A report of the U.S. Environmental Protection Agency Gene-Tox Program. Evaluation of mutagenicity assays for purposes of genetic risk assessment
Russell, L.B.; Aaron, C.S.; de Serres, F.; Generoso, W.M.; Kannan, K.L.; Shelby, M.; Springer, J.; Voytek, P.
Mutation Research 134(2-3): 143-157
1984
ISSN/ISBN: 0027-5107 PMID: 6504066 Document Number: 231036
For the vast majority of chemicals mammalian germ-line (MG) mutation data do not exist. The question was examined of how best to utilize results of non-MG genotoxicity assays that are included in the Gene-Tox data base to provide information of the likelihood that genetic damage might be induced in and transmitted by the reproductive cells of exposed human beings. Two approaches were used to assess the relative value of different assays for genetic hazard identification. Test results were weighted according to parameters by which conditions of an assay resemble those encountered in the potential induction of transmitted genetic damage in mammals. For this purpose, 35 assays were grouped into 16 categories that were assigned weights ranging from 1-15; there were 2367 chemicals in the data base. This system was evaluated by comparing the sum of weighted test results for each chemical with the outcome of MG-standard (MGst) tests where such were reported. (MGst tests used were the specific-locus and heritable-translocation assays [SLT and HTT] for gene mutations and chromosome aberrations, respectively.) The weighting system produced a few false positives with respect to the MGst results. It produced no false negatives, but the avaiable evidence is limited by the circumstance that MGst tests were evidently preferentially performed with chemicals that were already shown to be positive in several other assays. Findings from each MGst test were compared with those from each of the other asaays in turn, provided that at least 10 chemicals were tested in both of the assays. There were 11 such comparisons involving ths SLT, and 14 such comparisons involving the HTT. The observed concordance was above random expectation in several comparisons, particularly those involving certain mammalian in vivo tests, but in only 1 case (HTT vs. unscheduled DNA synthesis in the testis) did the degree of elevation approach statistical significance.