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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:
12/04/1983 - 05/06/1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study not performed according to a guideline or GLP, but results are acceptable as basic data.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A study was conducted to investigate the irritation effects of Peppermint Flavour – Brazilian when applied once to intact skin under a semi-occlusive dressing. A 4-hour semi-occlusive patch test was conducted on 8 New Zealand white rabbits, 9 - 12 weeks old. The dorsal region was clipped 3-4 days before the beginning of the study. A 0.5 ml aliquot of the undiluted test material and appropriate control standards were applied to gauze pads attached to strips of adhesive tape. The patches were placed on the clipped dorsum of animals, and the animals were then immobilized in body sleeves for 4 hours. After removal of the patches, the sites were wiped clean of the excess test material. Reactions were graded at 4, 24, 48 and 72 hours after patch removal. The sites are scored for erythema, oedema, cracking and scaling and any other feature using an 8-point anchored ordinate scale ranging from "a" (very slight) to "h" (severe). At the end of the test the irritation reaction produced by each test material at 2 and 72 hours after treatment is assigned an overall irritation score. In addition, the overall irritation scores for all treatment sites/group and the total irritation score/group were recorded.
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Peppermint brazilian triple rectified
IUPAC Name:
Peppermint brazilian triple rectified
Constituent 2
Reference substance name:
Peppermint Flavour - Brazilian
IUPAC Name:
Peppermint Flavour - Brazilian
Constituent 3
Reference substance name:
Peppermint oil
IUPAC Name:
Peppermint oil
Details on test material:
- Name of test material (as cited in study report): Peppermint Flavour - Brazilian
- Physical state: Liquid
- Analytical purity: No data
- Lot/batch No.: Confidential
- Stability under test conditions: stable
- Storage condition of test material: refrigarator

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 9 - 12 weeks

ENVIRONMENTAL CONDITIONS: no data

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 100 % (undiluted)

CONTROLS:
- Diethyl Phthalate and Geraniol were used as standards for comparison.
Duration of treatment / exposure:
4 hours
Observation period:
0, 24, 48, and 72 hours after treatment, and occasionally up to 7 days after treatment.
Number of animals:
8 (1 rabbit killed at 24 hours due to broken back)
Details on study design:
TEST SITE
- Area of exposure: the dorsal region
- Type of wrap if used: Patches were prepared by attaching flexible polythene (3cm x 3cm) to zinc oxide plaster (9cm x 2.5cm). Cotton guaze (2.5cm2) was laid on the polythene. 0.5 ml of test solution was applied to the dry patch. Animals were immobilised in a canvas body sleeve for 4 hours after application of the patch.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After removal of the patches, the sites were wiped clean of the excess test material.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
a (marginal/very slight)
b (slight)
c (fairly distinct)
d (quite distinct)
e (becoming well developed)
f (well developed)
g (becoming severe)
h (severe)

Overall irritation scores were assigned based on the following grading scale:
0 – Normal skin
1 – Marginal (grade a)
2 – Slight (grades up to bbbb at 24 and 72h)
3 – Slight/moderate (grades ca-cc at 24h and reduced to slight at 72h)
4 – Moderate (grades c and d at 24h, at least slight/moderate at 72h)
5 – Strong (as moderate but evidence of ¼ of site affected by necrosis)
6 – Severe (most of site affected by necrosis)
7 – Extreme (deep necrosis over whole site)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Mean scores were derived after conversion
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Mean scores were derived after conversion
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
1.8
Max. score:
4
Reversibility:
no data
Remarks:
after 72 hours
Remarks on result:
other: Mean scores were derived after conversion
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Mean scores were derived after conversion
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Mean scores were derived after conversion
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
1.8
Max. score:
4
Reversibility:
no data
Remarks:
after 72 hours
Remarks on result:
other: Mean scores were derived after conversion
Irritant / corrosive response data:
Peppermint Flavour - Brazilian showed mainly slight/moderate effects with one site showing pale brown tissue 24 and 72 hours after treatment. This response is similar to the control Geraniol.
Other effects:
Not applicable

Any other information on results incl. tables

Result expressed as overall irritation score for each animal as reported in the study:

Animal number

265

272

288

291*

311

313

317

322

Total irritation score per group

Group

 

 

 

 

 

 

 

 

 

Diethyl Phtalate

1

1

1

-

1

1

1

0

6

Geraniol

3

3

3

-

2

4

4

3

22

Peppermint Flavour - Brazilian

3

3

4

-

2

4

3

5

24

* rabbit 291 killed at 24h due to broken back

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Peppermint Flavour - Brazilian showed mainly slight/moderate effects with one site showing pale brown tissue 24 and 72 hours after treatment. This response is similar to the control Geraniol. However Geraniol showed no evidence of necrosis. In order to classify the test substance in accordance with EU classification, the irritation scoring from "a" to "h", as reported in the study, is converted to the grading of skin reactions as defined by OECD Guideline 404. The mean scores calculated from the numerical values given to the skin irritation observed at the 24, 48, and 72 hour examinations were 1.6, 1.6, and 1.8 resp., for erythema and also for oedema. Based on these conversed scores and according to EU criteria Peppermint Flavour - Brazilian was considered not irritating and the test substance does not have to be classified according to the classification criteria outlined in 67/548/EEC and 1272/2008.
Executive summary:

A study was conducted to investigate the irritation effects of Peppermint Flavour - Brazilian when applied once to intact skin under a semi-occlusive dressing. A 4-hour semi-occlusive patch test was conducted on 8 New Zealand white rabbits. The test material and 2 control substances (Diethyl Phthalate and Geraniol), were applied undiluted to the clipped dorsum of the 8 rabbits. Reaction grades for erythema, oedema, cracking and scaling were assessed 4, 24, 48, and 72 hours after treatment by using grades ranging from "a"(very slight) to "h"(severe). An overall irritation score was assigned to each tested substance ranging from 0 (normal skin) to 7 (extreme). Peppermint Flavour - Brazilian showed mainly slight/moderate effects with one site showing pale brown tissue 24 and 72 hours after treatment. This response is similar to the control Geraniol. However Geraniol showed no evidence of necrosis. In order to classify the test substance in accordance with EU classification, the irritation scoring from "a" to "h" as reported in this study, is converted to the grading of skin reactions as defined by OECD Guideline 404. The mean scores calculated from the numerical values given to the skin irritation observed at the 24, 48, and 72 hour examinations were 1.6, 1.6, and 1.8 resp. for erythema, and also for oedema. Based on these conversed scores and according to EU criteria Peppermint Flavour - Brazilian was considered not irritating and the test substance does not have to be classified according to the classification criteria outlined in 67/548/EEC and 1272/2008.

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