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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Under the conditions of the study, there were no adverse effects of treatment upon reproductive or developmental parameters up to the high dose level of 1 000 mg/kg/day.

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:
The study was performed in accordance with standardised guidelines and under GLP conditions. The study was assigned a reliability score of 1 in line with the principles for assessing data quality as defined by Klimisch et al. (1997). The quality of the database is therefore considered to be good.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

The potential for the test material to cause reproductive/developmental effects, was investigated in a GLP study conducted in accordance to the standardised guideline OECD 421.

The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Three groups of ten male and ten female rats received the test material at doses of 100, 300 or 1 000 mg/kg/day by oral (gavage) administration at a dose volume of 5 mL/kg. Males were treated daily for 15 days before pairing, during the pairing period, and then up to necropsy after a minimum of four consecutive weeks. Females were treated daily for 15 days before pairing, throughout pairing and gestation, and until Day 6 of lactation. Females were allowed to litter and rear their offspring before they were killed on Day 7 of lactation. The F1 generation received no direct administration of the test item; any exposure was in utero or via the milk. A similarly constituted Control group received the vehicle, corn oil, at the same dose volume as the treated groups.

During the study, clinical condition, body weight, food consumption, pre-coital interval, mating performance and fertility, gestation length, organ weight and macroscopic pathology and histopathology investigations of organs of the reproductive system were undertaken. The clinical condition, litter size, survival, sex ratio, body weight and macropathology for all offspring were also assessed.

The oral (gavage) administration of the test material to Han Wistar (RccHan™;WIST) rats for at least 4 weeks at dose levels of 100, 300 or 1 000 mg/kg/day was well tolerated, with no deaths and no effect of treatment upon the clinical condition of animals. There was no effect of treatment on body weight gain or food consumption at any of the dose levels investigated and pre-coital interval, mating performance and fertility and gestation length were unaffected. The number of offspring born, offspring sex ratio and offspring survival and growth to Day 7

of age were unaffected at dose levels up to 1 000 mg/kg/day and there were no clinical observations or macroscopic necropsy findings amongst offspring that were considered to relate to parental treatment.

There were no treatment-related macroscopic or microscopic findings in parent animals, and no differences in organ weights, which were considered to be related to treatment.

It is concluded that oral administration of the test material to male and female Han Wistar (RccHan™;WIST) for at least 4 weeks at dose levels of 100, 300 or 1 000 mg/kg/day was well tolerated, with no effect of treatment upon reproductive or developmental parameters up to the high dose level of 1 000 mg/kg/day.

Effects on developmental toxicity

Description of key information

Under the conditions of the study, there were no adverse effects of treatment upon reproductive or developmental parameters up to the high dose level of 1 000 mg/kg/day.

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:
The study was performed in accordance with standardised guidelines and under GLP conditions. The study was assigned a reliability score of 1 in line with the principles for assessing data quality as defined by Klimisch et al. (1997). The quality of the database is therefore considered to be good.
Additional information

The potential for the test material to cause reproductive/developmental effects, was investigated in a GLP study conducted in accordance to the standardised guideline OECD 421. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Three groups of ten male and ten female rats received the test material at doses of 100, 300 or 1 000 mg/kg/day by oral (gavage) administration at a dose volume of 5 mL/kg. Males were treated daily for 15 days before pairing, during the pairing period, and then up to necropsy after a minimum of four consecutive weeks. Females were treated daily for 15 days before pairing, throughout pairing and gestation, and until Day 6 of lactation. Females were allowed to litter and rear their offspring before they were killed on Day 7 of lactation. The F1 generation received no direct administration of the test item; any exposure was in utero or via the milk. A similarly constituted Control group received the vehicle, corn oil, at the same dose volume as the treated groups.

During the study, clinical condition, body weight, food consumption, pre-coital interval, mating performance and fertility, gestation length, organ weight and macroscopic pathology and histopathology investigations of organs of the reproductive system were undertaken. The clinical condition, litter size, survival, sex ratio, body weight and macropathology for all offspring were also assessed.

The oral (gavage) administration of the test material to Han Wistar (RccHan™;WIST) rats for at least 4 weeks at dose levels of 100, 300 or 1 000 mg/kg/day was well tolerated, with no deaths and no effect of treatment upon the clinical condition of animals. There was no effect of treatment on body weight gain or food consumption at any of the dose levels investigated and pre-coital interval, mating performance and fertility and gestation length were unaffected. The number of offspring born, offspring sex ratio and offspring survival and growth to Day 7

of age were unaffected at dose levels up to 1 000 mg/kg/day and there were no clinical observations or macroscopic necropsy findings amongst offspring that were considered to relate to parental treatment.

There were no treatment-related macroscopic or microscopic findings in parent animals, and no differences in organ weights, which were considered to be related to treatment.

It is concluded that oral administration of the test material to male and female Han Wistar (RccHan™;WIST) for at least 4 weeks at dose levels of 100, 300 or 1 000 mg/kg/day was well tolerated, with no effect of treatment upon reproductive or developmental parameters up to the high dose level of 1 000 mg/kg/day.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for reproductive or developmental toxicity.