Alcohols C13-15 (branched and linear, odd numbered), reaction product with 1-chloro-2,3-epoxypropane

Endpoint summary

Description of key information

There was no exposure-related mortality and no effects on body weight, weight gain or food consumption. Haematology, clinical chemistry, and urinalyses results also failed to reveal any differences between control and test animals. There were no gross or histopathological alterations attributed to test item. The NOAEL for systemic effect is proposed to be greater than 100 mg/kg/d. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

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:

adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

According to Regulation (EC) 1907/2006, repeated dose toxicity test only need to be performed via the most likely exposure route for human. Since the most likely route is considered to be via dermal, the test via oral can be waived.

This repeated dose study was conducted to evaluate the subchronic dermal toxicity potential of test substance in Fischer 344 rats following a 5 days per week dosing regimen for approximately 13 weeks.

A range finding study was conducted in which two rats/sex/dose level were dosed dermally with 0, 10, 100, or 1000 mg/kg/day of test substance, 5 days/week for up to a total of 10 applications. In-life observations and dermal scoring indicated an ungroomed appearance in high-dose group rats; erythema, edema, scaling/fissuring and scabs in high and middle-dose group rats and slight scaling in low dose group rats. Four doses of 1000 mg/kg/day exceeded the maximum-tolerated dose as defined by loss of integrity of the epidermis. Grossly, the skin of high-dose rats appeared scaly, thickened and was ulcerated. Microscopically, the response consisted of epidermal hyperplasia with hyperkeratosis and parakeratosis along with hyperplasia of the sebaceous glands with ulceration, inflammation and edema. The epidermal response was similar at 100 mg/kg/day, however the epidermis remained intact. Treatment-related effects in low dose rats were limited to slight scaling at the dermal test site.

Based on the results of the range finding study, non-occluded dermal doses of 0, 1, 10, or 100 mg/kg/day of test substance in acetone were administered to ten rats/sex/dose level 5 days/week for 13 weeks. Standard toxicologic parameters were evaluated. There were no treatment-related changes in clinical or ophthalmologic observations, body weights, feed consumption or clinical pathology during the thirteen-week study. Treatment-related gross and histopathologic lesions were limited to the skin of high-dose rats. Applications of 100 mg/kg/day reached the maximum-tolerated dose defined by the USEPA (1988) with a definitive, uniform reaction at the dermal treatment site consisting of epidermal hyperplasia, hyperkeratosis, sebaceous gland hyperplasia and a mild inflammatory response. The response was similar after 2 or 13 weeks, although the response was equivocally of greater severity after 2 weeks. Crusts, underlain by intact hyperplastic epidermis, were present after 2 weeks but not after 13 weeks. The no-observed effect level for systemic toxicity was considered to be greater than 100 mg/kg/day.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
According to Regulation (EC) 1907/2006, repeated dose toxicity test only need to be performed via the most likely exposure route for human. Since the most likely route is considered to be via dermal, the test via oral can be waived.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
According to Regulation (EC) 1907/2006, repeated dose toxicity test only need to be performed via the most likely exposure route for human. Since the most likely route is considered to be via dermal, the test via oral can be waived.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
According to Regulation (EC) 1907/2006, repeated dose toxicity test only need to be performed via the most likely exposure route for human. Since the most likely route is considered to be via dermal, the test via oral can be waived.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
guideline test with GLP

Justification for classification or non-classification

The health effects of test substance have been evaluated in a number of repeated-dose toxicity studies conducted in rats and no evidence of systemic toxicity has been seen at any concentration. The only treatment-related effects noted in these studies were changes to the dermal treatment site following repeated exposures, which were considered to be a local adaptive response and showed no dose relationship. Therefore, based on the dermal repeated toxicity study (subchronic) in absence of systemic effects, test substance is not classified for STOT repeated exposure under CLP (Regulation EC No. 1272/2008).