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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:
From 1991-07-09 to 1991-07-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 404 and in compliance with GLP with minor deviations (age of animals at study initiation not reported). Except for this minor deviation, the study was fully reliable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
age of animals at study initiation not reported
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
age of animals at study initiation not reported
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP (inspection date: 1990-06-19 / signature date: 1990-10-05)

Test material

Constituent 1
Chemical structure
Reference substance name:
(5E)-3-Methyl-5-cyclopentadecen-1-one
Cas Number:
101151-17-1
Molecular formula:
C16 H28 O
IUPAC Name:
(5E)-3-Methyl-5-cyclopentadecen-1-one
Constituent 2
Chemical structure
Reference substance name:
(5Z)-3-Methyl-5-cyclopentadecen-1-one
Cas Number:
21944-94-5
Molecular formula:
C16 H28 O
IUPAC Name:
(5Z)-3-Methyl-5-cyclopentadecen-1-one
Constituent 3
Chemical structure
Reference substance name:
(4E)-3-Methyl-4-cyclopentadecen-1-one
Cas Number:
62221-84-5
Molecular formula:
C16 H28 O
IUPAC Name:
(4E)-3-Methyl-4-cyclopentadecen-1-one
Test material form:
liquid
Details on test material:
- Physical state: colourless liquid
- Reception date: 1991-06-27
- Storage condition of test material: in the dark at about 4°C
Specific details on test material used for the study:
- Lot/batch No.: A/S/31635 (lab code)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex.
- Age at study initiation: no data
- Weight at study initiation: 2.6-3.0 kg
- Housing: individually in grid bottomed metal cages.
- Diet (e.g. ad libitum): antibiotic free rabbit diet ad libitum (SQC standard rabbits pellets, produced by Special Diets Services, Witham, Essex)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C. On 3 occasions the temperature exceeded this range by 1°C.
- Humidity (%): 59-69 % with the exception of one occasion when a value of 76 % relative humidity was recorded.
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, and 72 hours after patch removal. Additional examination on day 7.
Number of animals:
4 animals
Details on study design:
TEST SITE
- Area of exposure: dorsal surface of the trunk
- % coverage: 2.5 cm square (6.25 cm2)
- Type of wrap if used: surgical lint held in position with "Elastoplast" elastic adhesive bandage 7.5 cm wide.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton wool soaked in warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scale according to OECD guideline No. 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within:
Remarks:
7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
One hour after the end of the dosing period, erythema varying in degree from slight to well defined was apparent in all 4 rabbits and very slight oedema was noted in 2 of the 4 animals.
24 hours after patch removal erythema and oedema were observed in all 4 rabbits.
At the 72 hour assessment, irritation has entirely subsided in 2 animals. Erythema was slight to moderate in the remaining 2 rabbits.
7 days after the dosing, erythema and oedema were no longer apparent in any of the animal although skin thickening was noted in one of them.
Other effects:
none

Any other information on results incl. tables

Table 7.3.1/1: Irritant/corrosive response data at each observation time up to removal of animals from the test

 

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

1 h

2/2/2/1

1/0/1/0

24 h

1/1/1/2

2/1/1/1

48 h

2/1/0/3

1/1/0/1

72 h

3/0/0/3

1/0/0/2

Average 24h, 48h, 72h

2/0.7/0.3/2.7

1.3/0.7/0.3/1.3

Reversibility*)

c

c

Average time (day) for reversion**

7 days

7 days

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

**): correspond to the last day for which skin irritation signs in the last animal were observed

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material induced a slight irritation being largely reversible within 7 days of dosing.
Therefore the test material does not require a classification as irritant to the skin according to the Regulation (EC) No. 1272/2008 (CLP) as scores were below 2.3 and to the GHS as only 2 animals out of 4 had scores between 1.5 and 2.3.
Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted test material was dermally applied on the shaved skin of the dorsal surface of the trunk of 4 New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 7 days for oedema and erythema. 

Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hrs after the removal of the patch and on day 7.

The mean scores over all the animals tested within 3 scoring times (24, 48 and 72 hrs) were 2.0/0.7/0.3/2.7 for erythema and 1.3/0.7/0.3/1.3 for oedema.

Under the test conditions, the test material induced a slight irritation being largely reversible within 7 days of dosing.

Therefore the test material does not require a classification as irritant to the skin according to the Regulation (EC) No. 1272/2008 (CLP) as scores were below 2.3 and to the GHS as only 2 animals out of 4 had scores between 1.5 and 2.3.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

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