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Additional information

in vitro

Triethyleneglykoldivinylether 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 40M0283/964176). 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.

Triethyleneglykoldivinylether was assessed for its potential to induce structural chromosome aberrations in V79 cells in vitro in three independent experiments at doses of 50-2000 µg/ml with and without metabolic activation (GLP guideline study, BASF 32M0283/969014). Under the experimental conditions reported increased aberration frequencies were observed by the chromosome aberration test in V79 cells. With regard to the evaluation criteria Triethylenglycoldivinylether is classified to be weakly mutagenic. However, the induction of structural aberrations was observed only after treatment with high concentrations of the test substance (5-10 mM) at which cytotoxicity - reduced cell numbers in combination with reduced mitotic indices - was evident. Therefore, the observed DNA damage is most probably a secondary effect of cytotoxicity.

Triethyleneglycoldivinylether was assessed for its potential to induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in Chinese hamster ovary (CHO) cells in vitro (BASF, 50M0162/03M007). Two independent experiments were carried out, both with and without the addition of liver S9 mix from induced rats (exogenous metabolic activation) up to doses of 2100 µg/ml. The vehicle controls gave mutant frequencies within the range expected for the CHO cell line. Both positive control substances, EMS and MCA, led to the expected increase in the frequencies of forward mutations. The test substance did not cause any relevant increase in the mutant frequencies both without S9 mix and after adding a metabolizing system in two experiments performed independently of each other.

in vivo

In a GLP guideline study according to OECD 474 (BASF, 26M0283/964412), Triethyleneglycoldivinylether was tested for clastogenicity and for the ability to induce spindle poison effects in NMRI mice using the micronucleus test method. The test substance, dissolved in olive oil was administered twice intraperitoneally to male animals at dose levels of 250 mg/kg, 500 mg/kg and 1,000 mg/kg body weight in a volume of 10 ml/kg body weight in each case. As a negative control, olive 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. Both of the positive control chemicals, i.e. cyclophosphamide for clastogenic effects and vincristine for induction of spindle poison effects, led to the expected increase in the rate of polychromatic erythrocytes containing small or large micronuclei. Animals which were administered the vehicle or the positive control substances, cyclophosphamide or vincristine, did not show any clinical signs of toxicity. The administration of the test substance Triethylenglykoldivinylether led to evident signs of toxicity. The intraperitoneal administration of Triethylenglykoldivinylether did not lead to any increase in the number of polychromatic erythrocytes containing either small or large micronuclei. The rate of micronuclei was always in the same range as that of the negative control in all dose groups and at all sacrifice intervals. Thus, the test substance Triethylenglykoldivinylether does not have any chromosome-damaging (clastogenic) effect, and there were no indications of any impairment of chromosome distribution in the course of mitosis.


Short description of key information:
OECD 471 (Ames): negative
OECD 473 (chromosome aberration in vitro): negative
OECD 476 (HPRT): negative
OECD 474 (micronucleus test in vivo): negative

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.