Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Additional information

There were no chronic repeat-exposure studies conducted with 1 -isopropyl-2,2 -dimethyltrimethylene diisobutyrate available for review. However, results for five repeat-exposure studies in which male and female rats and beagle dogs were exposed to 1 -isopropyl-2,2 -dimethyltrimethylene diisobutyrate for up to 100 days by the oral route suggest that the test material is unlikely to pose a significant risk for the development of a carcinogenic effect. No target organ necrosis was observed in any of the five studies. In two guideline studies in which rats were administered 750 mg/kg bw/day in the diet for 13 weeks or by oral gavage for 44 (males) or 40-53 (females) consecutive days, there was no hyperplasia and no reported increase in peroxisomal content in any treatment group in the longer rat feeding study. Peroxisome proliferation has been associated with the development of liver tumors in rodents. A single instance of hyperplastic foci was seen in the liver of one male in the shorter gavage study. The only other microscopic lesions observed were associated with 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. No hyperplasia or chronic progressive nephropathy was observed at necropsy in three older non-guideline studies conducted in rats and beagle dogs.    

In addition, no mutagenicity/genotoxicity was observed in a bacterial reverse mutation assay, an in vitro chromosome aberration assay, or an in vitro forward mutation assay conducted according to current guideline specifications.

Justification for classification or non-classification

Except for a single instance of hyperplastic foci in the liver of one male rat exposed to 750 mg/kg bw/day for six weeks, no hyperplasia or necrosis was observed in groups of male and female rats and dogs exposed to 1 -isopropyl-2,2 -dimethyltrimethylene diisobutyrate by the oral route for up to 100 days, no increase in peroxisome proliferation was observed in rats exposed to up to 750 mg/kg bw/day in the diet for up to 13 weeks, and all genotoxicity studies were negative both in the presence and absence of metabolic activation. Based on a weight-of-the evidence evaluation, 1 -isopropyl-2,2 -dimethyltrimethylene diisobutyrate 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.