Isotridecan-1-ol

Endpoint summary

Additional information

There are no studies available that investigate the toxikokinetic properties of the target or source chemicals. The assessment is based on the physico-chemical properties of the substances and also on information provided in the OECD SIDS initial assessment report for SIAM 22 Long Chain Alcohols (18. - 21.04.2006)

Absorption

All substances are lipophilic and might require micellular solubilisation prior to gastrointestinal uptake. Alternatively, all chemicals should still be small enough to pass through aqueous pores. This is especially likely, since based on the physico-chemical properties, absorption of the target substance should be lowest, but effects after repeated exposure occur at comparable dose levels to the source substances. All in all, oral bioavailability is expected to be high.

Due to the low vapour pressure, inhalation is not a relevant route of exposure. But, if exposure occurs, the low water solubilty likely enhances penetration to the lower respiratory tract, where the material is absorbed similarly to the GI tract.

After dermal exposure, highly lipophilic materials will likely be retained in the stratum corneum, and systemic uptake via the dermal route will be limited. Consequently, the highest, though still low, uptake is expected for isononanol. Dermal absorption will decrease with increasing chain length and increasing lipophilicity. This is supported by comparative in vitro skin permeation data and dermal absorption studies in hairless mice. Aliphatic alcohols show an inverse relationship between absorption potential and chain length with the shorter chain alcohols having a significant absorption potential (Iwata et al., 1987). By comparison, uptake after dermal exposure is expected to be significantly lower than by other routes of exposure.

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.