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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Published study; non-standard method. The study is poorly reported and its value/relevance limited by the extreme dose level used, which is well in excess of the currently accepted limit dose.

Data source

Reference
Reference Type:
publication
Title:
EFFECTS OF UREA ON MITOTIC CHROMOSOMES OF MICE AND ONION
Author:
Chaurasia, O.P. & Sinha, S.P.
Year:
1987
Bibliographic source:
Cytologia 52(4): 877-882

Materials and methods

Principles of method if other than guideline:
Bone marrow cytogenetic assay in mice
GLP compliance:
not specified
Remarks:
: published study
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No information available; purity unknown

Test animals

Species:
mouse
Strain:
Swiss
Sex:
not specified
Details on test animals and environmental conditions:
Swiss albino mice

Administration / exposure

Route of administration:
oral: feed
Vehicle:
Diet
Details on exposure:
Mice were fed 500 mg/animal per day in food for 5 days
Duration of treatment / exposure:
5 days
Frequency of treatment:
Daily
Post exposure period:
Seven days
Doses / concentrations
Remarks:
Doses / Concentrations:
500 mg/animal
Basis:
nominal in diet
No. of animals per sex per dose:
No information available:
Control animals:
yes, plain diet
Positive control(s):
None

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
Bone marrow cells were separated, concentrated and stained with Giemsa
Evaluation criteria:
No information available
Statistics:
No information available

Results and discussion

Test results
Sex:
not specified
Genotoxicity:
positive
Toxicity:
not specified
Vehicle controls validity:
not specified
Negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
Bone marrow cell metaphases exhibited chromosome breaks, acentric fragments, translocations, gaps and constrictions at a 7-fold rate compared to controls.

Any other information on results incl. tables

Bone marrow cell metaphases exhibited chromosome breaks, acentric fragments, translocations, gaps and constrictions at a 7-fold rate compared to controls.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): ambiguous
Bone marrow cell metaphases exhibited chromosome breaks, acentric fragments, translocations, gaps and constrictions at a 7-fold rate compared to controls. However the interpretation of the clastogenic effect is limited by the usage of a single extremely high dose level.
Executive summary:

The potential of urea to cause chromosomal aberrations was investigated in the bone marrow of Swiss mice. Mice (number unspecified) were administered urea in the diet at a dose level of 500 mg/day for 5 days. Animals were sacrificed after a receivery period of 7 days and the bone marrow harvested. A total 300 metaphases from treated animals and untreated controls were assessed for chromosomal aberration.

A marked increase in the incidence of chromosomal aberrations was seen in the treated group (7x controls). However the dose level administered in this study is equivalent to 16 -17 g/kg bw/day and is thus far in excess of the limit dose of 1000 mg/kg bw. Signs of toxicity are not reported, but marked toxicity can be predicted at this dose level.