1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well reported study performed under GLP and usig a standard test method.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)

GLP compliance:

yes

Type of assay:

unscheduled DNA synthesis

Test material

Test material information

Constituent 1

Reference substance name:

1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea

EC Number:

278-928-2

EC Name:

1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea

Cas Number:

78491-02-8

Molecular formula:

C8H14N4O7

IUPAC Name:

1-[1,3-bis(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]-1,3-bis(hydroxymethyl)urea

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Approximately 7 weeks of age, 194-253g bodyweight at study start (main UDS test).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

Aqueous 0.25% methylcellulose

Details on exposure:

Single oral dosing at 10 ml/kg dose volume.

Post exposure period:

Animals terminated 12-14h (experiment1) or 2-4h (experiment 2) post-dose.

Doses / concentrations

Remarks:

Doses / Concentrations:
800 and 2000 mg/kg
Basis:
actual ingested
dosages selected following a preliminary toxicity test in which 3M, 3F dosed at 2000 mg/kg showed little sign of toxicity over 2 days.

No. of animals per sex per dose:

Experiment 1 (12-14h termination): 4M, 4F
Experiment 2 (2-4h termination): 4M, 4F.

Control animals:

yes, concurrent vehicle

Positive control(s):

Yes: 2-acetylaminofluorine (experiment 1), dimethylnitrosamine (experiment 2).

Examinations

Tissues and cell types examined:

Hepatocytes

Details of tissue and slide preparation:

Hepatocytes collected by liver perfusion at termination and allowed to attach to coverslips in multiwell plates, then radiolabelled by addition of 3H thymidine. Cells then fixed, washed and dipped for autoradiography.

Evaluation criteria:

100 cells/animal (where pssible) were scored for nuclear and cytoplasmic grain counts and net nuclear grain count (NNG) was determined. Cells showing S-phase synthesis, seen as heavily labelled nuclei, were excluded.
Positive result criteria: NNG >0 with 20% or more of cells responding, test >vehicle controls for NNG and % cells in repair.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Remarks:

no significant adverse reactions were seen up to termination

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Cell viabilities in test and control groups were within the range 55-76%.

Any other information on results incl. tables

NNG counts in all test group animals were <0: group mean values were -1.2 to -2.4. No more than 0.7% of cells were seen to be repairing DNA in any test group.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Single oral administration of the test substance at a dosage approaching the rat acute oral LD50 reported by others produced no evidence of DNA damage (as indicated by UDS) in this study.