Tris(triphenylphosphine)rhodium (I) chloride

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:

Toxicity test: January 4 1989; Mutagenicity assay: January 25-January 30 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was GLP compliant and was produced largely in accordance with the relevant OECD guideline. However, the study report omitted the following information: purity of the test substance, justification for the choice of solvent, and historical negative and positive control data. In addition, the study did not include a tester strain suitable for the detection of cross-linking mutagens, as recommended in OECD Guideline 471.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

the study did not include a tester strain suitable for the detection of cross-linking mutagens, as recommended in OECD Guideline 471

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tris(triphenylphosphine)rhodium (I) chloride

EC Number:

238-744-5

EC Name:

Tris(triphenylphosphine)rhodium (I) chloride

Cas Number:

14694-95-2

Molecular formula:

C54H45ClP3Rh

IUPAC Name:

tris(triphenylphosphine)rhodium (I) chloride

Details on test material:

- Name of test material (as cited in study report): Tris-(triphenylphosphan)-Rhodium(I)-chlorid
- Substance type: solid
- Physical state: magenta-red crystalline solid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date: no data
- Lot/batch No.: 6868-4
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: ambient temperature
- Other: Test substance was received from Degussa AG on December 13 1988

Method

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9

Test concentrations with justification for top dose:

12.3, 37, 111.1, 333.3, and 1000µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: [DMSO (prepared “under ultrasonic wave”]
- Justification for choice of solvent/vehicle: no data

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: sodium azide 2-nitrofluorene 9-aminoacridine other: [2-aminoanthracene]

Remarks:

see below

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: three days


NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other:


OTHER:
A preliminary toxicity test was carried out with six concentrations of the test substance in S. typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100.


Appropriate strain-specific positive controls were used in the absence of S9 metabolic activation. In the presence of S9 metabolic activation, 2-aminoanthracene was used as the sole positive control in all strains tested. The batch of S9 used was characterised in tests with the mutagens 4-aminobiphenyl and 2-aminoanthracene.

Evaluation criteria:

A positive response was indicated by a two-fold or greater increase in the mean number of revertant colonies appearing on the test plates over and above the background spontaneous reversion rate observed on the vehicle control plates, together with evidence of dose response.

Statistics:

No statistical analysis were presented in the report.

Results and discussion

Test results

Key result

Species / strain:

bacteria, other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: no data
- Precipitation: In the preliminary toxicity test, the test substance precipitated in the plates at dose levels of 1 and 10 mg/plate.
- Other confounding effects: no data

RANGE-FINDING/SCREENING STUDIES: A preliminary toxicity study was performed with the S. typhimurium tester strains.

COMPARISON WITH HISTORICAL CONTROL DATA: no data

ADDITIONAL INFORMATION ON CYTOTOXICITY: The results of a preliminary toxicity test found that 10 mg/plate was toxic in all tester strains both in the presence and absence of S9. At 1 mg/plate, slight toxicity was noted for TA 1535, TA 1537 (both in the presence and absence of S9), TA 1538 (in the absence of S9 only) and TA100 (in the presence of S9 only). Toxicity was not observed at dose levels of 0.1 mg/plate or lower.

Any other information on results incl. tables

Results were confirmed in an independent repeat of the mutation assay.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative

“Tris-(triphenylphosphan)-Rhodium(I)-chlorid” displayed no evidence of mutagenic activity when tested at up to cytotoxic levels in Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 100 or TA 98, either in the presence or in the absence of a rat liver metabolic activation system (S9).

Executive summary:

In an OECD Test Guideline 471 study, conducted according to GLP, “tris-(triphenylphosphan)-rhodium(I)-chlorid” was examined for the ability to induce gene mutations in Salmonella typhimurium (strains TA 1535, TA 1537, TA 1538, TA 98, and TA 100) in the presence and absence of Aroclor-induced rat liver metabolic activation system (S9). Tester strains were exposed to five concentrations (ranging from 12.3 to 1000 µg/plate), based on observed precipitation in a range-finding study, with tests performed in triplicate using the plate incorporation method. No evidence of mutagenic activity was seen, either in the presence or absence of S9, in tests with up to cytotoxic levels. The results were confirmed in a repeat experiment.

 

This study was largely conducted in accordance with current OECD guidelines. However, some information was omitted from the study report, including: the purity of the test substance, justification for the choice of solvent, and historical negative and positive control data. The guidelines also indicate that it is preferable to include tester strains that are able to detect certain oxidising mutagens and/or cross-linking agents (e.g. Salmonella typhimurium TA102) or to include a DNA repair-proficient strain of Escherichia coli.