Ammonium 2-(acryloylamino)-2-methylpropane-1-sulfonate

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:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented report of a guideline study conducted according to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

ammonium (1Z)-N-(2-methyl-1-sulfopropan-2-yl)prop-2-enimidate

EC Number:

611-646-3

Cas Number:

58374-69-9

Molecular formula:

C7H12NO4S.H4N

IUPAC Name:

ammonium (1Z)-N-(2-methyl-1-sulfopropan-2-yl)prop-2-enimidate

Constituent 2

Reference substance name:

Ammonium 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonate

EC Number:

421-680-9

EC Name:

Ammonium 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonate

IUPAC Name:

421-680-9

Constituent 3

Reference substance name:

2-Acrylamido-2-methylpropanesulfonic acid, ammonium salt

IUPAC Name:

2-Acrylamido-2-methylpropanesulfonic acid, ammonium salt

Details on test material:

- Name of test material: 2-Acrylamido-2-methylpropanesulfonic acid, ammonium salt (ammonium AMPS), CAS 58374-69-9
- Analytical purity: 50 % aqueous solution

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 week old

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle used: deionized water

Frequency of treatment:

single dose

Post exposure period:

24, 48 and 72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
175, 875 and 1750 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

5 male and 5 femal mice/dose/time period

Control animals:

yes, concurrent vehicle

Positive control(s):

Positive control: cyclophosphamide
- Route of administration: intraperitoneal injection
- Doses / concentrations: 60 mg/kg, single dose

Examinations

Tissues and cell types examined:

Bone marrow slides were prepared

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:Bone marrow slides were prepared, stained and scored for the number of micronucleated polychromatic erythrocytes (MPCE) in a total of 2000 polychromatic erythrocytes (PCE) per mouse.

Evaluation criteria:

The ratio of polychromatic to normochromatic erythrocytes (PCE/NCE ratio) was also determined for each mouse as an index of toxicity.

Statistics:

The frequency of MPCE in each test group was compared to its respective negative control group using a one-tailed Student's t-test
with a poss-hoc Cochran-Armitage test for possible dosing trends.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

Analysis of the by-sex data indicated that the test material did not induce any statistically significant or dose-dependant increases in MPCE frequencies at any harvest time evaluated, as compared to concurent negative controls (table 1). However, a single isolated increase in the frequency of MPCEs (combined-sex) was observed in mice treated with the test material at a dose of 175 mg/kg and harvested at 24 hours (p<0.05). Since this increase was within the historical negative control range as well as the acceptable negative control values for this assay, this isolated increase in MPCE frequency was considered a statistical aberration due to random fluctuation of the spontaneous MPCE frequency. In addition the test material did not induce any statistically significant depressions in PCE/NCE ratios compared to concurrent negative controls (table 2). MPCE frequencies for all negative control groups were within acceptale negative ranges, and the cyclophosphamide positive control groups produced statistically significant increases in MPCE frequencies (combined- and by-sex; p<0.01). Cyclophosphamide-treated animals experienced significant depressions in PCE/NCE ratios (p<0.05).

Table 1:

Male				Female
Time (hours)	Treatment	Dose (mg/kg)	% MPCE Frequencies	Time (hours)	Treatment	Dose (mg/kg)	% MPCE Freqeuncies
24	Vehicle		0.03	24	Vehicle		0.03
	OS114454	175	0.07		OS114454	175	0.08
		875	0.03			875	0.03
		1750	0.02			1750	0.05
	Cyclophosphamide	60	2.24		Cyclophophamide	60	1.39
48	Vehicle		0.04	48	Vehicle		0.05
	OS114454	175	0.01	OS114454		175	0.08
		875	0.04			875	0.03
		1750	0.03			1750	0.07
72	Vehicle		0;03	72	Vehicle		0.05
	OS114454	175	0.04		OS114454	175	0.05
		875	0.07			875	0.02
		1750	0.07			1750	0.03

Table 2:

PCE/NCE ratios
Dose (mg/kg)	Time (hours)	Ratio Mean (sd)
H20	24	1.217 (0.3)
175	24	1.265 (0.12)
875	24	1.294 (0.17)
1750	24	1.256 (0.19)
H20	48	1.374 (0.22)
175	48	1.369 (0.31)
875	48	1.317 (0.23)
1750	48	1.422 (0.24)
H20	72	1.281 (0.11)
175	72	1.266 (0.20)
875	72	1.364 (0.27)
1750	72	1.133 (0.25)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
The test material was considered to be non-clastogenic in the mouse micronucleus test, under the conditions and according to the criteria of the test protocol.