Registration Dossier

Administrative data

Description of key information

In an in vivo irritation study on rabbit skin according to the OECD Guideline 404 and in compliance with GLP, nerol was irritating but non corrosive to the skin.

In an in vivo eye irritation study in rabbits, nerol showed slight signs of irritation not fully reversible at Day 7.

Therefore it was considered as irritating to eyes in a conservative approach.

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:
2 -9 July 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
GLP study conducted according to OECD Guideline 404 with minor deviation: individual animal weights not reported.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
individual animal weights not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Sandbach, UK.
- Age at study initiation: Approximately 12-16 weeks
- Weight at study initiation: 2.50-2.72 kg
- Housing: Animals were housed individually in suspended metal cages.
- Diet: Food (Rabbit diet, Preston Farmers Limited, New Leake, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-21 °C
- Humidity: 60-65 %
- Air changes: Approximately 15 changes/h
- Photoperiod: 12 h dark / 12 h light
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (weight with unit): 0.5 mL
- Concentration (if solution): Undiluted test item
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48 and 72 h and 7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Dorsal/flank area
- Type of wrap if used: Test item was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 25 mm x 40 mm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 h

SCORING SYSTEM: According to OECD Guideline 404
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
- Very slight erythema was noted at one treated skin site one hour after removal of the patches.
- The irritation increased and very slight to well-defined erythema with or without very slight oedema was noted at all treated skin sites at subsequent 24, 48 and 72 h observations.
- Hyperkeratinisation of the skin was noted at all treated skin sites on Day 7.
- No corrosive effects were noted.
Other effects:
None

Table 7.3.1/1: Results of skin irritation

Skin reaction

Reading (h)

Individual scores – Rabbit no.

90

119

124

Erythema/Eschar formation

1

0

0

1

24

1

1

2

48

2

2

2

72

2

2

2

7 days

H

H

H

Mean (24, 48 and 72 h)

1.7

1.7

2.0

Oedema formation

1

0

0

0

24

0

0

1

48

1

0

1

72

1

0

0

7 days

0

0

0

Mean (24, 48 and 72 h)

0.7

0.0

0.7

H: Hyperkeratinisation over whole of test site

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Nerol induced an hyperkeratinisation of the skin on Day 7. Based on the absence of information on the reversibility of this effect, this substance is classified as irritating to skin according to Directive 67/548/EEC and nerol is classified in Category 2 (irritant) according to CLP Regulation (EC) N° 1272/2008.
Executive summary:

In a primary dermal irritation study performed according to OECD Guideline 404 and in compliance with GLP, three New Zealand white rabbits were dermally exposed to 0.5 mL of nerol under a semi-occlusive dressing for 4 h. After removal of the residual test item, irritation was scored as outlined in OECD Guideline 404 at 1, 24, 48 and 72 h and 7 days after exposure.

Very slight erythema was noted at one treated skin site one hour after removal of the patches. The irritation increased and very slight to well-defined erythema with or without very slight oedema was noted in all treated skin sites at subsequent 24, 48 and 72 h observations. Hyperkeratinisation of the skin was noted in all treated skin sites on Day 7. No corrosive effects were noted. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1.7, 1.7, 2.0 for erythema and 0.7, 0.0, 0.7 for oedema score, respectively.

Thus, nerol induced an hyperkeratinisation of the skin on Day 7. Based on the absence of information on the reversibility of this effect, this substance is classified as irritating to skin according to Directive 67/548/EEC and nerol is classified in Category 2 (irritant) according to CLP Regulation (EC) N° 1272 /2008.

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:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study conducted similarly to OECD Guideline 405 with deviations: age and body weight of animals and details of lighting cycle of animal house not reported; identification data and physical nature/physiochemical properties of test item not reported
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
age and body weight of animals and details of lighting cycle of animal house not reported; identification data and physical nature/physiochemical properties of test item not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Peter J. Flinn Rabbitry, Albany, USA.
- Housing: Animals were individually housed in stainless steel cages having a wire mesh floor measuring 16" x 19"
- Diet: Teklad rabbit feed, ad libitum
- Water: Water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C
- Humidity: 50 %
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted
Duration of treatment / exposure:
No washing was done.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6 females
Details on study design:
SCORING SYSTEM: Draize eye irritation procedure
Irritation parameter:
other: Eye irritation grade
Basis:
other: 6 animals
Time point:
other: Day 1
Score:
31
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
other: Eye irritation grade
Basis:
other: 6 animals
Time point:
other: Day 2
Score:
21
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
other: Eye irritation grade
Basis:
other: 6 animals
Time point:
other: Day 3
Score:
15
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
other: Eye irritation grade
Basis:
other: 6 animals
Time point:
other: Day 4
Score:
5
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
other: Eye irritation grade
Basis:
other: 6 animals
Time point:
other: Day 7
Score:
1
Max. score:
110
Reversibility:
not reversible
Irritant / corrosive response data:
Eye irritation was observed from Days 1 to 7, however complete reversibility was not observed at the end of observation.
Other effects:
No data.

None

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
Nerol was irritating to eyes of female rabbits.
Executive summary:

In an eye irritation study conducted similarly to OECD Guideline 405, 6 female rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted test item, nerol, in their right eye while the left eye remained untreated and served as control. The eyelids were then gently held together for several seconds to avoid any loss of test item. All eyes were examined at 24, 48 and 72 h and at 4 and 7 days after dosing and graded according to the Draize eye irritation procedure.

Eye irritation was observed from Days 1 to 7, however the complete reversibility was not observed at the end of observation. Eye irritation grade for 6 animals at days 1, 2, 3, 4 and 7 were 31, 21, 15, 5 and 1, respectively. Therefore, nerol is an eye irritant on female rabbits.

 

Therefore, as a conservative approach and as signs of irritation are not fully reversible at Day 7, nerol is classified as irritating to eyes according to Directive 67/548/EEC and nerol is classified in Category 2A according to CLP Regulation (EC) N° 1272 /2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a primary dermal irritation study performed according to OECD Guideline 404 and in compliance with GLP, three New Zealand White rabbits were dermally exposed to 0.5 mL of nerol under a semi-occlusive dressing for 4 h. After removal of the residual test item, irritation was scored as outlined in the OECD Guideline 404 at 1, 24, 48 and 72 h and 7 days after exposure. Very slight erythema was noted at one treated skin site one hour after removal of the patches. The irritation increased and very slight to well-defined erythema with or without very slight oedema was noted at all treated skin sites at subsequent 24, 48 and 72 h observations. Hyperkeratinisation of the skin was noted at all treated skin sites on Day 7. No corrosive effects were noted. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1.7, 1.7, 2.0 for erythema and 0.7, 0.0, 0.7 for oedema score, respectively.

In an eye irritation study conducted similarly to the OECD Guideline 405, 6 female rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted test item, nerol in their right eye while the left eye remained untreated and served as control. The eyelids were then gently held together for several seconds to avoid any loss of test item. All eyes were examined at 24, 48 and 72 h and at 4 and 7 days after dosing and graded according to the Draize eye irritation procedure. Eye irritation was observed from Days 1 to 7, however the complete reversibility was not observed at the end of observation. Eye irritation grade for 6 animals at days 1, 2, 3, 4 and 7 were 31, 21, 15, 5 and 1, respectively. In this study, test item is an eye irritant on female rabbits. Under the test conditions, nerol is irritating to eyes of female rabbits.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available for this endpoint.

Justification for selection of eye irritation endpoint:
Only one study available for this endpoint.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

In an acute dermal toxicity study performed on rabbits with nerol, slight to moderate erythema and edema were noticed throughout the observation period (up to 7 days). Nerol induced an hyperkeratinisation of the skin on Day 7. Based on the absence of information on the reversibility of this effect, nerol is classified as irritating to skin according to Directive 67/548/EEC and nerol is classified in Category 2 according to CLP Regulation (EC) N° 1272/2008.

In an eye irritation study, nerol induced signs of ocular irritation in rabbits. However, the scale of score does not allow to compare these results with the classification criteria of Directive 67/548/EEC and CLP Regulation (EC) N° 1272 /2008. Therefore, as a conservative approach and as signs of irritation are not fully reversible at Day 7, nerol is classified as irritating to eyes according to Directive 67/548/EEC and nerol is classified in Category 2A according to CLP Regulation (EC) N° 1272 /2008.