Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

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

Effects on developmental toxicity

Description of key information
In a read-across developmental toxicity study conducted on rats the NOEL for developmental toxicity was found to be 16.3 mg/kg bw/day and the NOEL for maternal toxicity was 0.81 mg/kg bw/day.
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: study conducted in accordance to GLP and OECD Guideline For justification of read-across please refer to section 13.
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
1991
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 83-3 (Prenatal Developmental Toxicity Study)
Deviations:
no
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage MI USA
- Age at study initiation: 10 weeks

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
VEHICLE
- Concentration in vehicle: 0, 0.2, 2.0 and 4.0 mg/mL
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Days 6-15 of gestation
Frequency of treatment:
once daily
Duration of test:
post exposure period: days 21 of gestation
Remarks:
Doses / Concentrations:
0, 1, 10 and 20 mg/kg/d nominal; which were calculated to be 0, 0.81, 8.1 and 16.2 mg/kg bw/day considering the test item purity
Basis:
actual ingested
No. of animals per sex per dose:
25 females/group
Control animals:
yes
Maternal examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice daily during dosing, daily thereafter

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6, 9, 12, 15, 18 and 21

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- 3 day intervals

POST-MORTEM EXAMINATIONS: Yes
- Organs examined: liver and gravid uterine (weights), number of corpora lutea, number and status of implanatation sites

Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
Fetal examinations:
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
Statistics:
Fisher’s Exact Test, Levene’s test for equal variances, analysis of variance, and t-tests with Bonferroni probabilities for pairwise comparisons. Furthermore, Kruskal-Wallis test followed by Mann-Whitney U test when appropriate, were used.
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
At the highest dose level, body weight gains and food consumption were reduced. Ulceration of the stomach and gas filled intestines were also observed. Audible respiration occured at the 20 and 10 mg/kg bw dose groups.
Dose descriptor:
NOEL
Effect level:
0.81 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOEL
Effect level:
16.2 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
other: developmental toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Developmental toxicity including teratogenicity was not observed at any dose level.
Abnormalities:
not specified
Developmental effects observed:
not specified
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
16.2 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
reliable study, conducted in accordance to GLP and OECD Guideline
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

A developmental toxicity study was carried out in accordance with U.S. EPA Guideline 83-3 and OECD Guideline 414. 25 pregnant rats were treated orally (by gavage) with the read-across substance at concentrations of 0, 1, 10 and 20 mg/kg bw/d. Based on the test item purity of 80.8 %, the actual doses were calculated to be 0, 0.81, 8.1, 16.2 mg/kg bw/day. The dams were treated once daily during days 6-15 of gestation and were sacrificed on day 21 and the foetuses were examined for visceral and skeletal variations and malformations. In adult rats treated with 20 mg/kg bw/day body weight gains and food consumption were reduced. Ulceration of the stomach and gas filled intestines were also observed. Audible respiration occurred at the 20 and 10 mg/kg bw dose groups. No abnormalities were found in the foetuses. Based on these findings, the NOEL for maternal toxicity was found to be 0.81 mg/kg bw/day and the NOEL for developmental toxicity was determined to be 16.2 mg/kg bw/day in this study.

Justification for classification or non-classification

Based on the results of the reproduction/developmental toxicity screening with the read-across substance, the test item is not to be classified and labelled for reproduction/developmental toxicity according to Regulation (EC) No 1272/2008 (CLP).