Registration Dossier

Administrative data

Description of key information


The key study for skin irritation (Biolab 1991; rel 2) reports a 24+48+72 hour mean score of 1.2 for erythema and 1 for oedema in response to an occlusive, 4 hour exposure to the test material. The key study for eye irritation found the test substance not irritating to the eye (Biolab 1991; rel 2).

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The most recent, high reliability studies were selected as key information. All the supporting studies for eye irritation were in accordance with the key study. Three supporting studies were available for skin irritation; a 4 hour occlusive study found the test material not irritating to skin (Biolab 1984; rel 2), a 24 hour occlusive study (Shell 1964; rel 2) presented the data as combined values for erythema and oedema and was therefore unsuitable for interpretation according to EU criteria, however irritation appeared minimal. The third supporting study for skin irritation (24 hour, occlusive) reported a 24 +48 +72 hour mean score for erythema of 2.3 and 1.7 for oedema (Clark&Coombs, 1978; rel 2), which would trigger classification according to EU criteria. However, the irritant effects are likely to be a consequence of the non-standard conditions (24 hours instead of 4 hours exposure period, occluded instead of semi-occluded application) and the data is therefore not considered to effect classification decision.

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 potential.

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 studies.

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 dodecan-1-ol (derived in the AGW paper) is 155 mg/m3, 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 only.

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 tested.

- 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 irritation.

- 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 published)

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.

- 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, 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 published)

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: 105-110

- 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 completeness only.

Kaestner, W. 1977. Zur Speziesabhangigkeit der Hautvertraglichkeit von Kosmetikgrundstoffen. J. Soc. Cos. Chem. 28:741-754.

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.


Justification for selection of skin irritation / corrosion endpoint:
The key study was conducted in accordance with an appropriate OECD guideline. It is the more recent of the available studies

Justification for selection of eye irritation endpoint:
The key study was conducted in accordance with an appropriate OECD guideline.

Justification for classification or non-classification

Based on the available information, there is no requirement for classification or labelling of Alcohols, C12-15-branched and linear for eye or skin irritation, in accordance with current EC regulation 1272/2008.