[(o-methoxyphenoxy)methyl]oxirane

Endpoint summary

Additional information

Ames test

Salmonella typhimurium strains TA1535, RA1537, TA98, TA100 and Escherichia coli strain WP2uvrA were treated using the Ames plate incorporation method at five dose levels, in triplicate, with and without the addition of a rat liver homogenate metaolising system.

The dose range was 50 to 5000 ug/plate in the first experiment. The experiment was repeated on a separate day using the same dose range as Exp. 1, fresh cultures of the bacterial strains and fresh test item formulations.

The test item caused no visible reduction in the growth of the bacterial background lawn at any dose level and was, threfore, tested up to the maximum recommended dose level of 5000 ug/plate. No test item precipitate was observed.

Dose-related, reproducible and statistically significant increases in the fequency of TA100, TA1535 and WP2uvrA revertant colonies were observed at each test item dose level, with and without S9 -mix. the increases observed were large and very much in excess of the in-house historical untreated/vehicle control ranges for each strain. Smaller increases were also noted for tester strains TA98 and TA1537 with and without S9 -mix at the upper dose levels.

The test item was considered to be mutagenic under the conditions of this test.

Chromosome aberration test

Duplicate cultures of human lymphocytes were evaluated for chromosome aberrations at 3 dose levels, together with vehicle and positive controls.

Dose levels used in the main exp.:

Group 4(20)-hrs without S9: 14.08, 28.16, 56.31, 112.63, 168.94, 225.25 ug/ml

Group 4(20)-hrs with S9 (2%): 56.31, 112.63, 225.25, 450.5, 675.75, 901 ug/ml

Group 24-hrs without S9: 3.52, 7.04, 14.08, 28.16, 56.31, 112.63 ug/ml

Group 4(20)-hrs with S9 (1%): 28.16, 56.31, 112.63, 225.25, 450.5, 675.75 ug/ml

The test item was toxic and did not induce any toxicologically significant increases in the frequency of cells with aberrations, in either of two separate experiments, using a dose range that included a dose level that induced app. 50% mitotic inhibition the optimum level of toxicity.

The test item was considered to be non-clastogenic to human lymphocytes in vitro.

Micronucleus test

In the range-finding test there was no marked difference in toxicity of the test item between the sexes; therefore the main test was performed using only male mice.

The Micronucleus test was conducted using the oral route in groups of seven mice at the MTD of 800 mg/kg and with 400 and 200 mg/kg as the two lower dose levels.

There were no premature deaths seen in any of the dose groups in the main test. Clinical signs were observed in animals dosed with the test item at 800 mg/kg in the 24 and 48 hr dose groups, and included hunched posture, ataxia, ptosis and splayed gait.

Statistically significant decreases in the PCE/NCE ratio were not observed in any of the test item dose groups. However, the observation of clinical signs was taken to indicate that systemic absorption had occurred and exposure to the target tissue had been achieved.

There was no evidence of any statistically significant increases in the incidence of micronucleated polychromatic erythrocytes in animals dosed with the test item when compared to the vehicle control group.

The test item was considered to be non-genotoxic under the conditions of the test.

Justification for selection of genetic toxicity endpoint
The studies were performed in compliance with the principles of the Good Laboratory Practice (GLP).
Experimental data: June (MNT) and November (Ames test and CA test) 2011.

Short description of key information:
-Reverse mutation aassy "Ames test" using Salmonella typhimurium and Escherichia coli was performed following the OECD Guidelines no. 471 "Bacterial Reverse Mutation Test", Method B.13/14 of Commission Regulation (EC) no.440/2008 and the USA, EPA (TSCA) OPPTS harmonised guidelines.
-Chromosome aberration test in Human lymphocytes in vitro was performed following the OECD Guidelines no. 473 "Genetic Toxicology: Chromosome Aberration Test", Method B.10 of Commission Regulation (EC) no.440/2008.
-Micronucleus test in mouse was performed following the OECD Guidelines no. 474 "Mammalian Erythrocyte Micronucleus Test", Method B.12 of Commission Regulation (EC) no.440/2008.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Classification for heritable effects in human germ cells is made on the basis of the three performed validated tests.

Ames test resulted positive, but the Chromosomal aberration test and the Micronucleus test resulted negative.

The substance is considered not classified for the Mutagenicity/genotoxicity hazard.