HDI oligomers, biuret

Endpoint summary

Additional information

The following remarks on the toxicokinetics of HDI, oligomers (biuret type) are based on physicochemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed. 

 

HDI, oligomers (biuret type) is an UVCB with a molecular weight of its generic representative structure (trimeric form) of 478.485 g/mol. It is a colourless, clear and viscous organic liquid (BASF SE, 2012), with a melting range between -100 and 50 °C (BASF SE, 2012), with a low vapour pressure (0.000001 hPa at 20 °C , BASF SE, 2012) and a high viscosity (dynamic viscosity 5380 mPa*s, BASF SE, 2012). 

In water the substance is hydolytically unstable (half-life <12 hours, cf. chapter "Water solubility"). Therefore experimental data such as pH, pKa, log Pow can not be obtained for HDI, oligomers (biuret type). 

 

Due to the low vapour pressure and the high viscosity inhalation exposure via vapour is not to be expected. Wherever aerosolization occurs exposure is possible. There are no indications of systemic toxicity and systemic availability after inhalative exposure of rodents to aerosols of the test substance (Pauluhn, 1985, 1988). No organ lesions other than at the 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. These effects most probably are related to the chemical nature of the residual isocyanate-groups of HDI, oligomers (biuret type). 

Limited human experience give some evidence of systemic availability after aerosol exposure to HDI, oligomers (biuret type). An 8 hour-exposure to air concentrations of maximally 5ppb was correlated to the hexamethylene diamine (HDA) level in urine, determined after an acid hydrolization work-up of the urine (Yu et. al., 2005). HDA (the degradation product of HDI, oligomers (biuret type)) has never been detected in blood, tissue, urine or faeces after exposure to HDI, oligomers (biuret type) without an acid hydrolysis procedure. By comparing excretion kinetics of two HDI oligomer isoforms indicated that HDI-Biuret has a shorter half-life (1.3 - 3.9 h) than HDI-Isocyanurate (4.9 - 8.6 h).

 

Dermal absorption ofHDI, oligomers (biuret 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). HDI, oligomers (biuret type) has shown skin sensitizing properties (e.g. OECD TG 429: Bayer, 2006; OECD TG 406: Rhone-Poulenc, 1983), thus indicating that a dermal uptake, even though small, can occur. 

 

In spite of the physico-chemical properties (e.g. presumably labile in gastric acid), an oral absorption can not be excluded. Though, no systemic signs of toxicity were observed after oral exposure with the limit dose of 5000 mg/kg (BASF SE, 1975). 

 

The excretion of absorbed HDI, oligomers (biuret type) or its degradation products should be at least partly via urine (Yu et. al., 2005). 

HDI, oligomers (biuret type) is a skin sensitizer (e.g. OECD TG 429: Bayer, 2006; OECD TG 406: Rhone-Poulenc, 1983), presumably due to the reactive nature of the residual NCO-groups. These functional groups can react with nucleophilic groups of proteins or peptides, resulting in immunogenic hapten-protein complexes or conjugate-antigens. 

Based on the results of several in vitro genotoxicity tests (OECD TG 471: Bayer AG, 2007; OECD TG 476: Bushy RRC, 1992; OECD TG 473: Bushy RRC, 1992); all performed with and without metabolic activation) it is concluded that DNA-reactive metabolites of HDI, oligomers (biuret type) will not be generated in mammals in the course of hepatic biotransformation.