HDI oligomers, allophanate

Endpoint summary

Additional information

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

HDI oligomerisation product, allophanate-type is a colourless organic liquid (Currenta, 2011) with a pourpoint of -54 °C (atmospheric pressure; Bayer Industry Services, 2006), a very low vapour pressure of 0.0004 Pa (20 °C; Bayer Technology Services, 2011) and a dynamic viscosity of 249 mPa*s (20 °C; Bayer Industry Services, 2006). The substance is hydrolytically unstable with a half-life of approx. 24 hours at 20 °C (Currenta, 2013). In addition, water solubility of the substance is low (7.4 mg/L at a conc. of 1000 mg/mL; Currenta, 2012). Therefore experimental data such as pH or pKa could not be obtained. The log Pow was determined to be 5.9 (25 °C; Currenta, 2012), indicating a possible accumulation potential.

Due to the low vapour pressure and the high viscosity inhalation exposure via vapour is not to be expected. Wherever aerosolisation occurs exposure is possible. In acute inhalation toxicity studies the irritant port of entry toxicity was identified as the toxicological mode of action following exposure to the aerosol (Bayer, 2011 and 2013). No systemic toxicity was observed in these studies. Read across data on repeated dose toxicity reveal also no indications of systemic toxicity; all clinical signs were related to respiratory distress as a consequence of the irritant properties of the substance. These effects are most probably related to the chemical nature of the isocyanate-groups of the substance. 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, passive diffusion or active transport of the substance or its degradation products cannot be fully excluded.

Dermal absorption of HDI oligomerisation product, allophanate-type is assumed to be very low, due to its physico-chemical properties (high mean molecular weight, low water solubility / reaction with water, reaction with nucleophiles e.g. OH-, NH-, SH-groups). However, HDI oligomerisation product, allophanate-type has shown skin sensitizing properties (OECD TG 429, Bayer, 2011), thus indicating 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 bw (BASF SE, 2012).

Despite the log Pow of 5.9 a possible accumulation of HDI oligomerisation product, allophanate-type in adipose tissues is not regarded to be of relevance, since the substance has such a limited systemic availability.

Based on the results of several in vitro genotoxicity tests (OECD TG 471: BASF SE, 2006; OECD TG 476: Harlan, 2012; OECD TG 487: Bayer AG, 2012; all performed with and without metabolic activation) it is concluded that DNA-reactive metabolites of HDI oligomerisation product, allophanate-type will not be generated in mammals in the course of hepatic biotransformation.