Registration Dossier

Administrative data

Description of key information

Skin: A single 4-Hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight to well-defined erythema and very slight to slight edema. Moderate desquamation was noted at one treated skin site. One treated skin site appeared normal at the 48-Hour observation, one other treated skin site appeared normal at the 7-Day observation and the remaining treated skin site appeared normal at the 14-Day observation.
Eye in vitro: Test was not needed as the test item was considered unlikely to have the potential to cause severe ocular irritancy in vivo.

Eye in vivo: A single application of the test item to the non-irrigated eye of three rabbits produced diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation. Two treated eyes appeared normal at the 72-Hour observation and one treated eye appeared normal at the 7-Day observation.

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:
17 June 2014 to 22 July 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK.
At the start of the study the animals weighed 2.08 to 2.62 kg and were twelve to twenty weeks old. After an acclimatization period of at least five days each animal was given a number unique within the study.
The animais were individually housed in suspended cages. Free access to mains drinking water and food was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal flank area using veterinary clippers. Only animais with a healthy intact epidermis by gross observation were selected for the study.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
Observation period:
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored
Number of animals:
3 (2 males + 1 female)
Details on study design:
The test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were retumed to their cages for the duration of the exposure period.
Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions. Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Male 74397
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Male 74398
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: Female 74485
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: Male 74397
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Male 74398
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Female 74485
Irritant / corrosive response data:
Individual scores for erythema / eschar and edema are given in Table 1 (attached).
Well-defined erythema and slight edema were noted at one treated skin site (male no. 74398) with very slight erythema and very slight edema noted at one other treated skin site (male no. 74397) immediately, 1 and 24 hours after patch removal.
Well-defined erythema and slight edema persisted at one of these treated skin sites (male no. 74398) at the 48 and 72-Hour observations. Very slight erythema was noted at the remaining treated skin site (female no. 74485) 1 hour after patch removal with well-defined erythema and very slight edema noted at the 24 and 48-Hour observations and well-defined erythema at the 72-Hour observation. Moderate desquamation was noted at this treated skin site at the 7-Day observation.
One treated skin site (male no. 74397) appeared normal at the 48-Hour observation, one other treated skin site (male no. 74398) appeared normal atthe 7-Day observation and the remaining treated skin site (female no. 74485) appeared normal at the 14-Day observation.
Other effects:
All animals showed expected gain in body weight during the study (see Table 2, attached).
Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not a skin irritant in rabbits. In accordance with EU CLP Regulation (EC) No. 1272/2008 classification of this substance is not required for dermal irritation because scores for erythema and edema did not fulfill the criteria for classification. In addition the primary effects, erythema and edema, were fully reversible by the end of the 14-day observation period.
Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit.

Method

On the day before the test two rabbits were clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study. On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period. Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water. Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the Draize scheme.

Results

A single 4-Hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight to well-defined erythema and very slight to slight edema. Moderate desquamation was noted at one treated skin site. One treated skin site appeared normal at the 48-Hour observation, one other treated skin site appeared normal at the 7-Day observation and the remaining treated skin site appeared normal at the 14-Day observation.

Conclusion

The test item produced a primary irritation index of 2.5 and was considered to be a moderate irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted.

According to GHS classification:

The test item produced a primary irritation index of respectively 0.33, 2 and 2 for erythema and Eschar formation for male 74397, male 74398 and female 74485 (considering observations at time 24h, 48h and 72h according to GHS requirements).

The test item produced a primary irritation index of respectively 0.33, 2 and 0.67 for oedema formation for male 74397, male 74398 and female 74485 (considering observations at time 24h, 48h and 72h according to GHS requirements).

In accordance with EU CLP Regulation (EC) No. 1272/2008 classification of this substance is not required for dermal irritation because scores for erythema and edema did not fulfil the criteria for classification. In addition the primary effects, erythema and edema, were fully reversible by the end of the 14-day observation period.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 March 2014 to 24 March 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
No
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three New Zealand White strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.51 to 3.29 kg and were twelve to twenty weeks old. After an acclimatization period of at least five days each animal was given a unique number .

The animals were individually housed in suspended cages. Free access to mains drinking water and food was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Vehicle:
unchanged (no vehicle)
Controls:
other: own control with other eye
Amount / concentration applied:
0.1 mL of the test item was placed into the conjunctival sac of the right eye
Duration of treatment / exposure:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977)
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977)
Number of animals or in vitro replicates:
3
After consideration of the ocular responses produced in the first treated animal, two additional animals were similarly treated.
Details on study design:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.
Initially, a single rabbit was treated. A subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Five minutes prior to test item application, a pre-dose anesthesia of ocular anesthetic (two drops of 0.5% tetracaine hydrochloride) was applied to each eye.
Initially, a single rabbit was treated. A volume of 0.1 mL of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made.
Eight hours after test item application, a subcutaneous injection of post-dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 12 hours later. No further analgesia was required.
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Any clinical signs oftoxicity, if present, were also recorded.
An additional observation was made in one treated eye on Day 7 to assess the reversibility of the ocular effects.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 74009 Female
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 74042 Male
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 74059 Male
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: 74009 Female
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: 74042 Male
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 74059 Male
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 74009 Female
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 74042 Male
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
mean score
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 74059 Male
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 74009 Female
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 74042 Male
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean score
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: 74059 Male
Irritant / corrosive response data:
Diffuse comeal opacity and iridial inflammation were noted in one treated eye at the 24 and 48-Hour observations.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in two treated eyes with minimal conjunctival irritation noted in one treated eye at the 24-Hour observation. Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in two treated eyes at the 48-Hour observation. Minimal conjunctival irritation was noted in one treated eye at the 72-Hour observation.
Two treated eyes appeared normal at the 72-Hour observation and one treated eye appeared normal at the 7-Day observation
Other effects:
One animal showed body weight loss and two animais showed expected gain in body weight during the study.

Interpretation of results:
GHS criteria not met
Conclusions:
The test item produced a maximum group mean score of 10.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The substance is not classified for eye irritation in regard to Regulation No. 1272/2008.
Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit.

Method

In the absence of information on the ocular irritancy potential of the test item, a Rabbit Enucleated Eye Test was performed prior to the in vivo test. The results indicated that the test item was unlikely to cause severe ocular irritancy.

A volume of 0.1 mL of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made . Eight hours after test item application, a subcutaneous injection of post-dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 0.5 hours later. No further analgesia was required. After consideration of the ocular responses produced in the first treated animal, a second animal was similarly treated. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977).

Results

A single application of the test item to the non-irrigated eye of three rabbits produced diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation. Two treated eyes appeared normal at the 72-Hour observation and one treated eye appeared normal at the 7-Day observation.

Conclusion

The test item produced a maximum group mean score of 10.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The substance does not meet the criteria for classification as an eye irritant under the terms of Regulation No. 1272/2008.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
05 March 2014 to 24 March 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
no guideline available
Principles of method if other than guideline:
The method involved application of the test item onto the cornea of the enucleated rabbit eye.
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
240 minutes
Number of animals or in vitro replicates:
Three
Details on study design:
The method for evaluation of ocular irritation by slit-lamp biomicroscopic examination using the McDonald-Shadduck score system is shown in the document attached.
Irritation parameter:
cornea opacity score
Run / experiment:
Rabbit enucleated eye test
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Irritation parameter:
fluorescein retention score
Run / experiment:
Rabbit enucleated eye test
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Irritation parameter:
percent corneal swelling
Run / experiment:
Rabbit enucleated eye test
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
other: 240 minutes post exposure
Irritant / corrosive response data:
Summary tables showing corneal opacity results, corneal epithelium condition, fluorescein uptake 240 minutes post dosing, and percentage corneal swelling are attached.
Interpretation of results:
other: eye irritation in vivo not expected
Conclusions:
Following assessment of data for corneal thickness, corneal opacity, alteration of corneal epithelium and fluorescein uptake, the test item was considered unlikely to have the potential to cause severe ocular irritancy in vivo.
Executive summary:

INTRODUCTION

Ocular irritancy potential of the test item was assessed using the rabbit enucleated eye test. The method involved the application of test item onto the cornea of the enucleated eye. The rabbit enucleated eye test is used as a first stage in the assessment of ocular irritancy potential. A negative ocular irritancy potential may require further investigation using an in vivo ocular irritation test. The test has undergone validation and has been shown to reliably detect substances that are negligible, or moderate to severe ocular irritants.

METHODS

Five enucleated eyes obtained from the New Zealand White strain of rabbit were maintained at a temperature of 32 ± 1.5 °C within the superfusion apparatus. Test item (0.1 mL) was applied to the cornea of each of three enucleated eyes. The direct effect of the test item on the cornea was assessed by evaluation of corneal thickness, corneal opacity, alteration of corneal epithelium and fluorescein uptake throughout the duration of the test. The data for all endpoints was assessed and an estimate of ocular irritancy potential was made. A further two enucleated eyes remained untreated for control purposes.

CONCLUSION

Following assessment of data for corneal thickness, corneal opacity, alteration of corneal epithelium and fluorescein uptake, the test item was considered unlikely to have the potential to cause severe ocular irritancy in vivo.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

SKIN

Introduction

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit.

Method

On the day before the test two rabbits were clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study. On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period. Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water. Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the Draize scheme.

Results

A single 4-Hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight to well-defined erythema and very slight to slight edema. Moderate desquamation was noted at one treated skin site. One treated skin site appeared normal at the 48-Hour observation, one other treated skin site appeared normal at the 7-Day observation and the remaining treated skin site appeared normal at the 14-Day observation.

Conclusion

The test item produced a primary irritation index of 2.5 and was considered to be a moderate irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted.

According to GHS classification:

The test item produced a primary irritation index of respectively 0.33, 2 and 2 for erythema and Eschar formation for male 74397, Male 74398 and female 74485 (considering observations at time 24h, 48h and 72h according to GHS requirements).

The test item produced a primary irritation index of respectively 0.33, 2 and 0.67 for oedema formation for male 74397, Male 74398 and female 74485 (considering observations at time 24h, 48h and 72h according to GHS requirements).

In accordance with EU CLP Regulation (EC) No. 1272/2008 classification of this substance is not required for dermal irritation because scores for erythema and edema did not fulfil the criteria for classification. In addition the primary effects, erythema and edema, were fully reversible by the end of the 14-day observation period.

EYE (in vitro)

An in vitro study does not need to be conducted because adequate data from an in vivo study is available.

EYE (in vivo)

Introduction

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit.

Method

In the absence of information on the ocular irritancy potential of the test item, a Rabbit Enucleated Eye Test was performed prior to the in vivo test. The results indicated that the test item was unlikely to cause severe ocular irritancy. A volume of 0.1 mL of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower li d away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made . Eight hours after test item application, a subcutaneous injection of post-dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 0.5 hours later. No further analgesia was required. After consideration of the ocular responses produced in the first treated animal, a second animal was similarly treated. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977).

Results

A single application of the test item to the non-irrigated eye of three rabbits produced diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation. Two treated eyes appeared normal at the 72-Hour observation and one treated eye appeared normal at the 7-Day observation.

Conclusion

The test item produced a maximum group mean score of 10.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The substance does not meet the criteria for classification as an eye irritant under the terms of Regulation No. 1272/2008.

Justification for classification or non-classification

The criteria for classification of the test item as an irritant to the skin or eye of rabbits in accordance with Regulation No 1272/2008 have not been fulfilled.

The substance is not classified for skin irritation in regard to Regulation No. 1272/2008.

The substance is not classified for eye irritation in regard to Regulation No. 1272/2008.