Nutrition and Health, 1992, Vol. 8, pp. 33-43 0260-1061/92 $10 © 1992 A B Academic Publishers. Printed in Great Britain
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A NEW THREAT TO PUBLIC HEALTH: ORGANOCHLORINES AND FOOD ROSS HUME HALL PO Box 239, Mount Tabor Road, Danby, Vermont 05739, United States ABSTRACT Ambient levels of persistent toxic chemicals, chemicals that persist for decades in the environment, have reached levels high enough to affect the health of children. The organochlorines (PCBs, DDT and the dioxin family) accumulate in human adipose tissue. Pregnant women pass the contamination to their fetuses. The developing nervous system is the most vulnerable. Neurobehavioral deficits, including short-term memory loss, are detected in children born to mothers at the high end of the distribution curve of organochlorines. Humans are not alone in their susceptibility to these subtle effects. Wildlife exposed to the same spectrum of organochlorines as humans suffer a variety of behavioral changes. Rats and Rhesus monkeys fed diets containing the organochlorines under laboratory conditions exhibit behavioral changes that persist into adulthood. For humans, food provides 80 percent of organochlorine contamination. Meat, fish, dairy and commercial fruit are the main sources. A vegetarian diet including unsprayed fruit minimizes contamination. The ultimate solution to this public health problem is elimination of the organochlorines from the environment.
The human body deploys a marvelous array of defenses against the toxic chemicals it encounters in the course ofliving. But the defenses do not arrive fully formed the instant of conception. Not until a few months following birth do detoxifying enzymes and systems take shape. Does mother protect? Not at all. The placenta, like a sieve, passes toxic substances the mother has accumulated into the fetal blood stream. The fetus, its energies channelled into development, lies vulnerable to attack. Of all the developing organ systems, the nervous system is one of the most easily disrupted. Damage at the fetal stage can result in behavioral changes that manifest after the child is born. Most disturbing, scientists detect such changes in children born to mothers exposed only to a background level of toxic chemicals in the environment. The culprits are the persistent toxic chemicals. These Ross Hume Hall is Professor Emeritus, Biochemistry, McMaster University, Hamilton, Ontario, Canada. He is author of the book, Health and the Global Environment (Basil Blackwell, 1990).
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substances break down in the environment slowly (decades) or not at all. They include organochlorines and heavy metals, such as arsenic, cadmium, lead and mercury. Some of the effects described below are seen in children exposed to low levels of heavy metals, particularly lead. But to illustrate the general threat to human well being, I focus on the organochlorines. These synthetic chemicals, distinguished by chlorine content, include the polychlorinated biphenyls (PCBs), DDT, and the dioxin family. We are dealing with a new type of health problem, one poorly recognized by public health authorities. They regard environmental exposure to toxic chemicals as being localized: living next to a toxic waste dump or working in a chemical factory. Two events now outdate this concept of environmental hazard. First, the background level of toxicity has risen due to global spread of the mobile organochlorines. It puts whole populations at risk. Second, scientists are improving their ability to detect subtle health effects due to environmental exposure. The ones I cover in this article are adverse neurobehavioral effects in children. That organochlorines are neurotoxic is not debated. A wealth of animal data and information about individuals acutely exposed to organochlorines shows the vulnerability of the central nervous system. The troubling question is: are the organochlorines neurotoxic to families going about their lives, exposed only to background levels of these chemicals in the environment? Unlike acute exposure episodes, where connection between adverse effect and exposure is easily _established, we can answer that question only by pulling together several clues. Any one clue may not persuade. But the weight of the clues together should persuade health authorities a new threat to public health is creeping into our populations. I start with studies on children in the Orient and the United States and follow with supporting observations in animals, both in the wild and in the laboratory. Then I come back to the question of how people are contaminated. It turns out food is the main source of contamination, and dietary changes can minimize exposure. NEUROTOXICITY IN CHILDREN
PCB Poisoning In Japan and Taiwan: Controlled experiments are obviously impossible in humans. Scientists, therefore, take the opportunity to study victims of accidental poisonings. Two accidents occurred in the Orient, both the result of eating rice oil contaminated with PCBs. Rice oil is heated during processing, and in these accidents the heating coils leaked PCBs. In the Japanese episode, (called Yusho after the Japanese word for rice oil)a group of families consumed rice oil contaminated with 30-900 parts per million (ppm) of PCBs. Thirteen infants were born to exposed women: one was stillborn, four were undersize, 10 had dark skin pigmentation, four had
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pigmented gums, nine had conjunctivitis and eight had jaundice. Significantly, nine years later, these children still suffered neurological and development impairment. 1 A similar accident occurred in Taiwan (the Yucheng incident after the Chinese word for rice oil). Investigators tracked 117 children born up to seven years following their mothers' one-time high exposure. 2 The children weighed less at birth and exhibited hyperpigmentation of nails and gum and susceptibility to bronchitis. The childrens' mental abilities were measured from the time they were infants to when they were in elementary school. Their abilities consistently fell below the standard of a matched set of children from unexposed mothers. It should be noted in both the Japanese and Taiwan incidents, the PCBs were a complex mixture which included polychlorinated dibenzofurans, known to be more toxic than the PCBs. Whether the observed toxicity is due to PCBs or the contaminants is not critical from the environmental view point. All these organochlorines exhibit a similar toxicity profile, differing only in degree. 3 The most devastating aspect of the toxicity is damage to the victim's nervous system. Main damage occurred during exposure at the fetal stage. Although for some of the children, additional exposure from their mothers' milk enhanced toxic effects. 1 Neurotoxicity in the United States: The question of organochlorine neurotoxicity at the fetal stage has been studied in two groups of children, one in Michigan, and a second in North Carolina. A recent review lists many of the papers referred to in this section. 4 A husband and wife team, Sandra and Joseph Jacobson, psychologists at Wayne State University, Detroit, Michigan, aware of the Yusho/Yucheng studies wondered if neurobehavioral effects could be detected in an ordinary population. Everyone carries PCBs and other organochlorines in their body fat. 5 A pregnant woman passes organochlorines to her fetus, in an amount proportional to the degree of her own contamination. The amounts vary in any group, some women being more contaminated than others. Thus, a distribution curve occurs with high and low ends of contamination. The Jacobsons took advantage of this fact to design their study, the idea being to compare children born to mothers across the distribution curve. 6 To ensure they had sufficient number of individuals at the high end, they selected women who ate a food rich in organochlorines-Lake Michigan fish. Lake Michigan fish are th'~ repositories of the dregs of the steel mills and oil refineries of Gary, Indi.ana, and the sludges of Cicago and other inland cities. The fish are heavily contaminated with organochlorines. The Jacobson team visited maternity wards of hospitals in Western Michigan: interviewing women about to give birth, asking whether or not they ate fish and if so how much. They assembled a cohort of 313 mothers. Seventy-seven mothers never ate lake fish. The rest ate varying amounts of fish ranging from a fish a month to a fish several times a week.
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The Jacobson cohort, thus, consisted of mothers at the high and low ends of ordinary exposure (and in between). This meant a range of exposures for the fetuses. To obtain an accurate measure of fetal exposure, the Jacobsons analyzed the PCB level of umbilical cord blood at time of birth. The PCB level, convenient to measure, serves as a marker for organochlorine contamination. When the babies were born, the Jacobsons found higher amounts of PCBs in umbilical cord blood correlated with the smaller birth size, smaller head circumference, shorter stature and diminished motor coordination. They conducted extensive psychological tests on the children, as newborns, at seven months and again at four years. They found memory deficits, particularly short term, in children born to mothers at the high end of PCB exposure. The deficits persisted over the four years. The Jacobsons are quick to point out: the deficits they observe are small and wouldn't be noticed by a physician examining an individual child. Nevertheless, on a group basis, they find the differences statistically significant. In North Carolina, a team of investigators led by Walter Rogan of the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, conducted a study using a similar experimental design. The Rogan team collected a cohort of 866 women, using the amount of PCBs in the mothers' milk as a measure of pre-natal exposure. 7 Although they made no attempt to identify women who ate highly contaminated food, such as lake fish, they found the distribution of PCB body burden varied more than 10 fold. That is, women at the high end of the distribution curve had over 10 times the level of PCBs as women at the low end. The team found a drop in mental development and motor coordination of newborns that correlated with the higher body burden of PCBs of the mother. But unlike the Jacobson cohort, differences in mental ability between infants at the high and low ends of fetal exposure to PCBs disappeared after age two. 8 Both research groups are pioneering a new approach to uncovering neurotoxic effects at the fetal stage. There may be inconsistency regarding permanency of the observed effects. But more to the point, both research teams observed adverse effects that correlated with degree of PCB exposure in the fetal stage. The two studies have attracted a great deal of interest and some nine research groups have under way or are planning similar studies. These studies are expensive, lengthy and subject to the vagaries of human lifestyle. The Rogan cohort is disintegrating because many of the participants have moved and cannot be traced. The Jacobson cohort, on the other hand, remains intact. The families live in small communities in western Michigan where people tend to stay put. The children are presently 10-11 years old. As they grow older, questions will arise concerning effects during and after puberty. The Jacobsons hope to follow these individuals into adulthood. Mammary tissue, no less than the placenta, passes the mother's contamination to the infant. The Rogan team, thus, used the PCB content of
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milk as a measure of the mother's body burden. Women in both the Michigan and North Carolina studies breast fed their babies. But the observed deficits correlate only with fetal exposure. Contamination of the milk by itself was not associated with any of the observed effects. Milk contamination, nevertheless, deserves some comment. The baby receives a dose of PCBs far higher than adults eating ordinary food. The milk of nursing mothers in Europe and North America average 26 ppb of PCBs (whole milk). 5 On this basis, the milk delivers to the baby about 3 micrograms/kilogram body weight/day (ug/kg/day), three times the World Health Organization (WHO) Acceptable Daily Intake (ADI) of 1 uk/kg bw/day. The ADI, however, may not be a useful comparison. It is based on a lifetime exposure and the baby's exposure is for a few months. On the other hand, the ADI is set as if PCBs were the only contaminant. The full spectrum of organochlorines can occur in mothers milk. Thus assessment of the significance of the milk contamination is difficult. In any event, the Jacobson and Rogan studies, as well as animal data that will be cited in a moment, point to fetal exposure as the problem. Health authorities continue to recommend strongly breast feeding. TOXICITY OF ORGANOCHLORINES IN ANIMALS
Behavioral Changes In Wildlife: Observation of wildlife gives some insight into adverse health effects of organochlorines. Like humans, creatures in the wild integrate the effects of total environmental exposure. Several species of birds and animals experience reproductive failures associated with the organochlorines. Failure, in case of birds, can be due to non-viable eggs or chicks, or to behavioral changes in the parents. Scientists of the Canadian Wildlife Service noticed, for instance, a decline in the normal aggressiveness of male herring gulls. Males fail to protect nests against predators because of feminization. 9 An explanation comes from the work of Michael Fry, a biologist at the University of California, Davis. Fry injected gull eggs with DDT in amounts equivalent to environmental exposure. DDT, acting like an estrogen, altered the hormonal balance of the male embryo at a key moment in development. The embryos hatched into a healthy birds except for failure to express male sexuality. 10 Feminization of males forces bizarre behavior among females. With lack of interest from males, female-female pairing occurs. DDT may not' be alone in stimulating such behavioral changes. Several other organochlorines, by virtue of chemical shape, mimic the actions of sex hormones. The adverse effects of organochlorines on wildlife have been documented since the 1960s. But health authorities missed the significance. Fish-eating gulls eat near the top of the food chain. Because of bioaccumulation, fish accumulate organochlorines some million fold over the concentration in
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water. Concentrations in fish-eating birds can go 25 fold higher. But health authorities thought contamination was confined to water bodies and therefore, wildlife observations were not relevant. With global contamination and with a high meat and diary diet, people, no less than herring gulls, bioaccumulate organochlorines high up the food chain. Rat Behavior Affected by Organochlorines: Further evidence behavioral changes provide a highly sensitive indicator of organochlorine exposure comes from studies on laboratory rats. Helen Daly, an animal psychologist, State University New York, Oswego, fed adult rats Lake Ontario salmon. Oswego is located on Lake Ontario making it easy for Daly to obtain quantities of fish. These fish, like Lake Michigan fish, are highly contaminated with a full range of organochlorines. She fed her control rats Pacific salmon, a species much less contaminated. The rats in the two groups behaved no differently as long-as she describes-"life was pleasant". When presented with adversity, such as altered food delivery, the "Pacific" rats easily handled the change. the "Lake Ontario" rats, in contrast, became excited and took a long time to adapt. 11 Daly conducted a second generation study. She fed adult females fish while pregnant and seven days into nursing. The offspring received normal, uncontaminated chow. As adults, the "Lake Ontario" offspring, compared to "Pacific" offspring, showed the same hyperexcitability and slowness to adapt to a changed routine. The diet Daly fed the rats consisted of 30 percent salmon and 70 percent rat chow. She did control experiments to rule out any possibility that the effects she saw were due to the fish per se. She made no attempt to sort out which of the fish contaminant(s) caused the effects. She wanted to give her rats a chemical exposure comparable to what humans receive. Daly comments that the rat results should predict human behavior, in particular reluctance to face novel situations. She notes at age four those Jacobson cohort children with high exposures resisted psychological testing. PCB Poisoning in Rhesus Monkeys: The reproductive system of the Rhesus is particularly sensitive to low level PCB exposure. Douglas Arnold and a team at Health and Welfare Canada, Ottawa, fed PCBs to adult females at 5 ug/kg/day until the animals reached a steady level of PCBs in their tissues (about three years). General health was minimally affected; weight, feed consumption and blood cell count were the same as untreated controls. But reproduction collapsed. Sixteen PCB-fed females, on mating, produced four live and six stillborn infants. Sixteen control females, in contrast, produced nine live and two stillborns. Arnold concludes a no-effect level (if there is one) is less than 5 ug/kg/day .12 This number is uncomfortably close to WHO's ADI for PCBs for humans, 1 ug/kg/day. The actual intake of humans (excluding nursing babies) according to United States food and Drug Administration (U.S. FDA) averages 0.003jg/kg/dayY These
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numbers suggest human exposure is far below that of the monkeys. But whereas the monkeys accumulated their body burdens over three years, human mothers accumulate their body burden over 20-30 years. More revealing, the body burden of the monkeys is not much above that of humans with no known extraordinary exposure. Residents of Southern Ontario average 2 ppm PCBs in their adipose tissue. 14 The Rhesus mothers (which experienced severe reproductive failure) averaged 7 ppm at time of pregnancy. More to the point, what toxic effects appear in the offspring? Scientists at the Harlow Primate Laboratory, Wisconsin, Madison, addressed this question. They fed Rhesus females PCBs until the animals attained an average level of 1.4 ppm in their subcutaneous fat. 15 This level, lower than that of the above group, did not cause reproductive failure. The 15 females of the group were mated and 11 live infants were born. The infants were breast fed four months. Their size and general health was normal, but all developed hyperpigmentation of the face-a sign of PCB toxicity. The level of PCBs in the milk averaged 50 parts per billion (ppb ), whole milk, at time . of weaning. The investigators attributed the toxic effects of PCBs, not to the milk, but to placental transfer. Robert Bowman of the Wisconsin laboratory took the baby monkeys from this experiment and subjected them as juveniles to a battery of psychological tests. Like Daly's Lake Ontario rats, they became hyperactive and confused when confronted with stress. 16 In a second experiment, Bowman and his team followed rhesus offspring until they were adults. Monkeys, born to PCB-exposed mothers and hyperactive as juveniles, became sluggish (hypoactive) as adolescents. 17 This behavioral change has unusual significance. Bowman notes: it is a toxic event that occurred during fetal development, but dido 't manifest until nearadulthood. In sum, a common thread runs through all the animal studies, both in the wild and in the laboratory: vulnerability to the organochlorines of the developing central nervous system. The Michigan and North Carolina studies suggest humans are no less vulnerable. The International Joint Commission, a body charged with overseeing clean-up of the Great Lakes, says this information brings fresh urgency to get on with cleaning up the environment. What particularly alarms the Commission is that human vulnerability manifests at ambient, environmental levels of persistent toxic chemicals (including the organochlorines). 18
FOOD IS THE MAIN EXPOSURE ROUTE
The toxic threat of organochlorines to wildlife was recognized in the 1960s. By the early 70s, use of DDT was banned in North America and worldwide production of PCBs stopped. During the decade of the 70s the
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environmental level of these particular substances declined. But by the early 80s decline ceased and the levels now hold steady. Continued injection of new amounts of organochlorines from industrial and municipal discharges and leaking dumps adds to the global burden. Because of volatility, organochlorines evaporate from water bodies, move in the global air currents, rain out over land and crops, and wash back to lakes and the sea. Analyses of fat samples from North Americans and Europeans and from Arctic natives show equivalent contamination. 5 We become contaminated from eating an ordinary diet. Katherine Davies, a biochemist at Toronto's Department of Health, analyzed a market basket of fruits, vegetables, meat and dairy products, produced in Southern Ontario. The foods were contaminated with dioxins, PCBs and several of the organochlorine pesticides. 19 She concluded about 80 percent of a person's daily intake of thexe toxic chemicals stems from food. U.S. FDA, analyzing typical market baskets of food, arrived at a similar conclusion. 13 The conclusion stunned government regulators. They assumed drinking water was the main source and, if necessary, they could remove that contamination. The province of Ontario in the early 1980s, for instance, initiated a pilot study in municipal water treatment plants. They found charcoal removes organochlorines from the water. But how do you use charcoal to purify a PCB-laden roast? Organochlorines ingested with food are readily absorbed into body tissues. Individuals who have just eaten a meal of Great Lakes fish, (an excellent source of organochlorines) experience an immediate rise in blood levels of the same organochlorines contaminating the fish. 20 Rhesus monkeys fed PCBs absorb 90 percent of the dose. 12 The body deals with toxic substances either by excreting or sequestering them. The organochlorines, being fat soluble, pass from the blood into the body fat where they accumulate. There is a slow release from the body, but it is very slow. If a person received a single dose of polychlorinated dibenzofurans, virtual elimination would require 58 years. 21 The half life for residence of PCBs in the human body, based on a one-time exposure, is estimated at 12 years. But with recontamination at every meal, body levels build up. Older people have higher levels of dioxins than children. 22 CONCLUSION: WHAT SHOULD BE DONE?
Clearly a new type of public health problem is at a stake. The biggest obstacle to overcoming the problem is mindset. Governments need to reassess the way they define health risks. In addition to diseases, where people are clearly sick, they need to pay attention to subtle damage that diminishes human capacities. WHO addressed this point 40 years ago when it offered an expanded view of health: "a state of complete physical, mental and social well-being, and not merely the absence of disease or injury."
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The WHO concept goes beyond defining health as a collection of negatives-of not suffering any clinically defined disorder. Neuro-deficits, detected in the Michigan and North Carolina children fall within the WHO definition. At a symposium, sponsored by the Michigan Audubon Society, Joseph Jacobson talked of "diminished potential". "The short term memory deficits we have seen could be quite significant for later cognitive development," he said. "[diminished] speed of information processing could have a marked impact on the child's ability to master basic reading and arithmetic skills in school. " 23 The problem is not a few exposed people. Everyone is contaminated. The Jacobson and Rogan studies reveal neuro-deficits in children exposed to organochlorines at the high end of the exposure curve. Five percent of the population falls into the high end. This doesn't mean individuals below the high end are unaffected. We cannot assume the existence of a threshold. Present day techniques are simply unable to reveal any damage below the high end. Government policy of dealing with persistent toxic chemicals has failed to prevent environmental contamination by the organochlorines. The policy, best described as end-of-pipe, tries to regulate discharge of toxic chemicals. The policy allows each factory or municipality to discharge small amounts but fails to control non-point sources, such as leaking dumps. Worse, regulatory bodies make no attempt to sum the total loss into the environment. PCBs leaked from a dump in Czechoslovakia, for instance, contaminate Lake Michigan fish. What is needed is global assessment of organochlorines used in commerce, with the goal of eliminating use or discharge of those that persist. Environmental groups call it zero discharge. Zero discharge is a long term goal. What can you do now to minimize contamination? The distribution of PCB body burden in the general population, as noted, ranges more than 10-fold. How can you move into the low end of the distribution range? Because food is the main source of contamination, the immediate answer is to eat far down the food chain. Vegetarians have an edge. PCBs and other organochlorines, being fatsoluble, lodge in fatty foods. Meat, fish and dairy products containing milk fat are major sources. Surprisingly, fruit also contains a high level of organochlorines. Heavy use of pesticides by commercial growers may explain this contamination. The obvious answer: eat non-sprayed fruit. In fact, as a personal goal, you should a void chemically treated food as much as possible. But at best, these measures are palliative. Until governments act to prevent further contamination and organochlorines now in the environment degrade, exposure will be a fact of life for another century or more. You can only hope to reduce your degree of contamination. Because of the long residence time in human flesh, it could take decades for a high-end person to move to the low end. Think ahead a generation. You can minimize exposure
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of future fetuses by minimizing contamination of their parents from the time they themselves are babies.
REFERENCES 1. Harada, M. (1976). Intrauterine poisoning: clinical and epidemiological studies of the problem. Bulletin Institute Constitutional Medicine (Kumamoto University), 25 (suppl) 26-74. 2. Rogan, W.J., et al (1988). Congenital poisoning by polychlorinated biphenyls and their contaminants in Taiwan. Science, 241, 334-336. 3. Safe, S. (1990). Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors. Critical Reviews in Toxicology, 21, 51. 4. Tilson, H.A., Jacobson, J.L. and Rogan, W.J. (1990). PCBs and the Developing Nervous System: Cross-Species Comparisons. Neurotoxicology and Teratology, 121, 239-248. 5. Toxic Chemicals In The Great Lakes And Associated Effects. (1990) Environment Canada, Department of Fisheries and Oceans, Health And Welfare Canada. Government of Canada. Cat. No. En 37-9511990-lE, March. 6. Jacobson, J.L. and Jacobson, S.W. (1988) New Methodologies for Assessing the effects of Prenatal Toxic Exposure on Cognitive Functioning in Humans. In Toxic Contaminants and Ecosystem Health; A Great Lakes Focus. (M.S. Evans, ed.) John Wiley and Sons, New York. 7. Rogan, W.J., Gladen, B.C. and McKinney, J.D. (1986). PCBs and DDEs in Human Milk: Effects of maternal factors and previous lactation. American Journal Public Health, 76, 172-177. Rogan, W.J., et al, (1986). Neonatal effects of transplacental exposure to PCBs and DDE. Journal Pediatrics, 109, 335-341. 8. Gladen, B.C. and Rogan, W.J. ( 1991 ). Effects of perinatal polychlorinated biphenyls and dichlordiphenyldichloroethene on later development. Journal Pediatrics, 119, 58-63. 9. Fox, G.A. and Weseloh, D.V. (1987) Colonial waterbirds as bio-indicators of environmental contamination of the Great Lakes. In The Value ofBirds. (A. W. Diamond and F.L. Filion, eds.) pp. 209-216. ICBP Technical Publication No. 6; Cambridge, England. Fox, G.A., Gilman, A.P., Peakall, D.P. and Anderka, F. W. (1978) Behavioral abnormality of nesting Lake Ontario Herring Gulls. Journal Wildlife Management, 42, 477-483. 10. Fry, D.M. and Toone, C.K. (1981) DDT-induced feminization of gull embryos. Science, 213, 922-924. 11. Daly, H.B. (In press) Consumption of Environmentally Contaminated Lake Ontario Salmon Causes Hyper-Activity to Negative Events in Laboratory Rats. In The Vulnerable Brain: Nutrition and Toxins. (R.L. Isaacson and K.F. Jensen, eds.) Plenum; New York. 12. Arnold, D.L. et al. (1991). Toxicity of PCBs (Aroclor 1254) In Adult Monkeys As A Consequence Of Continuous Exposure and In Infant Monkeys Exposed During Pregnancy And Nursing. The Toxicologist, 11, 220, Abstract 817. 13. Gartrell, M.J. et al, (1986). Pesticides, Selected Elements and Other Chemicals In Adult Total Diet Samples, October 1980-March 1982. Journal Association Official Analytical Chemists, 69, 146-159. 14. Williams, D. T., LeBel, G.L. and Junkins, E. A. (1988) Organohalogen residues in human adipose autopsy samples from six Ontario municipalities. Journal Association of Official Analytical Chemists, 71(2), 410-414.
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43 15. Allen, J.R., Barsotti, D.A. and Carstens, L.A. (1980) Residual Effects ofPCBs On Adult Nonhuman Primates And Their Offspring. Journal Toxicology and Environmental Health, 6, 55-66. 16. Shantz, S.L. and Bowman, R.E. (1983) Persistent locomotor hyperactivity in offspring of Rhesus monkeys exposed to PCBs or PBBs. Society of Neuroscience Abstracts, 9, 423. 17. Bowman, R.E. and Heironimus, M.P. (1981) Hypoactivity in Adolescent Monkeys Perina tally Exposed to PCBs and Hyperactive As Juveniles. Neurobehavioral Toxicology and Teratology, 3, 15-18. 18. Fifth Biennial Report. (1990) International Joint Commission, 100 Metcalife Street, Ottawa, Ontario, Canada, KIP 5Ml. 19. Davies, K.S. (1988) Concentrations And Dietary Intake Of Selected Organochlorines, Including PCBs, PCDDs and PCDFs In Fresh Food Composites Grown In Ontario, Canada. Chemosphere, 17, 263-276. 20. Humphrey, H.E.B. (1988). Chemical Contaminants In the Great Lakes: The Human Health Aspect. In Toxic Contaminants And Ecosystem Health: A Great lAkes Focus. (Marlene S. Evans, ed.) John Wiley & Sons; New York. 21. Kamrin, M.A. and Fisher, L.J. (1991). Workshop On Human Health Impacts of Halogenated Biphenyls and Related Compounds. Environmental Health Perspectives, 91, 157-164. 22. Schecter, A. (In press) Dioxins And Related Chemicals In Humans And the Environment. Banbury Report, Cold Spring Harbor Laboratory Press; Cold Spring Harbor, New York. 23. Jacobson, J.L. and Jacobson, S.W. (1991) Follow-up on children from the Michigan fish-eaters cohort study. Cause-Effect Linkages II Symposium, Michigan Audubon Society, Traverse City, Michigan, Sept. 27-28.
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A NEW THREAT TO PUBLIC HEALTH: ORGANOCHLORINES AND FOOD ROSS HUME HALL PO Box 239, Mount Tabor Road, Danby, Vermont 05739, United States ABSTRACT Ambient levels of persistent toxic chemicals, chemicals that persist for decades in the environment, have reached levels high enough to affect the health of children. The organochlorines (PCBs, DDT and the dioxin family) accumulate in human adipose tissue. Pregnant women pass the contamination to their fetuses. The developing nervous system is the most vulnerable. Neurobehavioral deficits, including short-term memory loss, are detected in children born to mothers at the high end of the distribution curve of organochlorines. Humans are not alone in their susceptibility to these subtle effects. Wildlife exposed to the same spectrum of organochlorines as humans suffer a variety of behavioral changes. Rats and Rhesus monkeys fed diets containing the organochlorines under laboratory conditions exhibit behavioral changes that persist into adulthood. For humans, food provides 80 percent of organochlorine contamination. Meat, fish, dairy and commercial fruit are the main sources. A vegetarian diet including unsprayed fruit minimizes contamination. The ultimate solution to this public health problem is elimination of the organochlorines from the environment.
The human body deploys a marvelous array of defenses against the toxic chemicals it encounters in the course ofliving. But the defenses do not arrive fully formed the instant of conception. Not until a few months following birth do detoxifying enzymes and systems take shape. Does mother protect? Not at all. The placenta, like a sieve, passes toxic substances the mother has accumulated into the fetal blood stream. The fetus, its energies channelled into development, lies vulnerable to attack. Of all the developing organ systems, the nervous system is one of the most easily disrupted. Damage at the fetal stage can result in behavioral changes that manifest after the child is born. Most disturbing, scientists detect such changes in children born to mothers exposed only to a background level of toxic chemicals in the environment. The culprits are the persistent toxic chemicals. These Ross Hume Hall is Professor Emeritus, Biochemistry, McMaster University, Hamilton, Ontario, Canada. He is author of the book, Health and the Global Environment (Basil Blackwell, 1990).
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substances break down in the environment slowly (decades) or not at all. They include organochlorines and heavy metals, such as arsenic, cadmium, lead and mercury. Some of the effects described below are seen in children exposed to low levels of heavy metals, particularly lead. But to illustrate the general threat to human well being, I focus on the organochlorines. These synthetic chemicals, distinguished by chlorine content, include the polychlorinated biphenyls (PCBs), DDT, and the dioxin family. We are dealing with a new type of health problem, one poorly recognized by public health authorities. They regard environmental exposure to toxic chemicals as being localized: living next to a toxic waste dump or working in a chemical factory. Two events now outdate this concept of environmental hazard. First, the background level of toxicity has risen due to global spread of the mobile organochlorines. It puts whole populations at risk. Second, scientists are improving their ability to detect subtle health effects due to environmental exposure. The ones I cover in this article are adverse neurobehavioral effects in children. That organochlorines are neurotoxic is not debated. A wealth of animal data and information about individuals acutely exposed to organochlorines shows the vulnerability of the central nervous system. The troubling question is: are the organochlorines neurotoxic to families going about their lives, exposed only to background levels of these chemicals in the environment? Unlike acute exposure episodes, where connection between adverse effect and exposure is easily _established, we can answer that question only by pulling together several clues. Any one clue may not persuade. But the weight of the clues together should persuade health authorities a new threat to public health is creeping into our populations. I start with studies on children in the Orient and the United States and follow with supporting observations in animals, both in the wild and in the laboratory. Then I come back to the question of how people are contaminated. It turns out food is the main source of contamination, and dietary changes can minimize exposure. NEUROTOXICITY IN CHILDREN
PCB Poisoning In Japan and Taiwan: Controlled experiments are obviously impossible in humans. Scientists, therefore, take the opportunity to study victims of accidental poisonings. Two accidents occurred in the Orient, both the result of eating rice oil contaminated with PCBs. Rice oil is heated during processing, and in these accidents the heating coils leaked PCBs. In the Japanese episode, (called Yusho after the Japanese word for rice oil)a group of families consumed rice oil contaminated with 30-900 parts per million (ppm) of PCBs. Thirteen infants were born to exposed women: one was stillborn, four were undersize, 10 had dark skin pigmentation, four had
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pigmented gums, nine had conjunctivitis and eight had jaundice. Significantly, nine years later, these children still suffered neurological and development impairment. 1 A similar accident occurred in Taiwan (the Yucheng incident after the Chinese word for rice oil). Investigators tracked 117 children born up to seven years following their mothers' one-time high exposure. 2 The children weighed less at birth and exhibited hyperpigmentation of nails and gum and susceptibility to bronchitis. The childrens' mental abilities were measured from the time they were infants to when they were in elementary school. Their abilities consistently fell below the standard of a matched set of children from unexposed mothers. It should be noted in both the Japanese and Taiwan incidents, the PCBs were a complex mixture which included polychlorinated dibenzofurans, known to be more toxic than the PCBs. Whether the observed toxicity is due to PCBs or the contaminants is not critical from the environmental view point. All these organochlorines exhibit a similar toxicity profile, differing only in degree. 3 The most devastating aspect of the toxicity is damage to the victim's nervous system. Main damage occurred during exposure at the fetal stage. Although for some of the children, additional exposure from their mothers' milk enhanced toxic effects. 1 Neurotoxicity in the United States: The question of organochlorine neurotoxicity at the fetal stage has been studied in two groups of children, one in Michigan, and a second in North Carolina. A recent review lists many of the papers referred to in this section. 4 A husband and wife team, Sandra and Joseph Jacobson, psychologists at Wayne State University, Detroit, Michigan, aware of the Yusho/Yucheng studies wondered if neurobehavioral effects could be detected in an ordinary population. Everyone carries PCBs and other organochlorines in their body fat. 5 A pregnant woman passes organochlorines to her fetus, in an amount proportional to the degree of her own contamination. The amounts vary in any group, some women being more contaminated than others. Thus, a distribution curve occurs with high and low ends of contamination. The Jacobsons took advantage of this fact to design their study, the idea being to compare children born to mothers across the distribution curve. 6 To ensure they had sufficient number of individuals at the high end, they selected women who ate a food rich in organochlorines-Lake Michigan fish. Lake Michigan fish are th'~ repositories of the dregs of the steel mills and oil refineries of Gary, Indi.ana, and the sludges of Cicago and other inland cities. The fish are heavily contaminated with organochlorines. The Jacobson team visited maternity wards of hospitals in Western Michigan: interviewing women about to give birth, asking whether or not they ate fish and if so how much. They assembled a cohort of 313 mothers. Seventy-seven mothers never ate lake fish. The rest ate varying amounts of fish ranging from a fish a month to a fish several times a week.
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The Jacobson cohort, thus, consisted of mothers at the high and low ends of ordinary exposure (and in between). This meant a range of exposures for the fetuses. To obtain an accurate measure of fetal exposure, the Jacobsons analyzed the PCB level of umbilical cord blood at time of birth. The PCB level, convenient to measure, serves as a marker for organochlorine contamination. When the babies were born, the Jacobsons found higher amounts of PCBs in umbilical cord blood correlated with the smaller birth size, smaller head circumference, shorter stature and diminished motor coordination. They conducted extensive psychological tests on the children, as newborns, at seven months and again at four years. They found memory deficits, particularly short term, in children born to mothers at the high end of PCB exposure. The deficits persisted over the four years. The Jacobsons are quick to point out: the deficits they observe are small and wouldn't be noticed by a physician examining an individual child. Nevertheless, on a group basis, they find the differences statistically significant. In North Carolina, a team of investigators led by Walter Rogan of the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, conducted a study using a similar experimental design. The Rogan team collected a cohort of 866 women, using the amount of PCBs in the mothers' milk as a measure of pre-natal exposure. 7 Although they made no attempt to identify women who ate highly contaminated food, such as lake fish, they found the distribution of PCB body burden varied more than 10 fold. That is, women at the high end of the distribution curve had over 10 times the level of PCBs as women at the low end. The team found a drop in mental development and motor coordination of newborns that correlated with the higher body burden of PCBs of the mother. But unlike the Jacobson cohort, differences in mental ability between infants at the high and low ends of fetal exposure to PCBs disappeared after age two. 8 Both research groups are pioneering a new approach to uncovering neurotoxic effects at the fetal stage. There may be inconsistency regarding permanency of the observed effects. But more to the point, both research teams observed adverse effects that correlated with degree of PCB exposure in the fetal stage. The two studies have attracted a great deal of interest and some nine research groups have under way or are planning similar studies. These studies are expensive, lengthy and subject to the vagaries of human lifestyle. The Rogan cohort is disintegrating because many of the participants have moved and cannot be traced. The Jacobson cohort, on the other hand, remains intact. The families live in small communities in western Michigan where people tend to stay put. The children are presently 10-11 years old. As they grow older, questions will arise concerning effects during and after puberty. The Jacobsons hope to follow these individuals into adulthood. Mammary tissue, no less than the placenta, passes the mother's contamination to the infant. The Rogan team, thus, used the PCB content of
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milk as a measure of the mother's body burden. Women in both the Michigan and North Carolina studies breast fed their babies. But the observed deficits correlate only with fetal exposure. Contamination of the milk by itself was not associated with any of the observed effects. Milk contamination, nevertheless, deserves some comment. The baby receives a dose of PCBs far higher than adults eating ordinary food. The milk of nursing mothers in Europe and North America average 26 ppb of PCBs (whole milk). 5 On this basis, the milk delivers to the baby about 3 micrograms/kilogram body weight/day (ug/kg/day), three times the World Health Organization (WHO) Acceptable Daily Intake (ADI) of 1 uk/kg bw/day. The ADI, however, may not be a useful comparison. It is based on a lifetime exposure and the baby's exposure is for a few months. On the other hand, the ADI is set as if PCBs were the only contaminant. The full spectrum of organochlorines can occur in mothers milk. Thus assessment of the significance of the milk contamination is difficult. In any event, the Jacobson and Rogan studies, as well as animal data that will be cited in a moment, point to fetal exposure as the problem. Health authorities continue to recommend strongly breast feeding. TOXICITY OF ORGANOCHLORINES IN ANIMALS
Behavioral Changes In Wildlife: Observation of wildlife gives some insight into adverse health effects of organochlorines. Like humans, creatures in the wild integrate the effects of total environmental exposure. Several species of birds and animals experience reproductive failures associated with the organochlorines. Failure, in case of birds, can be due to non-viable eggs or chicks, or to behavioral changes in the parents. Scientists of the Canadian Wildlife Service noticed, for instance, a decline in the normal aggressiveness of male herring gulls. Males fail to protect nests against predators because of feminization. 9 An explanation comes from the work of Michael Fry, a biologist at the University of California, Davis. Fry injected gull eggs with DDT in amounts equivalent to environmental exposure. DDT, acting like an estrogen, altered the hormonal balance of the male embryo at a key moment in development. The embryos hatched into a healthy birds except for failure to express male sexuality. 10 Feminization of males forces bizarre behavior among females. With lack of interest from males, female-female pairing occurs. DDT may not' be alone in stimulating such behavioral changes. Several other organochlorines, by virtue of chemical shape, mimic the actions of sex hormones. The adverse effects of organochlorines on wildlife have been documented since the 1960s. But health authorities missed the significance. Fish-eating gulls eat near the top of the food chain. Because of bioaccumulation, fish accumulate organochlorines some million fold over the concentration in
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water. Concentrations in fish-eating birds can go 25 fold higher. But health authorities thought contamination was confined to water bodies and therefore, wildlife observations were not relevant. With global contamination and with a high meat and diary diet, people, no less than herring gulls, bioaccumulate organochlorines high up the food chain. Rat Behavior Affected by Organochlorines: Further evidence behavioral changes provide a highly sensitive indicator of organochlorine exposure comes from studies on laboratory rats. Helen Daly, an animal psychologist, State University New York, Oswego, fed adult rats Lake Ontario salmon. Oswego is located on Lake Ontario making it easy for Daly to obtain quantities of fish. These fish, like Lake Michigan fish, are highly contaminated with a full range of organochlorines. She fed her control rats Pacific salmon, a species much less contaminated. The rats in the two groups behaved no differently as long-as she describes-"life was pleasant". When presented with adversity, such as altered food delivery, the "Pacific" rats easily handled the change. the "Lake Ontario" rats, in contrast, became excited and took a long time to adapt. 11 Daly conducted a second generation study. She fed adult females fish while pregnant and seven days into nursing. The offspring received normal, uncontaminated chow. As adults, the "Lake Ontario" offspring, compared to "Pacific" offspring, showed the same hyperexcitability and slowness to adapt to a changed routine. The diet Daly fed the rats consisted of 30 percent salmon and 70 percent rat chow. She did control experiments to rule out any possibility that the effects she saw were due to the fish per se. She made no attempt to sort out which of the fish contaminant(s) caused the effects. She wanted to give her rats a chemical exposure comparable to what humans receive. Daly comments that the rat results should predict human behavior, in particular reluctance to face novel situations. She notes at age four those Jacobson cohort children with high exposures resisted psychological testing. PCB Poisoning in Rhesus Monkeys: The reproductive system of the Rhesus is particularly sensitive to low level PCB exposure. Douglas Arnold and a team at Health and Welfare Canada, Ottawa, fed PCBs to adult females at 5 ug/kg/day until the animals reached a steady level of PCBs in their tissues (about three years). General health was minimally affected; weight, feed consumption and blood cell count were the same as untreated controls. But reproduction collapsed. Sixteen PCB-fed females, on mating, produced four live and six stillborn infants. Sixteen control females, in contrast, produced nine live and two stillborns. Arnold concludes a no-effect level (if there is one) is less than 5 ug/kg/day .12 This number is uncomfortably close to WHO's ADI for PCBs for humans, 1 ug/kg/day. The actual intake of humans (excluding nursing babies) according to United States food and Drug Administration (U.S. FDA) averages 0.003jg/kg/dayY These
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numbers suggest human exposure is far below that of the monkeys. But whereas the monkeys accumulated their body burdens over three years, human mothers accumulate their body burden over 20-30 years. More revealing, the body burden of the monkeys is not much above that of humans with no known extraordinary exposure. Residents of Southern Ontario average 2 ppm PCBs in their adipose tissue. 14 The Rhesus mothers (which experienced severe reproductive failure) averaged 7 ppm at time of pregnancy. More to the point, what toxic effects appear in the offspring? Scientists at the Harlow Primate Laboratory, Wisconsin, Madison, addressed this question. They fed Rhesus females PCBs until the animals attained an average level of 1.4 ppm in their subcutaneous fat. 15 This level, lower than that of the above group, did not cause reproductive failure. The 15 females of the group were mated and 11 live infants were born. The infants were breast fed four months. Their size and general health was normal, but all developed hyperpigmentation of the face-a sign of PCB toxicity. The level of PCBs in the milk averaged 50 parts per billion (ppb ), whole milk, at time . of weaning. The investigators attributed the toxic effects of PCBs, not to the milk, but to placental transfer. Robert Bowman of the Wisconsin laboratory took the baby monkeys from this experiment and subjected them as juveniles to a battery of psychological tests. Like Daly's Lake Ontario rats, they became hyperactive and confused when confronted with stress. 16 In a second experiment, Bowman and his team followed rhesus offspring until they were adults. Monkeys, born to PCB-exposed mothers and hyperactive as juveniles, became sluggish (hypoactive) as adolescents. 17 This behavioral change has unusual significance. Bowman notes: it is a toxic event that occurred during fetal development, but dido 't manifest until nearadulthood. In sum, a common thread runs through all the animal studies, both in the wild and in the laboratory: vulnerability to the organochlorines of the developing central nervous system. The Michigan and North Carolina studies suggest humans are no less vulnerable. The International Joint Commission, a body charged with overseeing clean-up of the Great Lakes, says this information brings fresh urgency to get on with cleaning up the environment. What particularly alarms the Commission is that human vulnerability manifests at ambient, environmental levels of persistent toxic chemicals (including the organochlorines). 18
FOOD IS THE MAIN EXPOSURE ROUTE
The toxic threat of organochlorines to wildlife was recognized in the 1960s. By the early 70s, use of DDT was banned in North America and worldwide production of PCBs stopped. During the decade of the 70s the
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environmental level of these particular substances declined. But by the early 80s decline ceased and the levels now hold steady. Continued injection of new amounts of organochlorines from industrial and municipal discharges and leaking dumps adds to the global burden. Because of volatility, organochlorines evaporate from water bodies, move in the global air currents, rain out over land and crops, and wash back to lakes and the sea. Analyses of fat samples from North Americans and Europeans and from Arctic natives show equivalent contamination. 5 We become contaminated from eating an ordinary diet. Katherine Davies, a biochemist at Toronto's Department of Health, analyzed a market basket of fruits, vegetables, meat and dairy products, produced in Southern Ontario. The foods were contaminated with dioxins, PCBs and several of the organochlorine pesticides. 19 She concluded about 80 percent of a person's daily intake of thexe toxic chemicals stems from food. U.S. FDA, analyzing typical market baskets of food, arrived at a similar conclusion. 13 The conclusion stunned government regulators. They assumed drinking water was the main source and, if necessary, they could remove that contamination. The province of Ontario in the early 1980s, for instance, initiated a pilot study in municipal water treatment plants. They found charcoal removes organochlorines from the water. But how do you use charcoal to purify a PCB-laden roast? Organochlorines ingested with food are readily absorbed into body tissues. Individuals who have just eaten a meal of Great Lakes fish, (an excellent source of organochlorines) experience an immediate rise in blood levels of the same organochlorines contaminating the fish. 20 Rhesus monkeys fed PCBs absorb 90 percent of the dose. 12 The body deals with toxic substances either by excreting or sequestering them. The organochlorines, being fat soluble, pass from the blood into the body fat where they accumulate. There is a slow release from the body, but it is very slow. If a person received a single dose of polychlorinated dibenzofurans, virtual elimination would require 58 years. 21 The half life for residence of PCBs in the human body, based on a one-time exposure, is estimated at 12 years. But with recontamination at every meal, body levels build up. Older people have higher levels of dioxins than children. 22 CONCLUSION: WHAT SHOULD BE DONE?
Clearly a new type of public health problem is at a stake. The biggest obstacle to overcoming the problem is mindset. Governments need to reassess the way they define health risks. In addition to diseases, where people are clearly sick, they need to pay attention to subtle damage that diminishes human capacities. WHO addressed this point 40 years ago when it offered an expanded view of health: "a state of complete physical, mental and social well-being, and not merely the absence of disease or injury."
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The WHO concept goes beyond defining health as a collection of negatives-of not suffering any clinically defined disorder. Neuro-deficits, detected in the Michigan and North Carolina children fall within the WHO definition. At a symposium, sponsored by the Michigan Audubon Society, Joseph Jacobson talked of "diminished potential". "The short term memory deficits we have seen could be quite significant for later cognitive development," he said. "[diminished] speed of information processing could have a marked impact on the child's ability to master basic reading and arithmetic skills in school. " 23 The problem is not a few exposed people. Everyone is contaminated. The Jacobson and Rogan studies reveal neuro-deficits in children exposed to organochlorines at the high end of the exposure curve. Five percent of the population falls into the high end. This doesn't mean individuals below the high end are unaffected. We cannot assume the existence of a threshold. Present day techniques are simply unable to reveal any damage below the high end. Government policy of dealing with persistent toxic chemicals has failed to prevent environmental contamination by the organochlorines. The policy, best described as end-of-pipe, tries to regulate discharge of toxic chemicals. The policy allows each factory or municipality to discharge small amounts but fails to control non-point sources, such as leaking dumps. Worse, regulatory bodies make no attempt to sum the total loss into the environment. PCBs leaked from a dump in Czechoslovakia, for instance, contaminate Lake Michigan fish. What is needed is global assessment of organochlorines used in commerce, with the goal of eliminating use or discharge of those that persist. Environmental groups call it zero discharge. Zero discharge is a long term goal. What can you do now to minimize contamination? The distribution of PCB body burden in the general population, as noted, ranges more than 10-fold. How can you move into the low end of the distribution range? Because food is the main source of contamination, the immediate answer is to eat far down the food chain. Vegetarians have an edge. PCBs and other organochlorines, being fatsoluble, lodge in fatty foods. Meat, fish and dairy products containing milk fat are major sources. Surprisingly, fruit also contains a high level of organochlorines. Heavy use of pesticides by commercial growers may explain this contamination. The obvious answer: eat non-sprayed fruit. In fact, as a personal goal, you should a void chemically treated food as much as possible. But at best, these measures are palliative. Until governments act to prevent further contamination and organochlorines now in the environment degrade, exposure will be a fact of life for another century or more. You can only hope to reduce your degree of contamination. Because of the long residence time in human flesh, it could take decades for a high-end person to move to the low end. Think ahead a generation. You can minimize exposure
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of future fetuses by minimizing contamination of their parents from the time they themselves are babies.
REFERENCES 1. Harada, M. (1976). Intrauterine poisoning: clinical and epidemiological studies of the problem. Bulletin Institute Constitutional Medicine (Kumamoto University), 25 (suppl) 26-74. 2. Rogan, W.J., et al (1988). Congenital poisoning by polychlorinated biphenyls and their contaminants in Taiwan. Science, 241, 334-336. 3. Safe, S. (1990). Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors. Critical Reviews in Toxicology, 21, 51. 4. Tilson, H.A., Jacobson, J.L. and Rogan, W.J. (1990). PCBs and the Developing Nervous System: Cross-Species Comparisons. Neurotoxicology and Teratology, 121, 239-248. 5. Toxic Chemicals In The Great Lakes And Associated Effects. (1990) Environment Canada, Department of Fisheries and Oceans, Health And Welfare Canada. Government of Canada. Cat. No. En 37-9511990-lE, March. 6. Jacobson, J.L. and Jacobson, S.W. (1988) New Methodologies for Assessing the effects of Prenatal Toxic Exposure on Cognitive Functioning in Humans. In Toxic Contaminants and Ecosystem Health; A Great Lakes Focus. (M.S. Evans, ed.) John Wiley and Sons, New York. 7. Rogan, W.J., Gladen, B.C. and McKinney, J.D. (1986). PCBs and DDEs in Human Milk: Effects of maternal factors and previous lactation. American Journal Public Health, 76, 172-177. Rogan, W.J., et al, (1986). Neonatal effects of transplacental exposure to PCBs and DDE. Journal Pediatrics, 109, 335-341. 8. Gladen, B.C. and Rogan, W.J. ( 1991 ). Effects of perinatal polychlorinated biphenyls and dichlordiphenyldichloroethene on later development. Journal Pediatrics, 119, 58-63. 9. Fox, G.A. and Weseloh, D.V. (1987) Colonial waterbirds as bio-indicators of environmental contamination of the Great Lakes. In The Value ofBirds. (A. W. Diamond and F.L. Filion, eds.) pp. 209-216. ICBP Technical Publication No. 6; Cambridge, England. Fox, G.A., Gilman, A.P., Peakall, D.P. and Anderka, F. W. (1978) Behavioral abnormality of nesting Lake Ontario Herring Gulls. Journal Wildlife Management, 42, 477-483. 10. Fry, D.M. and Toone, C.K. (1981) DDT-induced feminization of gull embryos. Science, 213, 922-924. 11. Daly, H.B. (In press) Consumption of Environmentally Contaminated Lake Ontario Salmon Causes Hyper-Activity to Negative Events in Laboratory Rats. In The Vulnerable Brain: Nutrition and Toxins. (R.L. Isaacson and K.F. Jensen, eds.) Plenum; New York. 12. Arnold, D.L. et al. (1991). Toxicity of PCBs (Aroclor 1254) In Adult Monkeys As A Consequence Of Continuous Exposure and In Infant Monkeys Exposed During Pregnancy And Nursing. The Toxicologist, 11, 220, Abstract 817. 13. Gartrell, M.J. et al, (1986). Pesticides, Selected Elements and Other Chemicals In Adult Total Diet Samples, October 1980-March 1982. Journal Association Official Analytical Chemists, 69, 146-159. 14. Williams, D. T., LeBel, G.L. and Junkins, E. A. (1988) Organohalogen residues in human adipose autopsy samples from six Ontario municipalities. Journal Association of Official Analytical Chemists, 71(2), 410-414.
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43 15. Allen, J.R., Barsotti, D.A. and Carstens, L.A. (1980) Residual Effects ofPCBs On Adult Nonhuman Primates And Their Offspring. Journal Toxicology and Environmental Health, 6, 55-66. 16. Shantz, S.L. and Bowman, R.E. (1983) Persistent locomotor hyperactivity in offspring of Rhesus monkeys exposed to PCBs or PBBs. Society of Neuroscience Abstracts, 9, 423. 17. Bowman, R.E. and Heironimus, M.P. (1981) Hypoactivity in Adolescent Monkeys Perina tally Exposed to PCBs and Hyperactive As Juveniles. Neurobehavioral Toxicology and Teratology, 3, 15-18. 18. Fifth Biennial Report. (1990) International Joint Commission, 100 Metcalife Street, Ottawa, Ontario, Canada, KIP 5Ml. 19. Davies, K.S. (1988) Concentrations And Dietary Intake Of Selected Organochlorines, Including PCBs, PCDDs and PCDFs In Fresh Food Composites Grown In Ontario, Canada. Chemosphere, 17, 263-276. 20. Humphrey, H.E.B. (1988). Chemical Contaminants In the Great Lakes: The Human Health Aspect. In Toxic Contaminants And Ecosystem Health: A Great lAkes Focus. (Marlene S. Evans, ed.) John Wiley & Sons; New York. 21. Kamrin, M.A. and Fisher, L.J. (1991). Workshop On Human Health Impacts of Halogenated Biphenyls and Related Compounds. Environmental Health Perspectives, 91, 157-164. 22. Schecter, A. (In press) Dioxins And Related Chemicals In Humans And the Environment. Banbury Report, Cold Spring Harbor Laboratory Press; Cold Spring Harbor, New York. 23. Jacobson, J.L. and Jacobson, S.W. (1991) Follow-up on children from the Michigan fish-eaters cohort study. Cause-Effect Linkages II Symposium, Michigan Audubon Society, Traverse City, Michigan, Sept. 27-28.
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