Registration Dossier

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:
weight of evidence
Study period:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation for a read-across substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1972
Report Date:
1972

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
- lack of details on test article (missing important information on purity, stability, & homogeneity) & information on verification of test concentrations.
GLP compliance:
no
Remarks:
- study predates GLP
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): FDA 71-31 (Sorbitol)
- Physical state: White crystals

Test animals

Species:
mouse
Strain:
CD-1
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: 28.2 to 30.6 g
- Fasting period before study: Not reported
- Housing: Individually Housed in disposable plastic cages in temperature and humidity-controlled quarters
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Not reported
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not reported
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: Not reported
- Length of cohabitation: Not reported
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy
Duration of treatment / exposure:
Test article administration = Day 6 to Day 15. Animals were killed on Day 17.
Frequency of treatment:
Once/day from Days 6 to 15.
Duration of test:
Approximately 20 days.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 16, 74, 350, or 1600 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
Between 19 and 21 pregnant females/dose.
Control animals:
yes, sham-exposed
Details on study design:
- Dose selection rationale: Not reported

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: on Days 0, 6, 11, 15, and 17 of gestation

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 17
- Organs examined: Uterus (more organs not reported)
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: one-third per litter
- Skeletal examinations: Yes: two-thirds per litter
- Head examinations: No
Statistics:
Statistics performed; however, statistical tests were not reported.
Indices:
Not reported
Historical control data:
Not reported

Results and discussion

Results: maternal animals

Maternal developmental toxicity

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

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Basis for effect level:
other: maternal toxicity
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Dose descriptor:
NOAEL
Basis for effect level:
other: developmental toxicity
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Results (fetuses)

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

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

NOAEL values were not reported by the study authors.  Review of the study data suggests that a NOAEL of 1600 mg/kg bw (the highest level administered) can be considered for both maternal and fetal toxicity based on a lack of toxicity.