CHEMICALS FOR EVALUATING THE SENSITIVITY AND SPECIFICITY OF REDUCED TRANSGENIC RODENT CANCER BIOASSAY PROTOCOLS

The standard two-species/two-gender lifetime carcinogenicity bioassay protocol is not practical when assessing the possible carcinogenicity of a large number of chemicals. This has led to consideration of reduc ed cancer bioassay protocols (e.g., male rat/female mouse), or to the use of genetically altered rodents that succumb to chemically induced cancer in a fraction of their lifespans. Two uncertainties accompany t hese endeavours. First, that use of reduced protocols may lead to the non-detection of some weak or tissue-specific carcinogens. Second, tha t genetically altered rodents may be so sensitive to chemical disturba nce of homoeostasis that their carcinogen specificity may be low. Such uncertainties lead to the requirement that the modified test protocol s should be validated using appropriate carcinogens and non-carcinogen s. Given that several such studies may take place over the coming year s it seems appropriate that a common pool of chemicals should be agree d upon for this purpose. To this end a selection of human carcinogens, and rodent carcinogens/non-carcinogens defined by the US National Tox icology Program (NTP), have been collected together. Six categories of chemicals are listed: (1) representative human carcinogens; (2) repre sentative trans-species genotoxic carcinogens; (3) all two-species non -carcinogens reported to be negative in the Salmonella mutation assay and lacking structural alerts to electrophilicity; (4) representative single-species/presumed non-genotoxic carcinogens; (5) all two-species non-carcinogens that are mutagens in the Salmonella mutation assay an d which are structurally alerting; (6) all chemicals possessing equivo cal evidence of carcinogenicity and which are both structurally alerti ng and mutagenic to Salmonella. Chemicals in the first four groups pro vide robust calibrants for determining the sensitivity and specificity of reduced/accelerated rodent carcinogenicity bioassay protocols. Che micals in the last two groups may be of value when studying the interf ace between the sensitivity and the specificity of modified rodent car cinogenicity bioassay protocols.