Application of U.S. EPA's Proposed Cancer Risk Assessment Guidelines to the Hazard Characterization of Mercury Species. R. Schoeny, National Center for Environmental Assessment-Cincinnati, U.S. EPA, Cincinnati, OH 45268
U.S. EPA has proposed revisions to its Guidelines for Carcinogen Risk Assessment (Federal Register FR61(79):17960-18011, 4/22/96). Revisions include use of narrative vs. alphanumeric classifications for weight of evidence and the increased use of data on mode of action to make integrated judgements on hazard characterization and dose response assessment. U.S. EPA evaluated data on carcinogenicity of three chemical species of mercury: elemental, inorganic and methylmercury. Elemental mercury was categorized on the Integrated Risk Information System (IRIS) as Group D, unable to classify and inorganic and methylmercury as Group C, possible human carcinogen. Under the Proposed Guidelines it is likely that elemental mercury would still be considered an agent for which likelihood of carcinogenicity cannot be determined; there is only one animal study, wherein metallic mercury was given by injection. In gavage studies with inorganic mercury, renal tumors were observed in mice and forestomach and thyroid tumors in rats; there is no clear evidence of genotoxicity. The relevance of both the forestomach and the thyroid tumors to human risk from mercury ingestion has been questioned. LOAELs for immunotoxic changes leading to kidney damage were observed at levels two to three orders of magnitude lower than those for tumors. A categorization for inorganic mercury should indicate that while inorganic mercury is an animal carcinogen at relatively high doses, it is unlikely to be carcinogenic for humans when ingested at concentrations typically reported in foods. Data for methylmercury are similar, but as there is strong evidence of chromosomal effects (including evidence in humans), the level of concern is somewhat greater that it be a human carcinogen at high levels of exposure.