Bis(8-hydroxyquinolinium) sulphate

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

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1988

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Quinolin-8-ol

EC Number:

205-711-1

EC Name:

Quinolin-8-ol

Cas Number:

148-24-3

Molecular formula:

C9H7NO

IUPAC Name:

Quinolin-8-ol

Method

Target gene:

Salmonella typhimunum strains TA97, TA98, TA100, TA1535, and TA1537 were obtained from Dr. Bruce Ames (University of California, Berkeley) and were stored as recommended [Maron and Ames, 1983]. Cultures were grown overnight with shaking at 37°C in Oxoid No. 2 broth, and their phenotypes were analyzed prior to their use for mutagenicity assays.

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

CELLS USED
- Source of cells: University of California, Berkley (Dr. Bruse Ames)
- Suitability of cells:
- Cell cycle length, doubling time or proliferation index: cultures were grown overnight with shaking at 37oC in Oxoid No.2 broth.
- Sex, age and number of blood donors if applicable:
- Whether whole blood or separated lymphocytes were used if applicable:
- Number of passages if applicable:
- Methods for maintenance in cell culture if applicable:
- Modal number of chromosomes:
- Normal (negative control) cell cycle time:

MEDIA USED
- Type and identity of media including CO2 concentration if applicable:
- Properly maintained: [yes/no]
- Periodically checked for Mycoplasma contamination: [yes/no]
- Periodically checked for karyotype stability: [yes/no)
- Periodically 'cleansed' against high spontaneous background: [yes/no]

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 97

Details on mammalian cell type (if applicable):

CELLS USED
- Source of cells: University of California, Berkley (Dr. Bruse Ames)
- Suitability of cells:
- Cell cycle length, doubling time or proliferation index: cultures were grown overnight with shaking at 37oC in Oxoid No.2 broth.
- Sex, age and number of blood donors if applicable:
- Whether whole blood or separated lymphocytes were used if applicable:
- Number of passages if applicable:
- Methods for maintenance in cell culture if applicable:
- Modal number of chromosomes:
- Normal (negative control) cell cycle time:

MEDIA USED
- Type and identity of media including CO2 concentration if applicable:
- Properly maintained: [yes/no]
- Periodically checked for Mycoplasma contamination: [yes/no]
- Periodically checked for karyotype stability: [yes/no)
- Periodically 'cleansed' against high spontaneous background: [yes/no]

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: distilled water, DMSO, 95% ethanol, acetone

Each laboratory made an independent assessment of the solvents to be used. Tests were performed at Microbiological Associates,
Inc. (MIC) and SFU International (NU);on e chemical was also tested at Case Western Reserve University (CWR). A number of chemicals were tested in more than one laboratory or at different times in the same laboratory. The laboratory repeating the test was not informed of the identity of the chemical or that it had been tested previously

Controls

Controls 1

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

in the absence of metabolic activation were sodium azide (TA1535 and TA 100)

Controls 2

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

in the absence of metabolic activation (TA97 and TA 1537)

Controls 3

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylenediamine

Remarks:

in the absence of metabolic activation (TA98)

Controls 4

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

positive control for metabolic activation with all strains

Controls 5

Negative solvent / vehicle controls:

yes

Remarks:

cuncurrent solvent: distilled water, DMSO, 95% ethanol, acetone

Remarks:

Concurrent solvent and positive controls were run with each trial

Details on test system and experimental conditions:

The preincubation assay was performed as here described: the test chemical (0.05 ml), Salmonella culture (0.10 ml), and S-9 mix or buffer (0.50 ml) were incubated at 37°C, without shaking, for 20 min. The top agar was added and the contents of the tubes were mixed and poured onto the surface of petri dishes containing Vogel-Bonner medium [Vogel and Bonner, 1956]. The histidine-independent (his+) colonies arising on these plates were counted following two days incubation at 37°C. Plates were machine counted.
The test item was tested initially in a toxicity assay to determine the appropriate dose range for the mutagenicity assay.

Four variations of protocol were used:
1)Testing in strains TA97, TA98, TA100, and TA1535, with some additional testing in strain TA1537; 10% S-9 was used.
2) The first test of the chemical was without activation and with 10% S-9 in the S-9 mix. If a positive result was obtained the test was repeated. If the tests were negative they were repeated without S-9 and with 30% S-9.
3) The order of use of 10% and 30% S-9 was reversed.
4) Initial testing was in strains TA98 and TA100 without activation and with 30% rat and hamster S-9s. If a positive result was obtained in one of these two strains it was repeated and the other strains were not used. If the tests were negative, the other strains were used with 30% and 10% S-9. A chemical was not designated non-mutagenic unless it had been tested in strains TA98, TA100, TA1535, and TA97 and/or TA1537, without activation and with 10% and 30% rat and hamster S9. Occasionally, 5% S-9 was also used in all protocol variations.

Evaluation criteria:

Individual trials were judged mutagenic (+), weakly mutagenic (+ W), questionable (?), or nonmutagenic (-), depending on the magnitude of the increase of his+ revertants, and the shape of the dose-response. A trial was considered questionable (?) if the dose-response was judged insufficiently high to support a call of “ +W,” if only a single dose was elevated over the control, or if the increase seen was not dose related.

Results and discussion

Test results

Species / strain:

not specified

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

The test item produced mutagenic responses.

Executive summary:

In this published review three hundred chemicals were tested for mutagenicity (Ames test) in Salmonella typhimurium, using a preincubation protocol by the U.S. National Toxicology Program. All tests were performed by many indipendent laboratories in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters.

The test item was tested in Microbial Genetics Department, SRI International, Menlo Park, California (K. M.) and produced mutagenic responses.