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3 -Isocyanatomethyl-3,5,5-trimethyl-cyclohexyl isocyanate homopolymer (IPDI homopolymer) (CAS-Nr. 53880-05-0); Information/Assumptions regarding toxicokinetics

The following remarks on the toxicokinetics of IPDI homopolymer are based on physiochemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

IPDI homopolymer is an odourless solid (pellets) with a very low vapour pressure (1.3 * 10 -11 hPa at 20 °C, AQura, 2010) under normal ambient conditions.

In water the substance hydrolyses rapidly with a half-live of clearly below 12 hours (23 °C) at different pH values.

Because of the hydrolyzation potential and a very low water solubility experimental data such as pKa or log Kow can not be obtained for IPDI homolpolymer. The octanol-water partition coefficient of the test substance was calculated using a well established QSAR method at log Kow approx. 14.48 (Evonik, 2009).

Due to the low vapour pressure inhalation exposure via vapour is not to be expected. Wherever aerosolization occurs exposure is possible. There are no indications of systematic toxicity and systemic availability after inhalative exposure of the aerosol. No organ lesions other than respiratory tract could be found, and the clinical signs could all be related to respiratory distress and were seen as a consequence of the irritant properties of the substance (BayerAG, 1996; Pauluhn, 2003; Ma-Hock et al., 2009). These effects most probably are related to the chemical nature of the isocyanate-groups of IPDI homopolymer.

Regarding oral absorption at least partial hydrolysis is assumed to occur in the gastro-intestinal tract. In fact, oral toxicity was very low with an LD50 (rat) of > 14000 mg/kg bw (IBR, 1976). No systemic signs could be observed.

Dermal absorption of IPDI homopolymer could not be excluded based on a calculated log Kow that shows a high lipophility (approx. 14.48; Evonik, 2009). In fact, no signs of systemic toxicity were observed in an acute dermal irritation/corrosion study (LPT, 2005). Nevertheless, the test substance has shown skin sensitizing properties in a guinea pig maximization test (Notox B.V., 2004), thus indicating that a dermal uptake, even though small, can occur. Deducing from that IPDI homopolymer has the property to react with nucleophilic groups of proteins or peptides and form hapten-protein complexes or conjugate-antigens.

No data are available regarding the excretion of absorbed IPDI homopolymer.

Based on the results of several in vitro genotoxicity tests (DeVogel, 2007; Schulz and Hellwig, 2007; Harlan, 2009 and Herbold, 2002; all performed with and without metabolic activation) it is concluded that DNA-reactive metabolites of IPDI homopolymer will not be generated in mammals in the course of hepatic biotransformation.

Supplementary information of 2017-registration: A Developmental Toxicity Study with repeated oral administration of the test substance (LPT, 2017) revealed no test item-related findings at all. This gives further proof that administration of the test substance, even after repeated oral exposure of doses up to 1000 mg/kg, does not lead to systemic toxicity and thus systemic availability is expected to be low after oral exposure