Registration Dossier

Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

Test guidelineopen allclose all
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous

Test animals

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

Administration / exposure

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
Doses / concentrations
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

Examinations

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.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

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.

Effect levels (maternal animals)

open allclose all
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

Results (fetuses)

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.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion