platinum(IV) nitrate/nitric acid solution

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 29 March 1999 and 17 May 1999.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD), to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

432-400-1

EC Name:

-

Cas Number:

10102-09-7

Molecular formula:

[Pt(NO3)x(OH)y]H2 where x = 2-5, y = 4-1, and x + y = 6

IUPAC Name:

platinum(4+) dihydrate tetranitrate

Test material form:

other: liquid

Details on test material:

Dark red liquid, batch number CH0139. The test material is only stable in nitric acid and is non-isolatable.

Method

Target gene:

histidine (Salmonella typhimurium)
tryptophan (Escherichia coli)

Species / strain

Species / strain 1

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

phenobarbitone/beta-naphthoflavone-induced rat liver S9

Test concentrations with justification for top dose:

Experiment 1: 0, 50, 150, 500, 1500 and 5000 µg/plate
Experiment 2: 0, 50, 150, 500, 1500 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: Well known solvent

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

3 µg/plate for TA100 +S9; 5 µg/plate for TA1535 +S9; 2 µg/plate for WP2uvrA +S9

Controls 2

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

80 µg/plate for TA1537 +S9

Controls 3

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

0.2 µg/plate for TA98 +S9

Controls 4

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

1 µg/plate for TA100 -S9; 2 µg/plate for TA1535 and TA1537 -S9 10 µg/plate for WP2uvrA- -S9

Controls 5

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

5 µg/plate for TA98 -S9

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48 hours

Evaluation criteria:

“The test material should have induced a reproducible, dose-related and statistically (Dunnett's method of linear regression) significant increase in the revertant count in at least one strain of bacteria.”

Statistics:

Dunnett's method of linear regression (Kirkland D J (Ed) (1989). Statistical evaluation of mutagenicity test data. UKEMS Sub-committee on Guidelines for Mutagenicity Testing. Report - Part III - Cambridge University Press.)

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium, other:

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium, other:

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: No toxicologically significant cytotoxicity observed at any concentration in any strain, so top concentration for main study set at limit concentration of 5000 µg/plate

COMPARISON WITH HISTORICAL CONTROL DATA:
Vehicle control scores were comparable to historical vehicle controls
Positive control scores were comparable to historical positive controls

OTHER DATA:
“Confirmatory testing in dried dimethyl sulphoxide… verified that the test material would still induce mutagenic increases using a non-aqueous vehicle.”

Remarks on result:

other: strain/cell type: TA100, TA98

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

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

In an OECD Test Guideline 471 study, to GLP, platinum dinitrate displayed evidence of mutagenicity when tested in four Salmonella typhimurium strains (TA1535, TA1537, TA98 and TA100) and Escherichia coli strain WP2 uvr A, either with or without S9.

Executive summary:

The mutagenic potential of platinum dinitrate was assessed in a reverse mutagenicity assay, conducted according to OECD Test Guideline 471 and to GLP. The test substance was assessed in four Salmonella typhimurium strains (TA1535, TA1537, TA98 and TA100) and in Escherichia coli WP2 uvrA, in an attempt to detect both base-pair substitution and frameshift mutations.

 

Strains were exposed to the test material (each in triplicate) via the plate incorporation method at doses of up to 5000 μg/plate (based on a preliminary assay), both in the absence and presence of amammalian (rat liver) metabolic activation (S9) system. A repeat experiment was conducted.

 

The vehicle and positive controls behaved as expected. Hence, the sensitivity of the assay and the efficacy of the S9-mix were validated. No evidence of cytotoxicity or precipitation was observed at any dose level in either the presence or absence of S9.

 

Dose-related, reproducible and statistically significant increases in revertant colony frequency were observed in S. typhimurium strains TA98 and TA100 and in E. coli both with and without S9. The study authors considered the test material to be mutagenic under the conditions of this test.