4,7-dichloroquinoline

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

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 is from peer reviewed journals

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity testing of the test chemical and its various derivatives

Author:

Minako Nagao et.al

Year:

1977

Bibliographic source:

Mutation Research, 1977

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Bacterial reverse mutation assay was performed to evaluate the toxic nature of the test chemical on Salmonella typhimurium TA98 and TA100 strains.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4,7-dichloroquinoline

EC Number:

201-714-7

EC Name:

4,7-dichloroquinoline

Cas Number:

86-98-6

Molecular formula:

C9H5Cl2N

IUPAC Name:

4,7-dichloroquinoline

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material: 4,7 Dichloroquinoline
- IUPAC name: 4, 7 Dichloroquinoline
- Molecular formula: C9H5Cl2N
- Molecular weight: 198.051 g/mole
- Smiles : c12c(cc(Cl)cc2)nccc1Cl
- Inchl: 1S/C9H5Cl2N/c10-6-1-2-7-8(11)3-4-12-9(7)5-6/h1-5H
- Substance type: Organic
- Physical state: Solid powder (pale cream)
- Purity: 99.4%(by GC)

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium TA100 and TA 98

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

other: Base-pair-change mutant and frameshift mutant. Both strains have the R-factor of pKM101 as a plasmid

Cytokinesis block (if used):

No data

Metabolic activation:

with and without

Metabolic activation system:

Type and composition of metabolic activation system: The S-9 fraction was prepared aseptically by centrifugation of the liver homogenate (25% in 0.15 M KCl) at 9000 g for 10 min as described by Ames et al.
- source of S9 : Male Sprague-Dawley rats weighing 100-120 g were injected intraperitoneally with polychlorinated biphenyl (Kanechlor 500) at a dose of 50 mg/100 g body weight, five days before they were killed
- concentration or volume of S9 mix and S9 in the final culture medium : S-9 mix contained 50 µmol of sodium phosphate buffer (pH 7.4), 4 µmol of MgCl2, 16.5 µmol of KCI, 2.5µmol of glucose-6-phosphate, 2 µmol of NADH, 2 µmol of NADPH, 2.5 µmol of ATP and 150µmol of S-9 fraction in a total volume of 0.5 ml.

Test concentrations with justification for top dose:

0, 0.5 or 1.0 µmoles/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test chemical was stable and soluble in DMSO.

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

NUMBER OF REPLICATIONS:
- Number of cultures per concentration (single, duplicate, triplicate) : no data available
- Number of independent experiments : no data available

METHOD OF TREATMENT/ EXPOSURE:
- Cell density at seeding (if applicable):
- Test substance added in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk : pre-incubation

TREATMENT AND HARVEST SCHEDULE
- Preincubation period, if applicable: 20 minutes
- Exposure duration/duration of treatment: 2 days
- Harvest time after the end of treatment (sampling/recovery times):

Rationale for test conditions:

No data

Evaluation criteria:

After 2-day incubation, colonies of histidine prototroph were counted as revertants.

Statistics:

No data

Results and discussion

Test results

Test results 1

Species / strain:

other: Salmonella typhimurium TA100 and TA 98

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

True negative controls validity:

not specified

Positive controls validity:

not specified

Test results 2

Species / strain:

other: S. typhimurium TA 100, S. typhimurium TA 98

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

True negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

Ames test: The test chemical was weakly mutagenic to both strains with S-9 mix and non mutagenic to both strains in the absence of S9 mix. Though there was weak mutagenic activity in the presence of S9 mix but dose dependent decrease in number of revertants was observed. Hence, we consider the test chemical can be considered to be non-mutagenic both in the presence and absence of S9 mix to S.Typhimurium TA 98 and TA 100 strains.

Remarks on result:

other: non-mutagenic

Applicant's summary and conclusion

Conclusions:

The test chemical was weakly mutagenic to both strains with S-9 mix and non mutagenic to both strains in the absence of S9 mix. Though there was weak mutagenic activity in the presence of S9 mix but dose dependent decrease in number of revertants was observed. Hence, the test chemical can be considered to be non-mutagenic both in the presence and absence of S9 mix to S.Typhimurium TA 98 and TA 100 strains.

Executive summary:

In vitro genetic toxicity study was performed to determine the mutagenic nature of the test chemical. Strains TA100 and TA98 of Salmonella typhimirium were used as the tester strains. Assay was carried out as described by Ames et al. with some modifications. The test chemical was freshly dissolved in 100 µl of DMSO were pre-incubated at 37°C for 20 min with 0.5 ml of S-9 mix or 0.5 ml of 0.1 M sodium phosphate buffer (pH 7.4) and 0.1 ml of bacterial culture. Two ml of molten soft agar at 45°C were added, and the resulting mixture was poured over 25 ml of minimal-glucose agar containing 0.1 µmol of L-histidine and 0.1 µmol of biotin. After 2-day incubation, colonies of histidine prototroph were counted as revertants. The test chemical was weakly mutagenic to both strains with S-9 mix and non mutagenic to both strains in the absence of S9 mix. Though there was weak mutagenic activity in the presence of S9 mix but dose dependent decrease in number of revertants was observed. Hence, the test chemical can be considered to be non-mutagenic both in the presence and absence of S9 mix to S.Typhimurium TA 98 and TA 100 strains.