Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

The test item was not tested itself. Two structural analogues were tested in a reproduction/developmental toxicity screening test in rats (according to OECD 421 and 422, GLP). According to these studies, the NOAEL for parental toxicity and for reproductive performance (mating and fertility) was considered to be 1000 mg/kg bw/day, which was the highest dose tested.

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
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No signs of test substance toxicity at a dosage of 1000 mg/kg bw/d applied (high dose equals limit dose)
Remarks on result:
other: CAS 31274-51-8
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: No treatment-related adverse effects observed up to and including the highest dose level of 1000 mg/kg bw
Remarks on result:
other: CAS 446824-06-2
Critical effects observed:
no
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No test substance related effects were observed on pups after birth, at a dosage of 1000 mg/kg bw/d applied (high dose equals limit dose)
Remarks on result:
other: CAS 31274-51-8
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: No treatment-related adverse effects observed up to and including the highest dose level of 1000 mg/kg bw
Remarks on result:
other: CAS 446824-06-2
Critical effects observed:
no
Reproductive effects observed:
no
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
Quality of whole database:
Read across sources according to OECD TG 421/422, GLP, Klimisch 1/2
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


Regarding toxicity to reproduction, there are no data of the test substance itself. Reliable experimental data on two read across substance are available (see justification attached to IUCLID section 7.8.1 and 13):


In a GLP-conform study according to OECD guideline 421, the structural analogue (CAS 446824-06-2) 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 (corn oil served as vehicle), 100 mg/kg bw/d, 300 mg/kg bw/d and 1000 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. All animals were assessed by gross pathology; weights of selected organs were recorded and a histopathological examination was performed. Clinical examinations, reproductive performance, clinical pathology, histopathology and gross pathology did not reveal any finding in treated animals. Viability, sex ratio and body weight of the pups was not affected. Examination of the ovaries and the uterine content did not overt any effect on uterus weight, number of implantations or resorptions.


In accordance with OECD guideline 422 and GLP, a combined repeated dose toxicity study with a reproduction/developmental toxicity screening test was performed using a formulation containing the structurally analogue substance CAS 31274-51-8 (47.6 % active substance). Three groups of 10 male and 10 female Sprague-Dawley rats received the test item formulation daily, by oral gavage administration before mating, through mating and, for the females, through gestation until day 4 post-partum, at dose-levels of 210, 1050 and 2100 mg/kg bw/d (equivalent to dose-levels of 100, 500 and 1000 mg/kg bw/d of the test item, respectively). Two other groups of 10 males and 10 females received either the vehicle (purified water) or placebo (respective formulation without test item) alone, under the same experimental conditions and acted as control groups. The dosing volume was 5 mL/kg bw/day. The litters were sacrificed on day 5 post-partum. At all dose-levels with the test item, treatment-related mortalities or clinical signs of toxicity did not occur. There were no effects on mean body weight gain or food consumption of males or females compared to the control group given purified water; however, when compared to the placebo control group the females had higher body weight gains and food consumption. Adverse effects did not occur based on hematology, blood biochemistry or urinalysis parameters. Estrous cycling, pairing, mating or fertility were not adversely affected in any dose-group and pups showed no effects after birth in any group. Test item-related effects did not occur on organ weights and macroscopic abnormalities were not apparent. Microscopic examination revealed aggregates of large histiocytes in the bronchioles of two females of the 1000 mg/kg/day dose-group, an effect attributed to accidental aspiration of the dosing mixture subsequent to administration and not to the test item directly. 


 


Conclusion


Under the conditions of the previously described Reproduction/Developmental Toxicity Screening Tests, the oral administration of two analogue substances by gavage to male and female Wistar rats did not reveal signs of toxicity. Thus, the NOAEL for parental toxicity, for reproductive performance (mating and fertility) and for developmental toxicity is 1000 mg/kg bw.


Due to the high comparability to the two structural analogues, the same outcome can be expected for CAS 204848-45-3.

Effects on developmental toxicity

Description of key information

The test item was not tested itself. Two structural analogues were tested in a reproduction/developmental toxicity screening test in rats (according to OECD 421 and 422, GLP) and the NOAEL for developmental toxicity was found to be 1000 mg/kg bw/day, which was the highest dose tested.

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
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: No treatment-related adverse effects observed up to and including the highest dose level of 1000 mg/kg bw
Remarks on result:
other: CAS 446824-06-2 (OECD 421)
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: No signs of test substance toxicity at a dosage of 1000 mg/kg bw/d applied (high dose equals limit dose)
Remarks on result:
other: CAS 31274-51-8 (OECD 422)
Key result
Abnormalities:
no effects observed
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: No treatment-related adverse effects observed up to and including the highest dose level of 1000 mg/kg bw
Remarks on result:
other: CAS 446824-06-2 (OECD 421)
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: No test substance related effects were observed on pups after birth, at a dosage of 1000 mg/kg bw/d applied (high dose equals limit dose)
Remarks on result:
other: CAS 31274-51-8 (OECD 422)
Abnormalities:
no effects observed
Developmental effects observed:
no
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
Quality of whole database:
Read across sources according to OECD TG 421/422, GLP, Klimisch 1/2
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

Please refer to section "Effects on fertility - Additional information" within this endpoint summary

Justification for classification or non-classification

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


The available screening study is reliable and suitable for classification purposes under Regulation 1272/2008. No adverse effects on fertility or development were observed in screening studies in rats (OECD 422/421). As a result, the substance is not considered to be classified for fertility or developmental toxicity under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.

Additional information