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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
750 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

In a GLP compliant combined repeated dose toxicity study with the reproductive/developmental toxicity screening test, performed according to OECD guideline 422, male and female Wistar F0 rats were administered to test substance orally by gavage. These animals received 0, 100, 250, and 750 mg/kg bw/day at a dose volume of 4 mL/kg bw day in olive oil, 10 animals/sex/dose. Males were treated for 2 weeks prior to mating until necropsy after 4 weeks of treatment. Females were treated for 2 weeks prior to mating, then throughout mating, gestation and until at least Day 4 of lactation. The following parameters and end points were evaluated in this study: clinical signs, body weights, food consumption, ophthalmology, detailed functional observations, clinical pathology parameters (haematology, coagulation and clinical chemistry), fertility, mating and pregnancy performance, maternal care, pup performance (litter survival and litter/pup weight), gross necropsy findings, organ weights, and histopathological examinations. Dosing with the test substance at dose levels of up to 750 mg/kg/day was not associated with treatment related body weight or food consumption changes, ophthalmoscopy findings or gross necropsy findings at any dose levels. In addition, fertility, mating and pregnancy performance and pup/litter performance were similar between all groups. Clinical observations of excess salivation and ploughing behaviour in both sexes at 250 and 750 mg/kg/day were considered not to be adverse due to their transient nature. Changes in clinical pathology (higher glucose levels in males at all dose levels, higher white blood cell, neutrophil, lymphocyte and basophil counts in males at 750 mg/kg/day, and higher alanine aminotransferase in females at 250 and 750 mg/kg/day) and higher liver and kidney weights in males at 250 and 750 mg/kg/day were considered not to be adverse or toxicologically significant as there were no histopathological findings or other findings to correlate with these changes and findings were only noted in one sex. In conclusion, it was considered that based on the results of this study, the parental and reproductive/developmental No Observed Adverse Effect Level (NOAEL) was 750 mg/kg/day.


Short description of key information:
The NOAEL for reproductive toxicity was determined to be 750 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:
There is only one study available.

Effects on developmental toxicity

Description of key information
The NOAEL for marental and developmental toxicity was determined to be 750 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
750 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 GLP compliant combined repeated dose toxicity study with the reproductive/developmental toxicity screening test, performed according to OECD guideline 422, male and female Wistar F0 rats were administered to test substance orally by gavage. These animals received 0, 100, 250, and 750 mg/kg bw/day at a dose volume of 4 mL/kg bw day in olive oil, 10 animals/sex/dose. Females were treated for 2 weeks prior to mating, then throughout mating, gestation and until at least Day 4 of lactation. The following parameters and end points were evaluated in this study: clinical signs, body weights, food consumption, ophthalmology, detailed functional observations, clinical pathology parameters (haematology, coagulation and clinical chemistry), fertility, mating and pregnancy performance, maternal care, pup performance (litter survival and litter/pup weight), gross necropsy findings, organ weights, and histopathological examinations. Dosing with the test substance at dose levels of up to 750 mg/kg/day was not associated with treatment related body weight or food consumption changes, ophthalmoscopy findings or gross necropsy findings at any dose levels. In addition, fertility, mating and pregnancy performance and pup/litter performance were similar between all groups. Clinical observations of excess salivation and ploughing behaviour at 250 and 750 mg/kg/day were considered not to be adverse due to their transient nature. Higher alanine aminotransferase in females at 250 and 750 mg/kg/day were considered not to be adverse or toxicologically significant as there were no histopathological findings or other findings to correlate with these changes and findings. In conclusion, it was considered that based on the results of this study, the maternal and reproductive/developmental No Observed Adverse Effect Level (NOAEL) was 750 mg/kg/day.


Justification for selection of Effect on developmental toxicity: via oral route:
There is only one study available.

Justification for classification or non-classification

No reproductive effects were observed related to the repeated oral exposure. Based on this classification for reproductive toxicity is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.