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Endocrine Modulators in the Food Chain and Environment
Robert Nilsson
Swedish National Chemicals Inspectorate, Solna, Sweden, robertn@ kemi.se
Recently, considerable attention has been focused on certain environmental contaminants—"endocrine disruptors"—of industrial origin that may mimic the action of sex hormones. Natural compounds and their effects on other types of hormonal activity (eg, on adrenal or thyroid function) have for some reason not provoked similar attention. As exemplified by tributyltin and certain bioaccumulating chlorinated compounds, available evidence indicates that "endocrine disruption" caused by xenobiotics is primarily an ecotoxicologic problem. In mammals, certain phenylmethyl-substituted siloxanes have been found to be by far the most potent endocrine disrupters among various synthetic xenobiotics. On the other hand, it has not been possible to scientifically substantiate either certain alarming reports of powerful synergistic effects between chlorinated pesticides or the alleged adverse effects on the male reproductive tract in rodents (induced by alkylphenols and plasticizers at extremely low exposures). Whereas there is compelling evidence that estrogens in certain foods and herbal medicines can induce hormonal changes in women as well as overt toxicity in men, existing data are insufficient to support a causal relationship between exposure of the general human population to nonpharmaceutical industrial chemicals and adverse effects operating via the endocrine system. Moreover, in terms of magnitude and extent, all such exposures to so-called endocrine disruptors are dwarfed by the extensive use of oral contraceptives and estrogens for treatment of menopausal and postmenopausal disorders. Also, the exposure to hormonally active xenobiotics is virtually insignificant when compared with the intake of the phytoestrogens that are present in food and beverages, and it is even more insignificant when compared with certain herbal potions used in "alternative medicine." Furthermore, while there has been much concern about negligible exposures to xenobiotics with weak hormonelike activities, the potent endocrine disruptor licorice is freely given to children. Long-term exposure to this substance induces severe toxic symptoms of mineral corticoid hormone imbalance. Although exposures to xenobiotics and many natural compounds occur by identical routes of administration and may contribute to the same toxicological end point, they are, regrettably, judged by completely different standards. As is the case with all other chemicals, rational risk assessment and risk management of man-made and natural endocrine modulators must be based on the mode of action and dose-response relationships. Such end points as the induction of reproductive developmental effects, cancer, etc, relating to actual exposures must also be taken into consideration.
Key Words: Endocrine disruptors • xenobiotics • phytoestrogens • risk assessment
References
- Adlercreutz H. (1995). Phytoestrogens: Epidemiology and a possible role in cancer protection. Environ Health Perspect 103(suppl 7): 103-112.
- Ahlborg U., Lipworth L., Titus-Ernstoff L., Hsieh C., Hanberg A., Baron J., Trichopoulos D., Adami H-O. (1995). Organochlorine compounds in relation to breast cancer: An assessment of the biological and epidemiological evidence. Crit Rev Toxicol 25: 463-531.[Web of Science][Medline]
[Order article via Infotrieve]
- Andersson C., Störmer F., Reistad R., Alexander J. (1995). Too much liquorice may induce hypertension in sensitive individuals. Var Foda 47: 15-21 (in Swedish).
- Arnold DL, Bryce F., Miller D., Stapley R., Malcolm S., Hayward S. (1998). The toxicological effects following the ingestion of chinook salmon from the Great Lakes by Sprague-Dawley rats during a two-generation feeding-reproduction study. Regul Toxicol Pharmacol 27: S18-S27.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Arnold SF, Klotz DM, Collins BM, Vonier PM, Guilette LJ, McLachlan JA (1996). Synergistic activation of estrogen receptor with combinations of environmental chemicals. Science 272: 1489-1492.[Abstract]
- Ashby J., Lefevre PA, Odum J., Harris CA, Routledge EJ, Sumpter JP (1997). Synergism between synthetic oestrogens? Nature 385: 494.[Medline]
[Order article via Infotrieve]
- Ashby J., Tinwell H., Lefevre PA, Odum J., Paton D., Millward SW, Tittensor S., Brooks AN (1997). Normal sexual development of rats exposed to butyl benzyl phthalate from conception to weaning. Regul Toxicol Pharmacol 26: 102-118.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Bennet DR, Åberg B. (1975). 2,6-cis-Diphenylhexamethyl cyclotetrasiloxane. Chemistry, analytical chemistry, biological effects and excretion. Acta Pharmacol Toxicol 36(suppl III): 5-147.[Medline]
[Order article via Infotrieve]
- Bjerke DL, Peterson RE (1994). Reproductive toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in male rats: Different effects of in utero vs. lactational exposure. Toxicol Appl Pharmacol 127: 241-249.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Boettger-Tong H., Murthy L., Chiappetta C., Kirkland JL, Goodwin B., Adlercreutz H., Stancel GM, Makela S. (1998). A case of a laboratory animal feed with high estrogenic activity and its impact on in vivo responses to exogenously administered estrogens. Environ Health Perspect 106: 369-373.[Web of Science][Medline]
[Order article via Infotrieve]
- Cagen SZ, Waechter JM, Dimond SS, Breslin WJ, Butala JH, Jekat FW, Joiner RL, Shiotsuka RN, Veenstra GE, Harris LR (1999). Normal reproductive organ development in CF-1 mice following prenatal exposure to bisphenol A. Toxicol Sci 50: 36-44.[Abstract/Free Full Text]
- Cassidy A., Bingham S., Setchell K. (1995). Biological effects of isoflavones in young women: Importance of the chemical composition of soybean products. Br J Nutr 74: 587-601.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- CEFIC, Centre European des Silicones (1998). CES Position Statement of March 31, 1998.
- Chapin RE, Stevens JT, Hughes CL, Kelce WR, Hess RA, Daston GP (1996). Endocrine modulation of reproduction. Fundam Appl Toxicol 29: 1-17.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Colborn T., vom Saal FS, Soto AM ( 1993). Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect 101: 378-384.[Web of Science][Medline]
[Order article via Infotrieve]
- De La Taille A., Hayek OK, Buttyan R., Bagiella E., Burchardt M., Katz AE (1999). Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: A preliminary investigation on human cell lines and patients. BJU Int 84: 845-850.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- DiPaola RS. Zhang H., Lambert GH, Meeker R., Licitra E., Rafi MM, Zhu BT, Spaulding H., Goodin S. Toledano MB, Hait WN, Gallo MA (1998). Clinical and biological activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. N Engl J Med 339: 839-841.[Free Full Text]
- Di Silverio F., Monti S., Sciarra A., Varasano PA, Martini C., Lanzara S., D'Eramo G., DiNicola S., Toscano V. (1998). Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia. Prostate 37: 77-83.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ellis DV, Pattisina LA (1990). Widespread neogastropod imposex: A biological indicator of global TBT contamination. Mar Pollut Bull 21: 248-253.[CrossRef][Web of Science]
- Fielden MR, Chen I., Chittim B., Safe S., Zacharewski R. (1997). Examination of the estrogenicity of 2,4,6,2',6'-pentachlorobiphenyl (PC 104), its hydroxylated metabolite 2,4,6,2',6'-pentachloro-4-biphenylol (HO-PCB 104), and a further chlorinated derivative 2,4,6,2',4',6'-hexachlorobiphenyl (PCB 155). Environ Health Perspect 105: 1238-1248.[Web of Science][Medline]
[Order article via Infotrieve]
- Fukutake M., Takahashi M., Ishida K., Kawamura H., Sugimura T., Wakabayashi K. (1996). Quantification of genistein and genistin in soybeans and soybean products. Food Chem Toxicol 34: 457-461.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Gavaler JS, Galvao-Teles A., Monteiro E., van Thiel DH, Rosenblum E. (1991). Clinical responses to the administration of bourbon phytoestrogens to normal postmenopausal women. Hepatology 14: 87A.
- Gellert RJ, Heinrichs WL, Swerdloff RS (1972). DDT homologues: Estrogen-like effects on the vagina, uterus and pituitary of the rat. Endocrinology 91: 1095-1099.[Abstract/Free Full Text]
- Giesy JP, Verbrugge DA, Othout RA, et al (13 coauthors) (1994). Contaminants in fishes from Great Lakes-influenced sections and above dams of three Michigan rivers. II: Implications for health of mink. Arch Environ Contam Toxicol 27: 213-223.[Web of Science][Medline]
[Order article via Infotrieve]
- Golden RJ, Noller KL, Titus-Ernstoff L., Kaufman RH, Mittendorf R., Stillman R., Reese EA (1998). Environmental endocrine modulators and human health: An assessment of the biological evidence. Crit Rev Toxicol 28: 109-225.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Hajjar NP (1985). Chitin synthesis inhibitors as insecticides. In: Insecticides: Progress in Pesticide Biochemistry and Toxicology, Vol 5, Hutson DH, Roberts TR (eds). Wiley, Chichester, United Kingdom, pp 279-303.
- Hall AJ, Green Njl, Jones KC, Pomeroy PP, Harwood J. (1998). Thyroid hormones as biomarkers in grey seals. Mar Pollut Bull 36: 424-428.[CrossRef][Web of Science]
- Hayden JF, Barlow SA (1972). Structure-activity relationships of oral organosiloxanes on the female reproductive system. Toxicol Appl Pharmacol 21: 68-79.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Heaton SN, Bursian SJ, Giesy JP, Tillitt DE, Render JA, Jones PD, Verbrugge DA, Kubiak TJ, Aulerich RJ (1995). Dietary exposure of mink to carp from Saginaw Bay, Michigan. 1. Effects on reproduction and survival, and the potential risks to wild mink populations. Arch Environ Contam Toxicol 28: 334-343.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Heindel JJ, Gulati DK, Mounce RC, Russel SR, Lamb JC ( 1989). Reproductive toxicity of three phthalic esters in a continuous breeding protocol. Fundam Appl Toxicol 12: 508-518.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Hill RN, Crisp TM, Hurley PM, Rosenthal SL, Singh DV (1998). Risk assessment of thyroid follicular cell tumors. Environ Health Perspect 106: 447-457.[Web of Science][Medline]
[Order article via Infotrieve]
- Hill RN, Erdreich LS, Paynter OE, Roberts PA, Rosenthal SL, Wilkinson CF (1989). Thyroid follicular cell carcinogenesis. Fundam Appl Toxicol 12: 629-697.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- International Programme on Chemical Safety (1990). Environmental Health Criteria No 116: Tributyl Compounds, World Health Organization, Geneva, Switzerland.
- Jobling S., Reynolds T., White R., Parker MG, Sumpter JP (1995). A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ Health Perspect 103: 582-587.[Web of Science][Medline]
[Order article via Infotrieve]
- Jobling S., Sheahan D., Osborne J., Matthiessen P., Sumpter JP (1996). Inhibition of testicular growth in rainbow trout (Oncorhynchus mykiss) exposed to estrogenic alkylphenolic chemicals. Environ Toxicol Chem 15: 194-202.[CrossRef][Web of Science]
- Kaldas RS, Hughes CL (1989). Reproductive and general metabolic effects of phytoestrogens in mammals. Reprod Toxicol 3: 81-89.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Kuiper-Goodman T., Scott PM, Watanabe H. (1987). Risk assessment of the mycotoxin zearalenone. Regul Toxicol Pharmacol 7: 253-306.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Kurata Y., Kidachi F., Yokoyama M., Toyota N., Tsuchitani M., Katoh M. (1998). Subchronic toxicity of di(2-ethylhexyl)phthalate in common marmosets: Lack of hepatic peroxisome proliferation, testicular atrophy, or pancreatic acinar cell hyperplasia. Toxicol Sci 42: 49-56.[Abstract/Free Full Text]
- Lamb JC, Chapin R., Teague J., Lawton AD, Reel JR ( 1987). Reproductive effects of four phthalate esters in the mouse. Toxicol Appl Pharmacol 88: 255-269.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Lamberts Swj, van den Beld AW, van der Lely A-J. (1997). The endocrinology of aging. Science 278: 419-424.[Abstract/Free Full Text]
- Levy JR, Faber KA, Ayyash L., Hughes CL (1995). The effect of prenatal exposure to the phytoestrogen genistein on sexual differentation in rats. Proc Soc Exp Biol Med 208: 60-66.[CrossRef][Medline]
[Order article via Infotrieve]
- MacLatchy DL, van der Kraak GJ (1995). The phytoestrogen β-sitosterol alters reproductive endocrine status of goldfish. Toxicol Pharmacol 134: 305-312.
- Markaverich BM, Webb B., Densmore CL, Gregory RR (1995). Effects of coumestrol on estrogen receptor function and uterine growth in ovariectomized rats. Environ Health Perspect 103: 574-581.[Web of Science][Medline]
[Order article via Infotrieve]
- Matthiessen P., Gibbs PE (1998). Critical appraisal of the evidence for tributyltin-mediated endocrine disruption in mollusks. Environ Toxicol Chem 17: 37-43.[CrossRef][Web of Science]
- McClain RM (1995). The use of mechanistic data in cancer risk assessment: Case example—Sulfonamides. In: Low-Dose Extrapolation of Cancer Risks, Olin S, Farland W, Park C, et al (eds). ILSI Press, Washington, DC, pp 163-173.
- McLachlan JA (1997). Synergistic effect of environmental estrogens: Report withdrawn. Science 277: 463-464.
- Mellanen P., Petänen T., Lehtimäki J., Mäkelä S., Bylund G., Holmbom B., Mannila E., Oikari A., Santti R. (1996). Wood-derived estrogens: Studies in vitro with breast cancer cell lines and in vivo in trout. Toxicol Appl Pharmacol 136: 381-388.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Milligan SR, Balasubramanian AV, Kalita JC (1998). Relative potency of xenobiotic estrogens in an acute in vivo mammalian assay. Environ Health Perspect 106: 23-26.[Web of Science][Medline]
[Order article via Infotrieve]
- Mylchreest E., Cattley RC, Foster Pmd (1998). Male reproductive tract malformations in rats following gestational and lactational exposure to di-(n-butyl)phthalate: An antiandrogenic mechanism? Toxicol Sci 43: 47-60.[Abstract/Free Full Text]
- Nagel SC, vom Saal FS, Thayer KA, Dhar MG, Boechler M., Welshons WV (1997). Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. Environ Health Perspect 105: 70-76.[Web of Science][Medline]
[Order article via Infotrieve]
- Neubert D. (1997). Vulnerability of the endocrine system to xenobiotic influence. Regul Toxicol Pharmacol 26: 9-29.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Odum J., Lefevre PA, Tittensor S., Paton D., Routledge EJ, Beresford NA, Sumpter JP, Ashby J. (1997). The rodent uterotrophic assay: Critical protocol features, studies with nonyl phenols, and comparison with a yeast estrogenic assay. Regul Toxicol Pharmacol 25: 176-188.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Olson KJ (1972). Preface-series of papers relating reproductive activity to selected organosiloxane chemicals. Toxicol Appl Pharmacol 21: 12-14.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Palmer BV, Montgomery Acv, Monteiro JC (1978). Ginseng and mastalgia. Br Med J 278: 1284.
- Pearce PT, Zois I., Wynne KN, Funder JW (1982). Panax ginseng and eleutrococcus senticosus extracts—In vitro studies on binding to steroid receptors. Endocrinol Jpn 29: 567-573.[Medline]
[Order article via Infotrieve]
- Pollack OJ, Kritchevsky D. (1981). Sitosterol. In: Monographs on Atherosclerosis, Vol 10, Clarkson Tb, Kritchevsky D, Pollack OJ (eds). Karger, New York, pp 4-22.
- Poon R., Lecavalier P., Mueller R., Valli VE, Procter BG, Chu I. ( 1997). Subchronic oral toxicity of di-n-octylphthalate and di(2-ethylhexyl)phthalate in the rat. Food Chem Toxicol 35: 225-239.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Punnonen R., Lukola A. (1980). Oestrogen-like effects of ginseng. Br Med J 281: 1110.[Free Full Text]
- Purdom CE, Hardiman PA, Bye VJ, Eno NC, Tyler CR, Sumpter JP (1994). Estrogenic effects of effluents from sewage treatment works. Chem Ecol 8: 275-285.[CrossRef]
- Ramamoorthy K., Wang F., Chen I-C., Safe S., McDonnell DP, Leonard LS, Gaido KW (1997). Additive estrogenic activities of a binary mixture of 2',4',6'-trichloro and 2',3',4',5'-tetrachloro-4-biphenylol. Toxicol Appl Pharmacol 147: 93-100.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ramamoorthy K., Wang F., Chen I-C., Safe S., Norris JD, McDonnell DP, Gaido KW, Bocchinfuso WP, Korach KS (1997). Potency of combined estrogenic pesticides. Science 275: 405.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Safe SH (1995). Environmental and dietary estrogens and human health: Is there a problem? Environ Health Perspect 103: 346-351.[Web of Science][Medline]
[Order article via Infotrieve]
- Safe S., Wang F., Porter W., Duan R., McDougal A. (1998). Ah receptor agonists as endocrine disruptors: Antiestrogenic activity and mechanisms. Toxicol Lett 103: 343-347.[CrossRef][Web of Science]
- Sharp RM, Fisher JS, Millar MM, Jobling S., Sumpter JP (1995). Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production. Environ Health Perspect 103: 1136-1143.[Web of Science][Medline]
[Order article via Infotrieve]
- Sharp RM, Turner KJ, Sumpter JP (1998). Endocrine disrupters and testis development. Environ Health Perspect 106: A220-A221.[Web of Science][Medline]
[Order article via Infotrieve]
- Shore LS, Gurevitz M., Shemesh M. (1993). Estrogen as an environmental pollutant. Bull Environ Contam Toxicol 51: 361-366.[Web of Science][Medline]
[Order article via Infotrieve]
- Sinha R., Rothman N., Brown ED, Mark SD, Hoover RN, Caporaso NE, Levander OA, Knize MG, Lang NP, Kadlubar FF (1994). Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P-4501A2 activity in humans. Cancer Res 54: 6154-6159.[Abstract/Free Full Text]
- Solomon KR (1998). Endocrine-modulating substances in the environment: The wildlife connection. Int J Toxicol 17: 159-172.[Abstract/Free Full Text]
- Soto AM, Lin TM, Justicia H., Silvia RM Sonnenschein C. (1992). An "in culture" bioassay to assess the estrogenicity of xenobiotics (E-screen). In: Chemically Induced Alterations in Sexual and Functional Development: The Wildlife/Human Connection, Colborn T, Clements C (eds). Princeton Science Publishing, Princeton, New Jersey, pp 295-309.
- Störmer FC, Reistad R., Alexander J. (1993). Glycyrrhizic acid in liquorice—Evaluation of health hazard. Food Chem Toxicol 31: 303-312.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Tou JC, Chen J., Thompson LU (1998). Flaxseed and its lignan precursor, secoisolariciresinol diglycoside, affect pregnancy outcome and reproductive development in rats. J Nutr 128: 1861-1868.[Abstract/Free Full Text]
- UK Environment Agency ( 1996 ). Identification of Oestrogenic Effects in Wild Fish. R&D Technical Report W119. Environment Agency, Bristol.
- UK Ministry of Agriculture, Fisheries and Food (1996). Phthalates in Food and Infant Formulae. Food Surveillance Information Sheet 82 and 83. UK Ministry of Agriculture, Fisheries and Food, London.
- US Environmental Protection Agency (1989). Ethylene bisdithiocarbamates. Fed Reg 54: 52158-52185.
- US Environmental Protection Agency (1994). Estimating Exposure to Dioxin-Like Compounds. Vol. I: Executive Summary, Report No EPA/600/6-88/005Ca, US Environmental Protection Agency, Washington, DC.
- US Environmental Protection Agency (1997). Special Report on Environmental Endocrine Disruption: An Effects Assessment and Analysis. Report No EPA/630/R-96/01, Risk Assessment Forum, US Environmental Protection Agency, Washington, DC.
- Whitten PL, Lewis C., Naftolin F. (1993). A phytoestrogen diet induces the premature anovulatory syndrome in lactationally exposed female rats. Biol Reprod 49: 1117.[Abstract]
Toxicologic Pathology, Vol. 28, No. 3,
420-431 (2000)
DOI: 10.1177/019262330002800311
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