1,3,2-dioxathiolane 2,2-dioxide

Endpoint summary

Description of key information

Skin Corrosion

This study was performed to evaluate irritation potential of ESA. In one male New Zealand White Rabbit, the test substance of 0.5 g was applied to the dorsal skin of NZW rabbits for 4 hours. Parameters measured were mortalities, clinical signs and body weight changes after test substance application. The response of each local irritation was evaluated by National Institute of Environmental Research Notification No. 2010-29. The skin reaction was assessed in comparison with application site for test substance and intact site for the control. The finding results were as follows :

1) No clinical signs and mortalities related to test substance treatment were observed.

2) No significant body weight changes related to test substance treatment was observed.

3) In the initial test, erythema, eschar, edema and necrotic lesion of skin were observed at 1 and 24 hours after patch removal. The test was terminated because the effect of test substance was not expected to be recovered. In the negative control, no signs were observed on the skin during the experimental period.

On the basis of the above results, ESA on skin application of New Zealand White rabbit is considered a corrosive material that causes irreversible response.

Eye irritation

This study was performed to evaluate ocular irritation potential of ESA. In one male New Zealand White Rabbit, the test substance of 0.1 g was dropped in the conjunctival sac of left eye of rabbit once. Parameters were measured mortalities, clinical signs and body weight changes after application. The ocular irritation response of cornea, iris and conjunctiva were evaluated by National Institute of Environmental Research Notification No.2010-29. The finding results were as follows :

1) No clinical signs and mortalities related to test substance treatment were observed.

2) No significant body weight changes related to test substance treatment was observed.

3) Redness, edema and discharge of conjunctiva were observed at 1 hour after application in the initial test. At 24 hours after application, severe changes of eyeball and surrounding tissues were observed. The test was terminated because the effect of test substance was not

expected to be recovered. In the right eye of negative control, no signs were observed during the experimental period.

On the basis of the above results, ESA on eye application of New Zealand White rabbit is considered a corrosive material that causes irreversible response.

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:

Study initiation: 25 January 2012 Final report: 09 March 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Remarks:

Korea

Specific details on test material used for the study:

Chemical Name: 1,3,2-Dioxathiolane, 2,2-dioxide
Product Name : ESA
Received date : 22 November 2011
Appearance : lemon-yellow solid
Purity : 99.1 %
Storage condition : Room temperature or refrigerator (2 - 8 ºC)
Stability: stable
Supplier: LG Chemicals Co., Ltd.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species and strain: Specific Pathogen Free (SPF) New Zealand White (NZW) rabbits.
Supplier: ORIENT BIO INC.(Address; 143-1, Sangdaewondong, Jungwon-gu, Seongnam-si, Gyeonggi-do, Korea)
Producer: Laboratory animals center, Cheonan yonam college (Address : San 3-1, Suhyang-ri, Seonghwan-eup, Seobuk-gu, Cheonan-si, Chungcheongnam-do, Korea)
Species selection Justification: The NZW rabbits used in this study are widely used in general dermal irritation experiments for toxicity testing. In addition, sufficient raw data associated with this species has been accumulated and is available for interpretation and evaluation of study results.
Date of the acquisition: 30 January 2012
Number of received animals: 5 male animals
Body weights and ages on arrival: 1783.78 - 1894.90 g, 10 weeks old
Quarantine and acclimation: On arrival, animals were examined based on the certificate provided by the supplier. The period of acclimation was 7 days. Only healthy animals was used for the test after observing general symptoms in the acclimated period.
Body weights and ages at administration: 2015.96 g, 11 weeks old
Number of animals administered test substance: 1 animal (male)
Grouping: After selection of animal weighed more than 2.0 kg, the dorsal skin of rabbits was shaved using an electric clipper to expose normal naked skin, within 24
hours, before administration. Attention was given not to make a wound. Rabbits with healthy skin were chosen randomly.
Identification of animals: Each animal was identified for this study by a unique number marked indelibly on the inner surface of the ear and written on the cage label. Information about animals and study was also posted on the door of the animals room.
Disposal of remaining animals: All remaining animals were euthanized by CO2 over-inhalation on experimental completion day.

Animal Care Facility
Range of temperature and humidity during test work: Temperature of 22.2±0.7 ºC, Relative humidity of 44.3±2.4 %
Ventilation frequency: 10-15 air changes /hr.
Lighting cycle: 12 hrs lighting duration (lighting on at 8 a.m. ~ lighting off at 8 p.m.)
Lighting intensity: 288 Lux.
Ambient noise level: 53.9 dB
Ammonia concentration : less than 5 ppm
Housing: All animals were individually housed in stainless steel cages (380W×500D×330H mm) during the test period.
Feed: Laboratory rabbit diet, Agribrands Purina Korea Inc. (Address: 8th Floor Hanlimwon Building, 7-1, Gu Mi-Dong, BunDang-Gu, Sung Nam-Shi, Kyong Gi-Do, Korea)
Supplied ad libitum. Analysis carried out by supplier. No significant factors to affect the experimental results were found.
Water: Incheon, Korea municipal tap water purified by reverse osmosis filtering system. Supplied ad libitum. Analysis was performed by national certificated inspection organization. No significant factors to affect the experimental results were found.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Amount / concentration applied:

0.5 g of test substance

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours

Observation period:

1 and 24 hours

Number of animals:

one male

Details on study design:

Application method
Preparation of test site:
Shaved area was divided into left and right sections. 6 cm2 areas were marked in each section. The left sections was used for application of test substance, and the right sections was used for control.
Application method and volume:
Before the administration, the dorsal back side of one rabbit were clipped free of fur. 0.5 g of test substance was applied onto left treated section of about 6 cm2 once. To ensure sufficient good skin contact, gauze patch moistened with the smallest amount of Physiological saline (87J6P61) covered on treated section. The entire trunk of the animals was wrapped with non-irritant adhesive tape (TegadermTM 1626W, 3M Health Care). Separately, 0.5 mL of physiological saline (87J6P61, DAIHAN Pharm Co. Ltd) was applied for the control in the same way as the test substance.
Frequency of administration & period of administration:
The test substance was applied once at dermal. In the initial test, the test substance was applied by patch in one rabbit. First patch was removed after 3 minutes and no skin reaction was observed. Second patch was applied at a different site and removed after 1 hour and some irritaion was observed. Third patch was applied and removed after 4 hours at another site and the corrosion was observed. Therefore, the confirmatory test was not performed.
After application, the treated sections were washed gently with the physiological saline (087J6P61, DAIHAN Pharm Co. Ltd) to remove the residual of test substance.
Selection of dosage:
The volume of test substance was determined 0.5 g in accordance with National Institute of Environmental Research Notification No.2010-29 "Designation of chemical hazard test research organization"(16 August 2010).

Observations
Clinical signs:
All animals were observed daily from on day of test substance application until experiment termination day for appearance, food and water consumption, clinical signs and survival.
Body weight:
Individual body weight was measured before test substance application, and at 24 hours after application.
Observation of application site:
Test sites were evaluated for corrosion and irritation (erythema, eschar and edema etc.) at 1 and 24 hours after patch removal.
Evaluation of dermal irritation/corrosion
The skin responses were scored according to 'Grading of skin reaction by National Institute of Environmental Research Notification No.2010-29 "Designation of chemical hazard test research organization"(16 August 2010). The corrosive responses were evaluated according to 'Skin and eye irritation assessment guidelines' by National Institute of Environmental Research Notification Guidelines (12 November 2008).
Histopathological examination:
The animal in the initial test was euthanized by CO2 over-inhalation at 24 hours after patch removal. The skins were collected in sites exposed to control and test substance. The skins were fixed in a 10% formalin solution containing neutral phosphate-buffered saline and stained with hematoxylin and eosin and examined under light microscopy to clarify skin corrosion.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

4 hr exposure

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

other: not expected to be reversible

Remarks on result:

other: animal humanely killed

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

4 hr exposure

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

other: not expected to be reversible

Remarks on result:

other: animal humanely killed

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Remarks on result:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Remarks on result:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Remarks on result:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Remarks on result:

other: not applicable

Irritant / corrosive response data:

Observation of application site
Erythema and eschar formation:
Moderate erythema was observed at 1 hour after exposure of test substance. Severe erythema and partially skin necrosis were observed at 4 hour after exposure of test substance.
Severe erythema and partially skin necrosis were observed at 1 and 24 hours after patch removal.
In the negative control, no signs were observed on the skin during the experimental period.
Edema:
No edema was not observed at 3 minutes and 1 hour after exposure of test substance. Severe edema was observed at 4 hour after exposure of test substance.
Severe edema was observed at 1 and 24 hours after patch removal. In the negative control, no signs were observed on the skin during the experimental period.

Histopathological examination:
Broadly diffuse necrosis and swelling in epidermis and dermis were observed at test site. Also, desquamation of stratum corneum in epidermis and congestion in dermis layer were observed.

Evaluation of corrosion
Based on the results of skin response at 1 and 24 hours after patch removal and histopathological examination, the test substance, ESA is considered a corrosive material.

Other effects:

Mortalities and clinical signs:
In the initial test, no significant clinical signs and mortalities was observed.
Body weight changes:
In body weight changes, temporary decrease was observed after test substance application.

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Remarks:

In the study report only initial observations were included for 3 minute and 1 hour treatment. It is not clear if further observations were made for these treatment times. Therefore, a sub-category cannot be assigned.

Conclusions:

This study was performed to evaluate first irritation and corrosion of ESA in one male New Zealand White Rabbits. 0.5 g of the test substance was applied to the skin of NZW rabbits for 4 hours. Parameters (mortalities, clinical signs, body weight changes and skin response) were measured.
No clinical sign and mortality was observed relating to test substance treatment. Decrease in body weight at the next day of application was observed, but the sign was considerd temporary by the stress of treatment.
In the initial test, erythema was observed at 1 hour after exposure of test substance. Erythema, edema and partially necrosis were observed at 4 hours after exposure of test substance.
Severe erythema and edema with skin necrosis were observed at 1 and 24 hours after patch removal. The animal was humanely killed without additional observation because the effects of test substance was not expected to be recovered. In the histopathological examination to clarify corrosion, broadly diffuse necrosis, swelling in epidermis and dermis, desquamation of stratum corneum in epidermis and congestion in dermis layer were observed. In the negative control, no signs were observed during the experimental period.
On the basis of the above results, ESA on skin application of New Zealand White rabbit is not related to clinical signs, mortality and body weights and is considered a corrosive material that causes irreversible response.

Executive summary:

This study was performed to evaluate irritation potential of ESA. In one male New Zealand White Rabbit, the test substance of 0.5 g was applied to the dorsal skin of NZW rabbits for 4 hours. Parameters measured were mortalities, clinical signs and body weight changes after test substance application. The response of each local irritation was evaluated by National Institute of Environmental Research Notification No. 2010-29. The

skin reaction was assessed in comparison with application site for test substance and intact site for the control. The finding results were as follows :

1) No clinical signs and mortalities related to test substance treatment were observed.

2) No significant body weight changes related to test substance treatment was observed.

3) In the initial test, erythema, eschar, edema and necrotic lesion of skin were observed at 1 and 24 hours after patch removal. The test was terminated because the effect of test substance was not expected to be recovered. In the negative control, no signs were observed on the skin during the experimental period.

On the basis of the above results, ESA on skin application of New Zealand White rabbit is considered a corrosive material that causes irreversible response.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

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:

Study initiation: 25 January 2012 Final report: 09 March 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Remarks:

Korea

Specific details on test material used for the study:

Chemical Name: 1,3,2-Dioxathiolane, 2,2-dioxide
Product Name: ESA
Received date : 22 November 2011
Appearance : lemon-yellow solid
Purity : 99.1 %
Storage condition : Room temperature or refrigerator (2 - 8 ºC)
Supplier : LG Chemicals Co., Ltd.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Supplier: ORIENT BIO INC. (Address; 143-1, Sangdaewondong, Jungwon-gu, Seongnam-si, Gyeonggi-do, Korea)
Producer: Laboratory animals center, Cheonan yonam college (Address : San 3-1, Suhyang-ri, Seonghwan-eup, Seobuk-gu, Cheonan-si, Chungcheongnam-do, Korea)
Species selection Justification: The NZW rabbits used in this study are widely used in general dermal irritation experiments for toxicity testing. In addition, sufficient raw data associated with this species has been accumulated and is available for interpretation and evaluation of study results.
Date of the acquisition: 30 January 2012
Number of received animals: 4 male animals
Body weights and ages on arrival:1798.64 ~ 1980.74 g, 10 weeks old
Quarantine and acclimation: On arrival, animals were examined based on the certificate provided by the supplier. The period of acclimation was 7 days. Only healthy animal were used for the test after observing general symptoms in the acclimated period.
Body weights and ages at administration: 2280.21 g, 11 weeks old
Number of animals administered test substance: 1 animal (the initial test)
Grouping: After selection animal having 2.0 to 3.0 kg weigh, animal with no corneal injury was used in this study using the eye examination (Slit Lamp, ECONOM SET, GERMANY), within 24 hours, before administration.
Identification of animals: Each animal is identified for this study by a unique number marked indelibly on the inner surface of the ear and written on the cage label. Information about animals and study was also posted on the door of the animals room.
Disposal of remaining animals: All remaining animals were euthanized by CO2 over-inhalation on experimental completion day.

Animal Care Facility
Range of temperature and humidity during test work: Temperature of 22.2±0.7 ºC, Relative humidity of 44.3±2.4 %
Ventilation frequency: 10 - 15 air changes /hr.
Lighting cycle: 12 hrs lighting duration (lighting on at 8 a.m. ~ lighting off at 8 p.m.)
Lighting intensity: 288 Lux.
Ambient noise level: 53.9 dB
Ammonia concentration: less than 5 ppm
Housing: All animals were individually housed in stainless steel cages (380W×500D×330H mm) during the test period.
Feed: Laboratory rabbit diet, Agribrands Purina Korea Inc. (Address: 8th Floor Hanlimwon Building, 7-1, Gu Mi-Dong, BunDang-Gu, Sung Nam-Shi, Kyong Gi-Do, Korea). Supplied ad libitum. The data analyzed by the feed supplier was used. No significant factors to affect the experimental results were found.
Water: Incheon, Korea municipal tap water purified by reverse osmosis filtering system. Supplied ad libitum. Analysis performed by national certificated inspection organization. No significant factors to affect the experimental results were found

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g of pulverized test item

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1 and 24 hours

Number of animals or in vitro replicates:

one male

Details on study design:

Application method
Group Description: Experimental group consisted of one healthy rabbit. One rabbit was used in the initial test. The test substance was applied to the left eye and the right eye remained as control without treatment.
Route of administration & dosage: 0.1 g of the test substance was applied once in a left conjuctival sac. After then, to prevent leakage of the test substance, both eyelids were closed for about 1 second by pulled down eyelids. Eyes were rinsed, because the test substance was not removed physiologically at 1 hour after application.
Initial Test: The eye irritation at 24 hours after application was considered severe to continue experiment. So the animal was humanely killed without additional observation.
Confirmatory Test: The confirmatory test was not performed because severe irritation and corrosive effects were observed in the initial test.
Selection of dosage: The volume of test substance was determined 0.1 g in accordance with National Institute of Environmental Research Notification No.2010-29 "Designation of chemical hazard test research organization"(16 August 2010).
Observations:
Clinical signs: Test animal was observed daily from on day of test substance application until experiment termination day for appearance, food and water consumption, clinical signs and survival.
Body weight: Individual body weight was measured before test substance application, and at 24 hours after application.
Observation of application site: Using the slit lamp(Slit Lamp, ECONOM SET, GERMANY), the eyes were examined ocular irritation of cornea, iris and conjunctiva at 1 and 24 hours after removal of test substance.
Evaluation of eye irritation/corrosion: The eye responses were scored at each examination time according to 'Grading of ocular lesions', National Institute of Environmental Research Notification No.2010-29 "Designation of chemical hazard test research organization"(16 August 2010), OECD TG No. 405 Acute Eye Irritation/Corrosion and SOPs of Korea Conformity Laboratories. The corrosive responses were evaluated according to 'Skin and eye irritation assessment guidelines' by National Institute of Environmental Research Notification Guidelines (12 November 2008).

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

other: not expected to be reversible

Remarks on result:

other: animal humanely killed

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

48 h

Remarks on result:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

72 h

Remarks on result:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

other: not expected to be reversible

Remarks on result:

other: animal humanely killed

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Remarks on result:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Remarks on result:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

other: not expected to be reversible

Remarks on result:

other: animal humanely killed

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

48 h

Remarks on result:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

72 h

Remarks on result:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

other: not expected to be reversible

Remarks on result:

other: animal humanely killed

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

48 h

Remarks on result:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Remarks on result:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #1

Time point:

24 h

Score:

3

Max. score:

3

Irritant / corrosive response data:

Observation of application site and evaluation of corrosion
In the initial test, corrosion was observed at cornea, iris and conjunctiva after test substance application. So, the observation for test site was performed until 24 hours after test substance application.
In the initial test, corneal opacity of grade 4, iris responses of grade 2, conjunctival redness of grade 3, conjunctival edema of grade 4 and conjunctival discharge of grade 3 were observed at 1 and 24 hours after test substance application. Also, the necrotic lesion was observed in conjunctiva at 24 hours after test substance application. In the right eye of negative control, no signs were observed during the experimental period.
As a results of eye corrosion evaluation at 1 and 24 hours after application for ESA, effects of cornea, iris and conjunctiva were not expected to be recovered. So the test was terminated and the test substance is considered a corrosive material.

Other effects:

Mortality and clinical signs:
No significant clinical signs and mortalities were observed in the initial test.

Body weight changes:
A temporary decrease was observed after test substance application.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

To evaluate ocular irritation potential of ESA, one male NZW rabbit was used to this study. After application of the test substance into the conjunctival sac at dosage 0.1 g, mortality, clinical signs, changes of the body weight and irritant signs of eyes were evaluated.
There was no mortalities, abnormal clinical signs and body weight changes induced by test substance treatment.
Cornea opacity, iris irritation and redness, edema and discharge of conjunctiva related to test substance were observed at 1 hour after application in the initial test. At 24 hours after application, severe changes of eyeball and surrounding tissues were observed. The animal was humanely killed without additional observation because the effects of test substance was not expected to be recovered and was considered severe to continue experiment. In the right eye of negative control, no signs were observed during the experimental period.
On the basis of the above results, ESA on eye application of New Zealand White rabbit is not related to clinical signs, mortality and body weights and is considered a corrosive material that causes irreversible response.

Executive summary:

This study was performed to evaluate ocular irritation potential of ESA. In one male New Zealand White Rabbit, the test substance of 0.1 g was dropped in the conjunctival sac of left eye of rabbit once. Parameters were measured mortalities, clinical signs and body weight changes after application. The ocular irritation response of cornea, iris and conjunctiva were evaluated by National Institute of Environmental Research Notification No.2010-29. The finding results were as follows :

1) No clinical signs and mortalities related to test substance treatment were observed.

2) No significant body weight changes related to test substance treatment was observed.

3) Redness, edema and discharge of conjunctiva were observed at 1 hour after application in the initial test. At 24 hours after application, severe changes of eyeball and surrounding tissues were observed. The test was terminated because the effect of test substance was not

expected to be recovered. In the right eye of negative control, no signs were observed during the experimental period.

On the basis of the above results, ESA on eye application of New Zealand White rabbit is considered a corrosive material that causes irreversible response.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin corrosion / irritation:

Skin corrosion is defined as the production of irreversible damage to the skin following application of the test substance. Skin irritation is the production of reversible damage to the skin following application of the test substance.

In in vivo studies a substance classified as corrosive to skin when it produces destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis in at least one tested animal after exposure for up to 4 hours.

In the study 0.5 g of test substance was applied to the dorsal skin of one NZW rabbit for 4 hours. Erythema, eschar, edema and necrotic lesion of skin were observed at 1 and 24 hours after patch removal. The effects were considered not to be reversible.

The substance is therefore classified as skin corrosion, category 1.

There is not sufficient data for sub-categorisation. The test substance was also applied for 3 minute and 1 hour exposure times. After 3 minutes exposure no skin reaction was observed. After 1 hour exposure moderate erythema was observed. However, no further observations were made for the 3 minutes and 1 hour exposures. According to CLP corrosive effects need to be observed within 1 hour after 3 minute exposure for classification as 1A, and within 14 days after 1 hour exposure for classification as 1B.

The test substance is therefore conclusively determined to be corrosive after 4 hours exposure, but it is not possible to conclusively determine if it is corrosive after a shorter period, although corrosion after 3 minutes is considered unlikely based on no skin reactions.

 

Eye irritation:

Serious eye damage is defined as the production of tissue damage in the eye, or serious physical decay or vision following application of the test substance to the anterior surface of the eye which is not fully reversible. Eye irritation means the production of changes in the eye following application of the test substance which is fully reversible.

An in vivo eye irritation study was conducted to assess eye irritancy potential. In one male New Zealand White Rabbit, the test substance of 0.1 g was dropped in the conjunctival sac of left eye of rabbit once. Redness, edema and discharge of conjunctiva were observed at 1 hour after application in the initial test. At 24 hours after application, severe changes of eyeball and surrounding tissues were observed. The test was terminated because the effect of test substance was not expected to be recovered.

According to irreversible effects seen in this study and the substances classification as corrosive, the test item is also classified for serious eye damage, category 1.