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Carcinogenicity

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Description of key information

The substance was not carcinogenic in the oral study in rats and not carcinogenic in the gavage study in mice.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
carcinogenicity: oral
Remarks:
other: gavage and oral feed (see: doses)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given, acceptable for assessment. Restrictions: survival and food intake (and thus quantitative availability of test substance) not specified.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Two F1 hybrid stocks of mice were used: strains (C57BL/6xC3H/Anf)F1 and (C57BL/6xAKR)F1. 18 animals per sex per strain received the test compound via gavage during weaning (day 7-28) and consecutively via the diet until 18 months of age. During gavage a maximum tolerated dose of 215 mg/kg bw/d (derived from zero mortality after 19 daily doses) in 0.5 % gelatine was administered. During the dietary phase, animals received 646 ppm (= ca. 80 mg/kg bw/day) via unrestricted consumption of feed (concentration calculated according to the weight and food consumption of 4-week old mice). Negative and positive control groups were run simultaneously. After 18 months mice were sacrificed and gross pathological and histological examinations were performed.
GLP compliance:
not specified
Species:
mouse
Strain:
other: see "details on test animals and environmental conditions"
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: "specific pathogen-free" mice were obtained from Cumberland View Farms, Clinton, Tennessee, to establish a breeding colony.
- Strain: Females of a C57BL/6 strain were mated with C3H/Anf or AKR males to obtain (C57BL/6 x C3H/Anf)F1 and C57BL/6 x AKR)F1, the two F1 hybrid stocks used.
- Age at study initiation: 7 days
- Housing: 6 animals per cage
- Diet: ad libitum
Route of administration:
other: gavage and oral feed (see: doses)
Vehicle:
other: 0.5% gelatin during gavage
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
18 months
Frequency of treatment:
Gavage: daily
Dietary period: continuously
Post exposure period:
None
Dose / conc.:
215 mg/kg bw/day (actual dose received)
Remarks:
during gavage (day 7-28)
Dose / conc.:
646 ppm
Remarks:
ca. 80 mg/kg bw/day; during dietary exposure (>28 days)
No. of animals per sex per dose:
18 mice per sex per strain
Control animals:
yes, concurrent no treatment
yes, concurrent vehicle
other: positive control: ethyl carbamate
Observations and examinations performed and frequency:
The postmortem procedure included an external examination and a thorough examination of thoracic and abdominal cavities, with histologic examination of major organs and of all grossly visible lesions.
Details on results:
Exposure to ethylene urea during the examination period (gavage plus dietary) caused no significant increase in tumors.
Though the test design does not meet current standards completely, the negative result at the high dose for almost lifetime gives evidence of no cancerogenic potential of the test substance on oral application in mice: no positive result is expected when another test is repeated (comp. McGregor et al., 1994). Ambiguities: survival, food intake and thus quantitative availability of test substance, not specified.
Key result
Dose descriptor:
other: No increase in tumours observed
Effect level:
>= 80 - <= 250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Exposure to ethylene urea during the examination period (gavage plus dietary) caused no significant increase in tumors.
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given, acceptable for assessment Restrictions: limited number of animals, limited documentation.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Two groups of 6 female rats received a diet containing 0.1% 2-imidazolidinone for 150 days. One of the groups in addition received 0.12% sodium nitrite via the drinking water. At the end of the exposure period animals were weighed and gross pathology and histopathology were examined.
GLP compliance:
not specified
Species:
rat
Strain:
SIV 50
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ivanovas, Kisslegg/Allgäu
- Weight at study initiation: 120 g
- Diet: ad libitum
- Water: ad libitum
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
150 days
Frequency of treatment:
Continuous
Dose / conc.:
0.1 other: % in feed
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
Post-exposure period: none
Details on results:
All animals survived, no tumors occurred, while in the group additionally treated with nitrite all animals died, suffering carcinomas (5 nephroblastomas, 1 squamous cell carcinoma).
Because of the low number of animals applied it is not possible to conclude whether 2-imidazolidinone is carcinogenic or not, but the combination with nitrite provides clear evidence of tumor generation.
Key result
Dose descriptor:
other: No tumours observed
Effect level:
1 000 ppm
Based on:
test mat.
Sex:
female
Basis for effect level:
other: All animals survived, no tumors occurred, while in the group additionally treated with nitrite all animals died, suffering carcinomas (5 nephroblastomas, 1 squamous cell carcinoma).

Additional information

The induction of malignant tumors in rats was tested by oral administration of the test substance (Sander, 1971). Two groups of 6 female rats each received for 150 days standard diet, which contained 2-Imidazolidine (0.1%). One group got, in addition, drinking water with 0.12% sodium nitrite. All animals survived, no tumors occurred, while in the group additionally treated with nitrite all animals died, suffering carcinomas (5 nephroblastomas, 1 squamous cell carcinoma).

The tumorigenicity of the test substance was tested by continuous oral administration to both sexes of two hybrid strains of mice, started at the age of 7 days (Innes, 1969). 18 animals per sex per strain received the test compound via gavage during weaning (day 7-28) and consecutively via the diet until 18 month of age. Maximal tolerated doses were given. Exposure to the test substance during the examination period (gavage plus dietary) caused no significant increase in tumors.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on carcinogenicity, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP).