5-nitroisophthalic acid

Endpoint summary

Description of key information

Skin Irritation:

No clinical signs of Erythema and Edema were observed during the observation period, thus indicating that the test chemical is not irritating to skin of rabbits.

Eye irriration:

The test substance was observed to be irritating to the Eye when eye irritation study was conducted on rabbits.

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Data is from study report

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Assesment of a possible irritating or corrosive potential of the skin

GLP compliance:

yes

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: Male: 2.79 gm
Female: 2.85 gm
- Housing: Cage made of stainless steel with wire mesh walk floors. (Floor area: 40cm x 51cm)
- Diet (e.g. ad libitum):
- Water : 250 ml tap water/animal/day
- Acclimation period: Atleast 8 days before the study. Same housing conditions as during the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Air changes (per hr): Fully air conditioned
- Photoperiod (hrs dark / hrs light): 12h/12h (6.00-18.00 hours/18.00-6.00 hours)

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

50% aqueous formulation (W/W)
THE TEST PATCH (2.5 CM X 2.5 CM) IS COVEREO WITH AN ABOUT 0.5 MM LAYER OF THE 50% SUSPENSION (THUS ABOUT 0.5 G OF THE SUSPENSION IS APPLIED; BECAUSE OF THE NATURAL MOISTURE OF TNE SKIN, DISTILLED WATER IS USED TO PREPARE THE SUSPENSIONS SO THAT THE TEST CAN BE CARRIED OUT UNDER AS PHYSIOLOGICAL CONDITIONS AS POSSIBLE.

Duration of treatment / exposure:

4 hours

Observation period:

30-60 minutes after the removal of the test patch.
24, 48 and 72 hours after the beginning of the application

Number of animals:

Total: 3
Male: 1
Female: 2

Details on study design:

TEST SITE
- Area of exposure: Upper third of the back or flanks
- % coverage: (2.5cm x 2.5 cm)
- Type of wrap if used: Porous dressing (Four layers of absorbent gauze+porous bandage)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, at the end of the exposure period with Lutrol and Lutrol/water (1:1)
- Time after start of exposure: 72 hrs

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 30-60 minutes after removal of the test patches and 24, 48 and 72 hours after the beginning of the application.

SCORING SYSTEM:
- Method of calculation:

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation potential observed

Other effects:

No other effects observed.

Table: Body weight data

Animal	1	2	3
Animal no.	0075	0100	0085
Body weight (kg)	2.79	2.72	2.97
Sex	Male	Female	Female

Interpretation of results:

other: Not irritating

Conclusions:

No clinical signs of Erythema and Edema were observed during the observation period, thus indicating that the test chemical is not irritating to skin of rabbits.

Executive summary:

Acute skin irritation test, according to OECD guidelines 404 for testing of chemicals, was conducted on the intact dorsal skin of the Vienna white rabbit for test substance. 50% aqueous solution of the test substance was applied in an area of 2.5 cm x 2.5cm on the upper third of the back of the test animals. The test animals were exposed for 4 hours and readings were taken 30 -60 minutes after the removal of test patches and 24 H, 48 H. 72 H, after the beginning of application. Untreated skin sites of the same animal were treated as negative control. Observations were made for appearance of any symptoms of Erythema and Edema on the tested skin sites. However, none of the observations taken at different intervals showed any clinical signs of Erythema and Edema. Based on the results, the test substance was considered as not irritating to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not 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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Data is from study report

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

Assesment of a possible irritating potential to the eye and to the eye mucosa

GLP compliance:

yes

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation:
Male: 2.66 kg
Female: 2.45 kg
- Housing: Cage made of stainless steel with wire mesh walk floors. Floor area: 40cm x 51 cm
- Diet (e.g. ad libitum): KLIBA 341. 4 MM; FIRMA KLINGENTALMUEHLE AG CH-4303 KAISERAUGST. SWITZERLAND (ABOUT 130 G PER ANIMAL PER DAY)
- Water : About 250ml tap water per animal per cage
- Acclimation period: Atleast 8 days before the beginning of the study: Same housing conditions as during the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Air changes (per hr): Fully air conditioned
- Photoperiod (hrs dark / hrs light): 12h/12h (6.00-18.00 hours/18.00-6.00 hours)

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 ml bulk volume ( About 43 mg of the comminuted test substance)

Duration of treatment / exposure:

1Hr; 24Hrs; 48Hrs; 72Hrs; 8D after application.

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

1 male
2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

72 h

Score:

> 3 - < 3.7

Max. score:

3.2

Reversibility:

not specified

Remarks on result:

other: Severe eye irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

72 h

Score:

>= 0 - <= 0.3

Max. score:

0.1

Reversibility:

not specified

Remarks on result:

other: Normal

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Score:

>= 1.3 - <= 2

Max. score:

1.7

Reversibility:

not specified

Remarks on result:

other: Well defined

Table 1: Body weight data

Animal	1	2	3
Animal no.	0201	0186	0161
Body weight (kg)	2.50	2.40	2.66
Sex	Female	Female	Male

Table 2: Scores of eye irritation study

Readings	Animal	Cornea OP	Iris	Conjunctiva		Symptoms
				Red	SW
1 hour	1	2	0	2	2	Pupil contracted
	2	3	0	2	2	Pupil contracted
	3	2	0	2	2
24 hour	1	3	0	2	2	S3
	2	3	0	2	2	S/RE/S3
	3	3	0	2	2	S3/S
48 hour	1	3	0	2	1	S3/S
	2	3	0	2	2	S/RE/S3
	3	4	0	2	2	S3/S
72 hour	1	3	1	2	1	S3/S
	2	3	0	2	1	S/RE/S3
	3	4	0	2	2	S3/S
8 day	1	3	1	2	0	S/RE/S3/PC/S4
	2	4	0	2	1	S/RE/S3/LH/S4
	3	4	1	2	2	S3/S/MV/S4
Mean	1	3.0	0.3	2.0	1.3
	2	3.0	0.0	2.0	1.7
	3	3.7	0.0	2.0	2.0
Mean		3.2	0.1	2.0	1.7

 

Explanation of symptoms:

S3: Loss of corneal tissue

S4: Study disconnected after 8 day because of severe opacity

LH: Loss of hair at margins of eyelids

MV: Marginal vascularization of the cornea

PC: Pupil contraction

RE: Small retraction in the eyelids

S: Suppuration

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The test substance was observed to be irritating to the Eye when eye irritation study was conducted on rabbits.

Executive summary:

Study, according to OECD guideline 405, was conducted on rabbit (strain Vienna White) to observe the eye irritation potential of test substance. 0.1 ml bulk volume (about 43 mg of comminuted test substance) was applied to the conjunctival sac of the right eyelid of the test animals. One male and two female animals were tested. Readings were taken at 1H, 24H, 48H, 72H, 8 Day after the application.Clinical symptoms were observed within one hour of the application and at the end of observations period (8 days), symptoms like loss of corneal tissue, loss of hair at the margins of eyelid, marginal vascularization of the cornea, small retractions in the eyelid were observed. Based on the symptoms, the following scores for ocular lesions were assigned: cornea score -3.2, iris score -0.1 and conjunctivae score 1.7. Accordingly the substance is classified as irritating to eyes. .

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin Irritation:

Acute skin irritation test, according to OECD guidelines 404 for testing of chemicals, was conducted on the intact dorsal skin of the Vienna white rabbit for test substance. 50% aqueous solution of the test substance was applied in an area of 2.5 cm x 2.5cm on the upper third of the back of the test animals. The test animals were exposed for 4 hours and readings were taken 30 -60 minutes after the removal of test patches and 24 H, 48 H. 72 H, after the beginning of application. Untreated skin sites of the same animal were treated as negative control. Observations were made for appearance of any symptoms of Erythema and Edema on the tested skin sites. However, none of the observations taken at different intervals showed any clinical signs of Erythema and Edema. Based on the results, the test substance was considered as not irritating to skin.

Eye Irritation:

Study, according to OECD guideline 405, was conducted on rabbit (strain Vienna White) to observe the eye irritation potential of test substance. 0.1 ml bulk volume (about 43 mg of comminuted test substance) was applied to the conjunctival sac of the right eyelid of the test animals. One male and two female animals were tested. Readings were taken at 1H, 24H, 48H, 72H, 8 Day after the application.Clinical symptoms were observed within one hour of the application and at the end of observations period (8 days), symptoms like loss of corneal tissue, loss of hair at the margins of eyelid, marginal vascularization of the cornea, small retractions in the eyelid were observed. Based on the symptoms, the following scores for ocular lesions were assigned: cornea score -3.2, iris score -0.1 and conjunctivae score 1.7. Accordingly the substance is classified as irritating to eyes.

Justification for classification or non-classification

Based on the above studies on test chemical, it can be concluded that the test chemical was not irritating to skin but was irritating to eyes. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for skin irritation and classified at 'Category 2' for Eye irritation.