Sub-chronic palladium nanoparticle effects on the endocrine reproductive system of female Wistar rats: Preliminary data.

The technologically interesting properties of palladium nanoparticles (Pd-NPs) allowed their widespread industrial application, although concerns emerged on increasing general and occupational levels of exposure. In this context, to assess the toxicological behavior of Pd-NPs, and particularly their endocrine disruptive potential, has become a public health priority. Therefore, we evaluated Pd-NP impact on the female endocrine reproductive system of Wistar rats sub-chronically treated for 90 days with increasing doses of this xenobiotic (0.12, 1.2, and 12 µg/kg, administered at days 1, 30, and 60 for cumulative doses of 0.36, 3.6, and 36 µg/kg) via the intravenous route. In this regard, we investigated potential alterations in different sex hormone, for example, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone, progesterone, and testosterone, serum concentrations. All treated groups showed significantly greater levels of FSH compared to controls, suggesting a possible impact of Pd-NPs on the regulatory system that controls the normal physiology of female reproductive function. Although relevant, since obtained under sub-chronic, low-dose conditions of exposure resembling those encountered in real-world scenarios, the present results are preliminary and require confirmation as well as identification of the possible underlining molecular mechanisms. From a public and occupational health perspective, implications for the reproductive health of exposed subjects and the next generations of women exposed during their childbearing age or pregnancy should be elucidated. This information is essential to elaborate adequate preventive strategies for assessing and controlling possible Pd-NPs adverse effects on the endocrine system.

Platinum, palladium, rhodium, molybdenum and strontium in blood of urban women in nine countries.

BACKGROUND: There is little reliable information on human exposure to the metals platinum (Pt), palladium (Pd) and rhodium (Rh), despite their use in enormous quantities in catalytic converters for automobile exhaust systems. OBJECTIVES: To evaluate blood concentrations of Pt (B-Pt), Pd (B-Pd) and Rh (B-Rh) in women from six European and three non-European countries, and to identify potentially influential factors. In addition, molybdenum (Mo) and strontium (Sr) were analysed. METHODS: Blood from 248 women aged 47-61 was analysed by high resolution inductively coupled plasma mass spectrometry under strict quality control. RESULTS: The medians were: B-Pt 0.8 (range <0.6-5.2), B-Pd <5 (<5-9.3), B-Rh <0.4 (<0.4-3.6)ng/L and B-Mo 2.0 (0.2-16) and B-Sr 16.6 (3.5-49) µg/L. Two women with highly elevated B-Pt (242 and 60ng/L), previously cancer treated with cis-platinum, were not included in the data analysis. All elements varied geographically (2-3 times) (B-Pd P=0.05; all other elements P<0.001); variations within each area were generally 5-10 times. Traffic was not associated with increased concentrations. CONCLUSIONS: General population blood concentrations of Pt, Pd and Rh are within or below the single digit ng/L range, much lower than in most previous reports. This is probably due to improved analytical performance, allowing for more reliable information at ultra-trace levels. In general, Mo and Sr agreed with previously reported concentrations. All elements showed geographical and inter-individual variations, but no convincing relationships with self-reported traffic intensity were found. Pt from the antineoplastic drug cis-platinum is retained in the body for years.

The metallobiochemistry of ultratrace levels of platinum group elements in the rat.

The use of platinum, palladium and rhodium (Platinum Group Elements - PGEs) and the possibility of exposure to their ultratrace levels is increasing. In fact, the exponential development of metallic PGE-based nanoparticles (<100 nm in size) opens extraordinary perspectives in the areas of electrocatalysts and catalytic converters, magnetic nanopowders, polymer membranes, cancer therapy, coatings, plastics, nanofibres and textiles. Like other metal-based nanoparticles, exposure to PGEs nanoparticles may result in a release of ultratrace amounts of Pt, Pd, Rh ions in the body whose metabolic fate and toxicity still need to be evaluated. Furthermore, PGEs can act as allergic sensitizers by acting as haptens and inducing both type I and IV allergic reactions. In this work we studied the in vivo metabolic patterns of ultratrace levels of potent allergens and sensitizers PGE halogenated salts. (191)Pt, (103)Pd and (101m)Rh radioisotopes were prepared via cyclotron irradiation and used for radiolabelling Na2(191)PtCl4, Na2(103)PdCl4 and Na2(101m)RhCl6 salts. These anionic chlorocomplexes were intraperitoneally injected into rats (114 ng Pt kg(-1) bodyweight; 24 ng Pd kg(-1) b.w.; 16 ng Rh kg(-1) b.w.). At 16 h post-exposure, PGEs were poorly but significantly retained in all tissues analysed. Kidneys, spleen, adrenal gland, liver, pancreas and small intestine were the organs with the highest Pt, Pd, Rh concentrations. In the blood 30-35% of (103)Pd and (191)Pt and 10% of (101m)Rh were recovered in the plasma, mainly bound to albumin and to a less extent to transferrin. The hepatic and renal intracellular distribution showed the highest recovery of (191)Pt, (103)Pd and (101m)Rh in the nuclear fraction (liver) and in the cytosol (kidney). Chromatographic separation and ultrafiltration experiments on kidney and liver cytosols showed the strong ability of biochemical macromolecules to bind (191)Pt, (103)Pd and (101m)Rh, and being responsible for the retention of the three elements in the body. The link to macromolecules is the basis for the sensitizing capacity of PGEs.

Change in metabolic status of glutathione by palladium nitrate in blood components.

This piece of research work present the toxicological impact of varied concentrations of palladium nitrate [Pd (NO3)2] by changing the chemical status of glutathione and the way how glutathione plays its role in detoxification and conjugation processes of [Pd (NO(3))(2))] in whole blood components (plasma and cytosolic fraction). The impact of different concentration of [Pd (NO3)2] on reduced glutathione level in whole blood component (plasma and cytosolic fraction) were measured spectrophotometrically following Standard Ellman's method. Compared with control sample, significant decrease in the GSH content in whole blood components (plasma and cytosolic fraction) was obtained with various concentrations (100µM-1000µM) of palladium nitrate. Depleted GSH level was more pronounced with time incubation period (0-90) minutes. These finding shows that changes in the GSH status produced by palladium nitrate could either be due to palladium nitrate and glutathione( Pd-SG) complex formation or by conversion of reduce glutathione (2GSH + Pd(+2) - GSSG). This change in the GSH metabolic status provides information regarding the mechanism of palladium, in blood components.

Distribution and elimination of palladium in rats after 90-day oral administration.

This study determined the distribution in internal organs and the elimination routes in rats after oral administration of potassium hexachloro-palladate. Forty male Wistar rats were exposed for 90 days to 0, 10, 100 and 250 ng/mL of the palladium (Pd) salt in drinking water. Samples of urine and feces were collected on days 1, 30, 60 and 90, while organs (kidney, liver, lung, spleen and bones) and blood were collected at the end of the experiment. Quantification method was based on the sector-field inductively coupled plasma mass spectrometry. Results indicated that Pd ions were rapidly eliminated from the body. The principal excretion was through the feces (650 +/- 72.7 ng/g dry weight, at the Pd dose of 250 ng/mL), but at the higher dosing Pd was also eliminated through the urine (6.16 +/- 1.91 ng/mL for the Pd intake of 250 ng/mL). A clear relationship between the Pd ingested dose and the Pd excretion amount was observed mainly in the feces. Absorbed Pd was mostly found in the kidney of rats (124.4 +/- 23.0 ng/g dry weight, following the highest dose), while liver, lung, spleen and bones did not accumulate the metal. At the higher dosing, Pd content in the kidney raised proportionally with the Pd dose. Our findings may be useful to help in the understanding of the health impact of Pd dispersed in the environment as well as in identifying appropriate biological indices of Pd exposure.

Release of palladium from biomechanical prostheses in body fluids can induce or support PD-specific IFNgamma T cell responses and the clinical setting of a palladium hypersensitivity.

The increased use of Palladium (Pd) for biomedical applications, which has more than doubled in the last ten years, appears to be associated with an increased frequency of adverse reactions to Pd. The aim of this study is to investigate the relationship between the implant of a biomechanical apparatus containing Pd and the setting of a hypersensitivity to Pd by determining the levels of the metal released in biological fluids, assessing the effects of Pd on peripheral blood mononuclear cell (PBMC) cytokine production and exploring the clinical setting of skin sensitization. Of a total of 3,093 subjects examined in 2006, sensitization to Pd alone or in association with nickel (Ni) was observed in 1.6% and 13.03% of the individuals, respectively. Of these, a group of six subjects positive to Pd and negative to Ni at patch testing were selected on the basis of the oral clinical symptoms in order to measure both the levels of Pd in biological fluids and the degradation of the dental prostheses. Specific Pd measurements were carried out on salivary fluid, urine and serum samples by High Resolution Inductively Coupled Plasma-Mass Spectrometry. In addition, the degradation of the dental prostheses was assessed by both a leaching test and an analysis of the micro morphology of orthodontic prostheses. The induction of IFN-gamma production by Pd was assessed in PBMC by the ELISpot assay. Skin sensitization to Pd was evaluated by patch testing and clinical examination. Ten healthy subjects were comparatively tested as controls. We found a specific induction of an IFN-gamma response by Pd in PBMC collected from all the subjects positive to Pd at patch testing. On the contrary, control subjects did not show any response to Pd as assessed by IFN-gamma ELISpot assay or by skin testing. Remarkably, the levels of Pd in all biological samples (saliva, sera, urine) were significantly higher in Pd-sensitized patients than in those collected from controls, reaching the highest concentrations in the urine. The leaching studies gave additional evidence that the dental appliances can release measurable levels of Pd in saliva. Oral clinical symptoms in patients with Pd dental prostheses were associated with measurable levels of Pd in the biological fluids, the induction of Pd-specific IFN-gamma responses in PBMC and the clinical evidence of skin sensitization to Pd. These data suggest that dental appliances may represent an active source of Pd in the body, and this, in turn, can favour the clinical setting of a hypersensitivity to this metal.

Assessment of workers' exposure to palladium in a catalyst production plant.

Airborne particulate matter was collected and biomonitoring of workers was performed by sampling blood, urine and hair of 84 exposed subjects, 17 occasionally exposed employees, 21 controls from administrative offices and 25 unexposed people (external controls). Determination of Pd was performed using Quadrupole and High Resolution Inductively Coupled Plasma Mass Spectrometry. The Production of Catalysts Department and the Refining Service presented the highest levels of Pd in airborne matter collected by means of an area sampler. The highest level of soluble Pd (1.66 microg m(-3)) was found in the Production of Catalysts Department. The highest concentration of Pd in airborne matter, collected by means of personal devices (7.90 microg m(-3)) was found in the Refining Service. Hair showed a clear distribution pattern among departments, with values ranging from 0.60 to 5.54 microg g(-1). Administrative workers presented blood levels of Pd between 2 and 500 times higher than external controls. Only urine levels correlated with the measurements of airborne Pd collected with personal devices. A very strong association between airborne Pd collected by personal devices and Pd levels in hair (r(2)= 0.569, with p< or = 0.01) and urine (r(2)= 0.684, with p< or = 0.01) was found. On the basis of these findings: (i) blood results appear to be an unsuitable biological marker for occupational exposure to Pd; (ii) urine could be considered as a satisfactorily responsive bio-marker for occupational monitoring; and (iii) hair cannot be considered a good index of time-related exposure.

Biomonitoring of titanium, mercury, platinum, rhodium and palladium in dental health care workers.

BACKGROUND: In dentistry, titanium, mercury, platinum, rhodium and palladium are used to produce dental fillings. Therefore, dental workers who apply such materials may be exposed to these metals. METHODS: The study concerned 40 healthy subjects-20 controls and 20 dental health care workers-to determine serum and urinary levels of the aforementioned metals by inductively coupled plasma mass spectrometry. RESULTS: Mean urinary and serum titanium did not reveal statistically significant differences in the two groups. The very low urinary and serum levels of mercury, platinum, rhodium and palladium prevented us from making a statistical evaluation between the two groups. CONCLUSIONS: We did not find a significant increase in serum and urinary titanium levels in dental health care workers. Measurement of mercury, platinum, rhodium and palladium in urine and serum was not useful in determining occupational exposure.

Gold and palladium burden from dental restoration materials.

From 81 volunteers (16 without dental restorations, 65 with gold crowns or inlays) samples of saliva before and after chewing gum, blood, serum, urine and faeces were taken and analysed for gold (Au) and palladium (Pd). The Au concentration in all analysed biomonitors correlates significantly to the number of teeth with gold restorations. For Pd the correlations were still significant, but weaker than for Au. Persons with gold restorations show maximal Au and Pd concentrations, 10(2)-10(3) higher than the background burden. The calculated maximal daily Au load in saliva (1.38 mg Au per day) reaches the range of an oral Au therapy for rheumatoid arthritis with 6 mg Auranofin (= 1.74 mg Au per day). During this therapy severe and frequent side effects are reported. In contrast, the Au concentration in serum maximally reached from Au restorations, amounts to only approximately 1/20 of the Au level during arthritis therapy. But even under subtherapeutic doses of 1 mg Auranofin/day severe side effects have been reported (4 out of 56 cases). The mean Au blood concentration from 1 mg Auranofin daily was only 3 times higher than our maximum value. A toxicological classification of the Pd values is difficult, because no toxicological threshold limit has been established, especially for the low-level long-term burden with Pd.

Determination of platinum, palladium, and lead in biological samples by atomic absorption spectrophotometry.

A flameless atomic absorption method for the coextraction of platinum and palladium from biological and environmental samples by high molecular weight amine (HMWA) is given. Also, methods for lead determination in biological samples by use of extraction flameless analysis and direct aspiration-flame analysis are reported. A study of lead contamination of Vacutainer tubes is given.