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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:
18 February 1985 to 09 May 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
0.5 mL of test material was applied to the clipped dorsum of rabbits for 4 hours under a semi-occlusive patch. The irritation reactions were assessed immediately after removal of the patch and after 24, 48 and 72 hours.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
3a,4,5,6,7,7a-hexahydro-5-methoxy-4,7-methano-1H-indene
EC Number:
258-296-4
EC Name:
3a,4,5,6,7,7a-hexahydro-5-methoxy-4,7-methano-1H-indene
Cas Number:
53018-24-9
Molecular formula:
C11H16O
IUPAC Name:
3a,4,5,6,7,7a-hexahydro-5-methoxy-4,7-methano-1H-indene
Test material form:
liquid
Details on test material:
- Appearance: colourless, clear liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: commercial supplier
- Age at study initiation: 9 - 12 weeks old
- Housing: rabbits were housed individually in suspended cages with wire mesh floors
- Diet: pelleted rabbit diet with vitamin and mineral supplements ad libitum
- Water: ad libitum
- Animals are used for testing when the hair is in a non-growth (telogen) phase of the hair cycle.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: undiluted
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
8
Details on study design:
TEST SITE
- Three to 4 days prior to testing the backs and flanks of the rabbits were clipped to identify those which were in telogen and which had no skin blemishes. Of these rabbits, 8 were selected for the test. The hair is given a final clip approximately 2 hours prior to treatment.
- Type of wrap if used: Each patch consisted of a 25 x 25 mm, 16-ply gauze pad backed by a 20 x 30 mm strips of thin polythene and stuck to a 25 x 75 mm strip of zinc oxide plaster.
- When all patches had been applied to a rabbit it was immobilised in a canvas body sleeve and placed in a quiet place for the 4 hour application period, at the end, of which the animals were removed from the body sleeves and the corners of each treatment site marked.

REMOVAL OF TEST SUBSTANCE
- The patches were removed and excess substance wiped from the skin with a damp tissue.

OBSERVATION TIME POINTS
- The skin treatment sites were assessed for irritation immediately after removal of the patches and at 24, 48 and 72 hours after treatment.

SCORING SYSTEM:
- Each animal was scored blind. Reactions were assessed for erythema, oedema, cracking and scaling on a 9-point scale ranging from very slight (a) to severe (h). Any other features of the responses were described and recorded as a fraction of treated area.
- Reaction grades:
- = no reaction: normal skin
a = marginal (very slight)
b = slight
c = fairly distinct:
d = quite distinct
e = becoming well developed
f = well developed
g = becoming severe
h = severe
- At the end of the test the irritation reaction produced by each test material at 24 and 72 hours after treatment was assigned a single overall irritation score which was recorded along with the irritation scores. This allowed for comparisons of responses within and between experimental groups. The effects of the test and control materials were compared along with any important or unusual features of the test.

- Overall irritation scores
0 = NORMAL SKIN
1 = MARGINAL: Slight erythema and oedema (grade a) at 24 hours but no effects observed at 72 hours.
2 = SLIGHT: Slight erythema and oedema (grades up to bbbb) at 24 and 72 hours.
3 = SLIGHT/MODERATE: Slight/moderate erythema and oedema (grades ca-cc) at 24 hours. The reaction generally reduces to slight at 72 hours but sometimes the slight/moderate reaction may be maintained.
4 = MODERATE: Moderate erythema and oedema (grades c and d) with slight cracking and scaling at 24 hours with the erythema and oedema being maintained at least at slight/moderate level with cracking and scaling developing at 72 hours.
5 = STRONG: As for 4 above or greater erythema and oedema with evidence of up to 1/4 of the site affected by necrosis.
6 = SEVERE: Moat of site affected by suspected necrosis.
7 = EXTREME: Deep necrosis over whole site identified by depressed, hard scab/tissue and surrounding inflammatory reaction.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
7
Reversibility:
not specified
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
7
Reversibility:
not specified
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
24/48/72 h
Score:
5
Max. score:
7
Reversibility:
not specified
Irritation parameter:
overall irritation score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
7
Reversibility:
not specified
Irritation parameter:
overall irritation score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
7
Reversibility:
not specified
Irritation parameter:
overall irritation score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
7
Reversibility:
not specified
Irritation parameter:
overall irritation score
Basis:
animal: #7
Time point:
24/48/72 h
Score:
4
Max. score:
7
Reversibility:
not specified
Irritation parameter:
overall irritation score
Basis:
animal: #8
Time point:
24/48/72 h
Score:
6
Max. score:
7
Reversibility:
not specified
Irritant / corrosive response data:
The test material produced distinct erythema and oedema at 4 hours which intensified slightly to show variable but generally slight/moderate effects at 72 hours. Two animals developed extensive areas of brown tissue.

Any other information on results incl. tables

Table 1: Daily Assessment of Irritation Reactions

Rabbit No.

4 Hours

24 Hours

48 Hours

72 Hours

er

oe

cr

sc

er

oe

cr

sc

er

oe

cr

sc

er

oe

cr

sc

1

d

c

-

-

d

b

a

a

c

b

b

a

c

b

b

b

2

d

b

-

-

d

c

-

-

c

b

-

-

b

a

-

-

3

b

a

-

-

d

c

-

-*

c

c

-

-*

e

b

a

a*

4

d

c

-

-

d

c

-

-

d

b

a

a

c

b

b

a

5

c

b

-

-

b

a

-

-

b

a

-

-

b

a

-

-

6

d

b

-

-

c

b

-

-

b

a

a

a

b

a

a

a

7

b

a

-

-

d

c

-

-

c

b

a

a

c

b

b

a

8

c

b

-

-

d

b

-

-*

d

b

-

-*

d

c

a

a*

er = erythema

oe = oedema

cr = cracking

sc = scaling

* Macroscopic reactions:

24 Hours:

Rabbit 1: 10 x 10 mm green/brown tissue

Rabbit 8: Whole area pale brown tissue

48 Hours:

Rabbit 1: 10 x 10 mm green/brown tissue

Rabbit 8: Whole area pale brown tissue

72 Hours:

Rabbit 1: 10 x 10 mm green/brown tissue

Rabbit 8: Whole area pale brown tissue

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study the test material was considered to be moderately irritating.
Executive summary:

The skin irritation potential of the test material was investigated in a patch test.

The test was performed using 8 New Zealand White rabbits, 0.5 mL of undiluted test material was applied to the clipped dorsum of the rabbits for 4 hours under a semi-occlusive patch. The irritation reactions were assessed immediately after removal of the patch and after 24, 48 and 72 hours.

The test material produced distinct erythema and oedema at 4 hours which intensified slightly to show variable but generally slight/moderate effects 72 hours after treatment. Two animals developed extensive areas of brown tissue.

Under the conditions of this study the test material was considered to be moderately irritating.