MUTAGENIC INTERACTIONS OF MODEL CHEMICAL-MIXTURES

Although current methodology for human health risk assessment assumes additive interactions among the contaminants of a complex mixture, che mical interactions may occur which produce synergistic or antagonistic effects. In this study, the mutagenic response of three model compoun ds, benzo(a)pyrene (B(a)P), pentachlorophenol (PCP) and 2,4,6-trinitro toluene (TNT), were tested individually and in binary and tertiary sol utions, using the Salmonella/microsome assay with each of three bacter ial tester strains (TA97a, TA98, and TA100). For all strains, B(a)P wa s mutagenic with metabolic activation (Arochlor 1254-induced Sprague-D awley rat liver S9 fraction), TNT was mutagenic without metabolic acti vation, and pentachlorophenol was inactive both with and without metab olic activation. In binary and tertiary solutions, pentachlorophenol h ad no effect on the mutagenicity of B(a)P or TNT, independent of metab olic activation. For strain TA97a, the mutagenicity of B(a)P with meta bolic activation was slightly decreased in the presence of TNT; the mu tagenicity of TNT without metabolic activation was slightly decreased in the presence of B(a)P and PCP; and the mutagenicity of the tertiary solution (496 revertants/10 ug) with metabolic activation was lower t han the mutagenicity of B(a)P alone (729 revertants/10 ug). The mutage nicity of B(a)P in strain TA98 with activation was inhibited by the ad dition of TNT. Studies conducted using several concentrations of TNT o r B(a)P indicate that the inhibition of B(a)P mutagenicity was increas ed as the concentration of TNT increased. Assays performed using four concentrations of S9 indicated the inhibition of B(a)P mutagenicity wa s relatively unaffected by the level of S9. The data suggest that an i nteraction in the presence of TNT limits the concentration of B(a)P th at is capable of reaching or binding with bacterial DNA. (C) 1998 Else vier Science Ltd. All rights reserved.