Reaction mass of diisobutyl adipate and diisobutyl glutarate and diisobutyl succinate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

There are no data available for the diisobutyl esters, therefore this endpoint is assessed using read across to data available on the methyl esters and also the hydroysis products, isobutanol, and the constituent acids (adipic, succinic, glutaric).

Three genotoxicity studies are available. Dibasic ester blend was tested in vitro in a bacterial reverse mutation assay, similar to an Ames test but using 3 strains of Salmonella typhimurium, and showed no mutagenic activity in this test system with or without S9 metabolic activation system (from liver or olfactory origin) up to the highest concentrations tested.

Dibasic ester blend was also tested in vitro in a chromosomal aberration assay in human lymphocytes. In the presence of liver S9 metabolic activation, a statistically significantly increased proportion of abnormal cells or cells with one or more aberration were observed at 0.3 and 0.4% (equivalent to 3.3 and 4.4 mg/mL, respectively), illustrating a clastogenic activity of the test substance under at high concentrations in the presence of S9. This result is not conistent with what is known about the hydrolysis products of the methyl esters. Methanol is not clastogenic or genotoxic. Adipic acid, glutaric acid and succinic acid are all endogenous and not considered to be clastogenic or genotoxic. As such it is possible that in the presence of S9, the esters were hydrolysed and the acids released affected the pH, making it more acidic. This is known to cause false positive effects in cytogenicity assays.

In accordance with the REACH regulation, an in vivo genotoxicity assay on somatic cells was performed. A bone marrow micronucleus assay was performed in mice following a single inhalatory nose-only exposure to dibasic ester blend for 6 hours. There was no statistically significant differences in the proportion of micronucleated polychromatic erythrocytes between mice of all groups including controls at any sampling time up to 72 hours following exposure up to a very bigh concentration of 19 mg/L (equivalent to19000mg/m3), illustrating the absence of clastogenicity of the test substance in vivo.

No data are available for the mammalian cell mutagenicity. However Isobutanol is not genotoxic to bacteria or mammalian cells, and the acids are endogenous in mammals and therefore highly unlikely to be be genotoxic at relevant exposure levels to humans.

In addition, in a 90 day study there was no evidence of pre-neoplastic lesions at the highest doses that could be tested. Therefore it is concluded that there is sufficient data available to conclude that this substance is not mutagenic or clastogenic to mammalian cells.

Short description of key information:

Clastogenic in vitro in a chromosomal aberration test on human lymphocytes but negative in an in vitro bacterial reverse mutation assay and an in vivo mouse bone marrow micronucleus assay.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Overall, based on the available read across information the genetic toxicity of dibasic ester blend is considered to be negative and therefore no classification is warranted according to the classification criteria of Annex VI Directive 67/548/EEC or UN/EU GHS.