Reaction mass of 2-ethylhexyl (6-isocyanatohexyl)-carbamate and bis(2-ethylhexyl) 1,6-hexan-1,6-diylbiscarbamate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Assessment based on physico-chemical properties and toxicological data

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The assessment of toxicokinetics of the substance is based on physico-chemical properties and on toxicological data. No experimental studies were performed.

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

Additional information

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

The substance is a colourless liquid at normal ambient conditions (Currenta GmbH & Co. OHG 2014 and 2015), with a very low vapour pressure (0.0022 Pa at 20 °C, Fonseca 2014) and a dynamic viscosity of 87.3 mPa s (at 20 °C, Neuland 2015). The major constituent, with an amount of 78-90 %, contains isocyanate groups, which are responsible for the unstable character of the substance towards nucleophiles, e.g. water, alcohol and amino groups. Due to the hydrolytic instability data like water solubility or log Pow are not available.

The substance has a molecular weight of 298 and 429 g/mol for the two constituents 2-ethylhexyl N-(6-isocyanatohexyl)carbamate  (78-90 %) and bis(2-ethylhexyl) hexane-1,6-diylbiscarbamate (10-22 %), respectively. These molecular weights are in a range that is favourable for absorption after oral exposure. However, the available studies with gavage administration, which is an acute oral toxicity study (Kroetlinger 2002; OECD 423) and a reproductive toxicity screening study (Hudson 2017; OECD 421), give no clear indication for systemic availability, since only unspecific effects (OECD 423: diarrhoea, decreased motility; OECD 421: slight effect on bodyweight gain, hepatic enzyme induction) were observed, which might be attributed solely to local effects at the gastrointestinal tract. Dermal absorption is expected to be low, due to the unstable nature of the isocyanate groups and due to the molecular weight well above a favourable limit for dermal absorption (cp. ECHA Guidance Chapter R.7c, 2017). This is not contradicted by the fact, that the substance has irritant properties (no classification required according to GHS; Leuschner 2002, OECD 404 and 405), which may impair the barrier of the skin.

With respect to inhalation the available studies (Kopf 2018, OECD 412; Kopf 2014, OECD 403) reveal as well no indications for systemic availability. Instead, the data especially from histopathology and broncho-alveolar lavage fluid analysis point to a local irritant “port-of-entry” toxicity. This is evidenced by inflammatory processes in the respiratory tract with squamous metaplasia in the larynx as secondary sequelae.

Overall, with the exception of a positive skin sensitisation potential (Vohr 2003; OECD 429) no indications for systemic availability are revealed from the available studies, however, due to this result it cannot be completely ruled out.

Based on the results of the in vitro genotoxicity tests (Herbold 2002, OECD TG 471; Wollny 2016, OECD TG 476; Sokolowski 2015, OECD 487; all with and without metabolic activation) it can be concluded that DNA-reactive metabolites of the substance will not be generated in mammals in the course of hepatic biotransformation.