Hexamethylene diisocyanate, oligomerisation product, blocked with 2-butanone oxime

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics

Type of information:

other: Toxicokinetics assessment

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Based on the known physico-chemical properties and the available toxicologic studies, a justified assessment of the toxicokinetic and biotransformational properties of HDI Trimer MEKO-blocked could be made, therefore an in vivo toxicokinetic study is at present not an urgent requirement.

Principles of method if other than guideline:

Assessment of Toxicokinetics

Based on the known physico-chemical properties and the available toxicologic studies, a justified assessment of the toxicokinetic and biotransformational properties of HDI Trimer MEKO-blocked could be made, therefore an in vivo toxicokinetic study is at present not an urgent requirement.

Description of key information

Due to the low vapor pressure, inhalation exposure via vapour is not to be expected.

Dermal absorption of HDI Trimer MEKO-blocked is assumed to be low, due to its physico-chemical properties (slight water soluble and high molecular weight)

Additional information

Basic Toxicokinetics

The following remarks on the toxicokinetics of HDI Trimer MEKO-blocked are based on physico-chemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

HDI Trimer MEKO-blocked is a viscous liquid at 20 °C and 1013 hPa with a low vapor pressure (1.10 -3 Pa at 20 °C and 4.10 -3 at 40 °C). Due to the low vapor pressure, inhalation exposure via vapour is not to be expected. Nevertheless, wherever aerosolization occurs, exposure is possible. There are no indications of systemic toxicity and systemic availability after inhalation exposure of the aerosol (L. Ma Hock, 2010). No organ lesions could be found outside the respiratory tract and these histopathological findings were seen as a consequence of the irritant properties of the substance.

The test substance is not stable at hydrolysis at ph=4, therefore it could be hydrolysed and may release HDI Trimer and MEKO or analogs.

Dermal absorption of HDI Trimer MEKO-blocked is assumed to be low, due to its physico-chemical properties (slight water soluble and high molecular weight). Furthermore, no signs systemic toxicity were observed in an acute dermal toxicity study (Gillessen U., 2010). However, HDI Trimer MEKO-blocked showed skin sensitising properties (Kolb J., 1993), indicating that a dermal uptake, even though small, can occur and deducting from that the substance has the property to react with nucleophilic groups of proteins or peptides and form hapten-protein complexes or conjugate-antigens.