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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
01/07/1994 - 01/25/1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report similar or equivalent to OECD 404. GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: low viscosity liquid hydrocarbon
Details on test material:
- Name of test material (as cited in study report): API 91-01 unleaded gasoline
- Physical state: clear pink liquid
- Storage condition of test material: stored at room temperature in a brown glass jar with a brown plastic screw top

- Name of test material (as cited in study report): API PS-6
- Physical state: clear yellow liquid
- Storage condition of test material: stored at room temperature in a metal canister with a blue plastic lid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Myrtle's Rabbitry Inc. 4678 Bethesda Rd. Thompson Station, TN 37179
- Housing: Individually housed in wire mesh suspension cages
- Diet (e.g. ad libitum): Purina laboratory rabbit chow
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 day


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
The application sites for each rabbit were observed and scored 1/2 - 1, 24, 48, and 72 hours and at 7 and 14 days after removal of the patches.
Number of animals:
A total of four groups of six rabbits (three males and three females per group) were used in this study. The group were divided into two groups per test material, each test material having a semi-occluded group and an occluded group.
Details on study design:
TEST SITE
- Type of wrap if used: Two Webril pads, which were removed from the adhesive, and placed on top of each other. The pads were held in place by adhesive tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test sites were wiped free of residual test material by a gentle sponging using a paper towel moistened with tap water.
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize system

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
6 animals
Time point:
24 h
Score:
ca. 2.33
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API 91-01
Irritation parameter:
erythema score
Basis:
mean
Remarks:
6 animals
Time point:
48 h
Score:
ca. 2.67
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API 91-01
Irritation parameter:
erythema score
Basis:
mean
Remarks:
6 animals
Time point:
72 h
Score:
ca. 2.67
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API 91-01; 3/6 - edges of site appeared coriaceus
Irritation parameter:
erythema score
Basis:
mean
Remarks:
6 animals
Time point:
other: Day 7
Score:
ca. 0.83
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API 91-01; 6/6 - desquamation on site
Irritation parameter:
erythema score
Basis:
mean
Remarks:
24/48/72 h average
Time point:
other: 24/48/72
Score:
ca. 2.56
Max. score:
2.67
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API 91-01
Irritation parameter:
edema score
Basis:
mean
Remarks:
6 animals
Time point:
24 h
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API 91-01
Irritation parameter:
edema score
Basis:
mean
Remarks:
6 animals
Time point:
48 h
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API 91-01
Irritation parameter:
edema score
Basis:
mean
Remarks:
6 animals
Time point:
72 h
Score:
ca. 1.67
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API 91-01
Irritation parameter:
edema score
Basis:
mean
Remarks:
6 animals
Time point:
other: Day 7
Score:
ca. 0.5
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API 91-01
Irritation parameter:
edema score
Basis:
mean
Remarks:
24/48/72 h average
Time point:
other: 24/48/72
Score:
ca. 1.89
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API 91-01
Irritation parameter:
erythema score
Basis:
mean
Remarks:
6 animals
Time point:
other: 24 hr
Score:
ca. 2.5
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API PS-6
Irritation parameter:
erythema score
Basis:
mean
Remarks:
6 animals
Time point:
other: 48 hr
Score:
ca. 2.5
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API PS-6
Irritation parameter:
erythema score
Basis:
mean
Remarks:
6 animals
Time point:
other: 72 hr
Score:
ca. 2.17
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API PS-6
Irritation parameter:
erythema score
Basis:
mean
Remarks:
6 animals
Time point:
other: Day 7
Score:
ca. 0.5
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API PS-6; 5/6 - desquamation on site
Irritation parameter:
erythema score
Basis:
mean
Remarks:
24/48/72 hr average
Time point:
other: 24/48/72
Score:
ca. 2.39
Max. score:
2.5
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API PS-6
Irritation parameter:
edema score
Basis:
mean
Remarks:
6 animals
Time point:
other: 24 hr
Score:
ca. 1.67
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API PS-6
Irritation parameter:
edema score
Basis:
mean
Remarks:
6 animals
Time point:
other: 48 hr
Score:
ca. 1.5
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API PS-6
Irritation parameter:
edema score
Basis:
mean
Remarks:
6 animals
Time point:
other: 72 hr
Score:
ca. 1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API PS-6
Irritation parameter:
edema score
Basis:
mean
Remarks:
6 animals
Time point:
other: Day 7
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API PS-6
Irritation parameter:
edema score
Basis:
mean
Remarks:
24/48/72 h average
Time point:
other: 24/48/72
Score:
ca. 1.39
Max. score:
1.67
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: API PS-6
Other effects:
In addition to the semi-occluded study, each test material was administered to a two groups of six rabbits via occlusive patches. Each animals received a 0.5 ml quantity of the appropriate undiluted test material onto a 1" x 1" guaze square. The patches were then held in place with adhesive tape. The test material was applied in this manner to one intact skin site per animal. After application of the patch, the trunk of each rabbit was wrapped with rubber dental dam which was secured with staples. An outer layer of gauze was then wrapped around the trunk of each animals and secured with tape. Following 4 hours of exposure, the patches were removed and the test sites were wiped free of residual test material in the same manner as the semi-occluded study. The erythema scores for API 91-01 at 24, 48, and 72 h were 2.67, 2.50, and 2.00, respectively. The edema scores at 24, 48, and 72h were 2.83, 2.33, and 2.00, respectively. The erythema scores for API PS-6 at 24, 48, and 72h were 2.33, 2.33, and 2.17, respectively. The edema scores at 24, 48, and 72h were 2.83, 2.33, and 2.17, respectively. The mean erythema and edema scores for API 91-01 were 2.39 and 2.39. The mean erythema and edema scores for API PS-6 were 2.28 and 2.44.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The mean erythema and edema scores for API 91-01 were 2.56 and 1.89, respectively. The mean erythema and edema score for API PS-6 were 2.39 and 1.39, respectively. This finding warrants classification of API 91-01 and API PS-6 as irritating under Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) and as an R38 skin irritant under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

Unleaded gasoline samples API 91-01 and API PS-6 were both administered via semi-occlusive patch for four hours to two groups of 6 New Zealand White rabbits (one group per test material) to assess dermal irritation. Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing and on Days 7, 10, and 14 according to the Draize method of scoring. Animals administered API 91-01 exhibited moderate to severe erythema (grade 3) at the 24h, 48h and 72h observation point. The erythema was fully reversible within 14 days. In the same group, maximum edema was noted in the 1st hour of observation and fluctuated with severity from slight (grade 2, 24 h) to very slight and no edema (grade 0/1, day 7); all animals were clear of edema by Day 14. Animals administered API PS-6 exhibited moderate erythema (grade 2) at the 24h, 48h, and 72 h observation point. The erythema was fullly reversible within 14 days. Maximum edema was observed 1h after removal of the patch and irritation due to edema subsided and was clear by Day 14 of the observation period. The mean erythema and edema scores for API 91-01 were 2.56 and 1.89, respectively. The mean erythema and edema score for API PS-6 were 2.39 and 1.39, respectively. This finding warrants classification of API 91-01 and API PS-6 as irritating under Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) and as an R38 skin irritant under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.