N-hydroxyphthalimide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Data source

Reference

Reference Type:

publication

Title:

Correlation of Ocular and Dermal Irritancy of Industrial Chemicals

Author:

Shayne C. Gad, Robert D. Walsh & Brendan J. Dunn

Year:

1986

Bibliographic source:

Journal of Toxicology: Cutaneous and Ocular Toxicology; Vol 5(3); Pg. no. 195-214; 1986.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Draize method

Principles of method if other than guideline:

Eye irritation study was conducted on New Zealand White rabbits for determining the irritant potency of the test substance potassium phthalimide.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

N-potassium phthalimide

EC Number:

214-046-6

EC Name:

N-potassium phthalimide

Cas Number:

1074-82-4

Molecular formula:

C8H5NO2.K

IUPAC Name:

potassium 1,3-dioxo-1,3-dihydroisoindol-2-ide

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Phthalimide, potassium salt
- Molecular formula :C8H5NO2.K
- Molecular weight 185.223 g/mol
- Smiles notation : c12c(C(=O)[NH-]C1=O)cccc2.[K+]
- InChl: 1S/C8H5NO2.K/c10-7-5-3-1-2-4-6(5)8(11)9-7;/h1-4H,(H,9,10,11);/q;+1/p-1
- Substance type: Organic
- Physical state: Solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Phthalimide, potassium salt
- Molecular formula : C8H5NO2.K
- Molecular weight 185.223 g/mol
- Smiles notation : c12c(C(=O)[NH-]C1=O)cccc2.[K+]
- InChl: 1S/C8H5NO2.K/c10-7-5-3-1-2-4-6(5)8(11)9-7;/h1-4H,(H,9,10,11);/q;+1/p-1
- Substance type: Organic
- Physical state: Solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Details on test animals:
Acclimation Period:The quarantine period which was imposed during the study on the test animal is 14 days.
 

Test system

Vehicle:

physiological saline

Controls:

yes

Amount / concentration applied:

no data available

Duration of treatment / exposure:

Exact duration of exposure to the test substance was not mentioned in the study paper but single exposure to the test substance was done at 0 day

Observation period (in vivo):

Observations were made at 1 hr, 1, 2, 3, 4, and 7 days after exposure.

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

9

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes of the three rabbits are irrigated for 1 min with room temperature tap water using a polyethylene squeeze bottle, starting 20 sec after instillation.
- Time after start of exposure: No data available

SCORING SYSTEM: Grading and scoring of ocular irritation are performed in accordance with the standard Draize grades for ocular lesions.
Grades for Ocular Lesions:
Cornea Grade
No ulceration or opacity = 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible = (1)a
Easily discernible translucent area; details of iris slightly obscured = 2
Nacreous areas; no details of iris visible; size of pupil barely discernible = 3
Complete corneal opacity; iris not discernible = 4
Iris
Normal = 0
Markedly deepened folds, congestion, swelling, moderate circumcorneal injection; (any of these or combination of any thereof); iris reactive to light (a sluggish reaction is positive) = (1)a
Hemorrhage, gross destruction, or no reaction to light = 2

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae; excluding cornea and iris)
Vessels Normal = 0
Some Vessels definitely injected = 1
Diffuse, crimson red; individual vessels not easily discernible = (2)a
Diffuse beefy red = 3
Chemosis
Normal = 0
Any swelling above normal (includes nictitating membrane) = 1
Obvious swelling, with partial eversion of lids = 2
Swelling, with lids about half closed = 3
Swelling, with lids more than half closed= 4
Where a= Lowest Grades considered positive under the Federal Hazardous Substances Regulation (FHSA) at 16 CFR1500.42

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

64

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

The mean Draize score was determined to be 64.0. Based on the mean Draize scores, Potassium phthalimide can be considered to be moderately irritating to eyes.

Any other information on results incl. tables

Table 2:

Ocular irritation results and Classification

Chemical Name	Greens Scale	Mean Draize Scores (24 hours)
Potassium Phthalimide	NA	64.0

NA = Not Applicable, only the standard FHSA eye irritation study was performed.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

When New Zealand White Rabbits were exposed to Potassium phthalimide, the mean Draize score was determined to be 64.0. Based on the mean Draize scores, Potassium phthalimide can be considered to be moderately irritating to New Zealand White rabbit eyes.

Executive summary:

Eye irritation study was conducted on rabbits to check the eye irritation potential of the test compound potassium phthalimide.

9 New Zealand white rabbits used for the study. The contralateral eye of each test animal remains untreated and served as a control. 1 hr prior to instillation of the test substance, both eyes of each of at least 12 rabbits are examined for signs of irritation and corneal defects with a handheld slit lamp. Eyes are stained with a 2.0% sodium fluorescein and examined for confirming the absence of corneal lesions. At least 1 hr after fluorescein staining, the test substance is placed on one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup (conjunctival cul-de-sac) into which the test substance is dropped. The upper and lower lids are then held gently together for 1 sec to prevent immediate loss of material. All corneas are examined with the aid of sodium fluorescein. If fluorescein staining appears, diagrams of the staining patterns of the corneal area involved are recorded.If signs of irritation persist at 7 days, reading are continued on day 10. If irritation is still persistent on day 10, then readings are taken on day 14. Most lesions, if reversible, will heal or clear within 21 days. Therefore, if ocular irritation is present at the 14-day reading, a 21-day reading is required to determine whether the ocular damage is reversible or non-reversible.

The Federal Hazardous Substances Act (FHSA) Regulations was used to determine whether the test substance was an eye irritant or not. Interpretation of data was made using only the six test eyes not irrigated with water, and only data from days 1, 2, and 3.Grading and scoring of ocular irritation are performed in accordance with the standard Draize grades for ocular lesions.

 

When the test animals were exposed to the test substance potassium phthalimide,mean Draize score was determined to be 64.0.

Based on the mean Draize scores, Potassium phthalimide can be considered to be moderately irritating to New Zealand White rabbit eyes.