6,10-dimethylundeca-5,9-dien-2-one

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD)

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Remarks:

Department of Toxicology, BASF Aktiengesellschaft

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

6,10-dimethylundeca-5,9-dien-2-one

EC Number:

211-711-2

EC Name:

6,10-dimethylundeca-5,9-dien-2-one

Cas Number:

689-67-8

Molecular formula:

C13H22O

IUPAC Name:

6,10-dimethylundeca-5,9-dien-2-one

Details on test material:

- Name of test material (as cited in study report): Geranylaceton
- Test substance No.: 97/3019
- Date of manufacture: December 4, 1996
- Physical state: Yellow liquid
- Analytical purity: 95.6 area%
- Lot/batch No.: PN.-Nr. 008626
- Storage condition of test material: Refrigerator
- Stability under test conditions: The stability of the test substance throughout the study period was not determined analytically. However, the characterization was performed from July 11, 1997 to August 21, 1997, indicating a stability of about 8 months after date of manufacture.

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:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S-9 mix

Test concentrations with justification for top dose:

0, 15, 20, 30, 60, 100, 125, 250, 500, 2500 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Due to the limited solubility af the test substance in water, DMSO was selected as the vehicle, which had
been demonstrated to be suitable in bacterial reverse mutation tests and for which historical control data are available.

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene; 2.5 µg/plate, dissolved in DMSO (TA 1535, TA 100, TA 1537, TA 98)

Remarks:

with metabolic activation

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene; 60 µg/plate, dissolved in DMSO (E. coli WP2 uvrA)

Remarks:

with metabolic activation

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

without metabolic activation

Migrated to IUCLID6: 5 µg/plate, dissolved in DMS0 (TA 1535, TA 100)

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylendiamine; 10 µg/plate, dissolved in DMSO (TA 98)

Remarks:

without metabolic activation

Controls 5

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

without metabolic activation

Migrated to IUCLID6: 100 µg/plate, dissolved in DMSO (TA 1537)

Controls 6

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

without metabolic activation

Migrated to IUCLID6: 10 µg/plate, dissolved in DMSO ( E. coli WP2 uvrA)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
- The experimental procedure of the standard plate test (plate incorporation method) is based an the method of Ames et al. (1975)

DURATION
- Exposure duration: 48 - 72 h, 37°C
- Expression time (cells in growth medium): 48 - 72 h, 37°C

NUMBER OF REPLICATIONS: 3


DETERMINATION OF CYTOTOXICITY
- Method: decrease in the number of revertants, clearing or diminution of the background lawn (= reduced his- or trp- background growth), reduction in the titer

Evaluation criteria:

The test chemical is considered positive in this assay if the following criteria are met:
- A dose-related and reproducible increase in the number of revertant colonies, i.e. about doubling of the spontaneous mutation rate in at least one
tester strain either without S-9 mix or after adding a metabolizing system.

A test substance is generally considered nonmutagenic in this test if:
- The number of revertants for all tester strains were within the historical negative control range under all experimental conditions in two experiments carried out independently of each other.

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:

cytotoxicity

Remarks:

TA 100, TA1537: >250 µg/plate; TA 98, TA 1535: > 500

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

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:

valid

Positive controls validity:

valid

Additional information on results:

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- A bacteriotoxic effect (reduced his- background growth, decrease in the number of his+ revertants,
reduction in the titer) was observed depending an the strain and test conditions from about 250 µg - 500 µg/plate onward.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Results:

			mean number of revertant colonies / plate
Strain	metabolic activation	Experiment	controls					µg substance / plate									Evaluation
			negative	solvent	positive	15	20	30	60	100	125	250	500	2500	5000
TA 1535	-	1		20	1037		15			17			8	5B	4B		-
	-	2		18	1050		20			18			14	7B	5B		-
	-	3		19	937		18			16			11	3B	3B		-
	+	1		17	228		19			21			15	14B	4B		-
	+	2		21	224		20			15			10	14B	6B		-
	+	3		23	204		18			19			13	11B	10B		-
TA 1537	-	1		9	725		8			7			0B	0B	0B		-
	-	2		10	805		8			5			0B	0B	0B		-
	-	3		9	801		8			7			0B	0B	0B		-
	+	1		11	112		8			7			0B	0B	0B		-
	+	2		10	100		10			7			0B	0B	0B		-
	+	3		9	98		7			8			0B	0B	0B		-
TA 1537	-	1		10	661	10		9	7		6	3					-
	-	2		9	725	9		10	5		4	5					-
	-	3		11	692	10		5	6		5	6					-
	+	1		10	176	7		8	9		6	3					-
	+	2		7	155	8		7	6		7	3					-
	+	3		12	169	10		8	7		6	4					-
TA 98	-	1		26	1206		23			27			14	10B	4B		-
	-	2		26	1173		24			21			14	7B	5B		-
	-	3		21	1112		25			21			13	11B	7B		-
	+	1		37	1304		41			27			20	17B	10B		-
	+	2		35	1377		34			33			18	13B	5B		-
	+	3		40	1299		31			30			19	12B	5B		-
TA 100	-	1		113	1206		94			105			37B	0B	0B		-
	-	2		124	1118		84			104			22B	0B	0B		-
	-	3		102	1112		84			100			12B	0B	0B		-
	+	1		104	1064		107			101			0B	0B	0B		-
	+	2		117	1036		105			102			0B	0B	0B		-
	+	3		120	1074		99			89			0B	0B	0B		-
TA 100	-	1		100	1142	115		114	106		100	91					-
	-	2		103	857	99		84	101		104	72					-
	-	3		110	976	113		100	121		101	88					-
	+	1		103	1294	135		92	120		100	80					-
	+	2		103	1037	106		121	98		127	70					-
	+	3		126	1169	114		119	104		101	62					-
E. coli WP2 uvrA	-	1		31	829		33			37			36	33	38		-
	-	2		31	876		30			39			35	27	29		-
	-	3		36	913		33			35			30	32	31		-
	+	1		39	286		42			35			37	31	30		-
	+	2		45	300		42			35			39	35	32		-
	+	3		37	287		38			42			44	35	40		-

B: reduced backround growth

- the sterility controls revealed no indication of bacterial contamination

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative