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Administrative data

Description of key information

Key value for chemical safety assessment

Additional information

There were no chronic repeat-exposure studies conducted with isobutyric acid, monoester with 2,2,4 -trimethylpentane-1,3 -diol available for review. However, results for a repeat-exposure study in which male and female rats were exposed to up to 1000 mg/kg bw/day of isobutyric acid, monoester with 2,2,4 -trimethylpentane-1,3 -diol for up to 51 days by oral gavage suggest that the test material is unlikely to pose a significant risk for the development of a carcinogenic effect. No necrosis or hyperplasia was observed in any organ at necropsy. Microscopic liver lesions found in both sexes were considered an adaptive metabolic rather than a toxic response. The only other adverse effect was an increase in chronic progressive nephropathy, a common spontaneous lesion in male rats and frequently exacerbated by chemical exposure. While very advanced chronic progressive nephropathy may be a risk factor for the spontaneous development of renal tumors in rats, chronic progressive nephropathy has not been observed in humans. 

In addition, no mutagenicity/genotoxicity was observed in a bacterial reverse mutation assay or an in vivo mammalian bone marrow mouse micronucleus assay. In addition, negative results were also observed in several in vitro mammalian mutagenicity/genotoxicity studies conducted with TXIB which shares a similar metabolic profile to isobutyric acid, monoester with 2,2,4 -trimethylpentane-1,3 -diol.

Justification for classification or non-classification

No hyperplasia or necrosis was observed in groups of male and female rats exposed to isobutyric acid, monoester with 2,2,4 -trimethylpentane-1,3 -diol by the oral route at dose levels up to 1000 mg/kg bw/day for up to 51 days and all genotoxicity studies were negative both in the presence and absence of metabolic activation. Based on a weight-of-the evidence evaluation, isobutyric acid, monoester with 2,2,4 -trimethylpentane-1,3 -diol is unlikely to pose a significant risk for the development of any tumor type in humans exposed to this chemical and is not considered to be classified for Carcinogenicity according to EU CLP.