e.hormone environmental signaling epigenetics lead in the environmental
Milestones In Environmental Hormone Research

First estrogen bioassay developed. The test detected estrogenic activity in biological extracts and determined relative potencies of compounds and mixed natural materials.

Allen, E. and E.A. Doisy. An ovarian hormone: Preliminary report on its localization, extraction and partial purification and action in test animals. Journal of the American Medical Association, 81:819 (1923).


DDT shown to be estrogenic.

Burlington, H. and V. Lindeman. Effect of DDT on testes and secondary sex characters of white leghorn cockerels. Proceedings of the Society for Experimental Biology and Medicine, 74:48-51 (1950).


Silent Spring published. Rachel Carson's book describes health problems observed in wildlife (egg shell thinning, deformaties, population declines) and links them to exposure to pesticides and other synthetic chemicals.

Carson, R. Silent Spring. Boston: Houghton Mifflin. (1962).


Study shows that newborn mice receiving estrogen injections developed tissue pathologies (cysts, cancers, lesions). Results indicated that exposure to naturally occurring hormones early in life can produce harmful health effects and pointed to possible early life causes of cancer in adult human populations.

Dunn, T. and A. Green. Cysts of the epididymis, cancer of the cervix, granular cell myoblastoma and other lesions after estrogen injection in newborn mice. Journal of the National Cancer Institute, 31:425-38 (1963).

Takasugi, N. and H.A. Bern. Tissue changes in mice with persistent vaginal cornification induced by early postnatal treatment with estrogen. J. Natl. Cancer Inst. 33:855-65 (1964).

Foresbert, J.G. The development of atypical epithlium in the mouse uterine cervix and vaginal fornix after neonatal estradiol treatment. Br. J. Exp. Pathol. 50:187-95 (1969).


DDT shown to be estrogenic in mammals and birds.

Bitman, J., H.C. Cecil, S.J. Harris, and G.F. Fries. Estrogenic activity of o,p'-DDT in the mammalian uterus and avian oviduct. Science, 162:371-72 (1968).


DES linked to vaginal cancer in daughters whose mothers had taken the drug during the first three months of pregnancy.

Herbst, A., H. Ulfelder, and D. Poskanzer. Adenocarcinoma of the vagina: Association of maternal stilbestrol therapy with tumor appearance in young women. New England Journal of Medicine, 284:878-881 (1971).

U.S. Food and Drug Administration directs doctors not to prescribe DES to pregnant women and bans the drug from animal use.


DDT use restricted in agriculture by the U.S. Environmental Protection Agency.

1975 and 1976

DES shown to cause developmental abnormalities in male mice.

McLachlan, J.A., R. Newbold and B. Bullock. Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol. Science, 190:991-992 (1975).

DES linked to human reproductive problems.

Herbst, A.L., D.C. Poskanzer, S.J. Robboy, L. Fiedlander, and R.E. Scully. Prenatal exposure to stilbestrol: A prospective comparison of exposed female offspring with unexposed controls. New England Journal of Medicine. 292:334-339 (1975).

Gill, W.B., G.F.B. Schumacher and M. Bibbo. Structural and functional abnormalities in the sex organs of male offspring of mothers treated with diethylstilbestrol (DES). Journal of Reproductive Medicine, 16:147-153 (1976).


Use and manufacture of PCBs restricted by the U.S. Environmental Protection Agency.


Estrogens in the Environment I. (September). Conference sponsored by the National Institute of Environmental Health Sciences. Inadvertent and advertent hormones were identified and evaluated.

Proceedings: Estrogens in the Environment. J.A. McLachlan, ed. New York: Elsevier. (1980).


DES shown to cause developmental abnormalities in female mice.

McLachlan, J.A., R.R. Newbold, and B.C. Bullock. Long-term effects on the female mouse genital tract associated with prenatal exposure to diethylstilbestrol. Cancer Research, 40:3988-3999 (1980).


Estrogens in the Environment II: Influences on Development. (April). Conference sponsored by the National Institute of Environmental Health Sciences. Presentations addressed the effects of environmental estrogens on puberty in young children, ubiquitous nature of the contaminants, their potency and their potential impact on public and environmental health.

Proceedings: Estrogens in the Environment II: Influences on Development. J.A. McLachlan, ed. New York: Elsevier. (1985).


Chemically Induced Alterations in Sexual Development: The Wildlife/Human Connection. (July). Wingspread Workshop convened by Theo Colborn. Presented evidence that compounds may have deleterious effects on sexual development in a variety of wildlife species, including reproductive decline in individuals, especially top predators; low population growth; and offspring born with adult features.

Proceedings: Chemically-induced Alterations in Sexual and Functional Development: The Wildlife/Human Connection. Colborn, T. and C.R. Clement, eds. Princeton, NJ: Princeton Scientific Pub. Co. (1992).

Some plastic compounds used in a variety of consumer products are shown to be estrogenic in laboratory research.

Soto, A.M., T.M. Lin, H. Justicia, J.W. Wray, and C. Sonneschein. p-Nonylphenol: An estrogenic xenobiotic released from "modified" polystyrene. Environmental Health Perspectives, 92:167-173 (1991).

Government Regulation of Reproductive Hazards. Report from the 102nd U.S. Congress, Senate Committee on Governmental Affairs.

Proceedings: Washington, DC: U.S. Government Publications Office. (1992).


Link between environmental estrogens and male reproductive problems hypothesized in scientific papers.

Sharpe, R.M. Falling sperm counts in men - Is there an endocrine cause? Journal of Endocrinology 137:357-360 (1993).

Sharpe, R.M. and N.F. Shakkebaek. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet 341:1392-95 (1993).

Sewage effluent shown to have estrogenic effects on fish (rainbow trout).

Jobling, S. and J.P. Sumpter. Detergent components in sewage effluent are weakly oestrogenic to fish: An in vitro study using rainbow trout (Oncorhyncus mykiss) hepatocytes. Aquatic Toxicology, 27:361-372 (1993).

Assault on the Male. A BBC documentary discussing the possible link between endocrine-disrupting chemicals and reproductive problems observed in both wildlife and humans worldwide.


Estrogens in the Environment III: Global Health Implications (January 9 - 11). Conference sponsored by the National Institute of Environmental Health Sciences.

Proceedings: Estrogens in the Environment III: Global Health Implications. Environmental Health Prospectives 103(Supplement 7):October. (1995).


Hormone Related Toxicants in the Environment. (October). 1st meeting of the National Academy of Sciences, National Research Council panel study.

Male Reproductive Health and Environmental Chemicals with Estrogenic Effects published by Ministry of Environment and Energy, Denmark. Report summarizes current scientific evidence on male human and wildlife reproductive disorders and environmental chemicals with estrogenic effects.

Toppari, J., J. Larsen, P. Christiansen, et. al. Male Reproductive Health and Environmental Chemicals with Estrogenic Effects. Miljoprojekt, nr. 290. Copenhagen: Ministry of Environment and Energy, Danish Environmental Protection Agency. (1995).


Our Stolen Future published. Book documents research on endocrine disrupting chemicals.

T. Colborn, D. Dumanoski and J.P. Myers. Our Stolen Future. New York: Penguin Books. (1996).

Combinations of estrogenic chemicals are shown to be synergistic in yeast estrogen system.

Arnold, S.F. et al. Synergistic activation of estrogen receptor with combinations of environmental chemicals. Science 272(June 7):1489-92 (1996).

Withdrawn, Science 277(July 25):459-463, 1997.

Online July 1996: Environmental Estrogens Internet site, maintained by the Center for Bioenvironmental Research at Tulane and Xavier Universities, New Orleans, Louisiana, USA. This site features background information on environmental estrogens, links to other pertinent Internet sites, bibliographies and reference lists and information on upcoming events.

Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) established in the fall to advise the US Environmental Protection Agency on a strategy for screening and testing chemicals and pesticides for their potential to disrupt endocrine functions in humans and wildlife.

Health Effects of Contemporary-use Pesticides: The Wildlife/Human Connection (September 27-29, Racine, Wisconsin). Second Wingspread Workshop convened by Theo Colborn and sponsored by the World Wildlife Fund and the Johnson Foundation. Presentations focused on how pesticides affect the endocrine system, the immune system and behavior.

Proceedings: Chemically induced alterations in functional development and reproduction of fishes. Rolland, RM., M Gilbertson, and R Peterson, eds. Pensacola, FL: Society of Environmental Toxicology and Chemistry (SETAC). 1997. 220 pp. Thirteen chapters assess the current threat to fish populations from environmental chemicals and present original research/reviews and ecoepidemiological research on the effects of environmental chemicals on freshwater and saltwater fish populations.

Food Quality Protection Act (FQPA) of 1996 enacted August 3, 1996.


Estrogens in the Environment IV: Linking Fundamental Knowledge, Risk Assessment, and Public Policy (July 20 - 23). Conference sponsored by the National Institute of Environmental Health Sciences.

Proceedings: Estrogens in the Environment IV: Linking Fundamental Knowledge, Risk Assessment, and Public Policy. Environmental Health Prospectives.

The first Arctic assessment report is released evaluating the current state of contamination in the Canadian Arctic environment and identifying contaminant sources and transport.

Canadian Arctic Contaminants Assessment Report. Indian and Northern Affairs Canada. (1997) 460 pp.


National Public Television's FRONTLINE airs the hour-long show Fooling with Nature Tuesday, June 2, 1998. Interviews with scientists, politicians, activists and business officials explore concerns that environmental toxins may be altering endocrine systems in animals and humans.

July 12 - 17: Gordon Research Conference on Environmental Endocrine Disruptors at Plymouth State College, Plymouth, New Hampshire.Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) makes final recommendations for a screening program then dissolves after two years of effort.

The Endocrine Disruptor Screening Program is convened by the US Environmental Protection Agency to use EDSTAC's final recommendations from September 1998 to develop a screening program with methods and procedures to detect and characterize endocrine activity of pesticides, commercial chemicals, and environmental contaminants and enabling the agency to gather the information necessary to identify endocrine disruptors and take appropriate regulatory action.


A National Research Council report (released August 3) published as a book finds that even though there is evidence of adverse effects from exposure to high levels of hormonally active substances, more research is needed to determine the compounds' overall health and ecological effects as well as their impact at low concentrations.

National Research Council. Hormonally active agents in the environment. Washington:National Academy Press. (1999). 560 pp


Global ban of 12 persistent organic pollutants (POPs) is solidified in a global treaty during a summit in Johannesburg, South Africa, in early December.Scientists begin monitoring and assessing the health risk of pharmaceutical and personal care products from treated and untreated sewage that end up in surface and groundwater used for drinking water.

Potera, C. Drugged drinking water. Environmental Health Perspectives, 108(10):446. (2000).

Book reviewing how endocrine disrupting chemicals became a social and political concern is published.

Krimsky, S. Hormone Chaos: The Scientific and Social Origins of the Environmental Endocrine Hypothesis. Baltimore:John Hopkins University Press. (2000). 256 pp.


Female Chinook salmon in wild populations are found to be genetically male and researchers speculate hormone-altering chemicals from land runoff up river or water temperature changes from hydroelectric dams are the two most likely suspects.

Nagler, JJ, J Bouma, GH Thorgaard, and DD Dauble. High incidence of a male-specific genetic marker in phenotypic female chinook salmon from the Columbia River. Environmental Health Perspectives, 109(1):67-69 (2001).

Center for Disease Control and Prevention (CDC) published the first National Exposure Report Card. The agency measured a variety of toxic substances in people's blood and urine to determine the kinds and amounts of chemicals found in the US population in an effort to better understand chemical risks.

More research finds that penta bromo diphenyl ether or PBDE is widely contaminating wildlife, the environment, and people.

Hale, RC et al. Polybrominated diphenyl ether flame retardants in Virginia freshwater fishes (USA). Environmental Science and Technology, 35(23, December 1):4585-4591 (2001).


The US Environmental Protection Agency (EPA) will ban lumber treated with the wood preservative chromated copper arsenate (CCA) for home use in the US by January 1, 2004.

The National Toxicology Program's (NTP) lists steroidal estrogens as a known cause of cancer in humans.

The Hormone Disruption Research Act of 2002, a bill to authorize the National Institute of Environmental Health Sciences (NIEHS) to conduct and coordinate a research program on hormone disrupting chemicals, was introduced to the US House of Representatives on May 9, 2002, by Rep. Louise Slaughter (New York, Democrat).

Frogs exposed during development to low levels of atrazine, the most widely used pesticide in the US, are feminized and hermaphrodites, according to published research.

Hayes, TB, et al. Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses. Proceedings of the National Academy of Sciences, 99(8, April 16): 5476-5480 (2002).

Hayes, TB, K Haston, M Tsui, A Hoang, C Haeffele, and A Vonk. Feminization of male frogs in the wild. Nature, 419, 895-896 (2002).

The synthetic hormone diethylstilbestrol (DES) is shown for the first time to affect a third generation in humans.

Klip, H. et al. Hypospadias in sons of women exposed to diethylstilbestrol in utero: A cohort study. The Lancet, 359(Mar 30):1102-1107 (2002).

A US Geologic Survey (USGS) study found low concentrations of human and animal drugs, natural and synthetic hormones, detergents, plasticizers, insecticides, and fire retardants in most of the 139 stream sites sampled in 30 states during 1999-2000.

Kolpin, DW, et al. Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999-2000: A national reconnaissance. Environmental Science & Technology, 36(6, Mar 15):1202-1211 (2002).

Velagaleti, R, et al. Impact of current good manufacturing practices and emission regulations and guidances on the discharge of pharmaceutical chemicals into the environment from manufacturing, use, and disposal. Environmental Health Perspectives, 110(3):213-22 (2002).

A global assessment of endocrine disrupter research finds that some wildlife species suffer adverse health effects from exposure to endocrine disrupting chemicals (EDCs) warranting concern for human health but strong evidence linking exposure to health problems is missing due to incomplete and insufficient data, understanding, and knowledge. The report recommends international research programs to prioritize and gather information about this global priority issue.

Global Assessment of the State-of-the-Science of Endocrine Disruptors. Report. International Programme on Chemical Safety (IPCS), World Health Organization. 180 pp. 12 August 2002. Online at http://www.who.int/pcs/emerg_site/edc/global_edc_TOC.htm.


Researchers find for the first time that human sperm quality varies regionally with lower quality in Midwestern rural farming areas and higher quality in urban areas suggesting environmental factors such as pesticides might affect sperm health.

Swan, SH et al. Geographic differences in semen quality of fertile US males. Environmental Health Perspectives, 111(4):414-420 (2003). doi:10.1289/ehp.5927 available via http://dx.doi.org/ (Online 11 November 2002).