Tris(triphenylphosphine)rhodium (I) chloride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In a guideline study, to GLP, “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) (Wilmer, 1998).

Link to relevant study records

Reference

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.

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

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

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.

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No data identified.

Endpoint conclusion

Endpoint conclusion:

no study available

Mode of Action Analysis / Human Relevance Framework

No data identified.

Additional information

Additional information from genetic toxicity in vitro:

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 (Wilmer, 1998). [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].

 

According to a review of rhodium and its compounds conducted by the Dutch Expert Committee on Occupation Standards (DECOS), information relating to the genotoxicity and carcinogenicity of rhodium (I) compounds is limited (DECOS, 2002). In one study, four water-soluble rhodium (I) complexes were tested. When dissolved in acetone, and without the addition of S9, a lack of mutagenicity was seen in S. typhimurium TA92, TA2410, TA100 and TA98. Whereas, when dissolved in DMSO , weakly positive results were observed in some of these strains for some of these complexes (Arestsa et al., 1984). In another study, six water-soluble rhodium (I) complexes induced mutations in Escherichia coli and S. typhimurium strains (Monti-Bragadin et al., 1987). No in vivo mutagenicity or genotoxicity tests, or carcinogenicity studies, were available for any rhodium (I) compounds. The available data were, therefore, considered insufficient for classification purposes (DECOS, 2002).

 

Overall there is some evidence, albeit quite limited, to suggest that rhodium (I) compounds have mutagenic potential in bacteria, particularly those that are soluble in water. However, tris(triphenylphosphine)rhodium chloride was shown to be a non-mutagen in one good-quality bacterial reverse mutation assay.

 

References

Aresta M, Treglia S, Collucia M, Correale M, Giordano D and Moscelli S (1984). Mutagenic activity of transition-metal complexes: Relation structure-mutagenic and antibacterial activity for some Pd(II), Pt(II) and Rh(I) complexes. Toxicological and Environmental Chemistry 8, 81.

 

DECOS (2002). Dutch Expert Committee on Occupational Standards, a committee of the Health Council of the Netherlands. Rhodium and compounds: Evaluation of the carcinogenicity and genotoxicity. https://www.gezondheidsraad.nl/sites/default/files/0208osh_0.pdf

 

Monti-Bragadin C, Giacca M, Dolzani L and Tamaro M. (1987). Mutagenic effects of rhodium(I) and ruthenium(II) organometallic complexes in bacteria. Inorganica Chimica Acta, 137, 31.USEPA (2008a) BIOWIN version v4.10. United States Environmental Protection Agency

Justification for selection of genetic toxicity endpoint
OECD guideline study, and the only in vitro genetic toxicity study available.

Justification for classification or non-classification

In conclusion, the available data provide no evidence to suggest that tris(triphenylphosphine)rhodium is mutagenic in germ cells. As such, tris(triphenylphosphine)rhodium should not be classified as a germ cell mutagen (category 1A or B).