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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: Acceptable, reasonably well documented publication

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.31 (Prenatal Developmental Toxicity Study)
Version / remarks:
, 1988
Deviations:
no
Principles of method if other than guideline:
The conduct of the sutdy was consistent to EC method B.31 (88/302/EEC) in all important aspects.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Potassium sorbate
- Physical state: Off-white powder
- Stability: the test substance was considered to be stable for the duration of the study.

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: a precise statement on the age of the test animals is lacking. Rats are transcribed as virgin adult females and young adult males.
- Weight at study initiation: 214-230 g

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
VEHICLE
- Concentration in vehicle: 0, 3.4, 15.8, 73.3, 170 mg/mL

TOTAL VOLUME APPLIED: 1 mL (0, 3.4, 15.8, 73.3 mg of test substance)
2 mL (340 mg of test substance)
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Mating procedures: with young adult males (1:1); the day of copulation was considered as day 0 of pregancy.
Duration of treatment / exposure:
Duration of expsoure: Day 6-15 post mating
Frequency of treatment:
daily
No. of animals per sex per dose:
Number of animals per group: 25 females
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: 5 days

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked: clinical signs

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

FOOD CONSUMPTION: Yes

Ovaries and uterine content:
Parameters assessed during Caesarean section on day 20: sex, numbers of corpora lutea, implantation sites, resoption sites, live and dead fetuses, body weight of the live pups, and anatomical normality of the urogenital tract of each dam. 
Fetal examinations:
Examinations on fetuses: presence of external cogenital abnormalities, visceral examinations (Wilson technique) 
Statistics:
Stastistical methods: not stated

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Details on maternal toxic effects:
The administration of up to 340 mg/kg bw of potassium sorbate had no clearly discernible effect on nidation or on maternal or foetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occuring spontaneously in the sham-treated controls.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
LOAEL
Effect level:
> 340 mg/kg bw/day (actual dose received)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
340 mg/kg bw/day (actual dose received)
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Details on embryotoxic / teratogenic effects:
The administration of up to 340 mg/kg bw of potassium sorbate had no clearly discernible effect on nidation or on maternal or foetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occuring spontaneously in the sham-treated controls.

Effect levels (fetuses)

open allclose all
Dose descriptor:
LOAEL
Effect level:
> 340 mg/kg bw/day (actual dose received)
Basis for effect level:
other: embryotoxicity
Dose descriptor:
LOAEL
Effect level:
> 340 mg/kg bw/day (actual dose received)
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOAEL
Effect level:
340 mg/kg bw/day (actual dose received)
Basis for effect level:
other: embryotoxicity
Dose descriptor:
NOAEL
Effect level:
340 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

Applicant's summary and conclusion

Conclusions:
LO(A)EL maternal toxic effects > 340 mg/kg b.w./day
NO(A)EL maternal toxic effects: 340 mg/kg b.w./day
LO(A)EL embryotoxic/ teratogenic effects > 340 mg/kg b.w./day
NO(A)EL embryotoxic/ teratogenic effects: 340 mg/kg b.w./day

The administration of up to 340 mg/kg bw of potassium sorbate had no clearly discernible effect on nidation or on maternal or foetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occuring spontaneously in the sham-treated controls.

The extrapolation from sorbic acid to potassium sorbate or vice versa is considered not to be restricted in any way, since the determinant of potential toxicity is on the "sorbate" anion.