Methyl methanesulphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from authoritative source

Data source

Reference

Reference Type:

publication

Title:

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans

Author:

World Health Organization

Year:

1999

Bibliographic source:

IARC Monograph. World Health Organization, International Agency for Research on Cancer, V71 1072 (1999)

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Details of guidelines not mentioned in the publication

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Methyl methanesulphonate

EC Number:

200-625-0

EC Name:

Methyl methanesulphonate

Cas Number:

66-27-3

Molecular formula:

C2H6O3S

IUPAC Name:

methyl methanesulfonate

Test material form:

other: Liquid

Details on test material:

CAS NO: 66-27-3
Chemical Name: Methyl methanesulfonate
Nature of chemical: Organic

Specific details on test material used for the study:

- Name of test material: Methyl methanesulfonate (MMS)
- Molecular formula: C2H6O3S
- Molecular weight: 110.1324 g/mole
- Substance type: Organic
- Physical state: Solid

Radiolabelling:

yes

Remarks:

[methyl-14C] methyl methanesulfonate 30 %

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Administration / exposure

Route of administration:

intravenous

Vehicle:

not specified

Details on exposure:

Rats were injected with [methyl-14C]methyl methanesulfonate

Duration and frequency of treatment / exposure:

Monitring period mentioned in the publication is 30 hrs

Doses / concentrations

Dose / conc.:

100 mg/kg bw/day

No. of animals per sex per dose / concentration:

not specified

Control animals:

not specified

Positive control reference chemical:

not specified

Details on study design:

not specified

Details on dosing and sampling:

not specified

Statistics:

not specified

Results and discussion

Preliminary studies:

not specified

Main ADME results

Main ADME results 1

Type:

absorption

Results:

[methyl-14C] methyl methanesulfonate is likely to be absorbed after intravenous injection since it is then rapidly distributed to other body parts.

Main ADME results 2

Type:

distribution

Results:

The chemical is rapidly distributed throughout the body of rats, including the central nervous system, and rapidly crosses the placenta. After intravenous injection of 100 mg/kg bw methyl methanesulfonate to rats none was detected in serum after 2 h.

Main ADME results 3

Type:

metabolism

Results:

Glutathione conjugation has been shown to occur in rat liver. Metabolites resulted from initial methylation of cysteine residues by methyl methanesulfonate.

Main ADME results 4

Type:

excretion

Results:

In rats injected with [methyl-14C]methyl methanesulfonate, about 30% of the label was exhaled as CO2 within 30 h. Urinary metabolites recovered within the first 16 h represented 80% of the excretion products.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

not specified

Details on distribution in tissues:

not specified

Details on excretion:

not specified

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Methylmercapturic acid sulfoxide, 2-hydroxy-3-methylsulfinylpropionic acid, methylsulfinylacetic acid, methylmercapturic acid and N-(methylthioacetyl) glycine.

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

not specified

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
When rats were injected with [methyl-14C]methyl methanesulfonate, the chemical was rapidly distributed to various body parts of the rats including the central nervous system, and also crosses the placenta. However, the chemical is metabolized to various metabolites that constitute 80% of the of the excretion products. 30% of the label was exhaled as CO2 within 30 h. Thus, considering that the chemical is metabolized and excreted out of the body of the rats in less than 2 days, the chemical is expected to have low bio-accumulation potential.

Executive summary:

There is no information available pertaining to the toxico-kinetics ofMethyl methanesulphonate in humans. Information available from in vivo study conducted in rats (strain not specified), indicates that the radiolabeled[methyl-14C]methyl methanesulfonate is rapidly distributed to the various body parts of the rats after intravenous injection. It is metabolized into various breakdown products that are dominantly excreted (80%) in urine within the first 16 hours. About 30% of the label was exhaled as CO₂within 30 h.

Thus, from the above, it can be concluded that the chemicalMethyl methanesulphonate is expected to have “low bio-accumulation potential” within the body of rats.