Sodium 3-mercaptopropanesulphonate

Repeated dose toxicity: other routes

Administrative data

Endpoint:

short-term repeated dose toxicity: other route

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: Acceptable well documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Studies on the Urotoxicity of Oxazaphosphorine Cytostatics and its Prevention-III. Profile of Action of Sodium 2-mercaptoethane Sulfonate (Mesna)

Author:

Brock, N., Pohl, J., Stekar, J., Scheef, W.

Year:

1982

Bibliographic source:

Eur J. Cancer Clin Oncol., Vol. 18. No. 12, pp: 1377-1387, 1982

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Repeated i.v. administartion with Mesna was carried out for six weeks on Sprague Dawley rats (10 per dose and sex) with three dose levels, including one toxic dose.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

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 (in the form of sodium salt)
- 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: 98%

The test material was tested for identity and purity by the chemical laboratories of Asta-Werke under the guidance of Drs. Niemeyer, Scheffler and Weigert.

Test animals

Species:

rat

Strain:

other: BD II and BD IX

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: the animals were obtained from breeding facilities of Degussa Pharma Group, Germany
- Housing: accordingly
- Diet (e.g. ad libitum): ad libitum (Altromin 1324 diet)
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

intravenous

Vehicle:

not specified

Remarks:

as a 40% solution

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

6 weeks

Frequency of treatment:

daily treatments

Doses / concentrations

Remarks:

Doses / Concentrations:
three dose levels including one non-toxic dose.

No. of animals per sex per dose:

10

Control animals:

not specified

Results and discussion

Effect levels

Dose descriptor:

dose level:

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: The dose was tolerated without side effects.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In a 6-week toxicity experiment Sprague Dawley rats tolerated daily intravenous doses of up to 1000 mg/kg bw .

Executive summary:

Mesna is a pharmacologically unremarkable, physiologically largely inert and almost totally non-toxic thio compound (Brock et al., 1982). In the frame of studies on prevention of urotoxicity induced by oxazaphosphorine, toxicity potential of Mesna was studied in studies of different durations in rats and dogs. Repeated i.v. administartion with Mesna was carried out for six weeks on Sprague Dawley rats (10 per dose and sex) with three dose levels, including one toxic dose. Low toxicity of Mesna was confirmed in this experiment. The animals tolerated daily intravenous doses of up to 1000 mg/kg bw. The only sign of toxicity under the highest dosage was a retardation of the weights development.