Reaction products of 1,4-Benzenedimethanol and 1-naphthol

Endpoint summary

Description of key information

In-Vivo Skin irritation:

SN-475N does not require classification as a skin irritant.

In-Vivo Eye irritation:

SN-475N does not require classification as a eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 October 2012 to 19 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

In-Vivo study carried out as substance is intended for global registration where In-Vivo data is required.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

See any other information section for details

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

See any other information section for details

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

yes

Remarks:

See any other information section for details

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

No further details specified in the study report

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

EXPERIMENTAL ANIMALS
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: ~14 - 15 weeks old
Sex: Male
Body weight range at the
beginning of the in-life phase: 3477 – 3618 g
end of the in-life phase: 3572 – 3701 g
Acclimation time: 33 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.

Husbandry
Number of animal room: 618
Lighting periods: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature range during
the study: 18.5-22.2 °C
Relative humidity during
the study: 38 – 82 %
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 temperature and relative humidity values were measured continuously. The measured range was checked at least daily during the acclimatisation and experimental phases.
Variation from the target relative humidity (max. 82 %) was observed during the acclimation period. 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.

Food and Feeding
Animals received UNI diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary, ad libitum. Animals were provided with the following batch:
• 0140 07 12, expiry date: 25 October 2012
The details of the diet used will be archived with the raw data and are not reported.

Water Supply
The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.

Water Analysis
The drinking water is routinely analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. The quality control analysis is performed once every three months and microbiological assessment is performed monthly by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A.u.36., Hungary). Copies of the relevant Certificates of Analysis are retained in the archives at CiToxLAB Hungary Ltd.

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

The test item was used as supplied, as a single dose of 0.5 g, applied to the test area.

Duration of treatment / exposure:

4 hours

Observation period:

To assess skin irritation, animals were examined at 1, 24, 48, and 72 hours after the patch removal. Additional general examinations were performed daily.

Number of animals:

3

Details on study design:

TREATMENT PERIOD
Day of treatment
Day 0
16 October 2012

Animal skin examination and assignment to study
Day 0 (pre-treatment)
16 October 2012

Body weight measurement
Day 0, 3
16 and 19 October 2012

Clinical observation
Scoring at 1, 24, 48 and 72 hours after treatment
(16, 17, 18 and 19 October 2012)

End of in life phase
Day 3
19 October 2012

ADMINISTRATION OF THE TEST ITEM

Dosage
The test item was used as supplied, as a single dose of 0.5 g, applied to the test area. The untreated skin of each animal served as a control. The test item was powdered which was dispensed for studies with this test item.

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

OBSERVATIONS AND SCORING

Clinical Observations
Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes and then at 24, 48 and 72 hours after patch removal.

Scoring and Assessment of Local Reactions
The dermal irritation scores were evaluated according to the scoring system by Draize (1959) shown in Appendix 1. The animals were observed for 72 hours and the duration of the study was sufficient to evaluate fully the reversibility or irreversibility of the effects observed.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Other effects:

Measurement of Body Weight
Body weights were recorded at the beginning and at the end of experiment.

Termination
At the end of the observation period, euthanasia of the animal was by intramuscular injections of CP-Ketamin 10 % and CP-Xylazin 2 % followed by i.v. Euthasol® 40% anaesthesia (see details in 3.1.2.). Death was verified by checking pupil and cornea reflex, absence of respiration and pulse.

SCORING OF ERYTHEMA FORMATION

 

Animal No./ Sex	Body weight (g)		1 h	24 h	48 h	72 h
	At the beginning of the study	At the end of the study
2607 / M	3618	3701	0	0	0	0
2643 / M	3477	3572	0	0	0	0
2606 / M	3552	3644	0	0	0	0
Total	-	-	0	0	0	0

 

M = male

h = hour

 

SCORING OF OEDEMA FORMATION

Animal No./ Sex	Body weight (g)		1 h	24 h	48 h	72 h
	At the beginning of the study	At the end of the study
2607 / M	3618	3701	1	0	0	0
2643 / M	3477	3572	0	0	0	0
2606 / M	3552	3644	0	0	0	0
Total	-	-	1	0	0	0

 

M = male

h = hour

Interpretation of results:

study cannot be used for classification

Conclusions:

SN-475N does not require classification as a skin irritant.

Executive summary:

An acute skin irritation study was performed with SN-475N in 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 (OECD No.: 404, 2002).

A volume of 0.5 g test item was applied to the skin of the experimental animals. The test item was applied as a single dose. Sufficient water to damp the material was used to ensure good contact with the skin. Sterile gauze pads were placed on the skin of rabbits. These gauze pads were kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control.

After 4 hours, the remaining test item was removed with water at body temperature.

To assess skin irritation, animals were examined at 1, 24, 48, and 72 hours after the patch removal. Additional general examinations were performed daily.

There was no mortality during the observation period.

There was no test item related effect on body weight.

At observation one hour after patch removal, oedema (score 1) on 1/3 animals were observed on the skin of the treated animals.

At observation 24, 48 and 72 hours after patch removal, there were no observed clinical signs noted on the skin of the treated animals.

As no clinical signs were observed at 72 hours after patch removal, the study was terminated after the 72 hours observation.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.00, 0.00 and 0.00 respectively.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.00, 0.00 and 0.00 respectively.

The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.00.

According to Directive 2001/59/EC, SN-475N does not require classification as a skin irritant.

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, SN-475N does not require classification as a skin irritant.

According to the classification system based on the scheme devised by Draize (1959), SN-475N is a "non-irritant"

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Justification for type of information:

In-vivo study carried out as substance is intended for global registration where in-vivo data is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Justification for type of information:

In-Vivo study carried out as substance is intended for global registration where In-Vivo data is required.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 October 2012 to 26 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

In-Vivo study carried out as substance is intended for global registration where In-Vivo data is required

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

See other information on method section for details

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

See other information on method section for details

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

See other information on method section for details

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

No further details specified in the study report

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

EXPERIMENTAL ANIMALS
Species and strain: New Zealand White rabbit
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 animal in acceptable health condition was used for the test. Both eyes of animal provisionally selected for testing were examined prior to starting the study.
Number of animals: 3 animals
Age of animals at treatment: ~14-15 weeks old (young adult)
Sex: Male
Body weight at the
beginning of the in-life phase: 3756-3828 g
end of the in-life phase: 3822-3897 g
Date of receipt: 13 and 19 September 2012

Acclimatization time: At least 34 days
Animal identification: The individual identification was by engraved ear tag. The cage was marked with individual identity card with information about study code, sex, dosage, cage number and individual animal number.

HUSBANDRY
Animal health: Only healthy animals were used for the test. The veterinarian certified health status.
Number of animal room: 609
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature
during the in-life phase: 17.5 – 22.2°C
Relative humidity
during the in-life phase: 40 – 82 %
Housing/Enrichment: Rabbit was individually housed in AAALAC approved metal wire rabbit cages. Cage was of an open wire structure and cage was placed together to allow some social interaction with rabbit(s) in adjoining cages.
Ventilation: 15-20 air exchanges/hour.
The temperature and relative humidity values were measured continuously. The measured range was checked at least daily during the acclimatisation and experimental phases.
Variations from the target relative humidity (max. 82 %) were observed during the acclimation period. 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.

FOOD AND FEEDING
Animals received diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum (Batch number: 0140 07 12 Expiry date: 25 October 2012,). The details of diets used will be archived with the raw data and are not reported.

WATER SUPPLY AND QUALITY CONTROL OF WATER
The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system. The quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201
Veszprém, József A.u.36., Hungary). The quality control results are retained in the archives of CiToxLAB Hungary Ltd.

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

A single volume of 0.1g of the solid test item SN-475N was administered to the animals.

Duration of treatment / exposure:

The treated eye was rinsed with physiological saline solution at 1 hour observation.

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

Not applicable

Number of animals or in vitro replicates:

3 animals

Details on study design:

ADMINISTRATION OF THE TEST ITEM
Dosage
A single volume of 0.1g of the solid test item SN-475N was administered to the animals.

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 a few seconds to prevent the loss of the test item. The contra lateral eye served as the control. Immediately after the administration of the test item, an assessment of the initial pain reaction was made according to the six point scale.
After consideration of the ocular responses produced in the first animal, one hour after the treatment of the first animal, two additional animals were treated.

Duration of Exposure
The treated eye was rinsed with physiological saline solution at 1 hour observation.

OBSERVATIONS AND SCORING
Clinical Observations
The eyes were examined at 1, 24, 48 and 72 hours after the application. 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, the animals were 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.

Scoring and Assessment of Local Reaction
The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (24 April 2002)

Classification of the Test Items
Individual reactions of the animal were recorded at each observation time. The nature, severity and duration of all lesions observed were described.
Results were presented and interpreted according to Regulation (EC) No 1272/2008 and UN Globally Harmonised System of Classification and Labelling of Chemicals.

Measurement of Body Weight
Individual body weight was recorded at the beginning (the day of treatment) and end of the experiment.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Examination of eye-irritancy
The eyes were examined at 1, 24, 48 and 72 hours after the application.
Initial Pain Reaction (IPR) (score 2) was observed in two animals and (score 1) in one animal.
One hour after the application, conjunctival redness (score 2) was seen in all animals, conjuctival chemosis (score 2) was observed in one animal and (score 1) in two animals, discharge (score 2) was seen in all rabbits.
At 24 hours after treatment, conjunctival redness (score 2) was seen in all animals, discharge (score 1) was seen in one rabbit.
At 48 hours after treatment, conjunctival redness (score 1) was seen in all animals.
At 72 hours after treatment, no signs of eye irritation or other clinical signs were observed.

Other effects:

MORTALITY
There was no mortality observed during the study.

BODY WEIGHTS
The body weight and body weight change were considered to be normal with no indication of a treatment related effect.

CLINICAL OBSERVATION
General daily examination
There were no clinical signs observed that could be related to treatment.

Study Code: 12/356-005N

Species: NZW Rabbit

Dose: 0.1 g

Sex: Male

Start of Exposure: 23 October 2012

Test Item: SN-475N

 

Abbreviations:

R = Redness, OD = Opacity degree of density,

CH = Chemosis, OE = Extent of opaque area,

D = Discharge, IPR = Initial pain reaction

 

Time of Observation: Day 0

Time	Animal No.	Score of irritation								IPR
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
1 hour	2639	2	2	2	0	0	0	0	0	1
	2646	2	1	2	0	0	0	0	0	2
	2601	2	1	2	0	0	0	0	0	2

 

 Time of Observation: Day 1

Time	Animal No.	Score pf irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
24 hours	2639	2	0	1	0	0	0	0	0
	2646	2	0	0	0	0	0	0	0
	2601	2	0	0	0	0	0	0	0

 

 Time of Observation: Day 2

Time	Animal No.	Score pf irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
48 hours	2639	1	0	0	0	0	0	0	0
	2646	1	0	0	0	0	0	0	0
	2601	1	0	0	0	0	0	0	0

Time of Observation: Day 3

Time	Animal No.	Score pf irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
72 hours	2639	0	0	0	0	0	0	0	0
	2646	0	0	0	0	0	0	0	0
	2601	0	0	0	0	0	0	0	0

 

 Mean Values of Eye Irritation (24, 48, 72 hour reading)

 

Study Code: 12/356-005N

Species: NZW Rabbit

Dose: 0.1 g

Sex: Male

Start of Exposure: 23 October 2012

Test Item: SN-475N

 

Animal Number	Sex	Cornea Opacity	Iris	Conjunctivae
				Redness	Chemosis	Discharge
2639	Male	0.00	0.00	1.00	0.00	0.33
2646	Male	0.00	0.00	1.00	0.00	0.00
2601	Male	0.00	0.00	1.00	0.00	0.00

 

 Body Weight Data

 

Animal Number	At the beginning of experiment (Day of treatment) (g)	At the end of experiment (72 hours after treatment) (g)	Body weight gain (g)
2639	3787	3846	59
2646	3756	3822	66
2601	3828	3897	69

 

Interpretation of results:

GHS criteria not met

Conclusions:

The test item SN-475N (Batch No.: 90603), applied to rabbit eye mucosa, caused conjunctival irritant effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 72 hours. Not classified as eye irritant.

Executive summary:

An acute eye irritation study of the test item SN-475N was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002).

The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. A single volume of 0.1 g of the test item was administered as a single dose.

Individual body weight was recorded at the beginning (the day of treatment) and end of the experiment. Morbidity and clinical signs of toxicity were checked daily. The eyes were examined at 1, 24, 48 and 72 hours after the application.

Initial Pain Reaction (IPR) (score 2) was observed in two animals and (score 1) in one animal.

One hour after the application, conjunctival redness (score 2) was seen in all animals, conjuctival chemosis (score 2) was observed in one animal and (score 1) in two animals, discharge (score 2) was seen in all rabbits.

At 24 hours after treatment, conjunctival redness (score 2) was seen in all animals, discharge (score 1) was seen in one rabbit.

At 48 hours after treatment, conjunctival redness (score 1) was seen in all animals.

At 72 hours after treatment, no signs of eye irritation or other clinical signs were observed.

As all signs of eye irritation had fully reversed the study was terminated after a period of 72 hours observation.

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

The body weight of the treated rabbits was considered to be within the normal range of variability.

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

chemosis : 0.00, 0.00, 0.00

discharge : 0.33, 0.00, 0.00

redness : 1.00, 1.00, 1.00

cornea opacity : 0.00, 0.00, 0.00

iris : 0.00, 0.00, 0.00

The test item SN-475N (Batch No.: 90603), applied to rabbit eye mucosa, caused conjunctival irritant effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 72 hours.

According to Regulation (EC) No 1272/2008, SN-475N does not require classification as an eye irritant.

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, SN-475N does not require classification as an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to Directive 2001/59/EC, SN-475N does not require classification as a skin irritant.

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, SN-475N does not require classification as a skin irritant.

According to the classification system based on the scheme devised by Draize (1959), SN-475N is a "non- irritant".