Disodium 2-hydroxyethyliminodi(acetate)

Endpoint summary

Description of key information

Treatment-related microscopic changes characterized by renal tubular vacuolation with a slight increase in the incidence of basophilic tubules were noted in high dose male animals (500 mg/kg bw nominal; 205 mg/kg bw actual) after 13 weeks of oral treatment. With the exception of one high dose male, which died during the treatment free period (19 week) and had marked tubular vacuolation of the kidneys, no microscopic observations related to treatment were noted after the 4 week interim sacrifice. Further, the minimal to moderate vacuolation appeared reversible as it was not apparent after 4 weeks without treatment.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

41 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Study well documented, followed method comparable to guideline. Results comparable to those of the structurally related substance NTA-Na3.

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

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

The NOAEL in a 90 -day oral toxicity study with EDG-Na2 was 41 mg/kg bw. With regard to the structurally related compound NTA-Na3, no full OECD guideline study is available for the assessment of repeated dose toxicity.However, the available studies on oral toxicity provide a sound base for a weight of evidence assessment. At lower concentrations nodular hyperplasia and urothelium lesions were shown to be reversible. Only at high doses (2% NTA-Na3) hydronephrotic response was sufficiently severe to preclude the restoration of normal renal structure in a few rats. A NOAEL of 92 mg/kg/d for cytotoxic effects was established in a 2 year carcinogenicity study (NCI, 1977).

In a subacute inhalation toxicity study with NTA-Na3, no mortality in either of the animal groups was found. A NOAEC of 0.21 mg/L was established. The LOAEC of 0.34 mg/L based on slight to severe respiratory distress (local) and some changes in blood biochemistry (systemic). All effects had disappeared on day 42, the end of the post-exposure observation period.

 

Justification for classification or non-classification

Based on a NOAEL of 41 mg/kg bw EDG-Na2 in a 90-day study, and limited findings at 205 mg/kg bw, no classification is needed for STOT repeated exposure.