Registration Dossier

Administrative data

Description of key information

In a study for skin irritation/corrosion with rabbits according to OECD TG 404 benzyl alcohol was evaluated as not irritating to the skin (Bayer AG 1990).
Based on the results of two eye irritation studies according to OECD TG 405 it was concluded that benzyl alcohol has an irritant potential to the eye (Bayer 1990, Elf Atochem 1998).
Based on acute and repeated inhalation studies (OECD TG 403 and 412, respectively) no potential for respiratory irritation was concluded.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study according OECD 404 and GLP
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: albino rabbits, HC:NZW
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England, UK
- Age at study initiation: adult rabbits
- Weight at study initiation: 3.1-3.4 kg
- Housing: individually under standardized conventional conditions in stainless steel cages with perforated floors
- Diet: approx. 100-120 g/animal and day; feeding once per day in the morning
- Water: ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): approx. 50
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: the opposite dorsal area of the trunk of each animal served as control
Amount / concentration applied:
500 µl (ca. 522 µg)
Duration of treatment / exposure:
4 hours
Observation period:
7 days (all changes had completely subsided after 7 days)
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorso-lateral area of the trunk, 6x6 cm
The test compound was applied to a hypoallergenic patch and a further patch was moistened with water for control; they were loosely held in contact with skin by means of a semiocclusive dressing for the exposure period

REMOVAL OF TEST SUBSTANCE
- Washing (if done): carefully with water
- Time after start of exposure: 4 h

SCORING SYSTEM:
The degrees of erythema/eschar formation and oedma formation was recorded as specified by Draize.
Irritation parameter:
erythema score
Basis:
animal: #1, #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: mean score: 0.7
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
see data above
Other effects:
no further data

no further data

Executive summary:

In a study for skin irritation/corrosion on rabbits according to OECD TG 404 benzyl alcohol showed only slight effects to the skin in one animal (exposure period: 4 hours, 2 rabbits without any irritant effects, 1 rabbit with erythema score 1 at maximum, fully resolved within 72 hours) (Bayer AG 1990).

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study according OECD 405 and GLP
Qualifier:
according to
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
- Strain: albino rabbits, HC:NZW
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England, UK
- Age at study initiation: adult rabbits
- Weight at study initiation: 3.1-3.4 kg
- Housing: individually under standardized conventional conditions in stainless steel cages with perforated floors
- Diet: approx. 100-120 g/animal and day; feeding once per day in the morning
- Water: ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): approx. 50
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the second eye of the respective animal served as control
Amount / concentration applied:
100 µl (ca 104.5 µg)
Duration of treatment / exposure:
24 hours (The treated eye was washed out 24 hours after instillation of the test compound)
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with physiological saline
- Time after start of exposure: 24 hours

SCORING SYSTEM:
as described by Draize

TOOL USED TO ASSESS SCORE:
hand-slit lamp, fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 d at the latest
Irritation parameter:
iris score
Basis:
animal: #1, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 1
Max. score:
2
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: mean score: 0.3
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 21 d at the latest
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal: #2, #3
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: mean score: 0.7
Irritant / corrosive response data:
Exposure of the test substance to the eye resulted in irritant effects of the mucous membranes and the cornea. Being more pronounced immediately following administration signs persisted on day 14 in 2 animals but proved to be reversible after 3 weeks. According to the author these evidences indicate an irritant potential of the product to the eye.
Other effects:
With fluorescein slight and reversible epithelial effects in the cornea were seen.
Executive summary:

According to OECD TG 405, 3 rabbits received a dose of 100 µl/animal into the conjunctival sac of one eye of each rabbit (the untreated eye served as control). Eyes were washed out 24 hours after start of exposure. The total post exposure period was 21 days. Benzyl alcohol was irritating to the eyes of rabbits, but full recovery occurred within the 21 days observation period (Bayer AG 1990).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

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

Additional information

Skin irritation

In a study for skin irritation/corrosion on rabbits according to OECD TG 404 benzyl alcohol showed only slight effects to the skin in one animal (exposure period: 4 hours, 2 rabbits without any effects, 1 rabbit with erythema score 1 at maximum, fully resolved within 72 hours) (Bayer AG 1990). A second animal study (24h-exposure of test substance inside rabbits ear) revealed no irritant effects at all (Bayer 1979). In a brief overview of numerous substances 1/32 volunteers revealed mild erythema when tested with benzyl alcohol whereas the positive control substance sodium dodecyl sulfate causes clear irritation effects in 17/32 volunteers (Basketer 1997, 2004).

Eye irritation

There are two studies available, which investigate eye irritation in rabbits, both performed according to OECD TG 405 and GLP (Bayer 1990 and Elf Atochem 1998). In both study 3 rabbits received 0.1 ml of benzyl alcohol into the concunctival sac of one eye (the other untreated eye served as control). In the study of Bayer (1990) the eyes were rinsed after 24 hours, this was not done in the study of Elf Atochem (1998). The post exposure observation time was 21 days in the Bayer study and at latest 18 days in the Elf Atochem study. The scores at the different time-points were somewhat higher in the Elf Atochem study. In both studies the result can be summarized as follows:

Eye exposure to benzyl alcohol resulted in irritant effects of the mucous membranes and the cornea. Also slight iritis was noted. Signs proved to be reversible within the respective observation time. Overall, benzyl alcohol revealed an irritant potential to the eye.

Respiratory irritation

A study on acute (4h) inhalation toxicity on rats (see chapter Acute Toxicity: inhalation) revealed only transient and slight clinical signs at the highest dose (4178 mg/m³; maximum technically achievable concentration) that were seen by the author as causally related to a slight irritant effect of the test article to the upper respiratory tract (reflex bradypnoea caused by sensory irritation). No indication of respiratory irritation was reported from repeated inhalation studies.


Justification for selection of skin irritation / corrosion endpoint:
Only one fully reliable in vivo study available.

Justification for selection of eye irritation endpoint:
One of the two fully reliable studies selected; in any case both studies would lead to classification as Eye Irrit. 2.

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation

According to legal classification (Directive 67/548/EEC and Regulation (EC) No. 1272/2008) benzyl alcohol is not classified as skin irritant.

Based on the available data and according to criteria of Regulation (EC) No. 1272/2008, Annex I, classification as skin irritant would not be justified.

Eye irritation

According to legal classification (Directive 67/548/EEC and Regulation (EC) No. 1272/2008) benzyl alcohol is not classified as eye irritant.

Based on the available data (Bayer 1990 and Elf Atochem 1998) and according to criteria of Regulation (EC) 1272/2008, Annex I, justification for classification as Eye Irrit. 2 (H319 = Causes serious eye irritation) is given. Note: All effects were fully reversible within the observation time. Therefore, under the condition of Regulation (EC) 1272/2008 a self-classification of benzyl alcohol as Eye Irrit. 2 is proposed.

Respiratory Irritation:

According to legal classification (Directive 67/548/EEC and Regulation (EC) No. 1272/2008) benzyl alcohol is not classified as respiratory irritant.

Based on the available data and according to Regulation (EC) 1272/2008, Annex I, classification for respiratory irritation would not be justified.