N-potassium phthalimide

Endpoint summary

Description of key information

Skin Irritation:

Moderate irritation effect was observed when the rabbits were exposed to the test substance potassium phthalimide for 24 hrs. The Primary Dermal Irritation Index (PDII) for Potassium Phthalimide after 24 hours was 2.3

Based on the scores, Potassium phthalimide can be considered to be moderate skin irritant.

Eye Irritation:

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.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

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

Qualifier:

according to guideline

Guideline:

other: Draize method

Principles of method if other than guideline:

Skin irritation study was performed on New Zealand White rabbits to evaluate the irritation potential of potassium phthalimide

GLP compliance:

not specified

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Accilmation Period:Animals were held for 14 days after arrival in the facility but prior to use in tests to ensure that they are healthy.

Type of coverage:

occlusive

Preparation of test site:

other: abraded and non abraded

Vehicle:

physiological saline

Controls:

yes

Amount / concentration applied:

0.5g

Duration of treatment / exposure:

24 hours

Observation period:

Observations were made at 25, 48 and 72 hrs.

Number of animals:

6

Details on study design:

Controls: Each animal served as its own control.As well as the test substance, a positive control substance (a known skin irritant, 1 % sodium lauryl sulfate in water) and a negative
control (plain gauze patch) are applied to the skin. Vehicle control was also used in case vehicle was used for the test substance.

TEST SITE
- Area of exposure: Rabbit’s back side was exposed with the test substance.
- % coverage: No data available
- Type of wrap if used: Saran Wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washing of the test substance with an appropriate solvent or vehicle is done if the test substance applied is a colored test substance (such as dye).
- Time after start of exposure: No data available

SCORING SYSTEM: Dermal irritation scores for erythema and edema formation was evaluated by the scale proposed by Draize.

Persistent irritation score are also recorded, as well as the occurrence of eschar (+ E) and/or necrosis (+ N).

Other effects / acceptance of results:

No data available

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24 h

Score:

2.3

Max. score:

8

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

Moderate irritation effect was observed when the rabbits were exposed to the test substance potassium phthalimide for 24 hrs.

Table 2: Dermal Irritation Results and Classification

Chemical type	Classification	PDII	FHSA
Potassium phthalimide	Moderate	2.3	Irritant

 

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Moderate irritation effect was observed when the rabbits were exposed to the test substance potassium phthalimide for 24 hrs. The Primary Dermal Irritation Index (PDII) for Potassium Phthalimide after 24 hours was 2.3
Based on the scores, Potassium phthalimide can be considered to be moderate skin irritant.

Executive summary:

Skin irritation study was performed on New Zealand White rabbits to evaluate the irritation potential of potassium phthalimide. 6 New Zealand White rabbits were used for the study.Animals were held for 14 days after arrival in the facility but prior to use in tests to ensure that they are healthy. Each animal served as its own control. Along with the test substance, a positive control substance (a known skin irritant, 1% sodium lauryl sulfate in water) and a negative control (plain gauze patch) are applied to the skin. A vehicle control patch was also used in case the chemical was moistened with a vehicle or suspended in vehicle. Four test sites, two on each side of the rabbit's back, were utilized for administration of test chemical and controls.

A standard random pattern of administration ensured that the test substance and controls are applied to each position at least once in each test group. Each test or control substance is held in place with a 1x1 inch2 12-ply surgical gauze patch. The gauze patch is applied to the appropriate skin site and secured with 1-inch wide strips of Blenderm surgical tape, at the four edges, leaving the center of the gauze patch non-occluded. A 0.5-g portion of Potassium Phthalimide was weighed and placed on the gauze patch prior to application of the patch. The test substance and patch are then placed on the appropriate skin site and secured. The patch is subsequently moistened with 0.5 ml physiological saline.The study was on performed on both abraded and non-abraded animals.The negative control site is covered with an untreated 12-ply surgical gauze patch (1X1 inch²). The impervious material (Saran Wrap) aids in maintaining the position of the patches and retards evaporation of volatile test substances.

A Saf-T-Shield collar is fitted and fastened around the neck of each test animal. The collar remains in place for a 24 hr exposure period. The collar prevents the animal from removing the wrapping and patches.After the exposure period, the test substance skin site is wiped with dry gauze to remove any test substance still remaining.Dermal irritation scores for erythema and edema formation was evaluated by the scale proposed by Draize.The primary dermal irritation index (PDII) was calculated by dividing the sum of total irritation scores by the number of observations, and classifying the test substance:

0.00 = non-irritant ,>0.00 - 0.50 = negligible irritant, >0.50 -2.00 = mild irritant, >2.00-5.00 = moderate irritant, >5.00-8.00 = severe (primary) irritant.

 

 

Moderate irritation effect was observed when the rabbits were exposed to the test substance potassium phthalimide for 24 hrs. The Primary Dermal Irritation Index (PDII) for Potassium Phthalimide after 24 hours was 2.3

Based on the scores, Potassium phthalimide can be considered to be moderate skin irritant.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

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:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

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

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

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.
 

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

A skin irritation study was performed (Journal of Toxicology: Cutaneous and Ocular Toxicology; Vol 5(3); Pg. no. 195-214; 1986) on New Zealand White rabbits to evaluate the irritation potential of potassium phthalimide. 6 New Zealand White rabbits were used for the study.Animals were held for 14 days after arrival in the facility but prior to use in tests to ensure that they are healthy. Each animal served as its own control. Along with the test substance, a positive control substance (a known skin irritant, 1% sodium lauryl sulfate in water) and a negative control (plain gauze patch) are applied to the skin. A vehicle control patch was also used in case the chemical was moistened with a vehicle or suspended in vehicle. Four test sites, two on each side of the rabbit's back, were utilized for administration of test chemical and controls.

A standard random pattern of administration ensured that the test substance and controls are applied to each position at least once in each test group. Each test or control substance is held in place with a 1x1 inch2 12-ply surgical gauze patch. The gauze patch is applied to the appropriate skin site and secured with 1-inch wide strips of Blenderm surgical tape, at the four edges, leaving the center of the gauze patch non-occluded. A 0.5-g portion of Potassium Phthalimide was weighed and placed on the gauze patch prior to application of the patch. The test substance and patch are then placed on the appropriate skin site and secured. The patch is subsequently moistened with 0.5 ml physiological saline.The study was on performed on both abraded and non-abraded animals.The negative control site is covered with an untreated 12-ply surgical gauze patch (1X1 inch2). The impervious material (Saran Wrap) aids in maintaining the position of the patches and retards evaporation of volatile test substances.

A Saf-T-Shield collar is fitted and fastened around the neck of each test animal. The collar remains in place for a 24 hr exposure period. The collar prevents the animal from removing the wrapping and patches.After the exposure period, the test substance skin site is wiped with dry gauze to remove any test substance still remaining.Dermal irritation scores for erythema and edema formation was evaluated by the scale proposed by Draize. The primary dermal irritation index (PDII) was calculated by dividing the sum of total irritation scores by the number of observations, and classifying the test substance:

0.00 = non-irritant ,>0.00 - 0.50 = negligible irritant, >0.50 -2.00 = mild irritant, >2.00-5.00 = moderate irritant, >5.00-8.00 = severe (primary) irritant.

Moderate irritation effect was observed when the rabbits were exposed to the test substance potassium phthalimide for 24 hrs. The Primary Dermal Irritation Index (PDII) for Potassium Phthalimide after 24 hours was 2.3

Based on the scores, Potassium phthalimide can be considered to be moderate skin irritant.

Eye Irritation:

An eye irritation study was conducted ( Journal of Toxicology: Cutaneous and Ocular Toxicology; Vol 5(3); Pg. no. 195-214; 1986) 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.

Justification for classification or non-classification

Available studies for Potassium Phthalimide indicate that it is likely to cause moderate irritation to skin and eyes.

Hence, Potassium Phthalimide can be evaluated as “Irritant” to eyes and skin and it can be classified under the category “Skin 2 and Eye 2” as per CLP regulation.