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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:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study conducted in accordance with GLP. However, no data on test substance purity were given.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987

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:
USA EPA FIFRA (40 CFR 158, 81-5)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: crystalline powder
Details on test material:
No purity given.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
Weight at study initiation: 2,35 - 3,07 kg
Age: 12 to 16 weeks old.
Sex not specified.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clippping of the fur
Vehicle:
water
Controls:
no
Amount / concentration applied:
Concentration: 0.5 g (moistened with 0.5 ml distilled water)
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
6
Details on study design:
The test group consisted of 6 New Zealand White rabbits. About 24 hours prior testing, the fur of the dorsal and flank area of each rabbit was clipped. The test material was prepared by moistening 0.5 g of test substance with 0.5 ml of distilled waterand was applied on a selected shorn skin area, on the back of each rabbit. The application site was covered by means of a patch, which again was maintained in place using a strip of adhesive tape. Furthermore, the trunk of each rabbit was wrapped in a corset to prevent the animals from interfering with the patches. Exposure period was 4 hours; thereafter removal of the dressing and the patch, residual test material on the application site of each rabbit was gently removed using cotton woolsoaked in distilled water. The scoring of the dermal findings was performed according to Draize JH (The appraisal of the safety of chemicals in foods, drugs and cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, 1959); the reading time points were 60 min, 24 h, 48 h and 72 h after removal of the patches. Additional readings were done on day 7 and day 14.

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24-72h
Score:
6.2
Reversibility:
not fully reversible within: 72 h
Irritant / corrosive response data:
One hour after removal of the dressing: all animals displayed very slight or moderate to severe erythema on the application sites (graded 1 to 3). Slight haemorrhage of the dermal capillaries, brown discoloration and small areas of blanching were seen, which resulted in an average score over all sixanimals of 2.5.
After 24 hours: erythema became severe (graded 4) in 4/6 cases and was accompanied by green/brown coloured necrosis over the whole application site. Small areas of blanching were seen in 5/6 animals, and slight hemorrhage of the dermal capillaries was seen in two of them. In two rabbits, the reaction area was extended to 3 to 4 cm beyond the application site. The average score over all six animals was 3.3.
After 48 hours: severe erythema (graded 4) with green/brown coloured necrosis over the whole application site was seen in 5/6 cases. In two of these 5 cases, small areas of blanching were seen and in one case, the reaction area was extended to 3 to 4 cm beyond the application site. The remaining animal showed well-defined erythema. The average score over all six animals was 3.7.
After 72 hours: severe erythema (graded 4) with green/brown coloured necrosis over the whole application site still was present in 5/6 cases. In the remaining animal, erythema turned to very slight (graded 2). The average score over all six animals was 3.5.
After 7 days: erythema still was severe (graded 4) in 5/6 animals and was accompanied by light brown-coloured eschar over the application site; in three of these 5 animals, pale yellow discoloration of the skin and/or fur also was seen. The remaining animal showed desquamation and pale yellow discoloration of the skin and/or fur. The average score over all six animals was 3.3.
After 14 days: at this time point, two animals showed a small area of slightly sunken brown-coloured eschar within the application site; no fur growth was observed within the remaining region of the application site. In one animal, a similar but more larger eschar area as described above was seen, with blood stained dermal tissue around the edge of the eschar. Furthermore, the skin showed a pale yellow discoloration and no fur growth was seen. Two further animals showed white scar tissue with no fur growth; in one case, this was accompanied by a pale yellow discoloration of the skin. One animal still showed desquamation and pale yellow discoloration of the skin and/or fur.
One hour after removal of the dressing: all animals displayed slight to moderate edema on the application sites (graded 2 to 3). The average score over all six animals was 2.8.
After 24 hours: four animals showed severe edema, which raised more than 1 mm and extended ventrally beyond the application site (graded 4). The remaining two animals showed slight to moderate edema (graded 2to 3). The average score over all six animals was 3.7.
After 48 hours: four animals showed moderate edema (graded 3) and one still showed severe edema, which raised more than 1 mm and extended ventrally beyond the application site (graded 4). The sixth animal was free from edema. The average score over all six animals was 2.7.
After 72 hours: three animals showed slight edema (graded 2) whereas two showed moderate edema (graded 3); the sixth animal still remained free of edema. The average score over all six animals was 2.0.
After 7 days: edema became slight in four cases (graded 2) and very slight in one case (graded 1); the sixth animal still was free of edema. The average score over all six animals was 1.5.
After 14 days: no more edema was seen.
Other effects:
A single, 4 hr semi-occluded dermal application of the test material to the skin of six rabbits produced severe dermal reactions, including eschar formation, necrosis and severe edema. Other adverse dermal reactions noted were slight haemorrhage of the dermal capillaries, blanching or brown discoloration of the skin, desquamation and scar tissue.The absence of fur growth was also occasionally noted on day fourteen.

Any other information on results incl. tables

Skin reaction

Reading (h)

Rabbit number

   

70

74

92

106  107  115 

Erythema/Eschar formation

1

3

3

1

24

4

4

2

   48  4
   7 days  4
   14 days  Su Su  0 DS  TS  SuS 
 Edema formation  1  3
   24  4
   48  3
   7 days  2
   14 days  0

Su = small area of slightly sunken brown-coloured eschar (approx. 5 mm x 5 mm). No fur growth over remainder of treatment site - corrosive effects noted.

S = pale yellow-coloured staining of skin/fur

D = desquamation

T = white scar tissue with no fur growth - evidence of corrosion

Applicant's summary and conclusion