12-hydroxystearic acid

Endpoint summary

Additional information

The toxicokinetics of fatty acids such as 12-hydroxystearic acid and triglycerides such as those contained in hydrogenated castor oil and castor oil are well known due to their widespread use in nutritional (food and feed), cosmetic and industrial applications.

ORAL

Upon oral uptake, triglycerides are first broken down into fatty acids and monoglycerides which are absorbed by the cells forming the intestinal barrier (enterocytes). Free fatty acids are absorbed directly. Within the entrocytes, triglycerides are (re)built and packaged together with cholesterol and proteins to form chylomicrons. These are excreted by the enterocytes, collected by the lymph system and transported to the large vessels near the heart before entering the blood.Eventually, they bind to the membranes of hepatocytes, adipocytes or muscle fibers, where they are either stored or oxidized for energy.When the body requires fatty acids as a source of energy, the hormone glucagon signals the breakdown of the triglycerides by hormone-sensitive lipases to release free fatty acids. The fatty acids are then broken down by stepwise elimination of C2-units in the mitochondrial β-oxidation. Alternate oxidation pathways can be found in the liver (ω-oxidation) and the brain (α-oxidation) (HERA, 2002). The C2-units are esterified to acetyl-coenzyme A which directly enters the citric acid cycle where it is converted to carbon dioxide and energy (Binderet al., 1970; MacDonald, 1973; Robinson, 1973; Chen and Farese, 2002).

The extent of absorption in the gastro-intestinal system varies depending on the chain length of the fatty acids and their degree of saturation. Generally, short-chain fatty acids are better absorbed than the long chain counterparts. Also, absorption decreases with increasing saturation (MacDonald, 1973; Robinson, 1973; Chen and Farese, 2002).

Binder et al. (1970) fed rats with diets containing 1 or 10% hydrogenated castor oil (main constituent: 12-hydrostearic acid) for 4, 8, 12 and 16 weeks. The maximum content of 12-hydroxystearic acid was 4.4% in adipose tissues after 4 weeks on the 10% diet. When hydrogenated castor oil was replaced with corn oil, 12-hydroxystearic acid was depleted from the tissues. 10-hydroxypalmitic and 8-hydroxymyristic acids were characterised as metabolites.

In an overview by the Cosmetic Ingredient Review Panel (CIR, 1987), stearic acid, a close structural analogue of 12-hydroxystearic acid, was cited as being the most poorly absorbed of the common fatty acids.

DERMAL

No experimental studies were located for absorption through the dermal route. However, as per Section R.7.12.2.1 of REACH guidance document R7.C (May 2008), the extent of dermal absorption may be predicted based on physico-chemical properties, including:

-        Water solubility

-        Partition coefficient

12-hydroxystearic acid is poorly water soluble and has an estimated log Kow > 4. As such, uptake into thestratum corneum of skin and further transfer into the epidermis are likely to be limited. This is in accordance with data from a dermal penetration study in rats (Butcher, 1951) in which ricinoleic acid was shown to be retained mainly in the outer strata of the epidermis.