Publications from the Carcinogenic Potency Project

Peto, R., Pike, M.C., Bernstein, L., Gold, L.S., and Ames, B.N. The TD50: A proposed general convention for the numerical description of the carcinogenic potency of chemicals in chronic-exposure animal experiments. Environmental Health Perspectives 58: 1-8 (1984). PDF

A generally accepted format for the numerical description of the carcinogenic potency of a particular chemical in a particular strain of animals is desirable so that statements from different sources about potency and attempts by different authors to correlate potency with particular laboratory measurements will be comparable. The choice of an appropriate standard format is to a certain extent arbitrary. In this paper we recommend that the TD50 (tumorigenic dose rate 50) be used. TD50 can be calculated for a single target site or combination of sites. The TD50 in analogy with the LD50, is defined as that chronic dose rate (in mg/kg body weight/day) which would halve the actuarially adjusted percentage of tumor-free animals at the end of a standard experiment time-- the "standard lifespan" for the species. This paper consists of a brief discussion of the TD50, sufficient to make the general reader familiar with the properties of such an index, an appendix discussing methods for its estimation and certain conventions we have adopted for use in analyzing "nonstandard" experiments. A major problem in calculating any index of carcinogenic potency is that much published material gives only the final crude percentage of tumor-bearing animals at each dose, instead of percentages adjusted for the effects of intercurrent mortality or data from which these adjusted percentages can be derived. If the dose level administered to the animals is toxic, then premature death from nonneoplastic causes may prevent some dosed animals that would have developed tumors from actually doing so. This will particularly affect the high-dose group. Consequently any estimate of carcinogenic potency that is based on crude percentages of tumor-bearing animals, not adjusted for intercurrent mortality, may underestimate the carcinogenicity of the test material.

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