Distillation residue, butyl alcohols production, rectification

Endpoint summary

Additional information

In vitro mutagenic activity of the test substance has been evaluated in one study with bacterial cells and in two studies with mammalian cells. These studies are performed according to the current guidelines and in accordance with GLP, and evaluated to be reliable without restrictions. Thus, it is justified to select all three studies as key studies.

The test item is a UVCB substance. GC-MS analysis was performed for the sample used in the cytogenicity and micronucleus tests by Elek, J. (2013). The detailed composition cannot be identified. The mixture is primarily composed of 2 -ethylhexanol, alcohols C<8, alcohols C8, alcohols C>8, alcohols C4 and acetales. No aromatics were found in the test item.

Surrogate material, 2 -ethylhexanol, is a weak nongenotoxic hepatic peroxisome proliferator in rat. Also, generally aliphatic alcohols do not exhibit carcinogenic properties.

Mutagenicity in bacterial test systems

A bacterial mutagenicity study by Bedranikova, M. (2010) was performed according to OECD guideline 473.

The study was conducted by using five strains of Salmonella typhimurium bacteria (TA97, TA98, TA100, TA102 and TA1535) with and without metabolic activation. The target substance was tested for its ability to induce mutations in the standard assay at the concentration range of 0.0001-0.5 mg/plate. The test substance in concentration range 0.0001-0.1 mg/plate was evaluated for mutagenic potential in test with preincubation in the absence and presence of metabolic activation. The test substance did not induce mutations under conditions of this study.

Cytogenicity in mammalian cells

The potential of the test substance to induce chromosome aberration was assessed in cultured hamster lung fibroblasts by Hargitai, J. (2013). This study was performed according to OECD guideline 473. In the assay 1, the test substance was tested up to 5 and 10 µg/ml for a 3 h exposure time with a 20 h fixation time in the absence and presence of S9-fraction, respectively. In the assay 2, the test substance was tested up to 5 µg/ml for a 3 h exposure time with a 28 h fixation time in the absence of S9 fraction and up to 20 µg/ml in the presence of S9-fraction. Each treatment was coupled to an assessment of cytotoxicity at the same dose levels. The compound was not clastogenic in this assay either in the presence or absence of metabolic activation, i. e., it did not increase the number of polyploid cells and cells with endoreduplicated chromosomes in the cells.

In vitro micronucleus test

The objective of this study by Sire, G. (2013) was to evaluate the potential of the test item to induce any increase in the frequency of micronucleated cells. Thus, the assay has potential to detect the both clastogenic and aneugenic chemicals. The test method was performed according to OECD guideline 487. The test substance was tested in two independent experiments, with and without metabolic activation system, the S9 mix. The test substance concentrations varied between 0.00078 - 0.1 mg/ml in the experiments without S9 mix and between 0.00156 - 0.4 mg/ml in the experiments with S9 mix. Each treatment was coupled to an assessment of cytotoxicity at the same dose levels. Exposure time without S9 mix was 3 and 24 hours, and with S9 mix 24 hours. Under the experimental conditions, the test item did not induce any chromosomal damage, or damage to the cell division apparatus, in cultured L5178Y TK+/- mouse lymphoma cells.

Justification for selection of genetic toxicity endpoint
No study was selected, since the conclusion is based on the following assays: Bacterial reverse mutation assay (Ames test), In vitro micronucleus test and In vitro mammalian chromosome aberration test.

Short description of key information:
Gene mutation (reverse mutation assay/Ames test): negative in all tested bacterial strains with and without metabolic activation (according to OECD 471).
Chromosome aberration study in mammalian cells: negative, with and without metabolic activation (according to OECD 473).
Micronucleus test in mammalian cells: negative, with and without metabolic activation (according to OECD TG 487).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of in vitro bacterial gene mutation study, in vitro mammalian chromosomal aberration test and in vitro micronucleus test no classification is proposed for genotoxicity according to the criteria of CLP regulation 1272/2008 and the EU directive 67/548/EEC.