Diammonium hexachloroplatinate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: similarities to OECD test guideline 476 and data are scientifically acceptable

Data source

Reference

Reference Type:

publication

Title:

Platinum-induced mutations to 8-azaguanine resistance in Chinese hamster ovary cells.

Author:

Taylor R. T. et al.

Year:

1979

Bibliographic source:

Mutation Research 67, 65-80

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

GLP compliance:

not specified

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Dipotassium hexachloroplatinate

EC Number:

240-979-3

EC Name:

Dipotassium hexachloroplatinate

Cas Number:

16921-30-5

Molecular formula:

Cl6Pt.2K

IUPAC Name:

dipotassium hexachloroplatinate(2-)

Test material form:

other: In [presumably aqueous] solution

Details on test material:

Potassium hexachloroplatinate (CAS 16921-30-5)
Purchased from Chemical Procurement Labs, Inc.
Stored in the dark; CAS not provided.

Method

Target gene:

HGPRT locus

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Details on mammalian cell type (if applicable):

CHO-S cells, a proline-requiring Chinese Hamster Ovary cells adapted to suspension culture

Metabolic activation:

without

Test concentrations with justification for top dose:

Including 10 and 60 uM [possibly 1-100 µM]

Vehicle / solvent:

Presumably distilled water

Controls

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Details on test system and experimental conditions:

Briefly, the test substance (or ethyl methanesulphonate) were added to exponentially growing cells, and the cultures were incubated at 37 deg C for 20 hours in the dark. The cells were then harvested by centrifugation and resuspended in mutagen-free medium at a density of 50,000/ml to begin the expression growth in suspension. Growth was monitored, and every 48 hours the cells were centrifuged and an aliqout transferred to fresh medium (50,000/ml) containing 10 µM of the test substance. After 5, 10, 15, 20 and 30 population doublings, the cells were harvested and plated for survival, and subcultured for mutant expression growth in fresh medium to determine the 8-AGR mutant frequency at the HGPRT locus [and possibly the OUAR mutants]; results were compared to control. It seems that the test substance was also tested at 60 µM and, after 7 population doublings, the OUAR and 8-AGR mutant frequencies were evaluated.

Evaluation criteria:

Only data for 10 and 60 uM are presented.
Resistant mutant frequencies were presumably compared to control.

Statistics:

None reported.

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

without

Genotoxicity:

positive

Remarks:

weak

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

not significant at 10 uM; growth/cloning efficiency reduced by 50% at 34/50 uM, respectively

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

A 2-3-fold increase in the 8-AGR mutant frequency versus the spontneous control was seen upon repeated subculture. This increase was apparent after 10 population doublings.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive without metabolic activation, weak with prolonged exposure

In a well-conducted in vitro mammalian gene mutation test using CHO cells, dipotassium hexachloroplatinate was weakly mutagenic when tested up to cytotoxic concentrations, in the absence of metabolic activation.

Executive summary:

Dipotassium hexachloroplatinate was tested for genotoxicity in an in vitro mammalian gene mutation test using Chinese Hamster Ovary (CHO) cells deficient in HPRT (hypoxanthine-guanine phosphoribosyl transferase). Cells were tested only in the absence of a metabolic activation system.

 

A 2-3-fold increase in the 8-AGR mutant frequency versus the spontaneous control was seen upon repeated subculture [prolonged exposure] with a non-cytotoxic concentration of 10 μM. This increase was apparent after 10 population doublings; the trend towards it was observed at 5 population doublings.