Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Jul. 5, 1985 to Nov. 7, 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 474). no GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Source : no data
- Lot/batch No.: 40
- Storage condition of test material: 4 ºC in the darkness.
- Physical state: Orange/yellow flakes
- Analytical purity: 97%

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, UK.
- Age : no data
- Weight at study initiation: 22 to 24 g.
- Housing: Animals kept in a plastic disposable cage.
- Diet (e.g. ad libitum): Scientific Feeds (Labsure) LAD 1 diet ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ºC
- Humidity : no data
- Air changes (per hr): 30
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Aqueous 1% methyl cellulose
Details on exposure:
All animals in all groupes were dosed with the standard volume of 20 ml/kg bw.
Duration of treatment / exposure:
Single dose administration
Frequency of treatment:
Single dose administration
Post exposure period:
Animals were sacrificed 24, 48, and 72 hours after administration.
Doses / concentrations
Remarks:
Doses / Concentrations:
1200 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
15 animals/sexe in control (vehicle) and test article group.
5 animals/sexe in positive control group.
Control animals:
yes, concurrent vehicle
Positive control(s):
Mitomycin C
- Route of administration: intraperitoneal injection
- Doses / concentrations: 4 mg/kg bw (0.2 mg/mL)

Examinations

Tissues and cell types examined:
Bone marrow cells.
Details of tissue and slide preparation:
The animals were killed and both femurs were dissected out from each animal. The femurs were cleared of tissue and one epiphysis removed from each bone. A direct bone marrow smear was made onto a slide (one smear/femur) and the prepared smears were air-dried, fixed in methanol, and stained.
Evaluation criteria:
The stained smears were examined by light microscopy to determine the incidence of micronucleated cells/1000 polychromatic erythrocytes/animal. The ratio of polychromatic to normochromatic erythrocytes for each animal was assessed by examination of at least 1000 erythrocytes.
Statistics:
Wilcoxon test

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
A preliminary toxicity test had been carried out to determine the toxicity of 1,2,4-triazole. From the results it was estimated that a dosage of 1200 mg/kg would be expected to kill approximately 10% of the animals within 72 hours of dosing.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
No evidence of mutagenic potential or bone marrow cell toxicity was noted in this study.
Executive summary:

In this assessment of the effect of 1,2,4 -triazole on the incidence of micronucleated polychromatic erythrocytes in mice, a dosage of 1200 mg/kg bw was administered by oral gavage. A negative and a positive controls were used. Bone marrow smears were obtained from the negative control and test compound groups at 3 sampling times; these being 24, 48 or 72 hours after dosing.

At all sampling times, mice treated with 1,2,4 -triazole showed no significant increase in the frequency of micronucleated polychromatic erythrocytes. There was no significant decrease in the ratio of polychromatic to normochromatic erythrocytes after treatment of the animals with 1,2,4 -triazole. The positive control produced large highly significant increases in the frequency of micronucleated polychromatic erythrocytes together with decreases in the ratio of polychromatic to normochromatic erythrocytes.

It is concluded from the results obtained that 1,2,4 -triazole shows no evidence of mutagenic potential or bone marrow cell toxicity when administered orally in this in vivo test procedure.