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Key value for chemical safety assessment

Effects on fertility

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 fertility toxicity was set to 1110 mg/kg bw/d in male and female Wistar rats.

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Further information are included as attachment in chapter 13 of the IUCLID dossier.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Key result
Dose descriptor:
NOAEL
Effect level:
1 100 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed
Critical effects observed:
no
Key result
Dose descriptor:
NOAEL
Effect level:
> 0 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 100 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed
Critical effects observed:
no
Key result
Dose descriptor:
NOAEL
Generation:
F2
Effect level:
> 0 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed
Critical effects observed:
no
Reproductive effects observed:
not specified
Conclusions:
Under the conditions of the Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test the oral administration by gavage to male and female Wistar rats did not reveal signs of toxicity.
The no observed adverse effect level (NOAEL) for general systemic toxicity was 1110 mg/kg bw/d in both sexes. 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 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

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.

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 general, systemic toxicity was1110 mg/kg bw/d.

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 developmental toxicity was set to 1110 mg/kg bw/d in male and female Wistar rats.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Further information are included as attachment in chapter 13 of the IUCLID dossier.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Key result
Dose descriptor:
NOAEL
Effect level:
1 100 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: no effects observed
Abnormalities:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
> 1 100 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed
Developmental effects observed:
not specified
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

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.

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.

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008, as amended for the thirteenth time in Regulation (EU) No 2018/1480. As a result the substance is not considered to be classified for reproductive toxicity under Regulation (EC) No. 1272/2008.