MUTAGENIC ACTIVITY OF CARCINOGENS DETECTED IN TRANSGENIC RODENT MUTAGENICITY ASSAYS AT DOSE LEVELS USED IN CHRONIC RODENT CANCER BIOASSAYS

Data on transgenic rodent mutagenicity of five human carcinogens were summarised and compared with the results from rodent carcinogenicity s tudies. Four out of five carcinogens showed mutagenic activity already at daily dose levels which induced cancer in long-term rodent bioassa ys in at least one target tissue of carcinogenesis. In several of thes e studies, even single dose applications were sufficient to significan tly increase the mutation frequency in vivo. Other genotoxic carcinoge ns required application of multiple dosing at dose-levels used in rode nt cancer bioassays to show their in vivo mutagenicity. A rodent respi ratory tract carcinogen, 1,2-dibromoethane (DBE), following inhalation exposure, displayed no mutagenic activity, neither in lung nor in nas al mucose, at a single 2-h exposure to 30 ppm, which is below the high est concentration used in a NTP cancer bioassay. In contrast, after mu ltiple treatment for 10 days at the same daily doses, a significant in crease of the mutation frequency in nasal mucosa was apparent. We conc lude, that especially when studying new chemicals in these transgenic rodent mutation assays, a multiple dosing protocol should be preferred . For dose selection, the same criteria could be applied as for chroni c rodent bioassays. (C) 1998 Elsevier Science B.V. All rights reserved .