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For assessment of toxicokinetic properties a read across to HDI oligomers, isocyanurate type (EC 931 -274 -8) is applied. This substance is a close structural analogue to HDI oligomers, iminooxadiazindione type, also derived from catalytic oligomerisation of 1,6 -hexamethylene diisocyanate (HDI; CAS 822 -06 -0) and also belonging to the CAS number 28182-81-2 (Hexane, 1,6 - diisocyanato-, homopolymer). The read across is based on physicochemical and toxicological similarity. In fact, comparison of the toxicological endpoints, that are available for both of the two substances reveal good correlation.

 Toxicological endpoint  HDI oligomers, isocyanurate type  HDI oligomers, iminooxadiazindione type
 Acute oral toxicity  > 2000 mg/kg  > 2000 mg/kg
 Acute inhalation toxicity (pulmonary irritant study) NOAEL 3 mg/m³   NOAEL 2.1 mg/m³
 Skin Irritation/Corrosion  slight irritation/no classification required  slight irritation/no classification required
 Eye Irritation/Corrosion  very slight irritation/no classification required  very slight irritation/no classification required
 Skin Sensitisation  classification required  classification required
 Bacterial Mutagenicity (Ames)  negative  negative

With respect to Inhalation Toxicity an expert statement is available justifying the read across (Pauluhn, Comparison of pulmonary irritation potency..., Bayer HealthCare AG, 2008; attached to this endpoint summary).

Therefore, test results obtained for HDI oligomers, isocyanurate type can be transferred to HDI oligomers, iminooxadiazindione type and the toxicokinetic properties of HDI oligomers, isocyanurate type are also valid for HDI oligomers, iminooxadiazindione type. This approach is in accordance with Annex XI, section 1.5 of the REACH Regulation (Regulation (EC) No 1907/2006).

See below the toxicokinetic assessment of the read-across substance HDI oligomers, isocyanurate type:

"The following remarks on the toxicokinetics of hexamethylene (HDI) oligomers, isocyanurate type, are based on physico-chemical properties of the substance and on toxicological data. Experimental toxicokinetic studies were not performed. 

HDI oligomers, isocyanurate type, is a colourless, clear and viscous organic liquid (Currenta GmbH & Co. OHG, 2010; melting range: between -51.3 and -28.4 °C; Laus GmbH, 2010) with a low vapour pressure (2.46*10exp-03 Pa at 20 °C and 2.55*10exp-03 Pa at 25°C; both calculated values; Laus GmbH, 2010) and a high viscosity (dynamic viscosity 3852 mPa*s, Laus GmbH, 2010). 

The substance is hydrolytically unstable. Regarding the disappearance of isocyanate groups, the half-life in a water/acetonitrile solution is approx. 8 hours at room temperature (cp. chapter “Hydrolysis”). Therefore experimental data such as pH, pKa, log Pow cannot be obtained for the substance. 

Due to the low vapour pressure and the high viscosity inhalation exposure via vapour is not to be expected. Wherever aerosolisation occur inhalation exposure is possible. Due to the physico-chemical properties of the oligomerisation product (high mean molecular weight, reaction with nucleophiles e.g. OH-, NH-, SH-groups) an extensive bioavailability via passive diffusion in the lung is not assumed, however, some degree of systemic bioavailability e.g. by internalization of protein adducts cannot be excluded. Acute and repeated inhalation toxicity studies have identified the irritant port of entry toxicity as the toxicological mode of action following exposure to the aerosol (report no's AT03922 (2007/2001), 22725 (1993), 16070 (1987); all Bayer AG). Indications of systemic toxicity were not observed in these studies. No organ lesions other than at the respiratory tract could be found, and all clinical signs were related to respiratory distress as a consequence of the irritant properties of the substance. These were most probably related to the reactive nature of the isocyanate-groups.

Human experiences give some evidence of systemic availability after aerosol exposure to HDI-based homopolymers (see IUCLID “Exposure related observations in humans – Group: Biomonitoring of exposure to HDI-based homopolymers”, e.g. Leng, ASU Zeitschrift fuer medizinische Praevention, 7, 2013, 392; Jones et.al., Annals of Occupational Hygiene, 57, 2, 2013, 200-209; Flack et.al., Biomarkers, 16, 3, 2011, 261-270). In the related publications a degradation product of HDI based-homopolmers, that is hexamethylene diamine (HDA), is quantified in urine or blood after acid hydrolysis as a biomarker for exposure to HDI or HDI-derived substances. HDA has never been detected in blood, tissue, urine or faeces without an acid hydrolysis work-up, therefore the biomonitoring studies demonstrate some bioavailability after HDI exposure, without further characterisation of toxicokinetic aspects, e.g. metabolism or quantitative absorption.

Dermal absorption of HDI oligomers, isocyanurate type, is assumed to be very low, due to its physico-chemical properties (lack of water solubility/ reaction with water; reaction with nucleophiles e.g. OH-, NH-, SH-groups). In fact, no signs of systemic toxicity were observed in acute dermal toxicity studies (report no 1053/036; Safepharm Labs. Ltd, 2004; report no 54-565, BRRC, 1991). Testing on full-thickness human skin give limited experience that HDI oligomers, isocyanurate, can penetrate at least into the skin (Thomasen & Nylander-French, J Environ Monit, 14, 2012, 951-960). The substance has shown skin sensitizing properties (OECD 429, report no 1053/039, Safepharm Labs. Ltd., 2004; OECD TG 406, report no. 25967, Bayer AG, 1997), thus giving further evidence, that a dermal uptake, even though small, can occur. 
Based on the physico-chemical properties (high mean molecular weight, low water solubility / reaction with water, reaction with nucleophiles e.g. OH-, NH-, SH-groups) a significant absorption of the substance from the gastro-intestinal-tract is not assumed. In fact, no systemic signs could be observed after oral exposure with 2000 mg/kg (report no 1053/029; Safepharm Labs. Ltd., 2004). 
Accumulation of HDI oligomerisation product, isocyanurate type in adipose tissues is not regarded to be of relevance, since the substance has such a limited systemic availability.
The excretion of absorbed HDI oligomers, isocyanurate type or its degradation products should be at least partly via urine (for instance Leng, ASU Zeitschrift fuer medizinische Praevention, 7, 2013, 392; Jones et.al., Annals of Occupational Hygiene, 57, 2, 2013, 200-209). 
Based on the results of several in vitro genotoxicity tests (OECD 471, report no. 169/207, Safepharm Labs. Ltd., 2004; OECD 476, BASF AG, 2006/2007; OECD 473, BASF AG, 2007; 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."