Registration Dossier

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: inquiry result
Title:
Unnamed
Year:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Annex V (Developmental toxicity study)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on mating procedure:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Number of dams and doses
25 at 0 mg/kg or mg/l
14
25 at 125 mg/kg or mg/l
25 at 500 mg/kg or mg/l
25 at 1000 mg/kg or mg/l

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Details on maternal toxic effects:
From a preliminary dose range finding study, dose levels of
125 mg/kg, 500 mg/kg and 1000 mg/kg were used.
All maternal animals survived to the scheduled necropsy on
gestation day 20. Treatment related clinical signs included
salivation immediately following dosing in all 3 treatment
groups between gestation days 10 and 19. Changes in general
appearance was also noted following dosing during the same
period in the 125 mg/kg, 500 mg/kg and 1000 mg/kg treatment
groups with animal rubbing their faces on the cage surface,
and excessive grooming and clonic tremors of the forelimbs.
In the 500 mg/kg and 1000 mg/kg treatment groups, animals
were observed to erratically paw the cage following dosing
between gestation days 11 and 19. All these findings had
subsided by 1 hour post dosing. Other clinical signs such
as hair loss on various body surfaces occurred also in the
control group and was not indicative of being treatment
related
At necropsy there were no macroscopic findings thought to be
treatment related.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: other:

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Details on embryotoxic / teratogenic effects:
Effects on fetus - Gross:
Gravid litter weights, litter size and fetal body weights
were unaffected by the test substance administration. In
the 500 mg/kg dose group one foetus had bilateral
anophthalmia and one foetus had unilateral anophthalmia. No
other external malformations and no external developmental
variations were observed in foetuses at any dose levels
Effects on fetus - Soft tissue:
In the 500mg/kg dose group one foetus had hydrocephaly
consisting of increased cavitation of both lateral
ventricles and the third ventricle. One foetus in the 1000
mg/kg group had a retroesophageal aortic arch. No other
soft tissue malformations were noted.
Effects on fetus - Skeletal:
No skeletal malformations were observed in foetuses at any
dose level.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion