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Description of key information

The available information showed some evidence that Lanolin fatty acids, is expected to be absorbed via the gastro-intestinal tract. Once absorbed, the substance may be distributed systemically and is supposed to be metabolised within the standard metabolic pathways for fatty acids resulting in complete oxidation to CO2. Biliary excretion may well be a significant route of excretion for the unmetabolised part of the substance.

Key value for chemical safety assessment

Additional information

In accordance with Annex VIII, Column 1, Item 8.8.1, of Regulation (EC) 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2012), assessment of the toxicokinetic behaviour of the substance is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physicochemical and toxicological properties according to the relevant Guidance (ECHA, 2012). There are no studies available in which the toxicokinetic behaviour of Lanolin fatty acids (CAS 68424-43-1) has been investigated.

Lanolin fatty acids is a UVCB substance, composed of fatty acids derived from the saponification of lanolin.Lanolin fatty acids is a brown waxy solid with a molecular weight range of 175 – 439 g/mol. Lanolin fatty acids has a melting temperature of 35-60°C at normal pressure (Atkinson, 2010), a low water solubility of 0.21 mg/L (Cook, 2010), vapour pressure of <700 Pa at 20 °C (Younis, 2012), and log Pow of 1.34 - >6.5 (Walker, 2013). Supporting values for the main representative components are 4.43 - >13.87 (calculated with EPI suiteTM).

Absorption

Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2012).

Absorption, oral

In general, molecular weights below 500 and log Pow values between -1 and 4 are favourable for absorption via the gastrointestinal (GI) tract, provided that the substance is sufficiently water soluble (> 1 mg/L). Lipophilic compounds may be taken up by micellar solubilisation by bile salts, but this mechanism may be of particular importance for highly lipophilic compounds (log Pow > 4), in particular for those that are poorly soluble in water (≤ 1 mg/L) which would otherwise be poorly absorbed (ECHA, 2012).

The results of the acute oral toxicity study in rats showed no evidence of absorption (Lewis, 1977). As the lack of effects may be based on the absence of absorption or the absence of toxicity of the substance no final conclusion can be drawn. Based on the low water solubility, the molecular weight range and the log Pow absorption of the substance or rather individual components is possible. For the components with a log Pow of <4 absorption may occur through passive diffusion, whereas components with a log Pow of >4 may be taken up by micellular solubilisation.

Absorption, dermal

The dermal uptake of liquids and substances in solution is higher than that of dry particulates, since dry particulates need to dissolve into the surface moisture of the skin before uptake can begin. Molecular weights below 100 g/mol favour dermal uptake, while for those above 500 g/mol the molecule may be too large. Dermal uptake is anticipated to be low, if the water solubility is < 1 mg/L; low to moderate if it is between 1-100 mg/L; and moderate to high if it is between 100-10000 mg/L. Dermal uptake of substances with a water solubility > 10000 mg/L (and log Pow < 0) will be low, as the substance may be too hydrophilic to cross the stratum corneum. Log Pow values in the range of 1 to 4 (values between 2 and 3 are optimal) are favourable for dermal absorption, in particular if water solubility is high. For substances with a log Pow above 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. Log Pow values above 6 reduce the uptake into the stratum corneum and decrease the rate of transfer from the stratum corneum to the epidermis, thus limiting dermal absorption (ECHA, 2012).

The physicochemical properties (waxy solid, log Pow and water solubility) of the substance and the molecular weight are in a range suggestive of low absorption through the skin. The results of the acute dermal toxicity study in rats showed no evidence of absorption (Bradshaw, 2010). As the lack of effects may be based on the absence of absorption or the absence of toxicity of the substance no final conclusion can be drawn.

If a substance shows skin irritating or corrosive properties, damage to the skin surface may enhance penetration. If the substance has been identified as a skin sensitizer then some uptake must have occurred although it may only have been a small fraction of the applied dose (ECHA, 2012).

For the test substance itself, slight effects regarding to skin and eye irritation were observed, which could enhance dermal penetration of the substance. Data on skin sensitisation show that the substance is not sensitising in a LLNA (Bradshaw, 2010).

Overall, taking all available information into account, the dermal absorption potential is considered to be rather low.

Absorption, inhalation

Lanolin fatty acids is a waxy solid with a vapour pressure of < 700 Pa at 20 °C (experimental data). The vapour pressure was deemed to be quite high for a solid, and it was suspected that the sample contained water hence the magnitude of the results. EPI suiteTMcalculated vapour pressure results in <0.01 Pa (at 25°C). In addition the boiling point is >320°C indicating that Lanolin fatty acids is not highly volatile. Therefore, under normal use and handling conditions, inhalation exposure and thus availability for respiratory absorption of the substance in the form of vapours, gases, or mists is not significant.

However, the substance may be available for respiratory absorption in the lung after inhalation of aerosols, if the substance is sprayed (e.g. as a formulated product). In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract (ECHA, 2012).

As for oral absorption, the molecular weight, log Pow and water solubility indicate that absorption via inhalation cannot be excluded, but is expected to be rather low.

Distribution and accumulation

Distribution of a compound within the body depends on the physicochemical properties of the substance; especially the molecular weight, the lipophilic character and the water solubility. In general, the smaller the molecule, the wider is the distribution. If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration, particularly in fatty tissues (ECHA, 2012).

After being absorbed, fatty acids are (re-)esterified along with other fatty acids into triglycerides and released in chylomicrons into the lymphatic system. Fatty acids of carbon chain length ≤ 12 may be transported as the free acid bound to albumin directly to the liver via the portal vein, instead of being re-esterified. Chylomicrons are transported in the lymph to the thoracic duct and eventually to the venous system. Upon contact with the capillaries, enzymatic hydrolysis of chylomicron triacylglycerol fatty acids by lipoprotein lipase takes place. Most of the resulting fatty acids are taken up by adipose tissue and re-esterified into triglycerides for storage. Triacylglycerol fatty acids are likewise taken up by muscle and oxidized for energy or they are released into the systemic circulation and returned to the liver (Lehninger, 1998; Stryer, 1996; WHO, 2001). Stored fatty acids underlie a continuous turnover as they are permanently metabolised for energy and excreted as CO2.

Metabolism

Lanolin fatty acids is supposed to be metabolised via the standard metabolism pathways for fatty acids.

Fatty acids are degraded by mitochondrial β-oxidation which takes place in the most animal tissues and uses an enzyme complex for a series of oxidation and hydration reactions resulting in the cleavage of acetate groups in form of acetyl CoA. The alkyl chain length is thus reduced by 2 carbon atoms in each β-oxidation cycle. The complete oxidation of unsaturated fatty acids such as oleic acid requires an additional isomerisation step. Alternative pathways for oxidation can be found in the liver (ω-oxidation) and the brain (α-oxidation). Thus iso-fatty acids such as isooctadecanoic acid have been found to be activated by acyl coenzyme A synthetase of rat liver homogenates and to be metabolised to a large extent by ω-oxidation. Each two-carbon unit resulting from β-oxidation enters the citric acid cycle as acetyl CoA, through which they are completely oxidized to CO2 (Lehninger, 1998; Stryer, 1996).

The results of the in vitro genotoxicity studies did not show any evidence that the addition of the metabolic system either enhances or diminishes the activity of the substance (Bowles & Thompson, 2010; Bowles, 2010; Brown, 2010).

Excretion

In general, fatty acids are catabolised entirely by oxidative physiologic pathways ultimately leading to the production of carbon dioxide and water. Small amounts of ketone bodies resulting from the oxidation of fatty acids are excreted via the urine (Lehninger, 1998; Stryer, 1996). Unmetabolised Lanolin fatty acids that may be absorbed is supposed to be excreted in the bile and thus excreted via the faeces, as poorly water-soluble products are not favourable for urinary excretion. Any test material that is not absorbed will be excreted in the faeces.

Conclusion

The available information showed some evidence that Lanolin fatty acids, is expected to be absorbed via the gastro-intestinal tract. Once absorbed, the substance may be distributed systemically and temporarily stored in the adipose tissue. The substance is supposed to be metabolised within the standard metabolic pathways for fatty acids resulting in complete oxidation to CO2. Biliary excretion may well be a significant route of excretion for the unmetabolised part of the substance.