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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
1 110 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

Read across justification

Toxicity after repeated dose administration of the test substance was not determined. Thus, it is acceptable to derive information on toxicity from structural analogues since all of the substances are salts and share high similarity in structure. Moreover, all analogue substances are minimal soluble in water. A detailed read across justification is given in Annex I of the CSR.

Procedure and observations

The test item was administered orally by gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at dose levels of 0 mg/kg body weight/day (drinking water served as vehicle), 110 mg/kg bw/d, 330 mg/kg bw/d and 1110 mg/kg bw/d. The duration of treatment covered a 2-week premating and a mating period in both sexes, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation and 2 weeks thereafter in 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 and FOB 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.

Regarding clinical examinations, no signs of general systemic toxicity were observed in male or female parental animals of all test groups during the entire study. The test item did not influence fertility or reproductive performence. Adverse effects regarding clinical pathology were not observed. Macroscopically yellow discoloration of the content of the digestive tract in numerous animals was observed. In single treated animals and single organs of the digestive tract these yellow pigments could also be observed histopathologically. Beside the discoloration no signs of toxicity in the respective tissues were noted.

Discussion

Yellowish discoloration of the digestive tract and feces is regarded to be a consequence to the oral intake of the yellow test substance and therefore treatment related but not adverse in nature. Thus, under the conditions of this reproduction/developmental toxicity screening test the NOAEL (no observed adverse effect level) for reproductive performance and fertility was 1110 mg/kg bw/d.

The NOAEL for developmental toxicityin the F1 progeny was found to be1110 mg/kg bw/d. The NOAEL for general, systemic toxicity was1110 mg/kg bw/d.


Short description of key information:
Reproductive toxicity of the test item(structural analogue) was determined in the course of a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening study (OECD 422, 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 1110 mg/kg bw/d in male and female Wistar rats.

Effects on developmental toxicity

Description of key information
Reproductive toxicity of the test item(structural analogue) was determined in the course of a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening study (OECD 422, 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 1110 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
1 110 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

Read across justification

Toxicity after repeated dose administration of the test substance was not determined. Thus, it is acceptable to derive information on toxicity from structural analogues since all of the substances are salts and share high similarity in structure. Moreover, all analogue substances are minimal soluble in water. A detailed read across justification is given in Annex I of the CSR

Procedure and observations

The test item was administered orally by gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at dose levels of 0 mg/kg body weight/day (drinking water served as vehicle), 110 mg/kg bw/d, 330 mg/kg bw/d and 1110 mg/kg bw/d. The duration of treatment covered a 2-week premating and a mating period in both sexes, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation and 2 weeks thereafter in 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 and FOB 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.

Regarding clinical examinations, no signs of general systemic toxicity were observed in male or female parental animals of all test groups during the entire study. The test item did not influence fertility or reproductive performence. Adverse effects regarding clinical pathology were not observed. Macroscopically yellow discoloration of the content of the digestive tract in numerous animals was observed. In single treated animals and single organs of the digestive tract these yellow pigments could also be observed histopathologically. Beside the discoloration no signs of toxicity in the respective tissues were noted.

Discussion

Yellowish discoloration of the digestive tract and feces is regarded to be a consequence to the oral intake of the yellow test substance and therefore treatment related but not adverse in nature. Thus, under the conditions of this reproduction/developmental toxicity screening test the NOAEL (no observed adverse effect level) for reproductive performance and fertility was 1110 mg/kg bw/d.

The NOAEL for developmental toxicityin the F1 progeny was found to be1110 mg/kg bw/d. The NOAEL for general, systemic toxicity was1110 mg/kg bw/d.

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.