Methanetrisulphonic acid

Endpoint summary

Description of key information

Skin Irritation:

The dermal irritation potential of Methanetrisulfonic acid was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor. Methanetrisulfonic acid was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated results, methanetrisulfonic acid can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of Methanetrisulfonic acid(CAS no: 54322-33-7)was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor. Methanetrisulfonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits. Based on the estimated results, methanetrisulfonic acid(CAS no: 54322-33-7)can be considered to be not irritating to eyes 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 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 v3.4 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 v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: methanetrisulfonic acid
- Molecular formula: CH4O9S3
- Molecular weight: 256.232 g/mol
- Smiles notation: O=S(=O)(C(S(=O)(=O)O)S(=O)(=O)O)O
- InChl: 1S/CH4O9S3/c2-11(3,4)1(12(5,6)7)13(8,9)10/h1H,(H,2,3,4) (H,5,6,7)(H,8,9,10)
- 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:

500 mg

Duration of treatment / exposure:

4 hours

Observation period:

24,48 and 72 hours

Number of animals:

3

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

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" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and "l" )  and "m" )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Sulfonic acid by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Overlapping groups AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Hydroxy, sulfur attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR S(=O)N{-S(=O); P(=O)}  OR Suflur {v+4} or {v+6} OR Sulfinic acid [-S(=O)OH] OR Sulphonate, aliphatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND S(=O)N{-S(=O); P(=O)}  AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulphonate, aliphatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes and Azoxyalkanes OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrobiphenyls and Bridged Nitrobiphenyls OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) >> Diazenes and Azoxyalkanes OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione 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 >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Acrylic acid esters OR High reactive >> Activated 1,3,5-triazine derivatives by DPRA Lysine peptide depletion

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "l"

Similarity boundary:Target: OS(=O)(=O)C(S(O)(=O)=O)S(O)(=O)=O
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: OS(=O)(=O)C(S(O)(=O)=O)S(O)(=O)=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -5.51

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.0255

Interpretation of results:

other: not irritating

Conclusions:

Methanetrisulfonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of Methanetrisulfonic acid was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

Methanetrisulfonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemicalMethanetrisulfonic acid (CAS no: 54322-33-7)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemicalMethanetrisulfonic acid (CAS no: 54322-33-7)and its structurally similar read across substancesMethallyl sulfonate(CAS No:-1561-92-8)andsodium 2-hydroxyethane-1-sulfonate (CAS No:-1562-00-1) .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, the skin irritation potential was estimated for test chemicalMethanetrisulfonic acid (CAS no: 54322-33-7) .The chemical Methanetrisulfonic acid (CAS no: 54322-33-7)is estimated to be not irritating to skin of New Zealand White rabbits.

 

The EUROPEAN COMMISSION European Chemicals Bureau (2000) reported skin irritation study of structurally similar read across substance Methallyl sulfonate (CAS No:-1561-92-8) in rabbits to determine its irritation potential. About 0.5 ml of the undiluted test substance was applied to the shaved back skin of 6 male rabbits. After occlusion for 24 hours, the bandage was removed. Skin reactions were scored 1–2 and 48 hours after removal of the bandage. The mean erythema and edema scores after 1-2 and 48 hours were 0.17 and 0.25 respectively. Based on the scores, Methallyl sulfonate (CAS No:- 1561-92-8) was considered to be not irritating to the rabbits’ skin

 

The above results were further supported by experimental study carried out by the Sodium Ethyl Sulfonates Coalition (2006) of otherstructurally similar read across substancesodium 2-hydroxyethane-1-sulfonate (CAS No:-1562-00-1) in rabbits according to OECD Guide-line 404 and EEC Directive 92/69,Publication No. L 383A, B.4 Guidelines. At least 24 hours before the test, the fur was removed by clipping the dorsal part of the trunk of the animals. 0.5 g of the test chemical was moistened with Aqua Bidest and applied under semi-occlusive conditions to the intact skin of 3 young adult(2 males and 1 female) New Zealand White rabbits. Untreated sites on the same animals acted as negative controls. After four hours the patch and test substance was removed with Lutrol. Readings were taken at 1, 24, 48 and 72 hours and scored for presence and severity of erythema/eschar formation and edema formation. Barely perceptible erythema (score of 1) was observed in all three animals at the 1 hour observation time, but this had completely disappeared by 24 hours. All the remaining scores were 0 (no effect) for the rest of the study. The Primary Irritation Index was 0.0. Based on these observations and scores, sodium 2-hydroxyethane-1-sulfonate was considered not irritating to skin. 

Thus on the basis of available data for thetarget chemicalMethanetrisulfonic acid (CAS no: 54322-33-7) andits structurally similar read across substancesMethallyl sulfonate (CAS No:-1561-92-8)andsodium 2-hydroxyethane-1-sulfonate (CAS No:-1562-00-1),itcan be concluded thatchemical Methanetrisulfonic acid (CAS no: 54322-33-7)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:

In different studies,the test chemicalMethanetrisulfonic acid (CAS no: 54322-33-7)has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemicalMethanetrisulfonic acid (CAS no: 54322-33-7)its structurally similar read across substances Methallyl sulfonate (CAS No:-1561-92-8)andsodium 2-hydroxyethane-1-sulfonate (CAS No:-1562-00-1).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, the ocular irritation potential was estimated for test chemicalMethanetrisulfonic acid (CAS no: 54322-33-7) .The chemical Methanetrisulfonic acid (CAS no: 54322-33-7)is estimated to be not irritating to eyes of New Zealand White rabbits.

 

The EUROPEAN COMMISSION European Chemicals Bureau (2000) reported skin irritation study ofstructurally similar read across substanceMethallyl sulfonate (CAS No:-1561-92-8) in rabbits to determine its irritation potential according to  USA Interagency Regulatory Liaison Group Testing Standards and Guidelines Work Group Guidelines. Methallyl sulfonate was instilled into the eyes of 6 rabbits and observed for signs of irritation. The rabbitts were scored for signs of irritation at 24,48 and 72 hours. The mean of 6 animals at 24, 48 and 72 hours was: cornea: 0.06, iris: 0.0, conjunctiva: redness: 0.5, chemosis: 0.3. The mean irritation score after 72 hours was 0.33/110. Hence, Methallyl sulfonate (CAS No:-1561-92-8) can be considered not irritating to rabbit eyes.

 

The above results were further supported by experimental study carried out by the Sodium Ethyl Sulfonates Coalition (2006) of otherstructurally similar read across substancesodium 2-hydroxyethane-1-sulfonate (CAS No:-1562-00-1) in rabbits according to OECD Guideline 405 and EEC Directive 92/69, Publication No. L 383A, B.5 Guidelines. Both eyes of the animals were examined before application of the test material for signs of pre-existing irritation, reaction or abnormality. The application volume was 0.1 mL bulk volume, which is approximately 58 mg of the test substance. A single application of the test substance was given to the right conjunctival sac of 3 young adult (1 male and 2 females) New Zealand White rabbits. The left eye remained untreated and served as control. The treated eyes were washed out with tap water after 24 hours. Readings were taken at 1, 24, 48 and 72 hours and scored for corneal opacity, conjunctival redness, chemosis, and iris effects. No effects were observed for corneal opacity or iris. Minor chemosis (score of 1) was observed at the 1 hour period only and disappeared shortly thereafter. Minor conjunctival redness was observed at the 1 and 24 hour periods but not thereafter. Conjunctival discharge (score of 2) was observed at 1 hour only. The mean irritation score (24, 48 and 72 hours) for corneal opacity, iris, and chemosis was 0.0 and 0.3 for conjunctival redness. Based on the scores and observations, sodium 2-hydroxyethane-1-sulfonate was considered to be not irritating to rabbit eyes.

 

Thus on the basis of available data for thetarget chemicalMethanetrisulfonic acid (CAS no: 54322-33-7) andits structurally similar read across substancesMethallyl sulfonate (CAS No:-1561-92-8)andsodium 2-hydroxyethane-1-sulfonate (CAS No:-1562-00-1),itcan be concluded thatchemical Methanetrisulfonic acid (CAS no: 54322-33-7) is unable to cause ocular lesions 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 of test chemicalMethanetrisulfonic acid (CAS no: 54322-33-7)and its structurally similar read across substancesMethallyl sulfonate (CAS No:-1561-92-8)andsodium 2-hydroxyethane-1-sulfonate (CAS No:-1562-00-1)were observed in various studies. The results obtained from these studies indicate that the chemicalMethanetrisulfonic acid isunlikely to cause skin and eye irritation. HenceMethanetrisulfonic acid (CAS no: 54322-33-7)can be classified under the category “Not Classified” for skin and eye as per CLP.