Search tips
Search criteria 


Logo of envhperEnvironmental Health PerspectivesBrowse ArticlesAbout EHPGeneral InformationAuthorsMediaProgramsPartnerships
Environ Health Perspect. 1993 October; 101(5): 378–384.
PMCID: PMC1519860
Research Article

Developmental effects of endocrine-disrupting chemicals in wildlife and humans.


Large numbers and large quantities of endocrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, transgenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistence of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Korach KS, Sarver P, Chae K, McLachlan JA, McKinney JD. Estrogen receptor-binding activity of polychlorinated hydroxybiphenyls: conformationally restricted structural probes. Mol Pharmacol. 1988 Jan;33(1):120–126. [PubMed]
  • Gray LE, Jr, Ostby J, Ferrell J, Rehnberg G, Linder R, Cooper R, Goldman J, Slott V, Laskey J. A dose-response analysis of methoxychlor-induced alterations of reproductive development and function in the rat. Fundam Appl Toxicol. 1989 Jan;12(1):92–108. [PubMed]
  • Guzelian PS. Comparative toxicology of chlordecone (Kepone) in humans and experimental animals. Annu Rev Pharmacol Toxicol. 1982;22:89–113. [PubMed]
  • Soto AM, Justicia H, Wray JW, Sonnenschein C. p-Nonyl-phenol: an estrogenic xenobiotic released from "modified" polystyrene. Environ Health Perspect. 1991 May;92:167–173. [PMC free article] [PubMed]
  • Rories C, Spelsberg TC. Ovarian steroid action on gene expression: mechanisms and models. Annu Rev Physiol. 1989;51:653–681. [PubMed]
  • McEwen BS. Neural gonadal steroid actions. Science. 1981 Mar 20;211(4488):1303–1311. [PubMed]
  • Leatherland JF, Sonstegard RA. Thyroid responses in rats fed diets formulated with Great Lakes coho salmon. Bull Environ Contam Toxicol. 1982 Sep;29(3):341–346. [PubMed]
  • Grossman CJ. Regulation of the immune system by sex steroids. Endocr Rev. 1984 Summer;5(3):435–455. [PubMed]
  • Adler AJ, Nelson JF. Aging and chronic estradiol exposure impair estradiol-induced cornification but not proliferation of vaginal epithelium in C57BL/6J mice. Biol Reprod. 1988 Feb;38(1):175–182. [PubMed]
  • DeKlerk DP, Coffey DS, Ewing LL, McDermott IR, Reiner WG, Robinson CH, Scott WW, Strandberg JD, Talalay P, Walsh PC, et al. Comparison of spontaneous and experimentally induced canine prostatic hyperplasia. J Clin Invest. 1979 Sep;64(3):842–849. [PMC free article] [PubMed]
  • Moccia RD, Fox GA, Britton A. A quantitative assessment of thyroid histopathology of herring gulls (Larus argentatus) from the Great Lakes and a hypothesis on the causal role of environmental contaminants. J Wildl Dis. 1986 Jan;22(1):60–70. [PubMed]
  • Moccia RD, Leatherland JF, Sonstegard RA. Quantitative interlake comparison of thyroid pathology in Great Lakes coho (Oncorhynchus kisutch) and chinook (Oncorhynchus tschawytscha) salmon. Cancer Res. 1981 Jun;41(6):2200–2210. [PubMed]
  • Reijnders PJ. Reproductive failure in common seals feeding on fish from polluted coastal waters. Nature. 1986 Dec 4;324(6096):456–457. [PubMed]
  • Kubiak TJ, Harris HJ, Smith LM, Schwartz TR, Stalling DL, Trick JA, Sileo L, Docherty DE, Erdman TC. Microcontaminants and reproductive impairment of the Forster's tern on Green Bay, Lake Michigan--1983. Arch Environ Contam Toxicol. 1989 Sep;18(5):706–727. [PubMed]
  • Bishop CA, Brooks RJ, Carey JH, Ng P, Norstrom RJ, Lean DR. The case for a cause-effect linkage between environmental contamination and development in eggs of the common snapping turtle (Chelydra S.serpentina) from Ontario, Canada. J Toxicol Environ Health. 1991 Aug;33(4):521–547. [PubMed]
  • Martineau D, Lagacé A, Béland P, Higgins R, Armstrong D, Shugart LR. Pathology of stranded beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary, Québec, Canada. J Comp Pathol. 1988 Apr;98(3):287–311. [PubMed]
  • Aulerich RJ, Ringer RK, Iwamoto S. Reproductive failure and mortality in mink fed on Great Lakes fish. J Reprod Fertil Suppl. 1973 Dec;19:365–376. [PubMed]
  • Faber RA, Hickey JJ. Eggshell thinning, chlorinated hydrocarbons, and mercury in inland aquatic bird eggs, 1969 and 1970. Pestic Monit J. 1973 Jun;7(1):27–36. [PubMed]
  • Wiemeyer SN, Lamont TG, Bunck CM, Sindelar CR, Gramlich FJ, Fraser JD, Byrd MA. Organochlorine pesticide, polychlorobiphenyl, and mercury residues in bald eagle eggs--1969-79--and their relationships to shell thinning and reproduction. Arch Environ Contam Toxicol. 1984 Sep;13(5):529–549. [PubMed]
  • Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971 Apr 15;284(15):878–881. [PubMed]
  • McLachlan JA, Newbold RR, Bullock B. Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol. Science. 1975 Dec 5;190(4218):991–992. [PubMed]
  • Driscoll SG, Taylor SH. Effects of prenatal maternal estrogen on the male urogenital system. Obstet Gynecol. 1980 Nov;56(5):537–542. [PubMed]
  • Bern HA, Edery M, Mills KT, Kohrman AF, Mori T, Larson L. Long-term alterations in histology and steroid receptor levels of the genital tract and mammary gland following neonatal exposure of female BALB/cCrgl mice to various doses of diethylstilbestrol. Cancer Res. 1987 Aug 1;47(15):4165–4172. [PubMed]
  • Noller KL, Blair PB, O'Brien PC, Melton LJ, 3rd, Offord JR, Kaufman RH, Colton T. Increased occurrence of autoimmune disease among women exposed in utero to diethylstilbestrol. Fertil Steril. 1988 Jun;49(6):1080–1082. [PubMed]
  • Arai Y, Chen CY, Nishizuka Y. Cancer development in male reproductive tract in rats given diethylstilbestrol at neonatal age. Gan. 1978 Dec;69(6):861–862. [PubMed]
  • Bulger WH, Muccitelli RM, Kupfer D. Studies on the in vivo and in vitro estrogenic activities of methoxychlor and its metabolites. Role of hepatic mono-oxygenase in methoxychlor activation. Biochem Pharmacol. 1978;27(20):2417–2423. [PubMed]
  • Cohn WJ, Boylan JJ, Blanke RV, Fariss MW, Howell JR, Guzelian PS. Treatment of chlordecone (Kepone) toxicity with cholestyramine. Results of a controlled clinical trial. N Engl J Med. 1978 Feb 2;298(5):243–248. [PubMed]
  • Hoel DG, Davis DL, Miller AB, Sondik EJ, Swerdlow AJ. Trends in cancer mortality in 15 industrialized countries, 1969-1986. J Natl Cancer Inst. 1992 Mar 4;84(5):313–320. [PubMed]
  • Nederlof KP, Lawson HW, Saftlas AF, Atrash HK, Finch EL. Ectopic pregnancy surveillance, United States, 1970-1987. MMWR CDC Surveill Summ. 1990 Dec;39(4):9–17. [PubMed]
  • Sharpe RM, Skakkebaek NE. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet. 1993 May 29;341(8857):1392–1395. [PubMed]
  • Bush B, Bennett AH, Snow JT. Polychlorobiphenyl congeners, p,p'-DDE, and sperm function in humans. Arch Environ Contam Toxicol. 1986 Jul;15(4):333–341. [PubMed]
  • Fein GG, Jacobson JL, Jacobson SW, Schwartz PM, Dowler JK. Prenatal exposure to polychlorinated biphenyls: effects on birth size and gestational age. J Pediatr. 1984 Aug;105(2):315–320. [PubMed]
  • Jacobson SW, Fein GG, Jacobson JL, Schwartz PM, Dowler JK. The effect of intrauterine PCB exposure on visual recognition memory. Child Dev. 1985 Aug;56(4):853–860. [PubMed]
  • Jacobson JL, Jacobson SW, Humphrey HE. Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive functioning in young children. J Pediatr. 1990 Jan;116(1):38–45. [PubMed]
  • Jacobson JL, Jacobson SW, Humphrey HE. Effects of exposure to PCBs and related compounds on growth and activity in children. Neurotoxicol Teratol. 1990 Jul-Aug;12(4):319–326. [PubMed]
  • Tilson HA, Jacobson JL, Rogan WJ. Polychlorinated biphenyls and the developing nervous system: cross-species comparisons. Neurotoxicol Teratol. 1990 May-Jun;12(3):239–248. [PubMed]
  • Safe S, Astroff B, Harris M, Zacharewski T, Dickerson R, Romkes M, Biegel L. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds as antioestrogens: characterization and mechanism of action. Pharmacol Toxicol. 1991 Dec;69(6):400–409. [PubMed]
  • Biegel L, Safe S. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cell growth and the secretion of the estrogen-induced 34-, 52- and 160-kDa proteins in human breast cancer cells. J Steroid Biochem Mol Biol. 1990 Dec 10;37(5):725–732. [PubMed]
  • Mably TA, Bjerke DL, Moore RW, Gendron-Fitzpatrick A, Peterson RE. In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3. Effects on spermatogenesis and reproductive capability. Toxicol Appl Pharmacol. 1992 May;114(1):118–126. [PubMed]
  • 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 May;114(1):97–107. [PubMed]
  • Mably TA, Moore RW, Goy RW, Peterson RE. In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 2. Effects on sexual behavior and the regulation of luteinizing hormone secretion in adulthood. Toxicol Appl Pharmacol. 1992 May;114(1):108–117. [PubMed]
  • Jensen AA. Polychlorobiphenyls (PCBs), polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs) in human milk, blood and adipose tissue. Sci Total Environ. 1987 Jul;64(3):259–293. [PubMed]
  • Trapp M, Baukloh V, Bohnet HG, Heeschen W. Pollutants in human follicular fluid. Fertil Steril. 1984 Jul;42(1):146–148. [PubMed]
  • Albertini DF. Cytoplasmic microtubular dynamics and chromatin organization during mammalian oogenesis and oocyte maturation. Mutat Res. 1992 Dec;296(1-2):57–68. [PubMed]
  • Saxena MC, Siddiqui MK, Agarwal V, Kuuty D. A comparison of organochlorine insecticide contents in specimens of maternal blood, placenta, and umbilical-cord blood from stillborn and live-born cases. J Toxicol Environ Health. 1983 Jan;11(1):71–79. [PubMed]
  • Sheehan DM, Young M. Diethylstilbestrol and estradiol binding to serum albumin and pregnancy plasma of rat and human. Endocrinology. 1979 May;104(5):1442–1446. [PubMed]
  • Ekins R. Measurement of free hormones in blood. Endocr Rev. 1990 Feb;11(1):5–46. [PubMed]
  • Siiteri PK, Murai JT, Hammond GL, Nisker JA, Raymoure WJ, Kuhn RW. The serum transport of steroid hormones. Recent Prog Horm Res. 1982;38:457–510. [PubMed]
  • Berwick P. 2,4-dichlorophenoxyacetic acid poisoning in man. Some interesting clinical and laboratory findings. JAMA. 1970 Nov 9;214(6):1114–1117. [PubMed]
  • Tjälve H. Fetal uptake and embryogenetic effects of aminotriazole in mice. Arch Toxicol. 1974;33(1):41–48. [PubMed]
  • JUKES TH, SHAFFER CB. Antithyroid effects of aminotriazole. Science. 1960 Jul 29;132(3422):296–297. [PubMed]
  • Simić B, Kniewald Z, Davies JE, Kniewald J. Reversibility of the inhibitory effect of atrazine and lindane on cytosol 5 alpha-dihydrotestosterone receptor complex formation in rat prostate. Bull Environ Contam Toxicol. 1991 Jan;46(1):92–99. [PubMed]
  • Babić-Gojmerac T, Kniewald Z, Kniewald J. Testosterone metabolism in neuroendocrine organs in male rats under atrazine and deethylatrazine influence. J Steroid Biochem. 1989 Jul;33(1):141–146. [PubMed]
  • Kniewald J, Peruzović M, Gojmerac T, Milković K, Kniewald Z. Indirect influence of s-triazines on rat gonadotropic mechanism at early postnatal period. J Steroid Biochem. 1987;27(4-6):1095–1100. [PubMed]
  • Porter WP, Green SM, Debbink NL, Carlson I. Groundwater pesticides: interactive effects of low concentrations of carbamates aldicarb and methomyl and the triazine metribuzin on thyroxine and somatotropin levels in white rats. J Toxicol Environ Health. 1993 Sep;40(1):15–34. [PubMed]
  • Hess RA, Moore BJ, Forrer J, Linder RE, Abuel-Atta AA. The fungicide benomyl (methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate) causes testicular dysfunction by inducing the sloughing of germ cells and occlusion of efferent ductules. Fundam Appl Toxicol. 1991 Nov;17(4):733–745. [PubMed]
  • Gocmen A, Peters HA, Cripps DJ, Bryan GT, Morris CR. Hexachlorobenzene episode in Turkey. Biomed Environ Sci. 1989 Mar;2(1):36–43. [PubMed]
  • Smith AG, Dinsdale D, Cabral JR, Wright AL. Goitre and wasting induced in hamsters by hexachlorobenzene. Arch Toxicol. 1987 Jul;60(5):343–349. [PubMed]
  • Haake J, Kelley M, Keys B, Safe S. The effects of organochlorine pesticides as inducers of testosterone and benzo[a]pyrene hydroxylases. Gen Pharmacol. 1987;18(2):165–169. [PubMed]
  • Arnold DL, Moodie CA, Charbonneau SM, Grice HC, McGuire PF, Bryce FR, Collins BT, Zawidzka ZZ, Krewski DR, Nera EA, et al. Long-term toxicity of hexachlorobenzene in the rat and the effect of dietary vitamin A. Food Chem Toxicol. 1985 Sep;23(9):779–793. [PubMed]
  • Laisi A, Tuominen R, Männistö P, Savolainen K, Mattila J. The effect of maneb, zineb, and ethylenethiourea on the humoral activity of the pituitary-thyroid axis in rat. Arch Toxicol Suppl. 1985;8:253–258. [PubMed]
  • Van Velsen FL, Danse LH, Van Leeuwen FX, Dormans JA, Van Logten MJ. The subchronic oral toxicity of the beta-isomer of hexachlorocyclohexane in rats. Fundam Appl Toxicol. 1986 May;6(4):697–712. [PubMed]
  • Cranmer JM, Cranmer MF, Goad PT. Prenatal chlordane exposure: effects on plasma corticosterone concentrations over the lifespan of mice. Environ Res. 1984 Oct;35(1):204–210. [PubMed]
  • Roy Chowdhury A, Venkatakrishna-Bhatt H, Gautam AK. Testicular changes of rats under lindane treatment. Bull Environ Contam Toxicol. 1987 Jan;38(1):154–156. [PubMed]
  • Cummings AM, Gray LE., Jr Methoxychlor affects the decidual cell response of the uterus but not other progestational parameters in female rats. Toxicol Appl Pharmacol. 1987 Sep 15;90(2):330–336. [PubMed]
  • Eil C, Nisula BC. The binding properties of pyrethroids to human skin fibroblast androgen receptors and to sex hormone binding globulin. J Steroid Biochem. 1990 Mar;35(3-4):409–414. [PubMed]
  • Cullen MR, Kayne RD, Robins JM. Endocrine and reproductive dysfunction in men associated with occupational inorganic lead intoxication. Arch Environ Health. 1984 Nov-Dec;39(6):431–440. [PubMed]
  • Allen-Rowlands CF, Castracane VD, Hamilton MG, Seifter J. Effect of polybrominated biphenyls (PBB) on the pituitary--thyroid axis of the rat. Proc Soc Exp Biol Med. 1981 Apr;166(4):506–514. [PubMed]
  • Sager DB, Shih-Schroeder W, Girard D. Effect of early postnatal exposure to polychlorinated biphenyls (PCBs) on fertility in male rats. Bull Environ Contam Toxicol. 1987 Jun;38(6):946–953. [PubMed]
  • Dieringer CS, Lamartiniere CA, Schiller CM, Lucier GW. Altered ontogeny of hepatic steroid-metabolizing enzymes by pure polychlorinated biphenyl congeners. Biochem Pharmacol. 1979 Aug 15;28(16):2511–2514. [PubMed]
  • Choudhury H, Coleman J, De Rosa CT, Stara JF. Pentachlorophenol: health and environmental effects profile. Toxicol Ind Health. 1986 Dec;2(4):483–571. [PubMed]
  • Treinen KA, Dodson WC, Heindel JJ. Inhibition of FSH-stimulated cAMP accumulation and progesterone production by mono(2-ethylhexyl) phthalate in rat granulosa cell cultures. Toxicol Appl Pharmacol. 1990 Nov;106(2):334–340. [PubMed]
  • Wams TJ. Diethylhexylphthalate as an environmental contaminant--a review. Sci Total Environ. 1987 Oct;66:1–16. [PubMed]
  • Lloyd SC, Foster PM. Effect of mono-(2-ethylhexyl)phthalate on follicle-stimulating hormone responsiveness of cultured rat Sertoli cells. Toxicol Appl Pharmacol. 1988 Sep 30;95(3):484–489. [PubMed]
  • Gray TJ, Gangolli SD. Aspects of the testicular toxicity of phthalate esters. Environ Health Perspect. 1986 Mar;65:229–235. [PMC free article] [PubMed]
  • Thysen B, Morris PL, Gatz M, Bloch E. The effect of mono(2-ethylhexyl) phthalate on Sertoli cell transferrin secretion in vitro. Toxicol Appl Pharmacol. 1990 Oct;106(1):154–157. [PubMed]
  • Laskey JW, Berman E. Steroidogenic assessment using ovary culture in cycling rats: effects of bis(2-diethylhexyl)phthalate on ovarian steroid production. Reprod Toxicol. 1993;7(1):25–33. [PubMed]
  • Arfini G, Mutti A, Vescovi P, Ferroni C, Ferrari M, Giaroli C, Passeri M, Franchini I. Impaired dopaminergic modulation of pituitary secretion in workers occupationally exposed to styrene: further evidence from PRL response to TRH stimulation. J Occup Med. 1987 Oct;29(10):826–830. [PubMed]
  • Mutti A, Vescovi PP, Falzoi M, Arfini G, Valenti G, Franchini I. Neuroendocrine effects of styrene on occupationally exposed workers. Scand J Work Environ Health. 1984 Aug;10(4):225–228. [PubMed]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Science