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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
30 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
Additional information

The purpose of this study was to generate information on possible effects on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus and parturition. The test item was administered orally by gavage to male rats at concentrations of 10, 30 and 90 mg/kg bw/day for 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum.

All pairs mated. Mean precoital time, fertility index and conception rate were not affected by the treatment with the test item. Mean number of corpora lutea and implantations per dam and the post-implantation loss were not affected by the treatment with the test item. The mean postnatal loss between days 0 and 4 post partum was higher and the mean number of living pup on day 4 post partum were lower consequently the viability index was statistically significantly lower in the high dose group therefore these were considered to be test item-related effects. No histological evidence of toxicological properties in the reproductive organs and tissues examined were detected at 90 mg/kg body weight/day.


Short description of key information:
An OECD 422 study was performed to generate information on possible effects on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus and parturition. The test item was administered orally by gavage to male rats at concentrations of 10, 30 and 90 mg/kg bw/day for 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. Mean precoital time, fertility index and conception rate were not affected by the treatment with the test item. Mean number of corpora lutea and implantations per dam and the post-implantation loss were not affected by the treatment with the test item.

Effects on developmental toxicity

Description of key information
An OECD 422 study was performed to generate information on possible effects on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus and parturition. The test item was administered orally by gavage to male rats at concentrations of 10, 30 and 90 mg/kg bw/day for 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. Based on the significantly lower body weight of pups and the decreased viability index on day 4 post partum at the high dose level of 90 mg/kg body weight/day, the NOAEL for reproduction/ developmental toxicity was considered to be 30 mg/kg body weight/day. 
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
30 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

The purpose of this study was to generate information on possible effects on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus and parturition. The test item was administered orally by gavage to male rats at concentrations of 10, 30 and 90 mg/kg bw/day for 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum.

The mean litter size of dams receiving 90 mg/kg body weight/day was slightly lower when compaired to controls. Mean postnatal loss between days 0 and 4 post partum was higher and the mean number of living pup on day 4 post partum was lower in the group receiving 90 mg/kg body weight/day. The sex ratio was not affected. No abnormal pup was noted at any dose level. At the dose level of 90 mg/kg body weight/day, three male pups in three different litters (nos. 72, 74, 79) had no milk in stomach at first litter check and they were missing afterwards on days 4, 2, 2 post partum, respectively.

Mean pup weights on day 1 post partum were unaffected, whereas, the mean body weight of pups on day 4 post partum (dose level of 90 mg/kg body weight/day) was significantly lower and therefore considered to be a test item-related effect. At necropsy of pups, there were no abnormal findings noted.

Based on the significantly lower body weight of pups and the decreased viability index on day 4 post partum at the high dose level of 90 mg/kg body weight/day, the NOAEL for reproduction/ developmental toxicity was considered to be 30 mg/kg body weight/day.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for reproductive toxicity under Directive 67 / 548 / EEC.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for reproductive toxicity under Regulation (EC) No. 1272/2008.

Additional information