N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 Nov 2004 to 03 Mar 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

EC Number:

204-029-1

EC Name:

N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

Cas Number:

113-48-4

Molecular formula:

C17H25NO2

IUPAC Name:

N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

impurity 1

Reference substance name:

(E)-1,4-Bis(2-ethylhexylamino)-2-butene-1,4-dione

Molecular formula:

C20H38N2O2

IUPAC Name:

(E)-1,4-Bis(2-ethylhexylamino)-2-butene-1,4-dione

impurity 2

Reference substance name:

1-(2-ethylhexyl)-1H-pyrrole-2,5-dione

Molecular formula:

C12H19NO2

IUPAC Name:

1-(2-ethylhexyl)-1H-pyrrole-2,5-dione

Test material form:

liquid

Details on test material:

Purity and characterisation analysis conducted on the following sample; Supplier: McLaughlin Gormley King ; Batch Number: AB9500

Specific details on test material used for the study:

MGK® 264
Lot No.: AA 7093
Purity: 95.2% MGK 264 (From CofA)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Description, Identification and Housing
Adult, New Zealand White rabbits were received from Myrtle's Rabbitry, Thompson Station, Tennessee. Upon receipt, plastic ear tags displaying unique identification numbers were used to individually identify the animals. Cage cards displaying at least the study number, animal number and sex were affixed to each cage. The animals were housed individually in suspended stainless steel cages. All housing and care were based on the standards recommended by the Guide for the Care and Use of Laboratory Animals.

Environment
The animal room temperature and relative humidity ranges were 68-70°F (20-21°C) and 37-46%, respectively. Environmental control equipment was monitored and adjusted as necessary to minimize fluctuations in the animal room environment. Light timers were set to maintain a 12-hour Iightll2-hour dark cycle and room ventilation was set to produce 10-15 air changeslhour. The animal room temperature and relative humidity were recorded a minimum of once daily.

Test system

Vehicle:

unchanged (no vehicle)

Remarks:

The test article was administered as received from the Sponsor.

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Concentration: 100% (as received)
Amount Instilled: 0.1 mL

Duration of treatment / exposure:

Following instillation, the eyelids were gently held together for approximately one second in order to limit test article loss and the animal was returned to its cage.

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

For each group, the ocular irritation score for each parameter (i.e., corneal opacity x area, iritis and conjunctival redness + swelling + discharge) was multiplied by the appropriate factor (i.e., corneal injury x 5, iritis x 5, conjunctivitis x 2) and the totals added for each animal/interval. The group mean irritation score was then calculated for each scoring interval based on the number of animals initially dosed in each group.

Ocular Observations
The eyes were macroscopically examined with the aid of an auxiliary light source for signs of irritation at 1, 24, 48 and 72 hours after dosing according to the Ocular Grading System presented in Appendix 2 which is based on Draize W. 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 article 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, or as directed by the Study Director.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(R) Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 Hours

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 Hours

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(R) Redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 Hours

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 Hours

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

conjunctivae score

Remarks:

(R) Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 Hours

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 Hours

Remarks on result:

no indication of irritation

Other effects:

Animal one had a secondary occular finding of SDL (Slight dulling of normal luster of the cornea) at the 1 Hour observation. This was not noted at any other timpoints (24, 48 and 72 hr).

Any other information on results incl. tables

Based on the EEC evaluation criteria, MGK® 264 is classified as a non irritant to the ocular tissue of the rabbit for corneal opacity, iritis, conjunctival redness and conjunctival edema.

EEC Ocular Evaluation
Mean Irritation Scores in Individual Animals
Animal No./Sex	Corneal Opacity	Iris Lesion	Conjunctival Redness	Conjunctival Edema
R2709/M	0.00	0.00	0.67	0.67
R27101M	0.00	0.00	1.00	0.33
R2711/M	0.00	0.00	0.33	0.33
Irritation Rating	Nonirritant	Nonirritant	Nonirritant	Nonirritant

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the EEC evaluation criteria, MGK® 264 is classified as a non irritant to the ocular tissue of the rabbit for corneal opacity, iritis, conjunctival redness and conjunctival edema.

Executive summary:

The potential irritant and/or corrosive effects of MGK® 264 were evaluated on the eyes of New Zealand White rabbits. Each of three rabbits received a 0.1 mL dose of the test article 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 72 hours following dosing.

Exposure to the test article produced conjunctivitis (redness, swelling, and discharge) in 3/3 test eyes at the 1h scoring interval. The conjunctival irritation resolved completely in 1/3 test eyes by the 48 -hour scoring interval and in the remaining test eyes by the 72-hour scoring interval.

Based on the Kay and Calandra evaluation criteria, MGK® 264 is considered to be a mild irritant to the ocular tissue of the rabbit.

Based on the EEC evaluation criteria, MGK® 264 is classified as a non irritant to the ocular tissue of the rabbit for corneal opacity, iritis, conjunctival redness and conjunctival edema.