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Description of key information

Key value for chemical safety assessment

Additional information

Two repeated dose studies are available for 2,2,4-trimethyl-1,3-pentanediol.

In a repeated dose toxicity study,  the test material was administered ad libitum at up to 2% in the diet for up to 57 days, the NOAEL was 0.5%. At the highest dose tested, there was a significant reduction in growth rate and body weight gain in females with a corresponding decrease in feed intake. There were no test substance-related deaths and no significant treatment-related effects on clinical signs, hematology, clinical chemistry, gross pathology or histopathology at any dose level tested. There were no significant functional changes in any organ system and target organ effects were limited to changes in absolute and/or relative organ weights. Using feed efficiency data, consumption of 0.5% of TMPD in diet corresponded to an actual average intake of 376 mg/kg/day (367 and 385 mg/kg/day for females and males, respectively).  

In another study, the potential for 2,2,4-trimethyl-1,3-pentanediol (TMPD) to cause target organ toxicity following repeated exposure was evaluated based on a key study conducted by Good Laboratory Practices and following regulatory guideline.

A key study, following OECD guideline amd GLP was conducted to determine adverse effects of TMPD for a period of 90 consecutive days on Wistar rats. The test item was administered orally at doses of 30, 120 and 480 mg/kg TMPD in male and female rats. Mortality was observed in two high dose tretaed male rats.In the 480 mg/kg tested group, mild to moderate salivation and mildtonic clonic convulsion were observed post dosing in all animals on multiple days of the study. However, all clinical signs were resolved by the following morning. Correlating parameters showed no treatment related effects in neurobehavioural parameters and functional observation battery parameters. Mean body weight, mean body weight change, and food consumption of treatment groups were comparable with that of the vehicle control group. Changes in haematology and clinical chemistry were considered toxicology insignificant. Increase in liver , adrenal and kidney weights were observed along with histologic changes, however, the changes were considered related to stress and were lower in incidence and in severity (minimal to mild) and not considered relevant to human. Further hepatocellular vacuolation in liver were also noted in control group and therefore the changes were considered as non-adverse. Based on the mortality and convulsions observed at 480 mg/kg b.wt/day treated animals, a NOAEL of 120 mg/kg/d was considered for the study and for DNEL calculations.

 

Justification for classification or non-classification

There were no treatment-related deaths; no significant functional changes in any organ system; no significant effects on hematology or clinical chemistry parameters; and no significant gross or histopathological organ damage in male and female rats exposed to up to 120 mg/kg/d of the test material given orally for 90 days. 2,2,4-Trimethyl-1,3-pentanediol is not classified for Target Organ Toxicity according to Annex I of Directive 67/548/EEC. Based on the results of a 90 day oarl study in rats, 2,2,4-trimethyl-1,3-pentanediol is not classified for Specific Target Organ Toxicity – Repeated Exposure according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).