Sodium 2-methylprop-2-ene-1-sulphonate

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: OECD protocl study under GLP; no deviations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 2-methylprop-2-ene-1-sulphonate

EC Number:

216-341-5

EC Name:

Sodium 2-methylprop-2-ene-1-sulphonate

Cas Number:

1561-92-8

Molecular formula:

C4H8O3S.Na

IUPAC Name:

sodium 2-methylprop-2-ene-1-sulfonate

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): natriummethallylsulfonat
- Substance type: organic
- Physical state: solid crystalline
- Analytical purity: 99.8 %
- Impurities (identity and concentrations):
- Composition of test material, percentage of components: < 0.2% water. 0.05% naCl
- Isomers composition:
- Purity test date: Oct 1989
- Lot/batch No.: unknown
- Expiration date of the lot/batch: undeterminate
- Stability under test conditions: stable
- Storage condition of test material: Normal lab conditions

Test animals

Species:

mouse

Strain:

other: BOR:NMRI (SPF Harlan)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Fa Winkelmann, 4799 Borchem , Germany
- Age at study initiation: young adult mice
- Weight at study initiation: male 23.3 +- 0.9 ; female 23.5 +- 0.7
- Assigned to test groups randomly: [no/yes, under following basis: ] yes
- Fasting period before study: 18 hrs
- Housing: sex-separated, 5 anmials / Makrolon cage type III
- Diet (e.g. ad libitum): Saniff R10, Fa. Sniff 4770, Soest
- Water (e.g. ad libitum): ad lib
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 C +-1
- Humidity (%): 60 %+- 10
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: within lab: from 19-04-1990 to 28-09-1990

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

aqua bidest

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

Duration of treatment / exposure:

24, 48 and 72 hrs

Frequency of treatment:

single dose

Post exposure period:

None

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1250 mg/kg bw
Basis:
actual ingested
dose determined on the basis of body weight immediately prior to dosing

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2500 mg/kg bw
Basis:
actual ingested
dose determined on the basis of body weight immediately prior to dosing

Doses / concentrations 3

Remarks:

Doses / Concentrations:
5000 mg/kg bw
Basis:
actual ingested
dose determined on the basis of body weight immediately prior to dosing

No. of animals per sex per dose:

5 / 5

Control animals:

yes

yes, concurrent vehicle

Positive control(s):

cyclophosphamide;
- Justification for choice of positive control(s): Known positive, historical data available
- Route of administration: oral gavage
- Doses / concentrations: 100 mg/kg bw

Examinations

Tissues and cell types examined:

1000 polychromatic erythrocytes / animal

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: dose-range finding with 5000, 6500, 7500 and 10000 mg/kg bw established confirmed highest LD (zero) of 5000 mg/kg bw


TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
after preparation of both femurs, the bone marrow is washed out using fetal bovine serum and a syringe. the cell suspension was centrifuged for 5 minutes at 160 g, then decanted and re-suspended. This suspension was cleaned by means of a cellulose chromatography tube.
The eluate from the tube was centrifuged (10 min/800 g) , the pellet was re-suspended in fetal bovine serum with 25mM EDTA.
DETAILS OF SLIDE PREPARATION:
From this suspension, 3-4 slides were prepared, dried for 24 hrs and colored with May-Gruenwald / Giemsa solution

METHOD OF ANALYSIS:
100-fold enlargement, Zeiss Microscope
1000 PCE cells/. animals
number of PCE cells with micronuclei
PCE /NCE determined
number of NCE cells with micronuclei .

Evaluation criteria:

Positive if a statistically significant increase in the frequency of micronucleus-containing PCE is found in at least one test group relatie to the neagative controls

Statistics:

Not specified

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

discolored feces (all animals and mild diarrhea in males

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: 500, 6500, 7500, 10000 mg/kg bw
- Solubility: 750 g/l
- Clinical signs of toxicity in test animals: sedation and 1/3 fatality in 6500 group, sedation and 1 / 5 fatalties in teh 7500 group, sedation and 3/ /5 fatalities in the 10000 group.
- Harvest times: 24, 48, 72 hrs

RESULTS OF DEFINITIVE STUDY


- Induction of micronuclei (for Micronucleus assay): see table
- Ratio of PCE/NCE (for Micronucleus assay): see tabel
- Appropriateness of dose levels and route: route is appropriate in view of exposure potential; dose: you can't go much higher, can you?.
- Statistical evaluation: see table.

Any other information on results incl. tables

Testgruppe	Dosis	Entnahme nach	% PCE mit	PCE/NCE
	(mg/kg KG)	Appl. (in h)	MK (x ± SD)	(x ± SD)
Positivkontrolle
(Cyclophosphamid)	100	24	* 3,95 ± 1,37	* 0,48 ± 0,2
	_	24	0,07 ± 0,05	1,13 ± 0,2
Negativkontrolle
(Wasser)	-	48	0,25 ± 0,12	1,31 ± 0,09
	-	72	0,28 ± 0,10	1,20 ± 0,33
	5000	24	0,09 ± 0,06	0,97 ± 0,2
NATRIUM­
METHALLYL­	5000	48	0,18 ± 0,08	1,26 ± 0,16
SULFONAT
(Gruppe I)	5000	72	0,18 ± 0,11	1,38 ± 0,20
MAS-Na (Gruppe II)	2500	24	0,13 ± 0,06	1,10 ± 0,3
MAS-Na (Gruppe III)	1250	24	0,05 ± 0,05	1,20 ± 0,2

* statistisch signifikante Veranderung gegenüber der Negativkontrolle (Vertrauensbereich = 95 %)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative No significant increase in frequency of miconuclei
Substance is not clastogenic in a mouse micronucleas test at dose levels of 1250, 2500 and 5000 mg/kg bw.

Executive summary:

Substance was tested in a mouse bone marrow micronucleus test according to OECD 474.

Substance is not clastogenic in this test at dose levels of 1250, 2500 and 5000 mg/kg bw.