The improper handling and dumping of the substance (including the waste materials generated in its manufacturing process) into the nearby James River (U.S.) in the 1960s and 1970s drew national attention to its toxic effects on humans and wildlife.

After two physicians, Dr. Yi-nan Chou and Dr. Robert S. Jackson of the Virginia Health Department, notified the Centers for Disease Control that employees of the company had been found to have toxic chemical poisoning, LifeSciences voluntarily closed its plant on 4 July 1975, and cleanup of the contamination began and a 100-mile section of the James River was closed to fishing while state health officials looked for other persons who might have been injured.

[10] Chlordecone can accumulate in the liver and the distribution in the human body is regulated by binding of the pollutant or its metabolites to lipoproteins like LDL and HDL.

In July 1975,[16] Virginia Governor Mills Godwin Jr. shut down the James River to fishing for 100 miles, from Richmond to the Chesapeake Bay.

[17] Due to the pollution risks, many fishermen, marinas, seafood businesses, and restaurants, along with their employees along the river suffered economic losses.

[20][21] Despite a 1990 ban on the substance in mainland France, the economically powerful banana planters lobbied intensively to obtain a waiver to keep using Kepone until 1993.

A 2018 large-scale study by the French public health agency, Santé publique France, shows that 95% of the inhabitants of Guadeloupe and 92% of those of Martinique are contaminated by the chemical.