Alcohols, C9-11-branched and linear

Endpoint summary

Description of key information

The key in vivo skin irritation study for Alcohols, C9-11-branched and linear, conducted according to a protocol similar to OECD Test Guideline 404 and in compliance with GLP, concluded Alcohols, C9-11-branched and linear to be irritating to skin (Shell, 1981a).

The key in vivo eye irritation study for Alcohols, C9-11-branched and linear, conducted according to a protocol similar to OECD Test Guideline 405 and in compliance with GLP, concluded Alcohols, C9-11-branched and linear to be not irritating to eyes (Shell, 1981b).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Method: Draize Test

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Camm Research Institute, New Jersey, USA
- Age at study initiation:
- Weight at study initiation: 2.2 - 3 kg
- Housing: individual, suspended, stainless steel cages
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period: 21 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:

Type of coverage:

occlusive

Preparation of test site:

other: shaved, abraded and intact skin

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml

Duration of treatment / exposure:

24 hour(s)

Observation period:

24 and 48 hours after exposure and at 7 days.

Number of animals:

3M, 3F

Details on study design:

TEST SITE
- Type of wrap if used: gauze patches were held in place with strips of Blenderm tape. The entire trunk was then covered in plastic covering, which was secured and sealed and then wrapped with elastic bandage to immobilize and occlude the patches.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was wiped away with a moist towel.
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Remarks on result:

other: intact skin

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.46

Max. score:

4

Remarks on result:

other: intact skin

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Remarks on result:

positive indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

4

Remarks on result:

positive indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3

Max. score:

4

Remarks on result:

positive indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3

Max. score:

4

Remarks on result:

positive indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.5

Max. score:

4

Remarks on result:

positive indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.5

Max. score:

4

Remarks on result:

positive indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.25

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

skin reactions were assessed at 24/72h

Irritant / corrosive response data:

AVERAGE SCORE
- Erythema: Mean 24 + 72 hour score for 6 animals intact skin 2.67,  abraded skin 2.75.
- Oedema: Mean 24 + 72 hour score for 6 animals intact skin 1.46, abraded  skin 1.54.
-PDII 4.2

REVERSIBILITY: At 7 days all the application sites had developed eschar  (scored as 4) so the effects had increased over the period of the study.  
PII 4.2.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The in vivo skin irritation study for Alcohols, C9-11-branched and linear, conducted according to a protocol similar to OECD Test Guideline 404 and in compliance with GLP, concluded Alcohols, C9-11-branched and linear to be irritating to skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02.02.1981-11.02.1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

Method: Draize Test

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Camm Research Institute, USA
- Weight at study initiation: 2.1 - 2.7 kg
- Housing: Individually housed in suspended stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): average 20.9C
- Humidity (%): average 56.3

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

0.5 minute(s)

Observation period (in vivo):

7 days (examination points at 1, 24, 48 and 72 hours and at 7 days)

Number of animals or in vitro replicates:

3M+3F unrinsed; 3M rinsed.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:

SCORING SYSTEM: Draize, 1963 plus Kay & Callandra 1962 (modified)

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Irritation parameter:

maximum mean total score (MMTS)

Basis:

other: nonwashed eyes

Time point:

other: 24 hours

Score:

8.8

Max. score:

110

Irritation parameter:

cornea opacity score

Remarks:

rinsed eyes

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

rinsed eyes

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

rinsed eyes

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

rinsed eyes

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

rinsed eyes

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

rinsed eyes

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

rinsed eyes

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

rinsed eyes

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

rinsed eyes

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

rinsed eyes

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

rinsed eyes

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

rinsed eyes

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

unrinsed eyes

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

unrinsed eyes

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

unrinsed eyes

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

unrinsed eyes

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

unrinsed eyes

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

unrinsed eyes

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

unrinsed eyes

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

unrinsed eyes

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

unrinsed eyes

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

unrinsed eyes

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

unrinsed eyes

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

unrinsed eyes

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

unrinsed eyes

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

unrinsed eyes

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

unrinsed eyes

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

unrinsed eyes

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

unrinsed eyes

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

unrinsed eyes

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

unrinsed eyes

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

unrinsed eyes

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

unrinsed eyes

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Remarks:

unrinsed eyes

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

AVERAGE SCORE (24+48+72 hour) rinsed
- Cornea: individual scores all 0 (group mean score 0)
- Iris: Individual scores all 0 (group mean score 0)
- Conjunctivae (Redness): individual scores 0.3, 0, 0.3 (group mean score  0.2)
- Conjunctivae (Chemosis): individual scores 0.3, 0, 0.3 (group mean  score 0.2)
- Overall irritation score: Maximum mean total score 4.7 at 1 hours after  instillation.

All scores were 0 at 7 days both rinsed and unrinsed.

Other effects:

Conjunctival discharge reported in some rabbits up to 48  hours post instillation (unrinsed) and 1 hour after instillation (rinsed).

Interpretation of results:

GHS criteria not met

Conclusions:

The in vivo eye irritation study for Alcohols, C9-11-branched and linear, conducted according to a protocol similar to OECD Test Guideline 405 and in compliance with GLP, concluded Alcohols, C9-11-branched and linear to be not irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key in vivo skin irritation study for Alcohols, C9-11-branched and linear, conducted according to a protocol similar to OECD Test Guideline 404 and in compliance with GLP, concluded Alcohols, C9-11-branched and linear to be irritating to skin (Shell, 1981a).

In the study, 0.5 ml of the undiluted test material was applied onto the shaved, abraded, or intact skin of 3 male and 3 female rabbits for 24 hours under occlusive dressing. Following the 24-hour application, any residual test item was wiped by using a moist towel and erythema and oedema skin reactions were assessed at 24 and 72 hours post-test substance removal. The mean erythema score for 24 and 72-hour observations for 6 animals was 2.67 for intact skin and 2.75 for abraded skin. The mean oedema score for 24 and 72-hour observations for 6 animals was 1.46 for intact skin and 1.54 for abraded skin.

The conclusion of the key study is supported by the in vivo skin irritation study for Alcohols, C9-11. The study was conducted according to a protocol similar to OECD Test Guideline 404 but prior to GLP, concluded Alcohols, C9-11 to be mildly irritating to skin (category 3) based on persistence of the response at the end of the 7 day observation period (Shell, 1978).

The studies for skin irritation included 24-hour dermal application of the test material on skin under occlusive dressing. The recommended exposure time according to current guideline standard is 4 hours by semi-occlusive application. This deviation results in more pronounced irritant effects than would likely to be evident in a study conducted according to the current guideline standards. In addition, the category trend and evidence that irritant effects which are present in animal studies are not seen in human studies in other alcohols of similar chain length (e.g. decan-1-ol) are taken into consideration in determining the classification outcome. A comparative 24-hour semi-occluded human skin patch study on decan-1-ol 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 decan-1-ol to be more pronounced in rabbits than man.

The key in vivo eye irritation study for Alcohols, C9-11-branched and linear, conducted according to a protocol similar to OECD Test Guideline 405 and in compliance with GLP, concluded Alcohols, C9-11-branched and linear to be not irritating to eyes (Shell, 1981b).

In the study, 0.1 ml of the undiluted test material was instilled into the eyes of male and female rabbits for 0.5 minutes. Following instillation, the eyes of 3 males and 3 females were unrinsed, while the eyes of further 3 males were rinsed. Eye reactions were assessed at 1, 24, 48 and 72 hours post exposure and on day 7. No effects were seen on corneal opacity or iris in any of the test animals for which the eyes were rinsed. Conjunctival redness and chemosis scores were 0.3 for 2 animals at 24, 48 and 72 hours for animals for which the eyes were rinsed. No effects on the iris were noted in animals for which the eyes were not rinsed. Mild corneal opacity with mean scores of 0.3 and 0.6 in two animals, conjunctival effects with mean values of 1, 1, 0.3 and 0.6 in four animals and chemosis scores of 0.6, 0.3 and 1 in three animals, were noted for the unrinsed eyes.

All scores were 0 at 7 days post-exposure for both rinsed and unrinsed eyes. The observed effects were no sufficient to trigger classification for the substance.

The conclusion of the key study is supported by the in vivo eye irritation study for Alcohols, C9-11, conducted according to a protocol similar to OECD Test Guideline 405 but prior to GLP, concluded Alcohols, C9-11 to be mildly irritating to eyes, but not sufficient to trigger classification. The substance meets the criteria for category 2B classification according to GHS, while no classification applies according to Regulation (EC) No 1272/2008 (Shell, 1978).

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; tetradecan-1-ol 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 the lowest mol weight constituent, nonan-1 -ol (not derivedin the AGW paper) is 118.0 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 octan-1-ol, 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 classification or non-classification

Based on the available information, Alcohols, C9-11 branched and linear is not classified for skin irritation but is classified for eye irritation Category 2, H319: "Causes serious eye irritation" according to Regulation (EC) No 1272/2008 and Category 2A, H319: "Causes serious eye irritation" according to GHS.