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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In a bacterial reverse mutation (Ames) test, conducted according to OECD Test Guideline 471 and to GLP, rhodium trinitrate solution induced mutations in histidine-requiring strains TA98 and TA102 of Salmonella typhimurium when tested up to precipitating concentrations in the absence and presence of a rat liver metabolic activation system (S9), and in strain TA100 in the presence of S9 alone (McGarry, 2016).

 

In two previously conducted OECD Test Guideline 471 studies using rhodium trinitrate hydrate (solid), no evidence of mutagenic activity was observed in strains of S. typhimurium and Escherichia coli (Kraft et al., 2006; Verspeek-Rip, 2003).

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:
weight of evidence
Study period:
3 September - 22 October 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Conducted according to GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
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
Metabolic activation:
with and without
Metabolic activation system:
mammalian liver post-mitochondrial fraction (S9) from male Sprague Dawley rats induced with Aroclor 1254
Test concentrations with justification for top dose:
Range-finder and Experiment 1: 5, 16, 50, 160, 500, 1600 and 5000 µg/plate
Experiment 2: 160, 300, 625, 1250, 2500 and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: purified water
- Justification for choice of solvent/vehicle: well-known solvent/vehicle
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
Strain TA98 -S9 5 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
TA100, TA1535 -S9 2 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
TA1537 -S9 50 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
TA102 -S9 0.2 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
TA98 +S9 10 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
TA100, TA1535, TA1537 +S9 5 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
TA102 +S9 20 µg/plate
Details on test system and experimental conditions:
METHOD OF APPLICATION: Range-finder experiment (with and without S9), Experiment 1 (with and without S9) and Experiment 2 (without S9): in agar (plate incorporation); Experiment 2 (with S9): preincubation

DURATION
- Preincubation period: 20 minutes
- Exposure duration: 3 days

DETERMINATION OF CYTOTOXICITY
- Method: The background lawns of the plates were examined for signs of toxicity. Other evidence of toxicity may have included a marked reduction in revertants compared to the concurrent vehicle controls and/or a reduction in mutagenic response.
Evaluation criteria:
Acceptance Criteria: The assay was considered to be valid if all the following criteria were met:
1. The vehicle control counts fell within the laboratory’s historical control ranges
2. The positive control chemicals induced increases in revertant numbers of ≥1.5 fold (in strain TA102), ≥2 fold (in strains TA98 and TA100) or ≥3 fold (in strains TA1535 and TA1537) the concurrent vehicle control confirming discrimination between different strains, and an active S9 preparation.
Evaluation Criteria: For valid data, the test article was considered to be mutagenic if:
3. A concentration related increase in revertant numbers was ≥1.5-fold (in strain TA102), ≥2-fold (in strains TA98 and TA100) or ≥3-fold (in strains TA1535 and TA1537) the concurrent vehicle control values
4. The positive trend/effects described above were reproducible.
The test article was considered positive in this assay if both of the above criteria were met.
The test article was considered negative in this assay if [n]either of the above criteria were met.
Statistics:
None
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
positive
Remarks:
in Experiments 1 and 2
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 2500 and 5000 µg/plate, with and without S9
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with
Genotoxicity:
positive
Remarks:
in Experiments 1 and 2
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 5000 µg/plate, with S9
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
without
Genotoxicity:
negative
Remarks:
in Experiments 1 and 2
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 2500 and 5000 µg/plate, without S9
Vehicle controls validity:
valid
Untreated negative controls validity:
not valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
in Experiments 1 and 2
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 5000 µg/plate, with and without S9, plate incorporation; at 1250, 2500 and 5000 µg/plate, with S9, pre-incubation
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
in Experiments 1 and 2
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 5000 µg/plate, with and without S9, plate incorporation; at 1250, 2500 and 5000 µg/plate, with S9, pre-incubation
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
positive
Remarks:
in Experiment 1, with and without S9; in Experiment 2, with S9; also just below +ve threshold in Experiment 2, without S9
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 5000 µg/plate, with and without S9
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: Range-finder experiment: stock solution, 50 mg rhodium (III) nitrate solution/ml, pH 1.86; Experiments 1 and 2: stock solution, 50 mg rhodium (III) nitrate solution/ml, pH 1.63. "There is no evidence that low pH causes mutations in the Ames test" (Kirkland DJ (2012). Review of the effect of pH on the integrity of in vitro and in vivo genotoxicity assays. Report prepared for The Precious Metals & Rhenium Consortium).
- Precipitation: at 2500 and 5000 µg/plate, pre-incubation (Experiment 2, with S9, TA1535 and TA1537)

RANGE-FINDER EXPERIMENT: strains TA98, TA100 and TA102; evidence of toxicity in the form of a slight thinning of the background bacterial lawn was observed at 5000 µg/plate in all strains in the absence of S9

COMPARISON WITH HISTORICAL CONTROL DATA: mean vehicle control counts were comparable with the laboratory’s historical ranges; mean positive control counts were generally within or higher than the laboratory's historical control ranges (except TA102, experiment 1, without S9: 528 (historical control range 568-1290)
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
In a guideline study, to GLP, rhodium (III) nitrate solution induced mutations in histidine-requiring strains TA98 and TA102 of Salmonella typhimurium when tested up to precipitating concentrations in the absence and presence of a rat liver metabolic activation system (S9), and in strain TA100 in the presence of S9 alone.
Executive summary:

Rhodium trinitrate solution (12.9% rhodium) was tested in a bacterial reverse mutation (Ames) assay, conducted according to OECD Test Guideline 471 and to GLP. The test substance was assayed at test concentrations of up to 5000 µg/plate (it is unclear whether this relates to rhodium nitrate itself or to rhodium nitrate solution), in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of S. typhimurium, both in the absence and in the presence of metabolic activation by an Aroclor 1254-induced rat liver post-mitochondrial fraction (S9). Two experiments were conducted (each in triplicate): initially a plate incorporation protocol was used; the experiment was repeated using a pre-incubation protocol for those strains that were negative in the first experiment.

There was some evidence of toxicity at the highest concentration tested with the plate incorporation protocol and at 1250 -5000 µg/plate with the pre-incubation protocol. Vehicle and positive controls performed as expected. Strain TA98 was positive for mutagenicity in both experiments, with and without S9. Strain TA100 was positive for mutagenicity in both experiments with S9 alone. Strain TA102 was positive in both experiments with S9, in the first experiment without S9 and approaching the threshold for a positive response in the second experiment without S9. Strains TA1535 and TA1537 were negative in both experiments, with and without S9.

Under the conditions of this study rhodium (III) nitrate solution was clearly mutagenic.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

Rhodium trinitrate hydrate failed to induce a biologically relevant, or dose-related, increase in the incidence of micronuclei in the immature erythrocytes of the bone marrow of mice following administration by intraperitoneal injection at up to 80 mg/kg bw (Becker et al., 2007).

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: other: chromosome damage
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 August - 6 September 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Conducted according 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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)
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 Winkelmann
- Age at study initiation: 6-12 weeks (minimum of 7 weeks old at start of treatment)
- Weight at study initiation: males 28.2-31.7 g, females 24.5-29.4 g
- Assigned to test groups randomly: yes
- Housing: 5 animals of identical sex/Macrolon Type III cage with Lignocel bedding
- Diet: Altromin 1324 maintenance diet for rats and mice, totally-pathogen-free, frequency of administration not specified
- Water: ad libitum
- Acclimation period: “adequate acclimatisation period”

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): artificial light 06:00 – 18:00
Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: 0.9% sodium chloride
- Justification for choice of solvent/vehicle: relatively non-toxic for the animals
Details on exposure:
No data
Duration of treatment / exposure:
Single injection.
Frequency of treatment:
once
Post exposure period:
44 hrs (for all groups) and 68 hrs (for negative control and highest dose group only)
Remarks:
Doses / Concentrations:
16, 40 and 80 mg/kg bw given in a single volume of 10 mL/kg bw.
Basis:
other: Covering a range of doses from the maximum tolerable dose (ascertained in a pre-experiment) to slight toxicity.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
yes, historical
Positive control(s):
cyclophosphamide
- Justification for choice of positive control(s): no data
- Route of administration: intraperitoneal
- Doses / concentrations: 40 mg/kg bw given as a single dose in a volume of 10 mL/kg bw

Tissues and cell types examined:
Peripheral blood
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: 0.2, 0.5 and 1 x the maximum tolerable dose obtained from a pre-experiment for toxicity

TREATMENT AND SAMPLING TIMES (in addition to information in specific fields): animals treated once and the blood sampled from the tail vein 44 hrs (all groups) and 68 hrs (highest dose group and negative control) after treatment

DETAILS OF SLIDE PREPARATION: Blood cells were immediately fixed in ultracold methanol, washed, at least 16 hrs after fixation, in Hank’s balanced salt solution and centrifuged at 600 g for 5 min. The supernatant was discarded and the blood cell populations were discriminated using specific antibodies against CD71 and CD61 and the DNA content of the micronuclei was determined by the use of propidium iodide, a DNA specific stain

METHOD OF ANALYSIS: Evaluation was performed using a flow cytometer. Anti-CD71 antibodies were labelled with fluoresceinisothiocyanate and anti-CD61 antibodies were labelled with phycoerythrin. Particles were differentiated using Forward Scatter and Side Scatter parameters of the flow cytometer and fluorescence intensity was recorded. At least 10000 immature erythrocytes/animal were scored for the incidence of micronucleated immature erythrocytes. The ratio between immature and mature erythrocytes was determined to detect an eventually occurring cytotoxic effect of the test material and the results were expressed as relative PCE (proportion of polychromatic (immature) erythrocytes among total erythrocytes).
Evaluation criteria:
A positive result is determined by a:
- dose-related increase in the number of micronucleated cells and/or
- biologically relevant increase in the number of micronucleated cells for at least one of the dose groups.

The biological relevance as well as the statistical significance of the results are the criterion for interpretation and 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.

The data generated are considered acceptable if:
- the weight variation of the animals at the start of the study is minimal and does not exceed ±20% of the mean weight of each sex,
- the background frequency of micronucleated cells is in the normal range as reported in the literature or is within the laboratory’s historical range and
- the test system is sensitive to the known mutagen as judged by the results in the concurrent positive control animals.
Statistics:
The non-parametric Mann-Whitney test was used.
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: 25 (1 male), 80 (3 males and 3 females), 125 (1 male), 500 (1 male and 1 female), 1000 (1 female), 2000 (1 female) mg/kg bw
- Solubility: administered as 10 mL/kg bw
- Clinical signs of toxicity in test animals: Reduction of spontaneous activity and rough fur was seen at 25 mg/kg bw, with slight cramps and palpebral closure also being seen at 80 mg/kg bw. The mice receiving 125, 500 and 1000 mg/kg bw were euthanised 24, 30 and 48 hrs after treatment respectively in consideration of animal welfare reasons. At the top dose level, the mouse died within 23 hrs of the intraperitoneal injection.
- Evidence of cytotoxicity in tissue analyzed: no data
- Rationale for exposure: “According to the OECD guideline 474”. The selection of the highest dose was conducted in accordance with OECD guidelines 420 and 423, particularly with respect to selection of dose spacing and animal welfare aspects. The volume to be administered was compatible with the physiological space available.

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): The mean values of micronuclei observed for the negative control at 44 hrs were 0.25 and 0.22% for males and females respectively and at 68 hrs were 0.21 and 0.19% respectively. The mean values for the positive control after 44 hrs were 2.31 and 1.46% in the males and females respectively. In the treated mice, the mean values after 44 hrs were 0.34, 0.4 and 0.31% in the males and 0.31, 0.26 and 0.29% in the females treated with 16, 40 and 80 mg/kg bw respectively. After 68 hrs, the mean values observed in the highest treated group were 0.21 and 0.19% for the males and females respectively.
- Appropriateness of dose levels and route: Three dose levels covering a range from the maximum tolerable dose, as determined in a range-finding experiment, down to slightly toxic were used.
- Statistical evaluation: Slight increases in the percentage of cells with micronuclei compared to the corresponding vehicle controls were noted at the lowest test dose level in both sexes, in the mid-dosed female group and in both sexes at the top-dose level after 44 hrs but these were not found to be statistically significant. In the mid-dosed male group, the mean value was significantly increased when compared with the vehicle control but this was within the range of the historical control data. After 68 hrs, the values were comparable with the controls. Using the non-parametric Mann-Whitney Test, no statistically significant enhancement (p<0.05) of cells with micronuclei was noted in the treated groups, except for the male mid-dosed group. However, these values were within the range of the historical control data of the vehicle control.

Toxic effects were noted in all of the animals treated with 40 and 80 mg/kg bw and included a reduction in spontaneous activity, cramps, palpebral closure and rough fur. Only one male in the low dosed group showed similar toxic effects.

 

The mean values noted for the relative PCE in the vehicle control animals after 44 hrs were 1.73 for the males and 1.43 for the females and after 68 hrs were 2.16 and 1.97 for the males and females respectively, which were within the range of the historical control data. The mean values of the relative PCE in the low-, medium- and high-dosed groups were 1.56, 1.63 and 1.44 for males and 1.66, 1.74 and 1.32 for females respectively after 44 hrs and 1.82 and 2.12 for the high-dosed males and females after 68 hrs respectively. No statistically significant effects were noted and the mean values observed were all within the range of the historical control data of the vehicle control.

Conclusions:
Rhodium trinitrate hydrate failed to induce a biologically relevant, or dose-related, increase in the incidence of micronuclei in the immature erythrocytes of the bone marrow of mice following administration by intraperitoneal injection at up to 80 mg/kg bw.
Executive summary:

Rhodium trinitrate hydrate was studied for the ability to induce micronuclei in bone marrow cells (polychromatic erythrocytes; PCE) in mice, in a study conducted in accordance with OECD Test Guideline 474, and to GLP. Mice (5/sex/group) received rhodium trinitrate hydrate by intraperitoneal injection (in a volume of 10 mL/kg bw) at a single dose of 16, 40 and 80 mg/kg bw (the maximum tolerable dose) and peripheral blood samples were collected and analysed for the induction of micronuclei 44 and 68 hrs after treatment. The non-parametric Mann-Whitney Test was used, but both biological relevance and statistical significance were considered. At least ten thousand cells per animal were scored for micronuclei and the ratio of polychromatic to mature cells (relative PCE) was calculated as a measure of toxicity.

Only one male in the low-dose group showed signs of slight systemic toxicity (up to 2 hours after treatment) whereas all animals in the mid- and high-dosed groups showed adverse effects (for up to 24 hours). The relative PCE of any of the test dose groups was not statistically significantly different from the vehicle controls, whereas the incidence of micronucleated immature erythrocytes was statistically significantly increased in the mid-dosed males after 44 hrs. However, as this increase was within the range of the historical control data of the vehicle control and the other mean values showed no statistical significance over the control values, this effect was regarded as not biologically relevant.

It is concluded that rhodium trinitrate hydrate did not increase the incidence of micronuclei in mice after a single intraperitoneal dose of up to 80 mg/kg bw (Becker et al., 2007).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Mode of Action Analysis / Human Relevance Framework

No data identified.

Additional information

Rhodium trinitrate solution (12.9% rhodium) was tested in a bacterial reverse mutation (Ames) assay, conducted according to OECD Test Guideline 471 and to GLP. The test substance was assayed at test concentrations of up to 5000 µg/plate (it is unclear whether this relates to rhodium nitrate itself or to rhodium nitrate solution), in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of S. typhimurium, both in the absence and in the presence of S9. Two experiments were conducted (each in triplicate): initially a plate incorporation protocol was used; the experiment was repeated using a pre-incubation protocol for those strains that were negative in the first experiment. There was some evidence of toxicity at the highest concentration tested with the plate incorporation protocol and at 1250 -5000 µg/plate with the pre-incubation protocol. Vehicle and positive controls performed as expected. Strain TA98 was positive for mutagenicity in both experiments, with and without S9. Strain TA100 was positive for mutagenicity in both experiments with S9 alone. Strain TA102 was positive in both experiments with S9, in the first experiment without S9 and approaching the threshold for a positive response in the second experiment without S9. Strains TA1535 and TA1537 were negative in both experiments, with and without S9. Under the conditions of this study rhodium (III) nitrate solution was clearly mutagenic (McGarry, 2016).

 

In a previously conducted OECD Test Guideline 471 study, to GLP, rhodium trinitrate hydrate failed to induce an increase in mutation frequency in four S. typhimurium strains (TA1535, TA1537, TA98 and TA100) and Escherichia coli strain WP2 uvr A, either with or without S9, when tested at up to the limits of cytotoxicity (Verspeek-Rip, 2003).

 

A further OECD Test Guideline 471 study, to GLP, with rhodium trinitrate hydrate showed no increase in mutation frequency in five S. typhimurium strains (TA98, TA100, TA1535, TA1537 and TA102), either with or without S9, when tested at up to the limits of cytotoxicity (Kraft et al., 2006).  

 

In a limited Ames spot test, rhodium trinitrate failed to induce mutations in strains of S. typhimurium (TA98, TA100, TA1535, TA1537 and TA1538) or E. coli (B/r WP2 try- and WP2 hcr- try-) when tested at up to 10 mM in the absence of metabolic activation (Kanematsu et al., 1980).

 

In a limited bacterial rec assay with rhodium trinitrate, the observed difference in inhibition of bacterial growth was described by the investigators as a strong positive rec effect, indicating possible damage DNA (Kanematsu et al., 1980).

 

Rhodium trinitrate hydrate was studied for the ability to induce micronuclei in bone marrow cells (polychromatic erythrocytes; PCE) in mice, in a study conducted in accordance with OECD Test Guideline 474, and to GLP. Mice (5/sex/group) received rhodium trinitrate hydrate by intraperitoneal injection (in a volume of 10 mL/kg bw) at a single dose of 16, 40 and 80 mg/kg bw (the maximum tolerable dose) and peripheral blood samples were collected and analysed for the induction of micronuclei 44 and 68 hrs after treatment. The non-parametric Mann-Whitney Test was used, but both biological relevance and statistical significance were considered. At least ten thousand cells per animal were scored for micronuclei and the ratio of polychromatic to mature cells (relative PCE) was calculated as a measure of toxicity. Only one male in the low-dose group showed signs of slight systemic toxicity (up to 2 hours after treatment) whereas all animals in the mid- and high-dosed groups showed adverse effects (for up to 24 hours). The relative PCE of any of the test dose groups was not statistically significantly different from the vehicle controls, whereas the incidence of micronucleated immature erythrocytes was statistically significantly increased in the mid-dosed males after 44 hrs. However, as this increase was within the range of the historical control data of the vehicle control and the other mean values showed no statistical significance over the control values, this effect was regarded as not biologically relevant. It is concluded that rhodium trinitrate hydrate did not increase the incidence of micronuclei in mice after a single intraperitoneal dose of up to 80 mg/kg bw (Becker et al., 2007).

 

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 (in vitro and in vivo) 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

Based on the evidence of a clear mutagenic effect in the recently conducted bacterial reverse mutation (Ames) assay with rhodium trinitrate solution, on a precautionary basis rhodium trinitrate is classified for germ cell mutagenicity (category 2) under EU CLP criteria (EC 1272/2008).