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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study according to OECD 422. Peer review was conducted by a Japanese toxicological expert group at March 5, 2001. However, only second source material available

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD TG 422 combined repeated dose and reproductive/developmental toxicity screening test
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity 100 %
- Batch/ LotNo. 4879

Test animals

Species:
rat
Strain:
Crj: CD(SD)

Administration / exposure

Route of administration:
oral: gavage
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Exposure period: male: 46 days from 14 days prior to mating; female: 41-45 days from 14 days prior to mating to day 4 postpartum throughout mating and pregnancy
Premating exposure period (males): 14 days
Premating exposure period (females): 14 days
Frequency of treatment:
once daily
Duration of test:
42 to 47 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 250, 500, 1000 mg/kg bw/day
Basis:

No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: 1, 2, 3, 5, 7, 10 and 14 d; then weekly

BODY WEIGHT: Yes
- Time schedule for examinations: 1, 2, 3, 5, 7, 10 and 14 d; then weekly

POST-MORTEM EXAMINATIONS: Yes
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
Fetal examinations:
- External examinations: Yes: all per litter
Indices:
Viability index, live birth index

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No effects observed.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No external anomalies were observed during macroscopic examination. Live birth index and viability index were not altered by treatment.
Sex ratio, number of pups alive on day 4 of lactation and body weight on day 0 and 4 post natal were comparable to control.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion