Propionic anhydride

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

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

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

(documentation deficiencies)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Calcium dipropionate

EC Number:

223-795-8

EC Name:

Calcium dipropionate

Cas Number:

4075-81-4

Molecular formula:

C3H6O2.1/2Ca

IUPAC Name:

calcium dipropanoate

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 or test system 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

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