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EC number: 946-101-1
CAS number: -
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.
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 pre‑mating
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
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).
above summary of combined repeated dose and reproduction / developmental
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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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