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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
A FDA study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974

Materials and methods

Principles of method if other than guideline:
Following mating, adult female albino CD-1 mice were dosed daily by oral intubation beginning on day 6 of gestation. Animals were observed daily and body weights recorded for 10 days. On day 17, Caesarian sections were performed on all dams and the numbers of implantation sites, resorption sites, and live and dead fetuses was recorded. General external and internal examinations were also made of the dams.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
CD-1

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Exposure period: 10 days (beginning on day 6 of gestation).
Frequency of treatment:
Daily
Duration of test:
17 days
Doses / concentrationsopen allclose all
Dose / conc.:
16 mg/kg bw/day (nominal)
Dose / conc.:
74 mg/kg bw/day (nominal)
Dose / conc.:
345 mg/kg bw/day (nominal)
Dose / conc.:
1 600 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Only female animals were used.
Control animals:
yes, concurrent no treatment

Examinations

Maternal examinations:
Animals were observed daily and body weights recorded for 10 days.
Ovaries and uterine content:
On day 17, Caesarian sections were performed on all dams and the numbers of implantation sites and resorption sites was recorded.
Fetal examinations:
After cesarea, the numbers of live and dead fetuses was recorded.
General external and internal examinations were also made of the dams.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No effects on maternal survival were observed at doses up to 1600 mg/kg bw/day.
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed

Maternal developmental toxicity

Number of abortions:
no effects observed
Description (incidence and severity):
No effects on nidation were observed at doses up to 1600 mg/kg bw/day.
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
No effects on nidation were observed at doses up to 1600 mg/kg bw/day.
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
no effects observed

Effect levels (maternal animals)

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested

Maternal abnormalities

Key result
Abnormalities:
no effects observed

Results (fetuses)

Fetal body weight changes:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No effects on fetal survival were observed at doses up to 1600 mg/kg bw/day.
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
no effects observed
Description (incidence and severity):
No effects on fetal survival were observed at doses up to 1600 mg/kg bw/day.
External malformations:
not specified
Skeletal malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The number of abnormalities seen in skeletal tissues of the test groups did not differ from the number occurring in the controls.
Visceral malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The number of abnormalities seen in soft tissues of the test groups did not differ from the number occurring in the controls.
Other effects:
no effects observed

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: Fetuses toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested

Fetal abnormalities

Key result
Abnormalities:
effects observed, non-treatment-related
Localisation:
other: soft and skeletal tissues

Overall developmental toxicity

Key result
Developmental effects observed:
no

Any other information on results incl. tables

No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.

Applicant's summary and conclusion

Conclusions:
No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.
Executive summary:

Following mating, adult female albino CD-1 mice were dosed daily by oral intubation beginning on day 6 of gestation. Tested doses were 0, 16, 74, 345, and 1600 mg/kg bw/day. Animals were observed daily and body weights recorded for 10 days. On day 17, Caesarian sections were performed on all dams and the numbers of implantation sites, resorption sites, and live and dead fetuses was recorded. General external and internal examinations were also made of the dams.

No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.