Registration Dossier

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Administrative data

Description of key information

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. The test item EMI-DBS, applied to rabbit eye mucosa, caused significant conjunctival irritant effects at one hour which were reduced at 2 weeks after application. The effects were not fully reversible within 3 weeks. According to Regulation (EC) No 1272/2008, EMI-DBS requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1)). In this in vitro eye irritation study in the Isolated Chicken Eyes model with EMI-DBS, the results suggest that the test item was moderate irritating. Based on the results of an in vitro eye irritation study, and according to the guideline OECD 438, EMI-DBS does not require a classification as a severe eye irritant; an in vivo rabbit study is therefore required for classification.

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

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.

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye 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 in a GLP laboratory using OECD Testing Guideline 405.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
see box below
Principles of method if other than guideline:
The relative humidity (38 - 76%) and temperature (16.6 – 23.4 oC) were out of the target range during the study.
These deviations are considered to have no impact on the outcome of the study and interpretation of the results.
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues 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 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. Both eyes of each animal provisionally selected for testing were examined approximately one hour before starting the study. Animals showing eye irritation, ocular defects or pre-existing corneal injury were not used.
Number of animals: 3
Age of animals at treatment: ~12 weeks old (adult)
Sex: Male
Body weight range at the
- beginning of the life phase: 3105-3202 g
- end of the life phase: 3780-3882 g
Date of receipt: 24 August 2011
Acclimatization time: 13 days
Animal identification: The individual identification was by engraved ear tag. The cages were marked with individual identity cards with information about study code, sex, dose group, cage number and individual animal number.
Animal health: Only healthy animals were used for the test. The veterinarian certified health status.
Number of animal room: 607
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 16.6 – 23.4°C
Relative humidity: 38-76%
Housing/Enrichment: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. 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 study. Variations from the target humidity and temperature range were observed during the study. These deviations were considered to have no impact on the animal health, as certified by the Clinical Veterinarian, or on the outcome of the study and interpretation of the results.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
A single dose of 0.1 ml of the paste test item EMI-DBS was administered to each animal.
Duration of treatment / exposure:
The test item was applied once and observations made up to 3 weeks after application.
Observation period (in vivo):
The eyes were examined at 1, 24, 48, 72 hours and 1, 2 and 3 weeks after treatment. The duration of the observation period was sufficient to identify reversibility or irreversibility of changes. Any clinical signs of toxicity or signs of ill- health during the study were recorded.
At the end of the observation period, each animal was sacrificed by intramuscular injections of CP-Ketamin 10% and CP-Xylazin 2% followed by iv. Euthasol® 40% anaesthesia. Death was verified by checking pupil and corneal reflex and the absence of respiration.
Number of animals or in vitro replicates:
3
Details on study design:
Application of the Test Item

Three male animals in acceptable health condition were selected for the test. Care was taken to select only those animals that had a normal eye condition and any with ocular lesions were rejected.
An initial test was performed using one animal. The test item was instilled into the conjunctival sac of the left eye. The eyelids were held closed for several seconds to prevent the loss of the test item. The contralateral eye served as the control. Immediately after the administration of the test item, an assessment of the initial pain reaction was made according a six point scale.
After consideration of the ocular responses produced in the first animal, two additional animals were treated.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: Considering readings at 24, 48 and 72 hours after treatment
Score:
1.33
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
1.67
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
1.67
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
iris score
Basis:
other: animal number 1, 2 and 3
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
0
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
other: Conjunctivae redness
Basis:
animal #1
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
2.33
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
other: Conjunctivae redness
Basis:
animal #2
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
2.67
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
other: Conjunctivae redness
Basis:
animal #3
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
2.67
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
3
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
2.33
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
other: Conjunctivae discharge
Basis:
animal #1
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
3
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
other: Conjunctivae discharge
Basis:
animal #2
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
2.33
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
other: Conjunctivae discharge
Basis:
animal #3
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
2.33
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: Considering readings at 24, 48 and 72 hours after the treatment
Score:
2.67
Reversibility:
not fully reversible within: 3 weeks
Remarks on result:
other: Animal's individual mean score
Other effects:
There was no mortality observed during the study. The body weight and body weight change were considered to be normal with no indication of treatment related effect. There were no clinical signs observed that could be related to treatment.

Examination of eye-irritancy

The eyes were examined at 1, 24, 48, 72 hours and 1, 2 and 3 weeks after the application.

Initial Pain Reaction (IPR) (score 2 or 3) was observed in all animals after test item administration.

One hour after the application: Conjunctival redness (score 2), conjunctival chemosis (score 3) and discharge (score 3) were observed in all animals. All animals showed corneal opacity (score 1, area 4).

At 24 hours after treatment: Conjunctival redness, chemosis and discharge (score 3) were seen in all rabbits. All animals showed corneal opacity (score 1, area 4).

At 48 hours after treatment: Conjunctival redness (score 2 or 3), chemosis and discharge (score 3 - 3) were seen in all rabbits. All animals showed corneal opacity (score 1 or 2 , areas 4, 3 or 2).

At 72 hours after treatment: Conjunctival redness (score 2), chemosis (score 1, 2 or 3) and discharge (score 1 or 3) were seen in all rabbits. All animals showed corneal opacity (score 2 , areas 1 or 3).

At 1 week after treatment: Conjunctival redness (score 1 or 2) and discharge (score 1 or 3) were seen in all rabbits. Conjuctival chemosis (score 1 or 2) was observed in two animals. Two animals showed corneal opacity (score 2 , area 3).

At 2 weeks after treatment: Conjunctival redness (score 1) was seen in all rabbits. Conjuctival chemosis (score 1) and discharge (score 1) were observed in two animals. Two animals showed corneal opacity (score 2 , areas 1 or 2). In two animals, vascularisation was observed on the surface of the cornea. the extension of the vascularisation is not greater than 1/4 of the surface of the cornea.

At 3 weeks after treatment: Conjunctival redness (score 1) was seen in all rabbits. Conjuctival chemosis (score 1) was observed in one animal and discharge (score 1) was observed in two animals. Two animals showed corneal opacity (score 2 , areas 1 or 2). In one animals, vascularisation was observed on the surface of the cornea. The extension of the vascularisation is greater than 1/4 of the surface of the cornea.

The study was terminated after the 3-week observation.

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

Animal Number

Cornea Opacity

Iris

Conjunctivae

Redness

Chemosis

Discharge

00369

1.33

0.00

2.33

3.00

3.00

00445

1.67

0.00

2.67

2.33

2.33

00443

1.67

0.00

2.37

2.67

2.33

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item EMI-DBS, applied to rabbit eye mucosa, caused significant conjunctival irritant effects at one hour which were reduced at 2 weeks after application. The effects were not fully reversible within 3 weeks. According to Regulation (EC) No 1272/2008, EMI-DBS requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1)).
Executive summary:

The eye irritation potential of the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 405. The study was conducted by applying 0.1 ml of the test item in a single dose into the conjunctival sac of the left eye of male New Zealand White rabbits. Individual body weight was recorded at the beginning and end of the study. Morbidity and clinical signs of toxicity were checked daily. The eyes were examined at 1, 24, 48, 72 hours and 1, 2 and 3 weeks after the application.

No adverse effects on body weight development were noted during the study period. The general state and behavior of animals were normal throughout the study period. During the study, no signs of eye irritation were observed in the control eye of all animals.

Initial Pain Reaction (IPR) (score 2 or 3) was observed in all animals after test item administration.

One hour after the application: Conjunctival redness (score 2), conjunctival chemosis (score 3) and discharge (score 3) were observed in all animals. All animals showed corneal opacity (score 1, area 4). At 24 hours after treatment: Conjunctival redness, chemosis and discharge (score 3) were seen in all rabbits. All animals showed corneal opacity (score 1, area 4). At 48 hours after treatment: Conjunctival redness (score 2 or 3), chemosis and discharge (score 3 - 3) were seen in all rabbits. All animals showed corneal opacity (score 1 or 2 , areas 4, 3 or 2). At 72 hours after treatment: Conjunctival redness (score 2), chemosis (score 1, 2 or 3) and discharge (score 1 or 3) were seen in all rabbits. All animals showed corneal opacity (score 2 , areas 1 or 3). At 1 week after treatment: Conjunctival redness (score 1 or 2) and discharge (score 1 or 3) were seen in all rabbits. Conjuctival chemosis (score 1 or 2) was observed in two animals. Two animals showed corneal opacity (score 2 , area 3). At 2 weeks after treatment: Conjunctival redness (score 1) was seen in all rabbits. Conjuctival chemosis (score 1) and discharge (score 1) were observed in two animals. Two animals showed corneal opacity (score 2 , areas 1 or 2). In two animals, vascularisation was observed on the surface of the cornea. the extension of the vascularisation is not greater than 1/4 of the surface of the cornea. At 3 weeks after treatment: Conjunctival redness (score 1) was seen in all rabbits. Conjuctival chemosis (score 1) was observed in one animal and discharge (score 1) was observed in two animals. Two animals showed corneal opacity (score 2 , areas 1 or 2). In one animals, vascularisation was observed on the surface of the cornea. The extension of the vascularisation is greater than 1/4 of the surface of the cornea. The study was terminated after the 3-week observation. The test item EMI-DBS, applied to rabbit eye mucosa, caused significant conjunctival irritant effects at one hour which were reduced at 2 weeks after application. The effects were not fully reversible within 3 weeks.

According to Regulation (EC) No 1272/2008, EMI-DBS requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1)).

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A study was conducted on the registered substance to determine the skin irritation potential of the substance. 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. 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.

The eye irritation potential of the test substance was determined via an in vitro study in accordance with the OECD Guideline for Testing of Chemicals 438. In this in vitro eye irritation study in the Isolated Chicken Eyes model with EMI-DBS, the results suggest that the test item was moderate irritating. According to the guideline OECD 438, EMI-DBS does not require a classification as a severe eye irritant; therefore an in vivo rabbit study is required for classification.

The eye irritation potential of the test substance was subsequently determined via an in vivo study in accordance with the OECD Guideline for Testing of Chemicals 405. The study was conducted by applying 0.1 ml of the test item in a single dose into the conjunctival sac of the left eye of male New Zealand White rabbits. The test item EMI-DBS, applied to rabbit eye mucosa, caused significant conjunctival irritant effects at one hour which were reduced at 2 weeks after application. The effects were not fully reversible within 3 weeks. According to Regulation (EC) No 1272/2008, EMI-DBS requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1)).

Justification for selection of skin irritation / corrosion endpoint:

This key study was conducted in a GLP laboratory using OECD Testing Guideline 404.

Justification for selection of eye irritation endpoint:

This key study was conducted in a GLP laboratory using OECD Testing Guideline 405.

Effects on skin irritation/corrosion: moderately irritating

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

An in vitro eye irritation study was unable to identify a classification for the EMI-DBS test substance, as such an in vivo eye irritation study was conducted. The results of this study, in accordance with Regulation (EC) No 1272/2008, showed that EMI-DBS requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1)). The results of the in vivo skin irritation study were evaluated in accordance with the classification scheme devised by Draize (1959), as such the substance was found to be classifed as a 'Category 2 Irritant' in accordance with the EU CLP, criteria.

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