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Toxicological information

Repeated dose toxicity: other routes

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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

Reference
Name:
Unnamed
Type:
Constituent
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 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.