This journal is © The Royal Society of Chemistry 2015 Metallomics Cite this: DOI: 10.1039/c4mt00240g The metallobiochemistry of ultratrace levels of platinum group elements in the rat E. Sabbioni, a S. Fortaner, b S. Manenti,* c F. Groppi, c M. Bonardi, c S. Bosisio d and M. Di Gioacchino a 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 (o100 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 Na 2 191 PtCl 4 , Na 2 103 PdCl 4 and Na 2 101m RhCl 6 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. Introduction Platinum (Pt), palladium (Pd) and rhodium (Rh) (Platinum Group Elements – PGEs) have historically been the metal components of the three-way catalytic converters of air pollution control devices mainly of cars and trucks. 1 In the form of highly dispersed particles with diameters in the 1–10 nm range 2 these auto- catalysts are unique in converting harmful hydrocarbons, carbon monoxide, and nitrogen oxide emissions from gasoline engines into less harmful CO 2 ,N 2 and H 2 O. 3 However, this type of device is not totally environmentally clean. The hot exhaust gases flowing through the catalytic converter cause abrasion and ablation of these latter, 4 leading to the release of micronic and nanosized PGEs particulates to air, roads, tunnels as well as roadside soil, 5 representing anthropogenic environmental pollutants for the general population. 6 Moreover, occupational exposure to PGEs occurs during mining, processing, refining and catalyst manufacture. 7 PGEs have other applications, representing a further source for human exposure. Platinum is used in biomedicine in anti- cancer drugs, 8 and as a component of pacemakers, catheters and defibrillators; 9 in industrial processes as a catalyst as in the polymerisation of olefins, and the refining of petroleum and ammonia oxidation; in electronic industries and glass manu- facturing; and in jewellery where it represents the second largest demand. 10 Palladium is used in electronic applications; in dentistry for dental crowns and bridges though they have been increasingly replaced by all-ceramic; in jewelry; in the chemical industry, in fuel cell technology; for coinage purpose; and in hydrogen purification. 11 Although catalytic converters use about 80% of the world’s rhodium production, this metal is applied in the glass industry, mostly for production of fiberglass a Aging Research Centre (Ce.S.I.), ‘‘G. d’Annunzio- University Foundation’’, Via dei Vestini-21, 66100 Chieti, Italy b European Commission, IHCP, JRC-Ispra, Via Fermi, 2749, 21027 Ispra, Varese, Italy c UNIMI e INFN Sezione di Milano LASA, Via F.lli Cervi-201, 20090 Segrate, Milan, Italy. E-mail: simone.manenti@mi.infn.it d Department of Radiation Science and Technology, Delft University of Technology, Mekelweg 15, 2629 JB Delft, The Netherlands Received 12th September 2014, Accepted 22nd December 2014 DOI: 10.1039/c4mt00240g www.rsc.org/metallomics Metallomics PAPER Published on 22 December 2014. Downloaded by Universita di Chieti -Pescara on 23/01/2015 07:39:08. View Article Online View Journal