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Available data on absorption, distribution, metabolism and excretion is very scarce, both for human and experimental animals. Therefore, an assessment of the toxicokinetic behavior of undecylenic acid solely relays on the read-across approach by drawing conclusion on the expected toxicokinetic behavior of undecyclenic acid from the toxicokinetic behavior of similar medium chain length fatty acids if such data exist.

Due to its low water solubility, undecylenic acid, absorption after oral exposure may not be high. A quantitative estimation is difficult, however, in that the role of gastrointestinal uptake mechanism for fatty acids may also work for undecyclenic acid, which in turn could markedly influence its oral bioavailability. Data on dermal absorption (i.e. dermal penetration) are not available and therefore estimates on systemic availability of undecyclenic acid after dermal exposure are currently not possible.

Undecylenic acid should be degradable within the available fatty acid metabolism system. Initial metabolic activation of undecylenic acid may involve several enzymatic systems. First, the double bond at carbon 10 of undecylenic acid may undergo epoxidation followed by further oxidation to yield aldehyde and eventually carboxylic acid intermediates or by hydrolysis to yield diol intermediates. These enzymatic activations to the respective intermediates are expected to be very similar to those that result in the activation of eicosatetraenoic acid to intermediate precursors of leukotriene biosynthesis (Capdevila et al., 1982). Secondly, the cytochrome P450 gene 4 family (CYP4) consists of a group of over 63 members that omega-hydroxylate the terminal carbon of fatty acids (Hardwick, 2008). In mammals, six subfamilies have been identified and three of these subfamily members show a preference in the metabolism of short (C7-C10)-CYP4B, medium (C10-C16)-CYP4A, and long (C16-C26)-CYP4F, saturated, unsaturated and branched chain fatty acids. These omega-hydroxylated fatty acids are converted to dicarboxylic acids, which are preferentially metabolized by the peroxisome beta-oxidation system to shorter chain fatty acids that are transported to the mitochondria for complete oxidation. Third, undecylenic acid may undergo beta-oxidation, the first step of metabolic activation in the chain shortening and turn over process of all fatty acids in the fatty acid cycle (Katz and Guest, 1994).

Several metabolic intermediates of undecylenic acid may react with coenzyme A (CoA) and then enter as the coenzyme A ester the fatty acid pathway and the tricarboxylic acid cycle. To a minor extent, aldehyde intermediates also may be reduced to alcohols or conjugated with labile sulfhydryl-containing substances, such as glutathione (Brabec, 1993).

Plasma concentrations and plasma half-lives of undecylenic acid and its possibly many intermediates may be difficult to measure since many low molecular weight fatty acid derived aldehydes and carboxylic acids (e.g., propionic acid) are endogenous, at least in humans (Lington and Bevan, 1994). Similarly, for the same reasons, excretion rates, both urinary and fecal, will be difficult to establish.

References

Brabec MJ. (1993)Patty’s Hygenie Toxicology, 4thEd.,, Vol. IIA, pages 283 – 327.

Capdevila J, Marnett LJ, Chacos N, Prough RA, Estabrook RW. (1982) Proc. Natl. Acad. Sci. USA.,79, 767-70.

Hardwick JP. (2008) Biochem Pharmacol. 75, 2263-2275.

Katz GV, and Guest D. (1994) Patty’s Hygenie Toxicology, 4thEd., Vol IID, Chapt. 36, pages 3523 – 3671.

Lington AW, and Bevan C. (1994) Patty’s Hygenie Toxicology, 4thEd., Vol. IID, Chapt. 30, pages 2585 – 2750.