Reaction mass of N,N’-ethane-1,2-diylbis(12-hydroxyoctadecan-1-amide), Octadecanamide, 12-hydroxy-N-[2-[(1-oxooctadecyl)amino]ethyl]- and Octadecanoic acid, 12-hydroxy-, 1-hexyl-12-[[2-[(12-hydroxy-1-oxooctadecyl)amino]ethyl]amino]-12-oxododecyl ester

Endpoint summary

Description of key information

No experimental toxicokinetic studies are available on the substance. However, as per 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 oral and dermal route 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 is around 625 g/mol,

-        Water solubility: the water solubility measured at 25°C according to OECD Guideline 105 is < 0.115 mg/L,

-        Partition coefficient: based on the read-across substance bisamide (UVCB), the log Kow measured according to OECD Guideline 117 is ≥ 5.86 while the calculated values gave a range of estimations between 11.3 and 18.64 for the three main constituents,

-        Particle size: The proportion of test substance having a particle size below 100 µm was found to be < 0.266%.

Absorption

The log Kow, the extremely low water solubility, the molecular weight and the solid form suggest a very low absorption from the gastro-intestinal (GI) 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 limits also the absorption because of the time taken for particle to dissolve, especially for poorly water-soluble substances.

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 with the read-across substance bisamide (UVCB) at 2,000 mg/kg bw in an acute toxicity study and at 1,000 mg/kg bw/day in a 14 day repeated dose 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 low although the substance exhibits a sensitizing potential.

Regarding the inhalation route, the size of the particles will favour 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 pulmonaryintersticium. Thus, absorption should be very limited. This assumption is confirmed in the inhalation toxicity studies: no systemic effects or mortalities were observed in rats exposed 4 h to 5.05 mg/L air in an acute toxicity study with the read-across substance bisamide (UVCB), and up to 2.02 mg/L air six hours per day, five days per week in a 14 day repeated dose toxicity study.

 

Distribution and metabolism

'By the dermal route, as the substance is highly lipophilic, it may persist in the lipid richstratum corneumand will eventually be cleared as this layer is sloughed off. By the inhalation route, as the particles of the substance are poorly water-soluble, they may stay in the pulmonaryintersticium, where they will be engulfed by macrophages, degrade and removed by mucus secretions.

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, excretion of the substance in urine is not expected. An excretion via bile and faeces is possible.