β-methylaziridine-1-propiononitrile

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980-03-26 to 1980-05-09

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable study report

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Reference 3

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Principles of method if other than guideline:

according to Ames, B. N.; McCann, J.; Yamasaki, E.: Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mut. Res. 31, 347 - 364 (1975)

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

β-methylaziridine-1-propiononitrile

EC Number:

223-798-4

EC Name:

β-methylaziridine-1-propiononitrile

Cas Number:

4078-19-7

Molecular formula:

C6H10N2

IUPAC Name:

3-(aziridin-1-yl)butanenitrile

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 rat liver S9 fraction

Test concentrations with justification for top dose:

4, 20, 100, 500 and 2500 µg/plate

Vehicle / solvent:

DMSO

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

with metaboblic activation, TA100 and TA1535

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracen

Remarks:

with metabolic activation, TA100, TA98, TA1538, TA1537 and TA1535

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-Methyl-N-nitro-N-nitroso-guanidin (MNNG)

Remarks:

without metabolic activation, TA100, TA98, and TA1535

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-Nitro-o-phenylendiamin

Remarks:

without metabolic activation, TA1538

Controls 5

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 9-Aminoacridiniumchlorid Monohydrat

Remarks:

without metabolic activation, TA1537

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: none
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 4

Evaluation criteria:

A substance is considered positivve if:
- doubling of spontanous colonie numbers
- a dose-effect-relationship can be established
- results are reproducible

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium, other: TA 1535, TA 100, TA 98

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

other: A bacteriotoxic effect was not present in the tester strains (with the exception of TA 1535).

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium, other: TA 1537, TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Dosis µg/plate	S9 Mix	TA98								TA100
		Experiment 1				Experiment 2				Experiment 1				Experiment 2
DMSO	+	40	-	33	35	38	35	41	39	110	105	107	103	139	120	151	128
4	+	38	31	32	39					99	112	113	115
20	+	41	38	44	64	34	35	36	35	242	157	125	141	297	286	299	251
100	+	78	75	85	61	68	79	74	64	579	330	189	218	709	630	655	626
500	+	109	76	87	92	81	94	104	88	368	181	483	1900	1700	1650	1600	1950
2500	+	118	87	106	114	156	142	132	138	2550	2600	3000	2400	2750	2650	2900	2700
10 2-Aminoanthracen	+	1220	758	1020	1180	1850	1880	1460	1800	2100	2500	2780	1850	2750	3150	2650	3000
500 Cyclophosphamid	+									260	232	268	338	255	243	218	286
DMSO	-	33	26	25	36	21	28	28	27	123	126	135	122	124	118	137	114
4	-	25	22	28	24					136	119	149	113
20	-	24	41	37	21	27	26	57	31	153	169	134	125	231	183	208	219
100	-	47	39	30	27	25	28	19	25	475	334	264	162	445	742	533	500
2500	-	53	45	51	41	18	27	22	24	985	710	750	760	1400	1360	1400	1400
500	-	58	40	39	18	29	24	23	28	-	2100	1950	1700	2700	2530	2450	2400
5 MNNG	-	1760	1730	1580	1520	1230	1010	1370	1300	2900	2600	2850	2600	2800	3150	3000	3350

Dosis µg/plate	S9 Mix	TA1535								TA1537				TA1538
		Experiment 1				Experiment 2
DMSO	+	13	12	14	12	16	16	18	14	6	7	6	6	22	22	24	21
4	+	34	24	16	26					5	4	11	5	24	23	25	28
20	+	105	110	33	117	265	164	291	279	5	5	9	8	21	19	24	25
100	+	227	377	152	407	895	742	901	707	4	9	7	-	21	20	24	30
500	+	1500	1000	380	600	2050	1700	1950	2000	6	6	8	9	18	23	30	25
2500	+	850	589	B	-	3100	2600	2000	3100	7	7	8	8	16	-	17	19
10 2-Aminoanthracen	+	340	277	251	298	367	360	327	318	103	122	116	163	920	1050	930	670
500 Cyclophosphamid	+	312	212	166	184	178	199	181	182
DMSO	-	14	12	16	15	18	13	17	18	5	5	7	6	13	14	11	12
4	-	17	29	19	15					7	6	6	5	14	15	14	10
20	-	87	141	82	74	206	143	185	166	9	6	9	4	16	14	12	14
100	-	356	284	254	269	750	613	544	620	8	8	5	5	14	12	10	11
500	-	422	-	317	556	1660	1500	1800	1680	5	5	6	8	10	12	15	13
2500	-	960	990	2700	366	2700	2700	2600	2800	7	5	5	9	12	11	9	11
5 MNNG	-	2600	3000	2900	2500	2950	2700	2500	2500
10 4-Nitro-o-phenylen-diamin	-													268	297	284	342
100 9-Aminoscridinium-chlorid-Monohydrat	-									332	437	308	421

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive

The test substance showed a mutagenic potential in the Ames test.

Executive summary:

The test substance was used in an Ames test in S. typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538. Concentrations of 4 - 2500 µg/plate were applied with an without metabolic activation (S9 mix). Mutagenicity was observed in strains TA100 and TA1535 with and without metabolic activation and in TA98 with metabolic activation. The test substance was not mutagenic in TA1537 and TA1538 with and without metabolic activation. Bacteriotoxicity was only detected for TA1535 at 2500 µg/plate in Experiment 1. Thus the test substance showed a mutagenic potential in the Ames test.