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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Remarks:
Toxi-Coop Zrt., Pálya u. 2., 2120 Dunakeszi, Hungary

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Petol PM 410-4N
- Physical state: yellow-brown (apparently yellow), viscous, clear liquid
- Storage condition of test material: Store in tightly closed container, in a dry and well ventilated area, between 20-30°C.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: S & K LAP Kft. 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: adult rabbits
- Weight at study initiation: 2707-2928 g
- Housing: Individually in metal cages.
- Diet: Rabbit fattening mixed diet produced by YAQ-TÁP Kft., Nyíregyháza (Tokaji út 22), Hungary, ad libitum.
- Water: Tap water from watering bottles ad libitum.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3
- Humidity: 30-70
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3 (males)
Details on study design:
TESTING PROCEDURE:
Three male animals in acceptable health condition were selected for this test. Each animal was examined 24 hours before starting the test. Approximately 24 hours prior to the test the hair was clipped from the back and flanks of the animals. The test item was applied to an approximately 6 cm² area of intact skin. Sterile gauze pads (10x10cm) were placed on the skin of rabbits. These gauze patches were kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The entire trunks of the animals were wrapped with plastic wrap for 4 hours. 4 hours after the application the rest of the test item was removed using body temperature water. In the first step an initial test was performed using one animal. One hour after application of the test item to the sentinel animal, the application site was examined. Severe irritation or corrosive effect could not be found in the initial test, therefore the bandage was replaced and the exposure continued for a further 3 hours (a total 4 hours exposure). Two additional animals were involved for this study.

CLINICAL OBSERVATIONS AND EVALUATION OF SKIN IRRITATION:
- Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes, 24, 48, 72 hours then at 1 and 2 weeks after the patch removal. At the end of the observation period the animals were humanely sacrificed.
- The body weights were recorded at the beginning and at the end of the experiment.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
2.66
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
all test animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
- 1 hour after the patch removal very slight erythema (score 1) occurred in all animals. Oedema was not observed in animals during the study.
- 24 hours after the patch removal moderate to severe erythema (score 3) was recorded in all animals.
- 48 hours after the patch removal moderate to severe erythema (score 3) was detected in two animals (No.: 01319, 01349) and very slight erythema (score 1) was observed in animal No.: 01348.
- 72 hours after the patch removal well defined erythema (score 2) was recorded in animal No.: 01319, very slight erythema (score 1) was detected in animal No.: 01348 and moderate to severe erythema (score 3) was observed in animal No.: 01349.
- 1 week after the patch removal very slight erythema (score 1) was detected in animal No.: 01319 and well defined erythema (score 2) was recorded in animal No.: 01349. However, other irritation signs occurred in animals. Crusting was observed in all animals and desquamation was detected in two animals (No.: 01319, 01349).
- 2 weeks after the patch removal all animals became free of irritation symptoms.
Other effects:
During the study the behaviour and general state of animals were normal. There were no notable body weight changes during the contact and observation period.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is, in a GLP compliant OECD 404 guideline study, considered to be irritating to the skin.
Executive summary:

In a GLP compliant acute skin irritation study performed according to OECD guideline 404, the irritating potential of Petol PM 410-4N was investigated. Three male new Zealand White rabbits were treated once with 0.5 mL pure test substance. Approximately 24 hours prior to the test the hair was clipped from the back and flanks of the animals. The test item was applied under occlusive conditions to the skin for 4 hours. After 4 hours the rest of the test item was removed with water at body temperature. Animals were examined for signs of erythema and oedema, and the responses scored at 1, 24, 48, 72 hours and at 1 and 2 weeks after the patch removal. Test item caused slight to severe skin irritant (erythema) effects, fully reversible within 2 weeks. The animals’ individual mean scores (average of the readings at 24, 48 and 72 hours after patch removal) were 2.66, 1.66, and 3.00. No edema was observed at any time point. After one week crusting and desquamation were observed which was no longer observed at the final observation time 14 days after treatment. During the study the behaviour and general state of animals were normal. There were no notable body weight changes during the contact and observation period. Based on the results of the study, the test substance is considered to be irritating to the skin.