Carcinogenicity studies short-term assay

The scope of the toxicity studies when surrogate molecules have been used includes pharmacology studies, subchronic and chronic studies, reproductive toxicity studies, immunotoxicity studies, and even carcinogenicity studies. Short-term assays like safety pharmacology studies are too short for there to be an antisense effect, so we have not used the surrogate approach in these assays. However, when safety pharmacology endpoints are included in subchronic or chronic studies, surrogates are assessed. 

With the exception of 2,3,7,8-TCDD, the 2,3,7,8-substituted HxCDDs and 2,3,7,8-TCDF, these TEFs are not based on the results of major animal (reproductive, carcinogenic) studies. Generally, TEFs are based on estimates of the relative toxicity from in vitro tests whose relationship to the chronic effects of concern is largely presumptive. Nevertheless, studies on systemic effects continue to reinforce the view that the short-term assays provide important fundamental information on the toxicity of the CDDs/CDFs. 

Careie, A., Conti, G, Conti, L. Crebelli, R. (1985) Assays in Aspergillus nidulans for the indnction of forward-mutation in haploid strain 35 and for mitotic nondisjunction, haploidization and crossing-over in diploid strain PI. In Ashby, J., de Serres, F.J., Draper, M., Ishidate, M., Jr, Margolin, B.H., Matter, B.E. Shelby, M.D., eds. Progress in Mutation Research, Volume 5, Evaluation of Short-Term Tests for Carcinogens. Report of the International Programme on Chemical Safety s Collaborative Study on in vitro assays, Amsterdam, Elsevier Science, pp. 307-312... 

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