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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:
From 2003-09-17 to 2003-10-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint mars d'Egrenne, France
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 2.7 kg
- Housing: individually in a polystyrene cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18±3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 air changes per hour
- Photoperiod : 12 hour light/dark cycle

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: each animal served as its own control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied : 0.5 ml undiluted




Duration of treatment / exposure:
Left flank: 3 minutes.
Right flank: 4 hours.
Observation period:
1, 24, 48, 72 hrs after removal the patch and then daily until day 14.
Number of animals:
1 male rabbit
Details on study design:
TEST SITE
- Area of exposure: right flank (application for 4 hours) and left flank (application for 3 minutes)
- % coverage: 2.5x2.5 cm
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was wiped off by means of a dry cotton pad.
- Time after start of exposure: 3 minutes or 4 hours

SCORING SYSTEM: according to OECD guideline 404 (draize scoring system)




Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
after a 3-minute exposure
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: The mean irritation score was not calculable because erythema was masked by a withish area at the 48 and 72-hour readings. The score of the 24-hour reading was 2.
Irritation parameter:
edema score
Remarks:
after a 3-minute exposure
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 11 days
Irritation parameter:
erythema score
Remarks:
after a 4-hour exposure
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: The mean irritation score was not calculable because erythema was masked by a withish area at the 48 and 72-hour readings. The score of the 24-hour reading was 2.
Irritation parameter:
edema score
Remarks:
after 4-hour 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: day 8
Irritant / corrosive response data:
- The mean scores over 24, 48 and 72 hours were not calculable for erythema (evaluation masked by the whitish area) whatever the exposure period.
- The mean scores over 24, 48 and 72 hours for oedema were 2.0 and 3.0 after a 3-minute and a 4-hour exposure period respectively.
The important cutaneous reactions observed after the 3-minute and 4-hour exposures were considered to be the consequence of a tissular destruction.
See freetext "remarks on results" for detailed descriptions of the test sites.

Any other information on results incl. tables

After a 3-minute exposure, a very slight then well-defined erythema (grade 1 then 2) was observed 1 hour and 24 hours after patch removal. From day 2 up to day 10, the evaluation of the erythema was masked by a whitish (days 2 and 3) or brownish (day 4) area, then by a crust (days 5 to 10). Then a well-defined erythema (grade 2) was noted from day 11 until the end of the observation period (day 14). A slight oedema (grade 2) was recorded 24 and 48 hours after patch removal. The oedema became more pronounced (grade 3) from day 3 up to day 6. The evaluation of the oedema was then masked by the crust from day 7 until day 10. Crusts and/or dryness of the skin were observed from day 5 and persisted at the end of the observation period (day 14).

After a 4-hour exposure, a well-defined erythema (grade 2) was noted 1 hour after patch removal. From day 1 up to day 7, the evaluation of the erythema was masked by a whitish (days 1 to 3) or brownish (day 4) area, then by a crust (days 5 to 7). A moderate to severe erythema (grade 3) was then observed on day 8, and a well-defined erythema (grade 2) persisted until the end of the observation period (day 14). A slight then moderate oedema (score 2 then 3), the evaluation of which was masked by a crust on day 7, was recorded 1 hour after patch removal and from day 1 up to day 5, respectively. Dryness of the skin was noted from day 4 and persisted at the end of the observation period (day 14).

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
Migrated information
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 1B, H314 and Corrosive R35 respectively.
Executive summary:

The potential of the test item to induce skin irritation was assessed in rabbit according to the OECD guideline 404 in compliance with the principles of Good Laboratory Practice regulations.

As possible irritant effetcs were anticipated, the test item was first evaluated in a single animal. The duration of exposure was 3 minutes on one flank and 4 hours on the other flank. A single dose of 0.5 ml was applied to the right flank (application for 4 hours) or the left flank (application for 3 minutes) of the rabbit under a semi-occlusive dressing. Skin reactions were observed 1, 24, 48, 72 hours after removal of the dressing and then daily until day 14.The mean values of the scores for erythema and oedema were calculated when possible.

After a 3-minute exposure, a very slight then well-defined erythema (grade 1 then 2) was observed on days 1 and 2. From day 3 up to day 11, the evaluation of the erythema was masked by a whitish (days 3 and 4) or brownish (day 5) area, then by a crust (days 6 to 11). Then a well-defined erythema (grade 2) was noted from day 12 until the end of the observation period (day 15).

A slight or moderate oedema (grade 2 or 3) was recorded on days 2 and 3 and from day 4 up to day 7, respectively. The evaluation of the oedema was then masked by the crust from day 8 until day 11.

Crusts and/or dryness of the skin were observed from day 5 and persisted at the end of the observation period (day 15).

 

After a 4-hour exposure, a well-defined erythema (grade 2) was noted on day 1. From day 2 up to day 8, the evaluation of the erythema was masked by a whitish (days 2 to 4) or brownish (day 5) area, then by a crust (days 6 to 8). A moderate erythema (grade 3) was then observed on day 9, and a well-defined erythema (grade 2) persisted until the end of the observation period (day 15).

A slight then moderate oedema (score 2 then 3), the evaluation of which was masked by a crust on day 8, was recorded on day 1 and from day 2 up to day 6, respectively.

Dryness of the skin was noted from day 5 and persisted at the end of the observation period (day 15).

 

As the test item showed corrosive properties on this first animal, the study was considered complete and the test item was not evaluated on other animals.

Whatever the exposure duration, well defined erythema was noted along with slight to moderate oedema, but scoring was made difficult by the appearance of white/brown areas and crusting. Symptoms had not disappeared after 14 days. The mean scores over 24, 48 and 72 hours for the animal were not calculable for erythema (evaluation masked by the whitish area); for oedema, the mean scores over 24, 48 and 72 hours were 2.3 and 3.0 after the 3-minute and the 4-hour exposure period respectively.

The test substance was evaluated as causing severe burns after a 3 minute exposure on rabbit skin.

As the full skin destruction developed over the course of two to three days following the 3 minute exposure, it should be classified Cat. 1B for skin corrosion.