Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

No effects.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 250 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

No effects.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
4 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In a teratogenicity study (Meyer 1975), rats were fed doses of 0, 1000, 2000 and 4000 mg/kg bw/d by gavage, during gestational days 1 to 20. No treatment-related teratogenic effects were observed with regard to number of corpora lutea, number of implantations and foetuses dead or alive, gross malformations, skeletal and internal malformations, foetal weight. Accordingly, a NOAEL of 4000 mg/kg bw/d was found.

A summary was available of a teratogenicity study (Momma 1981). the target substance was fed to groups of 12-16 pregnant (vaginal plug positive) STD-ddY mice (10 weeks old, 26-31 g) at doses of 0, 0.04, 0.2 and 1.0 % in the diet from day 0 to day 18 of gestation (Group A) or during gestation, the 21-days lactation period and for further 35 days (group B). General appearance and wellbeing as well as bodyweight and food consumption were recorded daily.

At gestation day 18, half of the animals were killed under ether anaesthesia and a caesarean section was performed. The presence of resorption sites and foetuses (live or dead) was examined. The number of implantation sites and corpora lutea was also determined. Each live foetus was weighed, sexed and examined for gross external malformations. After fixation and staining, a skeletal examination of the foetuses was performed.

The remaining dams were allowed to deliver and the postnatal development of newborn animals was examined for 56 days after birth. For each litter, number of pups, stillbirths and live births and the presence of gross anomalies were noted, the bodyweight of the neonates was determined weekly and the development (e.g. separation of ear auricula, eruption of low incisors, descent of testes, etc.) examined. After weaning, the F1 generation was treated further up to the 56 day after birth and food consumption was measured weekly. The general appearance, behaviour and survival of the offspring were checked daily.

No treatment-related effects in dams were noted with regard to bodyweight, food consumption, clinical observations and post-mortem findings.

The uterus weight with foetuses, the number of corpora lutea, and implantations were similar to control in all treated groups.

There were no treatment related effects with regard to litter size, foetal mortality, foetal bodyweight or external malformations. Similarly, no treatment-related skeletal effects were noted. The postnatal development was not affected by the target substance. No effects were noted on bodyweight development, except in the high dose group where there were significantly higher values for survival rate and lactation index. No adverse effect was noted with regard to the general and sexual development of the offspring. A NOEL of > 1 % in the diet, approximately 1200 mg/kg bw/d was derived.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), reproductive toxicity includes adverse effects on sexual function and fertility in adult males and females, adverse effects on development of the offspring and adverse effects on or via lactation.

Substances are classified in Category 1 for reproductive toxicity when they are known to have produced an adverse effect on sexual function and fertility, or on development in humans or when there is evidence from animal studies, possibly supplemented with other information, to provide a strong presumption that the substance has the capacity to interfere with reproduction in humans.

Substances are classified in Category 2 for reproductive toxicity when there is some evidence from humans or experimental animals, possibly supplemented with other information, of an adverse effect on sexual function and fertility, or on development, and where the evidence is not sufficiently convincing to place the substance in Category 1.

Test substance did not show any evidence of reproductive toxicity in a 3 -generation study and in embryotoxicity / teratogenicity studies. Accordingly, the highest tested doses, i.e. 1250 and 4000 mg/kg bw/d in rats and 1200 mg/kg bw/d in mice, were identified as no observed adverse effect levels.

On these bases, the substance is considered as non toxic for reproduction.