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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
300 mg/kg bw/day
Additional information

The test substance was administered by daily oral gavage to four groups of 10 male and female Wistar Han rats at dose levels of 0, 30, 100 and 300 mg/kg body weight/day. Rats of the control group received the vehicle water alone. Males were exposed for 2 weeks prior to mating, during mating, and up to termination (for 29 days). The females were exposed for 2 weeks prior to mating, during mating, during gestation, and at least 4 days of lactation (for 41-55 days). No treatment related parental toxicity was observed at any dose level. No treatment-related changes were noted in any of the parental parameters investigated in this study (i.e. clinical appearance, body weight, food consumption, macroscopic examination, organ weights, and microscopic examination). No treatment related reproduction toxicity was observed at any dose level. No treatment-related changes were noted in any of the reproductive parameters investigated in this study (i.e. mating, fertility and conception indices, precoital time, and numbers of corpora lutea and implantation sites). In conclusion, treatment with the test substance by oral gavage in male and female Wistar Han rats at dose levels of 30, 100 and 300 mg/kg body weight/day revealed no parental and reproduction toxicity up to 300 mg/kg body weight/day. Based on these results, a parental and reproduction No Observed Adverse Effect Level (NOAEL) of at least 300 mg/kg body weight/day was derived.


Short description of key information:
Reproduction/developmental toxicity screening test (NOTOX Project 495051, 2012): No treatment related parental, reproduction and developmental toxicity was observed at any dose level (30, 100 and 300 mg/kg bw/day).

Effects on developmental toxicity

Description of key information
Reproduction/developmental toxicity screening test (NOTOX Project 495051, 2012): No treatment related parental, reproduction and developmental toxicity was observed at any dose level (30, 100 and 300 mg/kg bw/day).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Additional information

In the same screening study no treatment related developmental toxicity was observed at any dose level. One female (no. 78) of the high dose group was killed on Day 22 post-coitum due to delivery difficulties. At necropsy, twelve fetuses without abnormalities were present in the uterus. In addition, one female (no. 74) of the high dose group showed a total litter loss on Day 2 of lactation. These findings were not considered treatment related, but rather to have occurred by chance, as these are normal findings in this type of study and it was noted for single animals only. No treatment-related changes were noted in any of the developmental parameters investigated in this study (i.e. gestation index and duration, parturition, maternal care and early postnatal pup development consisting of mortality, clinical signs, body weight and macroscopy). In conclusion, treatment with the test substance by oral gavage in male and female Wistar Han rats at dose levels of 30, 100 and 300 mg/kg body weight/day revealed no developmental toxicity up to 300 mg/kg body weight/day. Based on these results, a developmental No Observed Adverse Effect Level (NOAEL) of at least 300 mg/kg body weight/day was derived.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the data, classification for reproduction/developmental toxicity is not warranted under Directive 67/548/EEC.

 

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

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for reproduction/developmental toxicity is not warranted under Regulation (EC) No.1272/2008.

Additional information

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