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Diss Factsheets

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:
The study was conducted in 1984.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Animals are not observed during 14 days
Principles of method if other than guideline:
Primary irritation to the skin is measured by a patch-test technique on the clipped dorsum of albino rabbits under semi-occlusive conditions.
GLP compliance:
no
Remarks:
The study pre-dates GLP.

Test material

Constituent 1
Reference substance name:
Isocyclocitral - PM 896
IUPAC Name:
Isocyclocitral - PM 896
Test material form:
other: liquid
Details on test material:
- Name of test material: Isocyclocitral

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
The rabbits are housed individually in suspended cages with wire mesh floors. They have free acces to tap water and pelleted rabbit diet with vitamin and mineral suppléments.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
0.5 mL undiluated
Duration of treatment / exposure:
Patches applied for 4 hours.
Observation period:
assessments after 4, 24, 48 and 72 hours
Number of animals:
8 rabbits for test
Details on study design:
Protocol for Rabbit Single Application Covered Patch Skin Irritation Test.
The following is an outline description of how to carry out this skin irritation test. The precise details of how to carry out each operation are described in the skin irritaiton Standard Operation procedure SOP 12 held in the skin irritation area.

Experimental design - The test is designed to investigate the irritant effects of a single application of substance to skin under semi-occlusive conditions which enhance penetration and interaction of the test materials and the skin. The irritancy of test substances is normally compared with that of standard substances applied in the same way.

Animals - Eight healthy adult New Zealand White, brought from a commercial supplier, are used for testing when the hair is in a non-growth (telogen) phase of the hair cycle. Three to 4 days prior to testing the backs and flanks of 9 to 12 week old rabbits are clipped to identify those which are in telogen and which have no skin blemishes. Of these rabbits, 8 are selected for the test. The hair is given a final clip approximately 2 hours prior to treatment.

Patches - Each patch consists of a 25 x 25 mm, 16-ply gauze pad backed by a 20 x 20 mm strips of thin polythene and stuck to a 25 x 75 mm strip of zinc oxide plaster.

Treatment - Each substance is applied to every rabbit in the test: up to 6 patches can be applied to each rabbit. Prior to treatment a plan (based on random number sequences) is prepared of application sites of each substance on each rabbit. The concentration and quantities of substances and the nature of the application is specified in the protocol summary, and is detailed in the summary page and in table 1 of the report. When all patches have been applied to a rabbit it is immobilised in a canvas body sleeve and placed in a quiet place for the 4 hour aplication period, at the end , of which the animals are removed from the body sleeves and the corners of each treatment site marked. The patches are then removed and excess substance wiped from the skin with a damp tissue.

Assessment of Irritiation - The skin treatment sites are assessed for irritation immediately after removal of the patches and at 24, 48 and 72 hours after treatment. Each animal is scored blind; the scores are not linked to the substances tested until all assessments in the test have been carried out. Reactions are 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 are described and recorded as a fraction of treated area.

Evaluation of skin 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 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 erytheme and oedema being maintained at least 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 - Most of site affected by suspected necrosis.
7 - Extreme - Deep necrosis over whole site identified by depressed, hard scab/tissue and surrounding inflammatory reaction.

Summary and Analysis of Macroscopic Results:
At the end of the test the irritation reaction produced by each test material at 24 and 72 hours after treatment is assigned a single overall irritation score which is recorded along with the irritation scores on Table III a, b, et seq. (For full details of overall irritation scores see Appendix 1). The overall irritation scores for all treatment sites per group and the total irritation score per group are recorded in Table II (a).


Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 4/24/48/72 hours
Score:
3
Max. score:
7
Reversibility:
not fully reversible within: 72 hours.
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
other: 4/24/48/72 hours
Score:
6
Max. score:
7
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of severe irritation
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
other: 4/24/48/72 hours
Score:
6
Max. score:
7
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of severe irritation
Irritation parameter:
overall irritation score
Basis:
animal #4
Time point:
other: 4/24/48/72 hours
Score:
4
Max. score:
7
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of moderate irritation
Irritation parameter:
overall irritation score
Basis:
animal #5
Time point:
other: 4/24/48/72 hours
Score:
6
Max. score:
7
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of severe irritation
Irritation parameter:
overall irritation score
Basis:
animal #6
Time point:
other: 4/24/48/72 hours
Score:
4
Max. score:
7
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of moderate irritation
Irritation parameter:
overall irritation score
Basis:
animal: #7
Time point:
other: 4/24/48/72 hours
Score:
3
Max. score:
7
Reversibility:
not fully reversible within: 72 hours.
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal: #8
Time point:
other: 4/24/48/72 hours
Score:
3
Max. score:
7
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.6
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.3
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.3
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3.6
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3.3
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
erythema score
Basis:
animal: #7
Time point:
24/48/72 h
Score:
3
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
erythema score
Basis:
animal: #8
Time point:
24/48/72 h
Score:
2.6
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
edema score
Basis:
animal: #7
Time point:
24/48/72 h
Score:
2
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritation parameter:
edema score
Basis:
animal: #8
Time point:
24/48/72 h
Score:
1.6
Max. score:
8
Reversibility:
not fully reversible within: 72h
Remarks on result:
other: the result is done by overall irritation score
Irritant / corrosive response data:
Isocyclocitral - PM 896 showed slight/moderate effects with one animal showing pale brown tissue 24 hours after treatment. By 72 hours showed a variable slight/moderate to moderate response with three animals showing brown tissue. This response is very similar to the control Geraniol. The control Diethyl Phthalate showed the least effects with a minimal response 24 hours after treatment and no effects 72 hours after treatment.

Any other information on results incl. tables


In the study the scale for the evaluation of erythema and  oedema is:

-: no reaction

a: marginal (very slight)

b: slight

c: fairly distinct

d: quite distinct

e: becoming well developed

f: well develiped

g: becoming severe

h: severe

For the IUCLID completion need this scale has been transposed into numerical values (0= no reaction, 8=severe

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Isocyclocitral - PM 896 is slight/moderately irritant with evidence of necrosis. This response is similar to the control Geraniol. The control Diethyl Phthalate shows the least effects and is virtually non-ittitant.
Executive summary:

Isocyclocitral - PM 896 is slight/moderately irritant with evidence of necrosis. This response is similar to the control Geraniol. The control Diethyl Phthalate shows the least effects and is virtually non-irritant.