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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:
13 August 1979 to 01 October 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A non-GLP study performed to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
A 0.5 mL aliquot of the 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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid (undefined)
Details on test material:
- Name of test material (as cited in study report): phenoxyethyl iso butyrate
- Physical state: Clear liquid.

Test animals

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

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
8
Details on study design:
TEST SITE
- Area of exposure: Rabbits were exposed on their dorsum, the specific treatment site were randomised. The whole dorsal surface was clipped 3-4 days before exposure. Only animals in the telogen phase of hair growth were selected.
- Type of wrap if used: Occlusive patches were prepared by attaching a piece of thin flexible polythene (3 cm x 3 cm) to a piece of zinc oxide plaster 9 cm x 2.5 cm. A 2.5 cm square of cotton gauze (8 ply folded in two) was laid on the polythene such that the edges of the pad were attached to the zinc oxide plaster. The test material was applied to the dry patch. The patches were firmly attached to ensure good contact between the skin and the test material. During exposure, the animals were immobilised in a canvas body sleeve.

REMOVAL OF TEST SUBSTANCE
- Washing: The test site was wiped clean of excess test material.
- Time after start of exposure: 4 hours, immediately after patch removal.

REFERENCE STANDARDS
- Diethyl phthalate
- Cyclamen aldehyde
- Geraniol
These standards are perfumery materials that are regularly used as marker controls in skin irritation tests.
All three standards were applied to each of the test rabbits, alongside the test material. Application sites were randomised on the different animals.

SCORING SYSTEM: The skin sites were assessed for irritation immediately after treatment, and at 24, 48 and 72 hours. Each animal was scored blind and the scores for each skin site were not linked to the material tested until the scoring at 72 hours was completed. The sites were scored for erythema, edema, cracking and scaling and any other feature using an 8-point anchored ordinate scale ranging from "a" (very slight) to "h" (severe) see Table 1. At the end of the test the reaction grades for each treatment group were converted to numerical scores which were used to calculate the total irritation score per site.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
0.5
Max. score:
12
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
0.25
Max. score:
12
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
0.375
Max. score:
12
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours
Score:
0.375
Max. score:
12
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
0.375
Max. score:
12
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
0.25
Max. score:
12
Reversibility:
not fully reversible within: 72 hours
Irritant / corrosive response data:
A single application of test material produced marginal erythema in some animals and marginal edema in a few animals at 24 hours. By 48 hours and 72 hours there was marginal erythema and edema in a few animals. The response was broadly similar to that produced by the control, diethyl phthalate, but considerably less than that produced by the controls, cyclamen aldehyde and geraniol. Total irritation scores of the test material and standards for comparison are given in Table 2, where Table 3 shows the macroscopic findings.

Any other information on results incl. tables

Table 2: Total Irritation Scores

Rabbit No. Irritation scores
Diethyl Phthalate Test Material Cyclamen Aldehyde Geraniol
1216 0 0 23 32
1217 3 5 31 34
1218 2 3 30 28
1219 4 2 26 26
1220 4 3 35 22
1221 2 0 31 34
1224 2 6 27 38
1244 2 9 41 30
         
Overall irritation score 19 28 244 244
Mean score per site 2.38 4.0 30.5 30.5
Mean score per site per day 0.59 1.0 7.63 7.63
Mean irritation ranking 1.44 1.56 3.44 3.56

Table 3. Macroscopic Findings For Sites Exposed to the Test Material

Rabbit No. 4 Hours 24 Hours 48 Hours 72 Hours Totals Total Score
Erythema Edema Erythema Edema Erythema Edema Erythema Edema Erythema Edema
1216 0 0 0 0 0 0 0 0 0 0 0
1217 1 1 1 0 1 0 1 0 4 1 5
1218 1 1 1 0 0 0 0 0 2 1 3
1219 1 1 0 0 0 0 0 0 1 1 2
1220 1 2 0 0 0 0 0 0 1 2 3
1221 0 0 0 0 0 0 0 0 0 0 0
1224 0 0 1 1 1 1 1 1 3 3 6
2244 1 1 1 1 1 2 1 1 4 5 9

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test material elicited only very minor reactions in a few of the animals during the course of the study. The test material was concluded to be very slightly irritating. The persistency of this slight irritation continued until termination at 72 hours, no further observations were made.
Executive summary:

The skin irritation potential of the test material was investigated according to a methodology similar to that of OECD 404. During the study 0.5 mL of the undiluted test material was applied to the clipped dorsum of 8 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.

During the course of the study a single application of test material was seen to produce ‘marginal’ erythema and ‘slight’ edema in five out of eight animals at 24 hours. By 48 hours and 72 hours ‘marginal’ erythema and edema was observed in between two and four out of eight animals. The scores assigned in this study are roughly equivalent to a score of 1 according to the Draize scale (1977).

The response was broadly similar to that produced by the control, diethyl phthalate, but considerably less than that produced by the positive controls, cyclamen aldehyde and geraniol.

Under the conditions of the study, the test material was considered to be slightly irritating; however the elicited reaction was below the limits of classification.