12-hydroxyoctadecanoic acid, reaction products with 1,3-benzenedimethanamine and hexamethylenediamine

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 (May 2008), 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 weight ranges 649.15-1266.1 g/mol (excl. residual raw materials),

-Water solubility:  the water solubility measured at 20°C according to OECD guideline 105 is below 0.0089 µg/L,

-Partition coefficient Log Kow:  the Log Kow is >6,

-Particle size:  The proportion of test substance having a particle size below 10 µm was found to be 72.5% and the Mass Median Aerodynamic Diameter (MMAD) is equal to 5.99 µm.

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 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 28 -day repeated toxicity study.

With extremely low water solubility, a high value of log Kow, and a molecular mass above 500 g/mol, dermal absorption is also anticipated to be very low. This assumption is supported by the lack of toxicity in a dermal acute toxicity study, the lack of skin irritation and sensitisation in appropriate tests.

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.

The assumption of a very low absorption by inhalation is confirmed by the lack of systemic effects in in rats exposed to the test substance at concentrations up to 100 mg/m3 air for six hours per day, five days per week during 13 weeks. Nevertheless, the substance induces important respiratory local effets leading to death in the rats after 4 -hour acute exposure or leading to sustained inflammatory reactions in lungs after 13 -week repeated exposure.

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 upon solubilisation alone. 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.