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Administrative data

Description of key information

The key study in rabbit (Eurofins 2008; rel 1) and  human data (Robinson 1998, rel 2) indicate that  decan-1-ol is not irritating to skin. The key study for eye irritation (Eurofins 2008; rel 1) found the test substance to be an eye irritant based on corneal opacity readings of 1, iritis readings of  2 and conjunctival redness and chemosis of 2 in all animals.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Robinson Services Inc., Clemmons, NC
- Age at study initiation: young adults
- Housing: individually suspended stainless steel caging with mesh floors
- Diet: Purina rabbit chow, ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 55-83
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.2ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:
4 hours
Observation period:
The individual dose sites were scored at ca. 30-60 minutes, 24,48 and 72 hours and at 7 and 10 days after patch removal.
Number of animals:
3F
Details on study design:
TEST SITE
- Area of exposure: the back

- Type of wrap if used: The pad and the entire trunk of each animal were wrapped with semi-occlusive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):the test sites were gently cleansed with acetone, ethanol and a 3% soap solution followed by tap water using a clean paper towel to remove any residual test substance
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other:
Time point:
other: PDI for 30-60 minutes,24,48 and 72 hours/4
Score:
2.8
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritant / corrosive response data:
For the first 24 hours after patch removal, all three treated sites exhibited well-defined erythema and very slight edema. The overall incidence and severity of irritation decreased gradually with time. All animals were free of dermal irritation by day 10 (study termination).
Other effects:
All animals appeared active and healthy during the study. Apart from the dermal irritation noted, there were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.
Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
Under the conditions of this study, Alfol 10 is classified as moderately irritating to the skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Method: other: human 4-hr patch test
GLP compliance:
not specified
Species:
human
Type of coverage:
occlusive
Amount / concentration applied:
undiluted
Duration of treatment / exposure:
4 hour(s)
Number of animals:
30
Remarks on result:
other: Decanol produced a minimal response on human skin equivalent to that  produced by water.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Principles of method if other than guideline:
The humidity was above the targeted upper limit of 70% during the study due to exceptionally high seasonal humidity. Portable dehumidifiers were ised to lower the humidity levels during this time.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Robinson Services Inc., Clemmons
- Age at study initiation: young adult
- Weight at study initiation:
- Housing:suspended stainless steel caging with mesh floors
- Diet: Pelleted purina rabbit chow, ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 59-81
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:
single instillation, not washed
Observation period (in vivo):
Occular irritation was evaluated at 1, 24, 48 and 72 hours and at 4 and 7 days post-instillation.
Number of animals or in vitro replicates:
3F
Details on study design:
SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24 hours
Score:
28.3
Irritation parameter:
cornea opacity score
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:
cornea opacity score
Basis:
animal #2
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:
cornea opacity score
Basis:
animal #3
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:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.66
Max. score:
2
Reversibility:
fully reversible within: 72 hours
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: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.66
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
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).
Other effects:
None reported.

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

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

1/1/1

1/1/ 1

 2/2/2

2/ 2/2

24 h

 1/1/1

 1/1/1

 3/3/2

 2/2/2

48 h

 1/1/1

 1/1/1

 2/2/2

 1/1/1

72 h

 0/0/0

 1/0/0

 2/1/1

 1/1/0

Reversibility*)

 c

Average time (unit) for reversion

 72h

72h

Day 7

Day 7

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

 

Interpretation of results:
Category 2B (mildly irritating to eyes) based on GHS criteria
Conclusions:
The maximum mean score of 28.3 at 24 hours was reported in a high relaibility study, conducted according to an appropriate guideline and in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A well conducted skin irritation study in rabbits (Bagley, 1996, Rel 1) found 1-decanol to be a skin irritant under 1272/2008 Regulation (CLP), using 98% test solution and semi occluded test conditions and a test duration of 4 hours. Similarly another reliable skin irritation study using 50% decanol in occluded conditions for duration of 24 hours in rabbits indicated that decanol was irritating to skin ( Kaestner, 1977). In addition a 90 day repeated dose dermal study (WIL Research 1995) in rats where a multi-constituent solution containing circa 50% decanol (semi-occluded conditions) gave rise to marked dermal irritative effects. It is however important to take in to account the different test protocol that was used, that is a 90 day repeated dose dermal study compared to a standard 4 hour dermal irritation study and the different species (rats instead of rabbit) and test duration (90 days vs. 4 hours).

However, despite the fact that some of the high reliability animal studies suggest decanol to be irritating to skin, a reliable dermal irritation study conducted in rabbits (Eurofins, 2008; Rel 1) indicates that decanol is not irritating to skin by reporting scores of oedema and erythema below 2.3 (cut-off value for classification) for all test animals and skin reactions reversibility within 10 days. This is also confirmed in another well conducted dermal irritation study by Johnson et al (1996, Rel 1) where rabbits were exposed under semi occlusive conditions to decanol for a test period of four hours and also reported individual animal scores below 2.3 at all observations for all the animals. Human evidence also suggests decanol 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 1-decanol to be more pronounced in rabbits than man. The human evidence supplied by the Kaestner study (1977) is further supported by a human study which also shows no irritative effects in humans arising from a 4 hour occluded exposure to decanol (Robinson, 1998).

Summary: Although some of the animal studies indicate that decanol is irritating to skin under the conditions of the study, there are also a number of animal studies which indicate decanol is not irritating to skin. In addition human evidence also suggests that decanol is not a skin irritant, and a comparative study reported more pronounced irritation in rabbits than in man. Overall it is therefore concluded that decanol is not irritating to skin.

Eye irritation

The key study by Eurofins (2008; Rel 1) for eye irritation in rabbits found 1-decanol to be irritating to eyes under EU criteria (Regulation 1272/2008, CLP). The supporting study for eye irritation (Huntingdon Life Sciences, 1996; rel 1) found the test substance to be an eye irritant; the remaining studies reported 1 -decanol to be slightly irritating (BIBRA, 1995), to cause corneal injury (Bevan, 2001) and mild irritation (RTECS, 2004).

In conclusion, 1-decanol is considered 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 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 is 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 is discounted as a physical effect. However, under the CLP Regulation (440/2008/EC) 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 decan-1-ol (not derived in the AGW paper) is 129 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.


Justification for classification or non-classification

Due to the lack of effects of decan-1 -ol on skin in humans and other study results in animals, decan-1-ol is not classified as irritating to skin. The available data on eye irritation lead to classification of decan-1-ol as Category 2 Eye Irritant in accordance with Regulation 1272/2008 (CLP).