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Key value for chemical safety assessment

Additional information

EDTA-CuNa2 was negative in the Ames test and in the in vitro micronucleus test using a treatment period of 4 h (with and without S9 -mix). In the in vitro micronucleus test using a treatment period of 20 h (continuous treatment without S9 -mix), EDTA-CuNa2 was positive at levels >= 62.5 µg/mL, inducing aneugenic but no clastogenic effects. This long treatment period together with the high concentrations of chelant may have resulted in exchange and substantial binding of essential elements such as zinc. Similar results were obtained with EDTA-FeNa and DTPA-FeNaH (see robust summaries and read across document; section 13). Heimbach et al (2000; see also robust summary) concluded that the lack of effects by the Zn-EDTA salt in contrast to effects induced by Ca-, Na- and Mn-salts of EDTA, provided evidence that zinc is required for the initiation or continuation of DNA synthesis and maintaining cell function. As such, the significance of mutations produced by EDTA-CuNa2 (and also EDTA-FeNa and DTPA-FeNaH) at non-physiological concentrations in an in vitro screening system is difficult to extrapolate for relevance to intact organisms.

Although no in vivo genotoxicity studies have been carried out with EDTA-CuNa2, several in vivo genotoxicity studies are available for other EDTA-compounds such as EDTA-Na2H2. No genotoxic activity was observed (see also read across document in section 13).

Therefore, the overall findings indicate that EDTA-CuNa2 lacks significant genotoxic potential under conditions that do not deplete essential trace elements required for normal cell function.

Short description of key information:

EDTA-CuNa2 tested in the Ames test (standard plate and preincubation test) did not result in an increased number of revertant colonies in strains S. typhimurium strains TA 98, 100, 1537, 1538. An in vitro micronucleus test in human lympocytes did not result in an increased number of micronuclei following exposure for 4 h (with and without S9 mix), but it did following exposure for 20 h (without S9 mix).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The test substance gave negative results in two in vitro mutagenicity studies, viz. the Ames test and the micronuclueus test following exposure for 4 h (with and without S9 mix) but gave positive results (aneugenicity but not clastogenicity ) following exposure for 20 h (without S9 -mix). The latter was most probably explained by induction of Zn deficiency. Overall, it was concluded that classification for genotoxicity is not warranted.