Sodium [N-[2-[bis(carboxymethyl)amino]ethyl]-N-(2-hydroxyethyl)glycinato(4-)]ferrate(1-)

Endpoint summary

Additional information

DTPA-FeHNa 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), DTPA-FeHNa was positive at levels >= 2000 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 EDTA-CuNa2 (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 DTPA-FeHNa (and also EDTA-FeNa and EDTA-CuNa2) 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 DTPA-FeHNa and HEDTA-FeNa, 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 HEDTA-FeNa will lack significant genotoxic potential under conditions that do not deplete essential trace elements required for normal cell function.

Short description of key information:
DTPA-FeHNa tested in the Salmonella Typhimurium Reverse Mutation Assay and the Eschericha Coli reverse mutation assay did not result in an increased number of revertant colonies in strains S. typhimurium strains TA 98, 100, 1535, 1537. 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). See also at Discussion.

Endpoint Conclusion: No study available

Justification for classification or non-classification

Bases on the results of several in vitro and in vivo gentoxicity tests (see also read across documrnt in section 13), it was concluded that for HEDTA-FeNa classification for genotoxicity is not warranted.