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Administrative data

Description of key information

 Read across from testing with ethylenediamine, ethoxylated and propoxylated. A 28 -day oral (gavage) repeated dose NOAEL for (male/female) >= 1000 mg/kg b. w. /d (based on nominal).  A 90 -day oral (gavage) repeated dose guideline study (OECD 408) resulted with a NOEL for systemic toxicity of 300 mg/kg/day.  

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

Results 'read across' from study on ethylenediamine, ethoxylated and propxylated, as permitted by Annex XI para 1.5, based on the justification in the report by Paul Illing Consultancy Services Ltd and Marlin Consultancy (Illing and Barratt, 2009). The report identifies that ethylenediamine ethoxylated and propoxylated is the most bioavailable of the ethylenediamine NLP polyols linked by an amine group, and the lack of toxicity seen for it and and the toxicity/lack of toxicity for both components (ethylenedimaine and propane-1,2-diol) of ethylenediamine, propoxylated should be considered representative of the lack of toxicity of the amine linked polyol.

Thus, on animal welfare grounds this test should not be undertaken on ethylenediamine, propoxylated. For further details concerning the grouping, consult Illing and Barratt, 2009.

A 28-day oral (gavage) repeated dose toxicity study following the OECD guideline 407 is available for the endpoint. There were no adverse effects observed up to the highest concentration tested and the NOAEL for both sexes was concluded as >= 1000 mg/kg b.w./d ( based on nominal).

For the highest dose group, MCH was increased in females and MCHC was increased in both sexes. This effect was considered as non adverse.

The NOEL for both sexes was concluded as 300 mg/kg b.w./d (based on nominal).

A 90 -day oral gavage repeated dose guideline study (OECD 408) tested ten male and ten female F344/DuCrl rats per group were administered 0, 100, 300, or 1000 milligrams Ethylenediamine, ethoxylated and propoxylated (>1 - <8.5 mol of EO and PO) per kilogram body weight per day (mg/kg/day) in ultrapure water via oral gavage for at least 90 days to evaluate the potential for systemic toxicity. Based on the treatment-related point-of-contact irritative lesions in the nasal tissues that were present in some males and females from all treated dose levels, the overall no observed- effect level (NOEL) for F344/DuCrl rats of either sex was not determined. However, the only treatment-related effects indicative of systemic toxicity were lower red blood cell counts, hemoglobin concentrations and hematocrits in males and females administered 1000 mg/kg/day, with compensatory increased erythrocytic extramedullary hematopoiesis of the spleen in males administered 1000 mg/kg day. Therefore, the NOEL for systemic toxicity was 300 mg/kg/day Ethylenediamine, ethoxylated and propoxylated (>1 - <8.5 mol of EO and PO).

A prenatal developmental toxicity guideline study (OECD 414) was conducted for Ethylenediamine, ethoxylated and propoxylated (>1-<8.5 mol of EO and PO) in Crl:CD(SD) rats following repeated gavage administration. Gavage administration of Ethylenediamine, ethoxylated and propoxylated (>1-<8.5 mol of EO and PO) up to, and including the limit dose of 1000 mg/kg/day, resulted in no treatment-related maternal toxicity and no indication of embryo/fetal toxicity or teratogenicity. Therefore, under the conditions of this study, the no-observed-effect level (NOEL) for maternal toxicity and developmental toxicity was the limit dose of 1000 mg/kg/day.

Justification for classification or non-classification

On the basis of 'read across' from ethylenediamine, propoxylated and ethoxylated, the findings in the available studies do not warrant classification according to the EU criteria.