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Toxicological information

Genetic toxicity: in vitro

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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Similar to OECD guidelines, with certain deviations.
Remarks:
Lacks a strain capable of detecting cross-linking mutagens, only tested at up to 1 mg/plate (instead of the recommended 5 mg/plate) and only plated in duplicate rather than in triplicate.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Guideline recommends the use of a strain capable of detecting cross-linking mutagens, which was not done. Only tested at up to 1 mg/plate (instead of the recommended 5 mg/plate). Only plated in duplicate rather than in triplicate.
Principles of method if other than guideline:
Method carried out according to Ames et al. (1975). Mutation Research 31, 347-364.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): only cited by molecular formula Pt(NH3)4Cl2
- Substance type: cream powder
- Physical state: solid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: 2 batches used – 031099/A and “uncoded”
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data on storage of test substance; solutions prepared immediately before testing
- Other:

Method

Target gene:
histidine
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1537
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 98
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
without
Metabolic activation system:
Rat liver microsomal fraction (S9) from male, CD1 rats induced with Aroclor 1254
Test concentrations with justification for top dose:
1.6, 8.0, 40, 200 and 1000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: deionised water (uncoded batch); isotonic saline (batch 031099/A)
- Justification for choice of solvent/vehicle: no data

Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: N-methyl-N-nitro-N- nitrosoguanidine
Remarks:
10 µg/plate for TA1535 and TA100 without S9
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
20 µg/plate for TA1537, TA 98 and TA100, with and without S9
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
50 µg/plate for TA1537 without S9
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
20 µg/plate for TA1538 and TA98 without S9
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hr

OTHER: Plates prepared in duplicate.
Only tested up to 1 mg/ml although no problem with solubility was reported.
Tests with TA1537, TA98 and TA100 were conducted twice, both with and without S9 using the “uncoded” test compound in water. Three separate tests were performed with batch 031099/A dissolved in isotonic saline and TA1535, TA1537 and TA1538, only without S9.
Evaluation criteria:
No data, but reported the method to be according to Ames et al. (Mutation Research 1975, 31, 347-364), who considered a less than 2-fold increase in revertants, compared to spontaneous revertants, to be a negative response.
Statistics:
No data

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
other: weak positive
Cytotoxicity / choice of top concentrations:
other: cytotoxic at 1000 μg/plate in one of the duplicate tests, both in the presence and absence of S9
Vehicle controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
other: weak positive
Cytotoxicity / choice of top concentrations:
other: cytotoxic at 1000 μg/plate in one of the duplicate tests, both in the presence and absence of S9
Vehicle controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

TEST-SPECIFIC CONFOUNDING FACTORS

No data

 

RANGE-FINDING/SCREENING STUDIES: no data

 

COMPARISON WITH HISTORICAL CONTROL DATA: no data in the report [but revertants within the ranges given in the literature].

 

ADDITIONAL INFORMATION ON CYTOTOXICITY: in one of the duplicate tests there was a thinning of the background lawn reported for TA98 and TA100 together with a decrease in the number of revertants, both with and without S9. This was not evident with TA1537, or for TA 1535 and TA 1538 which were only tested without S9.

 

Applicant's summary and conclusion

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

In a limited study, tetraammineplatinum dichloride showed a dose-related mutagenic activity in TA 1537, and a weak positive response (about a 2-fold increase in mutant frequency, compared to the spontaneous frequency) in TA98 and TA100, both in the presence and absence of metabolic activation.
Executive summary:

Tetraammineplatinum dichloride was tested for mutagenic activity by reversion to histidine independence in five strains of Salmonella typhimurium, TA1535, TA1537, TA 1538, TA98 and TA100, using pour-plate assays.

 

Duplicate assays were carried out with strains TA98, TA100 and TA1537, both with and without a rat liver microsomal fraction (S9), using an aqueous solution of the test item. Three separate tests were conducted with strains TA1535, TA1537 and TA1538 in the absence of S-9 mix only, using the test substance dissolved in isotonic saline solution. In all experiments, test doses ranged from 1.6 to 1000 µg/plate (lower than the recommended top concentration).

 

A dose-related increase in mutant frequency (13- to 36-fold above that for spontaneous mutants) was observed in TA 1537, which detects frameshift mutations. A weak positive response (about a 2-fold increase in mutant frequency, compared to the spontaneous frequency) was also observed in TA98 and TA100, which also detect frameshift mutations. These increases in mutant frequencies were seen both in the presence and absence of S9.No increase was seen with strains TA1535 and TA1538, either in the presence or absence of S9.