The Delaney clause was a provision in the amendment which said that if a substance were found to cause cancer in man or animal, then it could not be used as a food additive.

When the law was passed, "neither advocates nor opponents of the policy, including FDA officials, believed it would have broad application, for only a handful of chemicals had then been shown to be animal carcinogens.

"[2] The Delaney Clause was invoked in 1959 when Arthur Sherwood Flemming, the Secretary of the Department of Health, Education and Welfare issued a statement advising the public about the possible contamination of substantial quantities of cranberries in Oregon and Washington with the herbicide aminotriazole, which the FDA had recently determined was a carcinogen (see Cranberry scare of 1959).

As analytical chemistry became more powerful and able to detect smaller quantities of chemicals, and as chemicals became more widely used, regulatory agencies had an increasingly difficult time administering the Delaney Clause as it "recognizes no distinctions based on carcinogenic potency and, at least in theory, it applies equally to additives used in large amounts and to those present at barely detectable levels.

[2] In 1988 the United States Environmental Protection Agency eased restrictions on several pesticides which posed a "de minimis" risk to humans.

This change was challenged by the Natural Resources Defense Council, and overturned in 1992 by the Ninth Circuit Court of Appeals.