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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:
June to Oct 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Lot no: 151105Purity - 101.39%

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
New Zealand White rabbits were obtained from Harlan UK Ltd., Biccster (Hsdif:NZW strain). Rabbit weights were recorded on the day of arrival. Before the first animal could be dosed, the pH of the test article was checked. A 50% w/v dispersion in purified water had a pH of 6. Since this was within the acceptable range of pH 2.0 to 11.5, the study continued.The dermal test site, a 30 x 20 mm area on the closely clipped dorsum of a single New Zealan d White rabbit (the "sentinel"), was dosed with 500 mg of powdered test article (moistened with sufficient water or other suitable vehicle immediately before application). The dose was spread unifonnly over the designated area and then covered by a dense gauze patch (30 x 20 mm) on Day 1. This in turn was covered by a larger gauze patch (40 x 40 mm) and an open weave, elasticated adhesive compression bandage which was wrapped firmly around the torso to secure the applied dose and patch in the correct position. The dressing was considered to be semi-occlusive. The test patch was removed after four hours and the treated skin was lightly brushed clean of any solid residues and swabbed with moist cotton wool. The location of the test site was marked on the dors um with indelible ink after completion of the cleansing process. The condition of the treated skin of the sentinel was assessed for a period of at least three days to ensure the test article did not cause severe dennal changes. Subsequently, two further rabbits were subjected to a single, four-hour, semi-occluded topical application of 500 mg of powdered and moistened test article. The 24-hour observation was not performed on the sentinel animal (animal number 28M). As such it was not possible to calculate the Primary irritation Index or to classify the test article according to the Draize scheme. An additional animal was therefore treated to allow the classification of irritancy to be determined. The condition of the animals was assessed daily throughout the acclimatisation period. The acclimatisation period was 5 to 14 days for animal numbers 28 M, 29M and 30 M and 49 days for animal number 37F. A clinical inspection was performed prior to study commencement to ensure the animals were suitable for the test procedures. Overtly healthy animals were arbitrarily allocated to the study on the day prior to dosing. Each animal was uniquely identified within the room by a number inscribed with indelible ink onto the inner surface of one ear. Information including study number, animal number, sex and the route of administration appearedon a card attached to each cage.Electric clippers were used to remove all hair from an area of the dorsum measuring approximately10 x 8 cm. Only rabbits with dorsal skin showing no pre-existing damage, irritation or multiple areas of active hair growth were accepted onto study.Animals were in a body weight range of2.22 to 2.96 kg on Day-l. Based on infonnation from the supplier the rabbits were approximately 12 to 14 weeks old on Day 1.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Remarks:
moistened
Amount / concentration applied:
500mg
Duration of treatment / exposure:
4h
Observation period:
Test sites examined 1, 24, 48 and 72 hours after patch removal.
Number of animals:
4
Details on study design:
See above under details of test animals and environmental conditions

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
7 d
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test article produced a primary irritation index of 0.0 No corrosive effects were noted. The test article did not meet the criteria for classification as irritant or corrosive according to the EU Commission Regulation (EC) 1272/2008
Executive summary:

This study was conducted to determine the dermal irritation caused to intact rabbit skin following a single

(4 hour) semi-occluded topical application of the test article, Beta Ketosulfide.

 

The test article (500mg) was applied to a 30 x 20 mm area on the closely clipped dorsum of each of three New Zealand White rabbits on Day 1. The treated area of skin was covered by a semi-occlusive bandage for four hours. Dermal reactions to treatment were assessed for up to three days after removal of the dressings.

 

No reactions were observed following a single semi-occluded,topical application of the test article to intact rabbit skin for four hours.

 

The test article produced a primary irritation index of 0.0 and was classified as NON-IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

 

The test article did not meet the criteria for classification as irritant or corrosive according to the EU

Commission Regulation (EC) 1272/2008