been spared a severe outbreak of obvious
chemical toxicity. This has a great deal to do with the scrutiny given food
and drugs, but should not be interpreted as a guarantee. The food supply
is complex and vulnerable to contamination at many levels. Household use
of pesticides and other agents is universal. Proper disposal of chemical
waste is an enormous problem only beginning to be solved. Experience implies
that suspicion of a chemical etiology is a necessary first step, typically
one taken by the patient, then by the clinician, then by authorities.
REFERENCES
1. Kuratsune M. Yusho, with reference to Yu-Cheng. In:
Halogenated Biphenyls, Terphenyls, Naphthalenes, Dibenzodioxins, and Related
Products. 2nd ed. Topics in Environmental Health, Vol 4. (Kimbrough RD,
Jensen AA, eds). Amsterdam:Elsevier, 1989;381-400.
2. Funatsu I, Yamashita F, Ito Y, Tsugawa S, Funatsu T,
Yoshikane T, Hayashi M, Polychlorobiphenyls (PCB) induced fetopathy. 1.
Clinical observation. Kurume Med J 19:43-51(1972).
3. Harada M. Intrauterine poisoning: clinical and epidemiological
studies of the problem. Bull Inst Const Med, Kumamoto Univ 25:1-60 (1976).
4. Hsu S-T, Ma C-I, Hsu S-K, Wu S-S, Hsu N-H, Yeh C, Wu
S-B. Discovery and epidemiology of PCB poisoning in Taiwan: a four year
follow-up. Environ Health Perspect 59:5-10 (1985).
5. Rogan WJ, Gladen BC, Hung K-L, Koong S-L, Shih L-Y,
Taylor JS, Wu Y-C, Yang D, Ragan NB, Hsu C-C. Congenital poisoning by polychlorinated
biphenyls and their contaminants in Taiwan. Science 241:334-336 (1988).
6. Chen Y-CJ, Yue-Liang G, Hsu C-C, Rogan WJ. Cognitive
development of Yu-Cheng ("oil disease") children prenatally exposed
to heat-degraded PCBs. JAMA 268:3213-3218 (1992).
7. Chen Y-CJ, Yu M-LM, Rogan WJ, Gladen BC, Hsu C-C. A
six-year follow-up of behavior and activity disorders in the Taiwan yu-cheng
children. Am J Public Health 84:415-421 (1994).
8. Rogan WJ, Gladen BC, McKinney JD, Albro PW. Chromatographic
evidence of polychlorinated biphenyl exposure from a spill. JAMA 249:1057-1058
(1983).
9. Peters HA. Hexachlorobenzene poisoning in Turkey. Fed
Proc 35:2400-2403 (1976).
10. Cripps DJ, Gocmen A, Peters HA. Porphyria turcica:
twenty years after hexachlorobenzene intoxication. Arch Dermatol 116:46-50
(1980).
11. Courtney KD. Hexachlorobenzene (HCB): a review. Environ
Res 20:225-266 (1979).
12. Rowley DL, Rab MA, Hardjotanojo W, Liddle J, Burse
VW, Saleem M, Sokal D, Falk H. Convulsions caused by endrin poisoning in
Pakistan. Pediatrics 79:928-934 (1987).
13. Lin-Fu JS. The evolution of childhood lead poisoning
as a public health problem. In: Lead Absorption in Children. (Chisolm JJ,
O'Hara DM, eds). Baltimore:Urban and Schwarzenberg, 1982;1-10.
14. Needleman HL. Low-level lead exposure and the IQ of
children. A meta-analysis of modern studies. JAMA 263:673-678 (1990).
15. Clarkson TW, Friberg L, Hursh JB, Nylander M. The prediction
of intake of mercury vapor from amalgams. In: Biological Monitoring of Toxic
Metals (Clarkson TW, Friberg L, Nordberg GF, Sager PR, eds). New York:Plenum
Press, 1988;247-260.
16. Bevenue A. The "bioconcentration" aspects
of DDT in the environment. Residue Rev 61:37-112 (1976).
17. Radcliffe DA. Decrease in eggshell weight in certain
birds of prey. Nature 215:208-210 (1967).
18. Kupfer D, Bulger WH. Estrogenic properties of DDT and
its analogues. In: Estrogens in the Environment (McLachlan J, ed). New York:Elsevier/North-Holland,
1980;239-263.
19. IARC. Some Organochlorine Pesticides, Vol 5. (Compiled
by IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals
to Man.) Lyon:World Health Organization, 1974.
20. Rogan WJ, Gladen BC, McKinney JD, Carreras N, Hardy
P, Thullen JD, Tingelstad J, Tully M. Polychlorinated biphenyls (PCBs) and
dichlorodiphenyl dichloroethene (DDE) in human milk: effects on growth,
morbidity, and duration of lactation. Am J Public Health 77:1294-1297 (1987).
21. Gladen BC, Rogan WJ. DDE and duration of breastfeeding
in a high exposure area (Abstract). Am J Epidemiol 136:980 (1992).
22. Anderson HA, Lilis R, Daum SM, Fischbein AS, Selikoff
IJ. Household contact asbestos neoplastic risk. Ann NY Acad Sci 271:311-323
(1976).
23. Wagner JC, Sleggs A, Marchand P. Diffuse pleural mesothelioma
and asbestos exposure in N.W. Cape Province. Br J Ind Med 17:260-271 (1960).
24. Rogan WJ, Gladen BC, Ragan NB, Anderson HA. U.S. prevalence
of occupational pleural thickening. Am J Epidemiol 126:893-900 (1987).
25. Brilliant LB, Wilcox K, VanAmburg G, Eyster J, Isbister
J, Bloomer AW, Humphrey H, Price H. Breast milk monitoring to measure Michigan's
contamination with polybrominated biphenyls. Lancet (2):8091-8095 (1978).
26. Bekesi JG, Holland JF, Anderson HA, Fischbein AS, Rom
W, Wolft MS, Selikoff IJ. Lymphocyte function of Michigan dairy farmers
exposed to polybrominated biphenyls. Science 199:1207-1209 (1978).
27. Barr M. Pediatric aspects of the Michigan polybrominated
biphenyl contamination. Environ Res 21:255-274 (1980).
28. Weil WB, Spencer M, Benjamin D, Seagull E. The effect
of polybrominated biphenyl on infants and young children. J Pediatr 98:47-51
(1981).
29. Seagull EW. Development abilities of children exposed
to polybrominated biphenyls (PBB). Am J Public Health 73:281-285 (1983).
[
Table
of Contents]
Last Update: September 14, 1998
