Alkanol reaction products with bis(aminoalkyl(C=1~6))carbomonocycle, alkoxy(C=3~8)alkanol(C=2~7) and 2,4-TDI

Endpoint summary

Description of key information

No experimental toxicokinetic studies are available on the substance. However, as cited in the REACH guidance document R7.C (June 2017), information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties.

Based on the toxicological data and the physicochemical properties, a very low absorption of the substance is expected by the oral and dermal routes while the physical form of the substance will favour the deposition on the surface of the respiratory tract.

Additional information

No experimental toxicokinetic study is available on the substance but information on absorption, distribution, metabolism and excretion may be deduced from the following physicochemical properties:

-Molecular weight: the molecular weight ranges from 510 to 1212 g/mol where the molecular weight of the first three components are 885, 1212 and 575 g/mol (present at 61, 16.5 and 8.8 % w/w respectively in the typical composition) and 90% w/w of the substance has a molecular weight above 800 g/mol.

-Water solubility: QSARs (WATERNT v1.01 and WSKOWWIN v1.42) were run to appraise fixed values for the three major components. The highest solubility value within the domain of applicability of this model was 5.75 *10 -7 mg/L. The substance is therefore highly insoluble.

-Partition coefficient Log Kow: the Log Kow measured according to OECD guideline 117 is above 6 while the estimated values with QSAR (Kowwin v1.68) gave a range of values between 13.15 and 16.1 for the three major components of the test substance.

-Physical state: the pure substance is a powder which is never marketed or used as such, but only in a viscous liquid formulation produced in-line in the process. Nevertheless it is anticipated that exposure to the test substance particles by inhalation could happen due to spraying applications.

Absorption

The value of the log Kow, the high water insolubility, the molecular weight and the solid form of the pure test substance suggest a very low absorption into the gastro-intestinal tract after oral absorption. Indeed the absorption of highly lipophilic substances may be limited by the inability of such substances to dissolve into GI fluids. The physical form also limits the absorption because of the time taken for the powder particles to disssolve, this is further accentuated for this poorly water-soluble substance.

This assumption of a very low oral absorption is confirmed in the oral toxicity studies: no systemic effects or mortalities were observed in rats treated at 2 000 mg/kg bw in an acute toxicity study and at 1000 mg/kg bw/day in a 14 -day repeated toxicity study.

With extremely low water solubility, a high value of log Kow and a molecular mass above 800 g/mol, dermal absorption is also anticipated to be very low.

Regarding the inhalation route, the particles will favour the deposition on the surface of the respiratory tract. As the particles are poorly water-soluble, those deposited in the alveolar region will mainly be engulfed by macrophages. The macrophages may either translocate particles to the ciliated airways for elimination or carry particles into the pulmonary intersticium. Thus, absorption should be very limited.

Distribution and Metabolism

By the dermal route, since the substance is highly lipophilic, it may persist in the lipid rich stratum corneum and will eventually be cleared as the stratum corneum is sloughed off. By the inhalation route, since the particles of the substance are poorly water-soluble, they may stay in the pulmonary intersticium and clearance will depend mainly upon solubilisation and other mechanisms. No specific data is available on the metabolism of the substance.

Elimination

Due to the extremely low water solubility and a relatively high molecular mass, the excretion of the substance in urine is not expected. An excretion via bile and faeces is possible.