Mutagenicity of 4-nitrodiphenyl thioether-derived products and their potential metabolites.

4-Nitrodiphenyl thioether (4-NO2TE) and its various potential metabolites 4-nitroso- (4-NOTE), 4-hydroxylamino- (4-NHOHTE), 4-hydroxyacetylamino- [4-N(OH)ACTE], 4-acetoxy-acetylamino- [4-N(OAc)-ACTE], 4-amino- (4-ATE) and 4-acetamido- (4-AATE) were tested for their mutagenicity toward Salmonella typhimurium TA98 in the presence and absence of S9 activation system. 4-NO2TE, 4-NOTE, 4-NHOHTE and 4-N(OAc)ACTE were direct-acting mutagens with 4-NHOHTE having the highest activity. With S9 mix, the mutagenicity of 4NO2TE almost doubled and that of 4-NOTE and 4-N(OAc)ACTE decreased. In TA98NR, 4-NOTE induced higher mutations, while with 4-NHOHTE the number of revertants decreased. Both 4-NHOHTE and 4-N(OAc)ACTE showed decreased mutagenicity in TA98/1,8-DNP6. 4-ATE, 4-AATE and 4-N(OH)ACTE expressed mutagenicity only with S9 mix. 4-Nitrodiphenyl sulphoxide (4-NO2SO) and 4-nitrodiphenyl sulphone (4-NO2SO2), the sulphur-oxidised products of 4-NO2TE, were non-mutagenic as such and after addition of S9 activation system.