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Toxicological information

Genetic toxicity: in vitro

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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

Referenceopen allclose all

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 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 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 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 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:
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

Reference
Name:
Unnamed
Type:
Constituent
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.

Applicant's summary and conclusion