Endocrine disruption: Historical perspectives and its impact on the future of toxicology testing

Toxicological Sciences

Volumn 120, Issue SUPPL.1, 2011, Pages

  Marty, Mary Sue ^a   Carney, Edward W ^a   Rowlands, Justin Craig ^a  

^a DOW CHEMICAL COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3,3' DIINDOLYLMETHANE; 4,4' ISOPROPYLIDENEDIPHENOL; CELL NUCLEUS RECEPTOR; DIETHYLSTILBESTROL; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; METHOXYCHLOR; POLYCHLORINATED BIPHENYL; POLYCHLORINATED DIBENZOFURAN; RESVERATROL; TAMOXIFEN;

BINDING AFFINITY; BREAST CANCER; CANCER INCIDENCE; CLEAR CELL CARCINOMA; CRYPTORCHISM; ENDOCRINE DISEASE; ENDOCRINE DISRUPTION; ENDOCRINE FUNCTION TEST; HUMAN; HYPOSPADIAS; NONHUMAN; PREGNANT WOMAN; PYROLYSIS; REVIEW; SCREENING; THYROID FUNCTION; TOXICITY TESTING;

ANIMALS; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOCRINE DISRUPTORS; ENDOCRINE SYSTEM; HUMANS; TOXICITY TESTS;

EID: 79952092370     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfq329     Document Type: Review

References (109)

1. Adams, N. R. (1995). Detection of the effects of phytoestrogens on sheep and cattle. J. Anim. Sci. 73, 1509-1515.
2. Ai, N., Krasowski, M. D., Welsh, W. J., and Ekins, S. (2009). Understanding nuclear receptors using computational methods. Drug Discov. Today 14, 486-494. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19429508.
3. Ankley, G. T., Bennett, R. S., Erickson, R. J., Hoff, D. J., Hornung, M. W., Johnson, R. D., Mount, D. R., Nichols, J. W., Russom, C. L., Schmieder, P. K., et al. (2010). Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ. Toxicol. Chem. 29, 730-741.
4. Aoki, Y. (2001). Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans as endocrine disrupters-what we have learned from Yusho disease. Environ. Res. 86, 2-11.
5. Arnold, S. F., Klotz, D. M., Collins, B. M., Vonier, P. M., Guillette, L. J., Jr., and McLachlan, J. A. (1996). Synergistic activation of estrogen receptor with combinations of environmental chemicals. Science 272, 1489-1492.
6. Ashby, J., Lefevre, P. A., Odum, J., Harris, C. A., Routledge, E. J., and Sumpter, J. P. (1997). Synergy between synthetic oestrogens? Nature 385, 494.
7. Ashby, J., Owens, W., Odum, J., and Tinwell, H. (2003). The intact immature rodent uterotrophic bioassay: possible effects on assay sensitivity of vomeronasal signals from male rodents and strain differences. Environ. Health Perspect. 111, 1568-1570.
8. Barlow, S., Kavlock, R. J., Moore, J. A., Schantz, S. L., Sheehan, D. M., Shuey, D. L., and Lary, J. M. (1999). Teratology Society Public Affairs Committee position paper: developmental toxicity of endocrine disruptors to humans. Teratology 60, 365-375.
9. Blair, R. M., Fang, H., Branham, W. S., Hass, B. S., Dial, S. L., Moland, C. L., Tong, W., Shi, L., Perkins, R., and Sheehan, D. M. (2000). The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol. Sci. 54, 138-153.
10. Boue, S. M., Wiese, T. E., Nehls, S., Burow, M. E., Elliott, S., Carter-Wientjes, C. H., Shih, B. Y., McLachlan, J. A., and Cleveland, T. E. (2003). Evaluation of the estrogenic effects of legume extracts containing phytoestrogens. J. Agric. Food Chem. 51, 2193-2199.
11. Bowers, J. L., Tyulmenkov, V. V., Jernigan, S. C., and Klinge, C. M. (2000). Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology 141, 3657-3667.
12. Bus, J. S., and Becker, R. A. (2009). Toxicity testing in the 21st century: a view from the chemical industry. Toxicol. Sci. 112, 297-302.
13. Carlsen, E., Giwercman, A., Keiding, N., and Skakkebaek, N. E. (1992). Evidence for decreasing quality of semen during past 50 years. BMJ 305, 609-613.
14. Carney, E., Woodburn, K. B., and Rowland, S. J. (2010). Endocrine active chemicals. In Principles and Practice of Mixtures Toxicology (M. M. Mumtaz, Ed.), pp. 421-442. WILEY-VCH Verlag GmbH & Co., Weinheim, Germany.
15. Chapin, R. E., Adams, J., Boekelheide, K., Gray, L. E., Jr., Hayward, S. W., Lees, P. S., McIntyre, B. S., Portier, K. M., Schnorr, T. M., Selevan, S. G., et al. (2008). NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A. Birth Defects Res. B 83, 157-395.
16. Charles, G. D., Gennings, C., Tornesi, B., Kan, H. L., Zacharewski, T. R., Gollapudi, B. B., and Carney, E. W. (2007). Analysis of the interaction of phytoestrogens and synthetic chemicals: an in vitro/in vivo comparison. Toxicol. Appl. Pharmacol. 218, 280-288.
17. Charles, G. D., Kan, H. L., Schisler, M. R., Gollapudi, B. B., and Marty, M. S. (2005). A comparison of in vitro and in vivo EDSTAC test battery results for detecting antiandrogenic activity. Toxicol. Appl. Pharmacol. 202, 108-120.
18. Colborn, T., Dumanoski, D., and Myers, J. P. (1996). In Our Stolen Future. Are We Threatening Our Fertility, Intelligence and Survival?-A Scientific Detective Story. Penguin Books USA, New York.
19. Colborn, T., vom Saal, F. S., and Soto, A. M. (1993). Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ. Health Perspect. 101, 378-384.
20. Davis, D. L., Bradlow, H. L., Wolff, M., Woodruff, T., Hoel, D. G., and Anton-Culver, H. (1993). Medical hypothesis: xenoestrogens as preventable causes of breast cancer. Environ. Health Perspect. 101, 372-377.
21. Diamanti-Kandarakis, E., Bourguignon, J.-P., Giudice, L. C., Hauser, R., Prins, G. S., Soto, A. M., Zoeller, R. T., and Gore, A. C. (2009). Endocrine disrupting chemicals: an Endocrine Society scientific statement. Endocr. Rev. 30, 293-342.
22. Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC). (1998). Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Final Report, August 1998. Available at: http://www.epa.gov/endo/pubs/edspoverview/finalrpt.htm. Accessed August 13, 2010.
23. Fisch, H. (2008). Declining worldwide sperm counts: disproving a myth. Urol. Clin. North Am 35, 137-146.
24. Fong, C. J., Burgoon, L. D., Williams, K. J., Forgacs, A. L., and Zacharewski, T. R. (2007). Comparative temporal and dose-dependent morphological and transcriptional uterine effects elicited by tamoxifen and ethynylestradiol in immature, ovariectomized mice. BMC Genomics 8, 151.
25. Food Quality Protection Act (FQPA). (1996). Public Law 104-170, 110 STAT. 1489, Available at: http://www.epa.gov/scipoly/oscpendo/pubs/fqpa.pdf Accessed August 13, 2010.
26. Freyberger, A., and Schladt, L. (2009). Evaluation of the rodent Hershberger bioassay on intact juvenile males-testing of coded chemicals and supplementary biochemical investigations. Toxicology 262, 114-120.
27. Gaido, K., Dohme, L., Wang, F., Chen, I., Blankvoort, B., Ramamoorthy, K., and Safe, S. (1998). Comparative estrogenic activity of wine extracts and organochlorine pesticide residues in food. Environ. Health Perspect. 106(Suppl. 6), 1347-1351.
28. Garrison, A. W., and Pope, J. D. (1975). In GC/MS Analysis of Organic Compounds in Domestic Wastewaters. Chemical Congress of the North American Continent. Ann Arbor Science, Ann Arbor, Michigan.
29. Gennings, C. (1996). Economical designs for detecting and characterizing departure from additivity in mixtures of many chemicals. Food Chem. Toxicol. 34, 1053-1058.
30. Gennings, C., Carter, W. H., Jr., Carney, E. W., Charles, G. D., Gollapudi, B. B., and Carchman, R. A. (2004). A novel flexible approach for evaluating fixed ratio mixtures of full and partial agonists. Toxicol. Sci. 80, 134-150.
31. Giusti, R. M., Iwamoto, K., and Hatch, E. E. (1995). Diethylstilbestrol revisited: a review of the long-term health effects. Ann. Intern. Med. 122, 778-788.
32. Goodman, J. E., Witorsch, R. J., McConnell, E. E., Sipes, I. G., Slayton, T. M., Yu, C. J., Franz, A. M., and Rhombert, L. R. (2009). Weight-of-evidence evaluation of reproductive and developmental effects of low doses of bisphenol A. Crit. Rev. Toxicol. 39, 1-75.
33. Green, S., Walter, P., Greene, G., Krust, A., Goffin, C., Jensen, E., Scrace, G., Waterfield, M., and Chambon, P. (1986). Cloning of the human oestrogen receptor cDNA. J. Steroid Biochem. 24, 77-83.
34. Gronemeyer, H., Gustafsson, J. A., and Laudet, V. (2004). Principles for modulation of the nuclear receptor superfamily. Nat. Rev. 3, 950-964.
35. Gutendorf, B., and Westendorf, J. (2001). Comparison of an array of in vitro assays for the assessment of the estrogenic potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens. Toxicology 166, 79-89.
36. Haseman, J. K., Bailer, A. J., Kodell, R. L., Morris, R., and Portier, K. (2001). Statistical issues in the analysis of low-dose endocrine disruptor data. Toxicol. Sci. 61, 201-210.
37. Hecker, M., Giesy, J. P., Jones, P. D., Higley, E. B., Newsted, J. L., and Mehrle, P. (2006). In Influence of Cell Passage and Freeze/Thaw Events on Basal Production of 17β-Estradiol and Testosterone by H295R Cells. Interim Draft Report, Contract Code # GS-10F-0041L. ENTRIX, Inc. September, 2006. Available at: www.epa.gov/endo/pubs/appendix_i-h295r_culture_protocol.pdf. Accessed August 13, 2010.
38. Hecker, M., Giesy, J. P., and Timm, G. (2008). Multi-laboratory Validation of the H295R Steroidogenesis Assay to Identify Modulators of Testosterone and Estradiol Production. Report, Contract Code # GS-10F-0041L. ENTRIX, Inc. February, 2008. Available at: www.epa.gov/endo/pubs/h295r_validation_study_interim_report.pdf. Accessed August 13, 2010.
39. Hignite, C., and Azarnoff, D. L. (1977). Drugs and drug metabolites as environmental contaminants: chlorophenoxyisobutyrate and salicylic acid in sewage water effluent. Life Sci. 20, 337-341.
40. Hotchkiss, A. K., Rider, C. V., Blystone, C. R., Wilson, V. S., Hartig, P. C., Ankley, G. T., Foster, P. M., Gray, C. L., and Gray, L. E. (2008). Fifteen years after "Wingspread"-environmental endocrine disrupters and human and wildlife health: where we are today and where we need to go. Toxicol. Sci. 105, 235-259.
41. ™ Tell Us about Endocrine Disruption? ISRTP Workshop: The Endocrine Disruptor Screening Program-What Can Screening Results Tell Us About Potential Adverse Endocrine Effects. Bethesda, MD. Available at: http://www.isrtp.org/index.htm. Accessed August 13, 2010.
42. Hunter, D. J., and Kelsey, K. T. (1993). Pesticide residues and breast cancer: the harvest of a silent spring? J. Natl. Cancer Inst. 85, 598-599.
43. International Programme on Chemical Safety (IPCS). (2002). Global assessment of the state-of-the-science of endocrine disruptors. Damstra T., Barlow, S., Bergman, A., Kavlock, R. and Van der Kraak, G., Eds., WHO publication no. WHO/PCS/EDC/02.2. World Health Organization, Geneva.
44. Jobling, S., Williams, R., Johnson, A., Taylor, A., Gross-Sorokin, M., Nolan, M., Tyler, C. R., van Aerle, R., Santos, E., et al. (2006). Predicted exposures to steroid estrogens in U.K. rivers correlate with widespread sexual disruption in wild fish populations. Environ. Health Perspect. 114(Suppl. 1), 32-39.
45. Jordan, V. C. (2003). Antiestrogens and selective estrogen receptor modulators as multifunctional medicines. 1. Receptor interactions. J. Med. Chem. 46, 883-908.
46. Kamrin, M. A. (2004). Bisphenol A: a scientific evaluation. MedGenMed. 6(3), 7.
47. Kamrin, M. A. (2007). The "low dose" hypothesis: validity and implications for human risk. Int. J. Toxicol. 26, 13-23.
48. Kanno, J., Onyon, L., Haseman, J., Fenner-Crisp, P., Ashby, J., and Owens, W. (2001). The OECD program to validate the rat uterotrophic bioassay to screen compounds for in vivo estrogenic responses: phase 1. Environ. Health Perspect. 109, 785-794.
49. Kanno, J., Onyon, L., Peddada, S., Ashby, J., Jacob, E., and Owens, W. (2003a). The OECD program to validate the rat uterotrophic bioassay. Phase 2: coded single-dose studies. Environ. Health Perspect. 111, 1550-1558.
50. Kanno, J., Onyon, L., Peddada, S., Ashby, J., Jacob, E., and Owens, W. (2003b). The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies. Environ. Health Perspect. 111, 1530-1549.
51. Klinge, C. M., Risinger, K. E., Watts, M. B., Beck, V., Eder, R., and Jungbauer, A. (2003). Estrogenic activity in white and red wine extracts. J. Agric. Food Chem. 51, 1850-1857.
52. Kortenkamp, A. (2008). Low dose mixture effects of endocrine disrupters: implications for risk assessment and epidemiology. Int. J. Androl. 31, 233-240.
53. Kuiper, G. G., Enmark, E., Pelto-Huikko, M., Nilsson, S., and Gustafsson, J. A. (1996). Cloning of a novel receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci. U.S.A. 93, 5925-5930.
54. Kuiper, G. G., Lemmen, J. G., Carlsson, B., Corton, J. C., Safe, S. H., van der Saag, P. T., van der Burg, B., and Gustafsson, J. A. (1998). Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139, 4252-4263.
55. Laetz, C. A., Baldwin, D. H., Collier, T. K., Herbert, V., Stark, J. D., and Scholz, N. L. (2009). The synergistic toxicity of pesticide mixtures: implications for risk assessment and the conservation of endangered pacific salmon. Environ. Health Perspect. 117, 348-353.
56. Laws, S. C., Ferrell, J. M., Stoker, T. E., and Cooper, R. L. (2003). Pubertal development in female Wistar rats following exposure to propazine, and atrazine biotransformation by-products, diamino-s-chlorotriazine and hydroxyatrazine. Toxicol. Sci. 76, 190-200.
57. Lintelmann, J., Katayama, A., Kurihara, N., Shore, L., and Wenzel, A. (2003). Endocrine disruptors in the environment. Pure Appl. Chem. 75, 631-681.
58. Lipscomb, J. C., Lambert, J. C., and Teuschler, L. (2010). Chemical mixtures and cumulative risk assessment. In Principles and Practice of Mixtures Toxicology (M. M. Mumtaz, Ed.). WILEY-VCH Verlag GmbH & Co., Weinheim, Germany.
59. Lonard, D. M., Lanz, R. B., and O'Malley, B. W. (2007). Nuclear receptor coregulators and human disease. Endocr. Rev. 28, 575-587.
60. Lubahn, D. B., Moyer, J. S., Golding, T. S., Couse, J. F., Korach, K. S., and Smithies, O. (1993). Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc. Natl. Acad. Sci. U.S.A. 90, 11162-11166.
61. Martin, R.-P., Wright, A. N., Miyamoto, J., and Wermuth, C. G. (1998). Natural and anthropogenic environmental oestrogens: the scientific basis for risk assessment. Pure Appl. Chem. 70, iv.
62. McKenna, N. M., and O'Malley, B. W. (2003). Nuclear receptor signaling: concepts and models. NURSA: The Nuclear Receptor Signaling Atlas. Available at: http://www.nursa.org/flash/gene/nuclearreceptor/start.html. Accessed July 15, 2010.
63. McLachlan, J. A. (1997). Synergistic effect of environmental estrogens: report withdrawn. Science 277, 462-463.
64. Melnick, R., Lucier, G., Wolfe, M., Hall, R., Stancel, G., Prins, G., Gallo, M., Reuhl, K., Ho, S.-M., Brown, T., et al. (2002). Summary of the National Toxicology Program's report of the endocrine disruptors low-dose peer review. Environ. Health Perspect. 110, 427-431.
65. Naciff, J. M., Hess, K. A., Overmann, G. J., Torontali, S. M., Carr, G. J., Tiesman, J. P., Foertsch, L. M., Richardson, B. D., Martinez, J. E., and Daston, G. P. (2005). Gene expression changes induced in the testis by transplacental exposure to high and low doses of 17{alpha}-ethynyl estradiol, genistein, or bisphenol A. Toxicol. Sci. 86, 396-416.
66. Naciff, J. M., Jump, M. L., Torontali, S. M., Carr, G. J., Tiesman, J. P., Overmann, G. J., and Daston, G. P. (2002). Gene expression profile induced by 17alpha-ethynyl estradiol, bisphenol A, and genistein in the developing female reproductive system of the rat. Toxicol. Sci. 68, 184-199.
67. Naciff, J. M., Khambatta, Z. S., Reichling, T. D., Carr, G. J., Tiesman, J. P., Singleton, D. W., Khan, S. A., and Daston, G. P. (2010). The genomic response of Ishikawa cells to bisphenol A exposure is dose- and timedependent. Toxicology 270, 137-149.
68. Naciff, J. M., Khambatta, Z. S., Thomason, R. G., Carr, G. J., Tiesman, J. P., Singleton, D. W., Khan, S. A., and Daston, G. P. (2009). The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol. Sci. 107, 40-55.
69. National Research Council (NRC) (1999). Hormonally Active Agents in the Environment. National Academy Press, Washington, DC.
70. National Research Council (NRC) Committee on Toxicity Testing and Assessment of Environmental Agents, Board of Environmental Studies and Toxicology, Institute for Laboratory Animal Research. (2007). Toxicity Testing in the 21st Century. A Vision and a Strategy. National Academies Press, Washington, DC.
71. Nettles, K. W., and Greene, G. L. (2005). Ligand control of coregulator recruitment to nuclear receptors. Annu. Rev. Physiol. 67, 309-333.
72. Newburgh, R. W. (1975). Toxicology of the reproductive system. In Toxicology The Basic Science of Poisons. (L. J. Casarett and J. Doull, Eds.), pp. 261-274. Macmillan Publishing Co., Inc, New York, NY.
73. Nieuwkoop, P. D., and Faber, J. (1994). In Normal Table of Xenopus laevis. Garland Publishing Inc., New York, NY.
74. O'Connor, J. C., Cook, J. C., Marty, M. S., Davis, L. G., Kaplan, A. M., and Carney, E. W. (2002). Evaluation of Tier I screening approaches for detecting endocrine-active compounds (EACs). Crit. Rev. Toxicol. 32, 521-549.
75. O'Connor, J. C., Davis, L. G., Frame, S. R., and Cook, J. C. (2000). Evaluation of a Tier I screening battery for detecting endocrine-active compounds (EACs) using the positive controls testosterone, coumestrol, progesterone, and RU486. Toxicol. Sci. 69, 79-91.
76. O'Connor, J. C., Frame, S. R., Davis, L. G., and Cook, J. C. (1999). Detection of the environmental antiandrogen p,p'-DDE in CD and Long-Evans rats using a Tier I screening battery and a Hershberger assay. Toxicol. Sci. 51, 44-53.
77. O'Connor, J. C., Marty, M. S., Becker, R. A., Snajdr, S., and Kaplan, A. M. (2008). Results of the negative control chemical allyl alcohol in the 15-day intact adult male rat screening assay for endocrine activity. Birth Defects Res. B Dev. Reprod. Toxicol. 83, 117-122.
78. Organization for Economic Co-operation and Development (OECD). (2003). Detailed Background Review of the Uterotrophic Bioassay, OECD Series on Testing and Assessment, No. 38, OECD Publishing.
79. Owens, W., Ashby, J., Odum, J., and Onyon, L. (2003). The OECD program to validate the rat uterotrophic bioassay. Phase 2: dietary phytoestrogen analyses. Environ. Health Perspect. 111, 1559-1567.
80. Owens, W., Gray, L. E., Zeiger, E., Walker, M., Yamasaki, K., Ashby, J., and Jacob, E. (2007). The OECD program to validate the rat Hershberger bioassay to screen compounds for in vivo androgen and antiandrogen responses. Phase 2 dose-response studies. Environ. Health Perspect. 115, 671-678.
81. Owens, W., and Koëter, H. B. (2003). The OECD program to validate the rat uterotrophic bioassay: an overview. Environ. Health Perspect. 111, 1527-1529.
82. Owens, W., Zeiger, E., Walker, M., Ashby, J., Onyon, L., and Gray, L. E., Jr. (2006). The OECD program to validate the rat Hershberger bioassay to screen compounds for in vivo androgen and antiandrogen responses. Phase 1: use of a potent agonist and a potent antagonist to test the standardized protocol. Environ. Health Perspect. 11, 1259-1265.
83. Powlin, S. S., Cook, J. C., Novak, S., and O'Connor, J. C. (1998). Ex vivo and in vitro testis and ovary explants: utility for identifying steroid biosynthesis inhibitors and comparison to a Tier I screening battery. Toxicol. Sci. 46, 61-74.
84. Ramamoorthy, K., Wang, F., Chen, I. C., Norris, J. D., McDonnell, D. P., Leonard, L. S., Gaido, K. W., Bocchinfuso, W. P., Korach, K. S., and Safe, S. (1997). Estrogenic activity of a dieldrin/toxaphene mixture in the mouse uterus, MCF-7 human breast cancer cells, and yeastbased estrogen receptor assays: no apparent synergism. Endocrinology 138, 1520-1527.
85. Roeder, R. G. (2005). Transcriptional regulation and the role of diverse coactivators in animal cells. FEBS Lett. 579, 909-915.
86. Safe, S., Connor, K., Ramamoorthy, K., Gaido, K., and Maness, S. (1997). Human exposure to endocrine-active chemicals: hazard assessment problems. Regul. Toxicol. Pharmacol. 26, 52-58.
87. Safe, S., Papineni, S., and Chintharlapalli, S. (2008). Cancer chemotherapy with indole-3-carbinol, bis(3'-indolyl)methane and synthetic analogs. Cancer Lett. 269, 326-338.
88. Schueler, F.W. (1946). Sex hormonal action and chemical constitution. Science 103, 221-223.
89. Sharpe, R. M., and Skakkebaek, N. E. (1993). Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet 341, 1392-1395.
90. Shelby, M. D., Newbold, R. R., Tully, D. B., Chae, K., and Davis, V. L. (1996). Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays. Environ. Health Perspect. 104, 1296-1300.
91. Sluczewski, A., and Roth, P. (1948). Effects of androgenic and estrogenic compounds on the experimental metamorphoses of amphibians. Gynecol. Obstet. 47, 164-176.
92. Smith, C. L., and O'Malley, B. W. (2004). Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr. Rev. 25, 45-71.
93. Stoker, T. E., and Zorrilla, L. M. (2010). The effects of endocrine disrupting chemicals on pubertal development in the rat: use of the EDSP pubertal assays as a screen. In Endocrine Toxicology, 3rd ed. (J. C. Eldridge and J. T. Stevens, Eds.), pp. 27-81. Informa Healthcare, New York, NY.
94. Stumm-Zollinger, E., and Fair, G. M. (1965). Biodegradation of steroid hormones. J. Water Pollut. Control Fed. 37, 1506-1510.
95. Sumpter, J. P. (1995). Feminized responses in fish to environmental estrogens. Toxicol. Lett. 82-83, 737-742.
96. Tabak, H. H., and Bunch, R. L. (1970). Steroid hormones as water pollutants. I. Metabolism of natural and synthetic ovulation-inhibiting hormones by microorganisms of activated sludge and primary settled sewage. Dev. Ind. Microbiol. 11, 367-376.
97. Takeyoshi, M. (2006). In Draft Report of Pre-validation and Inter-laboratory Validation for Stably Transfected Transcriptional Activation (TA) Assay to Detect Estrogenic Activity-The Human Estrogen Receptor Alpha Mediated Reporter Gene Assay Using hER-HeLa-9903 Cell Line. Chemicals Evaluation and Research Institute, Japan. Available at: http://www.oecd.org/document/62/0,3343,en_2649_34377_2348606_1_1_1_1,00.htm Accessed August 13, 2010.
98. Tanida, T., Warita, K., Ishihara, K., Fukui, S., Mitsuhashi, T., Sugawara, T., Tabuchi, Y., Nanmori, T., Qi, W.-M., Inamoto, T., et al. (2009). Fetal and neonatal exposure to three typical environmental chemicals with different mechanisms of action: mixed exposure to phenol, phthalate, and dioxin cancels the effects of sole exposure on mouse midbrain dopaminergic nuclei. Toxicol. Lett. 189, 40-47.
99. Tata, J. R. (2005). One hundred years of hormones. EMBO Rep. 6, 490-496.
100. Teeguarden, J. G., and Barton, H. A. (2004). Computational modeling of serum-binding proteins and clearance in extrapolations across life stages and species for endocrine active compounds. Risk Anal. 24, 751-770.
101. Teeguarden, J. G., Waechter, J. M., Jr., Clewell, H. J., III, Covington, T. R., and Barton, H. A. (2005). Evaluation of oral and intravenous route pharmacokinetics, plasma protein binding, and uterine tissue dose metrics of bisphenol A: a physiologically based pharmacokinetic approach. Toxicol. Sci. 85, 823-838.
102. Teuschler, L., Klaunig, J., Carney, E., Chambers, J., Conolly, R., Gennings, C., Giesy, J., Hertzberg, R., Klaassen, C., Kodell, R., et al. (2002). Support of science-based decisions concerning the evaluation of the toxicology of mixtures: a new beginning. Regul. Toxicol. Pharmacol. 36, 34-39.
103. The Nobel Assembly at Karolinska Institutet. (1950). The Nobel Prize in physiology or medicine 1950. (Edward C. Kendall, Tadeus Reichstein, and Philip S. Hench). Available at: http://nobelprize.org/nobel_prizes/medicine/laureates/1950/. Accessed July 15, 2010.
104. Touart, L. (2005). In The Story of the Fish Screening Assay in EPA's Endocrine Disruptor Screening Program. Available at: http://www.epa.gov/endo/pubs/edmvac/fish_screening_story.htm. Accessed April 4, 2002.
105. U.S. Environmental Protection Agency (U.S. EPA). (2002). EPA Statement Regarding Endocrine Disruptor Low-Dose Hypothesis. U.S. Environmental Protection Agency, Washington, DC. Available at: http://www.epa.gov/endo/pubs/edmvs/lowdosepolicy.pdf. Dated March 26, 2005. Accessed August 13, 2010.
106. U.S. Environmental Protection Agency (U.S. EPA). (2007). Integrated Summary Report for Validation of a Test Method for Assessment of Pubertal Development and Thyroid Function in Juvenile Male Rats as a Potential Screen in the Endocrine Disruptor Screening Program Tier-1 Battery. U.S. Environmental Protection Agency, Office of Science Coordination and Policy and Office of Research and Development, Washington, DC. Available at: http://www.epa.gov/endo/pubs/male_pubertal_isr.pdf Accessed August 13, 2010.
107. Walker, B. S., and Janney, J. C. (1930). Estrogenic substances. II. Analysis of plant sources. Endocrinology 14, 389-392.
108. Zhang, S., Rowlands, C., and Safe, S. (2008). Ligand-dependent interactions of the Ah receptor with coactivators in a mammalian two-hybrid assay. Toxicol. Appl. Pharmacol. 227, 196-206. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18048071.
109. Zhu, B. T. (2005). Mechanistic explanation for the unique pharmacologic properties of receptor partial agonists. Biomed. Pharmacother. 59, 76-89.