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Description of key information

In the key study Incorez 397 was tested for skin irritation properties in rabbits according to EU method B.4 and OECD guideline 404. The test item showed erythema with individual mean scores of 3.00, 3.33, 2.00 and oedema with individual mean scores of 1.66, 2.66, and 0.66 (after 24, 48, and 72 hours after patch removal). No signs of erythema/oedema were detectable at the end of the study. In conclusion, based on the severe findings noted in the in vivo assay, the substance is classified as corrosive to the skin.
In a supporting study Incorez 397 was tested for skin irritation potential in the Human Skin Model Test according to EU method B.46. Incorez 397 was considered irritant in the Human Skin Model Test.
In conclusion, based on the in vivo skin irritation assay, the substance is classified as corrosive to the skin. For animal welfare reasons no further testing for eye irritation was carried out.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-10-11 to 2011-01-31
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
31 May 2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
24 April 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: S & K LAP Kft. 2173 Kartal, Császár út 135, HUNGARY;
- Age at study initiation: Young adult rabbits, 10 weeks old;
- Weight at study initiation: 2918-3111 g;
- Housing: Animals were housed individually in metal cages;
- Diet: Hare fattening mixed diet produced by YAQ-TÁP Kft., Nyíregyháza (Tokaji út 22), Hungary, ad libitum.
- Water: Animals received tap water from watering bottles ad libitum,
- Acclimation period: 5 days;

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C;
- Humidity: 30 - 70 %;
- Air changes (per hr): not stated;
- Photoperiod: Artificial light, from 6 a.m. to 6 p.m.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3 male
Details on study design:
The test item was applied to an approximately 6 cm² area of intact skin. Sterile gauze pads (10x10cm) were placed on the skin of rabbits. These gauze patches were kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The entire trunks of the animals were wrapped with plastic wrap for 4 hours.
In the first step an initial test was performed using one animal. One hour after application of the test item to the sentinel animal, the application site was examined. Severe irritation or corrosive effect could not be found in the initial test, therefore the bandage was replaced and the exposure continued for a further 3 hours (a total 4 hours exposure). Two additional animals were involved for this study.
Observations and Scoring:
Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes and then at 24, 48, 72 hours then 1 and 2 weeks after the patch removal. At the end of the observation period the animals were humanely sacrificed.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.88
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.66
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
The test item was administered in pure state, in a single dose of 0.5 ml, to the hairless skin of all experimental rabbits. The untreated skin of each animal served as control.
After 4 hours the rest of the test item was removed with water of body temperature.
The animals were examined at 1, 24, 48, 72 hours then one and two weeks after the patch removal.
One hour after the patch removal very slight and well defined erythema were observed in two animals.
24 hours after the patch removal very slight to moderate erythema, slight oedema and dry skin surface were found in animals.
72 hours after the patch removal the signs were most serious. Moderate to severe erythema, very slight and moderate oedema, dry skin surface, wounds, bleedings, bloody scabs, scabs and crusting were detected.
Two weeks after the patch removal no primary irritation symptoms, like erythema and oedema or other signs occurred on the treated skin surfaces, so the study was terminated at this time.
Other effects:
During the study the control area was symptom-free.
General state and the behaviour of animals were normal throughout the study period.
There were no notable body weight changes during the contact and observation period.
The observed symptoms were evaluated as fully reversible alterations
Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
Incorez 397 was tested for Skin Irritation properties in rabbits according to OECD Guideline 404 / Commission Regulation (EC) 440/2008.
The test item showed erythema with individual mean scores of 3.00, 3.33, 2.00 and oedema with individual mean scores of 1.66, 2.66, and 0.66 (after 24, 48, and 72 hours after patch removal). No signs of erythema/oedema were detectable at the end of the study. In conclusion, based on the severe findings noted in the in vivo assay, the substance is classified as corrosive to the skin.
Executive summary:

The acute skin irritation study of the test item Incorez 397 was performed in New Zealand White rabbits. The irritation effect of the test item was evaluated according to the Draize method (OECD No.: 404, 2002).

The test item was administered in pure state, in a single dose of 0.5 ml, to the hairless skin of all experimental rabbits. The untreated skin of each animal served as control.

After 4 hours the rest of the test item was removed with water of body temperature.

The animals were examined at 1, 24, 48, 72 hours then one and two weeks after the patch removal. One hour after the patch removal very slight and well defined erythema were observed in two animals.

24 hours after the patch removal very slight to moderate erythema, slight oedema and dry skin surface were found in animals.

72 hours after the patch removal the signs were most serious. Moderate to severe erythema, very slight and moderate oedema, dry skin surface, wounds, bleedings, bloody scabs, scabs and crusting were detected.

Two weeks after the patch removal no primary irritation symptoms, like erythema and oedema or other signs occurred on the treated skin surfaces, so the study was terminated at this time.

The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the patch removal) were as follows:

- erythema: 3.00, 3.33, 2.00

- oedema: 1.66, 2.66, 0.66

During the study the control area was symptom-free. General state and the behaviour of animals were normal throughout the study period. There were no notable body weight changes during the contact and observation period. The observed symptoms were evaluated as fully reversible alterations.

In conclusion, based on the severe findings noted in the in vivo assay, the substance is classified as corrosive to the skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:


Two studies on skin irritation are available for Incorez 397. In the key study acute skin irritation was tested according to EU method B.4 and OECD guideline 404. In a supporting study Incorez 397 was tested according to EU method B.46.


 


Skin irritation in vivo


Following the Draize method Incorez 397 was administered in pure state, in a single dose of 0.5 ml, to the hairless skin of all experimental rabbits. The untreated skin of each animal served as control. After 4 hours the rest of the test item was removed with water of body temperature.


The animals were examined at 1, 24, 48, 72 hours then one and two weeks after the patch removal. One hour after the patch removal very slight and well defined erythema were observed in two animals. 24 hours after the patch removal very slight to moderate erythema, slight oedema and dry skin surface were found in animals. 72 hours after the patch removal the signs were most serious. Moderate to severe erythema, very slight and moderate oedema, dry skin surface, wounds, bleedings, bloody scabs, scabs and crusting were detected. Two weeks after the patch removal no primary irritation symptoms, like erythema and oedema or other signs occurred on the treated skin surfaces, so the study was terminated at this time.


The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the patch removal) were:


- erythema: 3.00, 3.33, 2.00


- oedema: 1.66, 2.66, 0.66


During the study the control area was symptom-free. General state and behaviour of animals were normal throughout the study period. There were no notable body weight changes during the contact and observation period. The observed symptoms were evaluated as fully reversible alterations.


In conclusion, based on the severe findings noted in the in vivo assay, the substance is classified as corrosive to the skin.


 


Skin irritation in vitro


Following the Human Skin Model Test three tissues of the human skin model EpiDerm (TM) were treated with Incorez 397 for 60 minutes. 30 µL of the liquid test item (using a nylon mesh) were applied to each tissue and spread to match the tissue size. DPBS-buffer was used as negative control, 5% SDS-solution was used as positive control. After treatment with the negative control, the absorbance values were within the required acceptability criterion of 1.0 < mean OD < 2.5. The positive control showed clear irritating effects. Variation within tissues was acceptable (< 18%).


After the treatment with the test item, the relative absorbance values were reduced to 6.3 %. This value is well below the threshold for irritation potential (50%). Therefore, Incorez 397 is considered as irritant in the Human Skin Model Test.


 


Eye Irritation:


In accordance with column 2 of REACH Annex VII, the test on eye irritation (required in section 8.2) does not need to be conducted as the available information indicates that the criteria are met for classification as corrosive to the skin. Incorez 397 is corrosive to the skin and in consequence also severely damaging to the eye, and is, thus, classified for severe skin burns and eye damage (H314). Testing for eye irritation was not carried out for animal welfare reasons.

Justification for classification or non-classification

Based on skin irritation data available, Incorez 397 is classified as skin corr. 1C (H314: Causes severe skin burns and eye damage) according to Regulation No (EC) 1272/2008 (CLP).