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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP status not known, near guideline study, published in peer reviewed literature, limitations in design and/or reporting but otherwise adequate for assessment.

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.31 (Prenatal Developmental Toxicity Study)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
FDA 71-78 (Apple cider vinegar (acetic acid); table strength 5%)
Clear amber coloured liquid

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
Virgin adult female albino rats (Wistar derived stock) were individually housed in mesh bottom cages in temperature and humidity controlled quarters with free access to food and fresh tap water.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
The females were dosed with the indicated dosages by oral intubations. The controls were sham treated with the vehicle at a level equivalent to the group receiving the highest test dose. The test material was prepared and doses calculated according to the following table:

Dosage Dose Concentration
(mg/kg) (ml/kg) (mg/ml)
250 1 250
251 - 540 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

Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
The females were mated with young adult males, and observation of the vaginal sperm plug was considered Day 0 of gestation.
Duration of treatment / exposure:
Days 6 - 15 of gestation
Frequency of treatment:
Daily
Duration of test:
Days 0-20 of gestation
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 16, 74.3, 345, 1600 mg/kg/day
Basis:
nominal conc.
No. of animals per sex per dose:
25 mated females
Control animals:
yes, sham-exposed
Details on study design:
An additional group of mated females was dosed with 150 mg/kg aspirin and served as a positive control

Examinations

Maternal examinations:
Body weights were recorded on Days 0, 6, 11, 15, and 20 of gestation.
All animals were observed daily for appearance and behaviour with particular attention to food consumption and weight, in order to rule out any abnormalities which may have occurred as a result of anorexic effects in the pregnant female animal
Ovaries and uterine content:
On Day 20 all dams were subjected to Caesarean section under surgical anesthesia, and the numbers of implantation sites, resorption sites, and live and dead fetuses were recorded. The urogenital tract of each dam was examined in detail for anatomical normality.
Fetal examinations:
The body weights of the live pups were recorded. All fetuses were examined grossly for the presence of external congenital abnormalities. One-third of the fetuses of each litter underwent detailed visceral examinations employing the Wilson technique. The remaining two-thirds were cleared in potassium hydroxide, stained with alizarin red S dye and examined for skeletal defects.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Details on maternal toxic effects:
The administration of up to 1600 mg/kg (body weight) of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on nidation or on maternal survival.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 600 mg/kg bw/day
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 administration of up to 1600 mg/kg (body weight) of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on 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.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The administration of up to 1600 mg/kg (body weight) to pregnant rats for 10 consecutive days had no clearly discernible effect on nidation or on maternal 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.