Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, 3,5-dimethyl-1H-pyrazole-blocked

Endpoint summary

Additional information

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

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers, reaction products with 3,5-dimethyl-1H-pyrazole is a white solid (powder). The substance consists of 3 to ≥ 7 IPDI units blocked with 3,5-dimethylpyrazole (UVCB). The molecular weight of the main component (n=3) is 955.24 g/mol (range 636.83 and 2036.64 g/mol, see IUCLID section 1.1). The vapour pressure of the substance is predicted to be very low (4.52 x 10E-32 Pa at 25°C; Sadler 2019) and the substance is practically insoluble in water (Neuland 2016). A log Pow of 8.6 (25 °C; Neuland 2016) indicates that the substance is highly lipophilic. In the molecular structure of the substance 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 de-blocking occurs and reactive groups will be released.

Oral and GI absorption: Due to the high molecular weight, the log Pow of 8.6 and the very low water solubility of the substance relevant oral absorption is not expected. In fact, oral toxicity was low with a LD50 (rat) of > 2000 mg/kg bw (Schuengel 2007). In that study necropsy showed no particular gross pathological findings.

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 8.6 does not fully exclude but limits absorption across the skin. The assumption of a low potential for dermal absorption is confirmed by data for skin irritation (Gmelin 2007) and skin sensitization (LLNA: neg.; Vohr 2007) which do not indicate 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), in particular those that are poorly soluble in water (1 mg/L or less), are expected to be poorly absorbed. In fact, there was no indication of systemic toxicity and systemic availability after inhalation exposure of the powder aerosol for 14 days. No treatment-related clinical abnormalities were observed in this study (Kopf, 2016).

Distribution: The physico-chemical information (high molecular weight, low vapour pressure, high lipophilicity and low water solubility) indicate that distibution of the substance, if any, will occur only to a very low amount.

Accumulation potential: A bioaccumulation potential cannot be excluded based on the log Pow of 8.6. However, due to the high mean molecular weight of the substance (about 900 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, Herbold 2007; HPRT, Wollny 2015; MNT in vitro, Sokolowski 2015; 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.