Registration Dossier

Administrative data

Description of key information

Skin irritation:

The dermal irritation potential of target chemical was assessed in various in- vitro and in-vivo experimental studies.Based on the available studies,it can be concluded that the test chemical is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified''.

Eye irritation:

The ocular irritation potential of 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) is estimated to be not irritating to the eye of rabbits. Based on the estimated result 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) can be considered to be not irritating to eye and can be classified under the category “Not Classified” as per CLP regulation

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 05, 2017 to July 17, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental study report
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Principles of method if other than guideline:
The purpose of this study was to assess potential for the test article to be dermal irritants. The dermal irritation potential of test article may be predicted by measurement of their cytotoxic effect, as reflected in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, in the MatTek EpiDerm™ model.
GLP compliance:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL- Source and lot/batch No.of test material:- Expiration date of the lot/batch:- Purity test date:RADIOLABELLING INFORMATION (Not applicable)- Radiochemical purity: N/A- Specific activity: N/A- Locations of the label: N/A- Expiration date of radiochemical substance: N/ASTABILITY AND STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: Room temperature or Fridge storage- Stability under test conditions: No data available- Solubility and stability of the test substance in the solvent/vehicle: No data available- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data availableTREATMENT OF TEST MATERIAL PRIOR TO TESTING- Treatment of test material prior to testing: Prior to the main test, the test articles are tested for their ability to reduce/interact with MTT and their ability to stain the tissues itself. All tests are performed according to the by MatTek provided test protocol. - Preliminary purification step (if any): No data available- Final dilution of a dissolved solid, stock liquid or gel: No data available- Final preparation of a solid: No data availableFORM AS APPLIED IN THE TEST: SolidOTHER SPECIFICS: No data available
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: as provided by MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia
Source strain:
other: Not applicable
Details on animal used as source of test system:
- Description of the cell system used:The normal human-derived keratinocytes were cultured at the air-liquid interface in a chemically defined medium on a permeable polycarbonate insert (surface 0.5 cm2). They were cultured in chemically defined serum free medium to form a multi-layered epithelium similar to that found in native epidermis. Each lot of tissues was Quality Assured by MatTek according to specific QC standards including: histology, tissue viability (MTT mean optical density), reproducibility (SD) and tissue thickness.Test System IdentificationAll of the EpiDerm™ 3-dimensional human tissues used in this study were identified by the date of arrival and the lot number. Certificate of Analysis for the tissues are included in this report. Tissue plates were appropriately labeled with study information.
Justification for test system used:
The 3-Dimensional Human Dermal Epithelial Model (EpiDerm™, MatTek, In Vitro Life Science Laboratories, Bratislava, Slovakia) is made up of normal human keratinocytes in serum free medium. The cells form an epithelial tissue that consists of organized basal, spinous, granular, and cornified layers analogous to those found in vivo. The EpiDerm™ model also contains epidermis-specific differentiation markers such as pro-filaggrin, the K1/K10 cytokeratin pair, involucrin, and type I epidermal transglutaminase, as well as keratohyalin granules, tonofilament bundles, desmosomes, and a multi-layered stratum corneum containing intercellular lamellar lipid layers arranged in patterns characteristic of in vivo epidermis. Each lot of tissues was Quality Assured by MatTek, Inc. according to specific QC standards including: histology (cell layers), tissue viability (MTT mean optical density) and reproducibility (SD). Tissue plates were appropriately labeled with study information. Bias was not a factor in this test system.
Vehicle:
unchanged (no vehicle)
Details on test system:
The tissues were exposed to the test article neat (undiluted) on April 25, 2018 (Run 1 of 1). EpiDerm™ tissues were purchased from MatTek. Quality control of the tissues was performed by MatTek and the Certificate of Analysis (CoA) for the tissues is provided and is kept in the study binder. Tissues were exposed for approximately 1 hour, with 35 minutes in an approximately 37°C, 5% CO2 humidified incubator and the remaining 25 minutes at room temperature. Following the exposure time, the tissues were rinsed and placed in fresh media for approximately 24 hours. The media was then changed again and the tissues were incubated in fresh media for another ~18 hours for a total of approximately 42 hour post-exposure recovery period. The tissue viability was then assessed by MTT assay. The tissue CoA was used instead of verification of barrier properties of the tissue.MTT and Color Pre-testsPretesting has actually been conducted for all chemicals, although the first intitial 8 test chemicals a pretesting was not conducted (for skin).MTT AssayFollowing the rinsing period, the MTT assay was performed by transferring the tissues to 24-well plates containing 300 µL MTT medium (1.0 mg/mL). After 3 hours MTT incubation at approximately 37°C, approximately 5% CO2 in a humidified incubator, the blue formazan salt was extracted by submerging tissues in 2 mL isopropanol in a 24-well plate. The extraction time was approximately 3 hours with gentle shaking. The optical density of the extracted formazan (200 µL/well of a 96-well plate) was determined using a Thermo Scientific Multiskan FC Microplate Photometer at 570 nm. Relative cell viability is calculated for each tissue as % of the mean negative control tissues.Evaluation of Test Article in the Cell Models:1. Cell system: Upon receipt, the MatTek EpiDerm™ tissue cultures were placed in 0.9 mL of fresh Maintenance medium (in a 6-well plate). The culture inserts are incubated for ~one hour. The tissues were then transferred to 6-well plates containing 0.9 mL fresh Maintenance medium and they were incubated overnight (18 ± 3 hrs) at ~37°C, 5% CO2 in a humidified incubator.2. Control and Test Article Exposures: On the day of dosing, the tissues are then removed from the incubator and the controls and the test article are applied topically to tissues by pipette(liquid) Tissues were exposed to controls and the test article for one hour, with ~35 minutes in a 37°C, 5% CO2 humidified incubator and the remaining 25 minutes at room temperature.a) Controls30 µL of negative control DPBS and 30 μL of the positive control 5% SDS was applied topically to the tissue and gently spread by placing a nylon mesh on the apical surface of each tissue, if necessary.b) Test Articles 25 mg of the test article was applied topically to the tissue 3. Post-exposure treatmentAfter the 1 hour exposure, the tissues were rinsed 15 times with sterile DPBS. After the 15th rinse from washing bottle, each insert wasw completely submerge 3 times in 150 ml DPBS. The apical surface was gently blotted with a cotton swab. The tissues were placed in 0.9 mL of fresh Maintenance medium (6-well plate) for 24 ± 2 hours. After this initial ~24 hour incubation, the tissues were placed in 6-well plates containing 0.9 mL fresh Maintenance medium and incubated for another 18 ± 3 hours, for a total of an approximately 42 hour post-exposure incubation.RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE- Model used: The EpiDerm™ 3 dimensional human tissue model- Tissue Lot number(s): 26459- Date of initiation of testing: 6/08/2017TEMPERATURE USED FOR TEST SYSTEM- Temperature used during treatment / exposure: 37°C- Temperature of post-treatment incubation (if applicable): 37°CREMOVAL OF TEST MATERIAL AND CONTROLS-Volume and number of washing steps: The test substance was rinsed from the tissues with sterile DPBS by filling and emptying the tissue insert 15 times to remove any residual test material. This was followed by completely submerge the insert 3 times in 150 ml DPBS.MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE- MTT concentration: 300 µL MTT medium (1.0 mg/mL).- Incubation time: After 3 hours- Spectrophotometer: Synergy H4 spectrophotometer - Wavelength: 570 nm- Filter: No data- Filter bandwidth: No data- Linear OD range of spectrophotometer: No dataNUMBER OF REPLICATE TISSUES: 3CALCULATIONS and STATISTICAL METHODSAll data were background subtracted before analysis. MTT data are presented as % viable compared to negative control. Data were generated as follows: MTT AssayBlanks:·        The optical density (OD) mean from all replicates for each plate (ODblank). Negative Controls (NC):·        The blank corrected value was calculated: ODNC= ODNCraw– ODblank. ·        The OD mean per NC tissue was calculated. ·        The mean OD for all tissues corresponds to 100% viability. ·        The mean, standard deviation (SD), standard error of the mean (SEM) and the percent coefficient of variation (% CV) was calculated. Positive Control (PC):·        Calculate the blank corrected value: ODPC= ODPCraw– ODblank. ·        The OD mean per PC tissue was calculated. ·        The viability per tissue was calculated: %PC = [ODPC/ mean ODNC] x 100. ·        The mean viability for all tissues was calculated: Mean PC = Σ %PC / number of tissues. ·        The standard deviation (SD), standard error of the mean (SEM) and the percent coefficient of variation (% CV) was calculated. Tested compound :·        Calculate the blank corrected value ODTT= ODTTraw– ODblank. ·        The OD mean per tissue was calculated. ·        The viability per tissue was calculated: %TT = [ODTT/ mean ODNC] x 100. ·        The mean viability for all tissues was calculated: Mean TT = Σ %TT / number of tissues. ·        The standard deviation (SD), standard error of the mean (SEM) and the percent coefficient of variation (% CV) was calculated. Data Correction Procedure for MTT Interfering Compounds (if applicable)True viability = Viability of treated tissue – Interference from test article = ODtvt– ODktwhere ODkt= (mean ODtkt– mean ODukt).ODtvt= optical density of treated viable tissueODkt= optical density of killed tissuesODtkt= optical density of treated killed tissueODukt= optical density of untreated killed tissue (NC treated tissue) Data Correction Procedure for Colored Compounds (if applicable)True viability = Viability of treated tissue incubated in MTT media – Viability of treated tissue incubated in media without MTT = ODtvt– ODvt.ODtvt= optical density of treated viable tissue incubated in MTT mediaODvt= optical density of viable tissues incubated in media alone - Evaluation of data The results of the assay was evaluated and compared to negative control. Table: Criteria for in vitro Interpretation: In VitroResults In VivoPredictionMean tissue viability ≤50% Irritant (I), R38Mean tissue viability >50% Non-irritant (NI)- Assay quality controls- Negative Controls (NC)The Dulbecco’s phosphate buffered saline (DPBS) was used as a NC. The assay passed all acceptance criteria if the ODs of the negative control exposed tissues were between ≥0.8 and ≤2.8.  - Positive Controls (PC)5% solution of sodium dodecyl sulfate was used as a PC. The assay is meeting the acceptance criteria if the viability of the PC is ≤20% of the negative control.   - Standard Deviation (SD)The standard deviation (SD) calculated from individual percent tissue viabilities of the test article exposed replicates was ≤18.
Control samples:
no
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit):25 mg- Concentration (if solution): neat VEHICLE (Not used)- Amount(s) applied (volume or weight with unit): none- Concentration (if solution): none- Lot/batch no. (if required): none- Purity: noneNEGATIVE CONTROL- Amount(s) applied (volume or weight): not mentioned (if solution): no data POSITIVE CONTROL- Amount(s) applied (volume or weight): no data- Concentration (if solution):Potassium hydroxide
Duration of treatment / exposure:
The exposure times were approximately 1 hour, with ~35 minutes exposure in the incubator and ~25 minutes at room temperature.
Duration of post-treatment incubation (if applicable):
For a total of an approximately 42 hour post-exposure incubation.
Number of replicates:
3 tissues were used for test compound and control.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Run 1
Value:
106.7
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: 3 min. endpoint; mean of OD:2.025
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Run 1
Value:
118.5
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: 1 hour endpoint; mean of OD:2.138
Other effects / acceptance of results:
The MTT data show the assay quality controls were met.
Interpretation of results:
other: non-corrosive
Conclusions:
The dermal irritation potential of test article was determined according to the OECD 439 test guideline followed for this study. The mean of OD for test chemical was determined to be 2.025 and 2.138 for 3 min. enpoint and 1 hour endpoint,respectively.The Mean % tissue viability compared to negative control (n=3) of the test chemical was determined to be 106.7% and 118.5% for 3 min. enpoint and 1 hour endpoint,respectively. Thus, test chemical was considered to be non-corrosive to the human skin.
Executive summary:

The dermal irritation potential of test article was determined according to the OECD 439 test guideline for this study. The MatTek EpiDerm™ model was used to assess the potential dermal irritation of the test article by determining the viability of the tissues following exposure to the test article via MTT. Tissues were exposed to the test article and controls for ~one hour, followed by a 42 hour post-exposure recovery period. The viability of each tissue was determined by MTT assay.

The MTT data show the assay quality controls were met and passed the acceptance of criteria.

The mean of OD for test chemical was determined to be 2.025 and 2.138 for 3 min. enpoint and 1 hour endpoint,respectively. The Mean % tissue viability compared to negative control (n=3) of the test chemical was determined to be 106.7% and 118.5% for 3 min. enpoint and 1 hour endpoint,respectively.Hence, under the current experimental test conditions it was concluded that test chemical was considered to be non-corrosive to human 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:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is from OECD QSAR Toolbox version 3.3 and QMRF report has been attached.
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 5-amino-2-chlorobenzenesulfonic acid
- Molecular formula: C6H6ClNO3S
- Molecular weight: 207.636 g/mol
- Smiles notation: S(c1c(ccc(c1)N)Cl)(O)(=O)=O
- InChl: 1S/C6H6ClNO3S/c7-5-2-1-4(8)3-6(5)12(9,10)11/h1-3H,8H2,(H,9,10,11)
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data available
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
No data available
Duration of treatment / exposure:
No data available
Observation period (in vivo):
No data available
Duration of post- treatment incubation (in vitro):
No data available
Number of animals or in vitro replicates:
No data available
Details on study design:
No data available
Irritation parameter:
overall irritation score
Basis:
mean
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
no eye irritating effects were observed.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and "p" )  and ("q" and "r" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4 ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR Low reactive OR Low reactive >> N-substituted aromatic amides OR Low reactive >> Sulfanilic acid derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Aromatic amines AND Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Esters of organic sulfonic or sulfuric esters OR Inclusion rules not met OR Ketones OR Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 15 - Phosphorus P OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Chlorine, aromatic attach [-Cl] AND Chlorine, olefinic attach [-Cl] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as 2-Aminoalkyl acetamide [NCOCN<] OR Acid, aromatic attach [-COOH] OR Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [C] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic Carbon, two phenyl attach [-C-]  OR Aliphatic Carbon, two phenyl attach [-CH2-]  OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aliphatic Oxygen, two aromatic attach [-O-] OR Aliphatic Suflur, one aromatic attach [-S-] OR Alpha-dicarbonyl compound [-C(=O)-] OR Amide, aromatic attach [-C(=O)N] OR Amino, aliphatic attach [-N<] OR Aromatic Nitrogen OR Aromatic Sulfur OR Carbonyl, aliphatic attach [-C(=O)-] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Ester, aliphatic attach [-C(=O)O] OR Ethane-diamide [-N-CO-CO-N-] OR Nitro, aromatic attach [-NO2] OR Nitrogen, hydrogen attach {v+5} OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH2] OR Oxygen, one aromatic attach [-O-] OR Oxygen, two olefinic attach [-O-] OR Pyridine, non fused rings  OR Sulfamide, aromatic attach [-SO2-N] OR Sulfonyl amide, aromatic attach [-S(=O)N-] OR Sulfur, nitrogen attach [-S-] OR Tertiary Carbon OR Urea [-OC(=O)N-] by Organic functional groups (US EPA)

Domain logical expression index: "o"

Similarity boundary:Target: Nc1ccc(Cl)c(S(O)(=O)=O)c1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: Nc1ccc(Cl)c(S(O)(=O)=O)c1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.03

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.387

Interpretation of results:
other: not irritating
Conclusions:
The substance 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) is estimated to be not irritating to the eye of rabbits. Based on the estimated result 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) can be considered to be not irritating to eye.
Executive summary:

The ocular irritation potential of 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) is estimated to be not irritating to the eye of rabbits. Based on the estimated result 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) can be considered to be not irritating to eye and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In different studies, the test chemical has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in- vitro and in-vivo experimental conducted in human and rabbits which have been summarized as below:

The dermal irritation potential of test article was determined according to the OECD 439 test guideline for this study. The MatTek EpiDerm™ model was used to assess the potential dermal irritation of the test article by determining the viability of the tissues following exposure to the test article via MTT. Tissues were exposed to the test article and controls for ~one hour, followed by a 42 hour post-exposure recovery period. The viability of each tissue was determined by MTT assay.The MTT data show the assay quality controls were met and passed the acceptance of criteria.The mean of OD for test chemical was determined to be 2.025 and 2.138 for 3 min. enpoint and 1 hour endpoint,respectively. The Mean % tissue viability compared to negative control (n=3) of the test chemical was determined to be 106.7% and 118.5% for 3 min. enpoint and 1 hour endpoint,respectively.Hence, under the current experimental test conditions it was concluded that test chemical was considered to be non-corrosive to human skin.

 

According to prediction model Danish (Q) SAR Database (2017), the skin irritation effects were predicted for target chemical in rabbits by using four different models i.e, Battery,CASE Ultra, Leadscope and SciQSAR. Based on estimation, no severe skin irritation effects were known when test chemical was exposed to rabbit skin. Thus it can be concluded that the test substance can be considered as not irritating to the rabbits skin.

 

The above results were supported by Primary Skin irritation study reported by IFA GESTIS and BG Chemie (2000) in rabbits in accordance with OECD guideline No. 404 for structurally similar read across substance. The animals were subjected to a single 4- hour exposure to 500 mg of the test substance, mixed into a paste with water and applied semi-occlusively to the mechanically depilated skin of the flanks. The findings were scored after 1, 24, 48 and 72 hours as well as 7 days in accordance with the Draize method. The average irritation scores according to the Draize scoring for erythema and oedema were 0.0. Hence, test chemical was considered to be not irritating to skin of female albino rabbits.

 

GREIM H., J. AHLERS, R. BIAS, B. BROECKER, H. HOLLANDER, H.P. GELBKE, H.-J. KLIMISCH, I. MANGELSDORF, A. PAETZ, N SCHGN, G. STROPP, R. VOGEL, C. WEBER, K. ZIEGLER-SKYLAKAKIS and E. BAYER in (1994) performed skin irritation test in 2 New Zealand White rabbits (male and female) of another structurally similar read across substance for the observation period of 7 days. In this skin irritation study, approx. 500 mg 7-amino-4-hydroxy-2-naphthalenesulfonic acid (I acid) was applied to the inner surface of the ears of 2 rabbits. The test chemical was applied under an adhesive dressing for 24 hours. At the end of the exposure period, the test substance was washed off with water and soap/vegetable oil. The observation period was 7 days. No skin irritation was observed after 7 days. Hence the test chemical can be considered non-irritant to rabbit skin.

 

Acute skin irritation study was performed by BG Chemie (2000) on 3 rabbits according to the OECD guideline No. 404 for read across substance. Rabbits were exposed to 500 mg of chemical under semi-occlusive cover for 4 hrs following application to the mechanically depilated dorsal skin. Skin reactions were observed at 30 to 60 minutes and 24, 48 and 72 hours after the end of exposure.  None of the rabbits showed any cutaneous reactions. Hence, test chemical was considered to be not irritating to the mechanically depilated dorsal skin of New Zealand albino rabbits.

All these studies lead to a conclusion that Test chemical is indeed not irritating to skin. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical can be classified under the category “Not Classified”.

 

Eye irritation:

In different studies,the test chemical1-[(2,4-dimethylphenyl)diazenyl]-2-naphthol (CAS No: 3118-97-6) has been investigatedto observe the potential forocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) and its structurally similar read across substances4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) and 7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor,ocular irritation potential was estimated for 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7). The substance 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) is considered to be not irritating to the eyes of rabbits.

 

The above result was supported by experimental study conducted by GREIM H., J. AHLERS, R. BIAS, B. BROECKER, H. HOLLANDER, H.P. GELBKE, H.-J. KLIMISCH, I. MANGELSDORF, A. PAETZ, N SCHGN, G. STROPP, R. VOGEL, C. WEBER, K. ZIEGLER-SKYLAKAKIS and E. BAYER  in 1994 forstructurally similar read across substance7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) in rabbits. In this study, 50 mg 7-amino-4-hydroxy-2-naphthalenesulfonic acid (I acid) was instilled into the conjunctival sac of 2 animals and each were observed for 7 days. No eye irritation was observed after 7 days. Hence the chemical 7-amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) can be considered non-irritant to rabbit eyes.

 

IFA GESTIS performed eye irritation study in 6 rabbits for another structurally similar read across substance 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) in accordance with OECD guideline 405. About 100 μl of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid was placed into the conjunctival sac of each rabbit and the results were recorded for 3 days. Slight reddening in only one of 6 animals was observed but this was reversible after 3 days. Since the observed eye effects were not persisted after 3 days ,the chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to rabbits’ eye.

 

The above results were further supported by Ocular irritation study conducted by BG Chemie (2000) for sameread across substance4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) in accordance with OECD guideline No. 405. The rabbits were given a single instillation of 100 μl (approx. 50 mg) into the conjunctival sac of one eye, and the results were recorded after 1, 24, 48 and 72 hours as well as after 7 days. Evaluation was carried out in accordance with the Draize method. The average irritation scores according to the Draize scoring for cornea, iris and conjunctivae were 0.0. Hence, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to eyes of albino rabbits.

 

Based on the available data for the targetchemical5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) and its structurally similar read across substances4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) and 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7),it can be concluded thatchemical7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5)is not able to cause eye irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential for targetchemical5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) and its structurally similar read across substances4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) and 7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) were observed in various studies. The results obtained from these studies indicates that the test chemical 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7)is not likely to cause skin and eye irritation. Hence 5-amino-2-chlorobenzenesulfonic acid (CAS No: 88-43-7) can be classified under the category “Not Classified”for skin and eye as per CLP.