Methyl methanesulphonate

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical Methyl methanesulfonate (CAS No: 66-27-3) was assessedin various experimental studies which were conducted on rabbits, guinea pigs and humans for target chemicalMethyl methanesulfonate (CAS No: 66-27-3)  and its structurally similar read across substancesMethanesulphonyl chloride (CAS no: 124-63-0) Sodium Lauryl Sulfate(CAS no:151-21-3),Methanesulfonyl fluoride[CAS: 558-25-8] and Thioglycolic acid TGA [CAS: 68-11-1]. The predicted data usingQSAR toolbox and Danish QSAR databasehas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical Methyl methanesulfonate (CAS No: 66-27-3)  is able to cause severe skin irritation and thus considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category  “Category 2”.

 

Eye irritation

An ocular irritation potential of target chemical Methyl methanesulfonate (CAS No: 66-27-3)  was assessedin various experimental studies which were conducted on rabbits for target chemicalMethyl methanesulfonate (CAS No: 66-27-3)  and its structurally similar read across substancesMethanesulphonyl chloride (CAS no: 124-63-0),Sodium Lauryl Sulfate(CAS no:151-21-3) and Methane sulphonicacid [CAS: 75-75-2]. The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical Methyl methanesulfonate (CAS No: 66-27-3)  is able to cause severe eye damage and thus can be considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category“Category 2”.

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 v3.3 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 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): Methyl methanesulfonate
- Molecular formula: C2H6O3S
- Molecular weight: 110.1324 g/mol
- Smiles notation: COS(=O)(=O)C
- InChl: 1S/C2H6O3S/c1-5-6(2,3)4/h1-2H3
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5ml

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

probability of severe irritation

Irritant / corrosive response data:

Severe irritation was observed

Estimation method: Takes mode value from the 5 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(not "n")) ) and("o" and "p") )

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Sulfonate ester by Organic Functional groups

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Sulfonate ester by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Miscellaneous sulfide (=S) or oxide (=O) AND Suflur {v+4} or {v+6} AND Sulphonate, aliphatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as Esters of organic sulfonic or sulfuric esters by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "f"

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: "g"

Referential boundary:The target chemical should be classified as Low reactive OR Low reactive >> N-substituted aromatic amides OR Moderate reactive OR Moderate reactive >> Activated 1,3,5-triazine derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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 by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "k"

Referential boundary:The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Vinyl carboxamides (MA) by Protein binding potency

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary:The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Imidol form by Tautomers unstable

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.15

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.18

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Methyl methanesulphonate was estimated to be severely irritating to the skin of New Zealand White rabbits.

Executive summary:

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

Methyl methanesulphonate was estimated to be severely irritating to the skin of New Zealand White rabbits.

Based on the estimated results, methyl methanesulphonate can be considered to be severely irritating to skin and can be classified under the category “Category 2” as per CLP regulation.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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 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): Methyl methanesulfonate
- Molecular formula: C2H6O3S
- Molecular weight: 110.1324 g/mol
- Smiles notation: COS(=O)(=O)C
- InChl: 1S/C2H6O3S/c1-5-6(2,3)4/h1-2H3
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

not specified

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 exposure

Observation period (in vivo):

24,48 and 72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

6

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

Irritation was 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 "i" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Sulfonate ester by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Sulfonate ester by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Miscellaneous sulfide (=S) or oxide (=O) AND Suflur {v+4} or {v+6} AND Sulphonate, aliphatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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 by Estrogen Receptor Binding

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.39

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.96

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Methyl methanesulfonate was estimated to be irritating to rabbit eyes.

Executive summary:

The ocular irritation potential of methyl methanesulphonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor. Methyl methanesulfonate was estimated to be irritating to rabbit eyes. Based on the estimated results, methyl methanesulphonate can be considered to be irritating to eyes and can be classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemicalMethyl methanesulfonate (CAS No: 66-27-3)  to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits guinea pigs and humans for target chemicalMethyl methanesulfonate (CAS No: 66-27-3)  and its structurally similar read across substancesMethanesulphonyl chloride (CAS no: 124-63-0) Sodium Lauryl Sulfate(CAS no:151-21-3),Methanesulfonyl fluoride [CAS: 558-25-8] and Thioglycolic acid TGA [CAS: 68-11-1].The predicted data using the OECD QSAR toolbox and Danish QSAR database 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 chemicalMethyl methanesulfonate (CAS No: 66-27-3) .The chemical Methyl methanesulfonate (CAS No: 66-27-3)  is estimated to be irritating to skin of rabbits.

 

According to Danish QSAR database , the skin irritation effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for Methyl methanesulfonate (CAS No: 66-27-3). Based on estimation, no skin irritation reactions were observed in rabbits. Therefore, Methyl methanesulfonate (CAS No: 66-27-3)  was considered to be irritating.

 

The above results were supported by a case report study conducted by van Joost T et.al, (Contact Dermatitis, Vol. 10, No. 3, pages 187-188, 1984) on a 40 years old man who worked for 2 years in a chemical factory for the read across chemical Methanesulphonyl chloride (CAS no: 124-63-0) in accordance with ICDRG batteries by performing patch test.During the patch test, a patient was tested at a dose of 1% in petrolatum which resulted into strong positive (+++) reaction after 48 and 72 hours. After 6 weeks the patient was retested at lower concentrations of0.5%, 0.2%,0.1% and 0.005% in petrolatum and skin was examined after 48 and 72 hours. Out of 10 control persons, no positive reactions were observed at 0.2% and a negative reaction was observed at 0.1% in test patient. From the tested concentrations, a strong positive(++)reaction was observed at 0.2%. Thus the chemical Methanesulphonyl chloride (CAS no: 124-63-0)considered as irritating to the skinin a patch test conducted ona 40 years old man.

 

Another experimental study was reported by HSDB (U.S. National Library of Medicine National Institutes of Health, Health & Human Services; 2017) on rabbits for same read across chemical Methanesulphonyl chloride (CAS no: 124-63-0). The rabbits were treated with single dermal application of Methanesulphonyl chloride at 2000 mg/kg which resulted into death of all the rabbits within 24 hours. Hence the chemical Methanesulphonyl chloride (CAS no: 124-63-0) was considered as severely irritating to the skin of rabbits.

 

The Cosmetic Ingredient Review (CIR) Expert Panel (Journal of the American College of Toxicology Volume 2, Number 7, 1983) conducted skin irritation study of read across chemical Sodium Lauryl Sulfate(CAS no:151-21-3) on skin of sixNew Zealand Whiterabbits according to Draize method.A 0.5 ml volume of the material was applied at concentration of 28.2% under occlusion for 24 h, and scores were graded on the Draize scale of O-8. The patches were then removed, sites were washed and then evaluated 24 and 72 h after exposure. In intact and abraded skin at 24 and 72 h, there occurred erythema and eschar. Edema occurred in intact skin at 24 h and in abraded skin at 24 and 72 h. The mean Draize score was of 4.54 out of 8.0.Therefore thechemicalSodium Lauryl Sulfate(CAS no:151-21-3) was considered as irritating to the intact and abraded skin of sixNew Zealand Whiterabbits according to Draize method.

 

These results were also supported by the experimental study summarized in Hazardous Substances Databank (HSDB), U.S National Library of Medicine, last updated 2005; for read across substance, Thioglycolic acid TGA [CAS: 68-11-1] at a dose of 9.0% Thioglycolic Acid (pH 8) using the open epicutaneous test. About 0.1ml of 9.0% Thioglycolic Acid (pH 8) was applied to an 8sq cm area of skin (clipped free of hair) on the flank of 8 guinea pigs daily for 21 days. Sites were graded at the end of each 24 hour period, weekends excluded. The scale used for grading the skin reactions was: 0 (no skin irritation) to 4 (severe skin irritation). Reactions ranging from slight skin irritation to well defined skin irritation was observed in 7 guinea pigs. Reactions ranging from slight skin irritation to moderate skin irritation were observed in 1 guinea pig. Based on these reactions, Thioglycolic acid TGA was considered as a severe skin irritant to guinea pig skin.

 

The above results were further supported by the experimental study summarized in EPA TSCATS Summary, EASTMAN KODAK COMPANY, last updated 1992; for theclosely related read across substance, Methanesulfonyl fluoride[CAS: 558-25-8].it was observed that the chemical Methanesulfonyl fluoride caused very slight irritation to guinea pig skin and hence can be considered as irritating .

 

Thus based on the available data for the target as well as read across substances and applying the weight of evidence approach,it can be concluded thatchemical Methyl methanesulfonate (CAS No: 66-27-3) is able to cause severe skin irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category  “Category 2”.

 

 

Eye irritation:

In different studies,the test chemicalMethyl methanesulfonate (CAS No: 66-27-3)  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 chemicalMethyl methanesulfonate (CAS No: 66-27-3)  its structurally similar read across substancesMethanesulphonyl chloride (CAS no: 124-63-0),Sodium Lauryl Sulfate(CAS no:151-21-3) and Methane sulphonicacid [CAS: 75-75-2].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 chemicalMethyl methanesulfonate (CAS No: 66-27-3).The chemical Methyl methanesulfonate (CAS No: 66-27-3)  is estimated to be severely irritating to eye of rabbits.

 

An ocular irritation study was reported by HSDB (U.S. National Library of Medicine National Institutes of Health, Health & Human Services; 2017) on rabbits for same read across chemical Methanesulphonyl chloride (CAS no: 124-63-0). The rabbits were treated with single application of Methanesulphonyl chloride which caused irrigation of the eye 20 to 30 sec after instillation and reduced the response, but corneal opacity and congestion of the iris with no pupillary light reaction were still noted. Hence the chemical Methanesulphonyl chloride (CAS no: 124-63-0)was considered as severely irritating to the eyesof rabbits.

 

The above results were supported by the ocular irritation study summarized by Cosmetic Ingredient Review (CIR) Expert Panel (Journal of the American College of Toxicology Volume 2, Number 7, 1983) for read across chemical Sodium Lauryl Sulfate(CAS no:151-21-3) on five rabbits according to Draize method.Approximately 20% (0.1mL) ofSodium Lauryl Sulfatewas instilled to the left eye of each rabbits. The untreated right eyes served as controls. The effects were assessed 1, 24, 48 and 72 hours as well as 4 and 7 days after application.The compound was cause severe irritation at 24 h, decreasing to mild irritation after seven days.Therefore thechemicalSodium Lauryl Sulfate(CAS no:151-21-3) was considered as irritating to the eyes of five albino rabbits according to Draize method.

 

These results were further supported by the experimental study reported in High Production Volume Information System (HPVIS) {November 20, 2009} for read across chemical Methanesulfonic acid (CAS No: 75‐75‐2). About 0.1ml of Methane sulfonic acid was instilled into the eyes of 2 albino rabbits for 0.333-0.5 minutes. One of the two animals had a rinse of the treated eye with flowing water initiated 20 to 30 seconds after instillation and continued for one minute. The washed and unwashed eyes were observed for signs of irritation at 10 min, 1h, 2h, 3h, 4h, 24h, 48h, 72h, 4 days, 5 days, 6 days and 7 days. Each instillation of Methane Sulfonic acid caused excruciating pain. The reactions in the unwashed eyes occurred immediately in all the ocular tissues. The conjunctivae became completely necrotic (white) without evident swelling. The iris was dilated with ragged edges and failed to react to light. The cornea was opacified completely within 24 hours. The reactions of the washed eyes did not differ significantly from that of unwashed eyes. Hence, Based on the above reactions Methane sulfonic acid was considered to be extremely corrosive to eyes.

 

Thus based on the available data for the target as well as read across substances and applying the weight of evidence approach,it can be concluded thatchemical Methyl methanesulfonate (CAS No: 66-27-3) is able to cause severe eye irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category  “Category 2”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical Methyl methanesulfonate (CAS No: 66-27-3)  and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicates that the chemical Methyl methanesulfonate (CAS No: 66-27-3)  is likely to cause severe skin and eye irritation. Hence Methyl methanesulfonate (CAS No: 66-27-3)  can be classified under the category “Category 2” for skin and eye as per CLP.