Role of epidemiologic studies in evaluating the carcinogenicity of chromium compounds

Epidemiologic and animal studies have identified intermediately-soluble chromates as human carcinogens. Epidemiologic studies also provide moderately strong evidence to conclude that chromates do not cause cancer at sites other than the respiratory tract. This information, combined with the evidence from animal studies and in vitro experiments, has led to the conclusion that chromates do not present a carcinogenic risk from ingestion. Unfortunately, epidemiologic studies have not provided definitive answers to other questions: (i) does trivalent chromium present a cancer risk?; (ii) is there a threshold for carcinogenic effects?; and (iii) what is the appropriate model for predicting cancer risk? Mechanistic research with supporting evidence from animal studies has provided the most useful information to answer these questions. Working hypotheses are: (i) trivalent chromium is not a carcinogen; (ii) there are probably substantial differences in carcinogenic potency between chromates, with the water-soluble compounds having lower potency than intermediately-soluble compounds; (iii) only respiratory tract cancers are caused by exposure to chromates, and ingestion and chromates does not constitute a carcinogenic risk; (iv) there is probably a threshold for carcinogenic effects from chromium due to detoxification mechanisms and lack of bioavailability of low doses; and (v) currently used models for quantitative risk assessment (e.g. the low dose linearized multi-stage model) are inappropriate to predict low dose cancer risks from exposure to chromates.