Octadecanoic acid, 12-hydroxy-, reaction products with decanoic acid and ethylenediamine

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, 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 lower 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 weights of the three components are 497, 625 and 369 g/mol (present at 37, 26 and 14 % w/w respectively in the typical composition) and more than 80% w/w of the substance has a molecular weight around or above 500g/mol.
-Water solubility: the three components (in section 1.2) of the test substance were estimated by QSAR modeling to have water solubility values of 0.21, 0.0005 and 83 µg/L. The substance is therefore considered as insoluble.
-Partition coefficient Log Kow: the Log Kow measured according to OECD guideline 117 is above 6 while the estimated values by QSAR modeling for the three components were 8.6, 10.6 and 6.5 (Sydney, 2009)
-Particle size: more than 80% of particles have a diameter below 10 µm (Sydney, 2009) .

Absorption
The value of the log Kow, the extremely low water solubility, the molecular weight and the solid form of the 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 'particle' form also limits the absorption because of the time taken for the particles to disssolve, this is further accentuated for this poorly water-soluble substance.
This assumption is supported in the oral toxicity studies: no systemic effects were observed in rats treated at 2000 mg/kg bw in an acute toxicity study and at 1000 mg/kg bw/day in a combined reproductive /developmental screening toxicity test, which could be consecutive to a low absorption of the registered substance.
With extremely low water solubility, a high value of log Kow and a molecular mass around or above 500 g/mol, dermal absorption is also anticipated to be very low. This assumption is supported in the dermal toxicity studies: no systemic effects were observed in rats treated at 2000 mg/kg bw in acute toxicity, and skin irritation and sensitisation studies, which could be consecutive to a low absorption of the registered substance.
Regarding the inhalation route, the size of the particles will favour the deposition on the surface of the lower 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. This assumption is supported in the inhalation toxicity studies: systemic effects observed following an acute or repeated exposure via inhalation can reasonably be viewed as secondary to local effects to the respiratory tract; this absence of direct systemic effects attributable to the registered substance could be a consequence of a low absorption by inhalation.

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. This assumption is supported by the observations made on recovery and clearance during a 13-week repeated dose toxicity study conducted via inhalation. 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.