3,3-dimethyl-8,9-dinorbornan-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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication.

Data source

Reference

Reference Type:

publication

Title:

Genetic Toxicity Evaluation of alpha-Fenchone in Salmonella/E.coli Mutagenicity Test or Ames Test. Study A18733

Author:

NTP

Year:

2018

Bibliographic source:

Chemical effect in biological system, U.S Department of Health and human Services, 2018

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

To evaluate the mutagenic potential of Fenchone in Salmonella Typhimurium strain TA 97, TA 98, TA 100 and TA 1535 by AMES assay.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3,3-dimethyl-8,9-dinorbornan-2-one

EC Number:

214-804-6

EC Name:

3,3-dimethyl-8,9-dinorbornan-2-one

Cas Number:

1195-79-5

Molecular formula:

C10H16O

IUPAC Name:

1,3,3-trimethylbicyclo[2.2.1]heptan-2-one

Details on test material:

- IUPAC Name: 3,3-Dimethyl-8,9-dinorbornan-2-one
- InChI: 1S/C10H16O/c1-9(2)7-4-5-10(3,6-7)8(9)11/h7H,4-6H2,1-3H3/t7-,10+/m0/s1
- Smiles: C[C@@]12CC[C@@H](C1)C(C)(C)C2 =O
- Name of test material:Fenchone
- Molecular formula:C10H16O
- Molecular weight:152.2354 g/mol
- Substance type:Organic

Specific details on test material used for the study:

- Name of test material :Fenchone
- Common name : 1,3,3-trimethylbicyclo[2.2.1]heptan-2-one
- Molecular formula : C10H16O
- Molecular weight : 152.2354 g/mol
- Smiles notation : C[C@@]12CC[C@@H](C1)C(C)(C)C2=O
- InChl : 1S/C10H16O/c1-9(2)7-4-5-10(3,6-7)8(9)11/h7H,4-6H2,1-3H3/t7-,10+/m0/s1
- Substance type: Organic
- Physical state: Liquid

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA 97, TA 98, TA 100 and TA 1535

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with and without

Metabolic activation system:

10 %and 30% induced male Sprague Dawley rat liver S9 and induced male Syrian hamster liver S9 were used

Test concentrations with justification for top dose:

0,3.3,10,33,100,217,333,1000,2167,3333and 10000µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

not specified

Details on test system and experimental conditions:

Details on test system and conditions
METHOD OF APPLICATION: in medium; Preincubation Method
DURATION
-- Exposure duration: 48 hours

Rationale for test conditions:

Not specified.

Evaluation criteria:

Evaluation was done considering a dose dependent increase in the number of revertants/plate.

Statistics:

Yes , Mean ±Standard deviation was observed

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium, other: TA 97, TA 98, TA 100 and TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: No mutagenic effct were observed

Any other information on results incl. tables

Strain: TA100

 

Dose   Protocol   ug/Plate	No Activation (Negative) Preincubation		No Activation (Negative) Preincubation		30% RLI (Negative) Preincubation		30% HLI (Negative) Preincubation		10% RLI (Negative) Preincubation		10% HLI (Negative) Preincubation
	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM
0	109	8	174	3.1	138	2.6	111	5.8	150	4.5	178	1.2
3.3	119	6.8
10	118	3.8	182	8.5	114	2.7	106	8.6	151	19	181	8.1
33	119	1.5	177	2.5	133	3.5	114	1.5	149	2.3	154	17.2
100	121	7.7	167	9.6	138	3.5	119	4.3	126	2.3	160	12.3
217
333	113	13.1	153	13.3	134	1.2	97	5	151	1.9	168	7.2
1000	t		50 s	23.8	97 s	8.6	83 s	5.9	67 s	4.6	t
2167					24 s	13.2	48 s	35
3333											t
10000											t
Positive Control	401	23	578	26	800	48.2	677	10.2	480	19.6	469	10.4

 

 

 

 

Strain: TA1535

 

Dose   Protocol   ug/Plate	No Activation (Negative) Preincubation		No Activation (Negative) Preincubation		30% RLI (Negative) Preincubation		30% HLI (Negative) Preincubation		10% RLI (Negative) Preincubation		10% HLI (Negative) Preincubation
	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM
0	12	2	8	1.7	18	3.4	13	.7	7	.3	6	.6
10	14	1.5	8	.3	16	2.3	13	2.4	7	.3	8	.3
33	8	.7	9	3.8	15	2.5	15	.3	7	2.3	9	1.2
100	13	.9	7	.9	17	1.5	13	3.8	8	1.5	5	1.5
333	11	1.8	7	1.5	15	2.2	12	.6	6	2.2	9	3
1000	4 s	1.7	0 s	0	17 s	5.1	11 s	2.3	3 s	1.3	5 s	2.7
Positive Control	285	8.7	55	4.5	234	19.7	75	7.5	183	9.6	23	2.5

 

 

 

Strain: TA97

 

Dose   Protocol   ug/Plate	No Activation (Negative) Preincubation		No Activation (Negative) Preincubation		30% RLI (Negative) Preincubation		30% HLI (Negative) Preincubation		10% RLI (Negative) Preincubation		10% HLI (Negative) Preincubation
	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM
0	126	6.9	98	15.8	192	18.4	155	1.9	153	13.3	132	5
10	123	19.6	123	1.3	207	15.5	159	18.5	156	20.4	129	13.6
33	100	11.7	117	10.4	213	15.6	181	16.2	159	10.2	113	5.8
100	131	4.7	111	1.5	200	4.7	135	5.2	159	2.7	143	21.1
333	114	5	94	9.7	201	5.4	145	16.3	147	14.3	120	2.5
1000	68 s	34.6	3 s	3	146 s	17.9	91 s	6.2	47 s	22.9	75 s	5.5
Positive Control	490	63.7	1079	95.2	590	55.2	745	47.8	1601	126.6	621	60.2

 

 

 

Strain: TA98

 

Dose   Protocol   ug/Plate	No Activation (Negative) Preincubation		No Activation (Negative) Preincubation		30% RLI (Negative) Preincubation		30% HLI (Negative) Preincubation		10% RLI (Negative) Preincubation		10% HLI (Negative) Preincubation
	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM	Mean	±SEM
0	17	4.4	19	1.7	16	3.5	18	3.5	27	6.3	22	3.2
3.3	18	3.4
10	12	2.5	20	2.3	17	2.5	22	1.5	24	3.2	23	3.9
33	11	1.7	17	3.9	19	3	18	1.3	19	1.2	25	4.1
100	13	1.2	18	2.4	21	2.3	20	2	28	4.1	18	1.7
333	12	1.7	17	1.8	24	2.6	18	1.5	13	3.2	23	1.2
1000	t		1 s	.5	0 s	.3	15 s	4.9	5 s	1.5	2 s	1.3
2167					t		t
Positive Control	483	38.7	84	5.7	232	2.8	368	23.4	157	11.7	239	17.6

 

Applicant's summary and conclusion

Conclusions:

Fenchone (1195-79-5) was evaluated for its mutagenic potential in Salmonella Strains TA 97, TA 98, TA 100 and TA 1535 in vitro Ames Assay. The test result was considered to be negative with and without S9 metabolic activation.

Executive summary:

In vitro Gene mutation study of Fenchone was assessed for its possible mutagenic potential. For this Purpose Ames Assay was performed as per similar to guideline study. The test material was exposed to Salmonella Strains TA 97, TA 98, TA 100 and TA 1535 both in the presence and absence of metabolic activation (10 %and 30% induced male Sprague Dawley rat liver S9 and induced male Syrian hamster liver S9 were used )by using aPreincubation Method. The test substance was exposed at the concentration of 0, 3.3, 10, 33, 100, 217, 333, 1000, 2167, 3333 and 10000µg/plate. No mutagenic effects were observed in all strain. Therefore Fenchone was considered to be non mutagenic in Salmonella Strains TA 97, TA 98, TA 100 and TA 1535 both in the presence and absence of metabolic activation. Hence the substance cannot be classified as gene mutant in vitro.