2-isopropoxyethanol

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:

2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP test according to guideline. The test report from the Japanese Ministry of Health, Labour and Welfare is not available, but all the data were validated by the Japanese authorities within the OECD SIDS program Information in this record is from therefore from the SIDS dossier, a reliable secondary source, and used as supportive information.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Unnamed

Year:

2009

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-isopropoxyethanol

EC Number:

203-685-6

EC Name:

2-isopropoxyethanol

Cas Number:

109-59-1

Molecular formula:

C5H12O2

IUPAC Name:

Propan-2-ol

Details on test material:

- Purity test date: >=99.50%- Manufacture: Mitsui Chemicals, INC.
- Lot/batch No.: 30321

Method

Species / strain

Species / strain 1

Species / strain / cell type:

E. coli WP2 uvr A

Species / strain 2

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

Rat liver, induced with phenobarbital and 5,6-benzoflavone

Test concentrations with justification for top dose:

the dose-finding study : 0, 8.19, 20.5, 51.2, 128, 320, 800, 2000, 5000 ug/plate
the main study : 0, 313, 625, 1250, 2500, 5000 ug/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Water for injection

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

Source: Wako Pure Chemical Industries, Ltd

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide

Remarks:

Source: Wako Pure Chemical Industries, Ltd

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 9-aminoacridine hydrochloride

Remarks:

Source: SIGMA-ALDRICH Corp

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

Source: Wako Pure Chemical Industries, Ltd

Details on test system and experimental conditions:

[METHOD OF APPLICATION]pre-incubation[DURATION]
- Preincubation period: 20 minutes
- Exposure duration: 48 hours
[plate/dose]=3

Evaluation criteria:

The chemicals were considered to be mutagenic when a dose-related increase in revertant colony count was observed and the number of revertant colonies per plate with the test substance was more than twice that of the negative control and when a reproducibility of test result was observed.

Statistics:

Not conducted

Results and discussion

Test results

Test results 1

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

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

Table 1	Summary data of dose-finding study with 2-(1-methylethoxy)ethanol [non-activation method:-S9 mix]
Compound	Dose (ug/plate)	Revertant colonies per plate [Mean +/- S.D.]
		TA 100			TA 1535			WP2 uvrA			TA 98			TA 1537
Test substance	0	113	121	115	11	11	13	25	26	23	23	25	26	7	5	7
		[116 +/- 46]			[12 +/- 1]			[25 +/- 2]			[25 +/- 2]			[6 +/- 1]
	8.19	105	103	115	9	7	11	26	20	22	19	23	20	7	9	7
		[108 +/- 6]			[9 +/- 2]			[23 +/- 3]			[21 +/- 2]			[8 +/- 1]
	20.5	102	110	109	11	8	12	23	32	25	18	21	26	8	6	11
		[107 +/- 4]			[10 +/- 2]			[27 +/- 5]			[22 +/- 4]			[8 +/- 3]
	51.2	101	112	104	6	5	8	31	26	25	19	21	16	8	8	10
		[106 +/- 6]			[6 +/- 2]			[27 +/- 3]			[19 +/- 3]			[9 +/- 1]
	128	127	106	102	12	7	7	22	30	31	18	24	21	7	8	8
		[112 +/- 13]			[9 +/- 3]			[28 +/- 5]			[21 +/- 3]			[8 +/- 1]
	320	119	116	129	12	11	6	26	28	27	28	26	23	5	8	5
		[121 +/- 7]			[10 +/- 3]			[27 +/- 1]			[26 +/- 3]			[6 +/- 2]
	800	101	101	92	11	10	12	23	30	23	28	25	25	8	10	7
		[98 +/- 5]			[11 +/- 1]			[25 +/- 4]			[26 +/- 2]			[8 +/- 2]
	2000	103	100	118	12	7	9	26	24	20	28	27	25	6	6	8
		[107 +/- 10]			[9 +/- 3]			[23 +/- 3]			[27 +/- 2]			[7 +/- 1]
	5000	104	96	98	15	13	19	26	27	18	30	30	23	11	9	8
		[99 +/- 4]			[16 +/- 3]			[24 +/- 5]			[28 +/- 4]			[9 +/- 2]
Positive control		589	631	558a)	531	543	515b)	166	187	149a)	703	680	726c)	314	255	285d)
		[593 +/- 37]			[530 +/- 14]			[167 +/- 19]			[703 +/- 23]			[285 +/- 30]
a) AF-2:2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide, 0.01ug/plate; b) NaN3:Sodium azide, 0.5ug/plate; c) AF-2,0.1ug/plate; d) 9-AA; 9-Aminoacridine hydrochloride, 80ug/plate

Table 2	Summary data of dose-finding study with 2-(1-methylethoxy)ethanol [activation method:+S9 mix]
Compound	Dose (ug/plate)	Revertant colonies per plate [Mean +/- S.D.]
		TA 100			TA 1535			WP2 uvrA			TA 98			TA 1537
Test substance	0	114	94	101	10	13	10	29	31	28	33	35	33	19	18	17
		[103 +/- 10]			[11 +/- 2]			[29 +/- 2]			[34 +/- 1]			[18 +/- 1]
	8.19	114	136	119	13	12	9	33	32	34	34	29	34	19	13	18
		[123 +/- 12]			[11 +/- 2]			[33 +/- 1]			[32 +/- 3]			[17 +/- 3]
	20.5	104	117	95	14	14	17	26	29	35	32	24	31	15	20	20
		[105 +/- 11]			[15 +/- 2]			[30 +/- 5]			[29 +/- 4]			[18 +/- 3]
	51.2	116	109	110	12	7	13	30	38	38	31	32	38	18	19	19
		[112 +/- 4]			[11 +/- 3]			[35 +/- 5]			[34 +/- 4]			[19 +/- 1]
	128	105	111	130	11	13	14	32	34	30	33	31	31	24	22	22
		[115 +/- 13]			[13 +/- 2]			[32 +/- 2]			[32 +/- 1]			[23 +/- 1]
	320	105	113	108	9	12	10	36	30	27	34	30	28	15	17	14
		[109 +/- 4]			[10 +/- 2]			[31 +/- 5]			[31 +/- 3]			[15 +/- 2]
	800	94	101	111	9	14	9	29	34	32	31	34	26	23	15	21
		[102 +/- 9]			[11 +/- 3]			[32 +/- 3]			[30 +/- 4]			[20 +/- 4]
	2000	125	114	123	15	11	11	31	37	33	27	27	26	17	21	16
		[121 +/- 6]			[12 +/- 2]			[34 +/- 3]			[27 +/- 1]			[18 +/- 3]
	5000	98	108	109	14	11	13	31	33	34	27	36	34	16	17	18
		[105 +/- 6]			[13 +/- 2]			[33 +/- 2]			[32 +/- 5]			[17 +/- 1]
Positive control		539	585	596^a)	282	336	304^b)	712	623	657^c)	513	543	480^d)	137	112	133^b)
		[573 +/- 30]			[307 +/- 27]			[664 +/- 45]			[512 +/- 32]			[127 +/- 13]
a)2-AA:2-Aminoanthracene, 1ug/plate; b)2-AA, 2ug/plate; c)2-AA, 10ug/plate; d)2-AA, 0.5ug/plate

Table 3	Result of the bacterial reversion test of 2-(1-methylethoxy)ethanol [non-activation method:-S9 mix]
Compound	Dose (ug/plate)	Revertant colonies per plate [Mean +/- S.D.]
		TA 100			TA 1535			WP2 uvrA			TA 98			TA 1537
Test substance	0	122	129	117	12	12	13	37	32	33	23	22	26	8	11	9
		[123 +/- 6]			[12 +/- 1]			[34 +/- 3]			[24 +/- 2]			[9 +/- 2]
	313	131	113	134	16	12	13	35	32	31	18	15	15	6	10	10
		[126 +/- 11]			[14 +/- 2]			[33 +/- 2]			[16 +/- 2]			[9 +/- 2]
	625	109	116	130	8	10	10	31	30	27	28	25	24	14	15	11
		[118 +/- 11]			[9 +/- 1]			[29 +/- 2]			[26 +/- 2]			[13 +/- 2]
	1250	125	127	141	11	14	10	32	31	33	31	29	34	13	13	10
		[131 +/- 9]			[12 +/- 2]			[32 +/- 1]			[31 +/- 3]			[12 +/- 2]
	2500	120	128	122	14	11	15	29	33	33	28	28	27	8	12	11
		[123 +/- 4]			[13 +/- 2]			[32 +/- 2]			[28 +/- 1]			[10 +/- 2]
	5000	150	132	145	16	11	17	28	34	32	23	25	30	14	11	11
		[142 +/- 9]			[15 +/- 3]			[31 +/- 3]			[26 +/- 4]			[12 +/- 2]
Positive control		572	615	531^a)	550	553	555^b)	177	165	180^a)	666	633	729^c)	330	382	354^d)
		[573 +/- 42]			[553 +/- 3]			[174 +/- 8]			[676 +/- 49]			[355 +/- 26]
a)AF-2:2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide, 0.01ug/plate; b)NaN3:Sodium azide, 0.5ug/plate; c)AF-2, 0.1ug/plate; d)9-AA: 9-Aminoacridine hydrochloride, 80 ug/plate

Table 4	Result of the bacterial reversion test of 2-(1-methylethoxy)ethanol [activation method:+S9 mix]
Compound	Dose (ug/plate)	Revertant colonies per plate [Mean +/- S.D.]
		TA 100			TA 1535			WP2 uvrA			TA 98			TA 1537
Test substance	0	113	129	124	13	10	15	31	37	33	26	27	31	17	19	16
		[122 +/- 8]			[13 +/- 3]			[34 +/- 3]			[28 +/- 3]			[17 +/- 2]
	313	124	120	130	10	9	10	37	31	30	26	29	25	18	15	13
		[125 +/- 5]			[10 +/- 1]			[33 +/- 4]			[27 +/- 2]			[15 +/- 3]
	625	118	122	135	6	8	8	28	37	30	26	27	20	20	20	23
		[125 +/- 9]			[7 +/- 1]			[32 +/- 5]			[24 +/- 4]			[21 +/- 2]
	1250	137	131	128	13	10	8	38	37	37	22	27	24	18	21	24
		[132 +/- 5]			[10 +/- 3]			[37 +/- 1]			[24 +/- 3]			[21 +/- 3]
	2500	120	125	134	17	11	14	44	47	46	27	21	25	17	19	24
		[126 +/- 7]			[14 +/- 3]			[46 +/- 2]			[24 +/- 3]			[20 +/- 4]
	5000	121	122	130	9	9	9	35	42	41	31	28	29	15	16	14
		[124 +/- 5]			[9 +/- 0]			[39 +/- 4]			[29 +/- 2]			[15 +/- 1]
Positive control		836	785	822^a)	257	264	300^b)	693	667	668^c)	425	473	408^d)	138	154	156^b)
		[814 +/- 26]			[274 +/- 23]			[676 +/- 15]			[435 +/- 34]			[149 +/- 10]
a)2-AA:2-Aminoanthracene, 1ug/plate; b)2-AA, 2ug/plate; c)2-AA, 10ug/plate; d)2-AA, 0.5ug/plate

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative without metabolic activation
negative with metabolic activation

The test substance was not mutagenic under the conditions of this study.

Executive summary:

The study was conducted under guideline and in compliance with GLP. The mutagenicity of 2-isopropoxyethanol was examined in four Salmonella typhimurium strains, TA98, TA100, TA1535 and TA1537, and in an Escherichia coli strain, WP2uvrA, at concentrations up to 5,000 μg/plate with or without an exogenous metabolic activation system. In this study, the substance did not show any mutagenic activity in any bacterial strain with or without metabolic activation.