Registration Dossier

Skin Irritation:

The dermal irritation potential of sodium benzenesulfinate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Sodium benzenesulfinate was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, sodium benzenesulfinate can be considered not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of sodium benzenesulfinate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Sodium benzenesulfinate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, sodium benzenesulfinate can be considered not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Reference

Endpoint:

skin 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 v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): sodium benzenesulfinate
- Molecular formula: C6H6O2SNa
- Molecular weight: 164.16 g/mol
- Smiles notation: c1(ccccc1)S(=O)[O-].[Na+]
- InChl: 1S/C6H6O2S.Na/c7-9(8)6-4-2-1-3-5-6;/h1-5H,(H,7,8);/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:

no data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5g

Duration of treatment / exposure:

4 hours

Observation period:

1,24,48 and 72 hours, day7 and day 14 after patch removal

Number of animals:

2

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1,24,48,72 hours and 7,14 days

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no irritation observed

Estimation method: Takes mode value from the 9 nearest neighbours
Domain logical expression:Result: In Domain

(((((((((((((((("a" or "b" or "c" or "d" ) and ("e" and ( not "f") ) ) and ("g" and ( not "h") ) ) and ("i" and ( not "j") ) ) and "k" ) and "l" ) and ("m" and ( not "n") ) ) and ("o" and ( not "p") ) ) and "q" ) and ("r" and ( not "s") ) ) and "t" ) and "u" ) and "v" ) and "w" ) and ("x" and ( not "y") ) ) and ("z" and "aa" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl OR Overlapping groups OR Sulfinic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl OR Overlapping groups OR Sulfinic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic Carbon [C] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Suflur {v+4} or {v+6} by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Anion OR Aromatic compound OR Cation OR Sulfinic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Similarity boundary:Target: O=S(c1ccccc1)O{-}.[Na]{+}
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Aliphatic amines (Mucous membrane irritation) Rank C OR Aliphatic nitriles (Hepatotoxicity) Rank B OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Tamoxifen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Metals, oxidative stress (Nongenotox) OR o-phenylphenol (Nongenotox) OR Primary aromatic amine,hydroxyl amine and its derived esters (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "r"

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: "s"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Vinyl pyridines by DPRA Cysteine peptide depletion

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Cation AND Sulfinic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as weeks - months by Biodeg ultimate (Biowin 3) ONLY

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Aliphatic Amines OR Alkoxysilanes OR Aluminum Compounds OR Benzotriazoles (Acute toxicity) OR Boron Compounds OR Lanthanides or Rare Earth Metals OR Nickel Compounds OR Soluble complexes of Zinc OR Zirconium Compounds by US-EPA New Chemical Categories

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.46

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.6

Interpretation of results:

other: not irritating

Conclusions:

Sodium benzenesulfinate was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of sodium benzenesulfinate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Sodium benzenesulfinate was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, sodium benzenesulfinate can be considered not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

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 v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): sodium benzenesulfinate
- Molecular formula: C6H6O2SNa
- Molecular weight: 164.16 g/mol
- Smiles notation: c1(ccccc1)S(=O)[O-].[Na+]
- InChl: 1S/C6H6O2S.Na/c7-9(8)6-4-2-1-3-5-6;/h1-5H,(H,7,8);/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:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

single application

Observation period (in vivo):

1,24,48 and 72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1,24,48 and 72 hours

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no irritation observed

Estimation method: Takes mode value from the 6 nearest neighbours
Domain logical expression:Result: In Domain

((((((((((((((((((("a" or "b" or "c" or "d") and("e" and(not "f")) ) and("g" and(not "h")) ) and "i") and "j") and("k" and(not "l")) ) and("m" and(not "n")) ) and("o" and(not "p")) ) and "q") and("r" and(not "s")) ) and "t") and("u" and(not "v")) ) and "w") and "x") and "y") and "z") and "aa") and "ab") and("ac" and "ad") )

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Aryl OR Overlapping groups OR Sulfinic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Aryl OR Overlapping groups OR Sulfinic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aromatic Carbon [C] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Suflur {v+4} or {v+6} by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Anion OR Aromatic compound OR Cation OR Sulfinic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Similarity boundary:Target: O=S(c1ccccc1)O{-}.[Na]{+}
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Referential boundary:The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C OR Aliphatic nitriles (Hepatotoxicity) Rank B OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Tamoxifen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "m"

Referential boundary:The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as Metals, oxidative stress (Nongenotox) OR o-phenylphenol (Nongenotox) OR Primary aromatic amine,hydroxyl amine and its derived esters (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "q"

Referential boundary:The target chemical should be classified as weeks - months by Biodeg ultimate (Biowin 3) ONLY

Domain logical expression index: "r"

Referential boundary:The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "s"

Referential boundary:The target chemical should be classified as Aliphatic Amines OR Alkoxysilanes OR Aluminum Compounds OR Benzotriazoles (Acute toxicity) OR Boron Compounds OR Lanthanides or Rare Earth Metals OR Nickel Compounds OR Soluble complexes of Zinc OR Zirconium Compounds by US-EPA New Chemical Categories

Domain logical expression index: "t"

Similarity boundary:Target: O=S(c1ccccc1)O{-}.[Na]{+}
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

Referential boundary:The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "v"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles >> Heterocyclic Aromatic Amines OR Radical mechanism OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "w"

Referential boundary:The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "x"

Referential boundary:The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "y"

Referential boundary:The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "z"

Referential boundary:The target chemical should be classified as Biodegrades Fast by Biodeg probability (Biowin 7) ONLY

Domain logical expression index: "aa"

Referential boundary:The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 6) ONLY

Domain logical expression index: "ab"

Referential boundary:The target chemical should be classified as Biodegrades Fast by Biodeg probability (Biowin 2) ONLY

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.46

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= -2.4

Interpretation of results:

other: not irritating

Conclusions:

Sodium benzenesulfinate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of sodium benzenesulfinate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Sodium benzenesulfinate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, sodium benzenesulfinate can be considered not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin irritation:

In different studies, sodium benzenesulfinate has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical sodium benzenesulfinate and its functionally similar read across substances, disodium benzene-1,3-disulfonate [CAS: 831-59-4] and Sodium benzene sulfonate [CAS: 515-42-4]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the dermal irritation potential was estimated for sodium benzenesulphinate. Sodium benzenesulphinate was estimated to be not irritating to the skin of New Zealand White rabbits.

This result is supported by the experimental study performed by Chin H. Tay et.al (International Journal of Toxicology, January 2004 vol. 23 no. 1 pp.11-16) on New Zealand White rabbits to assess the irritation potential of the functionally similar read across substance, disodium Benzene meta-disulfonate[CAS: 831-59-4]. The study was performed according to EPAOPPTS 870.2500, “Acute Dermal Irritation” Guidelines.

Two concentrations of disodium benzene meta-disulfonate were tested in separate groups of animals, 3 female and 3 male rabbits: 5000 and 2000 mg/L. The pH of the 5000 mg/L test substance ranged from 7.07 to 6.22 prior to dosing and after the 4-hour exposure. The pH of the 2000 mg/L test substances, measured prior to dosing and after the 4-hour exposure, ranged from 7.04 to 6.96.

Each dose of test compound (0.5 ml of each concentration for each dose cohort) was applied to a small area of skin (approximately 6cm2) and covered with four layers of gauze patch held in place with nonirritating tape. Since the compound was in liquid form, it was applied to the gauze before application to the skin. The patch was loosely held in contact with the skin using a semi-occlusive dressing for the exposure period of 4 hours. At the end of the 4-hour exposure period, the patches were removed and the skin wiped to remove any test substance still remaining. Animals were observed for signs of erythema and edema at 1, 24, 48, and 72 hours after patch removal. Observations of erythema or edema were scored according to the Draize Scale for Scoring Skin Reactions (USEPA 1998). This scale assesses irritation as follows: 0, no erythema or edema; 1, very slight erythema and/or edema (barely perceptible); 2, well-defined erythema and/or slight edema; 3, moderate to severe erythema or moderate edema, and 4, severe erythema and/or edema. Animals were weighed before exposure and at the end of the exposure period (day 3) and observed daily for the incidence of any clinical signs of toxicity (other than erythema and edema). Control skin showed no signs of irritation. At 5000 mg/L, very slight (one animal, Draize Score 1) and well defined erythema (two animals, Draize Score 2) were observed 1 hour after removal of the test substance. At the 24-hour observation point, only two animals demonstrated very slight irritation. By 48 hours, very slight irritation remained on only one of the two test animals. By 72 hours, no irritation was observed on any animal. No erythema or edema was observed in any test animals at 2000 mg/L.

Since the effects at 5000mg/l were fully reversible within 72 hours and not observed at 2000 mg/l, disodium Benzene meta-disulfonate can be considered not irritating to rabbit skin.

The above results are also supported by the experimental study performed by Chin H. Tay et.al (International Journal of Toxicology, January 2004 vol. 23 no. 1 pp.11-16) on New Zealand White rabbits to assess the irritation potential of the functionally similar read across substance, Sodium benzene sulfonate [CAS: 515-42-4]. Four doses were applied: 5000 mg/L, 2000 mg/L, 1000 mg/L, and 500 mg/l to 6 male and 6 female rabbits per dose group. The pH of the 1000 mg/L dosage was 7.01 and 6.98 prior to dosing and after the 4-hour exposure, respectively. For the 5000 mg/L dosage, the pH was 7.00 and 7.02 prior to dosing and after the 4-hour exposure, respectively.

Each dose of test compound (0.5 ml of each concentration for each dose cohort) was applied to a small area of skin (approximately 6cm2) and covered with four layers of gauze patch held in place with nonirritating tape. Since the compound was in liquid form, it was applied to the gauze before application to the skin. The patch was loosely held in contact with the skin using a semi-occlusive dressing for the exposure period of 4 hours.

At the end of the 4-hour exposure period, the patches were removed and the skin wiped to remove any test substance still remaining. Animals were observed for signs of erythema and edema at 1, 24, 48, and 72 hours after patch removal. Observations of erythema or edema were scored according to the Draize Scale for Scoring Skin Reactions (USEPA 1998). This scale assesses irritation as follows: 0, no erythema or edema; 1, very slight erythema and/or edema (barely perceptible); 2, well-defined erythema and/or slight edema; 3, moderate to severe erythema or moderate edema, and 4, severe erythema and/or edema. Animals were weighed before exposure and at the end of the exposure period (day 3) and observed daily for the incidence of any clinical signs of toxicity (other than erythema and edema). Control skin showed no signs of irritation.At a dose of 5000 mg/L, very slight erythema (Draize Score 1) was observed in all three test animals 1 hour after removal of the gauze containing the benzene sulfonate solution. At the 24-hour observation point, very slight irritation (Draize Score 1) was observed in one of the three test animals. At the 48- and 72-hour observation points, the irritation was reversed, and no irritation was observed in any of the animals. Edema was not observed at any time. Control skin showed no signs of irritation. At 2000 mg/L, very slight erythema (Draize Score 1) was observed in two of the three test animals 1 hour after removal of the benzene sulfonate solution. The irritation was reversed by 24 hours. No erythema was observed in any test animals at this dosage at 24, 48 or 72 hours.

Since the effects at all dose levels were fully reversible within 72 hours, Sodium Benzene sulfonate can be considered not irritating to rabbit skin.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, sodium benzene sulphinate can be considered not irritating to skin.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, sodium benzenesulfinate has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical sodium benzenesulfinate and its functionally similar read across substances, Sodium cumenesulphonate [CAS: 28348-53-0] andsodium 3 -nitrobenzenesulfonate[CAS: 127-68-4].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for sodium benzenesulphinate. Sodium benzenesulphinate was estimated to be not irritating to the eyes of New Zealand White rabbits.

This result is supported by the experimental study summarized in International Journal of Toxicology; Vol 30, Issue 6_suppl, pp. 270S - 283S, 2011; for the functionally similar read across substance, Sodium cumene sulphonate [CAS: 28348-53-0]. The test was performed in accordance with OECD 405 Guidelines. Undiluted Sodium cumene sulphonate instilled in to the rabbit eyes and effects were observed (dose and duration not specified). Sodium cumene sulphonate was not irritating to rabbit eyes.

The above results are also supported by the experimental study summarized in Chemosphere. Vol. 28, No. 12, pp. 2203.2236, 1994, for thefunctionally similar read across substance,sodium 3-nitrobenzenesulfonate[CAS: 127-68-4]. Undiluted sodium 3-nitrobenzenesulfonate was instilled into the rabbit eyes and observed for signs of irritation (duration not specified). No signs of irritation were observed. Hence, Sodium 3-nitrobenzenesulfonate was considered to be not irritating to eyes.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, sodium benzene sulphinate can be considered not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Available data for sodium benzenesulphinate suggests that it is not likely to cause any irritation to eyes and skin.

Sodium benzenesulphinate can be classified under the category “Not Classified” as per CLP regulation