Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Under the category of Genetic Toxicity, bacterial mutation assays were carried out by Perstorp AB using NesterolTM, the trade name for isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol and by the Eastman Kodak Company. Both studies were performed according to GLP and guideline, and were therefore both considered to be key studies for this particular endpoint. The mutagenic/genotoxic potential of isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol has been characterized in a well conducted bacterial in vitro mutagenicity test and an in vivo mammalian bone marrow mouse micronucleus assay. In bacterial reverse mutation assays conducted by a method similar to OECD Guideline 471, there were no increases in mutation frequency in any strain of Salmonella typhimurium at concentrations up to 3000 or 5000 μg/plate, in the presence or absence of metabolic activation. The positive and negative controls in these studies induced the appropriate responses. In an in vivo mammalian bone marrow mouse micronucleus assay conducted by a method similar to that prescribed in OECD 474, there was no evidence of a significant increase in the number of micronuclei in bone marrow polychromatic erythrocytes of mice administered a single dose of 2000 mg/kg bw isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol , the highest dose tested. The vehicle and positive controls in both studies induced the appropriate responses.

Based on the in vitro hydrolysis of isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol to TMPD and a similar in vivo metabolic profile for the diisobutyrate (TXIBTM), available in vitro mammalian mutagenicity data for TXIBTM should also be considered in the overall genetic toxicity evaluation of isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol . In an in vitro chromosome aberration assay conducted with TXIB™ by a method similar to that prescribed in OECD 473, OPPTS 870.5375 and EU B.10, there was no evidence of an increase in the number of CHO cells with chromosomal aberrations or polyploidy in the presence or absence of metabolic activation, even at dose levels that showed clear cytotoxicity. In an in vitro forward mutation assay conducted with TXIB™ according to OECD Guideline 476, there was no increase in mutation frequency at the HGPRT locus in CHO cells at concentrations up to 40 μg/mL in the absence of metabolic activation or up to 2000 μg/mL in the presence of activation. Under nonactivation conditions, the test material was excessively cytotoxic at concentrations ≥62.2 μg/mL. For all studies with TXIB™, vehicle and positive controls induced the appropriate responses.


Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Although no in vitro or in vivo germ cell mutagenicity/genotoxicity studies were available for review, the total weight of evidence available indicates that isobutyric acid, monoester with 2,2,4 -trimethylpentane-1,3 -diol is not expected to induce heritable mutations in the germ cells of humans and is not classified for “Mutagenicity/genotoxicity” according to EU CLP.