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

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

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.

Link to relevant study records

Reference

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.

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

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

Target gene:

Histidine

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

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

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

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Fenchone (1195-79-5) was evaluated for its mutagenic potential in F344 male rats by micronucleus assy. The test result was considered to be ambiguous.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

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.

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

To evaluate the mutagenic potential of Fenchone in F344 male rats by micronucleus assy.

GLP compliance:

not specified

Remarks:

Micronucleus Assay

Type of assay:

not specified

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

Species:

rat

Strain:

Fischer 344

Details on species / strain selection:

Not specified

Sex:

male

Details on test animals or test system and environmental conditions:

Not specified

Route of administration:

intraperitoneal

Vehicle:

Corn oil

Details on exposure:

Not applicable

Duration of treatment / exposure:

72 hours

Frequency of treatment:

3 times in 72 hours

Remarks:

0,156,312,625,1250 and 2500mg/kg

No. of animals per sex per dose:

5 animals per dose

Control animals:

yes, concurrent vehicle

Positive control(s):

Positive controls
Cyclophosphamide
- Route of administration: Intraperitoneal Injection
- Doses / concentrations: 20 mg/kg

Tissues and cell types examined:

Erythrocyte was examined

Details of tissue and slide preparation:

Details of tissue and slide preparation

METHOD OF ANALYSIS: Slide Scoring was performed

Evaluation criteria:

An increase in the frequency of micronucleated polychromatic erythrocytes was observed.

Statistics:

Yes Mean MN-PCE/1000 PCE ± SEM and Mean Percent PCE ± SEM were observed

Key result

Sex:

male

Genotoxicity:

ambiguous

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: No mutagenic effect were observed

		Dose mg/Kg	No. of animals Scored	Mean MN-PCE/1000 PCE ± SEM	Pairwise P
Vehicle control	Corn oil	0	5	0.500±0.160
Test substance	α Fenchone	156	5	0.500±0.160	0.500
		312	5	0.200±0.120	0.872
		625	5	0.900±0.190	0.142
		1250	5	0.600±0.190	0.382
		2500	5	1.200±0.680	0.045
Positive control	Cyclophosphamide	20	5	11.000±2.720	Value less than 0.0001

Conclusions:

Fenchone (1195-79-5) was evaluated for its mutagenic potential in F344 male rats by micronucleus assy. The test result was considered to be ambiguous.

Executive summary:

In vivo Gene mutation study of Fenchone was assessed for its possible mutagenic potential. For this Purpose micronucleus assay was performed as per similar to guideline study in F344 male rats. The test material was exposed 3 times in 72 hours by Intraperitoneal Injection at the concentration of 0,156,312,625,1250 and 2500mg/kg. The erythrocyte was examined for micronucleated polychromatic erythrocytes . The test result was compared to positive control Cyclophosphamide. The test result was considered to beambiguous. Therefore Fenchone test result was considered to be ambiguous for this study.

Endpoint conclusion

Endpoint conclusion:

no study available (further information necessary)

Additional information

Genetic toxicity In-vitro

Various experimental studies were reviewed to determine the mutagenic nature of target substance; Fenchone IUPAC name: 3,3-Dimethyl-8,9-dinorbornan-2-one (1195-79-5). The In vitro studies are as mentioned below:

Gene mutation toxicity study was performed by NTP (Chemical effect in biological system, U.S Department of Health and human Services, 2018) to determine the mutagenic nature of target substance Fenchone IUPAC name: 3,3-Dimethyl-8,9-dinorbornan-2-one (1195-79-5)using Salmonella typhimurium strains. 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.

Supported by an experimental study conducted by Anita C (Mutation Research, 2003) to determine the mutagenic nature of target substance Fenchone IUPAC name: 3,3-Dimethyl-8,9-dinorbornan-2-one (1195-79-5) . In vitro Gene mutation study of Fenchone was assessed for its possible mutagenic potential. For this Purpose is Ames Assay was performed was according to OECD 471 guideline study. The test material was exposed to Salmonella Strains TA98 and TA100 both in the presence and absence of metabolic activation by using a plate incorporation protocol. A clear positive response was judged to be a three-fold increase with TA98 and/or a two-fold increase with TA100. But no mutagenic effects were observed in both strains. Therefore Fenchone was considered to be non mutagenic with and without S9 metabolic activation. Hence the substance cannot be classified as gene mutant in vitro.

 

Based on the experimental data , available for the target chemical, Fenchone IUPAC name: 3,3-Dimethyl-8,9-dinorbornan-2-one (1195-79-5)does not induce gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Genetic toxicity In-vivo

Various experimental studies were reviewed to determine the mutagenic nature of target substance; Fenchone IUPAC name: 3,3-Dimethyl-8,9-dinorbornan-2-one (1195-79-5). The In vivo study are as mentioned below:

Gene mutation toxicity study was performed by NTP (Chemical effect in biological system, U.S Department of Health and human Services, 2018) to determine the mutagenic nature of target substance Fenchone IUPAC name: 3,3-Dimethyl-8,9-dinorbornan-2-one (1195-79-5)using mammalian cell. In vivo Gene mutation study of Fenchone was assessed for its possible mutagenic potential. For this Purpose micronucleus assay was performed as per similar to guideline study in F344 male rats. The test material was exposed 3 times in 72 hours by Intraperitoneal Injection at the concentration of 0,156,312,625,1250 and 2500mg/kg. The erythrocyte was examined for micronucleated polychromatic erythrocytes. The test result was compared to positive control Cyclophosphamide. The test result was considered to be ambiguous. Therefore Fenchone test result was considered to be ambiguous for this study.

Based on the experimental data , available for the target chemical, Fenchone IUPAC name: 3,3-Dimethyl-8,9-dinorbornan-2-one (1195-79-5)does not induce any effect by gene mutation in vivo. Therefore Fenchone test result was considered to be ambiguous for this study.

Justification for classification or non-classification

Based on above annotation and CLP criteria for the target chemical, Fenchone IUPAC name: 3,3-Dimethyl-8,9-dinorbornan-2-one (1195-79-5)does not induce gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.