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Administrative data

Key value for chemical safety assessment

Additional information

in vitro

Ames test

The test item was tested for mutagenicity in the Ames test and in the E. coli- reverse mutation assay both in the standard plate test and in the preincubation test with and without the addition of a metabolizing system obtained from rat liver (S-9 mix) using the Salmonella strains TA 1535, TA 100, TA 1537, TA 98 and Escherichia coli WP2 uvrA at a dose of 20-5000 µg/plate (GLP guideline study, BASF, 1998). Positive control substances caused increases in the number of revertants as expected, indicating proper test conditions. The test substance showed no mutagenic effects at any dose level including the recommended limit dose of 5000 µg/plate.

Chromosome aberration test

The test item was assessed for its potential to induce structural chromosome aberrations in primary lymphocytes in vitro in two independent experiments at doses of 125 - 1580 µg/ml with and without metabolic activation (GLP guideline study, BioReliance, 2007). Under the experimental conditions reported no increased aberration frequencies were observed by the chromosome aberration test. Based on the findings of this in vitro mammalian chromosome aberration test using human peripheral blood lymphocytes, the test item was negative for the induction of structural or numerical chromosome aberrations in both the non-activated and the S9-activated test systems.

HPRT (read across, for justification see repeated dose toxicity)

The structural analogue 3,6,9,12-Tetraoxatetradeca-1,13-diene (CAS 765-12-8) of the test item was tested with and without metabolic activation for mammalian gene mutation (HGPRT locus) in Chinese hamster ovary cells (GLP guideline study, BASF SE, 2011). The concentration range tested was up to 2100 µg/mL (without and with metabolic activation by S9-Mix). No induction of forward mutations was observed in any of the experiments. Positive and negative controls gave the expected results. Therefore, the structural analogue of the test item is non-mutagenic in CHO cells (HGPRT-/+).

 

in vivo

Mouse micronucleus test

In a GLP guideline study according to OECD 474 (BioReliance, 2007), the test item was tested for clastogenicity and for the ability to induce spindle poison effects in ICR mice using the micronucleus test method. The test substance, dissolved in corn oil was administered by gavage to male and female animals at dose levels of 500 mg/kg, 1000 mg/kg and 2000 mg/kg bw body weight in a volume of 20 mL/kg body weight. As a negative control, corn oil (the selected vehicle) was administered to male mice by the same route, and gave frequencies of micronucleated polychromatic erythrocytes within the historical control range. The test item reduced the ratio of polychromatic erythrocytes to total erythrocytes relative to the respective vehicle controls in both sexes. Although these reductions did not occur in a dose-related manner, they suggest that the test item was bioavailable to the bone marrow target tissue. The test item did not produce a significant increase in the incidence of micronucleated polychromatic erythrocytes in either sex of any group relative to the respective vehicle control groups at either 24 or 48 hours after dose administration. Based on the observations in this study and under the conditions described in this report, the test item was not clastogenic in the mouse micronucleus assay.

 


Justification for selection of genetic toxicity endpoint
No study was selected since all studies were negative.

Short description of key information:
The test substance was not mutagenic in a bacterial reverse mutation assay in Salmonella and E.coli (OECD 471, Ames). Also, no mutagnic effects were observed in an in vitro chromosome aberration test using primary human blood lymphocytes and in an in vivo mouse micronucleus test after oral administration. In addition the read across substance 3,6,9,12-Tetraoxatetradeca-1,13-diene (CAS 765-12-8) showed no mutagenic effects in a gene mutation test in vitro (HPRT).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Classification is not warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.