Hexane, 1,6-diisocyanato-2,2,4(or 2,4,4)-trimethyl-

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-diisocyanate were investigated.

Based on the molecular structure, molecular weight, water solubility, and results from octanol-water partition coefficient determination, it can be expected that oral, inhalative and dermal absorption rates are existent, distribution in the body is not wide. However, the results form acute and repeated dose studies shows that the substance has only low absorption rates. The test substance induces local effects by dermal irritation and corrosion as well as lung edema.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The following remarks on the toxicokinetics of 2,2,4 (or 2,4,4)-trimethylhexane-1,6 -diisocyanate are based on physiochemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

The substance is a colourless to yellowish liquid having a molecular weight of 210.27 g/mol. It has a vapour pressure of 0.31 Pa at 20°C(AQura, 2011) and has a very low solubility in water in the hydrolysis studies (20 mg/l at 20 °C, IUCLID Chapter 5.1.2) under normal ambient conditions. The partition coefficient determination was not possible, because the substance reacts with water indicating a hydrophilic character of the substance. The substance is completely miscible with water.

Oral and GI absorption: Due to the fact that the substance is completely miscible in water, the substance will most probably be hydrolysed in the gastro-intestinal tract. However, the oral toxicity was low with a LD₅₀(rat) of 4800 mg/kg bw (IBR, 1977).

Dermal absorption: Dermal absorption of the substance is anticipated to be moderate, due to the hydrophilic properties of the substance. The test substance showed clear dermal irritation and corrosion in an acute dermal irritation/corrosion study (Hüls AG, 1984), but no signs of systemic toxicity were observed. Furthermore, the test substance showed clear skin sensitizing properties in a guinea pig maximization test (Notox, 2000), thus indicating that significant dermal uptake is likely.

Inhalation absorption: Only the respiratory tract is concerned after acute and repeated inhalative aerosol exposure to rats (Kimmerle, 1972). All clinical signs and histopathological findings in these studies could be related to the irritant properties of the substance, indicating certain reactivity due to the chemical nature of the isocyanate-groups of the molecule. There are no indications supportive for an absorption or systemic availability of the substance or a metabolite.

Distribution:The physico-chemical information (molecular weight, low vapour pressure, hydropyhilicity and water solubility) indicates that the substance will be distributed.

Accumulative potential: Based on the physico-chemical information (e.g. water solubility), it is concluded that the potential for bioaccumulation is low as it is not proposed for classification as PBT substance.

No data are available regarding the excretion of absorbed substance.

Based on the results of several in vitro genotoxicity tests (LPT, 2011,2012; all performed with and without metabolic activation) it is concluded that DNA-reactive metabolites of the substance will not be generated in mammals in the course of hepatic biotransformation.