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EC number: 205-289-9
CAS number: 137-32-6
no selective or cumulative neurotoxicity
Experimental data from studies conducted
with3-methylbutan-1-ol and its structural analogue pentan-1-ol were
taken into consideration to assess the potential for neurotoxicity of
The effects of electrically evoked seizures
after inhalation of 3-methylbutan-1-ol were determined in a publication
(Frantík et al. 1994). The study was conducted in male Wistar rats and
female mice of the H strain. The animals were exposed to
3-methylbutan-1-ol for 4 h via inhalation of vapours at 3 different
concentrations (25 - 75 % of the maximum effective dose) (Frantík et al.
1994). Most animals went through 3 - 4 exposures to each concentration,
and the interval between exposures was at least 3 weeks. According to
the authors the characteristics of generation, spreading and maintenance
of the seizure discharge were found to permit the detection and
quantitative measuring of the acute solvent effects at very low
concentrations. A short electrical impulse was applied through ear
electrodes. The duration of tonic extension of hindlimbs in rats and the
velocity of tonic extension in mice were the most sensitive and
reproducible response measures. The concentration that evoked a 30 %
depression in the recorded activity in rats was determined to be 1700
ppm (= approx. 6.24 mg/L) after 3-methylbutan-1-ol exposure. In the same
study, the concentration that evoked a 30 % depression in the recorded
activity in female H strain mice was 950 ppm (= approx. 3.49 mg/L) after
3-methylbutan-1-ol exposure (Frantík et al. 1994).
In a combined repeated-dose / reproductive
developmental toxicity study according to OECD TG 422 in rats treated
orally with 3-methylbutan-1-ol at doses of 30, 100 and 300 mg/kg bw/day
detailed clinical observations, manipulative tests and measurement of
grip strength and motor activity were performed after an administration
period of at least 39 days (see Chapter “Repeated Dose Toxicity”).
Concerning the examined behavioural parameters no abnormalities in any
animal in the main groups or in the recovery group were noted (Kuraray
Co. Ltd. 2008).
The effect of pentan-1-ol on motor activity
was investigated in a published study, where 20 - 25 male Swiss-Cox mice
were orally administered doses of 500, 1000 and 2000 mg/kg bw in olive
oil (Maickel & Nash Jr. 1985). Testing of motor performance was
performed with a rotarod 10, 20, 40, 80 and 120 min after dosing, which
was repeated on five different days. In addition, body temperature and
levels of alcohol in blood were analyzed at the same time points.
Examination of the data on body temperature showed that there was no
consistent relationship between the time of maximal hypothermic effect
and the time course of blood levels of the alcohol. In general, the
maximum hypothermic response was observed at either 10 or 20 min after
the administration of alcohol. Analysis of the data concerning rotarod
performance indicated that no significant differences occurred for the
different test days; consequently test days 1-5 were combined. A
dose-related impairment of performance was observed for pentan-1-ol.
This impairment was time-related and was positively correlated, in
magnitude, with the levels of blood alcohol, i.e. the greater the blood
level of alcohol, the greater was the degree of impairment of rotarod
performance. The smallest dose was ineffective. All animals returned to
normal activity by 120 min after the administration of alcohol. Since
the observed effects were reversible, the NOAEL can be set at the
highest dose of 2000 mg/kg bw, under the conditions of this study.
In another publication, the effects of
electrically evoked seizures were determined in male Wistar rats and
female mice of the H strain after 4 h inhalation of pentan-1-ol vapours
at 3 different concentrations (25 - 75 % of the maximum effective dose)
(Frantík et al. 1994). Most animals went through 3 - 4 exposures to each
concentration and the interval between exposures was at least 3 weeks.
According to the authors the characteristics of generation, spreading
and maintenance of the seizure discharge were found to permit the
detection and quantitative measuring of the acute solvent effects at
very low concentrations. A short electrical impulse was applied through
ear electrodes. The duration of tonic extension of hindlimbs in rats and
the velocity of tonic extension in mice were the most sensitive and
reproducible response measures. The concentration that evoked a 30 %
depression in the recorded activity in rats was determined to be 1600
ppm (= approx. 5.85 mg/L) after pentan-1-ol exposure. In the same study,
the concentration that evoked a 30 % depression in the recorded activity
in female H strain mice was 2600 ppm (= approx. 9.55 mg/L) after
pentan-1-ol exposure (Frantík et al. 1994).
The loss of the righting reflex of Swiss
Webster mice after a single intraperitoneal injection of pentan-1-ol in
corn oil was investigated by Lyon et al. (1981). The concentration of
336.3 mg/kg bw was found to be the ED50 (effective dose that causes loss
of righting reflex in 50 % of treated animals).
As further information a publication (Silver
1992) is available in which the potential of several volatile chemicals
including pentan-1-ol to produce nasal irritation based on neural
stimulation is described. The characteristics of responses of nasal
trigeminal receptors to volatile chemicals were studied by recording
electrophysiological responses from the rat ethmoid nerve. High
concentrations of the stimulus elicited responses with an initial phasic
component followed by a steady state tonic level. Low concentrations
often produced a gradual increase in activity that last for the duration
of the stimulus. The concentration (ppm) that first elicits a response
larger than baseline is reported as the threshold. Responses at all
concentrations rapidly returned to baseline levels after removal of the
stimulus. A maximum response is the response to a saturated stimulus or
the response at which the concentration-response curve began to plateau.
This response is reported as a percentage of the response to the
standard stimulus (approx. 550 ppm cyclohexanone). For pentan-1-ol, a
discrimination dose of 59 ppm (0.22 mg/L air) was determined.The maximum
response is 48 % compared to the response to cyclohexanone.
To summarize, the available study data do
not give any indication on neurotoxicity. Although effect levels were
determined regarding selected, but isolated behavioural parameters
(Maickel & Nash Jr. 1985, Lyon et al. 1981, Frantík et al. 1994), these
effects were not persistent and do not extend the knowledge about toxic
effects obtained in acute and repeated dose toxicity studies.
Thus, based on the available data,
3-methylbutan-1-ol and pentan-1-ol were reported to cause transient
effects indicative for CNS depression after acute and repeated test
substance application which is a common effect of solvents at higher
concentrations. These narcotic effects were not observed in an OECD TG
422 compliant study conducted with the structural analogue
In summary, 2-methylbutan-1-ol and its
structural analogues do not exhibit selective or cumulative
neurotoxicity in laboratory animals. Classification regarding
neurotoxicity or CNS depression after inhalation exposure, STOT single
exposure, Cat. 3 (for narcotic effects) according to 1272/2008/EC (CLP)
criteria, is not considered necessary due to the minor degree and
transient character of the observed effects.
available data are considered reliable and suitable for classification
purposes under Regulation (EC) No 1272/2008 (CLP).
a result, the substance is not classified for neurotoxicity under
Regulation (EC) No 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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