Mutagenicity of aliphatic and aromatic nitro compounds. Industrial materials and related compounds

Abstract

Mutagenicity of 102 aliphatic and aromatic nitro compounds, industrial materials and related chemicals were tested by pre-incubation method using Salmonella typhimurium TA100 and TA98 strains with and without S9 mix. Escherichia coli WP2uvrA/pKM101 was also used in the mutagenicity assay of aliphatic nitro compounds. Four chemicals out of 8 aliphatic nitro compounds tested were mutagenic to TA100, TA98 and/or WP2 strains. Sixty-one out of 94 nitrobenzene derivatives were mutagenic to TA100 and/or TA98 strains. Thirty-seven chemicals among the 65 mutagens showed higher mutagenic activity than 1,000 rev./mg. The following 15 chemicals showed higher activity than 10,000 rev./mg: tetranitromethane, chloropicrin, 1,3,5-trinitrobenzene, 2,4-dinitrochlorobenzene, 2,3-dinitrophenol, 2,6-dinitroaniline, 3,5-dinitroaniline, 2-bromo-4,6-dinitroaniline, 2,4-dinitrofluorobenzene, p-nitrobenzylchloride, 3,5-dinitrobenzylchloride, p-nitrophenylhydrazine, 2,4-dinitrophenylhydrazine, 2,4-dinitrophenylthiocyanate and nitramine. Nitrobenzene was not mutagenic, but mono-substituted nitrobenzenes having-CH2Cl, -COCl, -NO2, -NH-NH2, -COOH, -OCH3, -NH2, -Br, -OH, -NH-NH2HCl, -OP(OC2H5)2S or -CHO group showed mutagenic. Introduction of-Cl, -CH3, -C2H5 or -SO3H group to nitrobenzene did not contribute to mutagenicity. Mutagenicity of dinitrobenzene was enhanced by the introduction of -F, -SCN, -NH2, -Cl, -CH2Cl, -NO2, -NH-NH2 or -COCl group, and suppressed by the introduction of -COOH or -CH3 group. Twenty-three out of 45 chemicals for which "exposure limits" are established from the stand point of industrial hygiene in many countries in the world, were mutagenic to TA100, TA98 and/or WP2 strains. Furthermore, 42 out of 57 chemicals for which "exposure limits" are not established were also mutagenic. The following three carcinogens, that is, 2-nitropropane, 2,4-dinitrotoluene and 2,6-dinitrotoluene, were all mutagenic, but their mutagenic activity was weak. Many chemicals were found to have a stronger mutagenic activity and a chemical structure similar to carcinogenic dinitrotoluenes. This fact suggests the necessity of conducting carcinogenic assay of these chemicals.