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Test (in vitro) : 3 Ames tests (Jones 1985 , Poth 1989 and Melly 1981)

Three Ames tests were carried out with 1,2,4 -triazole (OECD 471 guideline study).

In 2 out of the three studies the test material was tested on 5 S. typhimurium strains (TA 1535, TA1538, TA 1537, TA 98 and TA 100) with and without metabolic activation (S9 -mix).

No substantial increases in revertant colony numbers of any of the five tester stains were observed following treatment with 1-2-4 Triazole at any dose level, either in the presence or absence of metabolic activation in these two studies.

Test (in vitro): chromosomic aberrations on rat lymphocytes with 1, 2, 4 triazole (Schisler, 2007)

The study was performed according to international guideline (OECD 473) and in compliance with GLP. There were no significant increases in the frequencies of cells with aberrations in either the presence or absence of S9 activation. Cultures treated with the positive control chemicals {i.e., mitomycin C without S9 and cyclophosphamide with S9) in both assays had significantly higher incidences of abnormal cells in all assays. Based upon these results, 1,2,4-triazole was considered to be non-genotoxic in this in vitro chromosomal aberration assay utilizing rat lymphocytes.

Test (in vitro); Mouse lymphoma Gene mutation test in the HPRT locus (Schisler, 2006): The study was performed according to international guideline (OECD 476) and in compliance with GLP. Based upon the frequency of TGr mutants recovered in cultures treated with the test material, it was concluded that 1,2,4-triazole was non-mutagenic in the assay system employed.

Test (in vivo) : Micronucleus test (Allen 1985)

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 control group was dosed in an identical manner with the vehicle, aqueous 1% methylcellulose. A positive control group was dosed with mitomycin C by intraperitoneal injection.

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. Bone marrow smears were obtained from the positive control group 24 hours after dosing. One smear from each animal was examined for the rpesence of micronuclei in 1000 polychromatic erythrocytes.

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.

Justification for selection of genetic toxicity endpoint
No study was selected since all three in vitro studies and the in vivo study were negative.

Short description of key information:
Results are negative in Ames tests, negative in the in vitro mouse lymphoma assay and the in vitro abberation chromosomic test and negative in in vivo micronucleus test, performed on 1,2,4 -triazole.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to Directive 67/548/EEC and to regulation EC no.1272/2008 (CLP), 1,2,4 -triazole is not classified for genetic toxicity endpoint on the basis of weight of evidence.

Justification : Negative results in Ames tests, negative results in the in vitro mouse lymphoma assay and in the in vitro chromosomic aberration test performed on 1,2,4 -triazole sodium salt, and negative results in in vivo micronucleus test.

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