Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 204-000-3
CAS number: 112-72-1
The key study for skin irritation in human, which is based on a protocol similar to current guideline reports the test substance not to be irritating to skin (Henkel, 1996; rel 2). The key study for eye irritation, conducted according to the appropriate OECD test guideline, and in compliance with GLP, reports tetradecan-1-ol to be irritating to eye (SafePharm Laboratories, 1996; rel 1).
In the skin irritation study, undiluted test material was applied onto
human skin and kept in contact to the skin under semi-occlusive dressing
for 4 hours. Erythema and oedema scores were recorded at
1, 24, 48 and 72 hours after application.
No erythema and oedema were observed during the study period.
Table 1: Irritant/corrosive
response data for each animal at each observation time up to removal
of each animal from the test
Score at time point / Reversibility
Max. score: 4
Max. score: 2
Max. score: 3
Average 24h, 48h, 72h
Average time (unit) for reversion
*) Reversibility: c. = completely
= not completely
reversible; n. = not reversible
In the eye irritation study, fine powder of test material was applied
into the eyes of 3 rabbits. Assesment of ocular damage/irritation was
made approximately 1 hour, 24, 48 and 72 hours following treatment.
Total observation period was 14 days.
Diffuse corneal opacity was noted in 2 treated eyes at the 24, 48, and 72 hour observations.
Iridial inflammation was noted in 2 treated eyes at the 24 hour observation and persisted in 1 treated eye at the 48 and 72 hour observations.
Moderate conjunctival irritation was noted in all treated eyes 1 hour after treatment and persisted in 2 treated eyes at the 24 and 48 hour observations. Minimal conjunctival irritation was noted in 1 treated eye at the 24 and 48 hour observations and in 2 treated eyes at the 72 hour and 7 day observation.
Overall irritation score: Maximum group mean score 27.3 at 24 hours.
All corneal and iridial scores and scores for conjunctival chemosis were normal by day 7. Conjunctival redness persisted in 2
rabbits through day 7 but scores were 0 by day 14. The effects were therefore fully reversible.
The key study for skin irritation was chosen
as it was the most recent, high reliability study available with data
from man. However, a supporting study was also available, with results
in rabbit which finds tetradecan-1-ol a class 2 irritant when
interpreted according to EU criteria (Scientific Associates, 1977; rel
2). The rest of the supporting studies are reliability 4 and may not be
used for classification purposes; however, they support the existing key
study by finding the test material at the most slightly irritating to
skin. Human evidence also suggests tetradecan-1 -ol not to be irritating
by skin contact. A comparative 24 hour semi-occluded human skin patch
study by Kaestner (1977) reported only slight, readily reversible
irritation in humans. It should be noted that results from Kaestner’s
comparative study suggests the percutaneous irritative effects of
tetradecan-1 -ol to be more pronounced in rabbits than man.
The key study for eye irritation by
SafePharm Laboratories (1996) was chosen as key study as it is the most recent
study with tetradecan-1 -ol. The key study reports the test material to
be irritating to eyes.
Discussion of trends in the Category of
C6-24 linear and essentially-linear aliphatic alcohols:
Animal studies in the lower members of both
the linear alcohols and the UVCBs (C6-11) have a skin irritancy
potential ranging from mild to irritant, whereas alcohols in the range
of C12 and C16 are graded as mild, essentially non-irritant. Alcohols
with a carbon chain length C18 and above demonstrated no skin irritation
However, comparative studies in different
species demonstrate the increased sensitivity of rabbit as a test
species to aliphatic alcohols compared to man (Kaestner, 1977; Motoyoshi
et al., 1979). Read across from this study has been used consistently
across the LCAAs category for linear and UVCB substances, and no
classification is proposed for skin irritation based on category trend
of lack of irritant effects in humans despite positive data from animal
Longer-chain linear alcohols in pure form,
which are in a solid state at standard temperature, are produced in
powder form as well as liquids or pastes in some cases. Powders can
cause a transient eye irritation and trigger eye classification. This
was recognised by the Directive 67/548/EEC classification criteria to
the extent that if an irritation response is observed with a powder but
not with a paste or liquid, the classification was discounted as a
physical effect. However, under the CLP Regulation (Regulation (EC) No
1272/2008) criteria, this difference has been eliminated and irritation
as a result of testing with powders triggers a positive classification.
The nature of UVCBs means that they can only
be manufactured as liquid or amorphous forms; so UVCB alcohols are
commercially supplied as pastes only. This phenomenon is the reason for
some differences between eye irritation classifications for UVCB
alcohols compared to the linear constituents in pure form.
Studies with Alcohols, C7-9 have provided
evidence that this substance is classified as Eye irritant Category 2,
despite the physical form of the substance. This is thought to be
consistent with the category trend that shorter chain lengths are more
toxic, and hence more irritant, than longer chain lengths. There is
substantial experimental evidence that Alcohols, C9-11 and Alcohols,
C9-11-branched and linear are not eye irritants. Therefore, even though
this substance has the potential of being classified, the studies
conducted with this substance underline that this is not the case. The
UVCB LCAAs with chain lengths above C12-13 do not require classification
for eye irritation.
In the case of the single-constituent linear
LCAAs of the chain length between C6-C14, category 2 classification as
eye irritant is proposed, whereas linear alcohols of chain length
between C15-C24 are deemed not irritating. C14 is an exception due to a
positive test result determined with a powder test sample; tetradecanol
is therefore classified Category 2 eye irritant under CLP.
Data supporting respiratory irritation of
the linear and essentially linear LCAAs is not sufficient to trigger
classification via this route.
Respiratory irritation and the basis of
DNEL for inhalatory local effects
The registrant has referred to the AGW
values for several linear and essentially-linear aliphatic alcohols,
established by the German regulatory authority. These have been
extrapolated from a concentration of octan-1-ol at which respiratory
irritation levels had been found to be low/acceptable. The threshold
value is 20 ppm, which appears to derive from the 2-ethylhexanol test
results from Van Thriel et al. (2003). No additional assessment factors
have been applied. Respiratory irritation effects from three separate
published papers were cited in reference to this, which the registrant
has evaluated and drawn the following overview conclusions:
1. The extrapolation has been made based on
molecular weight correction i.e. making the assumption that the
equivalent effect would be caused by the equivalent ppm concentration.
The value for tetradecan-1 -ol (derived in the AGW paper) is 178 mg/m³.
2. The studies are concerned with local
effects, not systemic effects.
3. The effects investigated were
self-reported symptoms/changes, and physiological responses that do not
necessarily indicate harm or damage.
4. In view of the non-standard test design,
subjective assessment of results, and lack of evidence to connect the
reported effects with evidence of harmfulness, these results cannot be
considered to be key data. The summary is included for completeness
The approaches and findings from the three
studies (in brief) are as follows.
C. van Thriel, A. Seeber, E. Kiesswetter, M.
Blaszkewicz, K. Golka, G.A. Wiesmüller (2003). Physiological and
psychological approaches to chemosensory effects of solvents. Toxicology
Letters 140-141 (2003) 261-271
- Both 2-Ethylhexanol and octan-1-ol were
examined in this study. The AGW ultimately derives from the
high-concentration exposure of 2-ethylhexanol.
- In additional to self-reported symptoms,
physiological measurements (including anterior active rhinomanometry and
biochemical analysis of nasal secretions (lavage)) were also
investigated and compared with the subjective scores. The physiological
responses studied are not necessarily indicative of damage.
- 24 subjects exposed for up to 4 hours at
“high” min/max octanol concentrations of 0.4/12.5 ppm (mean 6.4 ppm).
Lower ranges also tested.
- Min/max “high” 2-ethylhexanol
concentrations were 1.76/42.07 ppm (mean 21.88 ppm). Lower ranges also
- No information is given in the paper
regarding the method for generating the dose or whether it would have
comprised vapour or aerosol.
- Statistical analysis was done
- Based on the effects reported, the
concentration(s) examined do not result in high scores for chemosensory
- The subjective (self reported) and
objective (physiological) responses did not correlate strongly.
- This paper is in a relevant and peer
reviewed journal (3 months elapsed between being submitted and
Andreas Seeber, Christoph van Thriel, Katja
Haumann, Ernst Kiesswetter, Meinolf Blaszkewicz, Klaus Golka (2002).
Psychological reactions related to chemosensory irritation. Int Arch
Occup Environ Health (2002) 75: 314–325:
- 8 substances were investigated, including
octan-1-ol, at up to 12 ppm.
- The paper is primarily concerned with the
investigation of chemosensory irritation based on perceived symptoms and
self-reported changes of well-being - i.e. not measured physiological
responses. As such the paper is not an investigation into “safe”
(inhalatory) concentrations of the substances investigated. These are
local and not systemic effects.
- For octanol, 24 volunteers were exposed
for periods up to 4 hours at peak concentrations of up to 12 ppm. Based
on the effects reported, the concentration(s) examined do not result in
high scores for chemosensory irritation.
- Statistical analysis was done, the paper
does not report this in detail. We have to presume that appropriate and
suitably powered methodology was used.
- This paper is in a relevant and peer
reviewed journal (5 months elapsed between being submitted and
J. Enrique Cometto-Muñiz, William S. Cain
(1998). Trigeminal and olfactory sensitivity: comparison of modalities
and methods of measurement. Int Arch Occup Environ Health (1998) 71:
- Primary aim of the study was to
investigate sensitivity to nasal irritation by psychophysical methods
(common detection procedure vs nasal lateralisation)
- Study group comprised 5 anosmics (no sense
of smell) and 4 normosmic (normal sense of smell)
- 1-propanol, 1-butanol, 1-hexanol and
1-octanol investigated, concentrations were 100% and subsequent 3-fold
dilutions (100%, 33.3%, 11.1% and 3.7%)
- Again this study was not intended or
powered to identify a “safe” concentration of any of the substances.
In view of the non-standard test design,
subjective assessment of results, and lack of relationship between the
reported effects and evidence of harmfulness, these results cannot be
considered to be key data. The above summary is included for
Kaestner, W. 1977. Zur Speziesabhangigkeit
der Hautvertraglichkeit von Kosmetikgrundstoffen. J. Soc. Cos. Chem.
Motoyoshi, K; et al. 1979 Comparative
studies on the irritancy of oils and synthetic perfumes to the skin of
rabbit, guinea pig, rat, miniature swine and man. Cosmetics and
Toiletries 94: 41-48.
Based on the available data from the key
skin irritation study, no classification is proposed for skin irritation
for tetradecan-1-ol. Based on the key study for eye irritation and the
current EU guideline, tetradecan-1-ol is a category 2 eye irritant
according to 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.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again