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Additional information

SMPO Heavy Ends was tested in an in vitro mammalian cell gene mutation test with L5178Y mouse lymphoma cells to studythe induction of forward mutations at the thymidine-kinase locus (TK-locus) in L5178Y mouse lymphoma cells (Verspeek-Rip, 2015). The test was performed in the absence of S9-mix with a 3 and 24 hour treatment period and in the presence of S9-mix with a 3 hours treatment period (rat liver S9-mix induced by a combination of phenobarbital and ß-naphthoflavone).

In the first experiment, SMPO Heavy Ends was tested up to concentrations of 65 µg/mL and 164 µg/mL in the absence and presence S9-mix, respectively. The incubation time was 3 hours. Relative total growth (RTG) was reduced to 9% and 6% in the absence and presence of S9-mix, respectively. SMPO Heavy Ends precipitated in the culture medium at the dose level of 164 µg/mL.

In the second experiment, SMPO Heavy Ends was tested up to concentrations of 60 µg/mL in the absence of S9-mix. The incubation time was 24 hours. The RTG was reduced to 13%.The spontaneous mutation frequencies in the solvent-treated control cultures were within the minimum and maximum value of the historical control data range and within the acceptability criteria of this assay.

In the absence of S9-mix, SMPO Heavy Ends did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent experiment with modifications in the duration of treatment time.

In the presence of S9-mix, SMPO Heavy Ends did not induce a significant increase in the mutation frequency.


Justification for selection of genetic toxicity endpoint
Key study

Short description of key information:
SMPO Heavy Ends was tested in an in vitro mammalian cell gene mutation test with L5178Y mouse lymphoma cells to study the induction of forward mutations at the thymidine-kinase locus (TK-locus) in L5178Y mouse lymphoma cells.
In the first experiment, the substance was tested up to concentrations of 65 µg/mL and 164 µg/mL in the absence and presence S9-mix, respectively. The incubation time was 3 hours. Relative total growth (RTG) was reduced to 9% and 6% in the absence and presence of S9-mix, respectively. SMPO Heavy Ends precipitated in the culture medium at the dose level of 164 µg/mL.
In the second experiment, the substance was tested up to concentrations of 60 µg/mL in the absence of S9-mix. The incubation time was 24 hours. The RTG was reduced to 13%.The spontaneous mutation frequencies in the solvent-treated control cultures were within the minimum and maximum value of the historical control data range and within the acceptability criteria of this assay.
In the absence of S9-mix, SMPO Heavy Ends did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent experiment with modifications in the duration of treatment time.
In the presence of S9-mix, SMPO Heavy Ends did not induce a significant increase in the mutation frequency.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on these results and according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments), it is concluded that SMPO Heavy Ends is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions described in this report. Although the in vitro mammalian gene mutation is not an Annex VII study but an Annex VIII study, it is considered relevant for the Genetic toxicity endpoint section and is closer to human than the bacterial mutation. Therefore the study is considered relevant, adequate and reliable instead of the Ames test.

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