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Key value for chemical safety assessment

Effects on fertility

Description of key information

Based on the results of the combined repeated dose and reproduction / developmental screening test, the test substance is not considered to be of reproductive and development toxicity concern.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Guideline compliant combined repeated dose and reproduction / developmental screening study.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A study was conducted to determine the toxicity to reproduction of the test substance according to OECD Guideline 422 EPA OPPTS 870.3650 and EPA OPPTS 870.3550, in compliance with GLP. In this study, male and female Wistar Han rats were exposed (by gavage) to the test substance at dose levels of 100, 300 and 1000 mg/kg bw/day from 14 days before mating (Day 1) until Day 31 for males or until Day 4 of lactation for females. A control group of 10 male and 10 female rats was given 5 mL/kg bw/day of the vehicle (corn oil) over the same periods. Clinical condition, body weight and food consumption of the animals were monitored throughout the study. Clinical laboratory determinations were performed at the end of the premating period (Day 14). After two weeks of treatment, one male and one female of the same group were paired for a maximum of 14 days. The females were allowed to give birth and litter parameters, including the number of pups born, pup survival, sex and pup weights were recorded up to postnatal day 4. Functional tests were performed at the end of the treatment period for 5 selected males in each group and on Day 4 of lactation for 5 selected females in each group. The males were necropsied after the pairing period. The dams and pups were necropsied on day 4 of lactation, where applicable. All animals were submitted to a macroscopic examination. For half of the animals/group, selected organs were weighed, and organ/tissue samples were fixed and preserved at necropsy. A limited list of organ/tissue samples were fixed and preserved at necropsy for the remaining animals. Selected organs/tissues, from half of the group 1 and 4 animals killed at the end of the treatment period were examined histopathologically. The reproductive organs (including additional PAS/haematoxylin-stained slides for testes) were examined histopathologically for the 5 randomly selected adult males of groups 1 (control) and 4 (high dose), all males suspected to be infertile and all females that failed to deliver healthy pups. Oral administration of the test substance was associated with a non-adverse minor decrease in mean body weight gain for males and females during lactation at 300 and 1000 mg/kg bw/day and a slight reduction of food consumption for all treated females (from Day 9 and Day 15 of pre-mating) and from Day 1 to Day 4 of lactation at 1000 mg/kg bw/dayand a dose-related decrease in bile acids in test substance-treated males at all dose levels and females at 300 and 1000 mg/kg bw/day. There was no effect of treatment on mating performance or fertility (including gonadal function, mating behaviour, conception and parturition). In addition, there were no test substance-related pathological changes in the male or female genital system. The treatment did not affect pup viability or pup weight at any dose on PND 1 and through to termination. Under the study conditions, the NOAEL for reproductive and developmental toxicity of the test substance was determined to be 1000 mg/kg bw/day (highest dose tested) (Mounier, 2017).

Effects on developmental toxicity

Description of key information

See above summary of combined repeated dose and reproduction / developmental screening test.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Guideline compliant combined repeated dose and reproduction / developmental screening study.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results of a combined repeated dose toxicity and reproductive/developmental screening study (OECD 422) with the read across substance, no classification is required for this endpoint according to CLP (Regulation 1272/2008/EC) criteria.​