Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-07-15 to 1996-08-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): POLYRAM SL
- Physical state: yellow oily liquid
- Analytical purity: 100 % (expressed in complex substance)
- Certificate of analysis date: 1996/03/04
- Lot/batch No.: 5788
- Expiration date of the lot/batch: 1997/03
- Storage condition of test material: in dark and at room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: elevage BERTHO (22120 Yffiniac, FRANCE)
- Age at study initiation: not reported
- Weight at study initiation: 2.8 kg
- Housing: environmental conditions and controls in accordance with the requirements of the 86/609/EEC guideline(individual housing on floor grid)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: Fur was removed by clipping from the dorsal area of the trunk of the animals.
Vehicle:
unchanged (no vehicle)
Controls:
other: each animal served as its own control
Amount / concentration applied:
0.5 mL / rabbit
Duration of treatment / exposure:
- Application for 4 hours
- Application for 3 minutes
Observation period:
60 min, 24, 48, 72 hrs after patch removal and then daily until day 14.
Number of animals:
3 female animals.
Details on study design:
TEST SITE
- Area of exposure: dorsal surfaces of the trunk
- % coverage: 2 x2 cm
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: the treated site of each animal was cleaned by using absorbent paper moistened with distilled water
- Time after start of exposure: 4 hours or 3 minutes after the start of exposure.

SCORING SYSTEM: according to OECD guideline 404


Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
: 4 hours exposure
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 12 days
Irritation parameter:
erythema score
Remarks:
: 4 hours exposure
Basis:
animal #2
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Remarks:
: 4 hours exposure
Basis:
animal #3
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Remarks:
: 4 hours exposure
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
edema score
Remarks:
: 4 hours exposure
Basis:
animal #2
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Remarks:
: 4 hours exposure
Basis:
animal #3
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
3.7
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Remarks:
: 3 minutes exposure
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Remarks:
: 3 minutes exposure
Basis:
animal #2
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Remarks:
: 3 minutes exposure
Basis:
animal #3
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Remarks:
: 3 minutes exposure
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 11 days
Irritation parameter:
edema score
Remarks:
: 3 minutes exposure
Basis:
animal #2
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Remarks:
: 3 minutes exposure
Basis:
animal #3
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritant / corrosive response data:
_ Application for 4 hours:
Moderate to severe erythema and oedema were observed in all animals. A slow reversibility was observed at about 1 week. Erythema regressed slowly and was no more visible on Day 13 in 1 animal but was still barely perceptible till the end of the observation period in the 2 others. Oedema disappeared on Day 5 in 1 rabbit and on Day 11 in 1 other ; a very slight oedema was observed in the third at the end of the observation period.
48 hours after application, lesions as burns and important loss of elasticity were noted in all animals. In one rabbit a slight scab has broken out 72 hours later, a scar formation was visible at the end of the observation period (See tables 1 and 2 in results and discussion free-text for details).

- Application for 3 minutes :
Slight to well visible erythema with slight oedema were observed in all animals. These reactions regressed slowly. They were totally reversible in 5 and 10 days in 2 rabbits. Only 1 animal still presented slight oedema till Day 11 and slight erythema till the end of the observation period (See tables 3 and 4 in results and discussion free-text for details).

Any other information on results incl. tables

Table 1: Erythema scores after a 4- hour exposure

 Animal  1 hour (D1) 24 hours (D2)  48 hours (D3) 72 hours  (D4) D5  D6  D7  D8  D9  D10  D11  D12  D13  D14  D15 
1 (5327) 1 3 3 3 3 3 2 2 1 1 1 1 0  -  -
2 (5328) 1 3 2 2 2 2 2 2 2 2 2 2 1 1 1
3 (5329) 2 3 3 3 3 3 3 3 2 2 1 1 1 1 1

Grading scale according to OECD 404 guidelines

Table 2: Oedema scores after a 4-hour exposure

 Animal  1 hour (D1) 24 hours (D2)  48 hours (D3) 72 hours  (D4) D5  D6  D7  D8  D9  D10  D11  D12  D13  D14  D15 
 1 (5327)  2  2  1  0  0  0 0  0  0  0  0  0  -  -
 2 (5328)  2  4  3  2  1  1 1  1 1  1  0 0  0  0  0
3 (5329)  3  4  4  3  3 2  1 1  1  1  1  1  1  1  1

Grading scale according to OECD 404 guideline

Table 3: Erythema scores after a 3- min exposure

 Animal  1 hour (D1) 24 hours (D2)  48 hours (D3) 72 hours  (D4) D5  D6  D7  D8  D9  D10  D11  D12  D13  D14  D15 
 1 (5327)  0  1  2  2  3  3  2  2  1  1  1  1  1  1  1
 2 (5328)  1  2  2  2  2  2  2 1  1 1  0  -  -  -  -
3 (5328)  0  0  0  1  1 0  -  -  -  - -  -  -  -

Grading scale according to OECD 404 guideline

Table 4: Oedema scores after a 3-min exposure

 Animal  1 hour (D1) 24 hours (D2)  48 hours (D3) 72 hours  (D4) D5  D6  D7  D8  D9  D10  D11  D12  D13  D14  D15 
1 (5327)  0  2  2  2 2  1 1  1  1  1  1  0  0  0  0
2 (5328)  0  1 1  1 0  0 0  0 0  0  -  -  -
3 (5328)  0  1  2  1  0 0  -  -  -  - -  -  -  -  -

Grading scale according to OECD 404 guideline

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (Reg. 1272/2008/EC) and Directive 67/548/EEC
Conclusions:
Under the experimental conditions of this study and according to the criteria laid down in CLP (Reg 1272/2008/EC) and directive 67/548/EEC, the test material is classified Skin corrosive category 1 C, H314 and Corrosive R34 respectively.
Executive summary:

The potential of the test substance to induce skin irritation was assessed in 3 rabbits according to the OECD 404 guideline in compliance with the

principles of Good Laboratory Practice regulations.

A single dose of 0.5 ml of the test substance was applied to the skin of the rabbits under a semi-occlusive dressing for a 4-hour exposure period and thereafter for 3 minutes . Skin reactions were observed 1, 24, 48, 72 hours after removal of the dressing and then daily until day 14 in order to observe their reversibility. The mean values of the scores for erythema and oedema were calculated for each animal.

After 4 hours of exposure, the mean scores over 24, 48 and 72 hours for individual animals were 3.0, 2.3 and 3.0 for erythema and 2.0, 3.0 and 3.7 for oedema. Burns and loss of elasticity was noted in all animals after 48 hours. In one animal, a slight scab had broken out 72 hours later , a scar formation was visible at the end of the observation period. For all animals, erythema regressed slowly. It cleared on day 13 in one animal but was still barely perceptible at the end of the observation period for the two remaining. Oedema disappeared on day 5 in one animal and on day 11 in one other, a very slight oedema was still observed in the third one at the end of the observation period.

After 3 minutes of exposure, the mean scores over 24, 48 and 72 hours for individual animals were 1.7, 2.0 and 0.3 for erythema and 2.0, 1.0 and 1.3 for oedema. Animals demonstrated slight to well visible erythema and slight oedema. These symptoms were reversible for two rabbits within 5 and 10 days with the last animal displaying slight erythema at the end of the study period.

Under these experimental conditions, the test substance was considered to be corrosive to the rabbit skin.