Oligomerisation products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with acrylic acid and fatty acids, C18-unsatd., dimers and nonanoic acid

Genetic toxicity: in vivo

Administrative data

Endpoint:

genetic toxicity in vivo, other

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

The test substance is not considered to be genotoxic, based on the overall negative results from an Ames test andin vitrochromosomal aberration assay conducted with the test substance as well as mouse lymphoma assays available with the read across substances.

Endpoint conclusion:

no adverse effect observed (negative)

Endpoint conclusion:

no study available

A study was conducted to determine the mutagenic potential of the test substance according OECD Guideline 471 and EU Method B.13/14. The substance was tested up to the dose level of 3330 µg/plate in strains TA1535, TA1537, TA98, TA100 and WP2uvrA with (5 or 10% (v/v)) and without metabolic activation (S9-mix). Precipitates, toxicity and mutagenicity were evaluated. All bacterial strains showed negative responses over the entire dose range, i.e. there was no significant dose-related increase in the number of revertants in two independently repeated experiments. The negative and strain-specific positive control values were within the laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly. Under the study conditions, the substance was not mutagenic in the Salmonella typhimurium and Escherichia coli reverse mutation assays (Verbaan, 2011).

A study was conducted to determine the clastogenecity potential of the test substance according to OECD Guideline 473 and EU Method B.10. In the first assay, the substance was tested up to 40 and 100 µg/ml for a 3 h exposure time with a 24 h fixation time in the absence and presence of 1.8% (v/v) S9-fraction, respectively. Appropriate toxicity was reached at these dose levels. In the second assay, the substance was tested up to 40 µg/ml for a 24 h continuous exposure time with a 24 h fixation time and up to 45 µg/ml for a 48 h continuous exposure time with a 48 h fixation time in the absence of S9-mix. In the presence of S9-mix the substance was tested up to 100 µg/ml for a 3 h exposure time with a 48 h fixation time. Appropriate toxicity was reached at these dose levels. The number of cells with chromosome aberrations found in the solvent control cultures was within the laboratory historical control data range. The number of polyploid cells and cells with endoreduplicated chromosomes in the solvent control cultures was within the laboratory historical control data range. The positive control chemicals both produced statistically significant increases in the frequency of aberrant cells. It was therefore concluded that the test conditions were adequate and that the metabolic activation system (S9-mix) functioned properly. Under the study conditions, the test substance was considered not clastogenic in human lymphocyte (Verbaan, 2011).

 

A study was conducted to determine the mutagenicity potential of a read across substance, BADGEDA, according to OECD Guideline 476 and compliance with GLP. In this study, mouse lymphoma L5178Y TK+/-(3.7.2C) cells were exposed to the read across substance BADGEDA in DMSO at concentrations of 0, 46.88, 93.75, 187.5, 375 or 750 μg/mL in RPMI 1640 medium with and without 2% S-9 metabolic activation for a preliminary cytotoxicity test. In the main test, two experiments were performed at the following concentrations:

- Experiment 1 (3 hour exposure): Without S-9: 0, 0.0977, 0.1953, 0.3906, 0.7813, 1.563, 3.125, 6.25, 12.5, 25 or 50 μg/mL; with S-9: 0, 3.75, 7.5, 15, 30, 35, 40, 45, 50, 60 or 75 μg/mL

- Experiment 2 (3 hour exposure): Without S-9: 0, 3, 6, 9, 12, 15, 18, 21, 24, 27 or 30 μg/mL; with S-9: 0, 15, 30, 40, 50, 60, 70, 80, 90, 100 or 125 μg/mL 

Mutant frequencies in negative control cultures fell within normal ranges and clear increases in mutation were induced by the positive control chemicals 4-nitroquinoline 1-oxide (without S-9) and benzo(a)pyrene (with S-9). In Experiment 1, statistically significant increases in mutant frequency were observed at 12.5 (without S-9) and 60 µg/mL (with S-9). A significant linear trend was observed in the presence of S-9 only. In Experiment 2, a statistically significant increase in mutant frequency was observed at 9 µg/mL in the absence of S-9 only. However, no significant increases were observed following treatment with S-9 and there were no significant linear trends in either the absence or presence of S-9. Further, in both experiments, the increases in mutant frequency at the significant concentrations were all within three times the historical mean value and the increases were not considered concentration related or biologically relevant. Under the test conditions, BADGEDA is not considered as mutagenic in L5178Y cells indicating absence of mutagenic potential of the test substance. 

A mouse lymphoma forward mutation assay was available on the metabolite, nonanoic acid. In this study, L5178TK+/- cells were exposed for 4 h to non-activated doses ranging from 150 to 1600 µg Nonanoic acid per mL and to S9-activated concentrations ranging from 37.5 to 600 µg a.i./mL. Nonanoic acid was not considered to be mutagenic under the conditions of this study without exogenous metabolic activation. Nonanoic acid, in the presence of S9 metabolic activation, induced a weak mutagenic response. Increases in the numbers of mutants per plate were seen at all test substance concentrations, and doubled at ≥300 µg/mL in trial 1, and at doses ≥100 µg/mL in trial 2. This occurred only in the presence of increasing moderate to severe cytotoxicity and small colony development and may indicate damage to the chromosome carrying the TK locus, rather than actual mutagenicity within the TK gene locus. Therefore, it was concluded that the results do not reflect intrinsic mutagenicity. However the study was considered to be of limited value since the purity of the substance tested was not available in the study summary and there was no access to the fully study. Further, nonanoic acid was not found to be genotoxic in two otherin vitroassays i.e., in an bacterial reverse mutation assay conducted with Salmonella and E.coli strains as well as in an chromosomal aberration assay conducted with peripheral human lymphocytes. It also did not show evidence of clastogenicity or aneunogenicity in anin vivomicronucleus assay conducted in mice (ECHA RAC, 2013).

Based on the overall negative genotoxicity results from an Ames test and in vitro chromosomal aberration assay conducted with the test substance as well as mouse lymphoma assays available with the read across substances, no classification is required for genotoxicity according to CLP (1272/2008) criteria.