Cinchonidine

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In the in vitro study published by Sideropoulos et al., 1984 the genetic toxicity of the read across substance quinine was determined using the Ames test. For the two Salmonella typhimurium strains TA 100 and TA 98 no mutations were detected. From the result it can be concluded, that quinine has no mutagenic effects. From this we conclude that cinchonidine, which differs in a methoxy group is not mutagenic, too.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is not done according to OECD guideline. But it is a well documented study.

Principles of method if other than guideline:

Ames test
Cell cultures were prepared by inoculating 10-15 ml of oxoid broth with the desired S. typhimurium strain and incubating in a 37°C shaking water bath for 18-20 h at 200 rpm. Three dose levels were chosen for each strain, with and without S-9 activation. A minimal salt plate containing medium E (Vogel-Bonner medium-l.5% agar) with 2% glucose was used. The top layer contained 2 ml soft agar, strain TA 100 or TA 98, test chemical and/or benzo[a]pyrene, 0.2 ml histidine-biotin, and 0.5 ml S-9 (0.1 ml S-9/ml mix). The actual procedure consisted of introducing 2.0 ml of the top agar containing the appropriate amounts of histidine-biotin solution to sterile tubes. This mixture was maintained at 47°C; 0.1 ml of the appropriate concentration of the test chemical was then added followed by 0.1 ml of the proper bacterial strain. For mixtures requiring S-9, 0.5 ml of S-9 mix was added. Tubes were mixed, immediately poured over medium E plates (2% glucose), and allowed to harden in the dark. Plates were incubated for 72 h at 37°C and then scored.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 98

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

S. typhimurium TA 100

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Rat, Liver, S-9

Test concentrations with justification for top dose:

20 - 50 µg/Plate

Untreated negative controls:

yes

Remarks:

untreated control

Negative solvent / vehicle controls:

other: not applicable

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/ml (quinine derivate)

Vehicle controls validity:

not applicable

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/ml (quinine derivate)

Vehicle controls validity:

not applicable

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: strain/cell type: Ames Salmonella typhimurium

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

The genetic toxicity of the read across substance quinine was determined using the Ames test with and without metabolic activation. For the two Salmonella typhimurium strains TA 100 and TA 98 no mutations were detected. From this we conclude that cinchonidine, which differs in a methoxy group is not mutagenic, too.

Executive summary:

In the in vitro study published by Sideropoulos et al., 1984 the genotoxicity of the read across substance quinine was determined with the Ames test on the two Salmonella typhimurium strains TA 100 and TA 98 with and without metabolic activation. For both strains no mutations were detected up to 50 µg quinine per plate. Therefore, we can conclude that quinine is not genotoxic and that cinchonidine which differs in a methoxy group is not genotoxic, too.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

In the in vitro study published by Sideropoulos et al., 1984 the genotoxicity of the read across substance quinine was determined with the Ames test on the two Salmonella typhimurium strains TA 100 and TA 98 with and without metabolic activation. For both strains no mutations were detected up to 50 µg quinine per plate. Therefore, we can conclude that quinine is not genotoxic and that cinchonidine, which differs in a methoxy group is not genotoxic, too.

Justification for selection of genetic toxicity endpoint
The study is not done according to OECD guideline, but it is a well documented study.

Justification for classification or non-classification

The result of the Ames test of the read across substance quinine was negative. Therefore, we can conclude that cinchonidine which differs in a methoxy group also has no mutagenic effects and does not need to be classified.