Reaction mass of 2,2,4-trimethylhexane-1,6-diol and 2,4,4-trimethylhexane-1,6-diol

Endpoint summary

Description of key information

There were no studies available in which the toxicokinetic properties (absorption, distribution, metabolism, elimination) of 2,2,4 (or 2,4,4)-trimethylhexane-1,6 -diol were investigated. A data waiver is claimed.

Based on the molecular structure, molecular weight, water solubility, vapour pressure and octanol-water partition coefficient it can be expected that only oral absorption rates is significantly existent. The results form the acute and repeated oral toxicity dose studies confirm that the substance has moderate oral absorption rates. Based on a very log Kow which indicates a low lipophilicity of the test item, significant dermal absorption is not expected. Due to the very low vapour pressure of the test item significant respiratory absorption via vapour is also not expected.

The test item could be distributed in the body in a certain amount.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There were no studies available in which the toxicokinetic properties (distribution, metabolism, elimination) of the test item were investigated. Therefore the following remarks on the toxicokinetics of 2,2,4 (or 2,4,4)-trimethylhexane-1,6 -diol are based on physico-chemical properties of the compound and on toxicological data.

2,2,4 (or 2,4,4)-Trimethylhexane-1,6 -diol is a colourless liquid with a molecular weight of 160.25 g/mol. It is highly soluble in water (35.5 g/L; Infracor GmbH, 2001) and has a very low vapour pressure (0.053 Pa; Infracor GmbH, 2002) under normal ambient conditions. The partition coefficient octanol/water was determined as log Kow = 0.45 at 25 °C (Lange, 2016), indicating no potential for bioaccumulation.

With regard to hydrolysis, there are no functional groups in the molecular structure that are liable to hydrolysis. Therefore, no significant dissociation is expected at physiological pH values.

Oral and GI absorption: Due to the fact, that there are no functional groups in the molecular structure that are liable to hydrolysis, it is not expected that the substance is significantly hydrolysed in the gastro-intestinal tract. In fact, the acute oral toxicity is low (LD50 (rat ) > 2000 mg/kg bw) and only slight signs of toxicity were observed (Hüls AG, 1996). No mortality occured. However, oral absorption could not be excluded based on the results of the repeated dose toxicity study (CitoxLab, 2016). In this study according to OECD 422 with Wistar rats exposed to 100, 300 and 1000 mg/kg bw/day, the test item caused some mortality in the adults at 1000 mg/kg/day. Minor changes in the liver in the Mid and High dose groups of the parental generation, as well as changes in kidneys in the High dose group were not considered to be adverse. Thus, an indication of oral uptake of the substance is given.

Dermal absorption: Based on a very log Kow which indicates a low lipophilicity of the test item, significant dermal absorption is not expected. In fact, the acute dermal toxicity is low with a LD50 (rat) > 2000 mg/kg bw (Hüls AG, 1996). No mortalities were observed and no signs of systemic toxicity. In addition, no erythema or edema were observed from patch removal to end of study. Furthermore, the test item shows neither skin irritating nor skin sensitizing properties (Hüls AG, 1996 and Hüls Infracor GmbH, 1998).

Respiratory absorption: Due to the very low vapour pressure of the test item significant respiratory absorption via vapour is not expected.

Distribution: The physico-chemical information (low molecular weight, low lipophilicity and high water solubility) indicates that the test item could be distributed to a certain amount.

Accumulative potential:The partition coefficient octanol/water was determined as log Kow = 0.45 at 25 °C (Lange, 2016), indicating no potential for bioaccumulation.

Excretion: No data are available regarding the excretion of absorbed 2,2,4 (or 2,4,4)-trimethylhexane-1,6 -diol.

Based on the results of several mammalian in vitro and in vivo genotoxicity tests (Hüls AG, 1996; LPT, 2015; all performed with and without metabolic activation) it is concluded that DNA-reactive metabolites of the test item will not be generated in mammals in the course of hepatic biotransformation.