Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Genetic mutation in vitro:

Data available for the test chemical was reviewed to determine its mutagenic nature of (2α,4aα,8β)-hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalen-8(5H)-one ( 29461-13-0).The studies are as mentioned below:

Gene mutation toxicity study was performed to determine the mutagenic nature of the testchemical . The study was performed by the Preincubation protocol using Salmonellatyphimurium strains TA1535, TA1537, TA98, and TA100 both in the presence and absence of S9 metabolic activation system. Preincubation was carried at 37°C for 20 mins followed by exposure period of 48 hrs at dose levels of 0, 3.3, 10, 33, 100, 333, 1000 or 3333µg/plate. DMSO was used as solvent control and concurrent positive control chemicals were included in the study. A dose related increase in the number of revertants was noted whether it be twofold over background or not. Test chemical did not induce mutation in the Salmonellatyphimurium strains TA1535, TA1537, TA98, and TA100 both in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Gene mutation toxicity study was performed to determine the mutagenic nature of the test chemical . The study was performed by the plate incorporation method using Salmonella typhimurium strains TA100 both in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in 100% ethanol and doses selected for the study were 0, 9.85, 19.7, 39.3, 78.5, 157, 313, 625, 1250, 2500 or 5000µg/plate. Concurrent solvent control and positive chemical was also included in the study. Test chemical did not induces mutation in the Salmonella typhimurium strains TA98 and TA100 both in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

 

The data available for the target chemical based on its read across substance and applying weight of evidence 2α,4aα,8β)-hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalen-8(5H)-one ( 29461-13-0)does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
experimental data of read across substances
Justification for type of information:
Data for the target chemical is summarized based on the structurally similar read across chemicals.
Reason / purpose:
read-across source
Related information:
Composition 1
Reason / purpose:
read-across source
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
WoE derived based on the experimental data from structurally and functionally similar read across chemicals
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Test material information:
Composition 1
Specific details on test material used for the study:
- IUPAC Name: (2α,4aα,8β)-hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalen-8(5H)-one
- Molecular Formula: C15H24O
- Molecular Weight: 220.3536 g/mole
- SMILES:CC1(C)[C@H]2CC[C@]3(C2)[C@@H]1C(=O)CCC3(C)C
- InChI:1S/C15H24O/c1-13(2)7-6-11(16)12-14(3,4)10-5-8-15(12,13)9-10/h10,12H,5-9H2,1-4H3/t10-,12+,15-/m0/s1
- Physical appearance : Liquid
- Substance type : Organic
Target gene:
Histidine
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell lines (if applicable):
Not applicable
Additional strain characteristics:
not specified
Cytokinesis block (if used):
No data
Metabolic activation:
with and without
Metabolic activation system:
Liver S-9 fractions were routinely prepared from male Sprague-Dawley rats and male Syrian hamsters that were injected, ip, with Aroclor 1254 (200 mg/ml in corn oil) at 500 mg/kg.
Species / strain:
other: TA 98 and TA100
Details on mammalian cell lines (if applicable):
Not applicable.
Additional strain characteristics:
not specified
Cytokinesis block (if used):
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 metabolic activation system was obtained from liver of Aroclor 1254 induced male Sprague
Test concentrations with justification for top dose:
1,0, 3.3, 10, 33, 100, 333, 1000 or 3333 µg/plate
2,0, 9.85, 19.7, 39.3, 78.5, 157, 313, 625, 1250, 2500 or 5000 µmoles/plate
Vehicle:
1,- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The chemical was soluble in DMSO
2,- Vehicle(s)/solvent(s) used: 100% ethanol
- Justification for choice of solvent/vehicle: The test chemical was soluble in 100% ethanol

Negative controls:
not specified
Solvent controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: 2-Aminoanthracene (2-AA), 4-Nitro-o-phenylenediamine (NOPD)
Negative controls:
not specified
Solvent controls:
yes
Remarks:
ethanol
True negative controls:
not specified
Positive controls:
yes
Remarks:
2- aminoanthracene (with S9), 2-nitrofluorene and sodium azide (without S9)
Details on test system and conditions:
1,METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 mins
- Exposure duration: 48 hrs
- Expression time (cells in growth medium): 48 hrs
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data

SELECTION AGENT (mutation assays): No data
SPINDLE INHIBITOR (cytogenetic assays): No data
STAIN (for cytogenetic assays): No data

NUMBER OF REPLICATIONS: Triplicate

NUMBER OF CELLS EVALUATED: No data

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data

OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Other: No data

OTHER: No data
2,Details on test system and conditions
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: No data
- Exposure duration: 48 hrs
- Expression time (cells in growth medium): 48 hrs

Rationale for test conditions:
No data
Evaluation criteria:
1,A dose related increase in the number of revertants was noted whether it be twofold over background or not
2,To be considered mutagenic, a test article treatment had to induce at least twice the number of revertants/plate in atleast 1 tester strain compared to those induced in the appropriate vehicle control and exhibit an increasing number of revertants/plate with increasing test article dosage
Statistics:
No data
Species / strain:
other: TA1535, TA1537, TA98, and TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
yes
Negative controls valid:
not specified
Positive controls valid:
yes
Remarks on result:
other: No mutagenic potential
Species / strain:
other: TA98 and TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
yes
Negative controls valid:
not specified
Positive controls valid:
yes
Remarks on result:
other: No mutagenic effect were observed.
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data
- Effects of osmolality: No data
- Evaporation from medium: No data
- Water solubility: No data
- Precipitation: No data
- Other confounding effects: No data

RANGE-FINDING/SCREENING STUDIES: To select the dose range for the mutagenesis assay, the test chemical was checked for toxicity to TA100 up to a concentration of 10 mg/plate or the limit of solubility, both in the presence and absence of S-9 mix. One or more parameters were used as an indication of toxicity: viability on complete medium and reduced numbers of revertant colonies per plate and/or thinning or absence of the bacterial lawn. If toxicity was not apparent in the preliminary toxicity determination, the highest dose tested was 10 mg/plate; otherwise the upper limit of solubility was used. If toxicity was observed, the doses of test chemical were chosen so that the high dose exhibited some degree of toxicity. Occasionally, in the earlier tests, the high dose was greater than 10 mg/plate.

COMPARISON WITH HISTORICAL CONTROL DATA: No data

ADDITIONAL INFORMATION ON CYTOTOXICITY: No data
Conclusions:
The test chemical (2α,4aα,8β)-hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalen-8(5H)-one ( 29461-13-0) is not mutagenic to the Salmonella typhimurium strains in the presence and absence of liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Genetic mutation in vitro:

Data available for the test chemical was reviewed to determine its mutagenic nature of (2α,4aα,8β)-hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalen-8(5H)-one ( 29461-13-0).The studies are as mentioned below:

Gene mutation toxicity study was performed to determine the mutagenic nature of the testchemical . The study was performed by the Preincubation protocol using Salmonellatyphimurium strains TA1535, TA1537, TA98, and TA100 both in the presence and absence of S9 metabolic activation system. Preincubation was carried at 37°C for 20 mins followed by exposure period of 48 hrs at dose levels of 0, 3.3, 10, 33, 100, 333, 1000 or 3333µg/plate. DMSO was used as solvent control and concurrent positive control chemicals were included in the study. A dose related increase in the number of revertants was noted whether it be twofold over background or not. Test chemical did not induce mutation in the Salmonellatyphimurium strains TA1535, TA1537, TA98, and TA100 both in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Gene mutation toxicity study was performed to determine the mutagenic nature of the test chemical . The study was performed by the plate incorporation method using Salmonella typhimurium strains TA100 both in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in 100% ethanol and doses selected for the study were 0, 9.85, 19.7, 39.3, 78.5, 157, 313, 625, 1250, 2500 or 5000µg/plate. Concurrent solvent control and positive chemical was also included in the study. Test chemical did not induces mutation in the Salmonella typhimurium strains TA98 and TA100 both in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

 

The data available for the target chemical based on its read across substance and applying weight of evidence 2α,4aα,8β)-hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalen-8(5H)-one ( 29461-13-0)does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Justification for classification or non-classification

Thus based on the above annotation and CLP criteria for target substance 2α,4aα,8β)-hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalen-8(5H)-one ( 29461-13-0)does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.