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

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Remarks:

Korea

Test material

Test material information

Constituent 1

Reference substance name:

1,3,2λ⁶-dioxathiolane-2,2-dione

EC Number:

600-809-4

Cas Number:

1072-53-3

Molecular formula:

C2H4O4S

IUPAC Name:

1,3,2λ⁶-dioxathiolane-2,2-dione

Test material form:

solid

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.

Test animals / tissue source

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

Test system

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).

Results and discussion

In vivo

Results

Results 1

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

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

48 h

Remarks on result:

other: not applicable

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

72 h

Remarks on result:

other: not applicable

Results 4

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

Results 5

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Remarks on result:

other: not applicable

Results 6

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Remarks on result:

other: not applicable

Results 7

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

Results 8

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

48 h

Remarks on result:

other: not applicable

Results 9

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

72 h

Remarks on result:

other: not applicable

Results 10

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

Results 11

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

48 h

Remarks on result:

other: not applicable

Results 12

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Remarks on result:

other: not applicable

Results 13

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.

Applicant's summary and conclusion

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.