1-hydroxyoctan-2-one

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb-April 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

This is a Klimisch 1 rated OECD 471 guideline study conducted on the registered substance 1-hydroxyoctan-2-one in accordance GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-hydroxyoctan-2-one

Cas Number:

7019-19-4

Molecular formula:

C8H16O2

IUPAC Name:

1-hydroxyoctan-2-one

Test material form:

liquid

Details on test material:

Batch 1203/16/100

Specific details on test material used for the study:

batch number 1203/16/100
Purity: 96.7%
Referred to in test report as EXPINN PC17032

Method

Target gene:

Histidine (in S. Tryphimurium)

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

The mammalian liver post-mitochondrial fraction (S-9) used for metabolic activation was obtained from Molecular Toxicology Incorporated, USA where it was prepared from male Sprague Dawley rats induced with Aroclor 1254. The S-9 was supplied as lyophilized S-9 mix (MutazymeTM), stored frozen at <-20°C, and thawed and reconstituted with purified water to provide a 10% S-9 mix just prior to use. Each batch was checked by the manufacturer for sterility, protein content, ability to convert ethidium bromide and cyclophosphamide to bacterial mutagens, and cytochrome P 450-catalysed enzyme activities (alkoxyresorufin-O-dealkylase activities).

Test concentrations with justification for top dose:

Calculations of all test article concentrations included a correction factor of 1.34, applied based on impurity content. Retrospectively, it was noted that the correct correction factor should be 1.034. Therefore, for accuracy all concentrations are expressed in terms of actual test article administered into the test system. The highest concentration tested was 6700 μg/plate, which is above the maximum concentration recommended for this assay of 5000 μg/plate. This does not affect the scientific integrity or interpretation of the study.

Experiment 1 treatments of all the tester strains were performed using final concentrations of test item at 6.7, 21.44, 67, 214.4, 670, 2144 and 6700 µg/plate, plus vehicle and positive controls. Following these treatments, evidence of toxicity was observed at 6700 µg/plate in all strains in the absence and presence of S-9 except strain TA102 in the absence of S-9 where toxicity was observed at 2144 µg/plate and above.

Experiment 2 treatments of all the tester strains were performed in the absence and in the presence of S-9. The maximum test concentration of 6700 µg/plate was retained for all strains. Narrowed concentration intervals were employed covering the range 214.4-6700 µg/plate, in order to examine more closely those concentrations of test item approaching the maximum test concentration and considered therefore most likely to provide evidence of any mutagenic activity. In addition, all treatments in the presence of S-9 were further modified by the inclusion of a pre-incubation step. In this way, it was hoped to increase the range of mutagenic chemicals that could be detected using this assay system. Following these treatments, evidence of toxicity was observed at 3350and/or 6700 µg/plate in all strains except TA100 in the absence of S 9, and at 1675 µg/plate and above in all strains in the presence of S-9.

Vehicle / solvent:

All test item treatments in this study were performed using formulations prepared in anhydrous analytical grade dimethyl sulphoxide (DMSO).

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

benzo(a)pyrene

mitomycin C

other: 2-aminoanthracene

Details on test system and experimental conditions:

Five strains of Salmonella typhimurium bacteria (TA98, TA100, TA1535, TA1537 and TA102) were used in this study. Strains TA98, TA1535 and TA1537 were originally obtained from the UK NCTC. Strains TA100 and TA102 were derived from cultures originally obtained from Covance Laboratories Inc., USA. For all assays, bacteria were cultured at 37±1°C for 10 hours in nutrient broth, containing ampicillin (TA98, TA100) or ampicillin and tetracycline (TA102) as appropriate, to provide bacterial cultures in the range of approximately 108 to 109 cells/mL, based on cell density assessments for each culture. Incubation was carried out with shaking in an anhydric incubator, set to turn on using a timer switch. All treatments were completed within 1.5 hours of the end of the incubation period.

The inocula were taken from master plates or vials of frozen cultures, which had been checked for strain characteristics (histidine dependence, rfa character, uvrB character, if applicable and resistance to ampicillin or ampicillin plus tetracycline).

Evaluation criteria:

Acceptance Criteria

The assay was considered valid if all the following criteria were met:
1. The vehicle control counts fell within the laboratory’s historical control ranges as defined in ATTACHMENTS
2. The positive control chemicals induced increases in revertant numbers of ≥1.5 fold (in strain TA102), ≥2-fold (in strains TA98 and TA100) or ≥3-fold (in strains TA1535 and TA1537) the concurrent vehicle control confirming discrimination between different strains, and an active S-9 preparation.

Evaluation Criteria

For valid data, the test article was considered to be mutagenic if:
1. A concentration related increase in revertant numbers was ≥1.5-fold (in strain TA102), ≥2-fold (in strains TA98 or TA100) or ≥3-fold (in strains TA1535 or TA1537) the concurrent vehicle control values
2. Any observed response was reproducible.

The test article was considered positive in this assay if both of the above criteria were met.

The test article was considered negative in this assay if neither of the above criteria were met.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

observed at top two dose concentrations with S9

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

observed at top two dose concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

observed at top two dose concentrations with S9

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

observed at top two dose concentrations with S9

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

observed at top two dose concentrations with S9

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

Experiment 1 treatments of all the tester strains were performed in the absence and in the presence of S-9, using final concentrations of EXPINN PC17032 at 6.7, 21.44, 67, 214.4, 670, 2144 and 6700 µg/plate, plus vehicle and positive controls. Following these treatments, evidence of toxicity in the form of a slight thinning of the background bacterial lawn was observed at 6700 µg/plate in all strains in the absence and presence of S-9 except strain TA102 in the absence of S-9, where a marked reduction in revertant numbers was observed at 2144 µg/plate and a complete killing of the test bacteria was observed at 6700 µg/plate.

Experiment 2 treatments of all the tester strains were performed in the absence and in the presence of S-9. The maximum test concentration of 6700 µg/plate was retained for all strains. Narrowed concentration intervals were employed covering the range 214.4-6700 µg/plate, in order to examine more closely those concentrations of EXPINN PC17032 approaching the maximum test concentration and considered therefore most likely to provide evidence of any mutagenic activity. In addition, all treatments in the presence of S-9 were further modified by the inclusion of a pre-incubation step. In this way, it was hoped to increase the range of mutagenic chemicals that could be detected using this assay system. Following these treatments, evidence of toxicity ranging from a slight thinning of the background bacterial lawn to a marked reduction in revertant numbers was observed at 3350 and/or 6700 µg/plate in all strains except strain TA100 in the absence of S-9. Toxicity ranging from a slight thinning of the background bacterial lawn to a complete killing of the test bacteria was observed at 1675 µg/plate and above in all strains in the presence of S-9.

As less than 5 analysable concentrations were available in Experiment 2 due to complete toxicity observed at 3350 µg/plate and above in all strains in the presence of S 9, an additional experiment was conducted using the pre-incubation method at a concentration range of 67-6700 µg/plate. Following these treatments, evidence of toxicity ranging from a slight thinning of the background bacterial lawn, with or without a concurrent marked reduction in revertant numbers, to a complete killing of the test bacteria was observed at 1675 µg/plate and above in all strains.

Precipitation was observed at 6700 µg/plate in all strains in the absence and presence of S-9 in Experiment 1.

Data Acceptibility and Validity
The individual mutagenicity plate counts were averaged to give mean values. Vehicle control counts fell within the laboratory’s historical ranges with the exception of two vehicle control counts in strain TA100 in the presence of S-9 in Experiment 2. These counts were slightly above, but sufficiently close, to the historical control range and were comparable to the vehicle control replicate counts and the laboratory historical control range, and therefore accepted as characteristic and valid. The positive control chemicals all induced increases in revertant numbers of ≥1.5-fold (in strain TA102), ≥2 fold (in strains TA98 and TA100) or ≥3-fold (in strains TA1535 and TA1537) the concurrent vehicle controls confirming discrimination between different strains, and an active S-9 preparation. The study therefore demonstrated correct strain and assay functioning and was accepted as valid.

Retrospectively, it was noted that the correct correction factor should be 1.034. Therefore, for accuracy all concentrations are expressed in terms of actual test article administered into the test system. The highest concentration tested was 6700 μg/plate, which is above the maximum concentration recommended for this assay of 5000 μg/plate. This does not affect the scientific integrity or interpretation of the study.

Mutation
Following test item treatments of all the test strains in the absence and presence of S-9, no increases in revertant numbers were observed that were ≥1.5-fold (in strain TA102), ≥2-fold (in strains TA98 and TA100) or ≥3-fold (in strains TA1535 and TA1537) the concurrent vehicle control. This study was considered therefore to have provided no evidence of any mutagenic activity of the test item in this assay system.

Any other information on results incl. tables

Raw Plate Counts and Calculated Mutagenicity Data, Experiment 1, ‑S‑9

Strain	Compound	Conc. Level (µg/plate)		Mean	Standard Deviation	Fold Increase			Revertant Numbers Per Plate
TA98	DMSO	-	24.0		5.3		-	26, 28, 18
	EXPINN PC17032	6.7	20.3		1.5		0.8	22, 20, 19
		21.44	22.7		0.6		0.9	22, 23, 23
		67	22.0		6.1		0.9	18, 29, 19
		214.4	17.0		2.0		0.7	15, 19, 17
		670	19.0		2.0		0.8	17, 19, 21
		2144	15.7		0.6		0.7	15, 16, 16
		6700	5.7		4.6		0.2	11 S P, 3 S P, 3 S P
	2NF	5	897.3		67.4		37.4	841, 879, 972
TA100	DMSO	-	119.7		12.0		-	132 M B, 108, 119
	EXPINN PC17032	6.7	113.0		13.7		0.9	98, 116, 125
		21.44	114.0		11.8		1.0	117, 124, 101
		67	114.3		15.6		1.0	129, 116, 98
		214.4	118.3		6.7		1.0	126, 114, 115
		670	126.3		2.1		1.1	124, 128, 127
		2144	159.3		14.8		1.3	163, 143, 172
		6700	181.7		26.6		1.5	207 S P, 184 S P, 154 S P
	NaN3	2	1318.3		19.2		11.0	1301, 1339, 1315
TA1535	DMSO	-	15.0		1.7		-	16, 16, 13
	EXPINN PC17032	6.7	19.0		1.7		1.3	20, 17, 20
		21.44	13.3		0.6		0.9	14, 13, 13
		67	13.3		7.0		0.9	20, 6, 14
		214.4	11.3		4.5		0.8	11, 7, 16
		670	15.3		1.2		1.0	14, 16, 16
		2144	18.7		4.7		1.2	15, 24, 17
		6700	9.7		4.0		0.6	14 S P, 9 S P, 6 M B S P
	NaN3	2	1020.7		60.0		68.0	962, 1018, 1082
TA1537	DMSO	-	12.7		3.1		-	12 M B, 16, 10
	EXPINN PC17032	6.7	12.0		4.4		0.9	9, 17, 10
		21.44	16.0		3.0		1.3	19, 13, 16 M B
		67	15.3		6.4		1.2	19, 8, 19
		214.4	21.0		5.3		1.7	25, 15, 23
		670	12.3		2.1		1.0	10, 13, 14
		2144	11.0		3.0		0.9	11, 8, 14
		6700	2.7		1.5		0.2	4 S P, 3 S P, 1 M B S P
	AAC	50	1076.0		113.0		84.9	1078, 1188, 962
TA102	DMSO	-	289.3		10.0		-	278, 297, 293
	EXPINN PC17032	6.7	276.0		14.0		1.0	270, 292, 266
		21.44	299.3		4.2		1.0	296, 298, 304
		67	284.7		8.1		1.0	280, 280, 294
		214.4	283.3		15.2		1.0	286, 297, 267
		670	279.7		12.5		1.0	280, 267, 292
		2144	154.7		27.3		0.5	130, 184, 150
		6700	-		-		-	- T P, - T P, - T P
	MMC	0.2	989.0		18.0		3.4	1009, 984, 974

 

Raw Plate Counts and Calculated Mutagenicity Data, Experiment 1, +S‑9

Strain	Compound	Conc. Level (µg/plate)	Mean	Standard Deviation	Fold Increase	Revertant Numbers Per Plate
TA98	DMSO	-	37.0	1.7	-	36 M B, 36, 39
	EXPINN PC17032	6.7	37.3	6.8	1.0	32, 35, 45
		21.44	32.7	4.6	0.9	38, 30, 30
		67	40.7	5.7	1.1	36, 39, 47
		214.4	38.0	6.6	1.0	31, 39, 44
		670	34.0	2.0	0.9	34, 36, 32
		2144	34.3	5.0	0.9	39, 29, 35
		6700	21.0	2.0	0.6	21 S P, 19 S P, 23 S P
	B[a]P	10	393.0	28.1	10.6	366, 422, 391
TA100	DMSO	-	138.7	14.0	-	150, 143, 123
	EXPINN PC17032	6.7	141.0	3.6	1.0	144, 137, 142
		21.44	127.3	11.2	0.9	137, 115, 130
		67	136.3	18.8	1.0	126, 125, 158
		214.4	133.3	9.1	1.0	123, 140, 137
		670	139.0	5.6	1.0	144, 133, 140
		2144	142.7	10.6	1.0	133, 141, 154
		6700	150.3	11.1	1.1	162 S P, 149 S P, 140 S P
	AAN	5	3468.7	112.3	25.0	3460, 3361, 3585
TA1535	DMSO	-	14.3	2.3	-	13 M B, 17, 13
	EXPINN PC17032	6.7	16.0	2.0	1.1	18, 14, 16
		21.44	10.7	3.1	0.7	10, 14, 8
		67	14.0	6.9	1.0	6, 18, 18
		214.4	16.3	2.9	1.1	18, 13, 18
		670	15.7	4.0	1.1	11, 18, 18
		2144	18.3	3.8	1.3	20, 21, 14
		6700	10.0	1.0	0.7	11 S P, 9 S P, 10 M B S P
	AAN	5	386.0	31.5	26.9	395, 412, 351
TA1537	DMSO	-	21.0	2.6	-	18, 22, 23
	EXPINN PC17032	6.7	29.0	9.2	1.4	39, 21, 27
		21.44	25.3	4.0	1.2	21, 26, 29
		67	24.0	6.6	1.1	23, 18, 31
		214.4	25.3	1.5	1.2	27, 25, 24
		670	23.3	5.1	1.1	19, 29, 22
		2144	24.0	7.0	1.1	29, 27, 16
		6700	9.7	1.2	0.5	9 S P, 11 S P, 9 S P
	AAN	5	322.3	9.3	15.3	312, 325, 330
TA102	DMSO	-	306.0	35.8	-	273, 301, 344
	EXPINN PC17032	6.7	355.3	24.8	1.2	384, 341, 341
		21.44	359.3	4.6	1.2	354, 362, 362
		67	383.0	16.8	1.3	370, 377, 402
		214.4	377.7	13.7	1.2	363, 380, 390
		670	381.3	16.3	1.2	374, 400, 370
		2144	288.7	19.1	0.9	283, 310, 273
		6700	18.3	9.5	0.1	18 M P V, 28 M P V, 9 M P V
	AAN	20	3919.7	761.0	12.8	4492, 4211, 3056

Raw Plate Counts and Calculated Mutagenicity Data, Experiment 2, ‑S‑9

Strain	Compound	Conc. Level (µg/plate)		Mean	Standard Deviation	Fold Increase			Revertant Numbers Per Plate
TA98	DMSO	-	15.7		5.5		-	10, 21, 16
	EXPINN PC17032	214.4	19.0		4.4		1.2	16, 17, 24
		402	19.3		3.8		1.2	21, 15, 22
		837.5	17.3		4.0		1.1	21, 18, 13
		1675	16.0		1.7		1.0	17, 14, 17
		3350	16.0		7.0		1.0	23, 16, 9
		6700	5.3		2.1		0.3	7 S, 3 S, 6 S
	2NF	5	1131.3		67.6		72.2	1179, 1161, 1054
TA100	DMSO	-	114.3		12.2		-	117, 101, 125
	EXPINN PC17032	214.4	129.3		18.3		1.1	115, 123, 150
		402	118.3		29.1		1.0	115, 91, 149
		837.5	112.3		19.3		1.0	124, 123, 90
		1675	119.7		10.7		1.0	132, 113, 114
		3350	146.3		14.4		1.3	163, 138, 138
		6700	134.7		5.0		1.2	134, 140, 130
	NaN3	2	1007.7		49.6		8.8	999, 963, 1061
TA1535	DMSO	-	17.3		1.5		-	19, 17, 16
	EXPINN PC17032	214.4	19.0		4.4		1.1	16, 24, 17
		402	25.3		5.5		1.5	25, 31 M C, 20
		837.5	21.0		2.6		1.2	23, 22, 18
		1675	19.3		7.1		1.1	27, 18, 13
		3350	16.3		2.5		0.9	19, 16, 14
		6700	5.7		1.2		0.3	5, 7, 5
	NaN3	2	649.7		13.3		37.5	661, 653, 635
TA1537	DMSO	-	8.7		4.6		-	6, 14, 6
	EXPINN PC17032	214.4	9.0		2.0		1.0	9, 11, 7
		402	14.3		2.9		1.7	11, 16, 16
		837.5	11.7		6.7		1.3	10, 19, 6
		1675	9.0		1.7		1.0	11, 8, 8
		3350	8.0		1.0		0.9	9, 8, 7
		6700	3.3		2.3		0.4	6, 2, 2
	AAC	50	343.7		70.3		39.7	397, 370, 264
TA102	DMSO	-	264.0		3.5		-	260, 266, 266
	EXPINN PC17032	214.4	262.0		24.6		1.0	241, 256, 289
		402	289.3		17.2		1.1	271, 305, 292
		837.5	272.7		32.0		1.0	305, 272, 241
		1675	194.0		28.6		0.7	209, 212, 161
		3350	65.0		5.0		0.2	70 S, 65 S, 60 S
		6700	-		-		-	- T, - T, - T
	MMC	0.2	948.3		121.6		3.6	1088, 891, 866

 

Raw Plate Counts and Calculated Mutagenicity Data, Experiment 2, +S‑9

Strain	Compound	Conc. Level (µg/plate)		Mean	Standard Deviation	Fold Increase			Revertant Numbers Per Plate
TA98	DMSO	-	27.0		1.7		-	25, 28, 28
	EXPINN PC17032	214.4	36.7		11.9		1.4	50, 33, 27
		402	34.7		1.2		1.3	34, 34, 36
		837.5	29.7		5.5		1.1	35, 24, 30
		1675	27.7		10.5		1.0	17 S, 28 S, 38 M B S
		3350	-		-		-	- T, - T, - T
		6700	-		-		-	- T, - T, - T
	B[a]P	10	404.3		2.1		15.0	405, 402, 406
TA100	DMSO	-	158.0		33.4		-	186, 121, 167
	EXPINN PC17032	214.4	153.0		6.9		1.0	145, 157, 157
		402	138.3		8.5		0.9	135, 132, 148
		837.5	146.7		19.1		0.9	131, 168, 141
		1675	104.7		3.5		0.7	108 S, 101 S, 105 S
		3350	-		-		-	- T, - T, - T
		6700	-		-		-	- T, - T, - T
	AAN	5	2689.0		132.2		17.0	2745, 2538, 2784
TA1535	DMSO	-	27.0		11.4		-	32, 14, 35
	EXPINN PC17032	214.4	17.3		1.5		0.6	16, 19, 17
		402	15.0		4.4		0.6	10, 17, 18
		837.5	17.3		5.1		0.6	23, 16, 13
		1675	17.7		3.5		0.7	14 S, 21 S, 18 S
		3350	-		-		-	- T, - T, - T
		6700	-		-		-	- T, - T, - T
	AAN	5	272.0		40.6		10.1	280, 228, 308
TA1537	DMSO	-	14.0		7.5		-	6, 21, 15
	EXPINN PC17032	214.4	18.3		2.1		1.3	19, 20, 16
		402	19.7		6.0		1.4	26, 19, 14
		837.5	12.0		2.6		0.9	11, 10, 15
		1675	9.0		0.0		0.6	9 S, 9 S, 9 S
		3350	-		-		-	- T, - T, - T
		6700	-		-		-	- T, - T, - T
	AAN	5	295.3		12.2		21.1	298, 282, 306
TA102	DMSO	-	316.7		22.0		-	295, 339, 316
	EXPINN PC17032	214.4	391.0		19.5		1.2	406, 398, 369
		402	361.3		13.4		1.1	367, 346, 371
		837.5	304.0		38.2		1.0	260, 324, 328
		1675	195.7		25.7		0.6	172 S, 223 S, 192 S
		3350	-		-		-	- T, - T, - T
		6700	-		-		-	- T, - T, - T
	AAN	20	1750.0		185.1		5.5	1939, 1742, 1569

 

Raw Plate Counts and Calculated Mutagenicity Data, Experiment 3, +S‑9

Strain	Compound	Conc. Level (µg/plate)		Mean	Standard Deviation	Fold Increase			Revertant Numbers Per Plate
TA98	DMSO	-	45.0		3.5		-	47, 47, 41
	EXPINN PC17032	67	36.3		7.2		0.8	40, 41, 28
		134	41.3		9.1		0.9	45, 48, 31
		214.4	42.0		7.0		0.9	35, 49, 42
		402	42.0		2.6		0.9	45, 41, 40
		837.5	47.0		6.0		1.0	41, 53, 47
		1675	26.0		2.6		0.6	29 S, 24 S, 25 S
		3350	-		-		-	- T, - T, - T
		6700	-		-		-	- T, - T, - T
	B[a]P	10	352.0		8.7		7.8	342, 356, 358
TA100	DMSO	-	128.0		6.1		-	131, 121, 132
	EXPINN PC17032	67	129.0		4.0		1.0	129, 125 M B, 133
		134	131.7		21.2		1.0	108, 138, 149
		214.4	119.0		13.1		0.9	105, 131, 121
		402	134.3		14.2		1.0	143, 118, 142
		837.5	127.0		14.5		1.0	126, 142, 113
		1675	92.3		10.0		0.7	93 S, 102 S, 82 S
		3350	-		-		-	- T, - T, - T
		6700	-		-		-	- T, - T, - T
	AAN	5	2713.0		82.9		21.2	2736, 2621, 2782
TA1535	DMSO	-	14.7		6.7		-	13, 22, 9
	EXPINN PC17032	67	9.0		1.7		0.6	10, 7, 10
		134	13.0		3.5		0.9	11, 17, 11
		214.4	15.3		5.9		1.0	11, 22, 13
		402	14.0		6.2		1.0	16, 7, 19
		837.5	14.3		5.1		1.0	10, 20, 13
		1675	9.0		4.6		0.6	5 S, 8 S, 14 S
		3350	-		-		-	- T, - T, - T
		6700	-		-		-	- T, - T, - T
	AAN	5	204.7		19.4		14.0	192, 195, 227
TA1537	DMSO	-	18.3		3.8		-	14, 20, 21
	EXPINN PC17032	67	16.3		5.5		0.9	20, 19, 10
		134	15.3		3.8		0.8	18, 11, 17
		214.4	16.3		3.2		0.9	15, 20, 14
		402	16.0		1.0		0.9	16, 15, 17
		837.5	16.0		4.6		0.9	11, 17, 20
		1675	10.0		4.6		0.5	14 S, 5 S, 11 S
		3350	-		-		-	- T, - T, - T
		6700	-		-		-	- T, - T, - T
	AAN	5	239.7		12.7		13.1	235, 254, 230
TA102	DMSO	-	324.7		14.0		-	338, 326, 310
	EXPINN PC17032	67	314.7		29.4		1.0	328, 281, 335
		134	314.7		29.7		1.0	281, 326, 337
		214.4	242.0		42.6		0.7	231, 289, 206
		402	324.7		9.9		1.0	318, 320, 336
		837.5	312.7		14.6		1.0	329, 301, 308
		1675	-		-		-	- S, - S, - S
		3350	-		-		-	- T, - T, - T
		6700	-		-		-	- T, - T, - T
	AAN	20	2080.3		203.1		6.4	2258, 2124, 1859

Applicant's summary and conclusion

Conclusions:

It was concluded that the test item did not induce mutation in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of Salmonella typhimurium when tested under the conditions of this study. These conditions included treatments at concentrations up to 6700 µg/plate (a concentration that exceeded the maximum recommended concentration of 5000 μg/plate, according to current regulatory test guidelines) in the absence and in the presence of a rat liver metabolic activation system (S-9).

Executive summary:

Following 1 -hydroxyoctan-2 -one treatments of all the test strains in the absence and presence of S-9, no increases in revertant numbers were observed that were ≥1.5-fold (in strain TA102), ≥2-fold (in strains TA98 or TA100) or ≥3-fold (in strains TA1535 or TA1537) the concurrent vehicle control. This study was considered therefore to have provided no evidence of any mutagenic activity of the test item in this assay system.

It was concluded that 1 -hydroxyoctan-2 -one did not induce mutation in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) ofSalmonella typhimuriumwhen tested under the conditions of this study. These conditions included treatments at concentrations up to 5000 µg/plate (the maximum recommended concentration according to current regulatory test guidelines and a toxic concentration) in the absence and in the presence of a rat liver metabolic activation system (S-9).