An analysis of the Gene-Tox Carcinogen Data Base.
The Gene-Tox Carcinogen Data Base is an evaluated source of cancer data on 506 chemicals selected in part for their previous assessment in genetic toxicology bioassays. This data base has been analyzed for the distribution of these chemicals into chemical classes. The major chemical classes (6% or greater of the total data base) are: acyl-, alkyl-, and aryl-halides; alcohols and phenols; aliphatic and aromatic amines, amides, and sulfonamides; benzene-ring-containing chemicals; organo-lead, -mercury, -phosphorous compounds, metals and derivatives, phosphoric acid esters, and phosphoramides; and polycyclic aromatic hydrocarbons. Cancer studies representing a subset of the Gene-Tox Carcinogen Data Base, 199 chemicals which were rated as Sufficient Positive/Negative or Limited Positive/Negative, were examined for distribution of those studies by animal species, gender, route of chemical administration, duration of study, major tumor sites, and major tumor types. These analyses revealed that the Gene-Tox Carcinogen Data Base contains a large number of lifetime studies involving the rat and mouse treated by oral routes of administration. The major organs that were targets were: liver, lung, skin, forestomach, bladder, and mammary gland, while the major tumor types were: carcinoma, sarcoma, papilloma, and adenoma. Chemicals in the data base have been assessed for species-specific carcinogenic effects, and these results indicate that for mice and rats there is a high correspondence (85%). This number is higher than that (71%) reported by Tennant et al. (1986) based on the recent results of 72 chronic cancer bioassays performed by the National Toxicology Program. This difference is probably based on the nature of the chemicals selected for inclusion in both data bases. Although the absolute value of this correspondence is unknown, it would seem to be within this range. When chemicals in the Gene-Tox Carcinogen Data Base were examined for their previous evaluation in 73 genetic toxicology bioassays, only 26 of these bioassays had 30 or more chemicals. In these 26 bioassays, the prevalence of positive chemicals was generally greater than 80-90%. This suggests that a thorough evaluation of genetic toxicology bioassays in regard to their ability to predict carcinogenic effects in animals is premature at this time.
Nesnow
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Genetic Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Bergman
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D000818:Animals; D001681:Biological Assay; D002273:Carcinogens / Q000008:administration & dosage / Q000145:classification; D004249:DNA Damage; D007256:Information Systems; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000145:classification / Q000473:pathology; D051381:Rats; D013329:Structure-Activity Relationship
D002273:Carcinogens