(R)-3,7-dimethyloct-6-enal

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

Remarks:

The test substance (Citronellal; CAS 106-23-0) represents the racemate of the registered substance (R)-3,7-dimethyloct-6-enal (CAS 2385-77-5).

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets basic scientific principles, sufficient documentation

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Mutagenicity testing of (±)-camphor, 1,8-cineole, citral, citronellal, (-)-menthol and terpineol with the Salmonella/microsome assay

Author:

Gomes-Carneiro M.R., Felzenswalb I., Paumgartten F.J.R.

Year:

1998

Bibliographic source:

Mutat Res 416, 129 - 136

Reference 2

Reference Type:

other: abstract

Title:

Evaluation of the mutagenic potential of monoterpenoid compounds

Author:

Gomes Carneiro M.R., Paumgartten F.J.R., Felzenswalb I.

Year:

1997

Bibliographic source:

Mutat Res 379, Suppl 1, S111

Reference 3

Reference Type:

other: abstract

Title:

Evaluation of the mutagenic potential of monoterpenoid compounds

Author:

Gomes Carneiro M.R., Paumgartten F.J.R., Felzenswalb I.

Year:

1997

Bibliographic source:

Mutat Res 379, Suppl 1, S110

Reference 4

Reference Type:

secondary source

Title:

Mutagenicity testing of (±)-camphor, 1,8-cineole, citral, citronellal, (- )-menthol and terpineol with the Salmonella/microsome assay

Author:

Gomes-Caneiro, et al.

Year:

1998

Bibliographic source:

cited in: WHO FOOD ADDITIVES SERIES (52): Safety evaluation of certain food additives and contaminants

Reference 5

Reference Type:

secondary source

Title:

Mutagenicity testing of (±)-camphor, 1,8-cineole, citral, citronellal, (- )-menthol and terpineol with the Salmonella/microsome assay

Author:

Gomes-Carneiro MR, et al.

Year:

1998

Bibliographic source:

cited in: RIFM-FEMA Database CAS 106-23-0 RIFM ID 156 FEMA 2307

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:

Plate incorporation assay performed according to the revised method of Maron and Ames (1983, Mutat. Res. 113, 173-215)

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Citronellal

EC Number:

203-376-6

EC Name:

Citronellal

Cas Number:

106-23-0

Molecular formula:

C10H18O

IUPAC Name:

3,7-dimethyloct-6-enal

Details on test material:

- Name of test material (as cited in study report): Citronellal

Method

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium TA 97a, TA 98, TA 100, TA 102

Metabolic activation:

with and without

Metabolic activation system:

rat liver S9 fraction (Aroclor 1254 induced)

Test concentrations with justification for top dose:

-S9: TA 100: 5 - 200 µg/plate; TA 98: 5 - 200 µg/plate; TA 97a: 5 - 150 µg/plate; TA 102: 1 - 50 µg/plate
+S9: TA 100: 5 - 200 µg/plate; TA 98: 5 - 300 µg/plate; TA 97a: 5 - 200 µg/plate; TA 102: 5 - 200 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: solubility of the test substance

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

ethanol

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene (TA 100 and 98, +S9), sodium azide (TA 100, -S9), nitro-o-phenylenediamine (TA 98, -S9), 4-nitroquinolone-n-oxide (TA 97a, -S9), 2-aminofluorene (TA 97a, +S9), mitomycin C (TA 102/-S9), benzo(a)pyrene (TA 102/+S9)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: none
- Exposure duration: 72 hr


NUMBER OF REPLICATIONS: 3, repeated in at least 2 assays

DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of revertants or as an alteration of the auxotrophic background growth

Evaluation criteria:

not specified

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 97a, TA 98, TA 100, TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

300 µg/plate

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

Dose finding study:

Table 1: Cytotoxicity of citronellal in S. typhimurium T100 strain

Dose (µg/plate)	mean mutant count/plate
	-S9	+S9
500	1/0/0^+	-
400	52/3/0^+	3/3^+
300	82/29/0^+	154/75 (*)/0^+
200	139 ± 12	179 ± 23
solvent ctrl	174 ± 15	184 ± 26
positive ctrl	924 ± 41	591 ± 69

(*) Toxicity apparent as an alteration of the background lawn

/⁺ Mutant counts of individual plates

(-) Dose not tested

Data are shown as mutant counts (mean ± SD) of three plates

Due to the cytotoxic effects after treatment with 400 µg/plate and higher, the main study was undertaken with concentrations below 400 µg/plate.

Main study:

Table 2: Mutagenity testing of citronellal in Salmonella / microsome assay with the strains TA100, TA98, TA97a, and TA102

Monoterpene	Dose (µg/plate)	Number of revertants (mean ± SD)
Citronellal		TA100		TA98		TA97a		TA102
		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
	300	-	-	-	47 ± 14 (*)	-	-	-	-
	200	131 ± 12	172 ± 11	29 ± 3	54 ± 1	-	174 ± 25	-	645 ± 50 (*)
	150	151 ± 11	-	34 ± 11	-	125 ± 8	-	-	706 ± 55
	100	152 ± 10	199 ± 12	42 ± 1	57 ± 6	146 ± 19	218 ± 30	-	655 ± 41
	50	167 ± 4	196 ± 18	31 ± 2	61 ± 4	153 ± 13	181 ± 31	548 ± 62	846 ± 28
	30	156 ± 11	-	-	-	-	-	674 ± 70	-
	25	-	203 ± 9	-	-	167 ± 16	225 ± 2	-	751 ± 66
	20	-	-	-	-	-	-	631 ± 35	-
	10	164 ± 14	205 ± 14	32 ± 6	70 ± 8	152 ± 16	187 ± 16	599 ± 81	787 ± 66
	5	186 ± 12	201 ± 14	36 ± 6	62 ± 11	158 ± 18	211 ± 19	612 ± 20	752 ± 26
	1	-	-	-	-	-	-	646 ± 56	-
	solvent ctrl	182 ± 14	201 ± 16	49 ± 16	70 ± 6	157 ± 2	212 ± 17	628 ± 12	771 ± 37
	positive ctrl	907 ± 63	1165 ± 151	208 ± 1	312 ± 33	749 ± 25	1002 ± 101	5351 ± 101	2024 ± 182

Solvent control: 100 µl ethanol p.a.

(-) Dose not tested.

(*) Toxicity apparent as an alteration of the background lawn.

Values are the means ± SD of three plates of one (out of two) representative experiment.