Potassium carbamoylcarbamate

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:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: No guideline followed. The study performed with relatively small numbers of animals and a single dose

Data source

Reference

Reference Type:

publication

Title:

Correlation between the molecular structure of N-alkylureas and N-alkylthioureas and their teratogenic properties

Author:

Teramoto S, Kaneda M, Aoyama H, and Shirasu Y

Year:

1981

Bibliographic source:

Teratology 23(3): 335–42

Materials and methods

Test guideline

Qualifier:

no guideline followed

Deviations:

not specified

Principles of method if other than guideline:

Dams were dosed via oral gavage to pregnant rats on day 12 of pregnancy and sacrificed on day 20 of pregnancy.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Urea

EC Number:

200-315-5

EC Name:

Urea

Cas Number:

57-13-6

Molecular formula:

CH4N2O

IUPAC Name:

urea

Test material form:

not specified

Details on test material:

Urea from Wako Pure Chemical Industries, Ltd

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: purchased from CLEA, Japan
- Age at study initiation: (P) 15 wks
- Diet: laboratory chow (Oriental Yeast MF), ad libitum
- Water: tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ±1
- Humidity (%): 55 ± 5

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Aqueous solutions of the compounds (10 mL/kg) were prepared and orally administered to dams.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

Females were paired overnight with a male. The following morning they were examined for the presence of vaginal plug and were designated as being in day 0 of pregnancy when the plug was observed.

Duration of treatment / exposure:

Dams were dosed at day 12 of pregnancy

Frequency of treatment:

Single dosing

Duration of test:

Dosed on day 12 of pregnancy, and sacrificed at day 20 of pregnancy

Doses / concentrations

Remarks:

Doses / Concentrations:

Basis:
nominal conc.
2000 mg/kg

No. of animals per sex per dose:

4

Control animals:

yes, concurrent vehicle

Examinations

Fetal examinations:

- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [ half per litter]
- Skeletal examinations: Yes: [ half per litter]
- Head examinations: No data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Mortality was not observed.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

2 000 mg/kg bw (total dose)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No significant changes were observed in number of implants, number of live fetuses, % of fetal resorptions, fetal weight or % fetal malformation.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

	No. Dams	Mean No of implants	Mean No. of live fetuses	% Fetal resorptions	Mean fetal weight (mg)	& Fetuses malformed
Urea (2000mg/kg)	4	13.8±2.2	13.8±2.2	0	3626±104	1.8
control	6	13.7±1.0	13.3±0.8	2.4	3671±197	0

 

Applicant's summary and conclusion

Conclusions:

Based on the study, no adverse developmental/teratogenicity effects were observed due to a single, high-dose urea treatment.