Isoquinoline

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Range-Finding Toxicity Data: List IV

Author:

Smyth HF, Carpenter CP, Weil CS

Year:

1951

Bibliographic source:

Arch.Ind.Hyg.Occup.Med. 4: 119-122

Materials and methods

Principles of method if other than guideline:

The individual numerical scores of eye treated with a given volume or concentration of a chemical are added together and then divided by the number of eyes (usually 5) to obtain the score injury caused by the treatment. We have selected a level of 5.0 as representative of severe injury. This figure corresponds to necrosis visible only after staining and covering about three fourths of the surface of the cornea; or a more severe necrosis covering a smaller area.
When a test is to be performed, normal albino rabbit eyes are selected on basis of absence of visible staining by a 5-percent aqueous solution of fluorescein sodium, flushed with distilled 20 seconds after application. After a two-hour interval to allow the eye to return to normal, 0.005 ml. of the undiluted material is applied to the center of the cornea while the lids are retracted. About one minute later, the lids are released. This procedure is necessary to prevent the removal of a portion of the dose by the very efficient wiping system of the lids before intimate contact has been made with the eye. Eighteen to 24 hours later, the eye is examined in strong diffuse daylight, then stained with fluorescein and the injury scored. Guided by the result and the table of injury grades below, additional applications are made until the chemical can be assigned to one of the grades we recognize. If large volumes are applied, the lids are held closed for one minute before the animal is released. Where dilution of a chemical is necessary, our preferred solvent is propylene glycol from a batch shown to cause no injury. Preference is next given to water, and in some cases a deordorized kerosene known as "Deobase" has been used.

Symptom visible before Fluorescein staining:

cornea dull: 2 points
cornea opaque, less than half of area: 4 points
cornea opaque, more than half of area: 6 points (Maximum points)

Keratoconus: 6 points (Maximum points)

Iritis, slight internal congestion: 1 point
Iritis, marked internal congestion: 2 points (Maximum points)

Symptom visible after Fluorescein staining:

Necrosis on less than 5% of cornea: 1 point
Necrosis on 5 to 12%: 2 points
Necrosis on 13 to 37%: 3 points
Necrosis on 38 to 62%: 4 points
Necrosis on 63 to 87%: 5 points
Necrosis on 88 to 100%: 6 points (Maximum points)

Total maximum points: 20 points

Injury grades with definition:

Grade 1: 0.5 ml undiluted gives injury of 0 to 1.0 points
Grade 2: 0.5 ml undiluted gives injury of over 1.0 up to 5.0 points
Grade 3: 0.1 ml undiluted gives injury of up to 5.0 points (0.5 ml gives over 5.0)
Grade 4: 0.02 ml undiluted gives injury of up to 5.0 points (0.1 ml gives over 5.0)
Grade 5: 0.005 ml undiluted gives injury of up to 5.0 points (0.02 ml gives over 5.0)
Grade 6: Excess of 40% solution gives injury of up to 5.0 points (0.005 ml gives over 5.0)
Grade 7: Excess of 15% solution gives injury of up to 5.0 points (40% gives over 5.0)
Grade 8: Excess of 5% solution gives injury of up to 5.0 points (15% gives over 5.0)
Grade 9: Excess of 1% solution gives injury of up to 5.0 points (5% gives over 5.0)
Grade 10: Excess of 1% solution gives injury of over 5.0 points

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Isoquinoline

EC Number:

204-341-8

EC Name:

Isoquinoline

Cas Number:

119-65-3

Molecular formula:

C9H7N

IUPAC Name:

isoquinoline

Details on test material:

- Name of test material (as cited in study report): Iso quinoline

Test animals / tissue source

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

no data

Test system

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

see principles of method

Duration of treatment / exposure:

see principles of method

Observation period (in vivo):

see principles of method

Number of animals or in vitro replicates:

5

Details on study design:

The individual numerical scores of eye treated with a given volume or concentration of a chemical are added together and then divided by the number of eyes (usually 5) to obtain the score injury caused by the treatment. We have selected a level of 5.0 as representative of severe injury. This figure corresponds to necrosis visible only after staining and covering about three fourths of the surface of the cornea; or a more severe necrosis covering a smaller area.
When a test is to be performed, normal albino rabbit eyes are selected on basis of absence of visible staining by a 5-percent aqueous solution of fluorescein sodium, flushed with distilled 20 seconds after application. After a two-hour interval to allow the eye to return to normal, 0.005 ml. of the undiluted material is applied to the center of the cornea while the lids are retracted. About one minute later, the lids are released. This procedure is necessary to prevent the removal of a portion of the dose by the very efficient wiping system of the lids before intimate contact has been made with the eye. Eighteen to 24 hours later, the eye is examined in strong diffuse daylight, then stained with fluorescein and the injury scored. Guided by the result and the table of injury grades below, additional applications are made until the chemical can be assigned to one of the grades we recognize. If large volumes are applied, the lids are held closed for one minute before the animal is released. Where dilution of a chemical is necessary, our preferred solvent is propylene glycol from a batch shown to cause no injury. Preference is next given to water, and in some cases a deordorized kerosene known as "Deobase" has been used.

Symptom visible before Fluorescein staining:

cornea dull: 2 points
cornea opaque, less than half of area: 4 points
cornea opaque, more than half of area: 6 points (Maximum points)

Keratoconus: 6 points (Maximum points)

Iritis, slight internal congestion: 1 point
Iritis, marked internal congestion: 2 points (Maximum points)

Symptom visible after Fluorescein staining:

Necrosis on less than 5% of cornea: 1 point
Necrosis on 5 to 12%: 2 points
Necrosis on 13 to 37%: 3 points
Necrosis on 38 to 62%: 4 points
Necrosis on 63 to 87%: 5 points
Necrosis on 88 to 100%: 6 points (Maximum points)

Total maximum points: 20 points

Injury grades with definition:

Grade 1: 0.5 ml undiluted gives injury of 0 to 1.0 points
Grade 2: 0.5 ml undiluted gives injury of over 1.0 up to 5.0 points
Grade 3: 0.1 ml undiluted gives injury of up to 5.0 points (0.5 ml gives over 5.0)
Grade 4: 0.02 ml undiluted gives injury of up to 5.0 points (0.1 ml gives over 5.0)
Grade 5: 0.005 ml undiluted gives injury of up to 5.0 points (0.02 ml gives over 5.0)
Grade 6: Excess of 40% solution gives injury of up to 5.0 points (0.005 ml gives over 5.0)
Grade 7: Excess of 15% solution gives injury of up to 5.0 points (40% gives over 5.0)
Grade 8: Excess of 5% solution gives injury of up to 5.0 points (15% gives over 5.0)
Grade 9: Excess of 1% solution gives injury of up to 5.0 points (5% gives over 5.0)
Grade 10: Excess of 1% solution gives injury of over 5.0 points

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 h

Score:

9

Max. score:

10

Reversibility:

not specified

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU