Increased mutagenicity of chromium compounds by nitrilotriacetic acid

Abstract

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.

Characterization of the genotoxicity of nitrilotriacetic acid

“…These results are in agreement with the literature [Loprieno et al, 1985;Zeiger et al, 1992]. Regarding results obtained in the presence of S9-mix, the lack of mutagenicity was noticed when using either liver or kidney rat microsomal fractions.…”

Interaction of nitrilotriacetic acid with heavy metals in the induction of sister chromatid exchanges in cultured mammalian cells

“…With the exception of monovalent insoluble Hg (as HgCI), we chose the soluble and insoluble salts of divalent Cd, Hg, Ni and Pb for a study of the interaction of heavy metal compounds with NTA in the induction of genetic and chromosomal effects by means of the Sulmonellaimicrosome assay and the SCE test in the CHO mammalian cell line. We had already observed an enhancement of both the frequency of mutations and SCE induced by insoluble Cr(V1) compounds in the presence of NTA [Loprieno et al, 1985;Venier et al, 19851. In the present study, we used the SCE test to investigate the interaction of NTA with metal compounds in the induction of chromosomal effects in mammalian cells.…”

“…Therefore, it was considered as an indirect nonmutagenic carcinogen, and its occasional clastogenic effects were attributed to nonspecific toxicity caused by the high active concentrations [Brusick, 19801. However, we have already observed that NTA enhances the direct rnutagenicity of several insoluble or scarcely soluble Cr(V1) compounds (Pb, Ba, Sr, Zn, and Ca chromates) in S typhimuriurn, and their ability to induce sister chromatid exchanges in CHO cells [Loprieno et al, 1985;Venier et al, 19851. The same was observed with some industrial pigments containing insoluble Pb and Zn chromates [Venier et al, 19851.…”

“…In accordance with the generally negative results produced in short-term mutagenicity assays by NTA, we found that NTA and its putative metabolite Nnitrosoiminodiacetic acid (NIDA) induced no gene reversions in Salmonella typhimuriurn, no forward gene mutations in Schizosaccharornyces pornbe, and no mitotic gene conversions in Succharomyces cerevisiae [Loprieno et al, 19851. NTA is, however, able to mobilize insoluble metal compounds and to form stable complexes with many metals [Perry et al, 19841, some of which are mutagenic and carcinogenic [Sunderman, 19841. We have previously observed that NTA enhances the induction of gene mutations in S typhimurium and sister chromatid exchanges (SCE) in Chinese hamster cells (CHO line) by several insoluble Cr(V1) compounds. The increased mutagenicity of Cr compounds was related to the actual amount of Cr(V1) solubilized as chromate anion [Loprieno et al, 1985;Venier et al, 19851. In this paper we present data on (1) the ability of NTA to induce SCE in the CHO cell line and in primary cultures of BALB/c and BALB/Mo mouse lymphocytes, which have shown particular sensitivity to chromosome damage when exposed to chemical carcinogens [Majone et al, 19831, and (2) the interactions between NTA and Cd, Hg, Ni, and Pb compounds in the induction of chromosomal effects.…”

Chromosomal effects of heavy metals (Cd, Cr, Hg, Ni and Pb) on cultured mammalian cells in the presence of nitrilotriacetic acid (NTA)†

“…18 " 20 Metal toxicity and genotoxicity are influenced by environmental factors, among which are the pH, the inorganic ion composition, and the type and concentration of chelating agents. 21 We have shown that the interaction of nitrilotriacetic acid (NTA) with insoluble Cr(VI) compounds causes an increase in the induction of gene mutations in S. typhimurium 22 ' 23 and SCE in cultured mammalian cells. 23 NTA also increases the ability of insoluble compounds of Cd(II), Hg(I), Ni(II) and Pb(II) to induce SCE in cultured hamster CHROMOSOMAL EFFECTS OF NTA-METALS 185 cells while apparently it does not affect the induction of SCE by soluble metal compounds.…”