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Diss Factsheets

Administrative data

Description of key information

Skin Irritation

Under the conditions of this study, the test material was not considered a dermal corrosive following a 3 minute, 1 or 4 hour exposure periods. The test material was considered to be a Category 2: irritant in accordance with EU criteria.

Eye Irritation

Under the conditions of this study the test material is classified as Category 2: irritating to eyes, according to EU criteria.

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:
01 May 2000 to 29 May 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, 59 NouSan No. 4200
Version / remarks:
1985
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: males: 11 to 12 weeks of age and females: 12 weeks
- Weight at study initiation: males 2.2 to 2.7 kg and females: 2.5 to 2.6 kg
- Fasting period before study: no
- Housing: The animals were housed individually in suspended stainless steel cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: a minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 to 22 °C
- Humidity: 46 to 82 %
- Air changes: 10-15 air changes/hour
- Photoperiod: Light timers were set to maintain a 12-hour light/12-hour dark cycle
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: 100 %
Duration of treatment / exposure:
Single application for 3 minutes, 1 and 4 hours
Observation period:
Examined either immediately (3 and 1 hour exposures only) or at 1 hour after patch removal (4 hour exposure period) and at approximately 24, 48 and 72 hours and up to 28 days after patch removal.
Number of animals:
4 males and 2 females per dose.
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk
- area of coverage: approximately 1 x 1 inch
- For the 3-minute, 1- and 4-hour dosing procedures, the test material was administered under the gauze patch. For the initial animal dosed, the 1" x 1" 4-ply gauze was held in contact with the skin at the cut edges with tape for the 3 minute and 1 hour exposure periods. This tape apparently produced an interaction. Therefore, for the 4-hour exposure period and for the remaining animals, a 2" x 2" single ply gauze was used to cover the 4-ply 1"x1" gauze patch. The gauze patch was held in contact with the skin at the cut edges with a non-irritating tape except on the bottom side, which was left un-taped. Additional gauze was used to catch any potential leakage from the test site rather than the tape.
- Removal and ingestion of the test material was prevented by placing an elastic wrap over the trunk and test area (semi-occlusive binding). The elastic wrap was then further secured with adhesive tape around the trunk at the cranial and caudal ends. Using an indelible marker, a dot was placed on the elastic wrap over the area where the 1-hour exposure test site was located in order to facilitate removal of the patch at the appropriate exposure time interval.
- After dosing, collars were placed on each animal and remained in place until removal on day 3.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the residual test material was removed using gauze moistened with deionised water, followed by dry gauze.
- Time after start of exposure: 3 minutes, 1 hour or 4 hours.
- Following completion of the 3-minute and 1 hour exposure periods, an approximate 2" x 2" window was cut into the elastic wrap over the first test site and the gauze patch and tape were removed. The comers of the test site were delineated using a marker and the residual test article was removed using gauze moistened with deionized water, followed by dry gauze. Following patch removal for the exposure, the elastic wrap was taped down with nonirritating tape around the cut window in order to insure that the test site remained nonoccluded during the remainder of the study.

OBSERVATION TIME POINTS
- Animals were examined for signs of erythema and oedema and the responses scored immediately after patch removal (for the 3-minute and 1-hour exposure periods) or at 1 hour after patch removal (4-hour exposure period) and at approximately 24, 48 and 72 hours and up to 28 days after patch application according to the Macroscopic Dermal Grading System based on Draize. The dermal sites were re-clipped as necessary to allow clear visualisation of the skin.
- Any unusual observations and/or mortality were recorded. A general health/mortality check was performed twice daily (in the morning and in the afternoon).
- Individual body weights were obtained for each animal prior to dosing on day 0.
- Each animal was euthanised by an intravenous injection of sodium pentobarbital following its final scoring interval. Gross necropsy examinations were not required for these animals.

ANALYSIS OF DATA
- Each exposure period was evaluated independently. Corrosion was considered to have resulted if the substance in contact with rabbit skin had caused destruction or irreversible alteration of the tissue on at least two of the rabbits tested. Tissue destruction was considered to have occurred if, at any of the readings, there was ulceration or necrosis. Tissue destruction does not include merely sloughing of the epidermis, or erythema, oedema or fissuring.
- In the event that any exposure period was non-corrosive, the data from that exposure period was classified as indicated below:
The 1 (or initial observation), 24, 48 and 72 hour erythema and oedema scores for all animals were added and the total divided by the number of test sites x 4. The calculated Primary Irritation Index (P.1.1.) was classified according to the Dermal Evaluation Criteria.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 3 minutes
Score:
3.58
Reversibility:
fully reversible within: 14 days
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1 hour
Score:
4.25
Reversibility:
fully reversible within: 14 days
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 4 hours
Score:
4.88
Reversibility:
not reversible
Remarks:
persisted through to study day 28
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
R2464/M
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
R2467/M
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
R2466/M
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
R2476/M
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
R2509/F
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
R2513/F
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
R2464/M
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
R2467/M
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
R2466/M
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
R2476/M
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
R2509/F
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: After 3 minute exposure
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
R2513/F
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: After 3 minute exposure
Irritant / corrosive response data:
- Exposure to the test material for a 3-minute exposure period produced very slight to well-defined erythema and very slight oedema on 6/6 and 4/6 test sites, respectively, immediately following patch removal. The dermal irritation resolved completely on all test sites by study day 14. Additional dermal findings included superficial lightening and desquamation; and erythema extends beyond the test site, which were noted on 6/6 and 3/6 test sites, respectively.
- Exposure to the test material for a 1-hour exposure period produced very slight to well-defined erythema and very slight to slight oedema on 6/6 test sites immediately following patch removal. The dermal irritation resolved completely on all test sites by study day 14. Additional dermal findings included superficial lightening, desquamation and erythema extends beyond the test site; and blanching which were noted on 6/6 and 1/6 test sites, respectively.
- Exposure to the test material for a 4-hour exposure period produced well-defined erythema to notable dermal lesions (blanching) and very slight to severe oedema on 6/6 test sites at the 1-hour scoring interval. In one animal, the dermal irritation progressed to notable dermal lesions (blanching} by the 24-hour scoring interval. The dermal irritation resolved completely on 5/6 test sites by study day 14 and persisted in the remaining test site through study day 28. Additional dermal findings included superficial lightening, erythema extends beyond the test site and desquamation; and focal areas of purple within test site, which were noted on 6/6 and 3/6 test sites, respectively.

Table 1: Summary of scoring

 

Erythema

Oedema

Animal No.

2464/M

2467/M

2466/M

2476/M

2509/F

2513/F (3 min and 1 hour) 2463/M(4hour)

2464/M

2467/M

2466/M

2476/M

2509/F

2513/F (3 min and 1 hour) 2463/M(4hour)

 

3 Minute exposure

24 h

2

2

2

2

2

2

4

3

4

3

4

3

48 h

2

2

2

2

2

2

4

2

2

1

2

2

72 h

1

2

2

1

1

2

1

1

2

1

1

1

24/48/72h

1.7

2

2

1.7

1.7

2

3

2

2.7

1.7

2.3

2

Reversible within

10 days

7 days

14 days

7 days

10 days

10 days

7 days

7 days

10 days

7 days

7 days

7 days

 

1 hour exposure

24 h

2

2

2

M4

2

2

4

4

4

4

4

4

48 h

2

2

2

M4

2

2

4

3

2

2

2

3

72 h

2

2

1

2

1

2

1

2

1

2

1

3

24/48/72h

2

2

1.7

3.3

1.7

2

3

3

2.3

2.7

2.3

3.3

Reversible within

14 days

10 days

14 days

14 days

10 days

10 days

7 days

10 days

10 days

10 days

10 days

10 days

 

4 hour exposure

24 h

2

M4

2

2

2

M4

4

4

4

4

4

2

48 h

2

2

2

2

2

M4

4

3

2

2

2

2

72 h

1

2

2

1

2

M4

1

1

2

1

1

1

24/48/72h

1.7

2.7

2

1.7

2

4

3

2.7

2.7

2.3

2.3

1.7

Reversible within

14 days

14 days

14 days

10 days

10 days

not in 28 days

7 days

10 days

10 days

7 days

10 days

28 days

 

Interpretation of results:
other: EU crieria category 2: irritant
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, the test material was not considered a dermal corrosive following a 3 minute, 1 or 4 hour exposure periods. The test material was considered to be a Category 2: irritant in accordance with EU criteria.
Executive summary:

The skin irritation potential of the test material was investigated in accordance with the standardised guidelines OECD 404, OPPTS 870.2500 and JMAFF 59 NohSan No. 4200, under GLP conditions.

The potential irritant and/or corrosive effects were evaluated on the skin of New Zealand White rabbits. Six rabbits received 0.5 mL doses of the test material at 3 minute, 1 hour and 4 hour intervals. Patches were removed at specified time intervals and any remaining test material was wiped from the skin using gauze moistened with deionized water followed by dry gauze. Test sites were subsequently examined and scored for dermal irritation for up to 28 days following patch removal. 3-Minute Exposure: Exposure to the test material for the 3-minute exposure period produced very slight to well-defined erythema and very slight oedema on 6/6 and 4/6 test sites, respectively, immediately following patch removal. The dermal irritation resolved completely on all test sites by study day 14. Additional dermal findings included superficial lightening and desquamation; and erythema extending beyond the test site, which were noted on 6/6 and 3/6 test sites, respectively.

1-Hour Exposure: Exposure to the test material for the 1-hour exposure period produced very slight to well-defined erythema and very slight to slight oedema on 6/6 test sites immediately following patch removal. The dermal irritation resolved completely on all test sites by study day 14. Additional dermal findings included superficial lightening, desquamation and erythema extending beyond the test site; and blanching which were noted on 6/6 and 1/6 test sites, respectively.

4-Hour Exposure: Exposure to the test material for the 4-hour exposure period produced well-defined erythema to notable dermal lesions (blanching) and very slight to severe oedema on 6/6 test sites at the 1-hour scoring interval. In one animal, the dermal irritation progressed to notable dermal lesions (blanching) by the 24-hour scoring interval. The dermal irritation resolved completely on 5/6 test sites by study day 14 and persisted in the remaining test site through study day 28. Additional dermal findings included superficial lightening (6/6 test sites), erythema extending beyond the test site (5/6 test sites) and desquamation (6/6 test sites); focal areas of purple within the test site (3/6 test sites), and blanching (3/6 test sites).

Under the conditions of this study, the test material was not considered a dermal corrosive following a 3 minute, 1 or 4 hour exposure periods. The test material was considered to be a Category 2: irritant in accordance with EU 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
Study period:
08 May 2000 to 29 May 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, 59 NouSan No. 4200
Version / remarks:
1985
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12 to 15 weeks
- Weight at study initiation: males: 2.8 to 3.4 kg and female: 2.6 kg
- Housing: The animals were housed individually in suspended stainless steel cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 to 23 °C
- Humidity: 30 to 70 %
- Air changes: room ventilation was set to produce 10 to 15 air changes/hour.
- Photoperiod: Light timers were set to maintain a 12-hour light/12-hour dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration: 100 %
Duration of treatment / exposure:
- Following instillation, the eyelids were gently held together for approximately one second in order to limit test material loss and the animal was returned to its cage.
- For the rinse group: 2 to 3 minutes later the eyes were rinsed with physiological saline to remove the test material. For the no rinse group the test material was not removed
Observation period (in vivo):
Up to 21 days
Number of animals or in vitro replicates:
- Rinse group: 2 males and 1 female
- No rinse group: 6 males
Details on study design:
PRELIMINARY OBSERVATIONS
- On day 0 prior or to dosing, both eyes of each animal provisionally selected for test use were examined macroscopically for ocular irritation with the aid of an auxiliary light source. In addition, the corneal surface was examined using fluorescein sodium dye. One drop of a fluorescein/physiological saline mixture was gently dropped onto the superior sclera of each eye. Following an approximate 15 second exposure, the eyes were rinsed with physiological saline. The corneal surface was then examined for dye retention under a long-wave UV light source. Animals exhibiting ocular irritation, pre-existing corneal injury or fluorescein dye retention were not used on study. All animals found to be acceptable for test use were returned to their cages until dosing.

DOSING
- The test material was instilled into the conjunctiva! sac of the right eye of each animal after gently pulling the lower lid away from the eye. Following instillation, the eyelids were gently held together for approximately one second in order to limit test material loss and the animal was returned to its cage.
- The contralateral eye remained untreated to serve as a control.

REMOVAL OF TEST MATERIAL
- Approximately 2-3 minutes after instillation of the test material, the test and control eyes of the three rabbits were rinsed with 0.9 % physiological saline to remove the test material (rinsed group). The remaining rabbits were not rinsed (no rinse group).

SCORING SYSTEM:
- The eyes were macroscopically examined with the aid of an auxiliary light source for signs of irritation at 1, 24, 48 and 72 hours and up to 21 days after dosing according to the Ocular Grading System based on Draize.
- Following macroscopic observations at the 24-hour scoring interval, the fluorescein examination procedure was repeated on all test and control eyes and any residual test material was gently rinsed from the eye at this time (if possible) using physiological saline. If any fluorescein findings were noted at 24 hours, a fluorescein exam was conducted on the affected eyes at each subsequent interval until a negative response was obtained and/or until all corneal opacity had cleared. A fluorescein exam may also have been conducted to confirm the resolution of corneal opacity from a previous scoring interval.

CLINICAL OBSERVATIONS
- Any unusual observations and/or mortality were recorded. A general health/mortality check was performed twice daily (in the morning and in the afternoon).
- Individual body weights were obtained for each animal prior to dosing on day 0.
- Each surviving animal was euthanised by an intravenous injection of sodium pentobarbital following its final scoring interval. Gross necropsy examinations were not required for these animals.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 Days
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 10 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 10 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
OCULAR OBSERVATIONS
- No Rinse Group: Exposure to the test material produced corneal opacity in 6/6 test eyes by the 24-hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24-hour scoring interval. The corneal opacity resolved in 4/6 test eyes by study day 21 but persisted in 2/6 test eyes at study day 21 (termination). lritis was observed in 6/6 test eyes at the 24-hour scoring interval which resolved completely in the affected test eyes by study day 21. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1-hour scoring interval. The conjunctival irritation resolved completely in 2/6 test eyes by study day 21 but persisted in the remaining 4/6 test eyes at study day 21. Additional ocular findings noted included corneal neovascularisation (6/6 test eyes), sloughing of the corneal epithelium (3/6 test eyes), apparent blanching of the nictitating membrane (4/6 test eyes) and corneal bulging, which was noted in 2/6 test eyes.
- No corneal opacity, iritis or conjunctivitis was observed in the control eyes .
- Rinsed Group: Exposure to the test material produced corneal opacity in 3/3 test eyes by the 24-hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24-hour scoring interval. The corneal opacity resolved in 2/3 of the affected test eyes by study day 14 but persisted in the remaining animals through study day 21. lritis was observed in 3/3 test eyes at the 1-hour scoring interval which resolved completely in all test eyes by study day 14. Conjunctivitis (redness, swelling and discharge) was noted in 3/3 test eyes at the 1- hour scoring interval. The conjunctival irritation resolved completely in all test eyes by study day 21. Additional ocular findings noted included corneal neovascularisation (2/3 test eyes), corneal oedema and corneal bulging (1/3 test eyes), and sloughing of the corneal epithelium, which was noted in 1/3 test eyes.
Interpretation of results:
other: Category 2: irritating to eyes, according to EU criteria.
Conclusions:
Under the conditions of this study the test material is classified as Category 2: irritating to eyes, according to EU criteria.
Executive summary:

The potential of the test material to cause irritation to the eye was investigated in accordance with the standardised guidelines OECD405, EPA OPPTS870.2400 and JMAFF59 NohSan No.4200, under GLP conditions.

The potential irritant and/or corrosive effects of the test material were evaluated on the eyes of New Zealand White rabbits. Each of nine rabbits received a 0.1 mL dose of the test material in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 21 days following dosing. One group had eyes rinsed with physiological saline 2 to 3 minutes after treatment, the other group did not.

In the no rinse group, exposure to the test material produced corneal opacity in 6/6 test eyes by the 24-hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24-hour scoring interval. The corneal opacity resolved in 4/6 test eyes by study day 21 but persisted in 2/6 test eyes at study day 21 (termination). lritis was observed in 6/6 test eyes at the 24-hour scoring interval which resolved completely in the affected test eyes by study day 21. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1hour scoring interval. The conjunctival irritation resolved completely in 2/6 test eyes by study day 21 but persisted in the remaining 4/6 test eyes at study day 21. Additional ocular findings noted included corneal neovascularisation (6/6 test eyes), sloughing of the corneal epithelium (3/6 test eyes), apparent blanching of the nictitating membrane (4/6 test eyes) and corneal bulging, which was noted in 2/6 test eyes.

In the rinsed group, exposure to the test material produced corneal opacity in 3/3 test eyes by the 24-hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24hour scoring interval. The corneal opacity resolved in 2/3 of the affected test eyes by study day 14 but persisted in the one remaining animal at study day 21 (termination). lritis was observed in 3/3 test eyes at the 1-hour scoring interval which resolved completely in all test eyes by study day 14. Conjunctivitis (redness, swelling and discharge) was noted in 3/3 test eyes at the 1-hour scoring interval. The conjunctival irritation resolved completely in all test eyes by study day 21. Additional ocular findings noted included corneal neovascularisation (2/3 test eyes}, corneal oedema and corneal bulging (1/3 test eyes), and sloughing of the corneal epithelium, which was noted in 1/3 test eyes. In general, the rinsing procedure slightly lessened the severity and duration of the ocular irritation.

Under the conditions of this study the test material is classified as Category 2: irritating to eyes, according to EU criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Effects on skin irritation/corrosion
The skin irritation potential of the test material was investigated in accordance with the standardised guidelines OECD 404, OPPTS 870.2500 and JMAFF 59 NohSan No. 4200, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The potential irritant and/or corrosive effects were evaluated on the skin of New Zealand White rabbits. Six rabbits received 0.5 mL doses of the test material at 3 minute, 1 hour and 4 hour intervals. Patches were removed at specified time intervals and any remaining test material was wiped from the skin using gauze moistened with deionized water followed by dry gauze. Test sites were subsequently examined and scored for dermal irritation for up to 28 days following patch removal. 3-Minute Exposure: Exposure to the test material for the 3-minute exposure period produced very slight to well-defined erythema and very slight oedema on 6/6 and 4/6 test sites, respectively, immediately following patch removal. The dermal irritation resolved completely on all test sites by study day 14. Additional dermal findings included superficial lightening and desquamation; and erythema extending beyond the test site, which were noted on 6/6 and 3/6 test sites, respectively.

1-Hour Exposure: Exposure to the test material for the 1-hour exposure period produced very slight to well-defined erythema and very slight to slight oedema on 6/6 test sites immediately following patch removal. The dermal irritation resolved completely on all test sites by study day 14. Additional dermal findings included superficial lightening, desquamation and erythema extending beyond the test site; and blanching which were noted on 6/6 and 1/6 test sites, respectively.

4-Hour Exposure: Exposure to the test material for the 4-hour exposure period produced well-defined erythema to notable dermal lesions (blanching) and very slight to severe oedema on 6/6 test sites at the 1-hour scoring interval. In one animal, the dermal irritation progressed to notable dermal lesions (blanching) by the 24-hour scoring interval. The dermal irritation resolved completely on 5/6 test sites by study day 14 and persisted in the remaining test site through study day 28. Additional dermal findings included superficial lightening (6/6 test sites), erythema extending beyond the test site (5/6 test sites) and desquamation (6/6 test sites); focal areas of purple within the test site (3/6 test sites), and blanching (3/6 test sites).

Under the conditions of this study, the test material was not considered a dermal corrosive following a 3 minute, 1 or 4 hour exposure periods. The test material was considered to be a Category 2: irritant in accordance with EU criteria.


Effects on eye irritation

The potential of the test material to cause irritation to the eye was investigated in accordance with the standardised guidelines OECD405, EPA OPPTS870.2400 and JMAFF59 NohSan No.4200, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The potential irritant and/or corrosive effects of the test material were evaluated on the eyes of New Zealand White rabbits. Each of nine rabbits received a 0.1 mL dose of the test material in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 21 days following dosing. One group had eyes rinsed with physiological saline 2 to 3 minutes after treatment, the other group did not.

In the no rinse group, exposure to the test material produced corneal opacity in 6/6 test eyes by the 24-hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24-hour scoring interval. The corneal opacity resolved in 4/6 test eyes by study day 21 but persisted in 2/6 test eyes at study day 21 (termination). lritis was observed in 6/6 test eyes at the 24-hour scoring interval which resolved completely in the affected test eyes by study day 21. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1hour scoring interval. The conjunctival irritation resolved completely in 2/6 test eyes by study day 21 but persisted in the remaining 4/6 test eyes at study day 21. Additional ocular findings noted included corneal neovascularisation (6/6 test eyes), sloughing of the corneal epithelium (3/6 test eyes), apparent blanching of the nictitating membrane (4/6 test eyes) and corneal bulging, which was noted in 2/6 test eyes.

In the rinsed group, exposure to the test material produced corneal opacity in 3/3 test eyes by the 24-hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24hour scoring interval. The corneal opacity resolved in 2/3 of the affected test eyes by study day 14 but persisted in the one remaining animal at study day 21 (termination). lritis was observed in 3/3 test eyes at the 1-hour scoring interval which resolved completely in all test eyes by study day 14. Conjunctivitis (redness, swelling and discharge) was noted in 3/3 test eyes at the 1-hour scoring interval. The conjunctival irritation resolved completely in all test eyes by study day 21. Additional ocular findings noted included corneal neovascularisation (2/3 test eyes}, corneal oedema and corneal bulging (1/3 test eyes), and sloughing of the corneal epithelium, which was noted in 1/3 test eyes. In general, the rinsing procedure slightly lessened the severity and duration of the ocular irritation.

Under the conditions of this study the test material is classified as Category 2: irritating to eyes, according to EU criteria.


Effects on respiratory irritation: irritating

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance is classified as:

Category 2: skin irritant and Category 2: irritating to eyes.