PMID- 6504066 OWN - NLM STAT- MEDLINE DCOM- 19850117 LR - 20190702 IS - 0027-5107 (Print) IS - 0027-5107 (Linking) VI - 134 IP - 2-3 DP - 1984 Sep-Nov TI - A report of the U.S. Environmental Protection Agency Gene-Tox Program. Evaluation of mutagenicity assays for purposes of genetic risk assessment. PG - 143-57 AB - 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. (1) 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 to 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 had been 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 available evidence is limited by the circumstance that MGst test have evidently been preferentially performed with chemicals that had already been shown to be positive in several other assays. (2) Findings from each MGst test were compared with those from each of the other assays in turn, provided that at least 10 chemicals had been tested in both of the assays. There were 11 such comparisons involving the 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 one case (HTT vs. unscheduled DNA synthesis in the testis) did the degree of elevation approach statistical significance. FAU - Russell, L B AU - Russell LB FAU - Aaron, C S AU - Aaron CS FAU - de Serres, F AU - de Serres F FAU - Generoso, W M AU - Generoso WM FAU - Kannan, K L AU - Kannan KL FAU - Shelby, M AU - Shelby M FAU - Springer, J AU - Springer J FAU - Voytek, P AU - Voytek P LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - Netherlands TA - Mutat Res JT - Mutation research JID - 0400763 RN - 0 (Mutagens) SB - IM MH - Animals MH - Chromosome Aberrations MH - Cricetinae MH - Female MH - Genes/*drug effects MH - Humans MH - Male MH - Mutagenicity Tests MH - Mutagens/*toxicity MH - *Mutation MH - Risk MH - Sister Chromatid Exchange/drug effects MH - Species Specificity MH - United States MH - United States Environmental Protection Agency EDAT- 1984/09/01 00:00 MHDA- 1984/09/01 00:01 CRDT- 1984/09/01 00:00 PHST- 1984/09/01 00:00 [pubmed] PHST- 1984/09/01 00:01 [medline] PHST- 1984/09/01 00:00 [entrez] AID - 0165-1110(84)90008-3 [pii] AID - 10.1016/0165-1110(84)90008-3 [doi] PST - ppublish SO - Mutat Res. 1984 Sep-Nov;134(2-3):143-57. doi: 10.1016/0165-1110(84)90008-3.