Octan-1-ol

Endpoint summary

Description of key information

The key study for skin irritation (Johnson 1996; rel 1), conducted according to OECD Test Guideline 404 and in compliance with GLP, reports octan-1-ol to be mildly irritating to skin, but not sufficient for classification.

Conclusion for eye irritation was based on weight of evidence of studies conducted with the registered substance octan-1-ol (Huntingdon Life Sciences, 1996; ECETOC, 1998). The registered substance, octan-1-ol, was concluded to be irritating to eyes.

In the first eye irritation study for octan-1-ol, conducted according to OECD Test Guideline 405 and in compliance with GLP, concluded octan-1-ol to be irritating to eyes (Huntingdon Life Sciences, 1996b).

In the second eye irritation study for octan-1-ol, conducted according to OECD Test Guideline 405 without information on GLP compliance, concluded octan-1-ol to be irritating to eyes (ECETOC 1998).

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:

1996/07/10-1996/07/25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Froxfield SPF Rabbits, Broadway Farm, Froxfield, Hampshire, England.

- Age at study initiation: ca. 3 months

- Weight at study initiation: 2.22-2.64kg

- Housing: The animals were individually housed in suspended stainless steel cages mounted in mobile batteries. The cages were fitted with perforated counter sunk floor panels. A tray beneath the floor was lined with absorbent paper which was changed regularly.

- Diet: (ad libitum) Standard pelleted rabbit diet (STANRAB (P) SQC Special Diets Services Limited, Witham, Essex, England). The diet contained no added antibiotic or other chemotherapeutic or prophylactic treatment. Samples of diet were taken for analysis at six-monthly intervals to detect the potential contaminants by a laboratory independent of the supplier.

- Water: Tap water (ad libitum)

- Acclimation period: Length of the acclimatization period not specified but in place.


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 18C (range 15-23C)

- Humidity (%): 55% R.H (range 40-70%)

- Air changes: 10 complete air changes (per hr)

- Photoperiod (hrs dark / hrs light): 12h/12h


IN-LIFE DATES: Not stated.

Type of coverage:

semiocclusive

Preparation of test site:

other: closely clipped dorsa

Vehicle:

unchanged (no vehicle)

Controls:

other: A control patch on the same animal without test substance.

Amount / concentration applied:

TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 0.5 ml of test material was applied.

- Concentration (if solution): undiluted

Duration of treatment / exposure:

4 hour(s)

Observation period:

Dermal reactions were assessed at 1,24,48 and 72 hours after removal of the dressing and on days 7, 10, 13 and 16.

Number of animals:

3 females

Details on study design:

TEST SITE

- Area of exposure: Two test areas were marked on either side of the clipped area of dorsum.

- % coverage: 6x6cm patch

- Type of wrap if used: Unmedicated gauze patch (3x2cm) which was held in place on the left test by strips of Blendern (Community Care Products, 3M Health Care, Loughborough, England). The right test site, acting as a control was covered by similar semi-occlusive dressing but remained untreated.


REMOVAL OF TEST SUBSTANCE

- Washing (if done): The treatment site was gently washed with warm water and dried with paper tissues to remove excess test material adhering to the skin.

- Time after start of exposure: 4 hours


SCORING SYSTEM: Reactions of the test sites were assessed according to the criteria of Draize 1959.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

group mean

Time point:

24/48/72 h

Score:

1.43

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: The mean values for erythema and oedema did not equal or exceed the EEC limit values considered to indicate a significant inflammatory response to treatment.

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Remarks on result:

no indication of irritation

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

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

AVERAGE SCORE

- Erythema: Individual mean 24+48+72 hour scores 1.0, 2.0 and 1.3. 

Other effects:

OTHER EFFECTS: 

The test site was sticky to touch at 1hour post-dosing. A loss of elasticity at the test site was reported at 48 and 72 hours. From day 7 until the end of the observation period (day 16) exfoliation was observed in all test animals. Control sites showed no skin irritation all scores 0.

Interpretation of results:

GHS criteria not met

Conclusions:

The C8 alcohol Kalcohl 0898 is not a skin irritant according to either EU criteria following a 4 hour semi-occlusive exposure. Kalcohl 0898 can be considered as a mild irritant under GHS criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1996/02/14 - 1996/03/04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS

- Source: Froxield SPF Rabbits, Broadway Farm, Froxfield, Hampshire, England.

- Age at study initiation: ca. 5 months old

- Weight at study initiation: 2.88-3.12kg

- Housing: Stainless steel cages mounted in mobile batteries. The cages were fitted with perforated countersunk floor panels, with a tray beneath the floor lined with absorbent paper which was changed at regular intervals.

- Diet: STANRAB (P) SQC Standard pelleted rabbit diet (ad libitum), Special Diets Services Ltd., Witham, Essex, England.

- Water: Public supply (ad libitum)

- Acclimation period: The report states that the animals were acclimatized but does not state duration.


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 18C (range 15-23C)

- Humidity (%): 55% (40-70%)

- Air changes (per hr): 10

- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye of each animal served as a control.

Amount / concentration applied:

TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 0.1ml, undiluted

Duration of treatment / exposure:

The animals were subjected to a single ocular instillation of the test material. Ocular reactions were assessed at 1, 24, 48 and 72 hours after treatment and on days 8, 15 and 22.

Observation period (in vivo):

The behaviour of each rabbit was observed for several minutes immediately following instillation of the test material. The animals were returned to their cages and checked at least twice during the first hour after dosing, at regular intervals throughout the day. Ocular reactions were assessed 1, 24, 48 and 72 hours after treatment. Additional observations were made on says 8, 15 and 22.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE

- Washing (if done): Not rinsed.


SCORING SYSTEM: As prescribed in OECD test method.


TOOL USED TO ASSESS SCORE: An opthalmoscope or pencil beam torch was used to facilitate inspection of the eyes. From the 24 hour examination onwards, fluorescein was used, if necessary, to aid the examination of the cornea.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72h

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

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:

cornea opacity score

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:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 22 days

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 22 days

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 22 days

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 22 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 22 days

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 22 days

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 22 days

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 22 days

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 22 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Iritis, slight to moderate conjuncitivitis and areas of very slight/slight corneal opacity during the first 72 hours. Very slight conjunctivitis observed in all 3 animals at days 8 and 15. Very slight conjunctivitis persisted in 2 animals until termination on day 22. Iritis persisted in one of these rabbits until day  22. 

Other effects:

Blepharitis of the lower lid seen in 2 rabbits at 72 hours persisting to day 8 in one rabbit. Very slight/slight initial pain response.

 Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animalfrom the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	2/1/1	1/ 1/1	2/ 2/2	2/2/2
24 h	2/1/1	1/1/1	2/2/2	1/1/1
48 h	2/1/1	1/1/1	2/2/1	1/2/0
72 h	2/1/1	1/1/1	3/1/1	1/1/1
Average 24h, 48h, 72h	2/1/1	1/1/1	2.3/1.7/1.3	1/1.3/0.7
Reversibility*)	nc	nc	nc	-
Average time (unit) for reversion	72 hours	Day 22	Day 22	-

 

*) Reversibility: c. = completely reversible;n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In the eye irritation study for octan-1-ol (Kalcol 0898), conducted according to OECD Test Guidelinen 405 and in compliance with GLP, concluded octan-1-ol to be irritating to eyes.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Details on test animals or tissues and environmental conditions:

TEST ANIMALS: Rabbit 
- Strain: New Zealand White
- Sex: Unspecified
- Source: No data

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

undiluted
Amount applied: 0.1 ml

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Details on study design:

Comment: not rinsed

EXAMINATIONS
- Ophthalmoscopic examination: No data
- Scoring system: No data
- Observation period: 1, 24, 48, 72 hours, 7, 10, 14 and 21 days (assessments made until the test eye for each animal showed complete reversal 
to normal up to 21 days)
- Tool used to assess score: No data

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

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

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Remarks on result:

probability of mild irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

AVERAGE SCORE (24+48+72 hour)
- Cornea: Individual 1, 2, 2 Mean 1.7
- Iris: Individual 0, 1, 1 Mean 0.7
- Conjunctivae (Redness): Individual 1.7, 2.3, 2.7 Mean 2.2
- Conjunctivae (Chemosis): Individual 1.7, 3, 2.7 Mean 2.5
- Overall irritation score: MMAS (modified maximum average score) 41.0

Other effects:

Complete reversal in 14 days for all 3 test animals, 1 eye appeared normal after 7 days.

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

In the supporting eye irritation study for octan-1-ol, conducted according to OECD Test Guideline 405 without information on GLP compliance, concluded octan-1-ol to be irritating to eyes. Octan-1-ol is classifiable as an eye irritant based on scores of =>2 for corneal opacity, =>1 for iritis and =>2 for chemosis. The lesions were reversible within 14 days. According to GHS criteria octan-1-ol is a Class 2A irritant based on individual mean 24+48+72 hour scores in at least 2 test animals of => 1 for corneal opacity and iritis and => 2 in at least 2 test animals for conjunctival chemosis and redness.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key study for skin irritation (Johnson 1996; rel 1), conducted according to OECD Test Guideline 404 and in compliance with GLP, reports octan-1-ol to be mildly irritating to skin, but not sufficient for classification. In the study, 0.5 ml of undiluted octan-1-ol was applied onto the skin of female rabbits for 4 hours under semiocclusive dressing. After exposure the treatment site was gently washed with warm water and dried with paper tissues to remove excess test material. Dermal reactions were assessed at 1, 24, 48 and 72 hours after removal of the dressing and on days 7, 10, 13 and 16. The mean erythema scores for each animal at 24/48/72 hours were 1, 2 and 1.3, respectively. No oedema was observed. The test site was reported to be sticky to touch at 1-hour post-dosing. A loss of elasticity at the test site was reported at 48 and 72 hours. From day 7 until the end of the observation period (day 16) exfoliation was observed in all test animals. Control sites showed no skin irritation all scores 0.

The findings of the Johnson (1996) study are supporting by another two skin irritation studies. A skin irritation study in human did not find octan-1-ol irritating to skin when tested in 25 volunteers, following a 48 closed application (Opdyke, 1973). 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 octan-1-ol to be more pronounced in rabbits than man.

Conclusion for eye irritation was based on weight of evidence of studies conducted with the registered substance octan-1-ol (Huntingdon Life Sciences, 1996a & b; ECETOC, 1998). The registered substance, octan-1-ol, was concluded to be irritating to eyes. The conclusion is supported by another study for octan-1-ol (Jacobs, 1987) and data for the category members hexan-1-ol and decan-1-ol (ECETOC, 1998; Eurofins, 2008).

In the first eye irritation study for octan-1-ol, conducted according to OECD Test Guideline 405 and in compliance with GLP, concluded octan-1-ol to be irritating to eyes (Huntingdon Life Sciences, 1996).

In the study, 0.1 ml of undiluted octan-1-ol was instilled into the eyes of three rabbits. Ocular reactions were assessed at 1, 24, 48 and 72 hours after treatment and on days 8, 15 and 22. The reported individual average scores for each animal were 2, 1, 1 for cornea; 1 for iris; 2.33, 1.33 and 1.66 for conjunctival redness; 1, 1.3 and 0.6 for chemosis, respectively. Iritis, slight to moderate conjuncitivitis and areas of very slight/slight corneal opacity during the first 72 hours were observed. Very slight conjunctivitis observed in all 3 animals at days 8 and 15. Very slight conjunctivitis persisted in 2 animals until termination on day 22. Iritis persisted in one of these rabbits until day 22.

In the second eye irritation study for octan-1-ol, conducted according to OECD Test Guideline 405 without information on GLP compliance, concluded octan-1-ol to be irritating to eyes (ECETOC 1998). In the study, 0.1 ml of undiluted octan-1-ol was instilled into the eyes of three rabbits. Ocular reactions were assessed at 1, 24, 48, 72 hours, 7, 10, 14 and 21 days. The reported scores were =>2 for corneal opacity, =>1 for iritis and =>2 for chemosis, with the lesions reversible within 14 days and the test substance.

In the supporting eye irritation study for octan-1-ol, conducted according to OECD Test Guideline 405 without information on GLP compliance, concluded octan-1-ol to be irritating to eyes (Jacobs, 1987). In the study, 0.1 ml of undiluted octan-1-ol was instilled into the eyes of six rabbits. Post-exposure observation period was 96 hours. Individual eye irritation scores were not given. The average mean scores for all the animals were: 2.23 for cornea opacity, 0.7 for iris, 2.57 for conjunctivae redness and 1.9 for chemosis. Reversibility was not observed by the end of the 96-hour observation period. However, all eye irritation scores had reduced by 96 hours.

In the in vivo eye irritation study for hexan-1-ol, conducted according to OECD Test Guideline 405 and in compliance with GLP, hexan-1-ol was concluded to be irritating to eyes (ECETOC, 1998). In the study, 0.1 ml of undiluted hexan-1-ol was instilled into the eyes of 2 rabbits. The eyes were not rinsed following instillation. Eye irritation reactions were made at 1 hour, 4, 24, 48, 72 hours and on day 7, 10, 14 and 21 post-instillation. Effects were seen on the cornea, iris and conjunctiva. Effects on the cornea and iris were fully reversible by day 7, redness and/or chemosis were still evident on day 7 in one rabbit, day 10 in 2

rabbits and day 14 in the final rabbit, all scores were 0 by day 21. Hexan-1-ol was concluded to be classified for eye irritation Category 2A according to GHS criteria and Category 2 according to Regulation (EC) No 1272/2008 based on individual mean 24+48+72-hour scores in at least 2 test animals of => 1 for corneal opacity and iritis and => 2 in at least 2 test animals for conjunctival chemosis and redness. Only 1 animal scored => 3 for corneal opacity or => 1.5 for iritis.

In the in vivo eye irritation study for decan-1-ol, conducted according to a protocol similar to OECD Test Guideline 405 and in compliance with GLP, decan-1-ol was concluded to be irritating to eyes (Eurofins, 2008). In the study, 0.1 ml of undiluted decan-1-ol was instilled into the eyes of three female rabbits. Ocular irritation was evaluated at 1, 24, 48 and 72 hours and at 4 and 7 days post-instillation. Within one hour of test substance instillation, all three treated eyes exhibited corneal opacity, iritis and 'positive' conjunctivitis with the maximum effect observed at 24 hours. The overall incidence and severity of irritation decreased after 24 hours. All animals were free of ocular irritation by day 7 (study termination). The reported individual average scores for each animal were 0.66 for cornea; 1, 0.66 and 0.66 for iris; 2.33, 2 and 1.66 for conjunctival redness; 1.3, 1.3 and 1.6 for chemosis, respectively.

Consideration of the data available for octan-1-ol, and for the category members hexan-1-ol and decan-1-ol, leads to the weight of evidence conclusion that octan-1-ol is irritating to eyes.

A full discussion of the Category and considerations of RAAF Assessment Entities can be found in the Human Health Alcohols C6-24 Category report (PFA, 2016).

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 octan-1-ol (derived in the AGW paper) is 106 mg/m.

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 classification or non-classification

Based on the available information, octan-1-ol does not require classification for skin irritation, but it does require Category 2 classification for eye irritation, H319: "Causes serious eye irritation", according to Regulation (EC) No 1272/2008.