Increased mutagenicity of chromium compounds by nitrilotriacetic acid

Nitrilotriacetic acid trisodium salt (NTA), which is a substitute for polyphosphates in household laundry detergents, and N-nitrosoiminodiacetic acid (NIDA), a derivative of NTA produced by metabolism of soil microorganisms, were tested for in vitro mutagenicity in bacteria and yeasts. No gene reversions in five strains of Salmonella typhimurium (TA 1535, TA1537, TA1538, TA98, and TA100), no forward gene mutations in Schizosaccharomyces pombe P1, and no mitotic gene conversions at two loci in Saccharomyces cerevisiae D4 were induced by NTA (up to 870 micrograms/plate or 40 micrograms/ml) and NIDA (up to 2,000 micrograms/plate or 1,000 micrograms/ml), independently of the presence of rat liver metabolic activation. The influence of NTA on the mutagenic and clastogenic activity of several chromium compounds was examined in the Salmonella/microsome assay and in the sister chromatid exchange (SCE) assay in mammalian cell cultures (Chinese hamster ovary [CHO] line). NTA does not affect the genetic inactivity of water-soluble Cr(III) (Cr2[SO4]3) and the direct mutagenicity of soluble Cr(VI) (Na2CrO4,K2Cr2O7) compounds. The very insoluble Cr(VI) compounds PbCrO4 and PbCrO4 X PbO are instead clearly mutagenic in the Salmonella/microsome assay (TA100 strain) only in the presence of NTA or NaOH. The mutagenicity of lead chromates is correlated with the amounts of Cr(VI) solubilized by NTA or alkali, as detected by the colorimetric reaction with diphenylcarbazide and atomic absorption spectrophotometry. In the SCE assay, the insoluble lead chromates are directly clastogenic owing to prolonged treatment conditions and cellular endocytosis. The chromosome-damaging activity of PbCrO4 is significantly increased by NTA but not by NaOH.