Skip to main content

Occupational and environmental agents as endocrine disruptors: Experimental and human evidence

Journal of Endocrinological Investigation volume 23, pages 771–781 (2000)Cite this article

Abstract

In the last few years great concern has arisen from the description of adverse endocrine effects of several occupational and environmental chemical agents on human and/or wildlife health. Such agents may exert their effects directly, specifically binding to hormone receptors, and/or indirectly, by altering the structure of endocrine glands and/or synthesis, release, transport, metabolism or action of endogenous hormones. Many studies have been focused on the outcomes of the exposure to those chemicals mimicking estrogenic or androgenic actions. Nonetheless, the disruption of other hormonal pathways is not negligible. This paper reviews the experimental and human evidence of the effects of occupational and environmental chemical agents on hypothalamus-pituitary unit, pineal gland, parathyroid and calcium metabolism and adrenal glands.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. Auld A.G. A further report on the suprarenal gland and the causation of Addison’s disease. BMJ 1984, 6: 745.

    Google Scholar 

  2. Dejerine J. Troubles de la motilité: La tétanie. In: Bouchard C. (Ed.), Traité de pathologie générale. Masson, Paris, 1901, pp. 453–474.

    Google Scholar 

  3. Pisenti G., Viola F. Beitrag zum normalen und pathologischen Histologie der Hypophise und Bezüglich der verhältnissen zwischen Hirnanhang und Schilddrüse. Centralbt. F.D. Med. Wiss. 1890, 1: 25.

    Google Scholar 

  4. Roger F., Garnier G. Lésion de la glande thyroïde dans l’intoxication phosphorée. Cpt. Rend. des Séances de la Soc. de Biol. 1900, 2: 110.

    Google Scholar 

  5. Ferranini L. Azione dei veleni professionali sulle glandole endocrine: fisiopatologia. Rapportes IV Réunion de la Comm. Intern. Perm. pour l’Etude des Maladies Professionelles. Lyon, 1929, 233–250.

    Google Scholar 

  6. Vigliani E. Sul Basedow da piombo. Rass. Med. Indust. 1934, 5: 193–224.

    Google Scholar 

  7. Porritt M. Cumulative effects of infinitesimal doses of lead. BMJ 1931, 2: 92–94.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Kavlock R.J., Daston G.P., DeRosa C., Fenner-Crisp P., Gray L.E., Kaattari S., Lucier G., Luster M., Mac M.J., Maczka C., Miller R., Moore J., Rolland R., Scott G., Sheehan D.M., Sinks T., Tilson H.A. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop. Environ. Health Perspect. 1996, 104 (Suppl. 4): 715–740.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Hammond B., Katzenellebogen B.S., Krauthammer N., McConnell J. Estrogenic activity of the insecticide chlordecone (Kepone) and interaction with uterine estrogen receptors. Proc. Natl. Acad. Sci. USA 1979, 76: 6641–6645.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Cannon S.B., Veazey J.M. Jr, Jackson R.S., Burse V.W., Hayes C., Straub W.E., Landrigan P.J., Liddle J.A. Epidemic kepone poisoning in chemical workers. Am. J. Epidemiol. 1978, 107: 529–537.

    PubMed  CAS  Google Scholar 

  11. Arnold S.F., Klotz D.M., Collins B.M., Vonier P.M., Guillette L.J. Jr., McLachlan J.A. Synergistic activation of estrogen receptor with combinations of environmental chemicals. Science 1996, 272: 1489–1492.

    Article  PubMed  CAS  Google Scholar 

  12. Segura-Aguilar J., Castro V., Bergman A. Effects of four organohalogen environmental contaminants on cytochrome P450 forms that catalyze 4-and 2-hydroxylation of estradiol in the rat liver. Biochem. Mol. Med. 1997, 60: 149–154.

    Article  PubMed  CAS  Google Scholar 

  13. Maureen P. Occupational reproductive hazards. Lancet 1997, 349: 1385–1388.

    Article  Google Scholar 

  14. Lemasters G.K. Occupational exposures and effects on male and female reproduction. In: Rom W. (Ed.), Environmental and occupational medicine. Little, Brown & C, Boston, 1998, 223–244.

    Google Scholar 

  15. Tas S., Lauwerys R., Lison D. Occupational hazards for the male reproductive system. Crit. Rev. Toxicol. 1996, 26: 261–307.

    Article  PubMed  CAS  Google Scholar 

  16. Neubert D. Vulnerability of the endocrine system to xenobiotics influence. Regul. Toxicol. Pharmacol. 1997, 26 (1 Pt 1): 9–29.

    Article  PubMed  CAS  Google Scholar 

  17. Olea N., Olea-Serrano M.F. Oestrogens and the environment. Eur. J. Cancer Prev. 1996, 5: 491–496.

    PubMed  CAS  Google Scholar 

  18. Kamrin M.A., Carney E.W., Chou K., Cummings A., Dostal L.A., Harris C., Henck J.W., Loch-Caruso R., Miller R.K. Female reproductive and developmental toxicology: overview and current approaches. Toxicol. Lett. 1994, 74: 99–119.

    Article  PubMed  CAS  Google Scholar 

  19. Sonnenschein C., Soto A.M. An updated review of environmental estrogen and androgen mimics and antagonists. J. Steroid Biochem. Mol. Biol. 1998, 65: 143–150.

    Article  PubMed  CAS  Google Scholar 

  20. Lancrajan J., Popescu H.J., Gavanescu O., Klepsch I., Serbanescu M. Reproductive ability of workmen occupationally exposed to lead. Arch. Environ. Health 1975, 30: 396.

    Article  Google Scholar 

  21. Ronis M.J., Gandy J., Badger T. Endocrine mechanisms underlying reproductive toxicity in the developing rat chronically exposed to dietary lead. J. Toxicol. Environ. Health 1998, 54: 77–99.

    Article  CAS  Google Scholar 

  22. Gustafson A., Hedner P., Schutz A., Skerfving S. Occupational lead exposure and pituitary function. Int. Arch. Occup. Environ. Health 1989, 61: 277–281.

    Article  PubMed  CAS  Google Scholar 

  23. Ronis M.J., Badger T.M., Shema S.J., Roberson P.K., Templer L., Ringer D., Thomas P.E. Endocrine mechanisms underlying the growth effects of developmental lead exposure in the rat. J. Toxicol. Environ. Health 1998, 54: 101–120.

    Article  CAS  Google Scholar 

  24. Ballew C., Khan L.K., Kaufmann R., Mokdad A., Miller D.T., Gunter E.W. Blood lead concentration and children’s anthropometric dimensions in the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994. J. Pediatr. 1999, 134: 623–630

    Article  PubMed  CAS  Google Scholar 

  25. Huseman C.A., Varma M.M., Angle C.R. Neuroendocrine effects of toxic and low blood lead levels in children. Pediatrics 1992, 90: 186–189.

    PubMed  CAS  Google Scholar 

  26. Govoni S., Battaini F., Fernicola C., Castelletti L., Trabucchi M. Plasma prolactin concentrations in lead exposed workers. J. Environ. Pathol. Toxicol. 1987, 7: 13–15.

    CAS  Google Scholar 

  27. Govoni S., Lucchi L., Battaini F., Spano P.F., Trabucchi M. Chronic lead treatment affects dopaminergic control of prolactin secretion in rat pituitary. Toxicol. Lett. 1984, 20: 237–241.

    Article  PubMed  CAS  Google Scholar 

  28. Alessio L., Apostoli P., Ferioli A., Lombardi S. Interference of manganese on neuroendocrinal system in exposed workers. Preliminary report. Biol. Trace Elem. Res. 1989, 21: 249–253.

    Article  CAS  Google Scholar 

  29. Smargiassi A., Mutti A. Peripheral biomarkers and exposure to manganese. Neurotoxicology 1999, 20: 401–406.

    PubMed  CAS  Google Scholar 

  30. Jadhao A.G., Paul P.L., Rao P.D. Effect of cadmium chloride on the pituitary, thyroid and gonads in the catfish, Clarias batrachus (Linn.). Funct. Dev. Morphol. 1994, 4: 39–44.

    PubMed  CAS  Google Scholar 

  31. Hsieh G.C., Sharma R.P., Parker R.D. Hypothalamic-pituitary-adrenocortical axis activity and immune function after oral exposure to benzene and toluene. Immunopharmacology 1991, 21: 23–31.

    Article  PubMed  CAS  Google Scholar 

  32. Shen C.L., Ting W.H., Chang T.K. Effects of toluene on the morphology of neuropeptide secretory neurons of the rat hypothalamus. Life Sci. 1992, 16: 162–168.

    CAS  Google Scholar 

  33. Gaworski C.L., Haun C.C., MacEwen J.D., Vernot E.H., Bruner R.H., Amster R.L., Cowan M.J. Jr. A 90-day vapor inhalation toxicity study of decalin. Fundam. Appl. Toxicol. 1985, 5: 785–793.

    Article  PubMed  CAS  Google Scholar 

  34. Bergamaschi E., Smargiassi A., Mutti A., Cavazzini S., Vettori M.V., Alinovi R., Franchini I., Mergler D. Peripheral markers of catecholaminergic dysfunction and symptoms of neurotoxicity among styrene-exposed workers. Int. Arch. Occup. Environ. Health 1997, 69: 209–214.

    Article  PubMed  CAS  Google Scholar 

  35. Badgy G., Arato M., Baraczka K., Fekete M.I. Comparative analysis of indices of central dopaminergic functions in man. Life Sci. 1983, 32: 2667–2676.

    Article  Google Scholar 

  36. Ferroni C., Selis L., Mutti A., Folli D., Bergamaschi E., Franchini I. Neurobehavioral and neuroendocrine effects of occupational exposure to perchloroethylene. Neurotoxicology 1992, 13: 243–247.

    PubMed  CAS  Google Scholar 

  37. Svensson B.G., Nise G., Erfurth E.M., Nilsson A., Skerfving S. Hormone status in occupational toluene exposure. Am. J. Ind. Med. 1997, 22: 99–107.

    Article  Google Scholar 

  38. Bestervelt L.L., Pitt J.A., Nolan C.J., Piper W.N. TCDD alters pituitary-adrenal function. II: Evidence for decreased bioactivity of ACTH. Neurotoxicol. Teratol. 1993, 15: 371–376.

    Article  PubMed  CAS  Google Scholar 

  39. Bestervelt L.L., Cai Y., Piper D.W., Nolan C.J., Pitt J.A., Piper W.N. TCDD alters pituitary-adrenal function. I: Adrenal responsiveness to exogenous ACTH. Neurotoxicol. Teratol. 1993, 15: 365–367.

    Article  PubMed  CAS  Google Scholar 

  40. Hontela A., Rasmussen J.B., Audet C., Chevalier G. Impaired cortisol stress response in fish from environments polluted by PAHs, PCBs, and mercury. Arch. Environ. Contam. Toxicol. 1992, 22: 278–283.

    Article  PubMed  CAS  Google Scholar 

  41. Khan I.A., Thomas P. Aroclor 1254-induced alterations in hypothalamic monoamine metabolism in the Atlantic croaker (Miropogonias undulatas): correlation with pituitary gonadotropin release. Neurotoxicology 1997, 18: 553–560.

    PubMed  CAS  Google Scholar 

  42. Jekat F.W., Meisel M.L., Eckard R., Winterhoff H. Effects of pentachorophenol (PCP) on the pituitary and thyroidal hormone regulation in the rat. Toxicol. Lett. 1994, 71: 9–25.

    Article  PubMed  CAS  Google Scholar 

  43. Stepanova M.G. Circadian rhythm of fluctuations in the level of gonadoliberin in the hypothalamus of rats and the influence on it of various xenobiotics. Neurosci. Behav. Physiol. 1995, 25: 357–360.

    Article  PubMed  CAS  Google Scholar 

  44. Ronco A.L., Halberg F. The pineal gland and cancer. Anticancer. Res. 1996, 16: 2033–2039.

    PubMed  CAS  Google Scholar 

  45. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Polychlorinated Dibenzo-para-dioxins and Polycholrinated dibenzofurans. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. IARC, Lyon, 1997, vol. 69.

    Google Scholar 

  46. Pohjanvirta R., Laitinen J.T., Vakkuri O., Linden J., Kokkola T., Unkila M., Tuomisto J. Mechanism by which 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) reduces circulating melatonin levels in the rat. Toxicology 1996, 107: 85–97.

    Article  PubMed  CAS  Google Scholar 

  47. Bartsch C., Bartsch H., Lippert T.H., Gupta D. Effect of the mammary carcinogen 7,12-dimethylbenz[ a]anthracene on pineal melatonin biosynthesis, secretion and peripheral metabolism. Neuroendocrinology 1990, 52: 538–544.

    Article  PubMed  CAS  Google Scholar 

  48. McKinney J.D., Waller C.L. Molecular determinants of hormone mimicry: halogenated aromatic hydrocarbon environmental agents. J. Toxicol. Environ. Health. B Crit. Rev. 1998, 1: 27–58.

    Article  PubMed  CAS  Google Scholar 

  49. Cheek A.O., Kow K., Chen J., McLachlan J.A. Potential Mechanism of thyroid disruption in humans: interaction of organochlorine compounds with thyroid receptor, transthyretin, and thyroid binding globulin. Environ. Health Perspect. 1999, 107: 273–278.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  50. Banerjee K.K., Bishayee A., Marimuthu P. Evaluation of cyanide exposure and its effect on thyroid function of workers in a cable industry. J.O.E.M. 1997, 39: 258–260.

    CAS  Google Scholar 

  51. Capen C.C. Pathophysiology of chemical injury of the thyroid gland. Toxicol. Lett. 1992, 64–65: 381–388.

    Article  PubMed  Google Scholar 

  52. Roberts F.P., Wright A.L., O’Hagan S.A. Hypothyroidism in textile workers. J. Soc. Occup. Med. 1990, 40: 153–156.

    Article  PubMed  CAS  Google Scholar 

  53. Christensen J.M., Poulsen O.M. A 1982–1992 surveillance program on Danish pottery painters. Biological levels and health effects following exposure to soluble and insoluble cobalt compounds in cobalt blue dyes. Sci. Total Environ. 1994, 150: 95–104.

    Article  PubMed  CAS  Google Scholar 

  54. Barregard L., Lindstedt G., Schutz A., Sallsten G. Endocrine function in mercury exposed chloralkali workers. Occup. Environ. Med. 1994, 51: 536–540.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  55. Wilson A.G., Thake D.C., Heydens W.E., Brewster D.W., Hotz K.J. Mode of action of thyroid tumor formation in the male Long-Evans rat administered high doses of alachlor. Fundam. Appl. Toxicol. 1996, 33: 16–23.

    Article  PubMed  CAS  Google Scholar 

  56. Zober A., Ott M.G., Messerer P. Morbidity follow up study of BASF employees exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) after a 1953 chemical reactor incident. Occup. Environ. Med. 1994, 51: 479–486.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  57. Murai K., Okamura K., Tsuji H. Thyroid function in Yusho patients exposed to polychlorinated biphenyls (PCB). Environ. Res. 1987, 44: 179–187.

    Article  PubMed  CAS  Google Scholar 

  58. Langer P., Tajtakova M., Fodor G., Kocan A., Bohov P., Michalek J., Kreze A. Increased thyroid volume and prevalence of thyroid disorders in an area heavily polluted by polychlorinated biphenyls. Eur. J. Endocrinol. 1998, 139: 402–409.

    Article  PubMed  CAS  Google Scholar 

  59. Bahn A.K., Mills J.L., Synder P.J., Gann P.H., Houten L., Bialik O., Hollmann L., Utiger R.D. Hypothyroidism in workers exposed to polybrominated biphenyls. N. Engl. J. Med. 1980, 302: 31.

    Article  PubMed  CAS  Google Scholar 

  60. Stross J.K. Hypothyroidism and polybrominated biphenyls. N. Engl. J. Med. 1980, 302: 1480.

    Article  Google Scholar 

  61. Hurley P., Hill R.N., Whiting R.J. Mode of carcinogenic action of pesticides inducing thyroid follicular tumors in rodents. Environ. Health Perspect. 1998, 106: 437–445.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  62. Curran P.G., DeGroot L.J. The effect of hepatic enzyme-inducing drugs on thyroid hormones and the thyroid gland. Endocr. Rev. 1991, 12: 135–150.

    Article  PubMed  CAS  Google Scholar 

  63. Pesatori A.C., Consonni D., Tironi A., Zocchetti C., Fini A., Bertazzi P.A. Cancer in a young population in a dioxin contaminated area. Int. J. Epidemiol. 1993, 22: 1010–1013.

    Article  PubMed  CAS  Google Scholar 

  64. Saracci R., Kogevinas M., Bertazzi P.A., Bueno de Mesquita B.H., Coggon D., Green L.M., Kauppinen T., L’Abbe K.A., Littorin M., Lynge E. Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols. Lancet 1991, 338: 1027–1032.

    Article  PubMed  CAS  Google Scholar 

  65. Tsuchiya K. Cadmium studies in Japan. A rewiew. Elsevier, Amsterdam, 1978.

    Google Scholar 

  66. Kjellstrom T. Mechanism and epidemiology of bone effects of cadmium. IARC Sci. Publ. 1992, 118: 301–310.

    PubMed  Google Scholar 

  67. Staessen J.A., Roels H.A., Emelianov D., Kuznetsova T., Thijs L., Vangronsveld J., Fagard R., for the Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group. Environmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Lancet 1999, 353: 1140–1144.

    Article  PubMed  CAS  Google Scholar 

  68. Rosen J.F., Chesney R., Hamstra A., DeLuca H.F., Mahaffey K.R. Reduction in 1,25,-dihydroxyvitamin D in children with increased lead absorption. N. Engl. J. Med. 1980, 302: 1128–1131.

    Article  PubMed  CAS  Google Scholar 

  69. Jeffery E.H., Abreo K., Burgess E., Cannata J., Greger J.L. Systemic aluminium toxicity: effects on bone, hematopoietic tissue, and kidney. J. Toxicol. Environ. Health 1996, 48: 649–665.

    Article  PubMed  CAS  Google Scholar 

  70. Ng T.B., Liu W.K. Toxic effect of heavy metals on cells isolated from the rat adrenal and testis. In Vitro Cell. Dev. Biol. 1990, 26: 24–28.

    Article  PubMed  CAS  Google Scholar 

  71. Lin F.H., Stohs S.J., Birnbaum L.S., Clark G., Lucier G.W., Goldstein J.A. The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the hepatic estrogen and glucocorticoid receptors in congenic strains of Ah responsive and Ah non responsive C57BL/6J mice. Toxicol. Appl. Pharmacol. 1991, 108: 129–139.

    Article  PubMed  CAS  Google Scholar 

  72. Chia S.E., Goh V.H., Ong C.N. Endocrine profiles of male workers with exposure to trichloroethylene. Am. J. Ind. Med. 1997, 32: 217–222.

    Article  PubMed  CAS  Google Scholar 

  73. Smargiassi A., Mutti A., Bergamaschi E., Belanger S., Truchon G., Mergler D. Pilot study of peripheral markers of catecholaminergic systems among workers occupationally exposed to toluene. Neurotoxicology 1996, 17: 769–775.

    PubMed  CAS  Google Scholar 

  74. Stanosz S., Kuligowski D., Pieleszek A., Zuk E., Rzechula D., Chlubek D. Concentration of dopamine beta-hydroxylase in serum and urinary excretion of free catecholamines and vanillylmandelic acid in women chronically exposed to carbon disulphide. Int. J. Occup. Med. Environ. Health 1994, 7: 257–261.

    PubMed  CAS  Google Scholar 

  75. Mutti A., Smargiassi A. Selective vulnerability of dopaminergic systems to industrial chemicals: risk assessment of related neuroendocrine changes. Toxicol. Ind. Health 1998, 14: 311–323.

    Article  PubMed  CAS  Google Scholar 

  76. Delitala G., Tomasi P., Virdis R. Prolactin, growth hormone and thyrotropin-thyroid hormone secretion during stress states in man. Baillieres Clin. Endocrinol. Metab. 1987, 1: 391–414.

    Article  PubMed  CAS  Google Scholar 

  77. Chang H.R., Chen S.S., Chen T.J., Ho C.H., Chiang H.C., Yu H.S. Lymphocyte beta2-adrenergic receptors and plasma catecholamine levels in lead-exposed workers. Toxicol. Appl. Pharmacol. 1996, 139: 1–5.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Endocrine Sciences, Ospedale Maggiore, IRCCS, Italy

    Andrea Baccarelli

  2. EPOCA Research Center for Occupational, Clinical and Environmental Epidemiology, University of Milan, Via San Barnaba 8, I-20122, Milano, Italy

    Andrea Baccarelli, A. C. Pesatori & P. A. Bertazzi

Authors
  1. Andrea Baccarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. C. Pesatori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. A. Bertazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Baccarelli.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Baccarelli, A., Pesatori, A.C. & Bertazzi, P.A. Occupational and environmental agents as endocrine disruptors: Experimental and human evidence. J Endocrinol Invest 23, 771–781 (2000). https://doi.org/10.1007/BF03345069

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345069

Key-words

  • Endocrine disruptors
  • xenobiotics
  • occupational health
  • environmental pollutants
  • pituitary
  • melatonin
  • thyroid
  • parathyroid
  • adrenal gland