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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:
08 May 2000 to 29 May 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Iodomethane
EC Number:
200-819-5
EC Name:
Iodomethane
Cas Number:
74-88-4
Molecular formula:
CH3I
IUPAC Name:
iodomethane
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Iodomethane
- Physical state: liquid
- Analytical purity: 99.7%
- Impurities (identity and concentrations): 0.2 % water and <0.1 % methanol
- Composition of test material, percentage of components: not stated
- Isomers composition: not stated

Test animals / tissue source

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

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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.

Applicant's summary and conclusion

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.