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Description of key information

3-Aminobenzenesulfonic acid is considered slightly irritating in the skin irritation test in rabbits. Furthermore, 3-Aminobenzenesulfonic acid is not irritant to skin in the Human Skin Model Test.
3-Aminobenzenesulfonic acid is not irritating in the eye irritation test in rabbits. Furthermore, 3-Aminobenzenesulfonic acid is not corrosive / not severe irritant to the eye in the BCOP assay.

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:
other: Non GLP, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Qualifier:
according to guideline
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.41
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: der Lippischen Versuchstierzucht, Extertal, Germany
- Weight at study initiation: average 2.1 kg
- Housing: The animals were kept in individual cages
- Diet (e.g. ad libitum): animals received "Mümmel z" (SSNIF, Soest, Germany) ad libitum.
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: 7 - 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12h light- / 12h dark cycle
Type of coverage:
occlusive
Preparation of test site:
other: Left flanks: clipped. Right flanks: abraded
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
500 mg of the test substance suspended with water
Duration of treatment / exposure:
24 hour
Observation period:
8 days
Number of animals:
6
Details on study design:
Test Procedure:
Hair was removed from a skin area of about 8 x 8 cm of the right and left flanks of 6 rabbits with an average weight of 2.1 kg using electric clippers 24 hours before the beginning of the test. In addition, the skin of the right flank was abraded at the site of application for the test patch by means of a scarificator. Test patches of 2.5 x 2.5 cm consisting of double layers of surgical gauze were coated with/soaked in 500 mg of the test substance suspended with water and covered with an indifferent, impermeable PVC foil (5 x 5 cm). The foil with the test patches underneath was fixed onto the two test sites by means of nonirritant adhesive tape (Leukoflex®). Subsequently, the total trunk of the animals was bandaged using an elastic bandage (EioflexR) for the total exposure period of 24 hours. The animals were immobilized.

Examinations:
The findings were recorded immediately (about 30 min) after removal of the patches (24-hour value) and then 48 hours and 72 hours after the beginning of the test (48 hours after the first reading). The 48-hour value was not included in the report sheet. The control finding obtained after 8 days was not included in the assessment of the irritation index.

Evaluation:
The findings were assessed according to the following scale and afterward the irritation index (index of primary irritation) was determined.

Scoring system:
1. Erythema and Eschar Formation:
No erythema; 0
Very slight erythema (barely perceptible); 1
Well defined erythema; 2
Moderate to severe erythema; 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth); 4

2. Edema Formation
No edema; 0
Very slight, barely perceptible edema; 1
Slight oedema (edges of area well defined by definite raising); 2
Moderate edema (raised approximately 1 mm); 3
Severe edema (raised more than 1 mm and extending beyond area of exposure); 4

The values for erythema and edema obtained on the intact and abraded skin of each test animal after 24 and 72 hours are added and the means are determined from these. The 8 means determined in this way are divided by 4 to give the primary irritation index to the skin.

Classification:
0.0 to 0.5 non-irritating
0.6 to 3.0 slightly irritating
3.1 to 5.0 moderately irritating
5.1 to 8.0 severely irritating
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: abraded skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: abraded skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: abraded skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: abraded skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within:
Remarks:
8 days
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
fully reversible
Remarks:
8 days
Remarks on result:
other: abraded skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: abraded skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: abraded skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: abraded skin
Irritant / corrosive response data:
Still weak erythema after 8 days.
Interpretation of results:
slightly irritating
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:
other: Non GLP, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Qualifier:
according to guideline
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.42
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: der Lippischen Versuchstierzucht, Extertal, Germany
- Weight at study initiation: average 2.1 kg
- Housing: The animals were kept in individual cages
- Diet (e.g. ad libitum): animals received "mümmel z" (SSNIF, Soest, Germany) ad libitum.
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: 7 - 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12h light- / 12h dark cycle

Vehicle:
unchanged (no vehicle)
Controls:
other: left, untreated eye
Amount / concentration applied:
100 µL
Duration of treatment / exposure:
8 days
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
6 male animals
Details on study design:
Test Procedure
The test was carried out using 6 rabbits that had been examined before and had an average weight of 2.1 kg. Treatment consisted of a single application of a
bulk volume of 100 µL of the amorphous test substance into the conjunctival sac of the lower right eyelid. Subsequently, the Iids were gently held together for 1 sec. The eye was not rinsed after application. The secend left eye of the animals remained always untreated as a control.
The eyes were examined using an ophthalmoscope.
The finding on the cornea was verified by means of the fluorescein test (instillation of 1 drop in an ophthalmological preparation directly onto the cornea. After rinsing with physiological saline, corneal damage appears yellowish green. UV light or cobalt blue filter).

Observations were made 24, 48 and 72 h and 8 days after the start of the experiment. The observations after 8 days were not included in the evaluation of the irritation index.

SCORING:
The pathological findings on the cornea (according to the degree and area of opacity), iris and conjunctivae (according to redness, swelling and discharge) were assessed. ln detail, the assessment was carried out on the basis of the scale that was used for determining the irritation index..
Scoring system used from: The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA, 1959, p .5 1

1) Cornea
(A) Opacity- degree of density (area most dense taken for reading)
- No opacity; 0
- Scattered or diffuse area, details of iris clearly visible; 1
- Easily discernible translucent areas, details of iris slightly obscured; 2
- Opalescent areas, no details of iris visible, size of pupil barely discernible; 3
- Opaque, iris invisible; 4

(B) Area of cornea involved
- One quarter (or less) but not zero; 1
- Greater than one quarter but less than half; 2
- Greater than half but less than three quarters; 3
- Greater than three quarters, up to whole area; 4

2)Iris - iris
(A) Values
- Normal; 0
- Felds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive); 1
- No reaction to light, hemorrhage, gross destruction (any or all of these); 2

3) Conjunctivae
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
- normal vessels; 0
- Vessels injected clearly; 1
- More diffuse, deeper crimson red, individual vessels not easily discernible; 2
- Diffuse beefy red; 3
(B) Chemosis
- No swelling; 0
- Any swelling above normal (includes nictitating membrane); 1
- Obvious swelling with partial eversion of Iids; 2
- Swelling with Iids about half closed; 3
- Swelling with Iids about half closed to completely closed; 4
(C) Discharge
- No discharge; 0
- Any amount different from normal (does not include small amounts observed in inner canthus of normal animals); 1
- Discharge with moistening of the Iids and hairs just adjacent to Iids; 2
- Discharge with moistening of the Iids and hairs, and considerable area areund the eye; 3

Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 8 days
Interpretation of results:
not irritating
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In a non-GLP skin irritation test according to guideline similar to OECD 404, the flanks of 6 New Zealand White rabbits were clipped 24 before start of treatment on both sides of the trunk (​​approx. 8 x 8 cm) (Fraunhofer-Institut 1981). The skin of the right flank at the receiving location for the test patch was additionally scarified by a Schröpfschneppers. 2.5 x 2.5 cm patches of double layers of surgical gauze were soaked in 500 mg of metanilic acid wet suspended in water and covered with indifferent, impermeable PVC film (5 x 5 cm). The film with the underlying patch was fixed by skin-friendly adhesive tape (Leukoflex ®). Subsequently, the total trunk of the animals was wrapped with an elastic duration bandage (EloflexR) during 24h exposure time. Examinations were made 24, 48, 72 hours and 8 days after start of treatment. The irritation index was based on the 24 and 72 hours scores. At 24 and 72 hours erythema score of 1.83 and 1.17, respectively, was found in the intact skin and respectively 2.17 and 1.0 in the abraded skin. The edema score showed a score of 0.5 in the intact skin, and in abraded skin 0.33 at 24 hours. Edema was fully reversible within 72 hours. After 8 days still weak erythema was observed. Primary irritation was 1.8. Based on these observation the test substance is considered slightly irritating.

In a GLP-compliant in vitro study according to OECD guideline 439 the irritation potential of the test item was assessed by means of the Human Skin Model Test (Harlan CCR 2012). Three tissues of the human skin model EpiDerm™ were treated with the test item, the negative or the positive control for 60 minutes. Approximately 25 mg of the test item were applied to each tissue, wetted with 40 μL DPBS, and spread to match the tissue size. 30 μL of either the negative control (DPBS) or the positive control (5% Sodium lauryl sulfate) were applied to each tissue. After treatment with the negative control the absorbance values were well above the required acceptability criterion of mean OD ≥ 1.0 and ≤ 2.5 for the 60 minutes treatment interval thus showing the quality of the tissues. Treatment with the positive control induced a sufficient decrease in the relative absorbance as compared to the negative control for the 60 minutes treatment interval thus ensuring the validity of the test system. After treatment with the test item the mean relative absorbance value decreased to 93.8% compared to the relative absorbance value of the negative control. This value is above the threshold for irritancy of ≤ 50%. Therefore, the test item is not considered to possess an irritant potential. In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item is not irritant to skin according to UN GHS and EU CLP regulation.

Eye irritation

In a non-GLP in vivo eye irritation test according to guideline similar to OECD 405, 6 New Zealand White rabbits were administered 100 µL of 3 -Aminobenzenesulfonic acid substance in the right lower eyelid (Fraunhofer-Institut 1981). The eyes were not rinsed after application. The left eye remaind untreated and served as control. Observations on cornea, iris and conjunctiva were performed 24, 48 and 72 hours and 8 days after the start of treatment. The mean cornea score and iris score for all time points were 0.0. The mean conjunctivae score at 24, 48 and 72 hours were respectively 8, 6, 1.67 with fully reversibility at 8 days. The primary irritatation score was 5.2 (24-72 hours). Based on these observations 3 -Aminobenzenesulfonic acid is considered to be not irritating to the eye.

A GLP-compliant in vitro study was performed according to OECD 437 guideline, to assess the corneal irritation and damage potential of 3-aminobenzenesulphonic acid by means of the BCOP assay using fresh bovine corneae (Harlan CCR 2012). After a first opacity measurement of the fresh bovine corneae (t0), the 20% (w/v) suspension in saline (0.9% (w/v) NaCl in deionised water of the test item, the positive, and the negative controls were applied to corneae and incubated for 240 minutes at 32 ± 1 °C. The posterior chamber contained MEM medium supplemented with sodium bicarbonate and L-glutamine and 1% fetal calf serum (FCS) (complete medium = cMEM). After the incubation phase the test item, the positive, and the negative controls were each rinsed from the corneae and opacity was measured again (t240). After the opacity measurements permeability of the corneae was determined by measuring spectrophotometrically the transfer of sodium fluorescein after incubation in a horizontal position for 90 minutes at 32 ± 1 °C. With the negative control (saline) neither an increase of opacity nor permeability of the corneae could be observed. The positive control (10% (w/v) Benzalkonium chloride in saline showed clear opacity of the corneae corresponding to a classification as corrosive / severe irritant to the eye (CLP/EPA/GHS (Cat 1)). Relative to the negative control, 3 -Aminobenzenesulfonic acid did not cause any increase of the corneal permeability. Slight opacity effects could be observed. The calculated mean in vitro irritation score of 19.83 was below the threshold of ≥ 55.1. Therefore the test item is classified as not corrosive / not severe irritant to the eye according to OECD 437. In conclusion, according to the current study and under the experimental conditions reported, 3 -Aminobenzenesulfonic acid is not corrosive / not severe irritant to the eye (CLP/EPA/GHS (Cat 1)).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered not to be classified for irritation/corrosion toxicity under Regulation (EC) No. 1272/2008, as amended for the 13th time in Regulation (EU) 2018/1480.