Reaction product of 2-Hexyldecan-1-ol, 2-Octyldodecan-1-ol and Lauric acid

Endpoint summary

Additional information

Toxicokinetics:

1.    Chemical and physic-chemical description of the UVCB substance

The substance is a mixture of the two Guerbet alcohols 2 -hexyldecan-1-ol & 2-octyldodecan-1 -ol and their corresponding esters with C12 and C14 fatty acids. No experimental data on absorption, metabolism and distribution are available for Guerbet alcohols or their esters.

Based on the physico-chemical properties of Guerbet alcohols and their esters, available literature and considering the toxicity data, the toxicokinetic behavior of the UCVB substance can be assessed. 

Description of the physico-chemical properties:

- physical state: liquid

- vapour pressure:<= 2.3*10-7 atm ( <= 2.3*10-2 Pa; <= 2.3*1o-4 mbar) at 20 °C) 

- molecular weight: ranging from 242 – 509 Da 

- logPow: >5.7

- water solubility: <0.05 mg/L

- Boiling point: >= 344 °C

 

 

2.     Toxicokinetic assessment

 

2.1 Absorption:

In the gastro-intestinal tract, the highly lipophilic UVCB substance (log Pow > 5.7) with low water solubility (<0.05 mg/L) and a relatively high molecular weight (range: 242-509 Da) is unlikely to be absorbed by passive diffusion. An uptake due to micellular solubilisation could be expected.

The UVCB substance to be registered has a low vapour pressure of <= 2.3*10-7 atm ( <= 2.3*10-2 Pa; <= 2.3*1o-4 mbar) at 20 °C) and a relatively high boiling point (>= 344 °C), indicating that inhalation as a vapour will be negligible. If the UVCB substance reaches the respiratory tract, passive diffusion is unlikely due to the high log Pow, the low water solubility the relatively high molecular weight. Theoretically, a systemic uptake could take place after micellular solubilisation.

The relatively high molecular weight (range: 242-509 Da) as well as the dermal penetration potential modeled withthe QSAR program DERMWIN (v1.43)point to a poor systemic availability due to a limited dermal uptake. Especially for the ester components in the UVCB substance, the dermal penetration is expected to be negliglible (MW: 425-509 Da, dermal penetration as calculated by DERMWIN: <=4.16x10^-3cm/hr).

2.2 Metabolism:

Once absorbed, the ester components of the UVCB substance (reaction products of 2 -hexyldecan-1-ol & 2-octyldodecan-1 -ol with C12 and C14 fatty acids) are likely to be metabolised like dietary fats. As shown by Mattson and Volpenhain, esters of fatty acids and branched alcohols (e.g. pentaerythritol) are potential substrates for endogenous lipases in the bile-pancreatic fluid. These enzymes catalyze the hydrolysis to the corresponding alcohol and acid. However, the rate of ester hydrolyzation is expected to be considerably slower for the Guerbet alcohol esters compared to dietary fats, such as triglycerides.

As cleavage products of the esters, C12 and C14 fatty acids and Guerbet alcohols (2 -hexyldecan-1-ol & 2-octyldodecan-1 –ol) are formed. The C12 and C14 fatty acids will be further metabolized like any other dietary fatty acid, undergoing an oxidation to carbon dioxide and water.

The Guerbet alcohols are components of the UVCB substance as such, but could also be formed during metabolic cleavage of the esters contained in the UVCB substance. These branched alcohols are expected to be extensively metabolisd, as demonstrated by Deisinger for the structurally related 2-ethylhexyanol. As first step of the biotransformation of resorbed 2-hexyldecan-1-ol or 2-octyldodecan-1-ol, mainly the oxidation of the alcohol to the corresponding carboxylic acid by phase I enzymes is expected. The carboxylic acid could then be glucoronised by the phase II enzymes UDP-glucuronosyltransferases to the ester glucuronides and excreted. Only minor parts of 2-hexyldecan-1-ol or 2-octyldodecan-1-ol are expected to be metabolized and excreted as alcohol glucuronides. The liver will be the primary site of phase I and phase II metabolism. This described metabolism is highly efficient and 2-hexyldecan-1-ol or 2-octyldodecan-1-ol is therefore not expected to have a tissue retention or bioaccumulation potential. This is supported by the available oral sub-chronic toxicity study of 2-octyldodecan-1-ol which shows no substance-dependent toxic effects at doses of 1000 mg/kg bw/d.

2.3 Excretion

The main route of excretion is expected to by expired air as CO₂. The second route of excretion is expected to be by biliary excretion and the feces. Exemplarily for the branched alcohols, experimental data of ethyl oleate (is the ethyl ester of oleic acid) provided this assumption: 14C-labeled carbon of 5 mL/kg of ethyl oleate (CAS No. 111-62-6) was rapidly excreted in respiration CO2 (approximately 70%), faeces (7 -10%), and urine (1-2%), with essentially complete elimination by 72 hours after administration (Bookstaff, 2003).