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Toxicological information

Skin irritation / corrosion

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Administrative data

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.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Name of test material (as cited in study report): NEROL 900A 575700 998
Physical state: colourless liquid

Test animals

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

Test system

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

Results and discussion

In vivo

Resultsopen allclose all
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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.