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Key value for chemical safety assessment

Additional information

The potential mutagenicity of 2 -allyloxymethyl-2 -ethylpropanediol in bacterial cells has been assessed in a bacterial reverse mutation assay (Ames test) conducted according to OECD Test Guideline 471 using the test substance trimethylolpropane monoallyl ether (TMPME). No evidence of mutagenicity was observed in the test using strains of S. typhimurium and E. coli,with or without metabolic activation(Sokolowski, 2006).

There are no studies available on the genotoxicity of 2 -allyloxymethyl-2 -ethylpropanediol in mammalian test systems. Based on existing datasets and structural and chemical considerations, read-across from 2 -allyloxymethyl-2 -ethylpropanediol to mammalian genotoxicity studies on 2,2 -bis(allyloxymethyl)butan-1 -ol is appropriate to meet the REACH Annex VII-IX data requirements. Read-across is scientifically justified and also enables the REACH requirements to be adequately addressed, while avoiding unnecessary animal testing in accordance with EU Directive 86/609/EEC.

The potential for 2,2 -bis(allyloxymethyl)butan-1 -ol to induce gene mutations in mammalian cells was assessed in a modern guideline-compliant mouse lymphoma assay (OECD TEST Guideline 476) conducted using the test substance trimethylolpropane diallyl ether (TMPDE; Riach, 2010). No evidence of mutagenicity was seen in the absence of metabolic activation. Weak responses (meeting the laboratory's criteria for a positive response) were seen in the presence of metabolic activation at higher concentrations. Positive responses were associated with marked cytotoxicity (relative total growth of 8 -15%). The report authors note a preponderance of small type colonies at these concentrations, indicating that the activity of TMPDE in this study is associated with large-scale (i.e. chromosomal) damage rather than deletions and/or point mutations. The authors further conclude that, while this result is insufficient evidence on its own to classify the substance as mutagenic according to GHS Category 2, it would contribute towards a Category 2 classification if supported by positive findings from relevant in vivo tests.

The results of the mouse lymphoma assay indicate that TMPDE is clastogenic in vitro, in the presence of metabolic activation but only at concentrations associated with marked cytotoxicity (Riach, 2010). Further studies of chromosomal aberration in vitro are not available, however, the substance has been investigated in a higher tier (in vivo) study.

The genotoxicity 2,2 -bis(allyloxymethyl)butan-1 -ol was assessed in a micronucleus test in male and female mice, according to OECD Test Guideline 474 using the test substance TMPDE (Herbold, 1993). In the study, the mice received a single intraperitoneal injection of the test substance at a dose level of 1250 mg/kg bw in corn oil. Vehicle controls and positive controls (cyclophosphamide) were included. The treated mice were sacrificed at 16, 24 and 48 hours after administration. All treated mice survived to sacrifice, however all showed signs of toxicity. There was an altered ratio between polychromatic and monochromatic erythrocytes. No evidence of a clastogenic effect was found in this study. The response to the positive control (CPA) confirmed the sensitivity of the assay.

The negative findings in the mouse micronucleus study therefore indicate that 2,2 -bis(allyloxymethyl)butan-1 -ol is not clastogenic in vivo. Based on read-across to the mammalian mutagenicity studies, 2 -allyloxymethyl-2 -ethylpropanediol is not predicted to have mutagenic potential.


Justification for selection of genetic toxicity endpoint
No study was selected since negative results were obtained in an in vitro study using 2 -allyloxymethyl-2 –ethylpropanediol and in an in vitro and an in vivo study using the read-across substance: 2,2 -bis(allyloxymethyl)butan-1 –ol.

Short description of key information:
No evidence of mutagenicity was seen for 2-allyloxymethyl-2-ethylpropanediol in a bacterial reverse mutation assay (Ames test). Based on available datasets and chemical and structural considerations, read across from 2-allyloxymethyl-2-ethylpropanediol to mammalian in vitro genotoxicity studies on 2,2-bis(allyloxymethyl)butan-1-ol is appropriate to address the REACH Annex VII-IX data requirements. In a mouse lymphoma assay, a weak positive response was reported in the presence of metabolic activation and only at concentrations associated with marked cytogenicity. No evidence of clastogenicity was seen in a standard mouse micronucleus assay.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

2 -allyloxymethyl-2 -ethylpropanediol is not mutagenic in bacterial cells in vitro. Based on read-across to a genotoxicity study on 2,2 -bis(allyloxymethyl)butan-1 -ol in mammalian cells in mice, 2 -allyloxymethyl-2 -ethylpropanediol is not predicted to have genotoxic potential in vivo. The substance does not meet the criteria for classification for genotoxicity according to Directive 67/548/EEC or Regulation 1272/2008/EC.