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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted by a GLP accredited laboratory using OECD Testing Guideline 404.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
see box below
Principles of method if other than guideline:
During the study, the humidity and the temperature were occasionally recorded out of the target range. The actual range was at the humidity 40-85% and the temperature 17.3-23.4 °C. Due to observed clinical signs, the observation period was longer than indicated in the study plan. These deviations have no presumed impact on the outcome or integrity of the study.
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
1H-Imidazolium, 3-ethyl-1-methyl-, C9-14-branched alkylbenzenesulfonates
IUPAC Name:
1H-Imidazolium, 3-ethyl-1-methyl-, C9-14-branched alkylbenzenesulfonates
Constituent 2
Reference substance name:
EMI-DBS
IUPAC Name:
EMI-DBS
Constituent 3
Reference substance name:
1065642-34-3
Cas Number:
1065642-34-3
IUPAC Name:
1065642-34-3
Test material form:
semi-solid (amorphous): gel
Remarks:
migrated information: paste
Details on test material:
Name: EMI-DBS
Appearance: Yellow paste
Storage conditions: Room temperature (15-30 C), in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Species and strain: New Zealand White rabbits
Source: S & K-LAP Kft, 2173 Kartal, Császár út 135, HUNGARY
Justification of strain: The New Zealand White albino rabbit is one of the standard strains used for acute irritation toxicity studies.
Animal health: Only animals in acceptable health condition were used for the test.
Number of animals: 3
Age of animals at treatment: ~11 weeks old
Sex: Male
Body weight range
- at the beginning of the life phase: 2643-2974 g
- at the end of the life phase: 3468-3716 g
Date of receipt: 24 August 2011
Acclimation time: 6 days
Animal identification: The animals were identified by engraved ear tags. The cages were marked with individual identity cards with information about study code, sex, cage number, dose group and individual animal number.
Number of animal room: 610
Lighting periods: 12 hours daily, from 6.00 am to 6.00 pm
Temperature: 17.3-23.4°C
Relative humidity: 40-85%
Housing/Enrichment: Rabbits were individually housed in AAALAC approved metal wire rabbit cages (65x65 cm with height of 45 cm). Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
Ventilation: 15-20 air exchanges/hour

The environmental parameters were recorded twice daily during the acclimatisation and experimental phases.

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
The test item was used as supplied, as a single dose of 0.5 g EMI-DBS, applied to the test area. The untreated skin of each animal served as a control.
Duration of treatment / exposure:
Duration of exposure: 4 hours. After the treatment period, the test item was removed with water at body temperature.
Observation period:
Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes and then at 24, 48, 72 hours, 1, 2 and 3 weeks after patch removal.
Number of animals:
3
Details on study design:
Application of the Test Item

Patch testing was used to detect primary irritating effects of the test item. Three male animals in acceptable health condition were selected for this test.
Approximately 24 hours prior to the test, the hair was clipped from the back and flanks of the animals. Removal of hair was performed in two steps. The majority of hair was clipped with an electronic hair clipper and the remaining hair was moistened with water and shaved with a razor.
The test item was applied to an approximately 6 cm2 area of intact skin as follows:
- A single layer of a fine medical gauze (open-weave with large holes) of approximately 5x5 cm was placed over the application area,
- The appropriate amount of test item was carefully spread over the application area (the gauze helped maintain the test item in place),
- Three more layers of gauze were placed over the test item,
- These gauze patches were kept in contact with the skin by a patch of clear plastic with a surrounding adhesive hypoallergenic plaster to ensure continued good contact between the moistened test item and the shaved skin.
- The entire trunks of the animals were wrapped with plastic wrap for 4 hours.
- Medical elastic tubing was placed over the plastic to keep it in place.

An initial test was performed using one animal. One hour after application of the test item, the application site was examined. No severe irritation or corrosive effect was 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 then included in the study.

Duration of exposure: 4 hours. After the treatment period, the test item was removed with water at body temperature.

Scoring and Assessment of Local Reactions

The dermal irritation scores were evaluated according to the scoring system by Draize (1959). The animals were observed for 3 weeks and the duration of the study was sufficient to evaluate fully the reversibility or irreversibility of the effects observed.

Classification of Test Item

Results were presented and interpreted according to (I) Directive 2001/59/EC, (II) Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006 and the (III) UN Globally Harmonised System of Classification and Labelling of Chemicals.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours after patch removal
Score:
2
Reversibility:
fully reversible within: 3 weeks
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours after patch removal
Score:
3
Reversibility:
fully reversible within: 3 weeks
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours after patch removal
Score:
3
Reversibility:
fully reversible within: 3 weeks
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours after patch removal
Score:
1.33
Reversibility:
fully reversible within: 3 weeks
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours after patch removal
Score:
1.33
Reversibility:
fully reversible within: 3 weeks
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours after patch removal
Score:
2
Reversibility:
fully reversible within: 3 weeks
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 hours after patch removal
Score:
4.22
Reversibility:
fully reversible within: 3 weeks
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 48 hours after patch removal
Score:
4.22
Reversibility:
fully reversible within: 3 weeks
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 hours after patch removal
Score:
4.22
Reversibility:
fully reversible within: 3 weeks
Other effects:
There was no mortality observed during the studty. There were no effects of treatment on body weight. No treatment-related clinical signs were noted.

Any other information on results incl. tables

At observation one hour after patch removal: moderate to severe erythema (score 3) was noted in one animal, well defined erythema (score 2) was noted in two animals, moderate oedema (score 3) was observed in two animals and slight oedema (score 2) was noted in one animal.

At observation 24 hours after patch removal: moderate to severe erythema (score 3) was noted in two animals, well defined erythema (score 2) was noted in one animal, and slight oedema (score 2) was noted in all animals. Dry skin surface was also noted in two animals.

At observation 48 and 72 hours after patch removal: moderate to severe erythema (score 3) was noted in two animals, well defined erythema (score 2) was noted in one animal, slight oedema (score 2) was observed in one animal and very slight oedema (score 1) was noted in two animals. Dry skin surface was also noted in one animal at 48 hours after patch removal and dry and callus skin surface was noted in two animals and at 72 hours after patch removal in all animals.

At observation 1 week after patch removal: well defined erythema (score 2) was observed in one animal, very slight erythema (score 1) was observed in two animals and very slight oedema (score 1) was noted in one animal. Dry and peeling skin surface was noted in all animals.

At observation 2 weeks after patch removal: very slight erythema (score 1) was observed in two animals.

As signs of irritation were observed after two weeks, irreversibility could not be determined and the study was therefore extended by one week.

At three weeks after the patch removal: full recovery was observed in all rabbits and the study was terminated.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 2.00, 3.00 and 3.00 respectively.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 1.33, 1.33 and 2.00 respectively.

The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 4.22.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to Directive 2001/59/EC, EMI-DBS should be classified as "R38, irritating skin". According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, EMI-DBS is "Category 2- Irritant". According to the classification system based on the scheme devised by Draize (1959), EMI-DBS is a "moderate irritant". Further, the substance is classifed as a 'Category 2 Irritant' in accordance with the EU CLP, criteria.
Executive summary:

The skin irritation potential of the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 404. The substance was applied to the clipped skin of 3 New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test item was evaluated according to the Draize method. To assess skin irritation, animals were examined at 1, 24, 48, 72 hours, 1, 2 and 3 weeks after the patch removal. Additional general examinations were performed daily. There was no mortality or systemic clinical changes related to EMI-DBS administration. There was no effect of treatment on body weight. At three weeks after the patch removal, full recovery was observed in all rabbits and the study was terminated. The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 2.00, 3.00 and 3.00 respectively. The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 1.33, 1.33 and 2.00 respectively. The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 4.22. According to Directive 2001/59/EC, EMI-DBS should be classified as "R38, irritating skin". According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, EMI-DBS is "Category 2- Irritant". According to the classification system based on the scheme devised by Draize (1959), EMI-DBS is a "moderate irritant". Further, the substance is classifed as a 'Category 2 Irritant' in accordance with the EU CLP, criteria.

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