1,3-divinylimidazolidin-2-one

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-01-22 - 2015-03-13

Reliability:

1 (reliable without restriction)

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 422

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3-divinylimidazolidin-2-one

EC Number:

237-457-2

EC Name:

1,3-divinylimidazolidin-2-one

Cas Number:

13811-50-2

Molecular formula:

C7H10N2O

IUPAC Name:

1,3-diethenylimidazolidin-2-one

Details on test material:

- Name of test material (as cited in study report): 1,3-Dinvinylimidazolodin-2-on
- Test substance No.: 14/450-1
- Physical state: Colourless to yellow solid
- Analytical purity: 99,8 corrected area %
- Lot/batch No.: P53/14
- Expiration date of the lot/batch: 11 August 2015
- Stability under test conditions: stable
- Storage condition of test material: At room temperature

Test substance handling: No specific handling conditions required

Test animals

Species:

rat

Strain:

other: Crl:WI(Han)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 313 g (males), 212 g (females)
- Fasting period before study: none
- Housing: groups of 5 animals/sex/cage (premating males and females and postmating males), otherwise single cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%,
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Formulations (w/w) are be prepared daily within 6 hours prior to dosing.

VEHICLE
- Justification for use and choice of vehicle (if other than water): Test item is insoluble in water, but soluble in corn oil
- Amount of vehicle (if gavage): 5 mL/kg body weight. Actual dose volumes were calculated according to the latest body weight.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Samples of formulations were analyzed for homogeneity (highest and lowest concentration) and accuracy of preparation (all concentrations). Stability in vehicle over 6 hours at room temperature was also determined (highest and lowest concentration).
The accuracy of preparation was considered acceptable if the mean measured concentrations were 90-110% of the target concentration.
Homogeneity was demonstrated if the coefficient of variation was ≤ 10%. Formulations were considered stable if the relative difference before and
after storage was maximally 10%.

Details on mating procedure:

- M/F ratio per cage: 1:1
- Length of cohabitation: 14 days
- Proof of pregnancy: evidence of sperm in the vaginal lavage or by the appearance of an intravaginal copulatory plug, this day was designated Day 0 post-coitum.

Duration of treatment / exposure:

29 days (males), 40 - 45 days (females)

Frequency of treatment:

once daily

Duration of test:

28 days (males), 40 - 45 days (females)

Doses / concentrations

Remarks:

Doses / Concentrations:
50, 100 and 450 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

10 animals/sex/group
5 animals/sex/group were selected for functional observations, locomotor activity, clinical pathology, organ weights and histopathology

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Based on the results of a 14-day range-finding study in rats in which dose levels of 100, 300 and 1000 mg/kg bw/day
were tested.

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

450 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No toxicologically relevant effects on gestation index and duration, parturition, maternal care and early postnatal pup development (mortality, clinical signs, body weight and macroscopy) were observed.