Dipotassium tetrachloroplatinate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / micronucleus study

Remarks:

Type of genotoxicity: other: chromosome damage (micronuclei)

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: Although not a standard (guideline) study, it could be considered to be well documented and scientifically acceptable

Data source

Reference

Reference Type:

publication

Title:

Genotoxicity of platinum and palladium compounds in human and bacterial cells.

Author:

Gebel T et al.

Year:

1997

Bibliographic source:

Mutation Research 389, 183-190.

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: non standard method as described by Fenech M (1993) Mut Res 285, 35-44

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 487 (In vitro Mammalian Cell Micronucleus Test)

Deviations:

yes

Remarks:

Mammalian cytokinesis-block micronucleus assay similar to that descrobed by OECD TG487. Principal difference was that test was carried out only in the absence of metabolic activation.

GLP compliance:

not specified

Type of assay:

in vitro mammalian cell micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

K2PtCl4 (II)

IUPAC Name:

K2PtCl4 (II)

Constituent 2

Reference substance name:

Dipotassium (II) tetrachloroplatinate

Cas Number:

10025-99-7

IUPAC Name:

Dipotassium (II) tetrachloroplatinate

Method

Species / strain

Species / strain / cell type:

mammalian cell line, other: Human peripheral mononuclear blood cells (lymphocytes)

Metabolic activation:

without

Test concentrations with justification for top dose:

Concentrations of 0, 5, 15, 150 or 300 µM

Vehicle / solvent:

Distilled water

Controls

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

mitomycin C

Details on test system and experimental conditions:

Briefly, blood from healthy donors (aged 25-35-years) was obtained, and the lymphocytes isolated, stained and counted. The lymphocytes were then cultured in medium at a concentration of 500,000/ml, and cell mitosis was stimulated. The test substance was disolved in distilled water and added 24 hr later to the culture in a volume of 20-30 µl. Seventy hours after cell mitosis was stimulated, the cells were harvested, fixed and prepared for microscopy. Micronuclei were scored in 1000 binucleate cells with two nuclei of equal size, and the nuclear division index (NDI) was calculated. Duplicate or triplicate experiments were carried out on different donors

Evaluation criteria:

Test substance was considered genotoxic if a statistically significant (p<0.05) increase in the mean number of micronuclei were observed.

Statistics:

Number of micronuclei analysed with the X2 test

Results and discussion

Test results

Species / strain:

mammalian cell line, other: Human peripheral mononuclear blood cells (lymphocytes)

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Toxicity reported at 300 µM

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The mean numbers of micronuclei in binucleate cells were 3.5, 3.5, 5.0 and 15.0 at concentrations of 0, 5, 15 and 150 µM, respectively. At 150 µM, this was statistically significant compared to the negative control. At 300 µM, cytotoxicity was seen.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive

Dipotassium tetrachloroplatinate induced micronuclei in the cytokinesis-block micronucleus test with human lymphocytes, when tested up to cytotoxic concentrations.

Executive summary:

In a non-guideline study, the ability of dipotassium tetrachloroplatinate to induce micronuclei in human peripheral mononuclear blood cells (lymphocytes) was assessed, in the absence of a metabolic activation system. The mean numbers of micronuclei in binucleate cells were 3.5, 3.5, 5.0 and 15.0 at test concentrations of 0, 5, 15 and 150 µM, respectively. At 150 µM, this was statistically significant compared to the negative control. At 300 µM, cytotoxicity was seen.

In conclusion, the test substance showed some ability to cause chromosome damage (micronuclei) in a cytokinesis-block micronucleus test with human lymphocytes.