Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Draize Testing method (Draize JH et al., J. Pharm. Exp. Ther. 82: 377-390, 1944; Draize JH, Assoc. Food Drugs Officials of the United States: 46-49, Topeka Kansas, 1965) as prescribed by the FDA (in The Federal Register 38 No.187 §15000.41, USA)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: L.I.T., Aptos, USA
- Weight at study initiation: 2 - 2.5 kg
- Housing: individually
- Diet: 2 oz/day (equivalent to 56.7 g/day) Purina Rabbit Chow
- Water: ad libitum

Test system

Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g mixed to a paste with 10 drops of water

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 drops
Duration of treatment / exposure:
24 h
Observation period:
6 days
Reading time points: 0 and 48 h, and 6 days
Number of animals:
6 males
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk
- Type of wrap if used: the treated skin was covered with a 2.5 cm² 2-layer surgical gauze patch, held in place by clear plastic wrap. The trunk of each animal was then wrapped in Spandex.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): if test substance was still present on the skin, the treated area was swabbed with warm water
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Intact skin:
For one of the rabbits no test substance was observed at the test site at patch removal, and very slight erythema (score 1) and no edema was noted (see Table 1 under 'Any other information on results incl. tables'). The results for this animal (number 4) were disregarded. Directly after patch removal (24 h), 5/5 animals had well defined to severe erythema (score 2 - 3), while 4/5 had slight to moderate edema (score 2 - 3) and 1/5 had very slight edema (score 1). 48 hours after patch removal, 5/5 rabbits had very slight to well defined erythema (score 1 - 2). The edema had cleared in 4/5 animals, while 1/5 still had very slight edema (score 1). 6 days after patch removal, 3/5 rabbits had very slight erythema (score 1) and 1/5 also had very slight edema (score 1), whereas in 2/5 rabbits all skin effects had cleared. The skin irritation effects were read 0 and 48 h after patch removal, while the exposure time was 24 h (as opposed to 4 h requirement in OECD guideline 404). No 24- and 72 h readings are available. However, a worst case approach was used to calculate the mean value (24/48/72 h) of the erythema and edema score, respectively. Since the animals were exposed 24 h with the test substance, the 0-h reading time point was assumed to be the 24-h reading time point and the 48-h reading time point was assumed to be the 72-h reading time point. The 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h).

Abraded skin:
For one of the rabbits no test substance was observed at the test site at patch removal, and very slight erythema (score 1) and no edema was noted. The results for this animal (number 4) were disregarded. Directly after patch removal (24 h), 5/5 animals had well defined to severe erythema (score 2 - 3) and 5/5 had slight to moderate edema (score 2 - 3). 48 hours after patch removal, 5/5 rabbits had very slight to well defined erythema (score 1 - 2). 1/5 rabbits had very slight edema (score 1), while the edema had cleared in 4/5 animals. 6 days after pach removal, 3/5 rabbits had very slight erythema, while the edema had cleared in 5/5 rabbits.

Any other information on results incl. tables

Table 1: Individual skin irritation scores (intact skin)

Observation time Rabbit no.
1 2 3 4 5 6
Erythema Edema Erythema Edema Erythema Edema Erythema Edema Erythema Edema Erythema Edema
24 h 2 2 2 2 3 2 1* 0 3 3 3 1
48 h No experimental data available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption)
72 h 2 0 1 0 1 0 - - 1 1 1 0

* The material was not present at the time of unwrapping (24 h reading). However, there was a slight erythema at the sites of application. These values will not be used in calculating.

Table 2. Calculation of mean scores

  Rabbit no.
1 2 3 4 5 6
Erythema Edema Erythema Edema Erythema Edema Erythema Edema Erythema Edema Erythema Edema
Mean value 24 + 48 + 72 h* 2,0 1,3 1,7 1,3 2,3 1,3 - - 2,3 2,3 2,3 0,7

*No 48 h data are available: for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h).

Applicant's summary and conclusion

Interpretation of results:
other: Cat. 2, H315 according to Regulation (EC) No 1272/2008
Conclusions:
CLP: Cat. 2, H315.
A worst case approach was used to calculate the mean value (24/48/72 h) of the erythema and edema score, respectively. Based on this, a skin irritant potential for the test substance is assumed and accordingly, classification is warranted.