Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 May 1984 - 04 May 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliability 2 is assigned because the study is conducted according to an equivalent of OECD TG 404 and in compliance with GLP, but has minor deviations that do not influence the quality of the results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
24 instead of 4 hours treatment, no reading at 24 and 72 hours after removal of patch, no 14-day observation period
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: clear liquid
Details on test material:
- Storage condition of test material: at ambient temperature in a brown glass screw-top

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leics and Rosemead Rabbits Limited, Lea Valley, Essex
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.25-3.09 kg
- Housing: individually in suspended metal cages
- Diet: standard laboratory diet (Rabbit Diet, A.W. Tindall Limited), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 60-65
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
occlusive
Preparation of test site:
other: clipped and abraded (one side)
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of test animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
24 hours
Observation period:
48 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: dorsal/flank area, approximately 6 cm2
- Type of wrap if used: Absorbant lint BPC, polythene, adhesive and elasticated corset (Setor's Tubigrip)

REMOVAL OF TEST SUBSTANCE
- Washing: gentle swabbing with cotton wool soaked in lukewarm water
- Time after start of exposure: 24 hours

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to Draize J.H. (1959) Association of Food and Drug Officials of the USA, Austin, Texas, "The Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics". This is comparable to the current OECD scoring system. Readings were performed at 1 hour and 48 hours after removal of the patch.

A primary cutaneous irritation index was calculated for the test material in the original study. Based on the raw data an erythema and oedema score was calculated for each animal (only intact site), based on the 48 hours reading (after removal of patch). This is the only reading that is available in correspondence with the CLP classification criteria and is therefore used for classification. The 1 hour reading (after removal of patch) provides supportive information.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 48 hrs
Score:
4
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 48 hrs
Score:
4
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 48 hrs
Score:
3
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 48 hrs
Score:
2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 48 hrs
Score:
2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 48 hrs
Score:
4
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 48 hrs
Score:
4
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 48 hrs
Score:
4
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 48 hrs
Score:
3
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 48 hrs
Score:
4
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 48 hrs
Score:
4
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 48 hrs
Score:
4
Max. score:
4
Reversibility:
no data
Remarks on result:
other: score for intact skin
Irritant / corrosive response data:
The test item produced considerable cutaneous irritation in 6 out of 6 rabbits. Well-defined to moderate erythema accompanied by moderate to severe oedema, raised greater than 1 mm and extended well beyond the site of application was observed in all animals after 1 hour (intact and abraded sites). At the 48 hours reading areas of skin necrosis or eschar formation surrounded by a well-defined to moderate erythema and accompanied by severe oedema extending beyond the site of application had developed at the intact and abraded sites of two rabbits and only the intact site of one rabbit. The three remaining rabbits revealed a well-defined to moderate erythema, accompanied by a slight to moderate oedema, although still generally extending beyond the site of application. Additionally skin fissures and desquamation were observed in one rabbit.

Any other information on results incl. tables

Individual scores for skin irritation as indicated in the test report:

Skin reaction Skin site Reading (hours after patch removal) Individual scores
Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6
Erythema and eschar formation Intact 1 3 2 2 3 2 3
48 4 4 3 2 2 4
Abraded 1 3 2 2 3 2 3
48 4 4 3 2 2 3
Oedema formation Intact 1 4 4 3 4 4 4
48 4 4 3 2 2 4
Abraded 1 4 4 3 4 4 4
48 4 4 3 2 2 4

Scores for abraded skin are considered not relevant as this type of testing is not included in the current OECD guideline and CLP classification criteria. The 48 hours reading has been used primarily for evaluation of the classification, as this is the only time point available in this study that can be used for classification according to CLP. Skin irritation is indicated if 2/3 of the animals show an erythema or oedema score ≥2.3. The skin irritating effects should be regarded as worst case due to the longer exposure period used in the study (24 instead of 4 hours according to OECD guideline).

At the 48 hour reading, 3 out of 6 animals showed signs related to corrosivity (necrosis on the skin). Taking into account the fact that the exposure of the animals was 24 hours instead of 4 hours, the effects are expected to be present to a larger extent as could be expected from a standard exposure time (OECD). Corrosiveness is indicated according to CLP if 2/3 animals show corrosive reactions (a.o. necrosis). Based on this information, it is anticipated that the observed effects are not sufficient to conclude on corrosive properties of the test substance.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a skin irritation study with 6 rabbits, performed similar to OECD 404, erythema scores in 4 out of 6 animals were ≥2.3 and oedema scores in 5 out of 6 animals were ≥2.3 as defined in the EU classification criteria. Based on the results of this study, the substance must be regarded as irritating to skin.
Executive summary:

The undiluted substance (0.5 ml) was applied to 2.5 cm2 skin in a skin irritation test in 6 rabbits with a method similar to OECD TG 404. Deviations consider a 24h instead of a 4h exposure time and only a 1 hour and 48 hour reading (after patch removal), with no prolonged observation time. The score for erythema and oedema from gradings at 48 hours after patch removal was ≥2.3 for a majority of the animals as defined in the EU classification criteria. Moderate to severe irritation was seen, with some signs of necrosis in 3 out of 6 animals. Despite of the necrosis, the substance was not considered corrosive as there was a significantly higher exposure period of 24 instead of the 4 hours (as according to OECD TG 404) used and due to the fact that the effect was not seen in a majority of the animals. Overall the substance must be regarded as irritating to skin.