, Volume 19, Issue 4, pp 419–427 | Cite as

Occurrence, use and potential toxic effects of metals and metal compounds

  • Ana-Maria Florea
  • Dietrich BüsselbergEmail author


Metals and metal compounds are constituents of our natural environment. Their distribution depends on the existence of natural sources (e.g. volcanoes or erosion) and their use in human’s activity. They are transformed naturally (e.g. by bacterial activity) with formation of organic species that influence their mobility and accumulation in abiotic as well as biotic systems. Up to date metal species are released into the environment questioning their influence on human health. Due to their widespread use in human activities such as industry, agriculture and even as medicine (e.g. As, Se, Pt), numerous health risks may be associated with exposure to these substances. Different reports on metal intoxication are documented and studies especially on neurotoxicity, genotoxicity, or carcinogenicity, are previously published in numerous articles. This mini-review gives an overview on the use and the actions of selected metal species of actual scientific concern, with a focus on neuronal cells.


metal toxicity arsenic lead mercury platinum tin neurotoxicity metal compounds 


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  1. Abdulla, M, Chmielnicka, J 1990New aspects on the distribution and metabolism of essential trace elements after dietary exposure to toxic metalsBiol Trace Elem Res232553CrossRefGoogle Scholar
  2. Akay, C, Thomas, C,3rd, Gazitt, Y. 2004Arsenic trioxide and paclitaxel induce apoptosis by different mechanismCell Cycle3324334PubMedGoogle Scholar
  3. Annau, Z, Cuomo, V 1988Mechanisms of neurotoxicity and their relationship to behavioral changesToxicology49219225PubMedCrossRefGoogle Scholar
  4. Atchison, WD, Hare, MF 1994Mechanisms of methylmercury-induced neurotoxicityFASEB J8622629PubMedGoogle Scholar
  5. Atkins, DS, Basha, MR, Zawia, NH 2003Intracellular signaling pathways involved in mediating the effects of lead on the transcription factor Sp1Int J Dev Neurosci21235244PubMedCrossRefGoogle Scholar
  6. Aykin-Burns N, Franklin EA, Ercal N. 2005 Effects of N-Acetylcysteine on Lead-Exposed PC-12 Cells. Arch. Environ. Contam. Toxicol. 49(1), 119–123Google Scholar
  7. Akila, R, Stollery, BT, Riihimaki, V 1999Decrements in cognitive performance in metal inert gas welders exposed to aluminiumOccup Environ Med56632639PubMedCrossRefGoogle Scholar
  8. Barbier, O, Jacquillet, G, Tauc, M, Cougnon, M, Poujeol, P 2005Effect of Heavy Metals on, and Handling by, the KidneyNephron Physiol99105110CrossRefGoogle Scholar
  9. Bargagli, R 2000Trace metals in Antarctica related to climate change and increasing human impactRev Environ Contam Toxicol166129173PubMedGoogle Scholar
  10. Barnes, JM, Stoner, HB 1958Toxic properties of some dialkyl and trialkyl tin saltsBr J Ind Med151522PubMedGoogle Scholar
  11. Barnes, JM, Stoner, HB 1959The toxicology of tin compoundsPharmacol. Rev11211231PubMedGoogle Scholar
  12. Basu, S, Ma, R, Boyle, PJ, Mikulla, B, Bradley, M, Smith, B, Basu, M, Banerjee, S 2004Apoptosis of human carcinoma cells in the presence of potential anti-cancer drugs: III. Treatment of Colo-205 and SKBR3 cells with: cis -platin, Tamoxifen, Melphalan, Betulinic acid, L-PDMP, L-PPMP, and GD3 gangliosideGlycoconj J.20563577PubMedCrossRefGoogle Scholar
  13. Bleecker, ML, Ford, DP, Lindgren, KN, Hoese, VM, Walsh, KS, Vaughan, CG 2005Differential effects of lead exposure on components of verbal memoryOccup Environ Med Mar62181187CrossRefGoogle Scholar
  14. Bellama, JM, Jewett, KL, Manders, WF, Nies, JD 1988A comparison of the rates of methylation of mercury(II) species in aquatic media by various organotin and organosilicon moietiesSci Total Environ733951PubMedCrossRefGoogle Scholar
  15. Bohrer, D, do Nascimento, PC, Becker, E, Carvalho, LM, Dessuy, M 2005Arsenic species in solutions for parenteral nutritionJPEN J Parenter Enteral Nutr2917PubMedCrossRefGoogle Scholar
  16. Brewster, UC, Perazella, MA 2004A review of chronic lead intoxication: an unrecognized cause of chronic kidney diseaseAm J Med Sci327341347PubMedCrossRefGoogle Scholar
  17. Bryan, GW, Langston, WJ 1992Bioavailability, accumulation and effects of heavy metals in sediments with special reference to United Kingdom estuaries: a reviewEnviron Pollut7689131PubMedCrossRefGoogle Scholar
  18. Büsselberg D, Platt B, Michael D, Carpenter DO, Haas HL. 1994 Mammalian voltage activated calcium channel currents are blocked by Pb2+, Zn2+ and Al3+. J Neurophys 71, 1491–1497.Google Scholar
  19. Büsselberg, D 1995Calcium channels as target sites of heavy metalsToxicol Lett82255261PubMedCrossRefGoogle Scholar
  20. Büsselberg, D 2004Actions of Metals on Membrane Channels, Calcium Homeostasis and Synaptic PlastivityHirner, AVEmons, H eds. Organometal and Metalloid Specism in the Environment: Analysis, Distribution, Processes and Toxicological EvaluationSpringerWien New York259281Google Scholar
  21. Canfield, RL, Gendle, MH, Cory-Slechta, DA 2004Impaired neuropsychological functioning in lead-exposed childrenDev Neuropsychol26513540PubMedCrossRefGoogle Scholar
  22. Cavaletti, G, Marmiroli, P 2004Chemotherapy-induced peripheral neurotoxicityExpert Opin Drug Saf3535546PubMedCrossRefGoogle Scholar
  23. Cavaletti, G, Bogliun, G, Marzorati, L, Zincone, A, Piatti, M, Colombo, N, Franchi, D, La Presa, MT, Dissoni, A, Buda, A, Fei, F, Cundari, S, Zanna, C 2004Early predictors of peripheral neurotoxicity in cisplatin and paclitaxel combination chemotherapyAnn Oncol1514391442PubMedCrossRefGoogle Scholar
  24. Centers for Disease Control and Prevention (CDC)2005aLead poisoning associated with use of litargirio – Rhode Island, 2003MMWR Morb Mortal Wkly Rep54227229Google Scholar
  25. Centers for Disease Control and Prevention (CDC)2005bMeasuring exposure to an elemental mercury spill – Dakota County, Minnesota, 2004MMWR Morb Mortal Wkly Rep54146149Google Scholar
  26. Chang, LW 1977Neurotoxic effects of mercury-a reviewEnviron Res14329373PubMedCrossRefGoogle Scholar
  27. Chattopadhyay, S, Bhaumik, S, Purkayastha, M, Basu, S, Nag Chaudhuri, A, Das Gupta, S 2002aApoptosis and necrosis in developing brain cells due to arsenic toxicity and protection with antioxidantsToxicol Lett1366576CrossRefGoogle Scholar
  28. Chattopadhyay, S, Bhaumik, S, Nag Chaudhury, A, Das Gupta, S 2002bArsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue cultureToxicol Lett1287384CrossRefGoogle Scholar
  29. Chuang, HY, Tsai, SY, Chao, KY, Lian, CY, Yang, CY, Ho, CK, Wu, TN 2004The influence of milk intake on the lead toxicity to the sensory nervous system in lead workersNeurotoxicology25941949PubMedCrossRefGoogle Scholar
  30. Clarkson, TW 1997The toxicology of mercuryCrit Rev Clin Lab Sci34369403PubMedCrossRefGoogle Scholar
  31. Clarkson, TW 1990Effects-general principles underlying the toxic action of metalsFriberg, GNordberg, GFVouk, VB eds. Handbook on the Toxicology of MetalsElsevierAmsterdam-New York-OxfordGoogle Scholar
  32. Cook, AG, Weinstein, P, Centeno, JA 2005Health effects of natural dust: role of trace elements and compoundsBiol Trace Elem Res103115PubMedCrossRefGoogle Scholar
  33. Devi, CB, Reddy, GH, Prasanthi, RP, Chetty, CS, Reddy, GR 2005Developmental lead exposure alters mitochondrial monoamine oxidase and synaptosomal catecholamine levels in rat brainInt J Dev Neurosci23375381PubMedCrossRefGoogle Scholar
  34. Donzelli, E, Carfi, M, Mieloso, M, Strada, A, Galbiati, S, Bayssas, M, Griffon-Etienne, G, Cavaletti, G, Petruccioli, MG, Tredici, G 2004Neurotoxicity of platinum compounds: comparison of the effects of cisplatin and oxaliplatin on the human neuroblastoma cell line SH-SY5YJ Neurooncol676573PubMedCrossRefGoogle Scholar
  35. Fent, K. 1996Ecotoxicology of organotin compoundsCrit Rev Toxicol261117PubMedCrossRefGoogle Scholar
  36. Fent, K 2003Ecotoxicological problems associated with contaminated sitesToxicol Lett140-141353365PubMedCrossRefGoogle Scholar
  37. Fergusson, JE, Kim, ND 1991Trace elements in street and house dusts: sources and speciationSci Total Environ100125150PubMedCrossRefGoogle Scholar
  38. Fitsanakis, VA, Aschner, M 2005The importance of glutamate, glycine, and gamma-aminobutyric acid transport and regulation in manganese, mercury and lead neurotoxicityToxicol Appl Pharmacol204343354PubMedCrossRefGoogle Scholar
  39. Florea, A-M, Dopp, E, Obe, G, Rettenmeier, AW 2004Genotoxicity of organometallic speciesHirner, AVEmons, H eds. Organic Metal and Metalloid Species in the Environment: Analysis, Distribution, Processes and Toxicological EvaluationSpringer-VerlagHeidelberg205219Google Scholar
  40. Florea, A-M 2005Toxicity of Alkylated Derivatives of Arsenic, Antimony and Tin: Cellular Uptake, Cytotoxicity, Genotoxic Effects, Perturbation of Ca2+ Homeostasis and Cell DeathShaker VerlagAachenGoogle Scholar
  41. Florea, A-M, Yamoah, EN, Dopp, E 2005aIntracellular calcium disturbances induced by arsenic and its methylated derivatives in relation to genomic damage and apoptosis induction: a mini-reviewEnvironm Health Perspect113659664CrossRefGoogle Scholar
  42. Florea, A-M, Dopp, E, Büsselberg, D 2005bElevated calcium transients in HeLa cells: types and levels of responseCell calcium37252258CrossRefGoogle Scholar
  43. Florea, A-M, Splettstoesser, F, Dopp, E, Rettenmeier, AW, Büsselberg, D 2005cModulation of intracellular calcium by trimethyltin chloride in human tumour cells: neuroblastoma SY5Y and cervix adenocarcinoma HeLa S3Toxicology21618CrossRefGoogle Scholar
  44. Florea, A-M, Büsselberg, D. 2005Toxic effects of metals: modulation of intracellular calcium homeostasisMat.-wiss.μ.Werkstofftech3614Google Scholar
  45. Gidlow, DA 2004Lead toxicityOccup Med (Lond)547681CrossRefGoogle Scholar
  46. Gielen M, Biesemans M, de Vos D, Willem RJ. 2000 Synthesis, characterization and invitro antitumor activity of di- and triorganotin derivatives of polyoxa- and biologically relevant carboxylic acids. Inorg. Biochem. 79, 139–145Google Scholar
  47. Gonzalez, P, Dominique, Y, Massabuau, JC, Boudou, A, Bourdineaud, JP 2005Comparative effects of dietary methylmercury on gene expression in liver, skeletal muscle, and brain of the zebrafish (Danio rerio)Environ Sci Technol3939723980PubMedCrossRefGoogle Scholar
  48. Grandjean, P, Nielsen, T 1979Organolead compounds: environmental health aspectsResidue Rev7297148PubMedGoogle Scholar
  49. Goulet, S, Dore, FY, Mirault, ME 2003Neurobehavioral changes in mice chronically exposed to methylmercury during fetal and early postnatal developmentNeurotoxicol Teratol25335347PubMedCrossRefGoogle Scholar
  50. Han, FX, Banin, A, Su, Y, Monts, DL, Plodinec, MJ, Kingery, WL, Triplett, GE 2002Industrial age anthropogenic inputs of heavy metals into the pedosphereNaturwissenschaften89497504PubMedCrossRefGoogle Scholar
  51. Hanlon, DP 1998Death after exposure to dimethylmercuryN Engl J Med33912431244PubMedCrossRefGoogle Scholar
  52. Harris, GK, Shi, X 2003Signaling by carcinogenic metals and metal-induced reactive oxygen speciesMutat Res533183200PubMedGoogle Scholar
  53. Huang, F, Schneider, JS 2004Effects of lead exposure on proliferation and differentiation of neural stem cells derived from different regions of embryonic rat brainNeurotoxicology2510011012PubMedCrossRefGoogle Scholar
  54. Hughes, MF 2002Arsenic toxicity and potential mechanisms of actionToxicol Lett133116PubMedCrossRefGoogle Scholar
  55. Humphrey, ML, Cole, MP, Pendergrass, JC, Kiningham, KK 2005Mitochondrial Mediated Thimerosal-Induced Apoptosis in a Human Neuroblastoma Cell Line (SK-N-SH)Neurotoxicology26407416PubMedCrossRefGoogle Scholar
  56. James, SJ, Slikker, W,3rd, Melnyk, S, New, E, Pogribna, M, Jernigan, S 2005Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursorsNeurotoxicology2618PubMedCrossRefGoogle Scholar
  57. Jenkins, SM, Ehman, K, Barone, S,Jr 2004Structure-activity comparison of organotin species: dibutyltin is a developmental neurotoxicant in vitro and in vivoBrain Res Dev Brain Res151112PubMedCrossRefGoogle Scholar
  58. Jonnalagadda, SB, Rao, PV 1993Toxicity, bioavailability and metal speciationComp Biochem Physiol C106585595PubMedGoogle Scholar
  59. Kalia, K, Flora, SJ 2005Strategies for safe and effective therapeutic measures for chronic arsenic and lead poisoningJ Occup Health47121PubMedCrossRefGoogle Scholar
  60. Landrigan, PJ 1994LeadRosenstock, lCullen, MR eds. Textbook of Clinical Occupational and Environmental MedicineSaunders CompanyPhiladelphiaGoogle Scholar
  61. Lehky, TJ, Leonard, GD, Wilson, RH, Grem, JL, Floeter, MK 2004Oxaliplatin-induced neurotoxicity: acute hyperexcitability and chronic neuropathyMuscle Nerve29387392PubMedCrossRefGoogle Scholar
  62. Leonhardt, R, Pekel, M, Platt, B, Haas, HL, Büsselberg, D 1996aVoltage-activated calcium channel currents of rat DRG neurons are reduced by mercuric chloride (HgCl2) and methylmercury (CH3HgCl)Neurotoxicology178591Google Scholar
  63. Leonhardt, R, Haas, HL, Büsselberg, D 1996bVoltage gated calcium potassium and sodium channel currents of rat DRG neurons are reduced by methylmercuryNaunyn Schmiedebergs Arch Pharmacol354532538CrossRefGoogle Scholar
  64. Liu, Y, Imai, H, Sadamatsu, M, Tsunashima, K, Kato, N 2005Cytokines participate in neuronal death induced by trimethyltin in the rat hippocampus via type II glucocorticoid receptorsNeurosci Res51319327PubMedCrossRefGoogle Scholar
  65. Magos, L, Butler, WH 1972Cumulative effects of methylmercury dicyandiamide given orally to ratsFood Cosmet Toxicol10513517PubMedCrossRefGoogle Scholar
  66. Marchetti, C 2003Molecular targets of lead in brain neurotoxicityNeurotox Res5221236PubMedCrossRefGoogle Scholar
  67. Markman, M 2003Toxicities of the platinum antineoplastic agentsExpert Opin Drug Saf2597607PubMedCrossRefGoogle Scholar
  68. McDonald, ES, Randon, KR, Knight, A, Windebank, AJ 2005Cisplatin preferentially binds to DNA in dorsal root ganglion neurons in vitro and in vivo: a potential mechanism for neurotoxicityNeurobiol Dis18305313PubMedCrossRefGoogle Scholar
  69. Milton, AG, Zalewski, PD, Ratnaike, RN 2004Zinc protects against arsenic-induced apoptosis in a neuronal cell line, measured by DEVD-caspase activityBiometals17707713PubMedCrossRefGoogle Scholar
  70. Morken, TS, Sonnewald, U, Aschner, M, Syversen, T 2005Effects of methylmercury on primary brain cells in mono and co-cultureToxicol Sci87169175PubMedCrossRefGoogle Scholar
  71. Moszczynski, P 1997Mercury compounds and the immune system: a reviewInt J Occup Med Envir Health10247258Google Scholar
  72. Needleman, H 2004Lead poisoningAnnu Rev Med55209222PubMedCrossRefGoogle Scholar
  73. Needleman, HL, Landrigan, PJ 1981The health effects of low level exposure to leadAnnu Rev Public Health2277298PubMedCrossRefGoogle Scholar
  74. Nordberg, GF, Goyer, RA, Clarkson, TW 1985Impact of effects of acid precipitation on toxicity of metalsEnviron Health Perspect63169180PubMedCrossRefGoogle Scholar
  75. Pekel, M, Platt, B, Büsselberg, D 1993Effects of mercury (Hg2+) on voltage activated calcium channel currents in Aplysia and cultured rat neuronsBrain Res632121126PubMedCrossRefGoogle Scholar
  76. Ratcliffe, HE, Swanson, MG, Fisher, LJ 1996Human exposure to mercury: a critical assessment of the evidence of adverse health effectsJ Toxicol Environ Health49221270PubMedCrossRefGoogle Scholar
  77. Ravindra, K, Bencs, L, Grieken, R 2004Platinum group elements in the environment and their health riskSci Total Environ318143PubMedCrossRefGoogle Scholar
  78. Reddy, GR, Suresh, A, Murthy, KS, Chetty, CS 2002Lead neurotoxicity: heme oxygenase and nitric oxide synthase activities in developing rat brainNeurotox Res43339PubMedCrossRefGoogle Scholar
  79. Rodriguez, VM, Jimenez-Capdeville, ME, Giordano, M 2003The effects of arsenic exposure on the nervous systemToxicol Lett145118PubMedCrossRefGoogle Scholar
  80. Sanfeliu, C, Sebastia, J, Cristofol, R, Rodriguez-Farre, E 2003Neurotoxicity of organomercurial compoundsNeurotox Res5283305PubMedCrossRefGoogle Scholar
  81. Schwartz, BS, Lee, BK, Bandeen-Roche, K, Stewart, W, Bolla, K, Links, J, Weaver, V, Stahnke, T, Richter-Landsberg, C 2004Triethyltin-induced stress responses and apoptotic cell death in cultured oligodendrocytesGlia46334344CrossRefGoogle Scholar
  82. Shafer, TJ, Atchison, WD 1991Methylmercury blocks N- and L-type Ca++ channels in nerve growth factor-differentiated pheochromocytoma (PC12) cellsJ Pharmacol Exp Ther258149157PubMedGoogle Scholar
  83. Shanker, G, Syversen, T, Aschner, M 2003Astrocyte-mediated methylmercury neurotoxicityBiol Trace Elem Res95110PubMedCrossRefGoogle Scholar
  84. Shenker, BJ, Guo, TL, Shapiro, IM 1998Low-level methylmercury exposure causes human T-cells to undergo apoptosis: evidence of mitochondrial dysfunctionEnviron Res7714959PubMedCrossRefGoogle Scholar
  85. Siegler, RW, Nierenberg, DW, Hickey, WF 1999Fatal poisoning from liquid dimethylmercury: a neuropathologic studyHum Pathol30720723PubMedCrossRefGoogle Scholar
  86. Sirois, JE, Atchison, WD 1996Effects of mercurials on ligand- and voltage-gated ion channels: a reviewNeurotoxicology176384PubMedGoogle Scholar
  87. Snoeij, NJ, Penninks, AH, Seinen, W 1987Biological activity of organotin compounds–an overviewEnviron Res44335353PubMedCrossRefGoogle Scholar
  88. Splettstoesser, F, Büsselberg, D 2005Calcium modulation in HeLa-S3 and U-2OS cells by the anti cancer agent cis-platinPfügers Archiv, EJP4491813Google Scholar
  89. Stahnke, T, Richter-Landsberg, C 2004Triethyltin-induced stress responses and apoptotic cell death in cultured oligodendrocytesGlia46334344PubMedCrossRefGoogle Scholar
  90. Stangle, DE, Strawderman, MS, Smith, D, Kuypers, M, Strupp, BJ 2004Reductions in blood lead overestimate reductions in brain lead following repeated succimer regimens in a rodent model of childhood lead exposureEnviron Health Perspect112302308PubMedCrossRefGoogle Scholar
  91. Stoner, HB, Barnes, JM, Duff, JI 1955Studies on the toxicity of alkyl tin compoundsBr J Pharmacol101625Google Scholar
  92. Takeuchi, T, Eto, K, Oyanag, S, Miyajima, H 1978Ultrastructural changes of human sural nerves in the neuropathy induced by intrauterine methylmercury poisoning (so-called fetal Minamata disease)Virchows Arch B Cell Pathol27137154PubMedGoogle Scholar
  93. Tanaka-Kagawa, T, Hanioka, N, Yoshida, H, Jinno, H, Ando, M 2003Arsenite and arsenate activate extracellular signal-regulated kinases 1/2 by an epidermal growth factor receptor-mediated pathway in normal human keratinocytesBr J Dermatol14911161127PubMedCrossRefGoogle Scholar
  94. Todd, A 2005Occupational lead exposure and longitudinal decline in neurobehavioral test scoresEpidemiology16106113PubMedCrossRefGoogle Scholar
  95. Torrente, M, Colomina, MT, Domingo, JL 2005Metal concentrations in hair and cognitive assessment in an adolescent populationBiol Trace Elem Res104215221PubMedCrossRefGoogle Scholar
  96. Trevisan, A, Borella-Venturini, M, Di Marco, L, Fabrello, A, Giraldo, M, Zanetti, E, Marzano, C, Fregona, D 2004Erythrocyte aminolevulinic acid dehydratase inhibition by cis-platinToxicol Lett152105110PubMedGoogle Scholar
  97. Tsunoda, M, Konno, N, Nakano, K, Liu, Y 2004Altered metabolism of dopamine in the midbrain of mice treated with tributyltin chloride via subacute oral exposureEnviron Sci11209219PubMedGoogle Scholar
  98. Wang, ZH, Miao, XP, Tan, W, Zhang, XR, Xu, BH, Lin, DX 2004Single nucleotide polymorphisms in XRCC1 and clinical response to platin-based chemotherapy in advanced non-small cell lung cancerAi Zheng23865868PubMedGoogle Scholar
  99. Webb, J 2005Use of the ecosystem approach to population health: the case of mercury contamination in aquatic environments and riparian populations, Andean Amazon, Napo River Valley, EcuadorCan J Public Health964446PubMedGoogle Scholar
  100. Weiss, B 1996Long ago and far away: a retrospective on the implications of MinamataNeurotoxicology17257263PubMedGoogle Scholar
  101. White, JS, Tobin, JM, Cooney, JJ 1999Organotin compounds and their interactions with microorganismsCan J Microbiol45541554PubMedCrossRefGoogle Scholar
  102. Wood, JM, Cheh, A, Dizikes, LJ, Ridley, WP, Rakow, S, Lakowicz, JR 1978Mechanisms for the biomethylation of metals and metalloidsFed Proc371621PubMedGoogle Scholar
  103. Zacks, R 1997Looking for alternatives. A scientist’s death raises questions about a toxic mercury compoundSci-Am277220Google Scholar

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© Springer 2006

Authors and Affiliations

  1. 1.Institut für Physiologie Universitätsklinium EssenUniversität Duisburg-EssenEssenGermany

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