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American Academy of Pediatrics
Article

Evidence of Effects of Environmental Chemicals on the Endocrine System in Children

Walter J. Rogan and N. Beth Ragan
Pediatrics July 2003, 112 (Supplement 1) 247-252;
Walter J. Rogan
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N. Beth Ragan
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Abstract

Pollutant chemicals that are widespread in the environment can affect endocrine signaling, as evidenced in laboratory experiments and in wildlife with relatively high exposures. Although humans are commonly exposed to such pollutant chemicals, the exposures are generally low, and clear effects on endocrine function from such exposures have been difficult to demonstrate. Several instances in which there are data from humans on exposure to the chemical agent and the endocrine outcome are reviewed, including age at weaning, age at puberty, and sex ratio at birth, and the strength of the evidence is discussed. Although endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real.

  • endocrine disruptors
  • puberty
  • lactation
  • thyroid
  • child

The most informative studies of the effects of environmental chemicals on the endocrine system in children concern 2 ubiquitous, persistent halogenated organic pollutant chemicals: dichlorodiphenyltrichloroethane (DDT) and its derivatives and polychlorinated biphenyls (PCBs) and chemicals similar to them. Although these agents have a variety of toxic effects, some of which might have an endocrine mechanism, the focus here is on several areas that are the most plausibly related to endocrine function: duration of lactation (age at weaning, not length of a feeding); growth, especially at puberty; sex ratio at birth among heavily exposed groups; and thyroid function. Much of the background material was originally prepared by the Committee on Environmental Health of the American Academy of Pediatrics for its Handbook of Pediatric Environmental Health,1 but it appears here with more detailed references and at somewhat greater length. The potential for PCBs specifically to act as endocrine disrupters at background exposures has been reviewed recently.2

BACKGROUND

The idea that certain pesticides could interfere with hormonal processes in vertebrates probably goes back to the observation that DDT decreased hatchability of the eggs of pelagic birds.3 The mechanism of this effect was likely a combination of induction of enzymes that metabolized endogenous estrogens and occupancy of the estrogen receptor by very weak but persistent compounds. Some forms of DDT, other pesticides such as methoxychlor and chlordecone, and industrial chemicals such as some PCBs have been proved to increase the wet weight of a virgin mouse uterus, which is the classic bioassay for estrogenicity.4 Compounds of diverse structures can be potent estrogens; the best example of this structural heterogeneity is the stilbene diethylstilbestrol, which looks nothing like a 17 ketosteroid. Examples of synthetic environmental chemicals acting as estrogens or more generally disrupting hormonal events have been documented in wildlife. Male alligators in Florida were feminized by exposure to a spill of the pesticide dicofol,5 and birds near the Great Lakes have failed to reproduce likely because of high body burdens of DDT.6 In addition to synthetic chemicals, there are also many naturally occurring phytoestrogens in plants, mostly isoflavones, that are less potent than estradiol and more readily cleared than pesticides. Infants who are fed soy formula have high exposures to these compounds,7 and there are some data suggestive of an estrogenlike effect on cholesterol synthesis in soy-fed infants.8 Endogenous and pharmaceutical estrogens are excreted in the urine in amounts close to those administered synthetically or produced naturally. Human sewage9 or runoff from feedlots in which animals are treated can contain significant amounts of estrogen.

Although estrogenicity is the most familiar of the hormonelike activities of exogenous chemicals, one form of dichlorodiphenyldichloroethene (DDE) is an antiandrogen.10 Some pesticides and congeners of PCBs can occupy thyroid hormone receptors, and other agents produce symptoms such as infertility in chlordecone11 and dibromochloropropane12 workers that are plausibly the result of interference with normal endocrine function, even if a hormonal basis is not established.

Secular trends in sperm counts and increased rates of testicular cancer, undescended testicles, and hypospadias all have been attributed to endocrine disruption by synthetic environmental agents, although no studies are available yet in which the outcome and the responsible chemical has been measured in the same people. There are such studies on breast cancer, and these so far do not show any consistent relationship between body stores of DDT or PCBs and disease risk.13

Three areas related to the hypothesized endocrine disruption caused by environmental chemicals directly concerning children are discussed: the endocrine modulation of breastfeeding and weaning; peripubertal growth and the onset of puberty in children; and sex ratio of births among heavily exposed individuals. For all of these, there are reasonably good data that include measures of exposure and outcome, usually at an individual level. There are also good data concerning child development and PCBs and DDT; however, it is not clear that these effects are produced through an endocrine mechanism, and there are enough data to warrant a separate discussion.

DDE AND DURATION OF LACTATION IN NORTH CAROLINA AND MEXICO

Very high levels of prolactin during pregnancy are accompanied by very high levels of circulating estrogen, which result in increased duct surface area within the breast but usually not in full milk synthesis. Only when estrogen levels fall at term can prolactin act unopposed to promote milk synthesis. Old-style, high-dose oral contraceptives given to lactating women were associated with decreased milk volume and perhaps early weaning.14 It was thought that the presence of a weak but persistent estrogen-like DDE might interfere with milk synthesis, which would be observed as early weaning. This is because a child who is fussing or not gaining weight while being breastfed is often given supplemental formula or food, and supplementation decreases sucking vigor and, thus, further decreases supply. This hypothesis was tested within the North Carolina Infant Feeding Study.15

The North Carolina Infant Feeding Study was a 900-child, prospective birth cohort study of children from central North Carolina enrolled between 1978 and 1982. At or near birth, samples of breast milk or colostrum, maternal serum, placenta, and cord blood were collected and analyzed for DDE, the most stable and persistent compound of the DDT family. The children were followed clinically and developmentally with periodic examinations and psychometric testing from birth until 5 years of age, and parents were surveyed by mail periodically after that. Information was gathered about how the child was fed and, if breastfed, when the child was weaned. Although the North Carolina study was primarily concerned with the possibility that PCBs and DDE in breast milk might produce detectable toxicity in the breastfed child, the process of lactation itself was also a focus.

Although such an effect had been hypothesized, the strength of the relationship was surprising: the women with the highest levels of DDE and PCBs (approximately >5 parts per million [ppm] of fat basis in milk) breastfed <40% as long as women with the lowest levels (approximately <2 ppm of fat basis in milk), unaccompanied by any increase in illness in the children.15 To replicate the association, a smaller study was conducted in the north central part of Mexico, in a region that had historically used DDT on cotton crops. The levels of DDE and PCBs in breast milk were several times higher than those in North Carolina, with a median of >5 ppm of fat basis in milk, compared with approximately 2 ppm in North Carolina. When data from all of the women were used, there was a very similar relationship between DDE concentration and weaning (Table 1). Although the study in Mexico was only of 230 women, for this purpose it was statistically approximately as powerful as the larger North Carolina study, because so many more of the women had higher levels of DDE in their milk.16

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TABLE 1.

Median Age at Weaning and DDE Concentration in Breast Milk, Mexico and North Carolina

Studies such as these are subject to a peculiar form of bias. The concentration of DDE (and PCBs) decreases over the course of lactation. The rate of this decrease was ∼20% for each 6 months of lactation.17 This occurs because the chemical is transferred to the child, making the concentration in the mother’s fat lower. Supposing that there are 2 kinds of breastfeeding women, those who naturally breastfeed for a long time and those who do not for reasons completely unrelated to DDE, when these women have children and nurse them, the long-term breastfeeder will end up with a lower concentration of DDE and PCBs at the time she weans than will the short-term breastfeeder. If the women are then observed in second and later lactations, they will likely proceed to breastfeed in a manner similar to what they did with their first pregnancy. If DDE is measured in their milk, even if it is measured very early in lactation, then the women with lower levels will breastfeed longer, but this will be an effect rather than a cause. The simplest way to avoid being misled by this bias is to study the phenomenon among first lactations. In the North Carolina data, the relationship was very similar when examined in women who were pregnant for the first time, but in Mexico, it was not. Although a statistical simulation that showed that it was improbable that the bias would have produced an effect as large as was seen in Mexico was performed, it was nonetheless not a completely clean confirmation of the previous result. There has not yet been another study specifically addressing this question. In Michigan, after an episode of food contamination with polybrominated biphenyls, women with higher levels in their milk weaned earlier than those with lower levels, but they had been advised to do so by health authorities, and so the effect could not be interpreted to be attributable to the chemical.18

There is a resurgence of interest in DDT for malaria vector control. Unfortunately, the same parts of the world in which malaria is a problem are also places where prolonged breastfeeding may be life saving, and the decision poses a public health dilemma.19

PCBs, HYPOTONIA, AND THYROID FUNCTION

In the early studies of background exposures to PCBs, hypotonia at birth was related to prenatal exposure to PCBs20 or to a history of consuming PCB-contaminated fish,21 which was suggestive of an effect on thyroid hormone. PCBs have long been known to be toxic to the developing thyroid gland.22 Subsequently, hypotonia was shown to be accompanied by higher thyroid-stimulating hormone in 1 study,23 and now there are data from 5 additional studies (Table 2).24 The level of PCB exposure in the Faeroe Islands25 was higher than in studies from Holland,23,26 North Carolina,27 and Germany.28 The combination of the highest exposures and the second largest sample size makes the Faeroe Islands study the most useful. In general, associations between PCBs and a variety of measures of thyroid hormone status have been weak, inconsistent, or absent. The hypothesis has a very reasonable basis in laboratory evidence, though, and is probably worth additional innovative study.

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TABLE 2.

Summary of Epidemiologic Data on Associations Between Levels of PCBs and Measures of Thyroid Hormone Economy From the Dietary Exposure Studies24

SEX RATIO

Perhaps because of the decreased redundancy of genetic information on the Y chromosome, the male human is the more delicate of species, with shorter life expectancy at all ages. Theoretically, a toxic exposure during pregnancy might selectively damage male fetuses, resulting in a greater ratio at birth of the hardier female infants. This would not necessarily involve a hormonal mechanism, but studies of sex ratio at birth have been a part of the discussion on endocrine disruption. Although there are some data on secular trends, the most relevant data from a toxicologic perspective come from Seveso, Italy, where in 1976 a factory exploded, releasing perhaps 1 kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin, one of the most toxic chemicals known. A variety of illnesses have been attributed to this exposure, but a clear pattern of severe toxicity has not emerged.29 In 1996, however, Mocarelli et al30 observed that between 1977 and 1984, 48 girls but only 26 boys were born to the most exposed families. This was a very large effect on a very stable number, and without obvious mechanistic explanation. There was information about the children who were born in Taiwan after the exposure there to PCBs and polychlorinated dibenzofurans, and there was clearly more toxicity apparent among the exposed Taiwanese than among the residents of Seveso. However, a change in sex ratio was not detected among families studied in which at least the mother had been exposed.31 This posed a problem in interpretation until the publication of more detailed data from Seveso showing that the decrease in male births occurred specifically among families in which the father was exposed: 50 boys and 81 girls were born in families in which the men had been exposed before 19 years of age.32 However, rather than clarify the issue, the detailed report noted that the ratio of boys to girls had begun to decrease in the area before the exposure took place in 1976. At this point, the very large departure in the sex ratio of Seveso births remains unexplained, and although it would seem straightforward to replicate in the laboratory, no report is yet available of such an experimental study. Because data on fathers’ exposures in Taiwan were unavailable, the failure to replicate the Seveso finding could have been attributable to a large number of families with only maternal exposure in the Taiwan study.

ADOLESCENT GROWTH AND SEXUAL MATURATION

When Herman-Giddens et al33 published data showing that many girls, especially black girls, had pubic or axillary hair and breast development before 7 years of age, it was viewed by many as evidence that puberty was occurring younger than it had been at some unspecified time in the past. Although there is good evidence that age at menarche has been decreasing in white girls for decades,34 there was no data on black girls or on the other stages of puberty to allow estimation of a secular trend. There was interest in onset of puberty among the children in the North Carolina study, and 594 of them were recontacted as they reached adolescence. Height, weight, and stage of pubertal development were assessed through annual mailed questionnaires. The child or the parent provided the assessment of pubertal stage, using line drawings of the 5 Tanner stages. These show characteristics of the pubic hair, penis, and scrotum in boys and pubic hair and breast in girls that range from 0 (prepubertal) to 5 (adult). There is good evidence that children can report their stage accurately using this instrument.35,36 It was found that the higher the prenatal exposure to DDE, the taller and heavier boys were at 14 years of age; those with the highest exposures (maternal concentration of DDE ≥4 ppm of fat) had an adjusted mean height of 6.3 cm and an adjusted mean body weight of 6.9 kg higher than those with the lowest exposures (0–1 ppm of fat). There was no effect on the ages at which pubertal stages were attained. Lactational exposures to DDE had no apparent effects, and neither did transplacental or lactational exposure to PCBs. Girls with the highest transplacental PCB exposures were heavier for their heights than other girls by an average of 5.4 kg, but differences were significant only when the analysis was restricted to white girls. Although there was some evidence that the girls with the highest PCB exposure reached the early stages of puberty sooner, the numbers were small, age at menarche seemed unaffected, and there was no previous hypothesis concerning individual stages of puberty. The conclusion was that prenatal exposures at background levels may have an impact on body size at puberty.

The North Carolina data are peculiarly well suited to this kind of study, because the observed associations all concerned prenatal exposure, which could be assessed because biological samples were collected perinatally. There was no relationship seen with the larger but later exposure through breastfeeding. Adolescents’ body burdens of these agents, however, seemed to be primarily determined by how much they were breastfed37; thus, a study done at the time of puberty using biological samples from the child could not determine the prenatal effect. There are several studies ongoing that will have the data to allow replication of the North Carolina findings, but none have appeared so far.

In Taiwan, male adolescents who were exposed in utero to high levels of PCBs or polychlorinated dibenzofurans had normal progression through the Tanner stages but smaller penises than controls. Puberty in girls was unaffected, as far as could be determined.38 This is a complicated effect, not obviously an estrogenic one, and its mechanism is not known.

CONCLUSIONS

What role, if any, environmental chemicals play in morbidity attributable to endocrine disruption is unclear. Many studies of breast cancer, endometriosis, testicular cancer, and other plausible end points are under way. Right now, environmental endocrine disruption in humans is much more speculation than demonstrated fact. In 1996, Congress enacted legislation requiring the Environmental Protection Agency to screen and test chemicals in food and water for estrogenic and possibly other hormonal activity. Most likely, such testing would serve to pick out agents for more intense study. It would not replace more traditional tests for general toxicity and carcinogenicity. Chemicals are not currently tested specifically for their ability to mimic, disrupt, or otherwise act as hormone agonists or antagonists, except on a research basis. However, the detailed studies of general toxicity, carcinogenicity, and reproduction that new chemicals undergo would be likely to identify potent endocrine toxicity.

DDT, dichlorodiphenyltrichloroethane • PCB, polychlorinated biphenyl • DDE, dichlorodiphenyldichloroethene • ppm, parts per million

REFERENCES

  1. ↵
    Etzel RA, Balk SJ, eds. American Academy of Pediatrics, Committee on Environmental Health. Handbook of Pediatric Environmental Health. Elk Grove Village, IL: American Academy of Pediatrics; 1999
  2. ↵
    Brouwer A, Longnecker MP, Birnbaum LS, et al. Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs. Environ Health Perspect.1999;107 :639– 649
    OpenUrlCrossRefPubMed
  3. ↵
    US Environmental Protection Agency. DDT: A Review of Scientific and Economic Aspects of the Decision to Ban its Use as a Pesticide. Washington, DC: Environmental Protection Agency; 1975
  4. ↵
    Kupfer D, Bulger WH. Estrogenic properties of DDT and its analogs. In: McLachlan JA, ed. Estrogens in the Environment. New York, NY: Elsevier/North-Holland;1980:239– 263
  5. ↵
    Guillette LJ Jr, Gross TS, Masson GR, Matter JM, Percival HF, Woodward AR. Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida. Environ Health Perspect.1994;102 :680– 688
    OpenUrlCrossRefPubMed
  6. ↵
    Fry DM, Toone CK. DDT-induced feminization of gull embryos. Science.1981;213 :922– 924
    OpenUrlAbstract/FREE Full Text
  7. ↵
    Setchell KD, Zimmer-Nechemias L, Cai J, Heubi JE. Exposure of infants to phyto-oestrogens from soy-based infant formula. Lancet.1997;350 :23– 27
    OpenUrlCrossRefPubMed
  8. ↵
    Cruz ML, Wong WW, Mimouni F, et al. Effects of infant nutrition on cholesterol synthesis. Pediatr Res.1994;35 :135– 140
    OpenUrlPubMed
  9. ↵
    Ternes TA, Stumpf M, Mueller J, Haberer K, Wilken RD, Servos M. Behavior and occurrence of estrogens in municipal sewage treatment plants: I. Investigations in Germany, Canada, and Brazil. Sci Total Environ.1999;225 :81– 90
    OpenUrlCrossRefPubMed
  10. ↵
    Kelce WR, Stone CR, Laws SC, Gray LE, Kemppainen JA, Wilson EM. Persistent DDT metabolite p, p′-DDE is a potent androgen receptor agonist. Nature.1995;375 :581– 585
    OpenUrlCrossRefPubMed
  11. ↵
    Cohn W, Boylan JJ, Blanke R, Fariss MW, Howell JR, Guzelian PS. Treatment of chlordecone (Kepone) toxicity with cholestyramine. Results of a controlled clinical trial. N Engl J Med.1978;298 :243– 248
    OpenUrlCrossRefPubMed
  12. ↵
    Goldsmith JR, Potashnik G, Israeli R. Reproductive outcomes in families of DBCP-exposed men. Arch Environ Health.1984;39 :85– 89
    OpenUrlPubMed
  13. ↵
    Key T, Reeves G. Organochlorines in the environment and breast cancer. BMJ.1994;308 :1520– 1521
    OpenUrlFREE Full Text
  14. ↵
    Harlap S. Exposure to contraceptive hormones through breast milk—are there long-term health and behavioral consequences? Int J Gynaecol Obstet.1987;25(suppl) :47– 55
    OpenUrl
  15. ↵
    Rogan WJ, Gladen BC, McKinney JD, et al. Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in human milk: effects on growth, morbidity, and duration of lactation. Am J Public Health.1987;77 :1294– 1297
    OpenUrlPubMed
  16. ↵
    Gladen BC, Rogan WJ. DDE and shortened duration of lactation in a Northern Mexican town. Am J Public Health.1995;85 :504– 508
    OpenUrlPubMed
  17. ↵
    Rogan WJ, Gladen BC, McKinney JD, et al. Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in human milk: effects of maternal factors and previous lactation. Am J Public Health.1986;76 :172– 177
    OpenUrlPubMed
  18. ↵
    Weil WB, Spencer M, Benjamin D, Seagull E. The effect of polybrominated biphenyl on infants and young children. J Pediatr.1981;98 :47– 51
    OpenUrlCrossRefPubMed
  19. ↵
    Rogan WJ. The DDT question. Lancet.2000;356 :1189– 1189
    OpenUrlPubMed
  20. ↵
    Rogan WJ, Gladen BC, McKinney JD, et al. Neonatal effects of transplacental exposure to PCBs and DDE. J Pediatr.1986;109 :335– 341
    OpenUrlPubMed
  21. ↵
    Jacobson JL, Jacobson SW, Fein GG, Schwartz PM, Dowler JK. Prenatal exposure to an environmental toxin: a test of the multiple effects model. Dev Psychol.1984;20 :523– 532
    OpenUrlCrossRef
  22. ↵
    Collins WT Jr, Capen CC. Fine structural lesions and hormonal alterations in thyroid glands of perinatal rats exposed in utero and by the milk to polychlorinated biphenyls. Am J Pathol.1980;99 :125– 142
    OpenUrlPubMed
  23. ↵
    Koopman-Esseboom C, Morse DC, Weisglas-Kuperus N, et al. Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants. Pediatr Res.1994;36 :468– 473
    OpenUrlPubMed
  24. ↵
    Longnecker MP. Endocrine and other human health effects of environmental and dietary exposure to polychlorinated biphenyls (PCBs). In: Robertson LW, Hansen LG, eds. Recent Advances in the Environmental Toxicology and Health Effects of PCBs. Lexington, KY: University of Kentucky Press; 2001:114
  25. ↵
    Steuerwald U, Wiehe P, Jorgensen PJ, et al. Maternal seafood diet, methylmercury exposure, and neonatal neurologic function. J Pediatr.2000;136 :599– 605
    OpenUrlCrossRefPubMed
  26. ↵
    Fiolet DCM, Cuijpers CEJ, Lebret E. Exposure to polychlorinated organic compounds and thyroid hormone plasma levels of human newborns. Organohalogen Compounds.1997;34 :459– 465
    OpenUrl
  27. ↵
    Longnecker MP, Gladen BC, Patterson DG Jr, Rogan WJ. Polychlorinated biphenyl (PCB) exposure in relation to thyroid hormone levels in neonates. Epidemiology.2000;11 :249– 254
    OpenUrlCrossRefPubMed
  28. ↵
    Osius N, Karmaus W, Kruse H, Witten J. Exposure to polychlorinated biphenyls and levels of thyroid hormones in children. Environ Health Perspect.1999;107 :843– 849
    OpenUrlPubMed
  29. ↵
    Bertazzi PA, Zocchetti C, Pesatori AC, Guercilena S, Sanarico M, Radice L. Ten-year mortality study of the population involved in the Seveso incident in 1976. Am J Epidemiol.1989;129 :1187– 1200
    OpenUrlAbstract/FREE Full Text
  30. ↵
    Mocarelli P, Brambilla P, Gerthoux PM, Patterson DG Jr, Needham LL. Change in sex ratio with exposure to dioxin. Lancet.1996;348 :409
    OpenUrlCrossRefPubMed
  31. ↵
    Rogan WJ, Gladen BC, Guo YL, Hsu CC. Sex ratio after exposure to dioxin-like chemicals in Taiwan. Lancet.1999;353 :206– 207
    OpenUrlPubMed
  32. ↵
    Mocarelli P, Gerthoux PM, Ferrari E, et al. Paternal concentration of dioxin and sex ratio of offspring. Lancet.2000;355 :1858– 1863
    OpenUrlCrossRefPubMed
  33. ↵
    Herman-Giddens ME, Slora EJ, Wasserman RC, et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics.1997;99 :505– 512
    OpenUrlAbstract/FREE Full Text
  34. ↵
    Tanner JM, Eveleth PB. Variability between populations in growth and development at puberty. In: Berenberg SR, ed. Puberty, Biologic and Psychosocial Components. Leiden, Netherlands: Stenfert Kroese; 1975:256–273
  35. ↵
    Brooks-Gunn J, Warren MP, Rosso J, Gargiulo J. Validity of self-report measures of girls’ pubertal status. Child Dev.1987;58 :829– 841
    OpenUrlCrossRefPubMed
  36. ↵
    Duke PM, Litt IF, Gross RT. Adolescents’ self-assessment of sexual maturation. Pediatrics.1980;66 :918– 920
    OpenUrlAbstract/FREE Full Text
  37. ↵
    Niessen KH, Ramolla J, Binder M, Brügmann G, Hofman U. Chlorinated hydrocarbons in adipose tissue of infants and toddlers: inventory and studies on their association with intake of mothers’ milk. Eur J Pediatr.1984;142 :238– 243
    OpenUrlCrossRefPubMed
  38. ↵
    Guo YL, Lai TJ, Ju SH, Chen YC, Hsu CC. Sexual developments and biological findings in Yucheng children. In: Fiedler H, Frank H, Hutzinger O, Parzefall W, Riss A, Safe S, eds. Organohalogen Compounds. 14th ed. Vienna, Austria: Federal Environmental Agency; 1993:235–238
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Evidence of Effects of Environmental Chemicals on the Endocrine System in Children
Walter J. Rogan, N. Beth Ragan
Pediatrics Jul 2003, 112 (Supplement 1) 247-252;

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Evidence of Effects of Environmental Chemicals on the Endocrine System in Children
Walter J. Rogan, N. Beth Ragan
Pediatrics Jul 2003, 112 (Supplement 1) 247-252;
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    • Abstract
    • BACKGROUND
    • DDE AND DURATION OF LACTATION IN NORTH CAROLINA AND MEXICO
    • PCBs, HYPOTONIA, AND THYROID FUNCTION
    • SEX RATIO
    • ADOLESCENT GROWTH AND SEXUAL MATURATION
    • CONCLUSIONS
    • REFERENCES
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