Review

Environment and health: 6. Endocrine disruption and potential human health implications

Gina M. Solomon and Ted Schettler
CMAJ November 28, 2000 163 (11) 1471-1476;

During the past 50 years, tens of thousands of chemicals have been synthesized and released into the general environment. Some of these chemicals inadvertently interfere with hormone function in animals and, in some cases, humans. The public health implications of these so-called endocrine disruptors have been the subject of scientific debate, media interest and policy attention over the past several years. The current scientific debate centres on whether there is evidence of significant risks to the general human population.1

The health care community should be familiar with this issue because it is increasingly a subject of the popular press and is a topic of concern to patients, who may present with questions. But health policy decisions are currently being made with little input from the medical and public health community. In this article we review the history of environmental endocrine disruption, the mechanisms of action of endocrine disruptors and the current evidence of effects on reproduction, infant development and neurobehavioural function. Finally, we discuss health policy activities worldwide that are relevant to endocrine-disrupting chemicals in the environment.

Historical background

Endocrine disruption is not a new phenomenon. In the 1930s studies involving laboratory animals demonstrated estrogenic properties of a number of industrial chemicals including bisphenol A, now widely used in plastics, resins and dental sealants.2 The feminizing effect of the pesticide DDT (dichlorodiphenyltrichloroethane) in roosters was reported in the 1950s.3

Although hormonally active chemicals are widely used for beneficial medical purposes, adverse effects have also occurred. In 1971 clinicians traced an epidemic of vaginal clear cell carcinoma in young women to maternal use of a synthetic estrogen, diethylstilbestrol (DES), during pregnancy. Daughters of these women have an increased risk of reproductive and immunologic abnormalities, and sons are at risk of genital anomalies and abnormal spermatogenesis.4 In animals, and possibly in humans, DES alters male- and female-typical behaviour patterns.5 The example of DES indicates that the fetus may be at greatest risk from the adverse effects of hormonal disruption.

Mechanisms of action and fetal vulnerability

Numerous assays have reproducibly shown that some pesticides and other industrial chemicals can directly bind to, or block, hormone receptors, thereby initiating or blocking receptor-activated gene transcription.6 Other exogenous chemicals act indirectly on hormonal homeostasis by altering steroidogenesis, hormone transport on binding proteins, receptor numbers on target organs or hormone metabolism.7 For example, polychlorinated biphenyls (PCBs) interfere with thyroid function through a variety of mechanisms, including increased metabolism of T4 (thyroxine), interference with T4 delivery to the developing brain by displacement from the carrier protein, and interference with the conversion of T4 to T3 (triiodothyronine).8

During development the fetus is particularly sensitive to hormonal fluctuations. Exposures to low levels of exogenous hormones or toxicants may result in permanent physiologic changes that are not seen in adults exposed at similar levels.9 For example, mild hypothyroidism in an adult is not expected to have long-term effects on the brain. In contrast, subtle hypothyroidism during fetal and neonatal life causes disruption of neurotransmitters, neurotropins, axonal growth and normal mitochondrial function in the developing brain, resulting in retarded cognitive and neuromotor development.10

Potential health implications

Reported abnormalities in laboratory animals and wildlife exposed to endocrine-disrupting chemicals include feminization of males, abnormal sexual behaviour, birth defects, altered sex ratios, decreased sperm density, decreased size of testes, breast cancer, testicular cancer, reproductive failure and thyroid dysfunction (Table 1).11,12

Epidemiologic studies involving workers have found associations between exposure to specific pesticides or industrial chemicals and levels of thyroid stimulating hormone (TSH), testosterone and prolactin in adults.28,29,30 Some of these studies have also found significant associations with other relevant end points, including diminished sperm quality, impaired sexual function and testicular cancer.31,32 Numerous studies have found associations between occupational exposure to solvents or pesticides and subfertility or adverse effects on offspring such as hypospadias or cryptorchidism, but it is unclear whether these effects are due to endocrine mechanisms.33,34

Population-based epidemiologic studies relevant to endocrine disruption are few and are limited by the time lag between exposure and clinical disease, the difficulty in defining exposed and control populations, and poor retrospective assessment of exposures during the prenatal period. Moreover, limited understanding of the role of gene-environment interactions increases the likelihood that susceptible subpopulations may remain unidentified. Perhaps as a result, epidemiologic data concerning the relation between breast cancer and tissue levels of certain organochlorines, such as DDT, its by-product DDE, PCBs or dieldrin, are conflicting.35,36

Surveillance-based studies in the general population show increases in some potentially hormone-related conditions (Table 2). These increases are not completely explained by improved detection or reporting.49,50 Although behavioural and nutritional factors are potential explanations for some of these observations, it is biologically plausible, and consistent with laboratory and wildlife evidence, that fetal exposure to endocrine-disrupting chemicals may play a role. Cancers and other health effects may manifest many years later as steroid hormones continue to stimulate cell growth and proliferation.51,52

Hormones and neurobehavioural effects

Prenatal or early postnatal exposure to certain environmental pollutants has been associated with learning and behavioural abnormalities. In some cases, there is evidence that these neurologic abnormalities may be due to an endocrine mechanism. For example, a single low dose of dioxin during the development of the hypothalamic- pituitary-gonadal axis in the rat has been shown to produce a feminizing effect on the behaviour of male offspring, reflecting altered sexual differentiation of the brain.53

Thyroid hormone is known to affect development of the fetal brain.10 Thyroid disruption, including goiter and neurobehavioural abnormalities, has been found in wildlife and laboratory animal populations feeding on the organochlorine-contaminated food chain of the Great Lakes.54,55,56 In utero and lactational exposure of non-human primates to environmentally relevant levels of PCBs has been shown to cause impaired learning.57 In humans, higher levels of PCBs in breast milk have correlated with higher TSH levels in nursing infants.58 Blood levels of certain PCBs have positively correlated with TSH levels and negatively correlated with free T4 levels in children aged 7-10.59 In addition to the antithyroid effects of PCBs, animal studies have revealed evidence of altered neurotransmitter and neuroreceptor levels, which may be primary or secondary to the thyroid effects.60

Cohort studies involving children environmentally exposed to PCBs in utero through maternal consumption of Great Lakes fish have revealed delayed psychomotor development and increased distractibility in those most highly exposed.61,62 In one study, at age 11, the most exposed children were more than 3 times as likely to perform poorly on intelligence quotient (IQ) tests and more than twice as likely to be at least 2 years behind in reading comprehension as the least exposed children in the study.16 Some entire population groups, such as the Inuit in Canada, currently have body burdens of PCBs that exceed levels known to affect cognitive functioning.63

Beyond endocrine disruption: other signalling pathways

Although much attention has focused on the endocrine system, disruption of other biological signalling pathways is an important related issue. The structural and functional development of the brain is dependent on the integration of hormones, neurotransmitters, neurotrophins and locally produced steroids.64

Chemicals that interfere with neurotransmitters, such as the organophosphate pesticides, have many similarities to chemicals that interfere with hormones. Toxic effects are generally reversible in adults. In the developing brain, however, effects may be permanent and result in functional deficits. For example, rodents exposed to a single low dose of an organophosphate pesticide in a critical period of neonatal life have been found to have permanently decreased brain density of muscarinic receptors and hyperactive behaviour when tested as adults.65 Recent research has demonstrated that, in the developing brain, neurotransmitters perform growth regulatory and morphogenic functions.66 For example, inhibition of acetylcholinesterase results in reduced axonal outgrowth and accumulation of neurofilaments in vitro.67 It appears that immature neurologic systems, like immature endocrine systems, are sensitive to low doses of exogenous agents that have no apparent effect on adults.

Implications and ongoing activities

Hormones act at extremely low levels (parts per trillion); therefore, in theory, even exposures to low levels of hormonally active agents may be of concern, particularly during sensitive periods of fetal development. Furthermore, endocrine-mediated effects may be subtle and manifest primarily in populations rather than in individuals. For example, slight overall declines in sperm density or IQ may have little relevance for an individual but important adverse implications for the population.68

Low-level exposures to endocrine-disrupting chemicals are ubiquitous in today's environment. Persistent chemicals such as DDT, PCBs and dioxins are detectable in nearly 100% of human blood samples, and even some of the shorter-lived potential endocrine disruptors are frequently detected in general population surveys of residues in blood or urine.69,70 The ubiquitous nature of the exposures combined with the nontrivial potential health effects justifies further research, education and preventive action to reduce human exposures to endocrine disruptors.

A great deal of work on endocrine disruptors is under way in government agencies, nongovernment organizations and international organizations (Table 3). The International Joint Commission (IJC), created by treaty between the United States and Canada in 1909 to prevent or resolve disputes over lake and river systems along the border, has taken a leadership role in defining a "persistent toxic substance" and targeting such chemicals for elimination. Many of the chemicals targeted by the IJC are also endocrine disruptors and some are still in commercial use today. In its tenth biennial report, issued in 2000, the IJC reiterated a commitment to virtual elimination and zero discharge of persistent toxic substances, but cautioned that

Every delay in achieving this purpose carries a price. With time the price will grow heavier, and the line between delay and outright failure will be stretched thinner. Governments need to show a new sense of urgency and a commitment to action in restoring and protecting the Great Lakes.72

Improved monitoring of disease and exposure is essential for tracking trends in subtle, delayed effects of environmental exposures. Birth defect registries that acquire data through active case ascertainment rather than passive reporting can provide important data on structural birth defects. Neurodevelopmental abnormalities are exceedingly difficult to monitor, yet the evidence suggests that further investigation of time trends and causes is urgently needed. Ongoing efforts around the world to develop accurate biological monitoring of blood and urine for numerous chemical toxicants will improve exposure assessment in epidemiological studies and may eventually provide tools for physicians to assess risks to individuals.73 As these tests become standardized and widely available, they will be useful clinically, just as blood lead testing has helped facilitate a range of interventions that have resulted in a major reduction in lead poisoning.

Finally, the topic of endocrine disruption has brought to the surface an underlying debate about the nature of scientific proof and decisions about whether to take action in the face of scientific uncertainty. Some argue that there is no proof of human health effects caused by endocrine disruption at current exposure levels in the general population. Others point to suggestive evidence and warn that the consequences of inaction may be significant to future generations. Medicine and public health have traditionally favoured a science-based precautionary approach aimed at preventing adverse health effects through education and practical exposure reduction whenever feasible.74 In the case of endocrine disruptors, such an approach will require the medical community to play a critical role in evaluating the science, educating the public and recommending steps to protect the next generation.

Acknowledgments

We gratefully acknowledge the support of the W. Alton Jones Foundation.

Footnotes

  • Articles to date in this series

    McCally M. Environment and health: an overview. CMAJ 2000;163(5):533-5.

    Speidel JJ. Environment and health: 1. Population, consumption and human health. CMAJ 2000;163(5):551-6.

    Haines A, McMichael AJ, Epstein PR. Environment and health: 2. Global climate change and health. CMAJ 2000;163(6):729-34.

    De Gruijl FR, van der Leun JC. Envoironment and health: 3. Ozone depletion and ultraviolet radiation. CMAJ 2000;163(7):851-5.

    Clapp R. Environment and health: 4. Cancer. CMAJ 2000; 163(8):1009-12.

    Leaning J. Environment and health: 5. Impact of war. CMAJ 2000;163(9):1157-61.

    This article has been peer reviewed.

    Contributors: Drs. Solomon and Schettler contributed equally to the writing of the article.

    Competing interests: None declared.

    Reprint requests to: Dr. Gina M. Solomon, Ste. 1825, 71 Stevenson St., San Francisco CA 94105; fax 415 495-5996; gsolomon@nrdc.org

  • Series editor: Dr. Michael McCally

References

  1. 1.↵
    Committee on Hormonally Active Agents in the Environment, National Research Council. Hormonally active agents in the environment. Washington: National Academy Press; 1999.
  2. 2.↵
    Dodds EC, Lawson W. Molecular structure in relation to oestrogenic activity. Compounds without a phenanthrene nucleus. Proc R Soc London 1938;125:222-32.
    OpenUrlFREE Full Text
  3. 3.↵
    Burlington H, Lindeman VF. Effect of DDT on testes and secondary sex characters of white leghorn cockerels. Proc Soc Exp Biol Med 1950;74:48-51.
    OpenUrl
  4. 4.↵
    Giusti RM, Iwamoto K, Hatch EE. Diethylstilbestrol revisited: a review of the long-term health effects. Ann Intern Med 1995;122:778-88.
    OpenUrlCrossRefPubMed
  5. 5.↵
    Reinisch JM, Ziemba-Davis M, Sanders SA. Hormonal contributions to sexually dimorphic behavior in humans. Psychoneuroendocrinology 1991;16:213-78.
    OpenUrlCrossRefPubMed
  6. 6.↵
    Cooper RL, Kavlock RJ. Endocrine disruptors and reproductive development: a weight-of-evidence overview. J Endocrinol 1997;152:159-66.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    Swartz WJ, Corkern M. Effects of methoxychlor treatment of pregnant mice on female offspring of the treated and subsequent pregnancies. Reprod Toxicol 1992;6(5):431-7.
    OpenUrlCrossRefPubMed
  8. 8.↵
    Brouwer A, Morse DC, Lans MC, Schuur AG, Murk AJ, Klasson-Wehler E, et al. Interactions of persistent environmental organohalogens with the thyroid hormone system: mechanisms and possible consequences for animal and human health. Toxicol Ind Health 1998;14:59-84.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    Bigsby R, Chapin RE, Daston GP, Davis BJ, Gorski J, Gray LE, et al. Evaluating the effects of endocrine disruptors on endocrine function during development. Environ Health Perspect 1999;107(Suppl 4):613-8.
    OpenUrl
  10. 10.↵
    Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999;341(8):549-55.
    OpenUrlCrossRefPubMed
  11. 11.↵
    Crisp TM, Clegg ED, Cooper RL, Wood WP, Anderson DG, Baetcke KP, et al. Environmental endocrine disruption: an effects assessment and analysis. Environ Health Perspect 1998;106(Suppl 1):11-56.
    OpenUrlCrossRefPubMed
  12. 12.↵
    Vom Saal FS, Cooke PS, Buchanan DL, Palanza P, Thayer KA, Nagel SC, et al. A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production, and behavior. Toxicol Ind Health 1998;14:239-60.
    OpenUrlAbstract/FREE Full Text
  13. 13.
    Vom Saal FS, Nagel SC, Palanza P, Boechler M, Parmigiani S, Welshons WV. Estrogenic pesticides: binding relative to estradiol in MCF-7 cells and effects of exposure during fetal life on subsequent territorial behavior in male mice. Toxicol Lett 1995;77(1-3):343-50.
    OpenUrlCrossRefPubMed
  14. 14.
    Gray LE. Xenoendocrine disruptors: laboratory studies on male reproductive effects. Toxicol Lett 1998;102-103:331-5.
    OpenUrl
  15. 15.
    Gray LE, Ostby J, Monosson E, Kelce WR. Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol Ind Health 1999;15(1-2):48-64.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    Jacobson JL, Jacobson SW. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N Engl J Med 1996;335:783-9.
    OpenUrlCrossRefPubMed
  17. 17.
    Zoeller RT, Dowling A, Vas AA. Developmental exposure to polychlorinated biphenyls exerts thyroid-like effects on the expression of RC3/neurogranin and myelin basic protein messenger ribonucleic acids in the developing rat brain. Endocrinology 2000;141:181-9.
    OpenUrlCrossRefPubMed
  18. 18.
    Bradlow HL, Davis DL, Lin G, Sepkovic D, Tiwari R. Effects of pesticides on the ratio of 16α/2-hydroxyestrone: a biologic marker of breast cancer risk. Environ Health Perspect 1995;103(Suppl 7):147-50.
    OpenUrlCrossRef
  19. 19.
    Tran DQ, Kow KY, McLachlan JA, Arnold SF. The inhibition of estrogen receptor-mediated responses by chloro-s-triazine-derived compounds is dependent on estradiol concentration in yeast. Biochem Biophys Res Commun 1996;227: 140-6.
    OpenUrlCrossRefPubMed
  20. 20.
    Cooper RL, Goldman JM, Stoker TE. Neuroendocrine and reproductive effects of contemporary-use pesticides. Toxicol Ind Health 1999;15:26-36.
    OpenUrlAbstract/FREE Full Text
  21. 21.
    Donna A, Crosignani P, Robutti F, Betta PG, Bocca R, Mariani N, et al. Triazine herbicides and ovarian epithelial neoplasms. Scand J Work Environ Health 1989;15:47-53.
    OpenUrlCrossRefPubMed
  22. 22.
    Kettles MA, Browning SR, Prince TS, Horstman SW. Triazine herbicide exposure and breast cancer incidence: an ecologic study of Kentucky counties. Environ Health Perspect 1996;105:1222-7.
    OpenUrlCrossRef
  23. 23.
    Brown NM, Manzolillo PA, Zhang JX, Wang J, Lamartiniere CA. Prenatal TCDD and predisposition to mammary cancer in the rat. Carcinogenesis 1998;19(9):1623-9.
    OpenUrlAbstract/FREE Full Text
  24. 24.
    Mably TA, Moore RW, Peterson RE. In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin: 1. Effects on androgenic status. Toxicol Appl Pharmacol 1992;114:97-107.
    OpenUrlCrossRefPubMed
  25. 25.
    Egeland GM, Sweeney MH, Fingerhut MA, Wille KK, Schnorr TM, Halperin WE. Total serum testosterone and gonadotropins in workers exposed to dioxin. Am J Epidemiol 1994;139(3):272-81.
    OpenUrlAbstract/FREE Full Text
  26. 26.
    Nagayama J, Okamura K, Iida T, Hirakawa H, Matsueda T, Tsuji H, et al. Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants. Chemosphere 1998;37(9-12):1789-93.
    OpenUrlCrossRefPubMed
  27. 27.
    Steenland K, Piacitelli L, Deddens J, Fingerhut M, Chang LI. Cancer, heart disease, and diabetes in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Natl Cancer Inst 1999;91(9):779-86.
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    Steenland K, Cedillo L, Tucker J, Hines C, Sorensen K, Deddens J, et al. Thyroid hormones and cytogenetic outcomes in backpack sprayers using ethylenebis(dithiocarbamate) (EBDC) fungicides in Mexico. Environ Health Perspect 1997;105:1126-30.
    OpenUrlCrossRefPubMed
  29. 29.↵
    Sweeney MH, Calvert GM, Egeland GA, Fingerhut MA, Halperin WE, Piacitelli LA. Review and update of the results of the NIOSH medical study of workers exposed to chemicals contaminated with 2,3,7,8-tetrachlorodibenzodioxin. Teratog Carcinog Mutagen 1997-98;17(4-5):241-7.
  30. 30.↵
    Manzo L, Artigas F, Martinez E, Mutti A, Bergamaschi E, Nicotera P, et al. Biochemical markers of neurotoxicity: a review of mechanistic studies and applications. Hum Exp Toxicol 1996;15(Suppl 1):S20-35.
  31. 31.↵
    Hardell L, Ohlson CG, Fredrikson M. Occupational exposure to polyvinyl chloride as a risk factor for testicular cancer evaluated in a case-control study. Int J Cancer 1997;73:828-30.
    OpenUrlCrossRefPubMed
  32. 32.↵
    Whelan EA, Grajewski B, Wild DK, Schnorr TM, Alderfer R. Evaluation of reproductive function among men occupationally exposed to a stilbene derivative: II. Perceived libido and potency. Am J Ind Med 1996;29:59-65.
    OpenUrlCrossRefPubMed
  33. 33.↵
    Gold EB, Tomich E. Occupational hazards to fertility and pregnancy outcome. Occup Med 1994;9:435-69.
    OpenUrlPubMed
  34. 34.↵
    Weidner IS, Moller H, Jensen TK, Skakkebaek NE. Cryptorchidism and hypospadias in sons of gardeners and farmers. Environ Health Perspect 1998;106: 793-6.
    OpenUrlCrossRefPubMed
  35. 35.↵
    Hunter DJ, Hankinson SE, Laden F, Colditz GA, Colditz GA, Manson JE, Willett WC, et al. Plasma organochlorine levels and the risk of breast cancer. N Engl J Med 1997;337:1253-8.
    OpenUrlCrossRefPubMed
  36. 36.↵
    Hoyer AP, Grandjean P, Jorgensen T, Brock JW, Hartvig HB. Organochlorine exposure and risk of breast cancer. Lancet 1998;352:1816-20.
    OpenUrlCrossRefPubMed
  37. 37.
    Paulozzi LJ. International trends in rates of hypospadias and cryptorchidism. Environ Health Perspect 1999;107:297-302.
    OpenUrlCrossRefPubMed
  38. 38.
    Younglai EV, Collins JA, Foster WG. Canadian semen quality: an analysis of sperm density among eleven academic fertility centers. Fertil Steril 1998;70:76-80.
    OpenUrlCrossRefPubMed
  39. 39.
    Swan S, Elkin EP, Fenster L. Have sperm densities declined? A reanalysis of global trend data. Environ Health Perspect 1997;105:1228-32.
    OpenUrlCrossRefPubMed
  40. 40.
    Liu S, Wen SW, Mao Y, Mery L, Rouleau J. Birth cohort effects underlying the increasing testicular cancer incidence in Canada. Can J Public Health 1999;90(3):176-80.
    OpenUrlPubMed
  41. 41.
    McKiernan JM, Goluboff ET, Liberson GL, Golden R, Fisch H. Rising risk of testicular cancer by birth cohort in the United States from 1973-1995. J Urol 1999;162(2):361-3.
    OpenUrlCrossRefPubMed
  42. 42.
    Bergstrom R, Adami HO, Mohner M, et al. Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon. J Natl Cancer Inst 1996;88:727-33.
    OpenUrlAbstract/FREE Full Text
  43. 43.
    Levy IG, Iscoe NA, Klotz LH. Prostate cancer. 1. The descriptive epidemiology in Canada. CMAJ 1998;159(5):509-13. Available: www.cma.ca/cmaj/vol-159/issue-5/0509.htm
    OpenUrlAbstract/FREE Full Text
  44. 44.
    Haas GP, Sakr WA. Epidemiology of prostate cancer. CA Cancer J Clin 1997;47:273-87.
    OpenUrlCrossRefPubMed
  45. 45.
    Wang PP, Cao Y. Incidence trends of female breast cancer in Saskatchewan, 1932-1990. Breast Cancer Res Treat 1996;37(3):197-207.
    OpenUrlCrossRefPubMed
  46. 46.
    Wolff MS, Collman GW, Barrett JC, Huff J. Breast cancer and environmental risk factors: epidemiological and experimental findings. Annu Rev Pharmacol Toxicol 1996;36:573-96.
    OpenUrlCrossRefPubMed
  47. 47.
    Allan BB, Brant R, Seidel JE, Jarrell JF. Declining sex ratios in Canada. CMAJ 1997;156(1):37-41. Abstract available: www.cma.ca/cmaj/vol-156/issue-1/0037.htm
    OpenUrlAbstract/FREE Full Text
  48. 48.
    Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, 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;99:505-12.
    OpenUrlAbstract/FREE Full Text
  49. 49.↵
    Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette LJ, et al. Male reproductive health and environmental xenoestrogens. Environ Health Perspect 1996;104(Suppl 4):741-803.
    OpenUrlCrossRefPubMed
  50. 50.↵
    Sharpe RM, Skakkebaek NE. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet 1993;341:1392-5.
    OpenUrlCrossRefPubMed
  51. 51.↵
    Gardner WA. Hypothesis: the prenatal origins of prostate cancer. Hum Pathol 1995;26:1291-2.
    OpenUrlCrossRefPubMed
  52. 52.↵
    Davis DL, Axelrod D, Osborne M, Telang N, Bradlow HL, Sittner E. Avoidable causes of breast cancer: the known, unknown, and the suspected. Ann N Y Acad Sci 1997;833:112-28.
    OpenUrlCrossRefPubMed
  53. 53.↵
    Mably TA, Moore RW, Goy RW, Peterson RE. In utero and lactational exposure of male rats to 2,3,7,8-tetrachlordibenzo-p-dioxin. 2. Effects on sexual behavior and the regulation of LH secretion in adulthood. Toxicol Appl Pharmacol 1992;114:108-17.
    OpenUrlCrossRefPubMed
  54. 54.↵
    Leatherland JF. Changes in thyroid hormone economy following consumption of environmentally contaminated Great Lakes fish. Toxicol Ind Health 1998; 14:41-57.
    OpenUrlAbstract/FREE Full Text
  55. 55.↵
    Daly HB, Stewart PW, Lunkenheimer L, Sargent D. Maternal consumption of Lake Ontario salmon in rats produces behavioral changes in the offspring. Toxicol Ind Health 1998;14:25-39.
    OpenUrlAbstract/FREE Full Text
  56. 56.↵
    Moccia RD, Fox GA, Britton A. A quantitative assessment of thyroid histopathology of herring gulls from the Great Lakes and a hypothesis on the causal role of environmental contaminants. J Wildl Dis 1986;22:60-70.
    OpenUrlAbstract
  57. 57.↵
    Rice DC. Behavioral impairment produced by low-level postnatal PCB exposure in monkeys. Environ Res 1999;80(2 pt 2):S113-21.
  58. 58.↵
    Koopman-Esseboom C, Morse DC, Weisglas-Kuperus N, Lutkeschipholt IJ, Van der Paauw CG, Tuinstra LG, et al. Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants. Pediatr Res 1994;36:468-73.
    OpenUrlCrossRefPubMed
  59. 59.↵
    Osius N, Karmaus W, Kruse H, Witten J. Exposure to polychlorinated biphenyls and levels of thyroid hormones in children. Environ Health Perspect 1999;107:843-9.
    OpenUrlCrossRefPubMed
  60. 60.↵
    Tilson HA, Kodavanti PR. Neurochemical effects of polychlorinated biphenyls: an overview and identification of research needs. Neurotoxicology 1997;18:727-43.
    OpenUrlPubMed
  61. 61.↵
    Jacobson JL, Jacobson SW. Effects of in utero exposure to PCBs and related contaminants on cognitive functioning in young children. J Pediatr 1990; 116:38-45.
    OpenUrlCrossRefPubMed
  62. 62.↵
    Lonky E, Reihman J, Darvill T, Mather J, Daly H. Neonatal behavioral assessment scale performance in humans influenced by maternal consumption of environmentally contaminated Lake Ontario fish. J Great Lakes Res 1996;22:198-212.
    OpenUrlCrossRef
  63. 63.↵
    Muckle G, Dewailly E, Ayotte P. Prenatal exposure of Canadian children to polychlorinated biphenyls and mercury. Can J Public Health 1998;89(Suppl 1):S20-5,22-7.
  64. 64.↵
    Lauder JM. Neurotransmitters as morphogens. Prog Brain Res 1988;73:365-87.
    OpenUrlCrossRefPubMed
  65. 65.↵
    Ahlbom J, Fredriksson A, Eriksson. Exposure to an organophosphate (DFP) during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behavior in adult mice. Brain Res 1995;677:13-9.
    OpenUrlCrossRefPubMed
  66. 66.↵
    Lauder JM, Schambra UB. Morphogenic roles of acetylcholine. Environ Health Perspect 1999;107(Suppl 1):65-9.
    OpenUrlCrossRefPubMed
  67. 67.↵
    Bigbee JW, Sharma KV, Gupta JJ, Dupree JL. Morphogenic role for acetylcholinesterase in axonal outgrowth during neural development. Environ Health Perspect 1999;107(Suppl 1):81-7.
    OpenUrlCrossRefPubMed
  68. 68.↵
    Rice DC. Issues in developmental neurotoxicology: interpretation and implications of the data. Can J Public Health 1998;89(Suppl 1):S31-6,S34-40.
  69. 69.↵
    Hill RH Jr, Head SL, Baker S, Gregg M, Shealy DB, Bailey SL, et al. Pesticide residues in urine of adults living in the United States: reference range concentrations. Environ Res 1995;71:99-108.
    OpenUrlPubMed
  70. 70.↵
    Archibeque-Engle SL, Tessari JD, Winn DT, Keefe TJ, Nett TM, Zheng T. Comparison of organochlorine pesticide and polychlorinated biphenyl residues in human breast adipose tissue and serum. J Toxicol Environ Health 1997;52:285-93.
    OpenUrlCrossRefPubMed
  71. 71.
    Reiter LW, DeRosa C, Kavlock RJ, Lucier G, Mac MJ, Melillo J, et al. The US Federal Framework for Research on Endocrine Disruptors and an analysis of research programs supported during fiscal year 1996. Environ Health Perspect 1998;106:105-13.
    OpenUrlCrossRefPubMed
  72. 72.↵
    International Joint Commission. Open letter to Great Lakes leaders and the Great Lakes community. In: Tenth biennial report on Great Lakes water quality. Washington/Ottawa: The Commission; 2000. p. v. Available: www.ijc.org/comm/10br/en (accessed 2000 Oct 27).
  73. 73.↵
    Division of Laboratory Sciences. Biomonitoring program. Atlanta: National Centre for Environmental Health, US Centers for Disease Control and Prevention. Available: www.cdc.gov/nceh/dls/biomonitoring.htm (accessed 2000 Oct 27).
  74. 74.↵
    Horton R. The new public health of risk and radical engagement. Lancet 1998;352:251-2.
    OpenUrlCrossRefPubMed
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Vol. 163, Issue 11
28 Nov 2000

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Environment and health: 6. Endocrine disruption and potential human health implications
Gina M. Solomon, Ted Schettler
CMAJ Nov 2000, 163 (11) 1471-1476;
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