Module 3 - Strategic case studies in practice

ICH Q3D(R1) Guideline

assay when fibroblasts were incubated with Rh(3+) chloride hydrate for 2 or 24 hours (Iavicoli et al , 2012). RhCl 3 was genotoxic in the human lymphocyte micronucleus assay and increased DNA migration (Comet assay) in white blood cells (Migliore et al , 2002). o In a lifetime carcinogenicity bioassay in mice administered rhodium chloride, a higher incidence of tumors in treated animals compared to controls was noted at a dose of 5 ppm in drinking water. The data on tumors were too limited to allow a conclusion of carcinogenicity, a, similar to palladium (Schroeder and Mitchener, 1971). o The PEL TWA for rhodium (as Rh) metal fume and insoluble compounds is 0.1 mg/m 3 . The PEL TWA for soluble compounds of Rh is 0.001 mg/m 3 (UsD0L, 2013). Ruthenium o Several Ru complexes cause genotoxic responses in vitro in Salmonella typhimurium strains TA98 and TA100 (Monti-Bragadin et al , 1975; Yasbin et al , 1980; Benkli et al , 2009). o Oral absorption of Ru is low (about 4%); the half-life of a parenteral dose is about 200 days. Ingested ruthenium compounds are retained in bones (Furchner et al , 1971). Benkli K, Tunali Y, Cantürk S, Artagan O, Alanyali F. Cytotoxic and genotoxic effects of [Ru(phi) 3 ] 2+ evaluated by Ames/Salmonella and MTT methods. Europ J Medic Chem 2009;44:2601-5. Bünger J, Stork J, Stalder K. Cyto- and genotoxic effects of coordination complexes of platinum, palladium and rhodium in vitro . Int Arch Occup Environ Health 1996;69(1):33- 8. Furchner JE, Richmond CR, Drake GA. Comparative Metabolism of Radionuclides in Mammals - VII. Retention of 106Ru in the Mouse, Rat, Monkey and Dog. Health Phuysics 1971;21(3):355-65. Gaylarde P, Sarkany I. Ruthenium tetroxide for fixing and staining cytoplasmic membranes. Science 1968;161(3846):1157-8. Goossens A, Cattaert N, Nemery B, Boey L, De Graef E. Occupational allergic contact dermatitis caused by rhodium solutions. Contact dermatitis 2011;64:158-61. Iavicoli I, Fontana L, Marinaccio A, Calabrese EJ, Alimonti M, Pino A et al. The effects of iridium on the renal function of female Wistar rats. Ecotoxicol Environ Safety 2011;74:1795-9. Iavicoli I, Cufino V, Corbi M, Goracci M, Caredda E, Cittadini A et al. Rhodium and iridium salts inhibit proliferation and induce DNA damage in rat fibroblasts in vitro . Toxicol in vitro 2012;26(6):963-9. Luttrell WE, Giles CB. Toxic tips: Osmium tetroxide. J Chemical Health Safety 2007;Sept/Oct:40-1. McLaughlin AIG, Milton R, Perry KMA. Toxic manifestations of osmium tetroxide. Brit J Ind Med 1946;3:183-6. Migliore L, Frenzilli G, Nesti C, Fortaner S, Sabbioni E. Cytogenic and oxidative damage induced in human lymphocytes by platinum, rhodium and palladium compounds.  R EFERENCES

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