1872 Polyvinyl chloride (PVC) synthesized by German chemist Eugen Baumann.
Baumann, E. (1872)“Ueber einige Vinylverbindungen” (On some vinyl compounds), Annalen der Chemie und Pharmacie, 163: 308–322.
1874 DDT synthesized by Austrian chemist Othmar Zeidler.
1876 Polychlorinated biphenyls (PCBs) synthesized by German chemist Oscar Doebner.
Doebner, O.G. (1876) “Constitution der Diphenyldisulfosäure und ihrer Umwandlungsprodukte,” Berichte der deutschen chemischen Gesellschaft. 9 (1): 129–131.
1891 Bisphenol A (BPA) synthesized by Russian chemist Aleksandr Dianin.
Reported in a scientific paper in 1905 by Theodor Zincke from Marburg University, Germany.
1900 PVC use attempted by Ivan Ostromislensky and Fritz Klatte of the German chemical company Griesheim-Elektron. Both attempted to use PVC in commercial products, but difficulties in processing the rigid, sometimes brittle polymer thwarted their efforts.
Semon, W. L., and Stahl, G. A. (1981). History of Vinyl Chloride Polymers. Journal of Macromolecular Science: Part A – Chemistry, 15(6), 1263–1278.
1904 Lead paint linked to childhood lead poisoning by Australian J. Lockhart Gibson, one of the the first to do so.
Markowitz, G. and Rosner, D. (2000). “Cater to the Children”: The Role of the Lead Industry in a Public Health Tragedy, 1900-1955. Am J Public Health. 90(1), 36–46.
1907 Bakelite, the first successful commercial synthetic plastic, synthesized by chemist Leo Baekeland (“The Father of the Plastics Industry”) in Yonkers, New York.
1923 The hormone estrogen identified
Allen, E. and E.A. Doisy. (1923). 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.
1929 Commercial production of PCBs by Swann Chemical Company and then in 1935 by Monsanto Chemical Company, with manufacturing taking place in Anniston, Alabama.
Kodavanti, P. (2017). Polychlorinated Biphenyls (PCBs). Neuroscience and Biobehavioral Psychology. Elsevier, Amsterdam, Holland.
1929 The hormone progesterone identified
Corner G.W., and Allen, W.M. (1929). “Physiology of the Corpus Luteum, II: Production of a Special Uterine Reaction (Progestational Proliferation) by Extracts of the Corpus Luteum.” American Journal of Physiology. 88 326–339.
Piette, P. (2018). The history of natural progesterone, the never-ending story. Climacteric, 21(4), 308–314.
1938 Synthetic estrogen diethylstilbestrol (DES) created by Dr. Leon Goldberg and Sir Edward Charles Dodds. DES was first prescribed to supplement a pregnant woman’s natural estrogen production, and approved by the FDA in 1941. In the U.S., an estimated 5-10 million people were exposed to DES between 1938-1971.
Dodds, E., Goldberg, L., Lawson, W. et al. (1938). OEstrogenic Activity of Certain Synthetic Compounds, Nature, 141, 247–248.
Nancy Langston, (2010). Toxic Bodies: Hormone Disruptors and the Legacy of DES. Yale University Press, New Haven, CT; DES Action timeline.
1939 DDT used as an insecticide. Swiss chemist Paul Hermann Müller discovered that DDT had insecticidal properties. DDT was initially used to successfully combat malaria, typhus, and other diseases among both military and civilian populations, and then used for insect control in crop and livestock production, homes, and gardens.
1941 Teflon patented by Kinetic Chemicals, a partnership of General Motors and DuPont. DuPont began marketing the polymer commercially in 1944 and filed to trademark it under the name of Teflon in February 1945.
Hagley Museum and Library. On this date (February 4) in 1941, Kinetic Chemicals, Inc., a…
World War 2 Widespread use of chemicals
1945 Rachel Carson proposes to write a story on the impact of DDT on fish and wildlife to Reader’s Digest, but was turned down.
Source: Rachel Carson to Harold Lunch, July 15, 1945, Rachel Carson Papers, Beinecke Library, Yale University. Cited in Douglas Brinkley, D. (2022). The Silent Spring Revolution, Harper Collins, New York, p. 51.
1947 DES granted FDA approval for use as a miscarriage preventative (it was used earlier than this off-label).
Smith O. W. (1948). Diethylstilbestrol in the prevention and treatment of complications of pregnancy. American journal of obstetrics and gynecology, 56(5), 821–834.
1948 Nobel Prize in Physiology or Medicine awarded to Paul Hermann Müller “for his discovery of the high efficiency of DDT as a contact poison against several arthropods.”
1962 Silent Spring, by Rachel Carson published. This seminal book focused on DDT, other pesticides and other synthetic chemicals causing eggshell thinning, deformities and population declines in wildlife.
1962 Agent Orange sprayed in Southeast Asia by the U.S. military from 1962 to 1971 during the Vietnam War to remove the leaves of trees and other dense tropical foliage. It was contaminated with dioxin.
1963 DDT production peaked in the U.S.
1964 Early life exposure to estrogen caused cancerous changes in mice.
Takasugi, N., Bern, H. A. (1964). Tissue Changes in Mice With Persistent Vaginal Cornification Induced by Early Postnatal Treatment With Estrogen, JNCI: Journal of the National Cancer Institute, 33(5), 855–865.
1966 The National Institute of Environmental Health Sciences (NIEHS) began as the Division of Environmental Health Sciences within the NIH. In 1969, the division was elevated to full NIH institute status.
1968 Yushō disease mass poisoning in Japan when rice bran oil produced by the Kanemi Company was contaminated with PCBs and polychlorinated dibenzofurans (PCDFs), leading to endocrine-related health effects.
Aoki Y. (2001). Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans as endocrine disrupters–what we have learned from Yusho disease. Environmental research, 86(1), 2–11.
1969 Cuyohoga River burns in Ohio, raising environmental awareness.
1970 First Earth Day
1970 EPA established
1970 PCB production peaks in the U.S.
1971 Mrs. Penny Stone questioned her doctor as to whether DES had caused her daughter’s cancer, and after denials, the doctors finally decided to investigate. This led to the important publication finding that the daughters of DES treated mothers had an increased risk of a rare vaginal cancer. FDA recommended not prescribing DES during pregnancy, but did not ban it.
Herbst, A. L., Ulfelder, H., & Poskanzer, D. C. (1971). Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. The New England journal of medicine, 284(15), 878–881.
DES Action: Meet the Woman who was the First to Connect DES and Cancer.
1971 Dioxin sprayed on Times Beach and Missouri horse arenas. Chemical waste from a local factory was mixed with waste motor oil and sprayed as a dust-suppressant on the roads of Times Beach and in horse arenas. Tetrachlorodibenzodioxin (TCDD) was later identified as the culprit that sickened humans and killed dozens of horses and many other animals at the horse arenas. The town of Times Beach was evacuated in 1983 and is now a “ghost town.”
Carter, C. D., Kimbrough, R. D., Liddle, J. A., Cline, R. E., Zack, M. M., Jr, Barthel, W. F., Koehler, R. E., & Phillips, P. E. (1975). Tetrachlorodibenzodioxin: an accidental poisoning episode in horse arenas. Science (New York, N.Y.), 188(4189), 738–740
1972 Lead found to affect IQ. Herbert Needleman, M.D. led pioneering studies providing first clear evidence that lead, even at very low levels, could affect a child’s IQ. Studies by other researchers established the role of low levels of lead in behavioral and neurological disorders. NIEHS support for continued research on the effects was key to establishing limits and, ultimately, bans on lead in gasoline and paint.
Needleman, H. L., Tuncay, O. C., & Shapiro, I. M. (1972). Lead levels in deciduous teeth of urban and suburban American children. Nature, 235(5333), 111–112.
1972 DDT banned for use in the U.S., a decision upheld by courts in 1973.
DDT Ban Takes Effect (EPA).
1973 Michigan PBB incident. A flame retardant mixture of polybrominated biphenyls (PBBs), was accidentally added to livestock feed distributed throughout Michigan. People ate the contaminated food until the animals were culled. Studies continue to find effects in the grandchildren of people who consumed the tainted food.
Carter L. J. (1976). Michigan’s PBB Incident: Chemical Mix-Up Leads to Disaster. Science (New York, N.Y.), 192(4236), 240–243.
Egginton, J. (2009). The Poisoning of Michigan. Michigan State University Press.
Some of the most important findings to come out of the PBB study include associations with:
Early puberty:
Blanck, H. M., Marcus, M., Tolbert, P. E., Rubin, C., Henderson, A. K., Hertzberg, V. S., Zhang, R. H., & Cameron, L. (2000). Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl. Epidemiology (Cambridge, Mass.), 11(6), 641–647.
Urinary/genital problems:
Small, C. M., DeCaro, J. J., Terrell, M. L., Dominguez, C., Cameron, L. L., Wirth, J., & Marcus, M. (2009). Maternal exposure to a brominated flame retardant and genitourinary conditions in male offspring. Environmental health perspectives, 117(7), 1175–1179.
Miscarriage:
Small, C. M., Murray, D., Terrell, M. L., & Marcus, M. (2011). Reproductive outcomes among women exposed to a brominated flame retardant in utero. Archives of environmental & occupational health, 66(4), 201–208.
Breast cancer:
Terrell, M. L., Rosenblatt, K. A., Wirth, J., Cameron, L. L., & Marcus, M. (2016). Breast cancer among women in Michigan following exposure to brominated flame retardants. Occupational and environmental medicine, 73(8), 564–567.
Birth outcomes:
Terrell, M. L., Hartnett, K. P., Lim, H., Wirth, J., & Marcus, M. (2015). Maternal exposure to brominated flame retardants and infant Apgar scores. Chemosphere, 118, 178–186.
1975 The Kepone disaster in Hopewell, Virginia. Workers at Life Science Products Company were poisoned while making the pesticide Kepone (chlordecone). Kepone and its waste materials were dumped into the James River and its tributaries from 1966 to 1975 by Allied Chemical Company and LifeSciences Product Company.
Toxic Dust: The History and Legacy of Virginia’s Kepone Disaster, Virginia Museum of History and Culture.
1976 Seveso Disaster. An industrial accident that resulted in the release of toxic chemicals and high exposure to TCDD to residents in and near Seveso, Italy. Health effects are still being studied, and include mortality, diabetes, cancer, neonatal thyroid function, and lower sperm counts.
Eskenazi, B., Warner, M., Brambilla, P., Signorini, S., Ames, J., & Mocarelli, P. (2018). The Seveso accident: A look at 40 years of health research and beyond. Environment international, 121(Pt 1), 71–84.
1976 Toxic Substances Control Act (TSCA) enacted; it grandfathered in thousands of unevaluated chemicals in commerce at the time.
1977 Pesticide workers develop infertility. A number of cases of infertility were discovered among men working in a California pesticide factory. The suspected cause was exposure to the chemical 1,2-dibromo-3-chloropropane (DBCP).
Whorton, D., Krauss, R. M., Marshall, S., & Milby, T. H. (1977). Infertility in male pesticide workers. Lancet (London, England), 2(8051), 1259–1261.
1977 CPSC bans brominated tris. The Consumer Product Safety Commission banned children’s pajamas treated with the flame retardant brominated tris (tris (2,3-dibromopropyl phosphate), in part due to work by Dr. Arlene Blum.
Blum, A., & Ames, B. N. (1977). Flame-retardant additives as possible cancer hazards. Science (New York, N.Y.), 195(4273), 17–23. [full text link]
1978 Additional flame retardants banned. The flame retardant tris-(1,3-dichloro-2-propyl)-phosphate (TDCPP), a “regrettable substitute” for brominated tris, was found to be a carcinogen, and also banned from children’s pajamas. It is still in widespread use in other products.
Gold, M. D., Blum, A., & Ames, B. N. (1978). Another flame retardant, tris-(1,3-dichloro-2-propyl)-phosphate, and its expected metabolites are mutagens. Science (New York, N.Y.), 200(4343), 785–787.
1978 National DES Task Force created by the U.S. Secretary of the Department of Health, Education & Welfare. It was charged with reviewing all aspects of the DES problem and with making recommendations for research and health care of the people exposed. DES Action USA was founded and incorporated, as a national non-profit consumer group for individuals exposed to DES.
1979 First “Estrogens in the Environment” symposium at NIEHS, organized by Dr. John McLachlan. The objectives were to “determine what an estrogen is, how it works, and what effect estrogenic substances might have on human health.”
1979 Manufacture of PCBs banned and uses curtailed in U.S.
EPA Bans PCB Manufacture; Phases Out Uses (EPA Press Release)
1979 Yucheng Rice Oil Contamination. In Taiwan, PCBs and PCDFs leaked into rice oil and intoxicated 2000 people who had consumed the oil, leading to numerous health effects.
Guo, Y. L., Lambert, G. H., Hsu, C. C., & Hsu, M. M. (2004). Yucheng: health effects of prenatal exposure to polychlorinated biphenyls and dibenzofurans. International archives of occupational and environmental health, 77(3), 153–158.
1984 Birth defects linked to Agent Orange exposure in veterans’ babies.
Vietnam veterans’ risks for fathering babies with birth defects. Erickson JD, Mulinare J, McClain PW, Fitch TG, James LM, McClearn AB, Adams MJ Jr. JAMA. 1984 Aug 17;252(7):903-12.
1985 Estrogens in the Environment II: Influences on Development Symposium, organized by Dr. John McLachlan.
Schiff I, Ravnikar VA. Estrogens in the Environment II: Influences on Development. JAMA. 1987;258(10):1397.
1985 EPA classified TCDD as a likely human carcinogen
Source: Dioxin (Environmental Working Group).
Seminal book Our Stolen Future published, bringing endocrine disruption to the general public.
Theo Colborn, Dianne Dumanoski, Pete Myers, Our Stolen Future; Are We Threatening Our Fertility, Intelligence, and Survival? A Scientific Detective Story (New York: Penguin Books).
Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) formed by EPA. EDSTAC was a federal advisory committee to make recommendations to EPA on how to develop an EDC screening program and take action to protect public health. EDSTAC was composed of representatives from industry, government, environmental and public health groups, worker safety groups, and academia.
Their final report was published in 1998.
Alligators with small penises: Dr. Lou Guillette, Jr. found that male alligators in Florida’s polluted Lake Apopka have strikingly low testosterone levels and abnormally small penis sizes.
Guillette LJ Jr, Pickford DB, Crain DA, Rooney AA, Percival HF. Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment. Gen Comp Endocrinol. 1996 Jan;101(1):32-42.
PCBs and IQ: Psychologists Sandra and Joe Jacobson report that exposure to high levels of PCBs before birth can lead to as much as a 6.2 point IQ deficit in children.
Jacobson JL, Jacobson SW. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N Engl J Med. 1996 Sep 12;335(11):783-9.
1998 Fooling with Nature: Are man-made chemicals in the environment hazardous to humans? What does science know? airs on Frontline on PBS.
First Gordon Research Conference (GRC) on Environmental Endocrine Disruptors. Held every two years since then.
Children’s Environmental Health Centers around the country funded by NIEHS and EPA.
Program on endocrine disruptors established in Japan, by Dr. Taisen Iguchi of Japan’s National Institute for Basic Biology.
PFOA in Parkersburg: When hundreds of Wilbur Tennant’s cows in Parkersburg, WV became sick or died, he sued 3M with attorney Rob Billot. Bilott uncovered DuPont internal documentation of PFOA exposure in plant workers and groundwater, as portrayed in the 2019 feature film Dark Waters.
Parkersburg, West Virginia, PFAS Project Lab
EPA’s Science to Achieve Results (STAR) Program on Endocrine Disruptors aimed to develop a government-wide coordinated effort to “stimulate innovative, multi-disciplinary research to address high priority scientific uncertainties related to the potential adverse effects of endocrine disrupting chemicals (EDC) in humans and wildlife.”
EDSTAC recommendations published: The Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) made final recommendations for a screening program to Congress then dissolves after two years of effort.
1999 First Environment and Hormone (e-hormone) conference held at Tulane, organized by Dr. John McLachlan.
No threshold or safe levels: This study showed that there was no threshold when an estrogen was added to a biological system that already had an above threshold level of estradiol, falsifying the assumption by the FDA and EPA that all non-genotoxic chemicals had a threshold below which no adverse effects occurred. The threshold assumption has still not been abandoned by regulatory agencies:
Sheehan DM, Willingham E, Gaylor D, Bergeron JM, Crews D. No threshold dose for estradiol-induced sex reversal of turtle embryos: how little is too much? Environ Health Perspect. 1999 Feb;107(2):155-9.
2000 Early puberty found in girls exposed to PBB in early life.
Blanck, H. M., Marcus, M., Tolbert, P. E., Rubin, C., Henderson, A. K., Hertzberg, V. S., Zhang, R. H., & Cameron, L. (2000). Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl. Epidemiology (Cambridge, Mass.), 11(6), 641–647.
National Toxicology Program (NTP) hosted a meeting on low doses in endocrine disruption.
Melnick R, Lucier G, Wolfe M, Hall R, Stancel G, Prins G, Gallo M, Reuhl K, Ho SM, Brown T, Moore J, Leakey J, Haseman J, Kohn M. Summary of the National Toxicology Program’s report of the endocrine disruptors low-dose peer review. Environ Health Perspect. 2002 Apr;110(4):427-31.
First Copenhagen Workshop on Endocrine Disruptors (COW) meeting focused on steroids used in beef production.
RFP issued on Endocrine Disruptors: Epidemiologic Approaches by NIEHS, EPA, NIOSH, NCER, NCI, and CDC.
FDA withdrew approval of DES so it could no longer be prescribed for human use.
Hormonal chaos: The Scientific and Social Origins of the Environmental Endocrine Hypothesis book by Dr. Sheldon Krimsky published. Reviewed in Nature by Dr. Taisen Iguchi.
2001 Stockholm Convention on Persistent Organic Pollutants signed to restrict or eliminate the production and use of numerous persistent organic pollutants (POPs) (e.g., PCBs, dioxins, DDT), with more POPs added in subsequent years.
Dr. Terry Collins argues that achieving sustainable chemistry requires a sea change in the chemical community:
Collins, T. Toward Sustainable Chemistry Science, 5 Jan 2001, Vol 291, Issue 5501, pp. 48-49.
Dr. Niels Skakkebaek presented the hypothesis of testicular dysgenesis syndrome for the first time:
Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001 May;16(5):972-8.
Dr. Ana Soto finds that fetal exposure to BPA alters the mammary gland in mice:
Markey, C. M., Luque, E. H., Munoz De Toro, M., Sonnenschein, C., & Soto, A. M. (2001). In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland. Biology of reproduction, 65(4), 1215–1223.
2002 Global Assessment of the State-of-the-Science of Endocrine Disruptors report published by the joint International Programme on Chemical Safety (IPCS) of the World Health Organization (WHO), the United Nations Environment Programme (UNEP), and the International Labour Organisation (ILO).
Fetal basis of adult disease: Role of the environment program by NIEHS funded grants and jump-started research on developmental programming and EDCs.
NIEHS Conference on EDCs and Thyroid Function
Watch Day 2: Thyroid Hormone and Brain Development: Translating Molecular Mechanisms to Population Risk.
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.
Dr. Tyrone Hayes found low dose effects of the pesticide atrazine on frogs:
Hayes TB, Collins A, Lee M, Mendoza M, Noriega N, Stuart AA, Vonk A. Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5476-80.
Multigenerational effects: DES was shown to affect a third generation in humans:
Klip H, Verloop J, van Gool JD, Koster ME, Burger CW, van Leeuwen FE; OMEGA Project Group. Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study. Lancet. 2002 Mar 30;359(9312):1102-7.
Science Communication Network founded by Dr. Pete Myers and Amy Kostant.
Environmental Health News and Environmental Health Sciences founded by Dr. Pete Myers.
2012 State of the Science of Endocrine Disrupting Chemicals by WHO, in collaboration with international experts.
CLARITY-BPA research program launched by FDA, NIEHS, and NTP.
Schug, T. T., Heindel, J. J., Camacho, L., Delclos, K. B., Howard, P., Johnson, A. F., Aungst, J., Keefe, D., Newbold, R., Walker, N. J., Thomas Zoeller, R., & Bucher, J. R. (2013). A new approach to synergize academic and guideline-compliant research: the CLARITY-BPA research program. Reproductive toxicology (Elmsford, N.Y.), 40, 35–40.
Issues of low doses and non-monotonicity receives focus
Vandenberg, L. N., Colborn, T., Hayes, T. B., Heindel, J. J., Jacobs, D. R., Jr, Lee, D. H., Shioda, T., Soto, A. M., vom Saal, F. S., Welshons, W. V., Zoeller, R. T., & Myers, J. P. (2012). Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocrine reviews, 33(3), 378–455.
EU Biocidal Products Regulation (EU) No 528/2012 and Commission Regulation (EU) 2017/2100. Excludes pesticides that have: “ active substances which, on the basis of the criteria specified ….are considered as having endocrine-disrupting properties that may cause adverse effects in humans…”
Food Packaging Forum founded by Dr. Jane Muncke.
Programmed to be Fat airs on The Nature of Things.
2014 Endocrine Disrupting Chemicals: Threats to Human Health a guide for public interest organizations and policymakers from the Endocrine Society and the International Pollutants Elimination Network (IPEN).
Navigation Guide methodology applied to PFAS by Dr. Tracey Woodruff:
Lam J, Koustas E, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. The Navigation Guide – evidence-based medicine meets environmental health: integration of animal and human evidence for PFOA effects on fetal growth. Environ Health Perspect. 2014 Oct;122(10):1040-51.