IARC and HHS lists of carcinogens: regulatory use based on misunderstanding of the scope and purpose of the lists.
In the last two decades there has been a tremendous increase in data on carcinogenic activity in experimental animals. While there have been few additions to the list of human carcinogens based on human data, the number of carcinogens based on animal data continues to increase unabated. The International Agency for Research on Cancer (IARC) list of carcinogens grew out of the IARC Monograph Series. The evidence classification system used to prepare the IARC lists in 1980, 1982, and 1988 is based on the sufficiency, i.e., strength, of the evidence of carcinogenic activity in one or more studies, not a full weight-of-the-evidence evaluation of all relevant data. Titles of categories of animal evidence referring to human risk potential were based on a presumption: "for practical purposes . . . as if." No evaluation was made of the predictive relevance of animal data to human risk. The IARC listing did not involve evaluation of potency or mechanism and was intended as a useful input but not as a basis for regulatory or legislative decisions. The Department of Health and Human Services (HHS) lists in the Annual Reports on Carcinogens are selected from the IARC lists and from reports of positive bioassay experiments conducted by the National Toxicology Program (NTP). The reports on the NTP bioassays relate to the strength of the evidence in each experiment and recognize that a "wider analysis" is necessary for determination of human risk. Because of a misunderstanding of the limited scope of the analysis involved, the IARC and HHS lists have recently been used as a basis for legislative and regulatory decisions. Examples of unanticipated use of the lists as triggers for regulatory and legislative decisions will be discussed. Some recommendations to mitigate the consequences of past unanticipated use of the lists and to prevent further misuse are discussed.