Add time:07/20/2019         Source:sciencedirect.com

Six kinds of chlorinated 4-nitrophenyl ethers (4-nitrobiphenyl ether, p-NO2; 2′-, 3′- and 4′-chloro-4-nitrobiphenyl ethers, 2-, 3- and 4-CNO2; 2′,4′-dichloro-4-nitrobiphenyl ether, 2,4-DCNO2; 2′, 4′, 6′-trichloro-4-nitrobiphenyl ether,2,4,6-TCNO2) and their nitroso- and amino-derivatives have been tested for mutagenicity using Salmonella typhimurium strains (TA98 and TA100) in the presence and the absence of rat, mouse and guinea pig liver homogenates, which were stimulated with Kaneclor-500. All the chlorinated 4 nitrobiphenyl ethers except for 2,4,6-TCNO2 induced mutations in TA100 strain without metabolic activation although their mutagenic activities were weak compared with the nitroso ±S-9) and amino (+S-9) derivatives. The mono-chloro-compounds were more effective in inducing mutations than those with multiple chlorines and their mutagenic activities were closely related to the rate of reduction of the nitro-moiety by tester strains. After metabolic activation the mutagenicity of these compounds was enhanced. All the nitroso derivatives (except for 2,4,6-TCNO which was inactive with TA98), without metabolic activation, induced mutations in both TA98 and TA100 strains. However, at high concentrations they showed antimicrobial activity. At low concentrations, the nitroso compounds having fewer chlorine atoms were more effective in inducing mutations and their mutagenic activities were closely related to their rate of reduction by tester strains. After metabolic activation with S-9, their antimicrobial activities at high concentrations were markedly decreased and their mutagenic activities were greatly enhanced. The amino derivatives all induced mutations in both TA98 and TA100 strains but only after metabolic activation. Here too, the amino-compounds having fewer chlorine atoms were more effective in inducing mutations than those having multiple chlorines. After addition of S-9, the mutagenic activity of the nitro compounds was lower than that of the analogous nitroso and amino compounds which showed almost the same mutagenic activity. It was observed that S-9 fraction from guinea pig liver was the most active in conversion of these chemicals to mutagens, whereas S-9 fractions from rat and mouse livers were about equal in potency.

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