Reaction products of tetraethylenepentamine and maleic anhydride

Endpoint summary

Description of key information

A key GLP-compliant, repeated dose toxicity study via oral exposure (Rashid H, 2015) was performed as combined study with reproduction/developmental toxicity screening test in rats according to OECD guideline 422. A NOAEL of 1000 mg/kg bw/day was derived for male systemic toxicity and maternal systemic toxicity.
Repeated dose toxicity: inhalation: A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the inhalation route of exposure.
Repeated dose toxicity: dermal: A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal route of exposure 

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

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

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

Repeated dose toxicity: oral:

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test is performed in rats. The substance was administered daily during 28 days to 12 animals/sex/group by gavage, on a 7 -day/week-basis, from 14 days before mating to 4 days post-delivery. The test item was administered at doses of 0 (vehicle - distilled water), 100, 300 and 1000 mg/kg bw/day via gavage (OECD 422).

There were no clinical observations or premature deaths observed related to treatment. Throughout the dosing period, there were no adverse effects on body weight development, food consumption, water consumption, hematology and clinical chemistry, sensory reactivity scores, or organ weights. Motor activity evaluation during the final treatment week revealed slightly but statistically significantly lower activity (last 20%) for males given the test item at 300 or 1000 mg/kg bw/day compared to controls (p<0.05). The remaining motor activity parameters for these animals were similar to controls and in the absence of any other signs of neurotoxicity, this finding was considered to be incidental.

No treatment-related findings were observed during macroscopic examinations. Histopathology of selected tissues from high dose animals of either sex did not reveal any abnormalities related to test item.

Oral gavage administration of the substance (active ingredient) to rats at dose levels of up to 1000 mg/kg bw/day was well tolerated. Based on the available data the NOAEL for systemic toxicity was considered to be 1000 mg/kg bw/day (based on active ingredient).

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Reliable repeated dose toxicity study.

Justification for classification or non-classification

Based on the available information and the criteria of the CLP Regulation, the test item (49.8% solution) should not to be classified after repeated dosing.