Rhodium chloride (RhCl3), hydrate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Rhodium trichloride hydrate displayed evidence of genotoxicity in two in vitro guideline bacterial reverse mutation assays with Salmonella typhimurium (Kraft, 2006a; Wilmer, 1986) and in the mouse lymphoma cell line L5178Y (Kraft, 2006b) as well as in an in vitro micronucleus assay in Chinese Hamster lung fibroblasts (Rodrigo, 2007a).

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:

17-29 May 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Microsomal fraction (S9) prepared from the liver of male Wister rats induced with phenobarbital and β-naphtoflavone on three consecutive days by oral gavage

Test concentrations with justification for top dose:

Experiment 1: 0.0316, 0.1, 0.316, 1, 2.5 and 5 μL/plate
Experiment 2: 0.25, 0.5, 1, 2, 3, 4 and 5 μL/plate

Pre-experiment (strains TA 98 and TA 100 only): 0.01, 0.0316, 0.1, 0.316, 1, 2.5 and 5 μL/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: Test guideline recommends use of aqueous solvent wherever possible

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

methylmethanesulfonate

other: 2-aminoanthracene (2-AA) and 4-nitro-o-phenylenediamine (4-NOPD)

Remarks:

Without S9: Sodium azide (NaN3; TA 100 and TA 1535 at 10 μg/plate); 4-NOPD (TA 98 at 10 μg/plate and TA 1537 at 40 μg/plate); Methyl methane sulfonate (MMS; TA 102 at 1 μL/plate). With S9: 2-AA (TA 102 at 10 μg/plate; All other strains at 2.5 μg/plate)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation)

DURATION
- Preincubation period: Not applicable
- Exposure duration: 48 hours
- Expression time (cells in growth medium): Not applicable
- Selection time (if incubation with a selection agent): Not applicable
- Fixation time (start of exposure up to fixation or harvest of cells): Not applicable

SELECTION AGENT (mutation assays): Not applicable
SPINDLE INHIBITOR (cytogenetic assays): Not applicable
STAIN (for cytogenetic assays): Not applicable

NUMBER OF REPLICATIONS: Plates prepared in triplicate for each experiment

NUMBER OF CELLS EVALUATED: Not applicable

DETERMINATION OF CYTOTOXICITY
- Method: other: thinning/absence of background lawn, reduction in number of mutant colonies

OTHER EXAMINATIONS:
- Determination of polyploidy: Not applicable
- Determination of endoreplication: Not applicable

Evaluation criteria:

A test item is considered as mutagenic if there is a clear and dose-related increase in the number of revertants and/or a biologically relevant positive response for at least one of the dose groups occurs in at least one tester strain with or without S9.

A biologically relevant increase was taken as a 2-fold increase in mutants for TA 100 and TA 102 and a 3-fold increase in TA 98, TA 1535 and TA 1537, compared to the spontaneous reversion rate.

A test item producing neither a dose related increase in the number of revertants nor a reproducible biologically relevant positive response at any of the dose groups is considered to be non-mutagenic in this system.

Statistics:

Not applicable. According to the OECD guidelines, the biological relevance of the results will be the criterion for the interpretation of results. Hence, a statistical evaluation is not regarded as necessary.

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Only in experiment 2

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

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: None
- Other confounding effects: No contamination noted

RANGE-FINDING/SCREENING STUDIES: Reduction in background lawn seen at 5 μL/plate in TA 98 (with and without S9). In TA 100, cytotoxicity was observed at 2.5 μL/plate and above without S9 and at 1 μL/plate and above with S9.

COMPARISON WITH HISTORICAL CONTROL DATA: Spontaneous frequencies were within the historical control data range.

MUTAGENICITY: Neither experiment noted any biologically relevant increases in revertant colony numbers in tester strains TA 1535 and TA 1537. A dose-response relationship was found in tester strains TA 98, TA 100 and TA 102 (with and without S9) in both experiments.

Experiment 1: Biologically relevant increases in revertant colony numbers were observed in TA 98 in a range from 0.316 to 2.5 μL/plate (without S9) and in a range from 0.316 to 1.11 μL/plate (with S9). In strain TA 100 biologically relevant increases in revertant colony numbers were noted from 0.316 to 1 μL/plate (without S9) and at a dose of 0.316 μL/plate (with S9). Biologically relevant increases of revertant colony numbers were observed in TA 102 in a range from 0.316 to 5 μL/plate (with and without S9). The threshold value of 2.0 was exceeded and a maximum mutation factor of 8.0 was reached in tester strain TA 102 at a dose of 2.5 μL/plate (without S9).

Experiment 2: No biologically relevant increases in revertant colony numbers were noted in tester strains TA 1535 and TA 1537. Biologically relevant increases in revertant colony numbers were observed in TA 98 in a range from 0.5 to 2 μL/plate (with and without S9). In strain TA 100 biologically relevant increases in revertant colony numbers were noted from 0.25 to 1 μL/plate (without S9) and at a dose of 0.5 μL/plate (with S9). Biologically relevant increases of revertant colony numbers were observed in TA 102 in a range from 0.5 to 5 μL/plate (without S9) and in a range from 0.25 to 5 μL/plate (with S9). The threshold value of 2.0 was exceeded and a maximum mutation factor of 8.2 was reached in tester strain TA 102 at a dose of 4 μL/plate (without S9).

The positive controls (NaN3, 4-NOPD, MMS and 2-AA) induced a distinct increase of revertant colonies indicating the validity of the experiments.

ADDITIONAL INFORMATION ON CYTOTOXICITY: Cytotoxic effects were noted in almost all tester strains evaluated in the two experiments.

Experiment 1: Toxic effects of the test item were observed in tester strain TA 98 at a dose of 5 μL/plate (with and without metabolic activation). In tester strains TA 100 and TA 1535 toxic effects of the test item were noted at a dose of 2.5 μL/plate and higher (without metabolic activation) and at a dose of 1 μL/plate and higher (with metabolic activation).

Experiment 2: In tester strain TA 98 toxic effects of the test item were observed at a dose of 4 μL/plate and higher (with and without metabolic activation). In tester strains TA 100 and TA 1535 toxic effects of the test item were noted at a dose of 2 μL/plate and higher (with and without metabolic activation). In tester strain TA 1537 toxic effects of the test item were observed at a dose of 4 μL/plate and higher (without metabolic activation) and at a dose of 3 μL/plate (with metabolic activation).

Remarks on result:

other: strain/cell type:

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
positive

In a guideline study, to GLP, rhodium (III) chloride hydrate solution exhibited mutagenic activity in a bacterial reverse mutation (Ames) assay using five Salmonella typhimurium strains (TA 98, 100, 1535, 1537 and 1538), when tested at up to cytotoxic concentrations in the presence and absence of a rat liver metabolic activation (S9) system.

Executive summary:

The potential of rhodium (III) chloride hydrate solution to induce gene mutations was studied in the Ames bacterial mutation assay (plate incorporation method) conducted according to OECD Test Guideline 471, and to GLP. The compound was tested in five strains of Salmonella typhimurium (TA98, TA100, TA102, TA1535 and TA1537).

 

Two independent experiments were carried out (each in triplicate), the first at concentrations of 0.0316, 0.1, 0.316, 1, 2.5 and 5 µL/plate and the second at 0.25, 0.5, 1, 2, 4 and 5 µL/plate, both with and without the presence of a rat microsomal activation fraction (S9).

 

No biologically relevant increases in mutant frequency were seen in either experiment with strains TA1535 or TA1537, either with or without S9. A dose-related increase in mutant frequency was observed with strains TA98, TA100 and TA102 at doses of 0.316 µL/plate or higher in experiment 1 and at 0.25 µL/plate and above in experiment 2, both with and without S9. The mutant frequency tended to be higher without S9. With the exception of TA1537 (in experiment 1), cytotoxicity was observed with all strains at concentrations of 2 µL/plate or higher, both with and without S9, and in addition at 1 µL/plate (in experiment 1), with S9.

 

Rhodium (III) chloride hydrate solution showed mutagenic activity in the Ames bacterial reverse mutation assay in strains TA98, TA100 and TA102 (with and without S9), indicating the ability of the test material to induce both base-pair and frameshift mutations in the gene sequence.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

In an in vivo guideline study, the compound induced a dose-related and statistically significant increase (compared to the vehicle controls) in the frequency of micronuclei in polychromatic erythrocytes of mice (5/sex/dose) following a single intraperitoneal injection at 200, 500, and 1000 mg/kg bw (Rodrigo, 2007b).

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 February - 15 March 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winklemann
- Age at study initiation: 6-12 weeks at start of acclimatisation (minimum 7 weeks at start of treatment)
- Weight at study initiation: Males, 27-32; females, 23-28 g
- Assigned to test groups randomly: Yes
- Fasting period before study: No data
- Housing: 5 animals of the same sex per cage. Macrolon Type III (Hereto) cage with lignocel bedding.
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 55 ± 10
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: No data

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: Sodium chloride
- Justification for choice of solvent/vehicle: Solvent was chosen “according to its relative non-toxicity for the animals”.

Details on exposure:

The test item was prepared and diluted in 0.9% NaCl within 1 hour before treatment. All anmals received a single volume intraperitoneal injection of 10 mL/kg bw

Duration of treatment / exposure:

Acute exposure

Frequency of treatment:

Single dose

Post exposure period:

44 and (for the highest dose only) 68 hours

Remarks:

Doses / Concentrations:
200, 500 and 1000 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide
- Justification for choice of positive control(s): No data
- Route of administration: Intraperitoneal
- Doses / concentrations: 40 mg/kg bw (10 mL/kg bw)

The solution is prepared on the day of administration.

Tissues and cell types examined:

Erythrocytes

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: Due to the results obtained in the range-finding study, 1000 mg/kg bw was chosen as the maximum tolerable dose (MTD). The MTD is defined as the dose producing signs of toxicity such as lethargy, palpebral closure, prone position etc. Higher doses are anticipated to produce lethality within 48 hr.

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Single intraperitoneal treatment; exposition times were 44 hr for all dose groups and 68 hr for the negative control and the highest dose group.

DETAILS OF SLIDE PREPARATION: Blood cells obtained from the tail vein were immediately fixed in “ultracold” methanol, washed in Hank’s balanced salt solution, and centrifuged at 600 x g for 5 minutes (supernatant was subsequently discarded).

METHOD OF ANALYSIS: Evaluation of all samples performed using a flow cytometer at least 16 hr after fixation. At least 10,000 immature erythrocytes were evaluated for the presence of micronuclei from each animal. The total numbers of polychromatic (immature) erythrocytes among total erythrocytes (relative PCE [rel. PCE]) was calulated in order to detect a cytotoxic effect.

Evaluation criteria:

A positive result is considered as either a dose-related increase in the number of micronucleated cells and/or a biologically relevant increase in the number of micronucleated cells for at least one of the dose groups.

A test item is considered to be negative if there is no biologically relevant and/or statistically significant increase in the number of micronucleated cells at any dose level.

Statistics:

Nonparametric Mann-Whitney Test (p<0.05)

Sex:

male/female

Genotoxicity:

positive

Toxicity:

yes

Remarks:

Observed at the highest two doses: effects at 1000 mg/kg bw included reduction of spontaneous activity, apathy, palpebral closure, rough fur and cramps. Slight toxicity was apparent at 500 mg/kg bw

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: 400 (one female), 1000 (3 mice/sex) and 2000 (one female) mg/kg bw
- Solubility: No data
- Clinical signs of toxicity in test animals: No toxic symptoms were seen in one female mouse following a single intraperitoneal injection of 400 mg/kg bw. In mice (3/sex) receiving an injection of 1000 mg/kg bw, systemic toxicity was seen (including reduction of spontaneous activity, prone position, cramps, apathy, palpebral closure and/or rough fur), but all survived 72 hours after treatment. One female received 2000 mg/kg bw, and died six hours after exposure.
- Evidence of cytotoxicity in tissue analyzed: No data
- Rationale for exposure: No data
- Harvest times: 30 minutes, 5 hours, 1 day and 2 days
- High dose with and without activation: 2000 mg/kg bw

RESULTS OF DEFINITIVE STUDY
- Types of structural aberrations for significant dose levels (for Cytogenetic or SCE assay): Not applicable
- Induction of micronuclei (for Micronucleus assay): All mean values of micronuclei formation following treatment with the test item were above the corresponding negative controls. A biologically relevant increase in the induction of micronucle was apparent. Further, this exhibited a dose-response relationship (see Table 1 for details).
- Ratio of PCE/NCE (for Micronucleus assay): The relative PCE was determined for each animal for the assessment of cytotoxicity. The negative control values noted at 44 hr were 2.13 for males and 1.57 for females while the analogous values at 68 hr were 2.67 and 2.62 respectively. These values were slightly above the range of the control data (1.38-2.08) as reported in the literature, aside from the 44-hr females. Relative PCE values for the treated groups were as follows (data for males and females respectively): 2.01 and 1.52 (0.2 MTD, 44 hr); 2.21 and 1.45 (0.5 MTD, 44 hr); 2.54 and 1.67 (1 MTD, 44 hr); 2.00 and 1.47 (1 MTD, 68 hr). These values were all within the range of the corresponding negative control.
- Appropriateness of dose levels and route: The dose levels were selected on the basis of the preliminary study
- Statistical evaluation: A statistically significant (p<0.05) increase in the frequency of blood cells with micronuclei was noted in the three test groups and the positive control group, when compared to the negative controls (see Table 2 for details).

Table 1: Percentage of blood cells with micronuclei

Dose group	Concentration (mg/kg bw)	Preparation time (h)	Male (%)	Female (%)
Vehicle control	0	44	0.31	0.20
Positive control	40	44	2.25	1.72
1 MTD	1000	44	2.57	2.48
0.5 MTD	500	44	1.65	1.52
0.2 MTD	200	44	0.90	0.97
Vehicle control	0	68	0.32	0.21
1 MTD	1000	68	0.73	0.56

MTD: Maximum tolerable dose

Table 2: Statistical significance at the 5% level (p<0.05)

Vehicle control versus test group	Preparation time (hr)	Significance		p-value
		Male	Female	Male	Female
Positive control	44	+	+	0.0079	0.0079
1 MTD	44	+	+	0.0159	0.0079
0.5 MTD	44	+	+	0.0079	0.0079
0.2 MTD	44	+	+	0.0317	0.0079
1 MTD	68	+	+	0.0159	0.0079

+: Significant

-: Not significant

The negative controls (24 and 48 hr) evaluated were within the range of the control data (0.15 -0.65%) reported in the literature.

The positive control (cyclophosphamide) induced a statistically significant increase in the induced micronucleus frequency (percentage of cells with micronuclei was 2.25 and 1.72% for males and females, respectively), thus demonstrating the validity of the assay.

The weight variation of treated animals (+/- 8.7 and 9.7% for males and females, respectively) did not exceed +/- 20% of the mean weight of each sex, thus fulfilling the data acceptance criteria.

Conclusions:

Interpretation of results (migrated information): positive
In an in vivo guideline study, to GLP, rhodium (III) chloride hydrate solution induced a dose-related and statistically significant increase in the frequency of micronuclei in polychromatic erythrocytes of mice (5/sex/dose) following a single intraperitoneal injection at 200, 500, and 1000 mg/kg bw, when compared to the vehicle controls.

Executive summary:

An in vivo mammalian erythrocyte micronucleus test (conducted according to OECD test guideline 474, and to GLP) was performed to assess the potential of rhodium (III) chloride hydrate, solution to induce micronuclei in the blood cells of mice.

 

Following a range-finding study, groups of young healthy mice (5/sex/dose) were administered the test material in sodium chloride solution at 0, 200, 500, and 1000 (the MTD) mg/kg bw by single intraperitoneal injection. Peripheral blood was obtained from the tail vein 44 hours and (at the highest dose only) 68 hours after treatment. At least 10,000 polychromatic (immature) erythrocytes (PCEs) were counted from each animal, and scored for the presence of micronuclei. Additionally, the proportion of PCEs among total erythrocytes was calculated for each animal (rel. PCE).

 

A biologically relevant and dose-related increase in the incidence of micronucleated polychromatic erythrocytes was observed in all treated groups compared to the concurrent vehicle controls. The rel. PCE values were in the range of the corresponding vehicle control. Clinical signs of toxicity were observed at the two highest doses. Cyclophosphamide (positive control), administered intraperitoneally at 40 mg/kg bw, induced a significant increase in micronucleus frequency, demonstrating the adequacy of the assay.

 

In conclusion, rhodium (III) chloride hydrate solution induced a dose-related and statistically significant increase in the frequency of micronuclei in erythrocytes of mice following a single intraperitoneal injection at 200, 500, and 1000 mg/kg bw, when compared to the vehicle controls.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Mode of Action Analysis / Human Relevance Framework

No data identified.

Additional information

The potential of rhodium (III) chloride hydrate solution to induce gene mutations was studied in the Ames bacterial mutation assay (plate incorporation method) conducted according to OECD Test Guideline 471, and to GLP. The compound was tested in five strains of Salmonella typhimurium (TA98, TA100, TA102, TA1535 and TA1537) at up to 5 µL/plate in two independent experiments (each in triplicate), both with and without S9. Rhodium (III) chloride hydrate solution showed mutagenic activity in strains TA98, TA100 and TA102 (with and without S9) indicating the ability of the test material to induce both base-pair and frameshift mutations in the gene sequence (Kraft, 2006a).

 

In another Ames bacterial mutation assay (plate incorporation method) conducted largely according to OECD Test Guideline 471, rhodium trichloride (hydrate) powder was tested in five strains of Salmonella typhimurium (TA98, TA100, TA 1535, TA1537 and TA1538) at up to 250 µg/plate in two independent experiments (each in triplicate), both with and without S9. Mutagenic activity was observed in strains TA98 and TA100 (with and without S9) (Wilmer, 1986).

 

In an OECD Test Guideline 476 study, conducted according to GLP, rhodium (III) chloride hydrate solution was tested for its ability to induce mutations at the thymidine kinase locus in an in vitro mouse lymphoma assay, both in the absence and presence of S9, at concentrations of up to 10 mM. Both with and without S9, a dose-related growth inhibition and a biologically relevant, dose-related, increase of the mutant frequency were observed. Colony sizing, conducted for the highest test concentrations, also indicated a potential clastogenic effect. In a guideline study (OECD Test guideline 476), conducted according to GLP, rhodium (III) chloride hydrate solution was tested for its ability to induce mutations at the thymidine kinase locus in an in vitro mouse lymphoma assay.

 

Mouse lymphoma (L5178Y) cells were exposed to test material for 4 hr, in the absence and presence of a rat liver metabolic activation system (S9), at concentrations of 2 to 10 mM and 1 to 10 mM respectively. Subsequently, cells were incubated for an expression and growth period of 72 hrs.

 

Both with and without S9, a dose-related growth inhibition and a biologically relevant, dose-related, increase of the mutant frequency were observed. Mutation factors for the various test concentrations were in the range of 2.02-15.46 and 5.33-26.60 with and without S9 respectively. Colony sizing, conducted for the highest test concentrations, also indicated a potential clastogenic effect. In conclusion, rhodium (III) chloride hydrate, solution is considered to be mutagenic in mammalian cells in vitro (Kraft, 2006b).

 

In a draft OECD Test Guideline 487 study, to GLP, rhodium (III) chloride hydrate solution was tested for the potential to induce micronuclei in Chinese Hamster lung fibroblasts (V79) at respective concentrations of up to 7.5 and 10 mM in the presence or absence of S9.The test item displayed evidence of clastogenicity and/or aneugenicity in Chinese Hamster lung fibroblasts (V79) (Rodrigo, 2007a).

 

In an in vivo mammalian erythrocyte micronucleus test (conducted according to OECD test guideline 474, and to GLP), mice (5/sex/dose) were administered rhodium (III) chloride hydrate solution in sodium chloride solution at 0, 200, 500, and 1000 (the MTD) mg/kg bw by single intraperitoneal injection. A biologically relevant and dose-related increase in the incidence of micronucleated polychromatic erythrocytes (PCEs) was observed in all treated groups compared to the concurrent vehicle controls. Clinical signs of toxicity were observed at the two highest doses (Rodrigo, 2007b).

In 2002, the Dutch Expert Committee on Occupational Standards (DECOS) reviewed the genotoxic and carcinogenic potential of rhodium and rhodium compounds. In its evaluation, the Committee found that several water-soluble rhodium (III) compounds were genotoxic in bacteria and in mammalian cells (DECOS, 2002). Based mainly on rhodium trichloride data, the Committee was of the opinion that all water-soluble rhodium (III) compounds are a human health concern in regards to these endpoints.

 

 

References

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.

Justification for classification or non-classification

The weight-of-the evidence indicates that the water-soluble rhodium (III) compounds should be considered as potentially mutagenic and, as such, rhodium trichloride (hydrate) is self-classified for germ cell mutagenicity (category 2) according to EU CLP criteria (EC 1272/2008).