3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers, reaction products with 2-butanone oxime

Endpoint summary

Description of key information

This toxicokinetic assessment is based on the physico-chemical properties of the substance and on toxicological data. Experimental studies on toxicokinetics were not performed.

Additional information

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers, reaction products with 2-butanone oxime is a white solid (powder) consisting of 3 to > 7 IPDI units blocked with 2-butanone oxime (UVCB). The mean molecular weight is calculated with about 930 g/mol (range 618 to 1991, see IUCLID section 1.1). The vapour pressure of the substance is very low (9.9 x 10 ^-5 Pa at 20 °C; Fonseca, 2012) and the substance is practically insoluble in water (< 0.1 mg/L at 20 °C; Neuland, 2012). With a log Pow of 5.5 to 6.5 (Neuland, 2012) the substance shows highly lipophilic properties.

In the molecular structure of 3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers, reaction products with 2-butanone oxime 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 are released.

Oral and GI absorption: Due to the high molecular weight, the log Pow of > 5.5 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 > 2000 mg/kg bw (limit dose, Notox, 2001). Necropsy showed no noticeable 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 > 5.5 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 (Notox, 2001) and skin sensitization (two Buehler skin sensitization tests, Vohr, 2002 and Kolb, 1993 and a guinea pig maximization test, RTC, 2000) 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), in 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 powder 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) indicates that IPDI oligomer, methyl ethyl ketone oxime-blocked could be distributed only to a low amount.

Accumulation potential: A bioaccumulation potential cannot be excluded based on the log Pow of > 5.5. However, due to the high mean molecular weight of the substance (about 930 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, LPT, 2012 and Gahlmann, 1993; HPRT Test, LPT, 2012; MNT in vitro, LPT, 2012; all performed with and without metabolic activation) it is concluded that DNA-reactive metabolites of 3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers, reaction products with 2-butanone oxime will not be generated in mammals in the course of hepatic biotransformation.