α-methyl-1H-imidazole-1-ethanol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

A study according to OECD 471 (Ames-test) was conducted. No significant increase of the number of revertant colonies in the treatments with and with-out metabolic activation could be observed. No concentration-related increase over the tested range was found. Therefore, the test item is stated as not mutagenic under the test conditions.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 09, 2017 - August 17, 2017

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 97

Species / strain / cell type:

S. typhimurium TA 98

Species / strain / cell type:

S. typhimurium TA 100

Species / strain / cell type:

S. typhimurium TA 102

Species / strain / cell type:

S. typhimurium TA 1535

Metabolic activation:

with and without

Test concentrations with justification for top dose:

In the first experiment, the test item (dissolved in DMSO) was tested up to concentrations of 5 µL/plate in the absence and presence of S9-mix in the strains TA97a, TA98, TA100, TA102 and TA1535 using the plate incorporation method. Based on the first experiment, the test item was tested up to concentrations of 5 μL/plate in the absence and presence of S9-mix in all bacteria strains using the pre-incubation method.

Vehicle / solvent:

solvent used: DMSO

Untreated negative controls:

yes

Remarks:

water and DMSO

Negative solvent / vehicle controls:

yes

Remarks:

water and DMSO

True negative controls:

yes

Remarks:

water and DMSO

Positive controls:

yes

Positive control substance:

sodium azide

benzo(a)pyrene

other: 4-Nitro-1,2-phenylene diamine; 2-Amino-anthracene

Details on test system and experimental conditions:

All Salmonella typhimurium strains were obtained from TRINOVA BioChem GmbH (batch: TA97a: 4997D, TA98: 5011D, TA100: 4996D, TA102: 4982D, TA1535: 5012D) and were stored as lyophilizates in the refrigerator at 2-8 °C.
The lyophilizates were used to prepare permanent cultures which were filled into vials and stored at < - 75 °C.

Evaluation criteria:

A substance is considered to have mutagenic potential, if a reproducible increase of re-vertant colonies per plate exceeding an increase factor of 2 in at least one strain can be observed. A concentration-related increase over the range tested is also taken as a sign of mutagenic activity.

Key result

Species / strain:

S. typhimurium TA 97

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Two test were conducted using the plate incorporation method in the first test and the pre-incubation method in the second test. In both test the maximum doese tested was 5 µL/plate for all strains. Nearly all determined values for the spontaneous revertants of the negative controls were in the normal range of the test laboratory. All positive controls (diagnostic mutagens) showed mu-tagenic effects with and without metabolic activation and nearly all were within the histori-cal control data ranges.

Table 1: Mean Revertants First Experiment

Strain		TA97a	TA100	TA98	TA98	TA100	TA100	TA102	TA102	TA1535	TA1535
Induction		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
Demin. water	Mean	83	69	52	50	82	102	356	345	24	22
	sd	6.7	5.0	5.2	10.7	20.6	18.5	62.9	72.6	8.0	7.5
DMSO	Mean	85	78	43	39	110	101	257	324	21	21
	sd	5.6	13.6	5.5	11.9	6.0	21.2	26.6	20.8	0.6	5.3
Positive Controls*	Mean	343	657	560	487	404	1001	689	1083	265	132
	sd	35.9	24.1	146.0	123.3	17.4	0.0	60.2	400.0	59.5	15.2
	f(I)	4.04	8.42	13.02	12.49	4.93	9.91	2.68	3.34	11.04	6.29
5 μL/plate	Mean	83	83	40	40	84	115	411	425	23	24
	sd	15.3	2.0	10.1	13.2	2.0	28.7	44.1	62.0	2.6	1.2
	f(I)	0.98	1.06	0.93	1.03	0.76	1.14	1.60	1.31	1.10	1.14
1.5 μL/plate	Mean	84	76	51	34	94	130	343	417	25	24
	sd	7.6	14.5	3.0	0.6	14.0	15.0	23.4	26.6	4.7	4.0
	f(I)	0.99	0.97	1.19	0.87	0.85	1.29	1.33	1.29	1.19	1.14
0.5 μL/plate	Mean	62	77	34	38	119	122	361	313	19	19
	sd	8.6	10.1	5.3	4.5	5.8	3.5	81.2	35.9	1.0	3.6
	f(I)	0.73	0.99	0.79	0.97	1.08	1.21	1.40	0.97	0.90	0.90
0.15 μL/plate	Mean	79	82	37	43	108	117	303	285	21	24
	sd	23.1	11.0	2.5	4.5	30.0	19.6	53.3	36.1	2.0	0.6
	f(I)	0.93	1.05	0.86	1.10	0.98	1.16	1.18	0.88	1.00	1.14
0.5 μL/plate	Mean	88	94	50	38	112	126	331	327	20	21
	sd	6.1	22.0	2.5	1.2	36.2	3.5	89.9	56.6	1.0	3.5
	f(I)	1.04	1.21	1.16	0.97	1.02	1.25	1.29	1.01	0.95	1.00

f(I) = increase factor

* Different positive controls were used

Table 2: Mean Revertants Second Experiment

Strain		TA97a	TA97a	TA98	TA98	TA100	TA100	TA102	TA102	TA1535	TA1535
Induction		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
Demin. water	Mean	80	117	38	37	97	101	292	303	16	17
	sd	16.9	6.1	3.5	8.9	23.5	21.9	40.6	66.5	3.5	8.9
DMSO	Mean	93	123	45	40	95	93	311	337	15	20
sd		12.2	3.1	9.3	7.0	26.0	18.1	19.7	73.8	4.7	8.3
Positive Controls*	Mean	656	607	477	421	413	531	1301	684	331	92
	sd	228.7	70.5	80.1	12.2	44.1	163.2	112.1	4.0	76.4	14.4
	f(I)	7.05	4.93	10.60	10.53	4.26	5.71	4.18	2.03	20.69	4.60
5 μL/plate	Mean	105	115	30	35	108	122	323	277	22	20
	sd	11.5	6.1	8.7	2.5	15.1	4.0	54.3	46.7	3.2	4.9
	f(I)	1.13	0.93	0.67	0.88	1.14	1.31	1.04	0.82	1.47	1.00
2.5 μL/plate	Mean	145	117	36	36	95	99	317	356	22	18
	sd	34.5	26.6	2.6	4.0	9.5	16.2	23.1	86.5	2.9	1.5
	f(I)	1.56	0.95	0.80	0.90	1.00	1.06	1.02	1.06	1.47	0.90
1.25 μL/plate	Mean	144	126	35	30	98	84	248	311	19	22
	sd	20.0	7.2	9.2	11.5	15.6	3.5	28.0	46.7	4.5	3.2
	f(I)	1.55	1.02	0.78	0.75	1.03	0.90	0.80	0.92	1.27	1.10
0.63 μL/plate	Mean	111	96	41	36	91	96	263	287	18	21
	sd	2.6	20.9	6.7	11.2	14.5	15.9	37.2	36.3	3.5	3.6
	f(I)	1.19	0.78	0.91	0.90	0.96	1.03	0.85	0.85	1.20	1.05
0.31 μL/plate	Mean	88	114	33	36	85	103	275	265	15	21
	sd	7.8	20.2	5.7	11.6	3.1	14.2	86.2	89.6	4.5	3.0
	f(I)	0.95	0.93	0.73	0.90	0.89	1.11	0.88	0.79	1.00	1.05
0.16 μL/plate	Mean	96	76	30	28	80	102	311	261	20	15
	sd	10.0	11.1	3.8	4.7	1.2	12.8	61.1	28.1	2.3	2.3
	f(I)	1.03	0.62	0.67	0.70	0.84	1.10	1.00	0.77	1.33	0.75

f(I) = increase factor

* Different positive controls were used

Conclusions:

No significant increase of the number of revertant colonies in the treatments with and with-out metabolic activation could be observed. No concentration-related increase over the tested range was found. Based on the results of this study it is concluded that N-(2-hydroxypropyl)imidazole is not mutagenic in the Salmonella typhimurium strains TA97a, TA98, TA100, TA102 and TA1535 in the absence and presence of metabolic activation under the experimental conditions in this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)