Gold, L.S., and Slone, T.H. Prediction of carcinogenicity from 2 vs. 4 sex-species groups in the Carcinogenic Potency Database. J. Toxicol. Environ. Health 39: 147-161 (1993).
Prediction of a positive result in rodent carcinogenesis bioassays using 2 instead of 4 sex-species groups is examined for the subset of chemicals in the Carcinogenic Potency Database that have been tested in 4 sex-species groups and are positive in at least one (N=212). Under the conditions of these bioassays, a very high proportion of rodent carcinogens that are identified as positive by tests in 4 groups is also identified by results from 1 sex of each species (86%-92%). Additionally, chemicals that are classified as "2-species carcinogens" or "multiple-site carcinogens" on the basis of results from 4 sex-species groups are also identified as 2-species or multiple-site carcinogens on the basis of 2 sex-species groups. Carcinogenic potency (TD50) values for the most potent target site are similar when based on results from 2 compared to 4 sex-species groups. Eighty-five percent of the potency values are within a factor of 2 of those obtained from tests in 4 sex-species groups, 94% are within a factor of 4, and 98% are within a factor of 10. This result is expected because carcinogenic potency values are constrained to a narrow range about the maximum dose tested in a bioassay, and the maximum doses administered to rats and mice are highly correlated and similar in dose level.
Information that can be known in advance of a 2-year bioassay (mutagenicity, class, route, and maximum dose to test) does not identify groups of rodent carcinogens for which 4 sex-species are required to identify carcinogenicity. The range of accurate prediction of carcinogenicity using only male rats and female mice is: 93% among mutagens and 88% among non-mutagens; for various routes of administration (88%-100%); for various chemical classes (75%-100%); for various levels of the maximum dose tested (81%-100%). Results are similar for the pair male rats and male mice.
Using a strength of evidence approach, weaker carcinogens are somewhat less likely than stronger carcinogens to be identified by 2 sex-species groups. Strength of evidence is measured using: the proportion of experiments on a chemical that are positive, the extent to which tumors occur in animals that die before terminal sacrifice, and whether the chemical induces tumors at more than one site and in more than one species.
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Last updated: November 10, 1995