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The bacterial reverse mutation assay (Ames Test) according to OECD 471 did not produce any positive results with the test substance Vinyl lauratein tester strains TA 98, TA 100, TA 1535 and TA 1537 both with and without metabolic activation up to concentrations of 5000 µg/l. Concentrations of 25, 50, 250, 500, 2500 and 5000 µg/plate were tested based on a dose range finding test. The substance was soluted in dimethyl sulphoxide and was administered via plate incorporation. No precipitation was seen whereas phase separation occured in the highest dose tested because of virtually insolubility of the test substance in water. Signs of toxicity were seen in the highest tested concentration of 500 µg/plate for tester strain TA 98 both with and without metabolic activation. The negative, solvent and positive controls worked as expected.

Vinyl laurate was assayed in an in vitro gene mutation assay using cultures of mouse lymphoma L5178Y wild type cells according to OECD Guideline 476. Induced mutants to 6 -thioguanine (HPGRT locus) resistance were determined both with and wthout metabolic activation by a rat liver post-mitochondrial fraction (S9) from Aroclor 1254 -induced rats. In the first experiment, comprisoing two independent experimants, cells were exposed to concentrations of 0.0047 to 0.60 µl/ml for 2 hours. In order to demonstrate the sensitivity of the assay, positive controls (4 -nitroquinoline-N-oxid without S9, benz-a-pyrene with S9) were used which worked properly. Depending on the cytotoxicity after treatment without metabolic activation, cultures trated with 0.0075, 0.15, 0.30, and 0.60 µl/ml Vinyl laurate were plated for mutation to 6-thioguanine resistance. No statistically significant differnces in mutant frequncies were found between trated and control cultures. With S9-mix, after treatment 0.038, 0.075, 0.15, 0.30 and 0.60 µl/ml at cytotoxic levels from 0 to 68%, Vinyl laurate induced weak but statistically significant increases in mutant frequencies at 0.075 and 0.15 µl/ml. The positive results nevertheless could not be verified at higher dose levels and there are some discrepancies in mutagenicity levels of the corresponding two replicates on same levels. Depending on the results of the first experiments, a second experiment was performed. The results of the first experiment could be confirmed in parts. With metabolic activation other dose levels showed the weak positive outcome. It is thus concluded that Vinyl laurate was able to induce gene mutations in mouse lymphoma L5178Y cells in the HGPRT-locus after metabolic activation in vitro at a weak level. Vinyl laurate did not induce gene mutations without metabolic activation in vitro when tested under the experimantal conditions reported.

Vinyl laurate was assayed in an in vitro cytogenetic assay using cultures of Chinese Hamster ovary cells (CHO) both in the absence and presence of metabolic activation by a rat liver post-mitochondriola fraction (S9) from Arochlor1254 -induced rats according to OECD Guideline 473. In an initial cytotoxicity experiment dose levels for the main study were determined on the basis of the mitotic indices. In the first experiment of the main study comprising two independent experiments, cells were exposed to concentrations of 0.0006, 0.002, 0.006, 0.02, 0.06 and 0.20 µl/ml in the absence of S9 for 15, 20 and 26 hours. In the presence of S9 cells were treated for two hours with the same concentrations followed by different recovery phases of either 13, 18 and 24 hours. This way metaphases were harvested at 15, 20 and 26 hours after start of treatment. In order to demonstrate the sensitivity of the assay system, methylmethynesulfonate (without metabolic activation) and cyclophospamide (with metabolic activation) were used as positive control agents and both compounds induced statistically significant increases in chromosomal abberations, including and excluding gaps. Without S9, at 15 hours sampling time with concentrations of 0.0006, 0.006 µl/ml and at 20 hours sampling time after treatment of cells with 0.06 µl/ml of Vinyl laurate, 98 -100 first division metaphases could be analyzed at different cytotoxic levels. No statistically significant differences in numbers of aberrations were found between treated and control cultures. With S9 in contrast after treatment with 0.02, 0.06 and 0.20 µl/ml at 26 hours sampling time Vinyl laurate induced statistically significant and dose-related increases in numbers of aberrations. Depending on the results of the first experiment, a second independent experiment was performed using duplicate cultures. The results of the first experiment could be qualitatively confirmed in this second experiment.

Vinyl laurate was able to induce chromosomal aberrations in Chinese Hamster Oveary cells in vitro with metabolic activation but not without metabolic activation when tested under the experimental conditions reported.

Vinyl laurate was tested in the Micronucleus test in mice according to OECD Guideline 474. The test substance was dissolved in corn oil and was administered via oral gavage. In a dose range finding study 6 animals (3 males and 3 females) were dosed with 2000 mg/kg bw, the highest dose requested by the OECD guideline. All animals showed no abnormalities after dosing.

In the main study, five animals were used in each of six treatment groups, including negative and positive controls. All groups received a single oral intubation. The negative and positive control groups were treated with vehicle and 50 mg/kg bw cyclophosphamide respecitvely. Animals were dosed with the test item Vinyl laurate at 2000 mg/kg bw (two groups), 1000 (one group) and 500 (one group) mg/kg body weight. All animals showed no abnormalities after dosing. Bone marrow of the groups treated with Vinyl laurate was sampled 24 and 48 (highest dose only)hours after dosing. No increase in the mean frequency of micronucleated polychromatic erythrocytes was observed in the polychromatic erythrocytes of the bone marrow of animals treated with Vinyl laurate.

The incidence of micronucleated polychromatic erythrocytes in the bone marrow of all negative control animals was within the historical solvent control data range. Cyclophospamid, the positive control substance, induced a statistically significant increase in the number of micronucleated polychromatic erythrocytes. Hence, both criteria for an acceptable assay were met. It is concluded that Vinyl laurate is not clastogenic in the micronucleus test.


Short description of key information:
Vinyl laurate is not mutagenic in the Ames test with and without metabolic activation and in the in vitro chromosome aberration test and the mouse lymphoma assay without metabolic activation. it is weakly positive in the mouse lymphoma assay with metabolic activation and positive in the chromosome aberration test with metabolic activation. In the in vivo micronucleus test is was not mutagenic.

Endpoint Conclusion:

Justification for classification or non-classification

The bacterial reverse mutation assay (Ames Test) according to OECD 471 did not produce any positive results with Vinyl laurate in tester strains TA 98, TA 100, TA 1535 and TA 1537 both with and without metabolic activation. Vinyl laurate is able to induce gene mutations in mouse lymphoma L5178Y cells in the HGPRT-locus after metabolic activation in vitro but not without metabolic activation at a weak level. It was also able to induce chromosomal aberrations in Chinese Hamster Oveary cells in vitro with metabolic activation but not without metabolic activation. Nevertehless in the in vivo micronucleus test according to OECD Guideline 474 no mutagenic effects were observed. Therefore there is no need for classification.