Nicotine dihydrogen ditartrate

Endpoint summary

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 for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

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.