Methyl methanesulphonate

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of Methyl methanesulfonate (66-27-3) was considered based on the experimental study conducted by Thompson et al. (Food and Cosmetic Toxicology, Vol.19, pp. 347-351, 1981) 225 mg/kg bw. The study concluded that the LD50 is between 50-300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Methyl methanesulfonate can be classified as “Category 3” for acute oral toxicity.

Acute Inhalation toxicity: 

Acute Inhalation toxicity dose (LC50) for Methyl methanesulfonate (66-27-3) was predicted based on OECD QSAR toolbox 22.58 mg/L (22580 mg/m3) and different study available for the structurally similar read across substance Methane sulfonic Acid (CAS no: 75-75-2) >330 ppm (330000 mg/m3). Both these studies concluded that the LC50 value is >5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, Methyl methanesulfonate cannot be classified for acute Inhalation toxicity.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for Methyl methanesulfonate (66-27-3) was predicted based on OECD QSAR toolbox 6926 mg/kg bw and different study available for the closely related read across substance sodium ethenesulfonate (CAS no: 3039-83-6) >2000 mg/kg bw. Both of these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Methyl methanesulfonate cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from peer- reviewed journal

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Acute toxicity study of Methyl methanesulfonate in rat.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Methyl methanesulfonate (MMS)
- Molecular formula (if other than submission substance): C2H6O3S
- Molecular weight (if other than submission substance): 110.1324 g/mole
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 190-270 g
- Fasting period before study: Fasted overnight

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0, 0.15 and 0.21 g/kg
- Amount of vehicle (if gavage): 1 % solution in water
DOSAGE PREPARATION (if unusual): Methyl methanesulphonate was administered as a 1% solution in water.
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The estimated LD50 value being between the middle two doses.

Doses:

0, 0.15 and 0.21 g/kg (0, 150 and 210 mg/kg)

No. of animals per sex per dose:

Total: 30
0 g/kg: 10 female
0.15 g/kg: 10 female
0.21 g/kg: 10 female

Control animals:

yes

Details on study design:

No data

Statistics:

Slopes of the dose-response curves and the range of the doses were analyzed by Probit analyses.

Preliminary study:

No data available

Sex:

female

Dose descriptor:

LD50

Effect level:

225 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

50% mortality was observed in treated rats at 225 mg/kg bw

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data

Results of acute LD50 studies in rats given methyl merhanesulphonare, glycidol or dimerhylsulphoxide

Compound	Oral administration
MMS†	Dose level (g/kg)	Lethal value*	LD50 (g/kg)
	0.15	4/10	0.225
	0.21	4/10

 

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

LD50 was considered to be 225 mg/kg (0.225 g/kg) for Sprague-Dawley female rat when treated with Methyl methanesulfonate (MMS) orally.

Executive summary:

The acute oral toxicity using Methyl methanesulfonate (66-27-3) in 30 female Sprague-Dawley rats at the concentration of 0, 0.15 and 0.21 g/kg (0, 150 and 210 mg/kg). The given test chemical was dissolved as 1% solution in water and administered via oral gavage route.Animals were observed fir mortality.Slopes of the dose-response curves and the range of the doses were analyzed by probit analyses.50% mortality was observed in treated rats at 225 mg/kg bw. Therefore, LD50 was considered to be 225 mg/kg (0.225 g/kg), when Sprague-Dawley female rats were treated with Methyl methanesulfonate (MMS) via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

225 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from peer-reviewed journal.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

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

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

head only

Vehicle:

not specified

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Remarks on duration:

not specified

Concentrations:

22.58 mg/L (22580 mg/m3)

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LC50

Effect level:

22.58 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

other: not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average 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 ("n" and ( not "o") )  )  and ("p" and "q" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom AND SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates by DNA binding by OASIS v.1.4

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 at an sp3 Carbon atom AND SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Sulfonates by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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 by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates by Protein binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Michael addition >> Polarised Alkenes by Protein binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as SN2 >> SN2 reaction at a sulphur atom >> Thiols by Protein binding by OECD

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 100 Da

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 116 Da

Interpretation of results:

other: Not classified

Conclusions:

LC50 was estimated to be 22.58 mg/L (22580 mg/m3), when 5 male and female Wistar rats were exposed with Methyl methanesulfonate (66-27-3) via inhalation route by aerosol head only exposure for 4 h.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for Methyl methanesulfonate (66-27-3). The LC50 was estimated to be 22.58 mg/L (22580 mg/m3), when 5 male and female Wistar rats were exposed with Methyl methanesulfonate via inhalation route by aerosol head only exposure for 4 h.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

22 580 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

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

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

6926 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

6 926 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and ( not "aa") )  )  and ("ab" and ( not "ac") )  )  and ("ad" and ( not "ae") )  )  and ("af" and ( not "ag") )  )  and ("ah" and ( not "ai") )  )  and ("aj" and ( not "ak") )  )  and ("al" and ( not "am") )  )  and ("an" and "ao" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom AND SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates by DNA binding by OASIS v.1.4

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 at an sp3 Carbon atom AND SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Sulfonates by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "h"

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

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"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "n"

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: "o"

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

Domain logical expression index: "p"

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: "q"

Referential boundary: The target chemical should be classified as Esters including acrylic and methacrylic esters by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

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: "s"

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

Domain logical expression index: "t"

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: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Phthalates by rtER Expert System ver.1 - USEPA

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 at sulphur OR SN2 >> SN2 at sulphur >> Thiols by Respiratory sensitisation

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Sulfonates by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as SN2 >> SN2 Reaction at a sp3 carbon atom by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Sulfonates by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as Michael Addition >> Michael addition on conjugated systems with electron withdrawing group by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "ah"

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: "ai"

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

Domain logical expression index: "aj"

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: "ak"

Referential boundary: The target chemical should be classified as Aromatic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "al"

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: "am"

Referential boundary: The target chemical should be classified as Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "an"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.39

Domain logical expression index: "ao"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.139

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 6926 mg/kg bw, when 2 female New Zealand White rabbits were treated with Methyl methanesulfonate (CAS no: 66-27-3) for 24 hours by dermal application occlusively.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Methyl methanesulfonate (CAS no: 66-27-3). The LD50 was estimated to be 6926 mg/kg bw, when 2 female New Zealand White rabbits were treated with Methyl methanesulfonate for 24 hours by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 926 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4.

Additional information

Acute oral toxicity:

The experimental study conducted by Thompson et al. (Food and Cosmetic Toxicology, Vol.19, pp. 347-351, 1981) was designed for acute oral toxicity using Methyl methanesulfonate (66-27-3) in 30 female Sprague-Dawley rats at the concentration of 0, 0.15 and 0.21 g/kg (0, 150 and 210 mg/kg). The given test chemical was dissolved as 1% solution in water and administered via oral gavage route. Animals were observed fir mortality. Slopes of the dose-response curves and the range of the doses were analyzed by probit analyses. 50% mortality was observed in treated rats at 225 mg/kg bw. Therefore, LD50 was considered to be 225 mg/kg (0.225 g/kg), when Sprague-Dawley female rats were treated with Methyl methanesulfonate (MMS) via oral gavage route.

This study is supported by another experimental study conducted by Tsuyoshi et al.(Mutation Research, 223, 383-386, 1989) was designed for acute oral toxicity test which was conducted according to OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure) using Methyl methanesulfonate (66-27-3) in 28 male MS/Ae and CD-1 mice at the concentration of 10, 100, 1000, 140, 225, 370 and 600 mg/kg bw. The given test chemical Methyl methanesulfonate(MMS) was dissolved in physiological saline and administered via oral gavage route. Control animals received saline. The animals were observed for mortality for 24 hours. LD50 was estimated according to the method described by Lorke (1983) with minor modifications.50% mortality was observed in treated male MS/Ae and CD-1 mice at 470 and 290 mg/kg bw respectively. Therefore, LD50 was considered to be 470 mg/kg for MS/Ac and 290 mg/kg for CD-1 male mice, when treated with Methyl methanesulfonate (MMS) via oral gavage route.

Thus, based on the above studies on Methyl methanesulfonate (66-27-3), it can be concluded that LD50 value is between 50-300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Methyl methanesulfonate can be classified as “Category 3” for acute oral toxicity.

Acute Inhalation Toxicity:

In different studies, Methyl methanesulfonate (66-27-3) has been investigated for acute Inhalation toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for Methyl methanesulfonate along with the study available on structurally similar read across substance Methane sulfonic Acid (CAS no: 75-75-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for Methyl methanesulfonate (66-27-3). The LC50 was estimated to be 22.58 mg/L (22580 mg/m3), when 5 male and female Wistar rats were exposed with Methyl methanesulfonate via inhalation route by aerosol head only exposure for 4 h.

This study is further supported by Jay A. Brown (Haz-Map®: Information on Hazardous Chemicals and Occupational Diseases, U.S. National Library of Medicine, October 2017) and John Wiley & Sons (Patty's Industrial Hygiene and Toxicology, 2012), for the structurally similar read across substance Methane sulfonic Acid (CAS no: 75-75-2).The acute inhalation toxicity study was conducted in rats at the concentration of 330 ppm (330000 mg/m3). No mortality was observed at 330000 mg/m3. Therefore, LC50 was considered to be >330 ppm (330000 mg/m3), when rats were treated with Methane sulfonic Acid by inhalation.

Thus, based on the above studies on Methyl methanesulfonate (66-27-3) and it’s read across substance, it can be concluded that LC50 value is >5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, Methyl methanesulfonate cannot be classified for acute Inhalation toxicity.

Acute Dermal toxicity:

In different studies, Methyl methanesulfonate (66-27-3) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbit and rat for Methyl methanesulfonate along with the study available on the structurally similar read across substance sodium ethenesulfonate (CAS no: 3039-83-6). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Methyl methanesulfonate (CAS no: 66-27-3). The LD50 was estimated to be 6926 mg/kg bw, when 2 female New Zealand White rabbits were treated with Methyl methanesulfonate for 24 hours by dermal application occlusively.

This study is supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the closely related read across substance sodium ethenesulfonate (CAS no: 3039-83-6).Acute Dermal toxicity study was conducted according to OECD guideline 402 in rats at the concentration of 2000 mg/kg bw. No mortality was observed in treated rats at 2000 mg/kg bw. Therefore, LD50 was considered to be >2000 mg/kg bw, when rats were treated with sodium ethenesulfonate by dermal application.

Thus, based on the above studies on Methyl methanesulfonate (66-27-3) and it’s read across substance, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Methyl methanesulfonate cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on Methyl methanesulfonate (66-27-3) and it’s read across substances, it can be concluded that LD50 value is between 50-300 mg/kg bw for acute oral; >2000 mg/kg bw for dermal; and LC50 value is >5 mg/L air for acute inhalation toxicity. Thus, comparing these values with the criteria of CLP regulation, Methyl methanesulfonate can be classified as “Category 3” for acute oral; cannot be classified for acute dermal and inhalation toxicity.