2-(Naphthalene-2'-sulphonylamino)-benzoic acid

Endpoint summary

Description of key information

In the first study the skin irritancy potential of 2-(Naphthalene-2'-sulfonylamino)-benzoic acid was assessed on rabbit (OECD guideline number 204 of 1981). 2-(Naphthalene-2'-sulfonylamino)-benzoic acid

did not produce positive criteria in any rabbit according to the EC labelling regulations and was classified as NON-IRRITANT to rabbit skin.

In the second study, the eye irritancy potential of the 2 -(Naphtalene-2'-sulphonylamino)-benzoic acid was assessed on one rabbit (OECD Guideline No. 405 of 1987). A single application of the test material to the non-irrigated eye of one rabbit produced grade 4 corneal opacity, iridial inflammation and moderate conjunctival irritation. The test has been stopped and the animal was killed after 48h due to the persistance of grade 4 opacy. The evidence shows, that the test material could be classified according to EC labeling regulations into the Category 1 - producing serious eye damage but as the test was only carried out with one animal, it is insufficient for classification.

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

Study period:

The study was performed between 11 February 1992 and 14 February 1992.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Data relating to the identity, purity and stability of the test material are the responsibility of the sponsor.
- Storage condition of test material: room temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: For the purpose of this study the test material was moistened with distilled water immediately before application.
- Final dilution of a dissolved solid, stock liquid or gel: 0.5g of the test material was moistened with 0.5 ml of distilled water

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: 2.26 - 2.34 kg
- Housing: individual housing in suspended metal cages
- Diet (e.g. ad libitum): Free access to food (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol) was allowed throughout the study.
- Water (e.g. ad libitum): free access to drinking water and food was allowed throughout the study.
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22°C
- Humidity (%): 41 - 43%
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g of the test material, moistened with 0.5 ml of distilled water
- Concentration (if solution): not specified

Duration of treatment / exposure:

4h

Observation period:

24, 48 and 72h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm gauze patch on the shorn skin
- Type of wrap if used: strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 h after application

OBSERVATION TIME POINTS
- Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later

SCORING SYSTEM:
- Scale from Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"
- Method of calculation: The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by 6 to give the primary irritation index of the test material.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

overall irritation score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No evidence of skin irritation was noted during the study period.

Interpretation of results:

GHS criteria not met

Conclusions:

The 2-(Naphthalen-2-sulfonylamino)benzoic acid did not produce positive criteria in any rabbit according to the EC labelling regulations and was classified as NON-IRRITANT to rabbit skin.

Executive summary:

Study was performed to assess the irritancy potential of 2-(Naphthalen-2-sulfonylamino)benzoic acid following a single, 4-hour, semi-occluded application on New Zealand White rabbit following OECD guideline number 204 of 1981. 2-(Naphthalen-2 -sulfonylamino)benzoic acid did not produce positive criteria in any rabbit according to the EC labelling regulations and was classified as NON-IRRITANT to rabbit 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

Study period:

From 19 February 1992 to 21 February 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Data relating to the identity, purity and stability of the test material are the responsibility of the sponsor.
- Storage condition of test material: room temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test material was used as provided

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: approximately twelve to sixteen weeks old
- Weight at study initiation: 2.77 kg
- Housing: individual housing in a suspended metal cage
- Diet (e.g. ad libitum): free access throughout the study (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol)
- Water (e.g. ad libitum): free access throughout the study
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 21°C
- Humidity (%): 50 - 56%
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml of the test material (approximately 59 mg)
- Concentration (if solution): not specified
- Control: left eye remained untreated and was used for control purposes

Duration of treatment / exposure:

48h

Observation period (in vivo):

1h, 24h, 48 h

Number of animals or in vitro replicates:

1

Details on study design:

SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24 and 48 hours following treatment, according to the numerical evaluation given in Appendix I, (from Draize J.H. 1959, Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics").

TOOL USED TO ASSESS SCORE: standard ophthalmoscope

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

15

Max. score:

40

Reversibility:

other: Not reversible. due to persistence of opacy (grade of 4), the animals were killed after the 48h observation period.

Remarks on result:

probability of severe irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

48 h

Score:

40

Max. score:

40

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48 h

Score:

2

Max. score:

2

Reversibility:

other: due to persistence of opacy (grade of 4), the animals were killed after the 48h observation period.

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48 h

Score:

2

Max. score:

4

Reversibility:

other: due to persistence of opacy (grade of 4), the animals were killed after the 48h observation period.

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Residual test material was noted around the treated eye one hour after treatment.
Areas of diffuse corneal opacity were noted in the treated eye one hour after treatment. A small area, approximately 5 mm x 5mm, of grade 4 corneal opacity was noted in the treated eye at the 24 and 48-hour observations with diffuse to translucent corneal opacity in the remaining affected area of the treated eye.
Iridial inflammation was noted in the treated eye one hour after treatment and at the 24 and 48-hour observations.
Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24 and 48-hour observations. Adherence of the test material to the nictitating membrane and lower conjunctival membrane was also noted at the 24 and 48-hour observations.
Due to the persistance of the grade 4 opacity the animal was killed for humane reasons immediately after the 48-hour observation in accordance with current U.K. Home Office guidelines. No further animals were treated.

For information, the individual scores and total scores on tested rabbit are provided below:

Time after treatment	1h	24h	48h
Cornea
E = degree of opacity	1	4ab	4ab
F = area of oapacity	3	2	2
Score (ExF)x5	15	40	40
Iris
D	1	1	1
Score (Dx5)	5	5	5
Conjunctivae
A = Redness	2	2tm	2tm
B = Chemosis	2	2b	2b
C = Discharge	3RE	3	3
Score (A+B+C)x2	14	14	14
Total score	34	59	59

a = grade 4 opacity over small area (5mm x 5mm) with grade 1 or 2 opacity over remainder of affected area

b = positive critria

tm = test material adhered to nictitating membrane and lower conjunctival membrane

RE = residual test material around treated eye

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The test was only carried out with one animal and is therefore insufficient for classification, but the evidence shows that 2 -(Naphtalene-2'-sulphonylamino)-benzoic acid could be classified according to EC labeling regulations, into Category 1 - producing serious eye damage.

Executive summary:

A study was performed to assess the irritancy potential of the 2 -(Naphtalene-2'-sulphonylamino)-benzoic acid to the eye of the New Zealand White rabbit, following the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" of 1987. A single application of the test material to the non-irrigated eye of one rabbit produced grade 4 corneal opacity, iridial inflammation and moderate conjunctival irritation. Although the test was only carried out with one animal and is therefore insufficient for classification, the evidence shows, that the test material could be classified according to EC labeling regulations into Category 1 - producing serious eye damage.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Justification for classification or non-classification

2-(Naphthalene-2'-sulfonylamino)-benzoic acid is classified as follows according to CLP criteria:

• Not classified for skin corrosion/irriation
• Serious eye damage - category 1 (based on corneal opacy of 4 at 24 and 48h after instillation of the test material)