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Biological Trace Element Research

, Volume 163, Issue 1–2, pp 2–10 | Cite as

Levels of Metals in the Blood and Specific Porphyrins in the Urine in Children with Autism Spectrum Disorders

  • Marta Macedoni-Lukšič
  • David Gosar
  • Geir Bjørklund
  • Jasna Oražem
  • Jana Kodrič
  • Petra Lešnik-Musek
  • Mirjana Zupančič
  • Alenka France-Štiglic
  • Alenka Sešek-Briški
  • David Neubauer
  • Joško Osredkar
Article

Abstract

The aim of the present study was to determine the levels of metals in blood (zinc (Zn), copper (Cu), aluminium (Al), lead (Pb) and mercury (Hg)), as well as the specific porphyrin levels in the urine of patients with autism spectrum disorder (ASD) compared with patients with other neurological disorders. The study was performed in a group of children with ASD (N = 52, average age = 6.2 years) and a control group of children with other neurological disorders (N = 22, average age = 6.6 years), matched in terms of intellectual abilities (Mann-Whitney U = 565.0, p = 0.595). Measurement of metals in blood was performed by atomic absorption spectrometry, while the HPLC method via a fluorescence detector was used to test urinary porphyrin levels. Results were compared across groups using a multivariate analysis of covariance (MANCOVA). In addition, a generalized linear model was used to establish the impact of group membership on the blood Cu/Zn ratio. In terms of blood levels of metals, no significant difference between the groups was found. However, compared to the control group, ASD group had significantly elevated blood Cu/Zn ratio (Wald χ 2 = 6.6, df = 1, p = 0.010). Additionally, no significant difference between the groups was found in terms of uroporphyrin I, heptacarboxyporphyrin I, hexacarboxyporphyrin and pentacarboxyporphyrin I. However, the levels of coproporphyrin I and coproporphyrin III were lower in the ASD group compared to the controls. Due to observed higher Cu/Zn ratio, it is suggested to test blood levels of Zn and Cu in all autistic children and give them a Zn supplement if needed.

Keywords

Autism Neurodevelopmental Children Metals Zinc Copper 

Notes

Acknowledgments

This study was financed by the Slovenian Research Agency (J3-9470-0312-06). The authors thank the children who participated in the study and their parents. We also thank the staff of the Clinical Department of Child, Adolescent and Developmental Neurology for their cooperation in the study and the Kobis Company for performing the analysis of urinary porphyrins.

References

  1. 1.
    American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders: DSM-IV-TR. American Psychiatric Association, WashingtonGoogle Scholar
  2. 2.
    American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders: DSM-5. American Psychiatric Association, WashingtonCrossRefGoogle Scholar
  3. 3.
    Autism and Developmental Disabilities Monitoring Network Surveillance Year (2008) Principal Investigators; Centers for Disease Control and Prevention (2012) Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ 61(3):1–19Google Scholar
  4. 4.
    Fombonne E (2009) Commentary: on King and Bearman. Int J Epidemiol 38:1241–1242PubMedCrossRefGoogle Scholar
  5. 5.
    King M, Bearman P (2009) Diagnostic change and the increased prevalence of autism. Int J Epidemiol 38:1224–1234PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Sinzig J, Walter D, Doepfner M (2009) Attention deficit/hyperactivity disorder in children and adolescents with autism spectrum disorder: symptom or syndrome? J Atten Disord 13:117–126PubMedCrossRefGoogle Scholar
  7. 7.
    Anholt GE, Cath DC, van Oppen P, Eikelenboom M, Smit JH, van Megen H, van Balkom AJ (2010) Autism and ADHD symptoms in patients with OCD: are they associated with specific OC symptom dimensions or OC symptom severity? J Autism Dev Disord 40:580–589PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T et al (2011) Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 68:1095–1102PubMedCrossRefGoogle Scholar
  9. 9.
    Rutter M (2005) Aetiology of autism: findings and questions. J Intellect Disabil Res 49:231–238PubMedCrossRefGoogle Scholar
  10. 10.
    Casey JP, Magalhaes T, Conroy JM, Regan R, Shah N, Anney R et al (2012) A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. Hum Genet 131:565–79PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Devlin B, Scherer SW (2012) Genetic architecture in autism spectrum disorder. Curr Opin Genet Dev 22:229–237PubMedCrossRefGoogle Scholar
  12. 12.
    Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN (2006) The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect 114:1119–1125CrossRefGoogle Scholar
  13. 13.
    Stoltenberg C, Schjølberg S, Bresnahan M, Hornig M, Hirtz D, Dahl C et al (2010) The autism birth cohort (ABC): a paradigm for gene-environment-timin research. Mol Psychiatry 15:676–680PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Schendel DE, Diguisseppi C, Croen LA, Fallin MD, Schieve LA, Wiggins LD (2012) The study to explore early development (SEED): a multisite epidemiologic study of autism by the centers for autism and developmental disabilities research and epidemiology (CADDRE) network. J Autism Dev Disord 42:2121–2140PubMedCrossRefGoogle Scholar
  15. 15.
    King MD, Fountain C, Dakhlallah D, Bearman PS (2009) Estimated autism risk and older reproductive age. Am J Public Health 99:1673–1679PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Shelton JF, Tancredi DJ, Hertz-Picciotto I (2010) Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Res 3:30–39PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Krakowiak P, Walker CK, Bremer AA, Baker AS, Ozonoff S, Hansen RL et al (2012) Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 129:1121–1128CrossRefGoogle Scholar
  18. 18.
    Wickramasinghe SN, Fida S (1994) Bone marrow cells from vitamin B12- and folate-deficient patients misincorporate uracil into DNA. Blood 83:1656–1661PubMedGoogle Scholar
  19. 19.
    Duthie SJ, Hawdon A (1998) DNA instability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes in vitro. FASEB J 12:1491–1497PubMedGoogle Scholar
  20. 20.
    Duthie SJ (1999) Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull 55:578–592PubMedCrossRefGoogle Scholar
  21. 21.
    Kapiszewska M, Kalemba M, Wojciech U, Milewicz T (2005) Uracil misincorporation into DNA of leukocytes of young women with positive folate balance depends on plasma vitamin B12 concentrations and methylenetetrahydrofolate reductase polymorphisms. A pilot study. J Nutr Biochem 16:467–478PubMedCrossRefGoogle Scholar
  22. 22.
    Fenech M (2010) Folate, DNA damage and the aging brain. Mech Ageing Dev 131:236–241PubMedCrossRefGoogle Scholar
  23. 23.
    Nakao LS, Augusto O (1998) Nucleic acid alkylation by free radical metabolites of ethanol. Formation of 8 (1-hydroxyethyl) guanine and 8-(2-hydroxyethyl)guanine adducts. Chem Res Toxicol 11:888–894PubMedCrossRefGoogle Scholar
  24. 24.
    Nakao LS, Fonseca E, Augusto O (2002) Detection of C8-(1-hydroxyethyl)guanine in liver RNA and DNA from control and ethanol-treated rats. Chem Res Toxicol 15:1248–1253PubMedCrossRefGoogle Scholar
  25. 25.
    Hori K, Miyamoto S, Yukawa Y, Muto M, Chiba T, Matsuda T (2012) Stability of acetaldehyde-derived DNA adduct in vitro. Biochem Biophys Res Commun 423:642–646PubMedCrossRefGoogle Scholar
  26. 26.
    Singh R, Gromadzinska J, Mistry Y, Cordell R, Juren T, Segerbäck D, Farmer PB (2012) Detection of acetaldehyde derived N(2)-ethyl-2’-deoxyguanosine in human leukocyte DNA following alcohol consumption. Mutat Res 737:8–11PubMedCrossRefGoogle Scholar
  27. 27.
    Kopf PG, Walker MK (2010) 2,3,7,8-tetrachlorodibenzo-p-dioxin increases reactive oxygen species production in human endothelial cells via induction of cytochrome P4501A1. Toxicol Appl Pharmacol 245:91–99PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Beedanagari SR, Taylor RT, Hankinson O (2010) Differential regulation of the dioxin-induced Cyp1A1 and Cyp1B1 genes in mouse hepatoma and fibroblast cell lines. Toxicol Lett 194:26–33PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Stejskalova L, Pavek P (2011) The function of cytochrome P450 1A1 enzyme (CYP1A1) and aryl hydrocarbonreceptor (AhR) in the placenta. Curr Pharm Biotechnol 12:715–730PubMedCrossRefGoogle Scholar
  30. 30.
    Shimada T, Inoue K, Suzuki Y, Kawai T, Azuma E, Nakajima T, Shindo M, Kurose K, Sugie A, Yamagishi Y, Fujii-Kuriyama Y, Hashimoto M (2002) Arylhydrocarbon receptor-dependent induction of liver and lung cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in genetically engineered C57BL/6J mice. Carcinogenesis 23:1199–1207PubMedCrossRefGoogle Scholar
  31. 31.
    Spink BC, Pang S, Pentecost BT, Spink DC (2002) Induction of cytochrome P450 1B1 in MDA-MB-231 human breast cancer cells by non-ortho-substituted polychlorinated biphenyls. Toxicol in Vitro 16:695–704PubMedCrossRefGoogle Scholar
  32. 32.
    Brown DJ, Van Overmeire I, Goeyens L, Denison MS, De Vito MJ, Clark GC (2004) Analysis of Ah receptor pathway activation by brominated flame retardants. Chemosphere 55:1509–1518PubMedCrossRefGoogle Scholar
  33. 33.
    Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R (2011) Residential proximity to freeways and autism in the CHARGE study. Environ Health Perspect 119:873–877PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hertiala J, Allayee H et al (2012) Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE case-control study. Am J Clin Nutr 96:80–89PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Shelton JF, Hertz-Picciotto I, Pessah IN (2012) Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environ Health Perspect 120:944–951PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R (2013) Traffic-related air pollution, particulare matter, and autism. JAMA Psychiatry 70:71–77PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Zerbo O, Iosif AM, Walker C, Ozonoff S, Hansen RL, Hertz-Picciotto I (2013) Is maternal influenza or fever during pregnancy associated with autism or developmetal delay? Results from the CHARGE study. J Autism Dev Disord 43:25–33PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Aschwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, van de Walter J (2011) Association of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. J Neuroimmunol 232:196–199CrossRefGoogle Scholar
  39. 39.
    Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J (2011) Altered T cell responses in children with autism. Brain Behav Immun 25:840–849PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Braunschweig D, Duncanson P, Boyce R, Hansen R, Ashwood P, Pessah IN, Hertz-Picciotto I, Van de Water J (2012) Behavioral correlates of maternal antibody status among children with autism. J Autism Dev Disord 42:1435–1445PubMedCrossRefGoogle Scholar
  41. 41.
    Shaw CA, Tomljenovic L (2013) Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity. Immunol Res 56:304–316PubMedCrossRefGoogle Scholar
  42. 42.
    Kern JK, Geier DA, Audhya T, King PG, Sykes LK, Geier MR (2012) Evidence of parallels between mercury intoxication and the brain pathology in autism. Acta Neurobiol Exp (Wars) 72:113–153Google Scholar
  43. 43.
    Landrigan PJ (2010) What causes autism? Exploring the environmental contribution. Curr Opin Pediatr 22:219–225PubMedCrossRefGoogle Scholar
  44. 44.
    Bjørklund G (2013) The role of zinc and copper in autism spectrum disorders. Acta Neurobiol Exp 73:225–236Google Scholar
  45. 45.
    Faber S, Zinn GM, Kern JC II, Kingston HMS (2009) The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders. Biomarkers 14:171–180PubMedCrossRefGoogle Scholar
  46. 46.
    Yasuda H, Yoshida K, Yasuda Y, Tsutsui T (2011) Infantile zinc deficiency: association with autism spectrum disorders. Sci Rep 1:129. doi: 10.1038/srep00129 PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 80:1611–1617PubMedGoogle Scholar
  48. 48.
    Bjørklund G (1991) Mercury in the dental office. Risk evaluation of the occupational environment in dental care (in Norwegian). Tidsskr Nor Laegeforen 111:948–951PubMedGoogle Scholar
  49. 49.
    Stejskal V (2013) Mercury-induced inflammation: yet another example of ASIA syndrome. Isr Med Assoc J 15:714–715PubMedGoogle Scholar
  50. 50.
    Brester MA (1988) Biomarkers of xenobiotic exposures. Ann Clin Lab Sci 18:306–317Google Scholar
  51. 51.
    Geier DA, Geier MR (2006) A prospective assessement of porphyrins in autistic disorders: a potential marker for heavy metal exposure. Neurotox Res 10:57–64PubMedCrossRefGoogle Scholar
  52. 52.
    Nataf R, Skorupka C, Amet L, Lam A, Springbett A, Lathe R (2006) Porphyrinuria in childhood autistic disorder: implications for enviromental toxicity. Toxicol Appl Pharmacol 214:99–108PubMedCrossRefGoogle Scholar
  53. 53.
    Wang L, Angley MT, Gerber JP, Sorich MJ (2011) A review of candidate urinary biomarkers for autism spectrum disorder. Biomarkers 16:537–552PubMedCrossRefGoogle Scholar
  54. 54.
    Kimbrough RD (1987) Porphyrins and hepatotoxicity. Ann N Y Acad Sci 514:289–296PubMedCrossRefGoogle Scholar
  55. 55.
    Van Meter JR, Tierney KR, Pittelkow MR (2011) Iron, genes, and viruses: the porphyria cutanea tarda triple threat. Cutis 88:73–76PubMedGoogle Scholar
  56. 56.
    Bonkovsky HL, Guo JT, Hou W, Li T, Narang T, Thapar M (2013) Porphyrin and heme metabolism and the porphyrias. Compr Physiol 3:365–401PubMedGoogle Scholar
  57. 57.
    Chauhan A, Chauhan V, Brown T (2010) Autism: oxidative stress, inflammation, and immune abnormalities. CRC Press, Boca RatonGoogle Scholar
  58. 58.
    Sarkany RP (1999) Porphyria. From Sir Walter Raleigh to molecular biology. Adv Exp Med Biol 455:235–241PubMedCrossRefGoogle Scholar
  59. 59.
    Gross U, Hoffmann GF, Doss MO (2000) Erythropoietic and hepatic porphyrias. J Inherit Metab Dis 23:641–661PubMedCrossRefGoogle Scholar
  60. 60.
    Woods JS (2005) The association between genetic polymorphisms of coproporphyrinogen oxidase and an atypical porphyrinogenic response to mercury exposure in humans. Toxicol Appl Pharmacol 206:113–120PubMedCrossRefGoogle Scholar
  61. 61.
    Cohen DJ, Johnson WT, Caparulo BK (1976) Pica and elevated blood lead level in autistic and atypical children. Am J Dis Child 130:47–48PubMedGoogle Scholar
  62. 62.
    Prasad AS (2012) Discovery of human zinc deficiency: 50 years later. J Trace Elem Med Biol 26:66–69PubMedCrossRefGoogle Scholar
  63. 63.
    Johnson F, Giulivi C (2005) Superoxide dismutases and their impact upon human health. Mol Aspects Med 26:340–352PubMedCrossRefGoogle Scholar
  64. 64.
    Nozik-Grayck E, Suliman HB, Piantadosi CA (2005) Extracellular superoxide dismutase. Int J Biochem Cell Biol 37:2466–2471PubMedCrossRefGoogle Scholar
  65. 65.
    Zimnicka AM, Maryon EB, Kaplan JH (2007) Human copper transporter hCTR1 mediates basolateral uptake of copper into enterocytes: implications for copper homeostasis. J Biol Chem 282:26471–26480PubMedCrossRefGoogle Scholar
  66. 66.
    DiGirolamo AM, Ramirez-Zea M (2009) Role of zinc in maternal and child mental health. Am J Clin Nutr 89:940S–945SPubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Plum LM, Rink L, Haase H (2010) The essential toxin: impact of zinc on human health. Int J Environ Res Public Health 7:1342–1365PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Suhy DA, Simon KD, Linzer DI, O’Halloran TV (1999) Metallothionein is part of a zinc-scavenging mechanism for cell survival under conditions of extreme zinc deprivation. J Biol Chem 274:9183–9192PubMedCrossRefGoogle Scholar
  69. 69.
    Banci L, Bertini I, Ciofi-Baffoni S, Kozyreva T, Zovo K, Palumaa P (2010) Affinity gradients drive copper to cellular destinations. Nature 465:645–648PubMedCrossRefGoogle Scholar
  70. 70.
    Kang YJ (2006) Metallothionein redox cycle and function. Exp Biol Med (Maywood) 231:1459–1467Google Scholar
  71. 71.
    Underwood EA (1977) Trace elements in human and animal nutrition, 4th edn. Academic, New YorkGoogle Scholar
  72. 72.
    Davis GK, Mertz W (1987) Copper. In: Mertz W (ed) Trace elements in human and animal nutrition, vol 1, 4th edn. Academic, San Diego, pp 301–364CrossRefGoogle Scholar
  73. 73.
    Wyatt AR, Wilson MR (2013) Acute phase proteins are major clients for the chaperone action of α2-macroglobulin in human plasma. Cell Stress Chaperones 18:161–170PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Russo AJ, deVito R (2011) Analysis of copper and zinc plasma concentration the efficacy of zinc therapy in individuals with Asperger’s syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS) and autism. Biomark Insights 6:127–133PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Carver PL (2013) Metal ions and infectious diseases. An overview from the clinic. Met Ions Life Sci 13:1–28PubMedCrossRefGoogle Scholar
  76. 76.
    Rainsford KD (1998) Copper and zinc in inflammatory and degenerative diseases. Kluwer Academic Publishers, DordrechtCrossRefGoogle Scholar
  77. 77.
    Goggs R, Vaughan-Thomas A, Clegg PD, Carter SD, Innes JF, Mobasheri A, Shakibaei M, Schwab W, Bondy CA (2005) Nutraceutical therapies for degenerative joint diseases: a critical review. Crit Rev Food Sci Nutr 45:145–164PubMedCrossRefGoogle Scholar
  78. 78.
    Strauss E, Shernan EM, Spreen O (2006) A compendium of neuropsychological tests, 3rd edn. Oxford University Press, New YorkGoogle Scholar
  79. 79.
    Parker SK, Schwartz B, Todd J, Pickering LK (2004) Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data. Pediatrics 114:793–803PubMedCrossRefGoogle Scholar
  80. 80.
    Boben D (2003) Slovenska standardizacija Ravenovih progresivnih matric: norme za CPM. SPM in APM. Center za psihodiagnostična sredstva, LjubljanaGoogle Scholar
  81. 81.
    Kiddie JY, Weiss MD, Kitts DD, Levy-Milne R, Wasdell MB (2010) Nutritional status of children with attention deficit hyperactivity disorder: a pilot study. Int J Pediatr 2010:767318. doi: 10.1155/2010/767318 PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Dufault R, Schnoll R, Lukiw WJ, Leblanc B, Cornett C, Patrick L, Wallinga D, Gilbert SG, Crider R (2009) Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children. Behav Brain Funct 5:44. doi: 10.1186/1744-9081-5-44 PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Hertz-Picciotto I, Green PG, Delwiche L, Hansen R, Walker C, Pessah IN (2009) Blood mercury concentrations in CHARGE Study children with and without autism. Environ Health Perspect 118:161–166PubMedCentralGoogle Scholar
  84. 84.
    Clarkson TW, Friberg L, Nordberg GF, Sager P (1988) Biological monitoring of metals. Plenum Press, New YorkCrossRefGoogle Scholar
  85. 85.
    IPCS—International Programme on Chemical Safety (1991) Environmental Health Criteria 118: inorganic mercury. WHO, GenevaGoogle Scholar
  86. 86.
    Vieira FM, Nakhle MC, Abrantes-Lemos CP, Cançado EL, dos Reis VM (2013) Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients. An Bras Dermatol 88:530–540PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Liu SW, Lien MH, Fenske NA (2010) The effects of alcohol and drug abuse on the skin. Clin Dermatol 28:391–399PubMedCrossRefGoogle Scholar
  88. 88.
    Peters HA, Gocmen A, Cripps DJ, Bryan GT, Dogramaci I (1982) Epidemiology of hexachlorobenzene-induced porphyria in Turkey: clinical and laboratory follow-up after 25 years. Arch Neurol 39:744–749PubMedCrossRefGoogle Scholar
  89. 89.
    Hornig M, Chian D, Lipkin WI (2004) Neurotoxic effects of postnatal thimerosal are mouse strain dependent. Mol Psychiatry 9:833–845PubMedCrossRefGoogle Scholar
  90. 90.
    Gerecht M, Austin DW (2011) The plausibility of a role for mercury in the etiology of autism: a cellular perspective. Toxicol Environ Chem 93:1251–1273CrossRefGoogle Scholar
  91. 91.
    Stamova B, Green PG, Tian Y, Hertz-Picciotto I, Pessah IN, Hansen R et al (2011) Correlations between gene expression and mercury levels in blood of boys with and without autism. Neurotox Res 19:31–48PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Thompson MR, Boekelheide K (2013) Multiple environmental chemical exposures to lead, mercury and polychlorinated biphenyls among childbearing-aged women (NHANES 1999-2004): body burden and risk factors. Environ Res 121:23–30PubMedCentralPubMedCrossRefGoogle Scholar
  93. 93.
    Sarigiannis DA, Hansen U (2012) Considering the cumulative risk of mixtures of chemicals – a challenge for policy makers. Environ Health 11 Suppl 1:S18. doi: 10.1186/1476-069X-11-S1-S18

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Marta Macedoni-Lukšič
    • 1
    • 2
  • David Gosar
    • 1
  • Geir Bjørklund
    • 3
  • Jasna Oražem
    • 1
  • Jana Kodrič
    • 1
  • Petra Lešnik-Musek
    • 1
  • Mirjana Zupančič
    • 1
  • Alenka France-Štiglic
    • 4
  • Alenka Sešek-Briški
    • 4
  • David Neubauer
    • 1
  • Joško Osredkar
    • 4
  1. 1.University Paediatric HospitalLjubljanaSlovenia
  2. 2.Institute of Autism Spectrum DisordersMedvodeSlovenia
  3. 3.Council for Nutritional and Environmental MedicineMo i RanaNorway
  4. 4.University Institute for Clinical Chemistry and Biochemistry, University Clinical CentreLjubljanaSlovenia

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