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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
other: unpublished report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Test Guideline 421 (1998).
Deviations:
yes
Remarks:
Enhance OECD 421 method including: 1) enhanced evaluation of toxicity in F0 generation, 2) evaluation of developmental landmarks in F1 generation, and 3) following F1 generation in adulthood with continued exposure and evaluation of toxicity.
Principles of method if other than guideline:
Method: other: see below This study exceeds the OECD 421 study design as follows: (1) enhanced evaluation of toxicity in the F0 generation, including the evaluation of a recovery group of F0 males; (2) evaluation of developmental landmarks in the F1 generation; and (3) following the F1 offspring to adulthood, with continued exposure and assessments of reproductive structures and functions, including potential effects on sperm.
GLP compliance:
yes

Test material

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

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
After the two-week prebreed exposure period, animals were randomly mated within treatment groups for a two-week mating period to produce the F1 generation, with continuing exposure.
Duration of treatment / exposure:
Males = 4 weeks (2 weeks pre-breeding, 2 weeks mating) Females = 10 weeks (2 weeks prebeed, 2 weeks mating, 3 weeks gestation, and 3 weeks lactation)
Frequency of treatment:
Daily
Control animals:
yes, concurrent vehicle
Details on study design:
Duration of test: F1 Generation dosed until Post natal day 85

Examinations

Maternal examinations:
See Additional remarks on Methods and Materials
Ovaries and uterine content:
See Additional remarks on Methods and Materials.
Fetal examinations:
On the day of birth (postnatal day [pnd] 0), anogenital distance (AGD) was measured and body weights recorded for all live F1 pups in all litters. F1 litters were culled on pnd 4 to yield, as nearly as possible, five males and five females per litter. The culled F1 pups were weighed, euthanized, and necropsied with complete external and visceral examinations. For the remaining F1 pups, survival indices were calculated at least weekly through weaning (pnd 21).
Statistics:
No data
Indices:
No data
Historical control data:
No data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

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

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

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

Any other information on results incl. tables

The examinations didn't reveal any developmental effect up to the dose level of 1000 mg/kg/day

Applicant's summary and conclusion

Conclusions:
Used for data submission
Executive summary:

Used for data submission