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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other: GLP compliant, guideline study, unpublished report available, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Date of receipt: November 25, 1993
Labeled: Sulphur tech
Name of the test substance: Sulfur Technical
Quantitiy: 4340.86 g (gross weight) in a brown, glass bottle
Batch no.: 1089 DLD
Purity: 100% (w/w)
General appearance: yellow powder
Storage conditions: in the dark at room temperature (approx. 20°C)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
Species: SPF bred New Zealand White albino rabbits
Supplier: Charles River Wiga, Sulzfeld, Germany
Sex and age: males or females, young adult
Date of arrival: October 15, 1993
Transferred to test room: December 7, 1993
Date of dosing: December 13, 1993
Acclimatization period: 6 days
Body weight range at start of study: 2969-3557 g
Identification: earmarking: 636-641
Caging: individually in suspended galvanized cages, fitted with wire-mesh floor and front
Diet: standard laboratory rabbit diet and tap water, ad libitum

ENVIRONMENTAL CONDITIONS
Lighting: 12 hours light/12 hours dark cycle
Temperature (7/12-20/12/93): 20 ±3°C
Humidity (7/12-20/12/93): 47.5-72.5%
Ventilation: ca. 10 air changes/hour

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
other: vaseline
Controls:
no
Amount / concentration applied:
0.5 g test substance mixed with 0.5 g vaseline
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
6
Details on study design:
Four days prior to the start of the study, the hair was removed from the back and flanks of the animals using electric clippers in a way as to avoid abrasions. One day and just prior to application of the test material, the skin site was inspected for hair growth. If needed, the clipping was repeated. The study was carried out with six rabbits and each rabbit was treated as follows:
A plastic cup with a diameter of ca 2.5 cm was loaded with ca 1.0 g of the test mixture (0.5 g of the test material and 0.5 g vaseline). Next, a skin site suitable for application of the test substance was selected on the clipped area on the back of the animal. The cup was placed on an intact skin site and fixed to the application site by means of adhesive tape. The entire trunk of the rabbit was wrapped with a self-adhesive-gauze to maintain the cup in position. The gauze was additionally fastened with two strips of tape. After an exposure period of 4 hours, the cup and the material applied were removed. Next, the application site was cleaned with a paper tissue and water, and ca 1 hour later, the resulting skin reactions were evaluated by the method of Draize et al.. Further skin readings were made at approximately 24, 48 and 72 hours, and at 7 days after treatment. The primary irritation index (PII) was calculated by dividing the sum of all skin scores obtained by the number of animals (6) multiplied by the number of observations (4).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 hr
Score:
0.8
Max. score:
4
Remarks on result:
other: mean, 6 animals
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean, 6 animals
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean, 6 animals
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean, 6 animals
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hr
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean, all animals, all timepoints
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 hr
Score:
0
Max. score:
4
Remarks on result:
other: mean, 6 animals
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean, 6 animals
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean, 6 animals
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
1.2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean, 6 animals
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hr
Score:
1.57
Max. score:
4
Remarks on result:
other: mean, all animals, all timepoints
Irritant / corrosive response data:
The report notes that skin reactions present in 5 of the 6 treated rabbits extended “over a large skin area outside the application site”, however this is not further characterized.
Dermal responses were initially quite mild and consisted of very slight erythema (no oedema) in 5 of 6 animals 1 hr after patch removal.
At 24 hours, moderate to severe erythema (grade 3) and slight oedema (grade 2) was present in all animals.
At 48 hours, moderate to severe erythema was present in 4 of 6 animals with well defined erythema present in the remaining 2 animals; very slight (3/6) or slight (3/6) oedema as also observed.
At 72 hours, moderate to severe erythema was present in 3 of 6 rabbits, with well defined (2/6) or very slight (1/6) erythema affecting the remainder; slight (3/6) or very slight (1/6) oedema was also present in 4 rabbits (resolved in others).
No dermal responses were present in any animal at observation day 7.
The results demonstrate that sulfur (50% in Vaseline) is irritating to rabbit skin following 4 hour semi-occluded contact. Irritation was absent at 1 hour after patch removal but showed a marked increase in intensity thereafter which was sustained to 72 hr.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Sulfur is irritating, but not corrosive, to rabbit skin.
Executive summary:

Sulfur was examined for acute dermal irritating/corrosive properties in an experiment with six albino NZW rabbits, in compliance with OECD guideline 404 and under GLP. The dermal exposure period was 4 hours under semi-occlusive conditions. Skin irritation scores were recorded using Draize criteria at 1, 24, 48 and 72 hours and at 7 days after removal of the test material. Irritation was initially absent, however 24 hr after patch removal moderate to severe erythema (grade 3) and slight oedema (grade 2) had developed in all animals, and was decreased only slightly at the 48 hr and 72 hr observation periods. Mean erythema and oedema scores of 2.67 and 1.57, respectively, were calculated for all animals taking into account responses at 24, 48 and 72 hr, however all skin effects had resolved completely by day 7.

On the basis of these results, it is concluded that sulfur is irritating, but not corrosive, to rabbit skin.