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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Genetic mutation in vitro;

Based on the data available for the test chemicals, Nicotine dihydrogen ditartrate (CAS no 65 -31 -6) did not induce gene mutation in vitro using Salmonella typhimurium bacterial strains in the presence and absence of S9 metabolic activation system is negative and hence the 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
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
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
WoE derived based on the experimental data from structurally and functionally similar read across chemicals for the target chemical.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
- Name of test material (IUPAC name): nicotine dihydrogen ditartrate
- Common name: Nicotine tartrate
- Molecular formula: C10H14N2.2C4H6O6
- Molecular weight: 462.4054 g/mol
- Smiles notation: CN1CCC[C@H]1c2cccnc2.O[C@H]([C@@H](O)C(=O)O)C(=O)O.O[C@H]([C@@H](O)C(=O)O)C(=O)O
- InChl: 1S/C10H14N2.2C4H6O6/c1-12-7-3-5-10(12)9-4-2-6-11-8-9;2*5-1(3(7)8)2(6)4(9)10/h2,4,6,8,10H,3,5,7H2,1H3;2*1-2,5-6H,(H,7,8)(H,9,10)/t10-;2*1-,2-/m011/s1
- Substance type: Organic
Target gene:
Histidine
Species / strain / cell type:
S. typhimurium, other: TA 1535, TA 1537, TA 98 and TA 100
Remarks:
1/2
Details on mammalian cell type (if applicable):
Not specified
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (5%) from male Sprague-Dawley rats given a single 500 mg/kg injection i.p. of Aroclor 1254
Test concentrations with justification for top dose:
1/2: 0 , 62.5, 125.0, 250.0, 500.0, 750.0 and 1000.0 µg/plate
Vehicle / solvent:
1/2
- Vehicle(s)/solvent(s) used: Phosphate buffer
- Justification for choice of solvent/vehicle: The test chemical was soluble in phosphate buffer
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 9-aminoacridine 2-nitrofluorene sodium azide 2-aminoanthracene
Remarks:
1/2
Details on test system and experimental conditions:
1/2
METHOD OF APPLICATION: Preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h
- Triplicate plates at each concentration
Rationale for test conditions:
Not specified
Evaluation criteria:
1/2
A sample was considered to be mutagenic if it induced a concentration-dependent increase in revertants number with at least one concentration being at least two times the solvent control.
Statistics:
1/2
Yes ,Mean standard deviation was observed
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 98 and TA 100
Remarks:
1/2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
Not specified
Remarks on result:
other: No mutagenic effect were observed
Conclusions:
Nicotine dihydrogen ditartrate did not induce gene mutation in vitro using Salmonella typhimurium bacterial strains in the presence and absence of S9 metabolic activation system is negative and hence the chemical is not likely to classify as a gene mutant in vitro.
Executive summary:

Data for the test chemicals was reviewed to determine the mutagenic nature of nicotine dihydrogen ditartrate. The studies are as mentioned below:

Genetic toxicity in vitro study was assessed for two test chemicals. The test material was exposed to Salmonella typhimurium TA 1535, TA 1537, TA 98 and TA 100 in the presence and absence of metabolic activation S9, and 20 min standard preincubation time. The test chemical was exposed at the concentration of 0, 62.5, 125, 250, 500, 750 and 1000 µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore the test chemical was considered to be non mutagenic in Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 by Ames test. Hence the two substances cannot be classified as gene mutants in vitro.

Based on the data available for the test chemicals, Nicotine dihydrogen ditartrate (CAS no 65 -31 -6) did not induce gene mutation in vitro using Salmonella typhimurium bacterial strains in the presence and absence of S9 metabolic activation system is negative and hence the chemical 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:

Ames test:

Data for the test chemicals was reviewed to determine the mutagenic nature of nicotine dihydrogen ditartrate. The studies are as mentioned below:

Genetic toxicity in vitro study was assessed for two test chemicals. The test material was exposed to Salmonella typhimurium TA 1535, TA 1537, TA 98 and TA 100 in the presence and absence of metabolic activation S9, and 20 min standard preincubation time. The test chemical was exposed at the concentration of 0, 62.5, 125, 250, 500, 750 and 1000 µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore the test chemical was considered to be non mutagenic in Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 by Ames test. Hence the two substances cannot be classified as gene mutants in vitro.

Based on the data available for the test chemicals, Nicotine dihydrogen ditartrate (CAS no 65 -31 -6) did not induce gene mutation in vitro using Salmonella typhimurium bacterial strains in the presence and absence of S9 metabolic activation system is negative and hence the chemical is not likely  to classify as a gene mutant in vitro.

Justification for classification or non-classification

Based on the data available for the test chemicals, Nicotine dihydrogen ditartrate (CAS no 65 -31 -6) did not induce gene mutation in vitro using Salmonella typhimurium bacterial strains in the presence and absence of S9 metabolic activation system is negative and hence the chemical is not likely  to classify as a gene mutant in vitro as per the criteria mentioned in CLP regulation.