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Description of key information

With regard to the evaluation of repeated dose toxicity for EDTA-Zn(NH4)2, results of the study with EDTA-CaNa2 were compared with studies with other metal chelates and with EDTA (see below). One repeated inhalation toxicity study was avalaible for DTPA-CaNa3, another, Ca-containing chelate.  

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:
The 2-year NOAEL in a rat study with EDTA-CaNa2 was >= 250 mg/kg bw. Other long term oral toxicity studies with other metal chelates or with EDTA showed comparable results. The highest NOAEL in these long term studies was 500 mg/kg bw. See also read across document in section 13.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
A repeated 12-day inhalation toxicity with another chelate (Ca-DTPA) at levels up to 1.18 mg/L induced only a mild, focal and reversible pulmonary histiocytosis in the rat.

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

A 2 -year oral toxicity study in rats with EDTA-CaNa2 revealed no toxicity up to and including 250 mg/kg bw. No toxicity was seen up to and including 338 mg/kg in a 1 -year oral study in dogs. Short-term studies with EDTA-CaNa2 in rats revelead a NOAEL of >= 3636 mg/kg (31 -day study) or a LOAEL of 2750 mg/kg bw (1 -month study; see also the read across document in section 13). A 61 -day study with another metal chelate (EDTA-FeNa) revealed a NOAEL of >= 84 mg/kg bw in rats (higest dose tested), whereas a 14 -week study in rats with EDTA-MnNa2 resulted in a NOAEL of 500 mg/kg bw. Chronic studies with EDTA-Na3H revealed a NOAEL of >= 500 mg/kg bw in rats, and >= 938 mg/kg bw in mice. Finally, a 13 -week study with EDTA-Na2H2 resulted in a NOAEL of >= 500 mg/kg bw. These results together show that EDTA-Zn(NH4)2 like other EDTA's will be of low toxicity following repeated oral exposure. The NOAEL observed with EDTA-CaNa2 in the 2 -year study in rats, which was at least 250 mg/kg bw, may therefore be higher. It is not expected that repeated inhalation exposure to EDTA-Zn(NH4)2 would result in harmful effects based on the results of a 12 -day exposure study with DTPA-CaNa3 in which a NOAEL of 420 mg/m3 was observed. Futher, because EDTA-Zn(NH4)2 is not irritating to the skin, local dermal effects are not expected and because the absorption via the skin is expected to be very low (EU RAR, 2004), no systemic toxicity is expected following dermal exposure.

Justification for classification or non-classification

Based on the results indicated above no classification is needed for EDTA-ZnNa2 following repeated exposure.