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

Endpoint summary

Description of key information

In an extended oral OECD 422 study with DTPA-FeHNa male animals were exposed for at least 13 weeks and females for almost 14 weeks. At the high dose level the following effects were observed: soft faeces (both sexes), decreased body weight gain (males), prolonged prothrombin time (males), increased haemoglobin concentration (males), decreased ALAT activity and chloride concentration (males) and decreased ALP activity and increased relative weights of kidneys and liver (both sexes). No toxicologically relevant changes were observed at the lower levels of 500 and 150 mg/kg bw. See also st Discussion.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Results are available for other chelates and metal chelates (see read across document in section 13).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

One inhalation study is available with another metal chelate (see also read across document in section 13).

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a repeated inhalation toxicity with DTPA-CaNa3 in rats only a mild, focal and reversible pulmonary histiocytosis was induced. At a level of 0.42 mg/L (420 mg/m3), the incidence and severity of the histiocytosis was comparable to that in the chamber- and aerosol control group; this level, therefore, was considered a NOAEC. Similar results are also expected for DTPA-FeHNa (see also read across document in section 13).

With regard to EDTA-FeNa, in the key study in which rats were administered NaFeEDTA via the food (Appel et al., 2001), no toxicologically significant effects were observed. It can be concluded from this study that the NOAEL is > 84 mg/kg bw/day. In the studyby Yeung et al (2005) rats received EDTA-FeNa at a level of 1200 mg Fe per kg diet for up to 39 days. Taking into account a consumption of ca. 25 g per day, and a mean weight of ca. 250 g during the study, rats received 30 mg Fe per day or 120 mg Fe per kg bw per day. This corresponds to: 421/56 x 120 = 900 mg EDTA-FeNa.3H2O per kg bw/day. At this level no changes in growth rate were seen. Therefore, the NOAEL most probably is much higher than 84 mg/kg bw day.     

Similar results are expected for HEDTA-FeNa.

Justification for classification or non-classification

Based on a NOAEL of 500 mg/kg bw in a study with DTPA-FeHNa in which male rats were treated for at least 13 weeks and females for almost 14 weeks, and in view of all other studies carried out with chelates and metal chelates (see also read across document in section 13), no classification is needed for STOT repeated exposure for HEDTA-FeNa.