On the carcinogenicity of cadmium by the oral route

Cadmium and cadmium compounds are carcinogenic both by inhalation and by injection. For purposes of risk assessment, a prudent public health approach has been that, if a chemical has been demonstrated to be carcinogenic by one route, it should be considered carcinogenic by all routes. This policy has been questioned for several toxic metals including cadmium. After reviewing the literature on cadmium carcinogenicity and genotoxicity, we think that cadmium should be considered noncarcinogenic by the oral route. The bases for this decision included: (1) a database for genotoxicity of cadmium with more negative test results than positive results and with most positive results in in vitro tests, indicating that cadmium has limited genotoxicity; (2) some epidemiologic evidence of respiratory tract cancer and prostatic cancer in people occupationally exposed to airborne cadmium but no reliable evidence of gastrointestinal tract cancers in workers; and (3) a large dietary oncogenicity study in rats of cadmium chloride at several dose levels, including a maximally tolerated dose (50 ppm) in males, which showed no increase of tumors due to cadmium ingestion in all of the 19 tissues examined. The conclusion that an agent, which has been shown to be carcinogenic by one route of exposure, is not carcinogenic by a second route should be made only in the presence of robust data which indicate the lack of effect via the second route of exposure.