Alcohols C13-15 (branched and linear, odd numbered), reaction product with 1-chloro-2,3-epoxypropane

Endpoint summary

Additional information

In vitro

A pre-GLP study of Ames test (central institute for nutrition and food research, 1979) was well conducted and recorded which was similar to OECD Guideline 471 and negative results were observed. Five strains, TA 1535, TA 1537, TA1538, TA98 and TA100 were tested to detect GC base pairs mutation. However, another study of Ames test (RCC, 1985) under GLP was well conducted and recorded according to previous OECD Guideline 471. The test material induced point mutations by base-pair changes in the strain 1535 with metabolic activation.

Both of the two in vitro studies discussed above were conducted according to previous OECD guideline, so it is insufficient to make an entire assessment to the mutagenicity of test substance.

The results of the CHO/HGPRT Mutation Assay following OECD guideline 476 (MA BioServices, Inc., 1998) indicated that, under the conditions of this study, alkyl glycidyl ether was concluded to be negative with and without S9 activation. A Mutational Assay System (Hazleton Lab, 1979) using the Thymidine Kinase Locus in Mouse Lymphoma Cells was employed for read-across. Under the experimental conditions the test substance did not show any evidence of mutagenicity, too.

In addition, there are two Bacteria Reverse Mutation Assay for read-across to investigate the potential of mutagenicity. Under the conditions of one test, alkyl glycidyl ether did cause a positive response with tester strain TA1535 in the presence and absence of metabolic activation. The result of another test is ambiguous.

In vivo

The key study (Microbiological Associates, Inc., 1997) was conducted to assess the clastogenic potential of test article to increase the incidence of micro-nucleated polychromatic erythrocytes in bone marrow of male and female mice.

The assay was performed for read-across in two phases. The first phase, designed to set dose levels for the definitive study, consisted of a pilot assay followed by a toxicity study. The second phase, the micronucleus study, evaluated the potential of the test article to increase the incidence of micro-nucleated polychromatic erythrocytes in bone marrow of male and female mice.

In the pilot assay, male mice were dosed with 1, 10, 100, or 1000 mg of test chemical/kg body weight and male and female mice were dosed with 5000 mg/kg. Mortality was observed in 2/5 male mice and 2/5 female mice at 5000 mg/kg. Clinical signs following dose administration included lethargy in male mice at 1000 mg/kg and lethargy and piloerection in male and female mice at 5000 mg/kg.

In the micronucleus assay following OECD guideline and GLP principle, male and female mice were dosed with 1000, 2000 or 4000 mg of test article/kg body weight. No mortality was observed in any male or female mice in the micronucleus study. Clinical signs following dose administration included: lethargy in male and female mice at all test article dose levels and piloerection in male and female mice at 4000 mg/kg. Bone marrow cells, collected 24, 48 and 72 hours after treatment, were examined microscopically for micro-nucleated polychromatic erythrocytes. Slight reductions (up to 11%) in the ratio of polychromatic erythrocytes to total erythrocytes were observed in some of the test article-treated groups relative to the respective vehicle controls.

No significant increase in micro-nucleated polychromatic erythrocytes in test article-treated groups relative to the respective vehicle control group was observed in male or female mice at 24, 48 or 72 hours after dose administration (p > 0.05, Kastenbaum-Bowman). The results of the assay indicate that under the conditions described in this report, alkyl glycidyl ether did not induce a significant increase in micro-nucleated polychromatic erythrocytes in either male or female mice. Alkyl glycidyl ether was concluded to be negative in the mouse micronucleus assay.

The rest reports (T. Pullin, 1977; Hazleton Lab, 1979) established as supportive studies also demonstrated that no mutagenicity of test substance occurred. One is performed following OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test) (T. Pullin, 1977), and another is of bone marrow micronucleus assay to present negative effect (Hazleton Lab, 1979).

Summary

Test substance has been examined for mutagenicity both in vitro and in vivo in a range of recognized core assay types. It has shown negative results for mutagenicity in vivo, but positive response in tester strain TA1535 in the presence and absence of metabolic activation. The reason is supposed that the metabolic activation of in vitro environment is different from that of human, which is subject to be affected by many items. Thus, the negative result of in vivo is proposed to interpret the mutagenic potential of test substance since the exposure pathway and metabolism of in vivo is more similar to human than that of in vitro. It is concluded that the available data indicate that test substance has no significant genotoxicity.

Justification for selection of genetic toxicity endpoint: In vivo test, guideline test with GLP principle

Short description of key information: Review of a comprehensive database indicates that test substance is not genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Test substance does not warrant classification for genotoxicity under CLP(Regulation EC No. 1272/2008).