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Description of key information

Members of the category "pentanols" are metabolised rapidly and to a high extent. The main metabolic pathway for the degradation of these primary pentanols is the formation of aldehyds via oxidation by alcohol dehydrogenases, and subsequently the formation of the corresponding acids. Additionally, oxidation of pentanols via hepatic CYP P450 enzymes and glucuronidation were observed. The metabolisation products are renally excreted.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

There are no state of the art pharmacokinetic studies available with pentan-1-ol or the other category members in animals or humans, but these substances have been subject of investigation in numerous in vivo and in vitro studies concerning their metabolism, distribution and elimination.

Due to their structural similarities, effects observed after administration of the single isomeric pentanols are expected to be caused by all members of this group of chemicals to the same or comparable extent (pentan-1-ol, 2-methylbutan-1-ol, 3-methylbutan-1-ol and pentanol, branched and linear).

Three studies regarding dermal absorption properties of pentan-1-ol are available:

As the solubility of the alcohols in nonpolar liquids increases from methanol to octanol, the rate of penetration from an aqueous solution also increases. The alcohols penetrate more rapidly from vehicles in which they are less soluble. When the dermal penetration of pentan-1-ol in saline and olive oil was analyzed on autopsied human abdominal skin, the rate of penetration from saline was about 20 times that of ethanol and about one-ninth that of octanol (Blank 1964).

In another study by the same author, the skin permeability of pentan-1-ol in water ranged from about 20 cm/hr at 5°C to 900 cm/hr at 50°C (Blank et al. 1967).

The third study determined permeability data of pentan-1-ol for human epidermis (Scheuplein & Blank 1971):

1. as aqueous solution:

- partition coefficient (Km) = 5.0;

- permeability constant at zero volume flow (kp) = 6.0 cm/hr

- membrane diffusivity (Dm) = 0.88 E-09 cm2/sec;

2. as pure liquid:

- partition coefficient (Km) = 0.11;

- permeability constant at zero volume flow (kp) = 0.051 cm/hr

- membrane diffusivity (Dm) = 0.17 E-09 cm2/sec.


Generally, pentanols were found to be metabolised rapidly and to a high extent (Haggard et al. 1945, Greenberg 1970). Absorption of the alcohols from the intraperitoneal cavity after i.p. administration at 1000 mg/kg bw was completed within 1 hour (Haggard et al. 1945). The amounts of unchanged pentanols exhaled into air or excreted into urine were found to be low (Haggard et al. 1945).


In vitro experiments conducted with Class I, II and III alcohol dehydrogenases (ADH) isolated from human liver demonstrated that oxidation of 2-methylbutan-1-ol and 3-methylbutan-1-ol (at 10-100 µM) to the corresponding aldehydes was mainly mediated by the isoenzymes of Class I ADH. At pharmacologically relevant concentrations of ethanol, the oxidation of the isoamyl alcohols was inhibited in vitro since these congeners and ethanol compete for the same metabolising enzymes (Ehrig et al. 1988).

This notion is supported by in vivo experiments in rats (Greenberg 1970) and in the isolated perfused rat liver (Auty & Branch 1976). Isovaleraldehyde has been identified as intermediary metabolite of 3-methylbutan-1-ol (Greenberg 1970). The formed aldehydes are again rapidly metabolised, presumably to the corresponding acids (Haggard et al. 1945).

Hepatic and pulmonary alcohol dehydrogenase activities were investigated in cytosolic fractions prepared from Sprague-Dawley male rats after addition of pentan-1-ol. Pulmonary ADH activity was considerably lower than hepatic ADH activity. Optimum conditions for pulmonary ADH activity were found to require an alkaline pH and high substrate concentrations suggesting a minimal role for the lung in the metabolism of alcohols in the intact animal (Carlson & Olson 1995).


After inhalative exposure (2 hours) to vapour concentrations of 2000 ppm (corresponding to approx. 7.32 mg/L) pentan-1-ol and a mixture of pentan-1-ol and 2-methylbutan-1-ol, respectively, in the blood of male Sprague-Dawley rats the corresponding acid metabolites valeric acid and methyl butyric acid were detected. Valeric acid was found at all times at only trace amounts between 3 – 7 µM, whereas methyl butyric acid was detected at blood concentrations between 5.2 and 25.1 µM (Oxo Process Panel – ACC 2004).


In vitro experiments have demonstrated additional oxidation of pentan-1-ol, 3-methylbutan-1-ol, and 2-methylbutan-1-ol by rat liver microsomes via CYP P450 enzymes, and glucuronidation (Iwersen & Schmoldt 1995). Only at very high concentrations (300-400 mmol/L) ethanol was a competitive inhibitor of the glucuronidation of e.g. 3-methyl-butan-1-ol. By comparison, the competitive inhibiting effect of ethanol on oxidation of 2-methylbutan-1-ol could already be seen at very low ethanol concentrations of 5-10 mmo/L.

After gavage administration of a dose of 25 mmol amyl alcohol/rabbit (corresponding to approx. 735 mg/kg bw) 7 %, 9 %, and 10 % of the dose was excreted by the rabbits into urine as glucuronides, when they had received pentan-1-ol, 3-methylbutan-1-ol, and 2-methylbutan-1-ol, respectively (Kamil et al. 1953).


Taken together, in vivo and in vitro experiments demonstrated that the main metabolic pathway for the degradation of pentanols is via oxidation by alcohol dehydrogenase to the corresponding aldehydes and subsequently to the acids. Additionally, oxidation of pentanols via hepatic CYP P450 enzymes and glucuronidation was shown to play a role in metabolism of these alcohols.