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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:
other: Comparable to guideline without detailed documentation

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:
(documentation deficiencies)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:

- Name of test material (as cited in study report): calcium propionate
- Physical state: fine white crystalline
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: adult
- Average body weight at study initiation: 229.5 g
- Fasting period before study: no data
- Housing: individually
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): tap water, free access
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Animals were housed in temperature and humidity controlled quarters

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: no data

Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: no data
- Length of cohabitation: no data
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as day 0
- Any other deviations from standard protocol: no
Duration of treatment / exposure:
days 6-15 of gestation
Frequency of treatment:
daily
Duration of test:
20 days
Doses / concentrations
Remarks:
Doses / Concentrations:
3, 14, 65, 300 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
24 females
Control animals:
yes, sham-exposed
Details on study design:
- Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Positive control: Acetylsalicyl acid (ASA) administered at 250 mg/kg bw

Examinations

Maternal examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

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


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Frequency of measurement: daily


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice: on gestation day 20 by surgical anaesthesia
- Organs examined: no data


Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes, the number of live and dead foetuses were recorded
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of 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

Results and discussion

Results: maternal animals

Maternal developmental toxicity

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

Details on maternal toxic effects:
The administration of up to 300 mg/kg (body weight) of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on on dams.

Effect levels (maternal animals)

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

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
TEST SUBSTANCE:
- The administration of up to 300 mg/kg (body weight) of the test material to pregnant rat for 10 consecutive days had no clearly discernible effect on nidation or fetal survival.
- 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 sham-treated controls


POSITIVE CONTROL (ASA)
- Weight reduction in foetuses of dams treated with 250 mg/kg bw with a reduction of the average weight of about 41.4 compared to controls
- Increased number of total resorptions with a total number of resorptions in the positive control reaching 102 as compared to only 6 in the controls. There was also an increased percentage of partial and complete resorption in comparison to negative control animals. The percentage of partial resorptions in positive control animals was 79.2% compared to only 17.4 in negative control animals. Twenty five percent of the embryos were completed resorbed as compared to 0% in the negative control animals.
- An average of 6.6 fetuses/ dam were alive at necropsy in the positive control group totalling 160 in all. In comparison, 10.6 fetuses/ dam were alive in the negative control group making a total of 243 fetuses
- Skeletal investigations revealed malformations and variations of the sternebrae, ribs, verterbrae, skull and extremities in animals of the positive control group (see attachment). Miscellaneous findings included missing and reduced hyoids
- Soft tissue investigations included exencephaly, spina bifida, enterohepatocele

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day (actual dose received)
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

see attachment for summary of results

Applicant's summary and conclusion