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EC number: 241-620-3 | CAS number: 17636-10-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well documented publication which meets basic scientific principles.
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Mesna - a short review
- Author:
- Shaw., I., C., Graham, M., I.
- Year:
- 1 987
- Bibliographic source:
- Cancer Treatment Reviews (1987), Vol. 14., pp.67-86
- Reference Type:
- publication
- Title:
- The fate of sodium [U14C]-mercaptoethanesulphonate in the rat.
- Author:
- Shaw, I. C., Graham, M. I., Jones, M.
- Year:
- 1 986
- Bibliographic source:
- Arzneim. Forsch. 36: 487 489.
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
- toxicokinetics
- other: binding to plasma proteins
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Mesna was studies in rats for its toxicokinetic behaviour. Serum half-life, binding to proteins, distribution to organs and excretion have been investigated.
- GLP compliance:
- no
Test material
- Reference substance name:
- Mesna
- EC Number:
- 243-285-9
- EC Name:
- Mesna
- Cas Number:
- 19767-45-4
- IUPAC Name:
- sodium 2-sulfanylethanesulfonate
- Test material form:
- other: solution
- Details on test material:
- - Name of test material (as cited in study report): MESNA (Asta Werke, Bielefeld, F.R.G.)
- Molecular formula (if other than submission substance): C2H5NaO3S2
- Molecular weight (if other than submission substance): 164.18
- Smiles notation (if other than submission substance): C(S)CCS(=O)(=O)O{-}.[Na]{+}
- InChl (if other than submission substance): 1S/C2H6O3S2.Na/c3-7(4,5)2-1-6;/h6H,1-2H2,(H,3,4,5);/q;+1/p-1
- Structural formula attached as image file (if other than submission substance): see Fig.1
- Substance type: organosulphur compound
- Physical state: pulver (Sigma Aldrich)
- Analytical purity: purity using hplc followed by fraction collection and liquid scintillation counting (=96%)
- Specific activity (if radiolabelling): 12.1 µCi/mmol
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 549 ± 126 g
Administration / exposure
- Route of administration:
- intravenous
- Vehicle:
- physiological saline
- Duration and frequency of treatment / exposure:
- single injection
Doses / concentrations
- Remarks:
- Doses / Concentrations:
50 mg/5 µCi in saline
- No. of animals per sex per dose / concentration:
- 9
- Control animals:
- no
- Positive control reference chemical:
- no
- Details on study design:
- no data
Results and discussion
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- Mesna and dimesna do not enter most cells. Mesna is very well absorbed from the GI tract but dimesna is less readily absorbed; i.v. mesna and dimesna are pharmacokinetically undistinguishable.
- Type:
- distribution
- Results:
- mesna is predominantly present in plasma and extracellular fluids but it is taken up by kidney cells.
- Type:
- other: binding to plasma proteins
- Results:
- small proportion (9.7%) of circulating mesna/dimesna is bound to plasma proteins, including albumin and immunoglobulins.
- Type:
- excretion
- Results:
- The high water solubility of mesna and dimesna facilitate their rapid clearance from plasma by the kidney (within 24 h approx. 77% of the administered dose appeared in the urine).
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Both mesna and dimesna are too hydrophilic to cross lipid biological membranes passively and therefore they do not enter most cells.
Surprisingly, in view of its high polarity, mesna is very well absorbed from the gastrointestinal tract following oral dosing. It has a high apparent bioavailability, it is well tolerated by the oral route, and therefore this route of administration is potentially very useful as part of cancer chemotherapy regimens. - Details on distribution in tissues:
- The calculated volume of distribution for mesna in the rat is 0.3 L/kg, which supports the hypothesis that mesna is predominantly present in plasma and extracellular fluids. It is, however, possible that membrane carrier systems (perhaps thiol amino acid carriers) might permit uptake of mesna or dimesna by specific cells. Indeed, this possibly explains why mesna or dimesna appear to enter kidney cells.
- Details on excretion:
- The high water solubility of mesna and dimesna facilitate their rapid clearance from plasma by the kidney. This is reflected in their short plasma half-lives. The proportion of mesna to dimesna excreted into the urine is very much greater than the corresponding proportion in plasma. This is important, since it is mesna (rather than dimesna) which is responsible for detoxification of oxazaphosphorine metabolites. The reason for the free thiol being excreted in urine is that
enzymes in kidney cells are able to reduce dimesna to mesna. This reaction appears to involve concomitant oxidation of GSH. Mesna forms a mixed disulphide with cysteine, and one would expect that reduction of this disulphide, in a manner analogous to the postulated reduction of dimesna by kidney cells prior to urinary elimination, would result in excretion of cysteine in the urine. Indeed, the excretion of cysteine in urine following mesna administration has been demonstrated in both animals and man. There are other possible mechanisms which might account for the enhanced elimination of cysteine during mesna administration. Interaction of mesna with cystine is known to release cysteine with concomitant formation of mesna-cysteine disulphide. If this occurs in the circulatory system, enhanced cysteine elimination might result. Another possible mechanism, strictly speaking an in vitro artefact, results in the release of cysteine from
cystine following its reaction with mesna in the urinary bladder. This again would result in enhanced levels of cysteine in the urine.
Toxicokinetic parametersopen allclose all
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: 4 h (following administration of [35S]-mesna
- Test no.:
- #2
- Toxicokinetic parameters:
- half-life 2nd: 17 min (following administration of [14C]-mesna
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- On entering the blood stream, mesna is almost immediately oxidized to its dimeric form, dimesna (dithio-bis-mercaptoethanesulphonate) by forming a disulphide bridge between two monomeric units. This reaction is possibly spontaneous, being catalysed by transition metals present in the circulatory system, although it is possible that enzymic catalysis is involved. Mixed disulphides with endogenous thiols are also formed, for example cysteine-mesna disulphide. Dimesna is chemically less reactive than mesna and so is less likely to react with metabolites of anticancer drugs.
Any other information on results incl. tables
Binding to plasma proteins
A small proportion (10%) of circulating mesna/dimesna is bound to plasma proteins, including albumin and immunoglobulins. This has been studied in animals using [14C]-mesna. The binding mechanism is thought to involve both disulphide formation between mesna and cysteinyl thiol groups on the protein molecule and/or electrostatic interactions between positive regions of the protein molecule and the negatively charged sulphonate group of mesna or dimesna.
Plasma half-life
Pharmacokinetic studies using radiolabelled mesna have produced apparently conflicting results relating to plasma half-life values. If radioactivity is determined in whole blood following i.v. administration of [35S]-mesna and the half-life calculated, a value of some 4 h is obtained, while measurement of plasma radioactivity in a similar experiment using [14C]-mesna gives a half-life of some 17 min. This large discrepancy might be attributable to sequestration of mesna/dimesna by erythrocytes. Erythrocytes contain high levels of free thiols (e.g. GSH), and formation of disulphides with mesna is therefore very likely. This increased half-life would be related to the slow release of sequestrated mesna from the erythrocytes
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
Mesna is well absorbed from GI tract. In blood stream, it is rapidly oxidized to dimesna. Its plasma half-life is 17 min. Mesna binds to plasma proteins (albumin and immunoglobulins). It is taken up by kidney cells and rapidly eliminated in the urine. - Executive summary:
In the review, the role of mesna as an uroprotective drug in anticancer therapy is presented. Mesna acts as a scavenger of acrolein and chloroacetaldehyde, reactive metabolites of oxazaphosphorines (cyclophosphamide, ifosfamide), preventing bladder toxicity during chemotherapy. The free thiol group of mesna can react with an electrophilic centre of the reactive compounds (epoxides, chlorinated hydrocarbons, free radicals etc.) forming a thioether, facilitating its excretion. Mesna is very well absorbed from GI tract following oral dosing. Mesna does not enter most cells due to its hydrophilicity and therewith does not reduce cytotoxicity of anticancer drugs in tumor cells. It is predominantly present in plasma and extracellular fluids but is taken up by kidney cells. On entering the blood stream, mesna is almost immediately oxidized to its dimeric form dimesna by forming a disulphide bridge. Dimesna is chemically less reactive than mesna and so is less likely to react with oxazaphosphorine metabolites. A small proportion (9.7%) of circulating mesna/dimesna is bound to plasma proteins, including albumin and immunoglobulins. The half-life of 17 min and 4 hours were calculated using [14C]-mesna and [35S]-mesna in radioactivity measurements in experimental animals, respectively. Mesna can be sequestred by erythrocytes, increasing its half-life. Mesna is rapidly eliminated in the urine.
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