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Administrative data

Key value for chemical safety assessment

Additional information

In vitro gene mutation in bacteria

The gene mutation potential of the target substance Basic Cr(III) acetate was examined in a bacterial reverse mutation assay performed according to OECD 471 and GLP (Paulus and Rudolf, 2008). Test substance concentrations of 50 -5000 µg/plate were investigated in S. typhimurium strains TA 1535, TA 97a, TA 98, TA 100 and TA 102 in two independant experiments (plate incubation and preincubation method). The used positive controls were valid. No cytotoxicity was observed, except in strain TA 97a in which a significant reduction of revertants was observed. The test substance did not induce reversions in any of the strains tested with or without metabolic activation.

In vitro gene mutation in mammalian cells

Gene mutation at the thymidine kinase locus was investigated in two mouse lymphoma assay with the source substance Cr(III) picolinate at 50 -1000 µg/mL (Whittaker et al., 2005) and with the source substance niacin-bound chromium at 1 -200 µg/mL (Shara et al., 2005) similar to OECD 476. L5178Y cells were incubated with and without metabolic activation. The used positive controls were valid in both studies. Cr(III) picolinate was positive (with and without S9 mix), whereas a second MLA with niacin-bound chromium was negative, albeit at lower concentrations.

In vitro chromosomal aberration

The clastogenic potential of the source substance Cr(III) picolinate was assessed in a chromosomal aberration test in mammalian cells according to OECD 473 (Gudi et al., 2005). Chinese hamster ovary cells were treated with test substance concentrations of 96 -770 µg/mL with and without metabolic activation in medium. Slight cytotoxicty (ca. 15%) in the highest concentration tested with precipitated test substance was observed. The used positive controls were valid. Cr(III) picolinate was tested negative in CHO cells with and without metabolic acitvation.

In vivo chromosomal aberration; DNA damage and/or repair

The single positive in vitro result is overruled by two in vivo results. One of these studies was performed according to OECD 474 with the source substance Cr(III) picolinate at concentrations of 0.75, 1.5 and 3 mg/kg bw. Mice (3 males/group) were treated intraperitoneally and 42 h after application, the micronucleus formation was investigated in the bone marrow erythrocytes (Andersson et al., 2007). The used positive controls were valid. No signs of toxicity in the animals were observed and no genotoxic effects were induced by the test substance.

The second study was a Comet assay which was also performed with Cr(III) picolinate. The substance was administered intraperitoneally at 3 mg/kg bw to 12 male mice (Andersson et al., 2007). 16 h after application, lymphocytes and hepatocytes were isolated and investigated for DNA damage. The used positive controls were valid. The test substance did not induce genotoxic effects.

The overall conclusion is that Cr(III), and thus basic Cr(III) acetate, has no genotoxic potential in vivo.

 


Justification for selection of genetic toxicity endpoint
There was one study available showing positive results for in vitro gene mutation in mammalian cells. The available studies on in vitro gene mutation in bacteria, in vitro/in vivo chromosome aberration and in vivo DNA damage and/or repair were negative.

Short description of key information:
Ames test: negative (-/+ S9)
MLA: positive (-/+ S9)
in-vitro CA, CHO cells: negative (-/+ S9)
in-vivo micronucleus test, mouse, i.p.: negative
in-vivo Comet assay, mouse, i.p., hepatocytes and lymphocytes: negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.