Alcohols, C13-15-branched and linear

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Absorption

Alcohols, C13 -C15, branched and linear are highly lipophilic (Log Pow > 6, water solubtility <1mg/L). After oral uptake, the substance might require micellular solubilisation, but some molecules might also still be small enough (average molecular weight of 214g/mol) to pass through aqueous pores. Oral bioavailability is also supported by the systemic effects especially on the liver that were observed in repeated dose oral studies with all read across substances.

Because of the low vapour pressure (0.06Pa), inhalation is not a very relevant route of exposure, but as for the oral route, absorption is assumed via this route of exposure. The low water solubilty likely enhances penetration to the lower respiratory tract, where the material is absorped similarly to the GI tract.

After dermal exposure, the high lipophilicity the material will likely be retained in the stratum corneum, and systemic uptake via the dermal route will be limited. Consequently, a maximum of 50% absorption compared to the oral route is assumed.

Metabolism

The initial step in the mammalian metabolism of primary alcohols is the oxidation to the corresponding carboxylic acid, with the corresponding aldehyde being a transient intermediate. These carboxylic acids are susceptible to further degradation via acyl-CoA intermediates by the mitochondrial b-oxidation process. This mechanism removes C2 units in a stepwise process. Linear acids are more efficiently processed than the corresponding branched acids. An alternative metabolic pathway for aliphatic acids exists through microsomal degradation via w-or w–1 oxidation followed by β-oxidation. This mechanism provides an efficient stepwise chain-shortening pathway for branched aliphatic acids (Verhoeven, et al., 1998). The acids formed from the longer chained aliphatic alcohols can also enter the lipid biosynthesis and may be incorporated in phospholipids and neutral lipids (Bandi et al, 1971a&b and Mukherjee et al. 1980). A small fraction of the aliphatic alcohols may be eliminated unchanged or as the glucuronide conjugate (Kamil et al., 1953). As a consequence, long chain aliphatic carboxylic acids are efficiently eliminated, and aliphatic alcohols are therefore not expected to have a tissue retention or bioaccumulation potential (Bevan, 2001).

A comparison of the linear and branched aliphatic alcohols shows a high degree of similarity in biotransformation. For both sub-categories the first step of the biotransformation consists of an oxidation of the alcohol to the corresponding carboxylic acids, followed by a stepwise elimination of C2 units in the mitochondrial β-oxidation process. The presence of a side chain does not terminate the β-oxidation process, however metabolism for branched alcohols is expected to be slower than that of linear alcohols, but still sufficiently efficient to not give rise to any concerns regarding bioaccumulation.