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EC number: 205-289-9
CAS number: 137-32-6
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 aldehydes 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.
There are no state of the art pharmacokinetic studies available
with 2 -methylbutanol or its structural analogues 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
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).
Absorption of 3-methylbutan-1-ol occured after oral (Kamilet al.1953)
and also inhalative exposure (Kumagaiet al.1999). Pentan-1-ol was
shown to be dermally absorbed at rates depending on the vehicle and
temperature (skin permeability from pentan-1-ol in water was determined
to be 20 cm/hr at 5°C to 900 cm/hr at 50°C) (Blanket al.1967).
A further 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.
Taken together, pentanols are considered to be absorbed via oral,
inhalation and dermal route. This assumption is confirmed by the results
of the toxicity studies described in section 5, as clinical symptoms and
mortality evidence systemic availability of the substances.
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 conclusion, after absorption the molecules will be readily
metabolised and their metabolisation products will be distributed
through the bloodstream. The category members and their acid metabolites
are generally highly water soluble but nevertheless seem to be able to
pass the blood-brain barrier and have access to the CNS. This assumption
was further confirmed by results of a repeated dose toxicity study with
3-methylbutan-1-ol, where sedation in behaviour was observed in some
animals. Transient narcotic effects of pentan-1-ol and
3-methylnutan-1-ol were reported in publications (Maickel & Nash 1985,
Frantiket al. 1994). No selective or cumulative neurotoxicity was
The amounts of unchanged pentanols exhaled into air or excreted
into urine were found to be low (Haggardet al.1945).Generally,
pentanols were found to be metabolised rapidly and to a high extent
(Haggardet al.1945, Greenberg 1970). Pentanols are mainly
metabolized in the liver. Several in vitro studies are available
assessing the metabolisation of pentanols:
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 (Ehriget
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 (Haggardet
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).
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). 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 (Kamilet al. 1953).
The amounts of unchanged pentanols exhaled into air or excreted
into urine were found to be low (Haggardet al.1945). After
metabolisation to acids or glucuronidation the molecules are renally
excreted. No major differences were found and are to be expected
regarding excretion of the metabolised category members.
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