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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 February 2017 - 3 March 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
An in vivo study was conducted for registration purposes in China.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2 October 2012
Deviations:
no
Qualifier:
according to
Guideline:
other: Regulation on Test Methods for Chemical Substances, Notification No. 2016-27, National Institute of Environmental Research, Republic of Korea
Version / remarks:
19 December 2016
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
Appearance: colourless or light yellow viscous liquid
Storage conditions: at room temperature, container tightly closed, flushed with nitrogen.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Yonam College, Yonam Laboratory Animal (breeder); OrientBio Inc., Republic of Korea (supplier)
- Age at study initiation: 11-12 weeks old
- Weight at study initiation: 2.11-2.28 kg
- Housing: one animal per cage in stainless wire mesh cages
- Diet: Purina experimental diet for rabbit 38302AF (Cargill Agri Purina, Inc.), ad libitum
- Water: tap water (filtered and irradiated by UV), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19.1–21.7°C
- Humidity: 41.3–53.7%
- Air changes: 10–15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 February 2017 to 3 March 2017

Test system

Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:
single instillation
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 male rabbits in a sequential manner
Details on study design:
ANESTHETICAL PROCEDURE:
Sixty minutes prior to test substance application, buprenorphine was administered at 0.01 mg/kg by subcutaneous injection to provide a therapeutic level of systemic analgesia. Five minutes prior to test substance application, one drop of 0.5% proparacaine
hydrochloride was applied to the right and left eyes.

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: eye response was evaluated by visual observations and with the use of a slit lamp.

OTHER OBSERVATIONS:
- Clinical signs: once daily
- Body weights: on the day of dosing (day 0) and on the day of final observations (day 3).

Because no corrosion and severe irritant effects were observed in the initial test, a confirmatory test was conducted with another animal in a sequential manner. Because no corrosion and severe irritant effects were observed in the animal of the confirmatory test, another confirmatory test was conducted with a third animal.

STUDY COMPLETION: All animals were euthanized under pentothal sodium anesthesia and discarded after the completion of the study.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Scores for both opacity-degree and area of cornea involved were 0.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Scored for both opacity-degree and area of cornea involved were 0.
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Scores for both opacity degree and area of cornea involved were 0.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
2
Reversibility:
fully reversible
Remarks:
Iris scores were 0 after both 48 and 72 hours.
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
2
Reversibility:
fully reversible
Remarks:
Iris scores were 0 after both 48 and 72 hours.
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
2
Reversibility:
fully reversible
Remarks:
Iris scores were 0 after both 48 and 72 hours.
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks:
Redness score after both 48 and 72 hours: 0
Remarks on result:
other: Redness score after 1 hour: 1
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks:
Redness score after 48 and 72 hours: 0
Remarks on result:
other: Redness score after 1 hour: 1
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks:
Redness score after both 48 and 72 hours: 0
Remarks on result:
other: Redness score after 1 hour: 1
Irritation parameter:
conjunctivae score
Remarks:
Chemosis
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks:
Chemosis score after both 48 and 72 hours: 0
Irritation parameter:
conjunctivae score
Remarks:
Chemosis
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks:
Chemosis score after both 48 and 72 hours: 0
Irritation parameter:
conjunctivae score
Remarks:
Chemosis
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks:
Chemosis score after both 48 and 72 hours
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks:
Discharge score after both 48 and 72 hours: 0
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks:
Discharge score after both 48 and 72 hours: 0
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks:
Discharge score after both 48 and 72 hours: 0
Other effects:
No reactions on the conjunctivae, cornea or iris were observed in any of three animals at 48 and 72 hours. The mean total score was ‘0.0’, respectively.
No reactions on the conjunctivae, cornea or iris were observed in any of control animals during the observation period.

- Lesions and clinical observations: No adverse signs or symptoms were observed in any animal throughout the course of the study.
- Body weight: All animals exhibited normal body weight gain. The mean body weight gain throughout the observation period was 0.09 kg.
- Other observations: no abnormal signs of pain and distress were observed in any animal immediately after test substance application, at each observation time and prior to administration of systemic analgesics.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of an acute eye irritation study in rabbits, performed according to OECD guideline 405 and GLP principles, STABiO D-376N is not classified for eye irritation according to GHS.
Executive summary:

An acute eye irritation study was performed, according to OECD guideline 405 and GLP principles, to evaluate the potential eye irritation and/or corrosion after application of STABiO D-376N to three New Zealand White rabbits. First, an initial test was conducted with one animal. Because no corrosion or sever irritation was observed, two consecutive confirmatory tests were performed using one animal each. For all tests, 0.1 mL of the test substance was applied undiluted into one eye, where the other eye served as a control. Topical anesthetic and systemic analgesics were used to avoid or minimise pain and distress. Observations were recorded at 1, 24, 48 and 72 hours after test substance application. No effects were seen on the cornea in all animals. Iris scores after 24 hours were 1 for animals, this effect was fully reversed after 48 hours (score 0). Redness, chemosis and discharge of the conjunctivae were observed in all animals after 24 hours (score 1), whereas redness was already noted after 1 hour (score 1). These effects were fully reversed after 48 hours as well (score 0). Based on these results, STABiO D-376N is not classified according to GHS.