Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 248-324-3 | CAS number: 27206-35-5
- 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
Carcinogenicity
Administrative data
Description of key information
Carcinogenicity: Chronic study oral (drinking water), rats (Sprague-Dawley), male, OECD 451: NOAEL = 350 mg/kg bw/day
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The OECD QSAR Toolbox, is a harmonized system for OSAR application and grouping chemicals into categories, which OECD principles are met.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Deviations:
- not specified
- Principles of method if other than guideline:
- 92 male Sprague-Dawley rats, 8 weeks old, were divided into two groups. Group A received 70 mg/kg N-nitroso-N-butyl-N-(4-hydroxybutyl)amine (BBNOH) twice a week by gavage, whereas to Group B, BBNOH was administered at the same dose level together with 350 mg/kg Mesna given 5 times a week in drinking water. Two control groups of 40 animals each were given Mesna alone or were totally untreated.
- GLP compliance:
- not specified
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Süddeutsche Versuchstierfarm, Tuttlingen, F.R.G
- Age at study initiation: 8 weeks
- Weight at study initiation: no data (the weight was checked regularly during the entire period of the treatment).
- Fasting period before study: no data
- Housing: 2 per cage
- Diet (e.g. ad libitum): Altrominm pellets diet; ad libitum
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
No data - Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: 20 mL Mesna solutions were given to rats 5 days a week.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 39 weeks
- Frequency of treatment:
- 5 times a week
- Post exposure period:
- No data
- Remarks:
- Doses / Concentrations:
350 mg/kg bw
Basis:
nominal in water - No. of animals per sex per dose:
- 40
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: The high dose of Mesna was chosen in order to provide an excess amount that could interfere with the metabolites of BBNOH in the urinary bladder.
- Positive control:
- N-nitroso-N-butyl-N-(4-hydroxybutyl)amine (BBNOH) alone.
- Observations and examinations performed and frequency:
- The body weight was checked regularly during the entire period of the treatment.
- Sacrifice and pathology:
- At the end of the treatment animals were observed for life, with the exception of a few that were killed when moribund. After dissection, urinary bladders and all other organs showing macroscopical alterations were collected for histological examination.
- Statistics:
- Kaplan-Meier method.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- Negative
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No significant differences were observed in the animals of the 4 experimental groups from a general point of view. Control animals did not show any pathological alteration at the end of the experiment. There were no signs of toxicity in the animals that received Mesna alone. A statistically significant increase of the lifespan of the Mesna treated animals was observed (P< 0.05).
BODY WEIGHT AND WEIGHT GAIN
Administration of Mesna did not have a significant effect on the weight; an increase in body weight was observed at the beginning of the treatment, up to the eighteenth week, followed by a slight decrease and a steady phase at the end of the experiment. Values ranged between 300 g and 500 g for all experimental groups.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
Mesna solutions were completely consumed within 24 h from the time of administration. The total Mesna consumption was 63.35 g/kg.
GROSS PATHOLOGY
No findings.
HISTOPATHOLOGY: NON-NEOPLASTIC
No findings.
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
No findings. - Relevance of carcinogenic effects / potential:
- The carcinogenicity study conducted with the structural analogue Mesna provides an information on toxicity potential of the substance of interest sodium 3-mercaptosulfonate after a prolonged exposure and can serve as additional information for the assessment of its genotoxicity potential.
- Dose descriptor:
- NOAEL
- Effect level:
- 350 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: see 'Remark'
- Remarks on result:
- other: Effect type: carcinogenicity
- Conclusions:
- Mesna was not carcinogenic in a two-year carcinogenicity study in rats. 350 mg/kg bw, which rats received daily during the exposure period of 39 weeks, can be considered as NOAEL since no clinical signs of toxicity and no findings of necropsy were noted in treated animals.
- Executive summary:
Mesna is known as a cytoprotective agent that helps to prevent haemorrhagic cystitis caused by a widely used class of antineoplastic drugs, comprising cyclophosphamide, ifosfamide, and trofosfamide (Tacchi et al., 1984). A direct chemical interaction between Mesna and the active metabolites of antineoplastic drugs is supposed to be involved in the protective effects on the urinary bladder. In this respect, the influence of Mesna on urinary bladder cancer induced by N-nitroso-N-butyl-N-(4 hydroxybutyl)amine (BBNOH) was studied in male Sprague-Dawley rats.
The treatment consisted of the administration of BBNOH alone per gavage, BBNOH with Mesna, Mesna alone and untreated control. The health effects in treated animals receiving Mesna alone is relevant for this endpoint. The group of 40 male animals (8-week old) received 350 mg/kg bw (total Mesna consumption was 63 g/kg bw (mean for all animals)) in drinking water over a period of 39 weeks. The rats received daily the dose in 20 mL water solution 5 days a week. Health condition of the animals and their body weights were checked regularly during the entire period of the treatment. At the end of the treatment animals were killed and dissected and urinary bladders and all other organs showing macroscopical alterations were collected for histological examination.
No significant differences were observed in the animals of the 4 experimental groups from a general point of view. Mesna solutions were completely consumed within 24 h from the time of administration. Administration of Mesna did not have a significant effect on the weight; an increase in body weight was observed at the beginning of the treatment, up to the eighteenth week, followed by a slight decrease and a steady phase at the end of the experiment. Values ranged between 300 g and 500 g for all experimental groups. Control animals (untreated and receiving Mesna alone) did not show any pathological alteration at the end of the experiment and there were no signs of toxicity. A statistically significant increase of the lifespan of the Mesna treated animals was observed (P< 0.05).There were no findings at necropsy.
As no toxicological findings were observed in animals treated with Mesna alone, 350 mg/kg bw can be considered as chronic NOAEL.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "Summary carcinogenicity"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain logical expression:Result: Out of Domain
("a"
and ("b"
and "c" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Sulfonic acid AND Thioalcohol by
Organic functional groups
Domain
logical expression index: "b"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -4.09
Domain
logical expression index: "c"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= -4.09
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 350 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- The available study suffices to cover the tonnage-driven information requirements under REACH as it is not required. The negative results for genotoxicity testing consistently indicate the plausibility of the negative result in carcinogenicity testing.
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Carcinogenicity testing gave negative results in the tested dose of 350 mg/kg bw/d, no neoplastic lesions or other relevant adverse effects were found.
Additional information
The current endpoint is not required under REACH. It is however sufficient to support the negative results for genotoxicity testing, which also consistently indicate the plausibility of the negative result in carcinogenicity testing.
Justification for selection of
carcinogenicity via oral route endpoint:
Only information available.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.