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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive toxicity of the test item was determined in the course of a Reproduction/Developmental Toxicity Screening study (OECD 421, GLP). Oral administration by gavage to male and female Wistar rats did not reveal signs of toxicity. The NOAEL for reproductive performance, fertility and developmental toxicity was set to 1000 mg/kg bw/d in male and female Wistar rats.

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
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Procedure and observations

The test item was given daily by gavage as a suspension in drinking water containing 1% Carboxymethylcellulose to groups of 10 male and 10 female Wistar rats (F0 animals) at dose levels of 100, 300 and 1000 mg/kg body weight/day (mg/kg bw/d). The duration of treatment covered a 2-week premating and mating period in both sexes, about one week postmating in males, and the entire gestation period as well as approximately 4 days of the lactation period in females with litters, and about 3 weeks of postmating period in nonpregnant females. A detailed clinical observation was performed in all animals. Body weights and food consumption were determined in F0 animals. Clinicochemical and hematological examinations as well as urinalyses were performed in all animals towards the end of the administration period. All animals were assessed by gross pathology; weights of selected organs were recorded and a histopathological examination was performed. The pups were sexed and examined for macroscopically evident changes on PND 0. They were weighed on PND 1 and on PND 4. Their viability was recorded. At necropsy on PND 4, all pups were sacrificed with CO2 and examined macroscopically for external and visceral findings.

Clinical examinations, reproductive performance, clinical pathology, histopathology and gross pathology did not reveal any finding in treated animals. Clinical examination and gross pathology did not reveal any effect on pups.

 

Discussion

Thus, under the conditions of this Reproduction/Developmental Toxicity Screening Test the oral administration by gavage to male and female Wistar rats did not reveal signs of toxicity. Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 1000 mg/kg bw/d in both sexes. The NOAEL for reproductive performance, fertility and developmental toxicity was set to 1000 mg/kg bw/d in male and female Wistar rats.

 Short description of key information: Reproductive toxicity of the test item was determined in the course of a Reproduction/Developmental Toxicity Screening study (OECD 421, GLP). Oral administration by gavage to male and female Wistar rats did not reveal signs of toxicity. The NOAEL for reproductive performance, fertility and developmental toxicity was set to 1000 mg/kg bw/d in male and female Wistar rats.

Effects on developmental toxicity

Description of key information

Reproductive toxicity of the test item was determined in the course of a Reproduction/Developmental Toxicity Screening study (OECD 421, GLP). Oral administration by gavage to male and female Wistar rats did not reveal signs of toxicity. The NOAEL for reproductive performance, fertility and developmental toxicity was set to 1000 mg/kg bw/d in male and female Wistar rats.

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
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

Procedure and observations

The test item was given daily by gavage as a suspension in drinking water containing 1% Carboxymethylcellulose to groups of 10 male and 10 female Wistar rats (F0 animals) at dose levels of 100, 300 and 1000 mg/kg body weight/day (mg/kg bw/d). The duration of treatment covered a 2-week premating and mating period in both sexes, about one week postmating in males, and the entire gestation period as well as approximately 4 days of the lactation period in females with litters, and about 3 weeks of postmating period in nonpregnant females. A detailed clinical observation was performed in all animals. Body weights and food consumption were determined in F0 animals. Clinicochemical and hematological examinations as well as urinalyses were performed in all animals towards the end of the administration period. All animals were assessed by gross pathology; weights of selected organs were recorded and a histopathological examination was performed. The pups were sexed and examined for macroscopically evident changes on PND 0. They were weighed on PND 1 and on PND 4. Their viability was recorded. At necropsy on PND 4, all pups were sacrificed with CO2 and examined macroscopically for external and visceral findings.

Clinical examinations, reproductive performance, clinical pathology, histopathology and gross pathology did not reveal any finding in treated animals. Clinical examination and gross pathology did not reveal any effect on pups.

Discussion

Thus, under the conditions of this Reproduction/Developmental Toxicity Screening Test the oral administration by gavage to male and female Wistar rats did not reveal signs of toxicity. Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 1000 mg/kg bw/d in both sexes. The NOAEL for reproductive performance, fertility and developmental toxicity was set to 1000 mg/kg bw/d in male and female Wistar rats.

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, as amended for the 30th time in Directive 2008/58/EC.

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, as amended for the second time in Directive (EC 286/2011).