Toxicological Implications of Platinum Group Elements (PGEs): A Systematic Review of In Vivo and In Vitro Studies Using Mammalian Models.

BACKGROUND: The six Platinum group metal elements (PGEs) comprising Ruthenium, Rhodium, Palladium, Platinum, Iridium and Osmium are grouped together in the periodic table. Human activities are mostly responsible for releasing PGEs into the environment. This systematic review focused on three PGEs with the greatest anthropogenic use, including in vehicle catalytic converters: Platinum (Pt), Palladium (Pd), and Rhodium (Rh). Consequently, these represent the greatest contributors to environmental pollution. The current review of in vivo toxicological studies (mammalian models) and in vitro cell exposure studies examined the potential harmful effects of these metalloids to mammalians, and their possible toxicity to human health. METHODS: We applied Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to conduct a comprehensive search and evaluation of records in the available literature published between 01/01/2009 and 01/15/2024 in four databases. PROSPERO code ID: CRD42024471558. Results concerning the health effects of PGEs were extracted from articles according to the inclusion and exclusion criteria. After screening the records for eligibility, 22 studies were included in the final analysis. RESULTS: This systematic review revealed that airborne PGEs significantly increased the activation of pathologic pathways in several human organs and/or perturbed various metabolic pathways. In view of the known pro-inflammatory and organ-degenerative effects of PGEs, the paucity of studies on the effect of PGEs on the central nervous system and on possible correlations with neurodegenerative diseases were particularly evident. CONCLUSIONS: The clinical complexity and chronic nature of PGE-related pathologies indicate that targeted research is essential. In light of the increasing incidence of non-communicable diseases, particular attention should be paid to the design of epidemiological studies and to environmental monitoring services.

Systematic Study on the Cytotoxic Potency of Commonly Used Dimeric Metal Precursors in Human Cancer Cell Lines.

The cytotoxicities of seven dimeric metal species of the general formula [M(arene)Cl2 ]2 , commonly used as precursors for complex synthesis and deemed biologically inactive, are investigated in seven commonly employed human cancer cell lines. Four of these complexes featured a ruthenium(II) core, where p-cymene, toluene, benzene and indane were used as arenes. Furthermore, the osmium(II) p-cymene dimer, as well as the Cp* dimers of rhodium(III) and its heavier analogue iridium(III) were included in this work (Cp*=1,2,3,4,5-pentamethylcyclopentadienide). While the cytotoxic potencies of the ruthenium(II) and osmium(II) dimers are very low (or not even detectable at applicable concentrations), surprising activity, especially in cells from ovarian malignancies (with one or two-digit micromolar IC50 values), have been found for the rhodium(III) and iridium(III) representatives. This publication is aimed at all researchers using synthetic procedures based on functionalization of these dimeric starting materials to rationalize changes in biological properties, especially cytotoxicity in cancer cells.

Bimetallic nanoparticles against multi-drug resistant bacteria.

We discovered two antibacterial bimetallic nanoparticles (AuRh and AuRu NPs), that possess antibacterial activities against multi-drug resistant (MDR) Gram-negative bacteria and can cure wound infections. None of the nanoparticles comprising just one of these metals elements shows any antibiotic activities.

Evaluation of phytotoxicity and cytotoxicity of industrial catalyst components (Fe, Cu, Ni, Rh and Pd): A case of lethal toxicity of a rhodium salt in terrestrial plants.

Until recently, chemical derivatives of platinum group metals have not been in a systematic direct contact with living organisms. The situation has changed dramatically due to anthropogenic activity, which has led to significant redistribution of these metals in the biosphere. Millions of modern cars are equipped with automotive catalytic converters, which contain rhodium, palladium and platinum as active elements. Everyday usage of catalytic technologies promotes the propagation of catalyst components in the environment. Nevertheless, we still have not accumulated profound information on possible ecotoxic effects of these metal pollutants. In this study, we report a case of an extraordinarily rapid development of lethal toxicity of a rhodium (III) salt in the terrestrial plants Pisum sativum, Lupinus angustifolius and Cucumis sativus. The growth stage, at which the exposure occurred, had a crucial impact on the toxicity manifestation: at earlier stages, RhCl3 killed the plants within 24 h. In contrast, the salt was relatively low-toxic in human fibroblasts. We also address phytotoxicity of other common metal pollutants, such as palladium, iron, nickel and copper, together with their cytotoxicity. None of the tested compounds exhibited phytotoxic effects comparable with that of RhCl3. These results evidence the crucial deficiency in our knowledge on environmental dangers of newly widespread metal pollutants.

Platinum, palladium, and rhodium in airborne particulate matter.

Measurable quantities of platinum, palladium, and rhodium, even in remote areas of the planet, evidence the global nature of pollution with these metals, mostly from catalytic converters of modern vehicles (other sources are jewellery production, chemical industry, and anticancer drugs). The amount of the platinum group metals (PGMs) emitted from automobile catalysts varies with the type, age, and condition of the engine and the catalyst, as well as the style of driving. Current literature suggests that the concentrations of these metals have increased considerably over the last twenty years, palladium concentrations in particular, as it has been proved more effective catalyst than platinum. However, whether and to what extent the emitted PGMs are toxic for people is still a controversy. The potential health risk from exposure to these elements is most likely for those living in urban environments with busy roads or along major highways. Because of the importance of PGMs and their trace levels in particulate matter, sensitive methods are required for reliable determination. This review discusses particular steps of analytical procedures for PGM quantification in airborne particulate matter and addresses the common preparation, detection, and determination methods.

Lessons learned from studies with the freshwater mussel Dreissena polymorpha exposed to platinum, palladium and rhodium.

The platinum group elements (PGE) platinum, palladium and rhodium gain increasing (eco-)toxicological interest due to their cumulative introduction into ecosystems. So far, most PGE exposure studies investigating biological availability, uptake and bioaccumulation of PGE as well as their effects on different toxicological endpoints were performed under non-standardized conditions which occasionally make an interpretation and comparison of the results difficult. Here we compare the results of different PGE exposure studies with zebra mussels (Dreissena polymorpha) showing influences due to the PGE source, the exposure medium, the exposure concentration and period as well as the test system. Problems associated to the performance and evaluation of these studies were identified and recommendations as well as needs for future studies are given. As nominal exposure concentrations often did not reflect real exposure conditions the reference for exposure concentration has to be chosen with caution, i.e. nominal versus quantified aqueous concentrations. The determination of bioaccumulation factors can be problematic when PGE concentrations in the exposure medium and in the test organism did not reach steady state even after several weeks of exposure. For future studies it would be advantageous to regularly correlating PGE bioaccumulation and biomarker responses to increase the knowledge on potential adverse effects of these metals, preferably using environmentally relevant PGE concentration scenarios. Many aspects discussed in the present study for zebra mussels and PGE can be transferred to other aquatic animals and other metals, respectively.

Rhodium metalloinsertor binding generates a lesion with selective cytotoxicity for mismatch repair-deficient cells.

The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family of rhodium metalloinsertors that bind DNA mismatches with high specificity and are preferentially cytotoxic to MMR-deficient cells. Here, we characterize the cellular mechanism of action of the most potent and selective complex in this family, [Rh(chrysi)(phen)(PPO)]2+ (Rh-PPO). We find that Rh-PPO binding induces a lesion that triggers the DNA damage response (DDR). DDR activation results in cell-cycle blockade and inhibition of DNA replication and transcription. Significantly, the lesion induced by Rh-PPO is not repaired in MMR-deficient cells, resulting in selective cytotoxicity. The Rh-PPO mechanism is reminiscent of DNA repair enzymes that displace mismatched bases, and is differentiated from other DNA-targeted chemotherapeutics such as cisplatin by its potency, cellular mechanism, and selectivity for MMR-deficient cells.

Assessment of sublethal endpoints after chronic exposure of the nematode Caenorhabditis elegans to palladium, platinum and rhodium.

The aim of this study was to investigate chronic effects of the platinum-group elements (PGE) palladium (Pd), platinum (Pt) and rhodium (Rh) on the nematode Caenorhabditis elegans. Aquatic toxicity testing was carried out according to ISO 10872 by determining 96 h EC50 values for sublethal endpoints, including growth, fertility and reproduction. Single PGE standard solutions were used as metal source. Based on the EC50 values for Pt, reproduction (96 h EC50 = 497 µg/L) was the most sensitive endpoint followed by fertility (96 h EC50 = 726 µg/L) and growth (96 h EC50 = 808 µg/L). For Pd, no precise EC50 values could be calculated due to bell-shaped concentration response curves, but the 96 h EC50 for reproduction ranged between 10 and 100 µg/L. Pd and Pt had effects on all endpoints. With raising element concentrations reproduction was inhibited first. At a certain concentration, fertility was also affected, which in turn had an additional effect on reproduction. Growth inhibition can also lead to a loss of fertility if the worms do not reach an appropriate body size to become fertile. Rhodium showed no inhibition of any endpoint between concentrations of 100 to 10,000 µg Rh/L. The results of this study allow the following order of PGE with respect to decreasing toxicity to C. elegans: Pd > Pt ¼ Rh.

Toxicity of platinum, palladium and rhodium to Daphnia magna in single and binary metal exposure experiments.

Mainly due to automobile traffic, but also due to other sources, the platinum group elements (PGE) platinum (Pt), palladium (Pd) and rhodium (Rh) are introduced into aquatic biotopes where they accumulate in sediments of lakes and rivers. However, the toxicity of these noble metals to aquatic organisms is not well understood and especially toxicity studies under standardized condition are lacking. Thus, the toxicity of Pt, Pd and Rh to Daphnia magna was tested in single metal exposure experiments according to OECD guideline 202. Immobility and lethality was recorded after 24 h and 48 h of exposure and EC50 and LC50, respectively, were determined. As the nominal exposure concentration of Pd differed significantly from the quantified concentration, the control of the real exposure concentration by chemical analysis is mandatory, especially for Pd. The toxicity decreased in the order Pd > Pt â‰« Rh with e.g. LC50(48 h) values of 14 µg/L for Pd, 157 µg/L for Pt and 56,800 µg/L for Rh. The exposure period had a clear effect on the toxicity of Pt, Pd and Rh. For Pt and Rh the endpoint immobility was more sensitive than the endpoint lethality whereas Pd toxicity was similar for both endpoints. The Hill slopes, which are a measure for the steepness of the concentration-response curves, showed no significant discrepancies between the different metals. The binary metal exposure to Pt and Pd revealed a more-than-additive, i.e. a synergistic toxicity using the toxic unit approach. The present study is a start to understand the toxicity of interacting PGE. The modes of action behind the synergistic effect are unclear.

Antitumor effect of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles on mice bearing breast cancer: a systemic toxicity assay.

Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.

In vitro permeation of platinum and rhodium through Caucasian skin.

During platinum group metals (PGMs) refining the possibility exists for dermal exposure to PGM salts. The dermal route has been questioned as an alternative route of exposure that could contribute to employee sensitisation, even though literature has been focused on respiratory exposure. This study aimed to investigate the in vitro permeation of platinum and rhodium through intact Caucasian skin. A donor solution of 0.3mg/ml of metal, K2PtCl4 and RhCl3 respectively, was applied to the vertical Franz diffusion cells with full thickness abdominal skin. The receptor solution was removed at various intervals during the 24h experiment, and analysed with high resolution ICP-MS. Skin was digested and analysed by ICP-OES. Results indicated cumulative permeation with prolonged exposure, with a significantly higher mass of platinum permeating after 24h when compared to rhodium. The mass of platinum retained inside the skin and the flux of platinum across the skin was significantly higher than that of rhodium. Permeated and skin retained platinum and rhodium may therefore contribute to sensitisation and indicates a health risk associated with dermal exposure in the workplace.

A histopathological study of Hudson River crayfish, Orconectes virilis, exposed to platinum group metals.

Platinum group metals (PGMs), such as platinum (Pt), palladium (Pd), and rhodium (Rh), are of increasing concern due to rising anthropogenic input to aquatic systems. In this study, PGMs' effects on bioaccumulation and histopathological changes were investigated using Orconectes virilis, a native Hudson River crayfish, as a model. Organisms were exposed to varying concentrations of water-soluble PGM salts for 10 days. The following experimental treatments were established: 0.0, 1.0, 5.0, 10.0 ppm Pt(IV), 1.0 ppm Rh(III), 1.0 ppm Pd(II), and a PGM mix (1.0 ppm Pt(IV), Rh(III), Pd(II) each) dissolved in raw Hudson River water. Metal content in the tissue samples were analyzed by a Spectro Genesis ICP-OES. The relationship between Pt, Pd, and Rh concentrations in different treatments and observed behavioral changes during the experiment was analyzed through One-Way ANOVA Student-Newman-Keuls multiple comparison test (P ≤ 0.05). Paraffin sections, 6-µm-thick, were prepared in standard eosin-Y and hematoxylin-2 stain and examined for histological abnormalities within hepatopancreas, exoskeleton, brain, and ganglia tissue. Statistically significant differences in PGM bioaccumulation were observed in all organs, with highest concentrations found in the hepatopancreas, 81.68 mg g(-1) dw in 1.0 ppm Pd treatment, 20.03 mg g(-1) dw Rh in 1.0 ppm Rh treatment, and 81.58 mg g(-1) dw Pt in the 5.0 ppm Pt treatment. Pt bioaccumulation in the hepatopancreas and exoskeleton decreased at the highest Pt exposure treatment, suggesting severe structural damage to tissue. Hyper-segmentation of vacuoles and swelling of the vascular channels were observed in the hepatocyte structure of the hepatopancreas. Exoskeleton exhibited visible bands in the exocuticle indicating demineralization. Brain and ganglia demonstrated extensive vacuolization. Behavioral analysis showed an increase of maximum response intensity over the experimental period within each treatment. Bioaccumulation and cellular abnormalities observed in exposed aquatic organisms raise concern of PGM bio-magnification within the food chain and its effect on the environment and human health.

The effects of rhodium on the renal function of female Wistar rats.

In recent years, the increased use of rhodium (Rh) as an active catalyst material in modern three-way automobile catalytic converters has led to a parallel rise in environmental levels of this metal. In spite of this, the literature contains few studies of the effects of Rh on human health. The aim of this study is to assess the effects of Rh on the renal function of female Wistar rats. Our findings show that sub-acute exposure to six increasing concentrations, ranging from 0.001 to 1 mg L(-1), of Rh (III) chloride hydrate in drinking water does not induce alterations in urinary albumin levels, while, at concentrations from 0.1 to 1 mg L(-1), a significant rise in urinary levels of Retinol Binding Protein is evident and an increasing trend in urinary ß2-microglobulin, which becomes significant at 1 mg L(-1), is observed. These results therefore demonstrate a nephrotoxic action of Rh at tubular level in a wide range of doses. Interestingly, because of the recent increase in environmental Rh levels, these findings may have relevant implications both for occupationally exposed subjects and for the general population, especially children.

Comparative study of hematological responses to platinum group metals, antimony and silver nanoparticles in animal models.

Research was conducted to examine the hematological effects of heavy metals (platinum (Pt ((IV))), palladium (Pd ((II))), rhodium (Rh ((III))), antimony (Sb ((III)) and Sb ((V))), and silver nanoparticles (AgNPs)) on white blood cells in mammalian (rat) and avian (chick embryo) models. These metals are used in many everyday products and are accumulating in our environment. Six-week old Sprague-Dawley female rats were treated daily by gavage and six-day old, fertile, specific pathogen-free white leghorn strain chick embryos' eggs were injected on days 7 and 14 of incubation with 0.0, 1.0, 5.0 or 10.0 ppm concentrations of Pt ((IV)) and a platinum group metal (PGM) mix of Pt ((IV)), Pd ((II)) and Rh ((III)). Chick embryos were also tested with 1.0 or 5.0 ppm of antimony compounds (Sb ((III)) and Sb ((V))) and 0.0, 15.0, 30.0, 60.0, or 100.0 ppm of silver nanoparticles (AgNPs). After 8 weeks of treatment, blood was obtained from the rats by jugular cut down and from chick embryos on day 20 of incubation by heart puncture. Blood smears were made and stained and a differential white cell count was performed on each. Examination of the smears revealed unconventional dose responses, stimulation of the immune response, and decreases in leukocyte production with various metals and concentrations. Chick embryos responded differently than rats to Pt and the PGM mix; suggesting that species differences and/or stage of development are important components of response to heavy metals. Route of administration of the metals might also influence the response. All of the heavy metals tested affected the immune responses of the tested animals as demonstrated by changes in the types and numbers of leukocytes. Our findings warrant further research to determine the mechanism of these effects and to understand and prevent toxicological effects in humans and other living organisms.

Study of the influence of platinum, palladium and rhodium on duckweed (Lemna minor).

OBJECTIVES: Road traffic pollutants and the residues of cytostatics that are widely used in anti-cancer therapy are a significant sources of platinum group elements (PGE; Pt, Pd and Rh) in environment. These metals can migrate into sewage and thus pollute surface waters. The purpose of our study was to evaluate the effect of PtCl4 on the antioxidant and enzymatic activity of duckweed (Lemna minor), a bioindicator of the aquatic environment. METHODS: The study was performed using a 7-day conventional test based on the OECD 221 (CSN EN ISO 20079)--Lemna sp. Growth Inhibition Test. We also conducted a microbiotest to analyse the effects of PtC4, PdCl2 and RhCl3 on the morphology and vegetative growth of colonies of this plant and compared their inhibitory effects during the microbiotest. RESULTS: We observed inhibition of colony growth and clear morphological changes. Antioxidant and enzymatic activities increased with platinum doses increased. The 168hEC50 of PtCl4 was 12.16 µM (95% confidence interval = 9.88-14.44) and the 168hEC50 of PdCl2 was 50.39 (95% confidence interval = 23.83-76.96). The greatest inhibition of growth by RhCl3 was observed at 25 µM. CONCLUSIONS: The obtained results suggest that L. minor phytotoxicity tests should be widely used in the biomonitoring.

Impact of platinum group elements on the soil invertebrate Enchytraeus crypticus.

OBJECTIVES: The platinum group elements (PGE) platinum (Pt), palladium (Pd), and rhodium (Rh) are used in automobile catalytic converters, from which they have been emitted into the environment to an increasing degree over the last 20 years. Despite the bioavailability of these metals to plants and animals, studies determining the effects of PGE on organisms are extremely rare. Enchytraeids are ecologically relevant soil organisms, due to their activity in decomposition and bioturbation in many soil types worldwide. DESIGN: The experiments were carried out as described in the OECD Guideline 220 [CSN EN ISO 16387--Soil quality--Effects of pollutants on Enchytraeidae (Enchytraeus sp.)--Determination of effects on reproduction]. The reproductive effects of platinum (PtCl4), palladium (PdCl2) and rhodium (RhCl3) were examined. The concentrations of PGE tested were as follows: 5, 10, 25, 50 and 100 µmol x L(-1) PdCl2; 50, 100, 150, 200 and 250 µmol x L-1 PtCl4/RhCl3. The EC50 (medium effective concentration) was determined after 28 days of exposure. The inhibition of the reproduction of PGE-exposed enchytraeids was compared against controls. RESULTS: Values of 28dEC50 of PtCl4, PdCl2 and RhCl3 amounted to 161.9 µmol x L(-1), 70.0 µmol x L(-1) and 246.6 µmol x L(-1), respectively. We can confirm that the relative order of toxicities is Pd (II) >Pt(IV) >>Rh(III). CONCLUSION: To the best of our knowledge, this is the first study to use Enchytraeus crypticus as an indicator species to assess the risk of soil contamination by platinum, palladium and rhodium. Results of this study contribute important data on the ecotoxicity of a rarely studied elements.

Impact of platinum group elements on the soil invertebrate Folsomia candida.

OBJECTIVES: Trace concentrations of the platinum group elements (PGE; Pt, Pd and Rh) are nowadays an irreplaceable part of environmental analysis and assessment. These rare elements are used as effective substances in automotive catalysts to reduce pollution by emissions originating from fuel combustion. Due to their harmful potential, it is necessary to monitor their content and behaviour in different samples. Effect assessment using ecotoxicological bioassays with organisms at different trophic levels can provide valuable pieces of information on the risk of chemical substances in the ecosystem. DESIGN: The experiments were carried out as described in the OECD Guideline 232 [CSN ISO 11267 - Soil quality - Inhibition of reproduction of Collembola (Folsomia candida) by soil pollutants]. The reproductive effects of palladium (PdCl2) and rhodium (RhCl3) were examined. Concentrations of PGE tested were as follows: 5, 10, 25, 50 and 100 µmol.L-1. The EC50 (medium effective concentration) was determined after 28 days of exposure. Inhibition of reproduction of PGE-exposed collembolans was compared against controls. RESULTS: Values of 28dEC50 of PdCl2 and RhCl3 amounted to 21.0 µmol.L-1 and 266.22 µmol.L-1, respectively. We can confirm that the relative order of toxicities is Pd (II) > Pt(IV) >> Rh(III). CONCLUSION: To the best of our knowledge, this is the first study to use Folsomia candida as an indicator species to assess the risk of soil contamination by palladium and rhodium. However, more toxicity data for various species are needed to evaluate the environmental risks of PGEs in soils.

Evaluating the abnormal ossification in tibiotarsi of developing chick embryos exposed to 1.0ppm doses of platinum group metals by spectroscopic techniques.

Platinum group metals (PGMs), i.e., palladium (Pd), platinum (Pt) and rhodium (Rh), are found at pollutant levels in the environment and are known to accumulate in plant and animal tissues. However, little is known about PGM toxicity. Our previous studies showed that chick embryos exposed to PGM concentrations of 1mL of 5.0ppm (LD50) and higher exhibited severe skeletal deformities. This work hypothesized that 1.0ppm doses of PGMs will negatively impact the mineralization process in tibiotarsi. One milliliter of 1.0ppm of Pd(II), Pt(IV), Rh(III) aqueous salt solutions and a PGM-mixture were injected into the air sac on the 7th and 14th day of incubation. Control groups with no-injection and vehicle injections were included. On the 20th day, embryos were sacrificed to analyze the PGM effects on tibiotarsi using four spectroscopic techniques. 1) Micro-Raman imaging: Hyperspectral Raman data were collected on paraffin embedded cross-sections of tibiotarsi, and processed using in-house-written MATLAB codes. Micro-Raman univariate images that were created from the ν1(PO4(3-)) integrated areas revealed anomalous mineral inclusions within the bone marrow for the PGM-mixture treatment. The age of the mineral crystals (ν(CO3(2-))/ν1(PO4(3-))) was statistically lower for all treatments when compared to controls (p≤0.05). 2) FAAS: The percent calcium content of the chemically digested tibiotarsi in the Pd and Pt groups changed by ~45% with respect to the no-injection control (16.1±0.2%). 3) Micro-XRF imaging: Abnormal calcium and phosphorus inclusions were found within the inner longitudinal sections of tibiotarsi for the PGM-mixture treatment. A clear increase in the mineral content was observed for the outer sections of the Pd treatment. 4) ICP-OES: PGM concentrations in tibiotarsi were undetectable (<5ppb). The spectroscopic techniques gave corroborating results, confirmed the hypothesis, and explained the observed pathological (skeletal developmental abnormalities) and histological changes (tibiotarsus ischemia and nuclear fragmentation in chondrocytes).

Effects of sub-acute exposure to rhodium (as Rh (III) chloride hydrate) on cytokines in female Wistar rats.

Quantitative changes in different cytokines were determined in serum of female Wistar rats exposed to Rhodium (III) chloride hydrate to evaluate its early effects on the immune system. Findings revealed an inhibitory effect of Rh salt since each cytokine, with the exceptions of IL-1α and IL-2 levels observed at the highest doses of exposure, was reduced compared to the controls and interestingly, the lowest doses induced the greatest inhibition. This generalized decrease of cytokine levels was not related to a specific cytokine pathway, and may suggest an anti-inflammatory role of Rh salt.

Rhodium and iridium salts inhibit proliferation and induce DNA damage in rat fibroblasts in vitro.

Environmental concentration of the platinum group elements is increased in the last years due to their use in automobile catalytic converters. Limited data are available on the effects of such elements at a cellular level and on their toxicity, especially for rhodium and iridium which have been more recently introduced in use. The toxic effects of rhodium and iridium salts were analyzed on a normal diploid rat fibroblast cell line in vitro. Both salts halted cell growth in a dose- and time-dependent fashion by inhibiting cell cycle progression, inducing apoptosis and modulating the expression of cell cycle regulatory proteins. In fact, they both caused an accumulation of cells in the G2/M phase of the cell cycle and affected the expression levels of pRb, cyclins D1 and E, p21(Waf1) and p27(Kip1). DNA strand breaks, as assessed by comet test, and an increase in the intracellular levels of reactive oxygen species also occurred in exposed cell cultures. These findings suggest a potential toxicity of both iridium and rhodium salts and emphasize the need for further studies to understand their effects at a cellular level to enable a better assessment of their toxic effects and to identify ways for their modulation and/or prevention.