Hexane, 1,6-diisocyanato-, homopolymer, 3,5-dimethyl-1H-pyrazole-blocked

Endpoint summary

Additional information

The following remarks on the toxicokinetics are based on the physico-chemical properties of the substance and on toxicological data. Experimental studies on toxicokinetics were not performed.

Hexamethylene diisocyanate, oligomerisation product, blocked with 3,5-dimethyl-1H-pyrazole is a colourless solid. Since the glass transition temperature is 9.2 °C, the substance appears to be resinous and somewhat sticky at ambient temperature. The substance contains of a range of different oligomeric structures with n = 3, 5, 7, 9, ... HDI units blocked with 3,5-dimethyl-1H-pyrazole and is thus defined as UVCB (Substances of Unknown or Variable composition, Complex reaction products or biological materials). The molecular weight ranges between approx. 500 and 2000 g/mol with a molecular weight of 793 g/mol for the main constituent (see IUCLID section 1.1). The vapour pressure of the substance is predicted to be very low (3.3 x 10E-29 Pa at 25 °C; Sadler, 2018) and the substance is practically insoluble in water (< 0.1 mg/L at 20 °C; Neuland, 2012). With a log Pow of 6.4 (Neuland, 2012) the substance shows highly lipophilic properties.

In the molecular structure of Hexamethylene diisocyanate, oligomerisation product, blocked with 3,5-dimethyl-1H-pyrazole no functional groups with relevant acidic or basic character can be found. Therefore, no significant dissociation is expected at physiological pH values and beyond. The site of blocking is known to be physically stable. Only at elevated temperatures of > 90 °C a de-blocking occurs and reactive groups are released.

Oral and GI absorption: Due to the high molecular weight, the log Pow of 6.4 and the very low water solubility of the substance oral absorption is not expected. In fact, oral toxicity was shown to be low with a LD50 (rat) of > 1500 mg/kg based on active ingredient (limit dose, LD50 of test item > 2000 mg/kg bw, Stropp, 1998). No effects at all were observed in this study.

Dermal absorption: Due to the high molecular weight and the very low water solubility of the substance dermal absorption is not expected. The log Pow of 6.4 does not fully exclude but limit absorption across the skin. The assumption of a low dermal absorption potential is confirmed by the data for skin irritation (Leuschner, 1998) and skin sensitization (Buehler test, Stropp, 1998) which do not show systemic effects after dermal exposure.

Respiratory absorption: Due to the very low vapour pressure of the substance significant respiratory absorption via vapour is not expected. Furthermore, highly lipophilic compounds (log Pow > 4), particular those that are poorly soluble in water (1 mg/l or less), are expected to be poorly absorbed. In fact, there is no indication of systemic toxicity and systemic availability after inhalative exposure of the liquid aerosol for 14 days. No treatment-related clinical abnormalities were observed in this study (Pauluhn, 2013).

Distribution: The physico-chemical information (high molecular weight, low vapour pressure, lipophilicity and low water solubility) indicate that Hexamethylene diisocyanate, oligomerisation product, blocked with 3,5-dimethyl-1H-pyrazole can be distributed only to a low amount.

Accumulation potential: A bioaccumulation potential cannot be excluded based on the log Pow of 6.4. However, due to the high molecular weight of the substance (above 500 g/mol) together with the absence of systemic toxicity and availability in the existing animal studies accumulation in adipose tissues is not expected. 

 

Based on the results of several in vitro genotoxicity tests (Ames Test, Jarzombek, 2012; HPRT Test, Wollny, 2013; MNT in vitro, Sutter, 2012; all performed with and without metabolic activation) it is concluded that DNA-reactive metabolites of Hexamethylene diisocyanate, oligomerisation product, blocked with 3,5-dimethyl-1H-pyrazole will not be generated in mammals in the course of hepatic biotransformation.