Methanesulphonic acid

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Reference 2

Reference Type:

publication

Title:

HPVIS, IUCLID Data Set for Methanesulphonic acid, CAS no. 75-75-2

Author:

US-EPA

Year:

2003

Bibliographic source:

HPV Chemicals Challenge Program OPPT NCIC 201-14249B

Reference 3

Reference Type:

review article or handbook

Title:

Methanesulfonic acid.

Author:

Shertzer HG

Year:

2001

Bibliographic source:

Patty's Toxicology, 5th edition, Vol 7, Ch. 94: 745-746

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Remarks:

Life Science Research Limited, England

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Methanesulphonic acid

EC Number:

200-898-6

EC Name:

Methanesulphonic acid

Cas Number:

75-75-2

Molecular formula:

CH4O3S

IUPAC Name:

methanesulfonic acid

Details on test material:

- Name of test material (as cited in study report): Methanesulfonic acid
- Physical state: clear colourless liquid
- Composition of test material, percentage of components: methanesulphonic acid (70%)
- Storage condition of test material: room temperature

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories (UK)
- Age at study initiation: ca. 5 weeks
- Housing: 2 or 5 per sex per cage
- Diet (e.g. ad libitum): Laboratory animal diet LAD 1
- Water (e.g. ad libitum): drinking water via a polythene bottle
- Acclimation period: 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Humidity (%): 55±15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Volume-dosage was 10 ml/kg bw

Duration of treatment / exposure:

not applicable

Frequency of treatment:

single

Post exposure period:

24, 48, 72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 20, 100, 500 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

Chlorambucil
- Route of administration: oral gavage
- Doses / concentrations: 30 mg/kg bw in aqueous 10% ethanol

Examinations

Tissues and cell types examined:

bone marrow erythrocytes

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: The preliminary test was conducted as range finder, using dosages of 125, 250, 500, 1000 and 2500 mg/kg bw.


TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): samples were collected at 24, 48, 72 hours after treatment.


METHOD OF ANALYSIS: Analysis of at least 2000 cells per animal by light microscopy, determination of frequency of micronucleated cells.

Evaluation criteria:

Number of micronucleated erythrocytes compared to the control group.

Statistics:

Statistical test: Mann-Whitney U-test

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Clinical signs of toxicity in test animals: one female dosed with methanesulphonic acid at 2500 mg/kg bw died approximately 30 s post dose. One male was killed in extremis approximately 30 s post-dose and the remaining male and female killed in extremis 2.5 h post-dose. Signs included hunched posture, piloerection, slow laboured breathing and inability to move. Of the animals dosed with 1000 mg/kg bw, one male was found dead in its cage approxiumately 21 h post-dose and the remaining male and both females were killed in extremis approximately 21 h post-dose. Signs included hunched posture, piloerection, slow laboured breathing and inability to move. All other animals dosed with methanesulphonic acid survived to scheduled termination. Piloerection was noted in all animals in the 24 h period following dosing at 500 mg/kg bw. No adverse reactions to treatment were recorded for any other group of animals dosed with methanesulphonic acid. No dose related decrease in body weight loss were noted.


RESULTS OF DEFINITIVE STUDY
- Clinical signs and mortality: Two males dosed with 500 mg/kg bw were found dead in their cage approximately 21 hours post-dose. One animal exhibiting pilo-erection, severe rales and loss of facial hair was killed approximately 48h after treatment. Results from those three animals were excluded from the analysis. All surviving male mice of the 500 mg/kg bw group showed piloerection. One of them exhibited rales. One female presented such rales, as well. All other animals remained without symptoms.
- Induction of micronuclei (for Micronucleus assay): No significant variation in treated animals was reported in any treatment group 24, 48 and 72 hours after administration. However, the chlorambucil group exhibited a significant increase of micronucleated polychromatic erythrocytes.
- Ratio of PCE/NCE (for Micronucleus assay): Ratio of all treatment groups were closely similar to those of their respective vehicle control groups.

Any other information on results incl. tables

The micronucleus test: observations at 24, 48 and 72 h after treatment 

Dose groups	Micronuclei per 1000 cells (mean ± SD), 24 h after treatment		Polychromatic cells/ mature cells
	Polychromatic	Mature
Vehicle control	0.7±0.7	0.6±0.8	0.9
20 mg/kg bw	0.5±0.7	0.5±0.7	0.9
100 mg/kg bw	0.5±0.8	0.4±0.6	0.9
500 mg/kg bw	0.4±0.5	0.4±0.7	0.9
Positive control	56.9±10.8	1.2±0.9	0.7

 

Dose groups	Micronuclei per 1000 cells (mean ± SD), 48 h after treatment		Polychromatic cells/ mature cells
	Polychromatic	Mature
Vehicle control	0.6±0.8	0.5±0.6	0.8
20 mg/kg bw	0.7±0.9	0.9±0.4	0.8
100 mg/kg bw	0.7±0.7	0.7±0.7	0.9
500 mg/kg bw	1.2±1.2	0.2±0.4	0.8
Positive control	-	-	-

 

Dose groups	Micronuclei per 1000 cells (mean ± SD), 72 h after treatment		Polychromatic cells/ mature cells
	Polychromatic	Mature
Vehicle control	0.3±0.7	0.3±0.6	0.8
20 mg/kg bw	0.3±0.5	0.5±0.7	0.9
100 mg/kg bw	0.8±1.0	0.5±0.5	0.8
500 mg/kg bw	0.0±0.0	0.6±0.7	0.8
Positive control	-	-	-