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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Type of information:
other: toxicokinetics assessment
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The assessment of the toxicokinetics of Metalink U (Desmodur TT) is based on physico-chemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.
Principles of method if other than guideline:
assessment on toxicokinetics

The remarks on the toxicokinetics of Desmodur RC (TDI Trimer) are based on physico-chemical properties of the compound and on toxicological data (Jäger, 2012). Experimental toxicokinetic studies were not performed.

 

Description of key information

Key value for chemical safety assessment

Additional information

The following remarks on the toxicokinetics of Metalink U (Desmodur TT) are based on physico-chemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

The substance is a white organic solid with a very low vapour pressure under normal ambient conditions (7.7 x 10-8 Pa at 25°C), therefore inhalation exposure to the vapour is expected to be negligible. Acute inhalation of a solid aerosol of Metalink U inhalable to rats did not reveal signs of systemic toxicity at the maximum attainable concentration of 1120 mg/m3 (Kopf, 2015). Even subacute (4-week) inhalation of Metalink U solid aerosol to rats revealed no signs of systemic toxicity (Kopf, 2016). Due to the lack of systemic toxicity there is no proof of systemic availability after inhalation exposure.

The physico-chemical characteristics of the substance (limited water solubility of < 0.0032 mg/L at 20°C, calculated log Pow of 5.69 and a molecular mass of 348 g/mol) suggest a low intestinal absorption after oral intake. This assumption is confirmed by the data on acute oral toxicity in rats (LD50 > 2500 mg/kg bw). In this study doses of up to 2500 mg/kg bw were tolerated without mortalities. At doses of 1000 mg/kg bw and above clinical signs (poor general condition, accelerated breathing) were observed (Kimmerle, 1961).

Because of the lipophilicity of the substance accumulation of the unchanged compound in fatty tissues might be possible depending on both the absorption in the GI tract as well as the efficiency of metabolic and excretory processes.

Due to the limited water solubility, a calculated log Pow of 5.69 at 25°C and a molecular mass of 348 g/mol no appreciable dermal or mucosal absorption is anticipated. This is confirmed by a study on skin sensitisation (LLNA; Leidenfrost, 2015) in which no signs of systemic toxicity were observed. As the skin sensitisation study revealed a moderate skin sensitising potential after dermal contact of the substance formulated in methyl ethyl ketone, at least for a solution of the substance in methyl ethyl ketone some dermal absorption has to be assumed.

Based on the results of three in vitro genotoxicity tests (negative with and without metabolic activation in an Ames test (Jarzombek, 2015), in a HPRT test (Wollny, 2016) as well as in a mammalian cell micronucleus test (Sutter, 2015) it is concluded that DNA-reactive metabolites of the substance will most probably not be generated in mammals in the course of hepatic biotransformation.