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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
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
Purity, source of test substance, analytical verification, statistical methods, temperature, humidity, age, acclimation, environmental conditions, not reported
GLP compliance:
no
Remarks:
Study pre-dates GLP
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Glucono Delta Lactone

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: Average weight on day 0 = 217.83 g
- Fasting period before study: Not reported
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:Not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature and humidity was controlled but numbers not reported
- Humidity (%): temperature and humidity was controlled but numbers not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light):Not reported


IN-LIFE DATES: Not reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Test material was prepared and doses calculated according to the following table:

Dosage (mg/kg) Dose(ml/kg Concentration (mg/ml)
<250 1 <250
251-500 2 125-250
501-750 3 133-250
751-1000 4 187-250
1001-1250 5 200-250
1251-1500 6 208-250
1501-1600 6.4 235-250

- No further details on preparation of dosing solutions

VEHICLE
- Amount of vehicle (if gavage): Not reported
- Lot/batch no. (if required): Not reported
- Purity:Not reported


Analytical verification of doses or concentrations:
no
Details on mating procedure:
- Impregnation procedure: mated with young adult males, no further details
- If cohoused: Not reported
- M/F ratio per cage: Not reported
- Length of cohabitation: Not reported
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. Not reported
- Further matings after two unsuccessful attempts: Not reported
- Verification of same strain and source of both sexes: Not reported
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy
- Any other deviations from standard protocol: Not reported
Duration of treatment / exposure:
Day 6 to day 15 of gestation
Frequency of treatment:
Daily
Duration of test:
17 days (mating to death)
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg bw/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
5.94 mg/kg bw/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
27.6 mg/kg bw/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
128.0 mg/kg bw/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
594.0 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
21 to 24 pregnant females per group
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: according to table included in report however no further rationale or reference for table
- Rationale for animal assignment (if not random): random

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations checked in table included: No


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: End of treatment


BODY WEIGHT: Yes
- Time schedule for examinations:days 0, 6, 11, 15, and 20 of gestation


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Not applicable - Oral gavage study


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not applicable - Oral gavage study


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: reproductive organs
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: No
- Number of implantations: Yes
- Number of resorptions: Yes
- Number of early resorptions: No
- Number of late resorptions: No
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter
- Head examinations: Yes: 2/3 per litter
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 effects

Details on maternal toxic effects:
None

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
594 mg/kg bw/day (actual dose received)
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the controls.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion