Theodora Colborn studied how chemicals affect organisms as they develop and reproduce during the twentieth and twenty first centuries in the US. By the 1940s, researchers had reported that chemicals from agricultural and industrial processes affected how wild organisms developed, but in 1991, Colborn organized the Wingspread Conference in Racine, Wisconsin, at which a group of scientists classed these chemicals as environmentally harmful substances. Colborn and her colleagues called those chemicals endocrine disruptors, as they mimic or block the body's endocrine system. After scientists identified these chimicals and showed that they harm humans and wildlife, US Congress passed several acts to regulate these chemicals and to protect both wildlife and humans from their harmful effects.

Diethylstilbestrol (DES) is an artificially created hormone first synthesized in the late 1930s. Doctors widely prescribed DES first to pregnant women to prevent miscarriages, and later as an emergency contraceptive pill and to treat breast cancer. However, in 1971, physicians showed a link between DES and vaginal cancer during puberty in the children of women who had taken DES while pregnant. Consequently, the US Food and Drug Administration (FDA) banned its use during pregnancy. In the late 2000s, several studies showed that the grandchildren of women who had consumed DES also suffered medical issues. By the early decades of the twenty-first century, roughly ten million people in the US had been exposed to DES, and three generations of individuals had suffered medical issues due to DES exposure. Researchers class DES as an endocrine disruptor, which affects the form and function of the hormone (endocrine) system.

Published in 1971, Adenocarcinoma of the Vagina: Association of Maternal Stilbestrol Therapy with Tumor Appearance in Young Women, by Arthurs L. Herbst and colleagues, was the first piece of literature connecting maternal use of the drug diethylstilbestrol (DES), also called stilbestrol, with the development of a rare and severe form of vaginal cancer in young women. Diethylstilbestrol was later classified as an endocrine disruptor, a substance that disrupts the hormonal function of the body in those exposed to it during development or later in life. After Herbst and his team established the connection between DES and the occurrence of breast cancer, cervical cancer, infertility, and reproductive abnormalities, the US federal government banned use the drug for pregnant women. The article was published in the New England Journal of Medicine.

Sindell v. Abbott Laboratories was a 1980 California case that established the doctrine of market share liability for personal injury cases. For such liability, when a drug causes personal injury and the manufacturer of the drug cannot be identified, each producer is responsible for paying the settlement in proportion to the percentage of the market they supplied. Judith Sindell and Maureen Rogers brought the case against the producers of diethylstilbestrol (DES), which their mothers had taken during pregnancy to prevent miscarriage and other complications. Sindell and Rogers alleged that their mothers' ingestions of DES during pregnancy later caused Sindell and Rogers to develop cancers at the onset of puberty, but they could not identify the specific manufacturer of the drug. The market share liability ruling in Sindell allowed millions of DES-affected individuals to seek restitution for reproductive cancers caused by prenatal exposure to DES.

In 1996, the US Congress mandated that the US Environmental Protection Agency (EPA) create and regulate the Endocrine Disruptor Screening Program. The program tests industrial and agricultural chemicals for hormonal impacts in humans and in wildlife that may disrupt organisms' endocrine systems. The endocrine system regulates the release of small amounts of chemical substances called hormones to keep the body functioning normally. Some chemicals can impede the endocrine system's function by mimicking or blocking hormone reception, which can disrupt processes of development and reproduction and harm organisms. As of 2017, the Endocrine Disruptor Screening Program is the largest US program to identify and regulate chemicals that affect the normal production of sex hormones like estrogen and androgen, which can have long-term effects on development and reproduction.

In 1948, Olive Watkins Smith published 'Diethylstilbestrol in the Prevention and Treatment of Complications of Pregnancy' in the American Journal of Obstetrics and Gynecology. In 632 women treated with diethylstilbestrol, Smith demonstrated that the drug stimulated the production of progesterone, a hormone that regulates the uterine condition during pregnancy. On the basis of her article, and several follow up articles authored by Smith and her husband, George Van Siclen Smith, physicians around the world began prescribing DES to women at risk for pregnancy complications like miscarriage and premature delivery. However, in 1953, researchers at found that DES did not prevent pregnancy complications. In 1970, researchers linked fetal exposure to DES to rare and severe cancers later in life. Researchers labeled DES as an endocrine disruptor, a substance that disrupts the hormone system of the body across multiple generations.

In the legal case In re Agent Orange Product Liability Litigation of the early 1980s, US military veterans of the Vietnam War sued the US chemical companies that had produced the herbicide Agent Orange, and those companies settled with US veterans out of court. Agent Orange contains dioxin, a chemical later shown to disrupt the hormone system of the body and to cause cancer. As veterans returned to the US from Vietnam, scientists further confirmed that exposure to Agent Orange caused a variety of cancers in veterans and developmental problems in the veterans' children. The veterans and their families held the chemical manufactures of Agent Orange liable for their injuries and the injuries to their children. The chemical companies settled the case out of court in 1984 for $180 million, to be used for medical expenses or compensation for death relating to veterans' exposure to Agent Orange. Agent Orange's use in the Vietnam War affected close to ten million people in the US, including members of the US military directly exposed to it, and their children conceived years after direct exposure.

Developmental Effects of Endocrine-Disrupting Chemicals in Wildlife and Humans, was published in 1993 in Environmental Health Perspectives. In the article, the authors present an account of two decades' worth of scientific research that describes the effects of certain pollutants on the health of wildlife, domestic animals, and humans, particularly when exposure takes place during embryonic growth. The term endocrine disruptor was coined in the article to describe the chemical pollutants that target the development and function of the endocrine system. Since its publication, Developmental Effects has increased research interest in endocrine disruption and has raised awareness among the general public, the scientific community, and government organizations about the effects that some chemicals may have on development and reproduction.