Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

2,3 -Epoxypropyl neodecanoate induced gene-mutation in Salmonella typhimurium tester strains TA 1535 and TA 100 in the presence of a rat liver derived S-9, metabolic activation perparation in three independent studies. These data suggest that the test substance must be metabolized to the ultimate bacterial mutagenic form. 2,3 -Epoxypropyl neodecanoate did not induce gene-conversion in yeast cells with rat liver S-9. The test substance also did not induce significant chromosome damage in rat primary RL1 cells in culture. These primary rat liver derived cell are capable of endogenous metabolic activation. In an O.E.C.D. Test guideline No. 473 in vitro chromosome aberration assay treatment with 2,3 -epoxypropyl neodecanoate did not induce a significant increase in the chromosome aberration of CHO cells under any treatment condition. Furthermore, 2,3 -epoxypropyl neodecanoate did not induce transformed clones in hamster derived BHK cells. In an in vivo study conducted in rats, 2,3 -epoxypropyl neodecanoate did not induce evidence of DNA damage detectable by alkaline elution. In an O.E.C.D. Test Guideline No. 486 in vivo study the test substance did not induce in male rat livers any evidence of unscheduled DNA synthesis (DNA repair) up to the high oral gavage dose level of 2000 mg/kg of body weight. In the in vivo gene-mutation MutaMouse study conducted at oral gavage dose levels of 0, 250, 500, and 1000 mg/Kg/day, the test substance inducted a statistically significant dose-related increase of the mutant frequency in the liver, kidney and bone marrow. There was no evidence of an increase of the mutant frequency in the developing sperm cells.

Justification for selection of genetic toxicity endpoint
Significant positive mutation findings in vitro and in vivo.

Short description of key information:
2,3-Epoxypropyl neodecanoate induced gene-mutations in Ames/Salmonella tester strains TA 1535 and TA 100 in the presence of rat liver derived S-9 metabolic activation preperation in multiple independent studies. However, the test substance failed to induce evidence on genotoxicity in yeast, rat liver cells, CHO cells and hamster derived BHK cells. 2,3-Epoxypropyl neodecanoate did not not induce DNA damage in vivo in a rat alkaline elution study at a dose level of 4850 mg/kg of body weight. The test substance was also accessed for its ability to induce unscheduled DNA synthesis (UDS) a measure of DNA repair in vivo in male rats by an O.E.C.D. test guideline No. 486 protocol with GLP compliance. An O.E.C.D. test guideline 488 Transgenic Rodent gene-mutation assay was also conducted in the liver kidney, bone marow and male germ cells of the MutaMouse.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

Because the test substance, 2,3 -epoxypropyl neodecanoate induced gene-mutation in the liver, kidney and bone marrow of the MutaMouse, it is a GHS/CLP Category 2, Mutagen H341.