Neurochemical Research

, Volume 42, Issue 10, pp 2673–2685 | Cite as

Abating Mercury Exposure in Young Children Should Include Thimerosal-Free Vaccines

Review Paper

Abstract

Pediatric immunization is essential to prevent, control and eradicate children`s infectious diseases. Newborns and infants in less developed countries have a concentrated schedule of Thimerosal-containing vaccines (TCVs); pregnant mothers are also immunized with TCVs. Metabolic changes during early development are demonstrably an important risk factor for ethylmercury (EtHg) effects on neurodevelopment, while exposure to Thimerosal sensitizes susceptible individuals to life-long contact dermatitis. Concerns regarding toxicity of Hg have moved rich nations to withdraw it from medicines and, in particular, Thimerosal from pediatric vaccines; it has been more than 20 years since rich countries started using Thimerosal-free vaccines. TCVs and Thimerosal-free vaccines show dissimilar profiles of adverse effects. Thimerosal-free vaccines have shown a decrease in contact dermatitis, while TCVs showed a significant association with increased risk of tic disorders; in some circumstances, EtHg in combination with other neurotoxic substances negatively impacted neurobehavioral tests. In studies that explored vaccines and risk of tics, Thimerosal was a necessary factor. However, when the binary exposure to organic Hg forms (TCV–EtHg and fish-MeHg) was considered, effects on neurobehavioral tests were inconsistent. Conclusions: (a) The indiscriminate use of pediatric-TCVs in less developed countries carries an unjustifiable and excessive EtHg exposure with an unnecessary risk of neurotoxicity to the developing brain; (b) measurable benefits (of Thimerosal-free) and measurable risks of tic disorders have been associated with the (Thimerosal-containing) type of vaccine; (c) Thimerosal-free vaccines are clinically and toxicologically justifiable and they should be available to children in less developed countries.

Keywords

Thimerosal-free vaccines Ethylmercury Infants Contact dermatitis Tic disorders 

Notes

Funding

This study was supported by a CNPq (Brazil).

Compliance with Ethical Standards

Competing interest

The authors declare that they have no competing interests.

References

  1. 1.
    Dórea JG, Farina M, Rocha JB (2013) Toxicity of ethylmercury (and Thimerosal): a comparison with methylmercury. J Appl Toxicol 33:700–711PubMedCrossRefGoogle Scholar
  2. 2.
    Geier DA, King PG, Hooker BS et al (2015) Thimerosal: clinical, epidemiologic and biochemical studies. Clin Chim Acta 444:212–220PubMedCrossRefGoogle Scholar
  3. 3.
    Hessel L (2003) [Mercury in vaccines]. Bull Acad Natl Med 187:1501–1510PubMedGoogle Scholar
  4. 4.
    Dórea JG (2017) Low-dose Thimerosal in pediatric vaccines: adverse effects in perspective. Environ Res 152:280–293PubMedCrossRefGoogle Scholar
  5. 5.
    Wigzell H (1990) Difficulties in replacing mercury as a preservative in bacterial vaccines. Lakartidningen 87:621PubMedGoogle Scholar
  6. 6.
    Sykes LK, Geier DA, King PG et al (2014) Thimerosal as discrimination: vaccine disparity in the UN Minamata Convention on mercury. Indian J Med Ethics 11:206–218PubMedGoogle Scholar
  7. 7.
    Hem SL (2002) Elimination of aluminum adjuvants. Vaccine 20(Suppl. 3):S40–S43PubMedCrossRefGoogle Scholar
  8. 8.
    Pichichero ME, Gentile A, Giglio N et al (2008) Mercury levels in newborns and infants after receipt of Thimerosal-containing vaccines. Pediatrics 121:e208–e214PubMedCrossRefGoogle Scholar
  9. 9.
    Dórea JG (2013) Low-dose mercury exposure in early life: relevance of thimerosal to fetuses, newborns and infants. Curr Med Chem 20:4060–4069PubMedCrossRefGoogle Scholar
  10. 10.
    Stajich GV, Lopez GP, Harry SW et al (2000) Iatrogenic exposure to mercury after hepatitis B vaccination in preterm infants. J Pediatr 136:679–681PubMedCrossRefGoogle Scholar
  11. 11.
    Zhou J, Lou Y, Zhan Q et al (2007) Analysis of blood mercury levels in premature infants before and after vaccination of hepatitis B. J Clin Pediatr 25:478–480Google Scholar
  12. 12.
    Ramezani A, Ali Eslamifar A, Gachkar L et al (2008) High blood mercury levels in Iranian infants: a cause for concern. Iran J Pathol 3:186–190Google Scholar
  13. 13.
    Gu L, Lü H, Song G et al (2012) Analysis and evaluation to mercury content in the blood and hair of neonates in Wujiang. J Pediatr Pharm 18:5–7Google Scholar
  14. 14.
    Schofield K (2016) Autism, chemicals, probable cause and mitigation: a new examination. Autism Open Access 6(184):2Google Scholar
  15. 15.
    Rahbar MH, Samms-Vaughan M, Dickerson AS et al (2015) Concentration of lead, mercury, cadmium, aluminum, arsenic and manganese in umbilical cord blood of Jamaican newborns. Int J Environ Res Public Health 12:4481–4501PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Marques RC, Bernardi JV, Dórea JG et al (2014) Perinatal multiple exposure to neurotoxic (lead, methylmercury, ethylmercury, and aluminum) substances and neurodevelopment at 6 and 24 months of age. Environ Pollut 187:130–135PubMedCrossRefGoogle Scholar
  17. 17.
    Wantke F, Hemmer W, Jarisch R et al (1996) Patch test reaction in children, adults and the elderly: a comparative study in patients with suspected allergic contact dermatitis. Contact Dermat 34:316–319CrossRefGoogle Scholar
  18. 18.
    Santucci B, Cannistraci C, Cristaudo A et al (1999) Thimerosal positivities: patch testing to methylmercury chloride in subjects sensitive to ethylmercury chloride. Contact Dermat 40:8–13CrossRefGoogle Scholar
  19. 19.
    Förström L, Hannuksela M, Kousa M et al (1980) Merthiolate hypersensitivity and vaccination. Contact Dermat 6:241–245CrossRefGoogle Scholar
  20. 20.
    Admani S, Jacob SE (2014) Allergic contact dermatitis in children: review of the past decade. Curr Allergy Asthma Rep 14:421PubMedCrossRefGoogle Scholar
  21. 21.
    Thyssen JP, Linneberg A, Engkilde K et al (2012) Contact sensitization to common haptens is associated with atopic dermatitis: new insight. Br J Dermatol 166:1255–1261PubMedCrossRefGoogle Scholar
  22. 22.
    Lindemayr H, Becerano S (1985) Interaction of mercury compounds and aluminium. Contact Dermat 13:274CrossRefGoogle Scholar
  23. 23.
    Jacob SE, Brod B, Crawford GH (2008) Clinically relevant patch test reactions in children—a United States based study. Pediatr Dermatol 25:520–527PubMedCrossRefGoogle Scholar
  24. 24.
    Krob HA, Fleischer AB Jr, D’Agostino R Jr et al (2004) Prevalence and relevance of contact dermatitis allergens: a meta-analysis of 15 years of published T.R.U.E. test data. J Am Acad Dermatol 51:349–353PubMedCrossRefGoogle Scholar
  25. 25.
    Schäfer T, Ring J (1997) Epidemiology of allergic diseases. Allergy 52(38 Suppl):14–22PubMedCrossRefGoogle Scholar
  26. 26.
    Milingou M, Tagka A, Armenaka M et al (2010) Patch tests in children: a review of 13 years of experience in comparison with previous data. Pediatr Dermatol 27:255–259PubMedCrossRefGoogle Scholar
  27. 27.
    Dórea JG, Rooney JP (2011) Increases in Thimerosol patch tests in Greece. Pediatr Dermatol 28:214PubMedCrossRefGoogle Scholar
  28. 28.
    Czarnobilska E, Obtulowicz K, Dyga W et al (2011) The most important contact sensitizers in Polish children and adolescents with atopy and chronic recurrent eczema as detected with the extended European Baseline Series. Pediatr Allergy Immunol 22:252–256PubMedCrossRefGoogle Scholar
  29. 29.
    Czarnobilska E, Dyga W, Krzystyniak D et al (2012) Influence of environment exposures on the frequency of contact allergies in children and adolescents. Ann Agric Environ Med 19:11–16PubMedGoogle Scholar
  30. 30.
    Thyssen JP, Linneberg A, Menne´ T et al (2007) The epidemiology of contact allergy in the general population—prevalence and main findings. Contact Dermat 57:287–299CrossRefGoogle Scholar
  31. 31.
    Thyssen JP, Linneberg A, Menné T et al (2009) Contact allergy to allergens of the TRUE test (panels 1 and 2) has decreased modestly in the general population. Br J Dermatol 161:1124–1129PubMedCrossRefGoogle Scholar
  32. 32.
    Fortina AB, Fontana E, Peserico A (2016) Contact sensitization in children: a retrospective study of 2614 children from a single center. Pediatr Dermatol 33:399–404CrossRefGoogle Scholar
  33. 33.
    Rodrigues DF, Goulart EM (2015) Patch test results in children and adolescents. Study from the Santa Casa de Belo Horizonte Dermatology Clinic, Brazil, from 2003 to 2010. An Bras Dermatol 90:671–683PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Wattanakrai P, Rajatanavin N (2007) Thimerosal allergy and clinical relevance in Thailand. J Med Assoc Thail 90:1775–1779Google Scholar
  35. 35.
    Gao L, Hu Y, Ni C et al (2014) Retrospective study of photopatch testing in a Chinese population during a 7-year period. Dermatitis 25:22–26PubMedCrossRefGoogle Scholar
  36. 36.
    Yu DS, Kim HJ, Park YG et al (2016) Patch-test results Using Korean standard series: a 5-year retrospective review. J Dermatol Treat. doi: 10.1080/09546634.2016.1219015 Google Scholar
  37. 37.
    Heine G, Schnuch A, Uter W et al (2004) Frequency of contact allergy in German children and adolescents patch tested between 1995 and 2002: results from the Information Network of Departments of Dermatology and the German Contact Dermatitis Research Group. Contact Dermat 51:111–117CrossRefGoogle Scholar
  38. 38.
    Tozzi AE, Bisiacchi P, Tarantino V et al (2009) Neuropsychological performance 10 years after immunization in infancy with thimerosal-containing vaccines. Pediatrics 123:475–482PubMedCrossRefGoogle Scholar
  39. 39.
    Andrews N, Miller E, Grant A et al (2004) Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United Kingdom does not support a causal association. Pediatrics 114:584–591PubMedCrossRefGoogle Scholar
  40. 40.
    Heron J, Golding J, ALSPAC Study Team (2004) Thimerosal exposure in infants and developmental disorders: a prospective cohort study in the United Kingdom does not support a causal association. Pediatrics 114:577–583PubMedCrossRefGoogle Scholar
  41. 41.
    Iqbal S, Barile JP, Thompson WW et al (2013) Number of antigens in early childhood vaccines and neuropsychological outcomes at age 7–10 years. Pharmacoepidemiol Drug Saf 22:1263–1270PubMedCrossRefGoogle Scholar
  42. 42.
    Thompson WW, Price C, Goodson B, Vaccine Safety Datalink Team et al (2007) Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med 357:1281–1292PubMedCrossRefGoogle Scholar
  43. 43.
    Barile JP, Kuperminc GP, Weintraub ES et al (2012) Thimerosal exposure in early life and neuropsychological outcomes 7–10 years later. J Pediatr Psychol 37:106–118PubMedCrossRefGoogle Scholar
  44. 44.
    Li AM, Chan MH, Leung TF et al (2000) Mercury intoxication presenting with tics. Arch Dis Child 83:174–175PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Golding J, Steer CD, Hibbeln JR et al (2013) Dietary predictors of maternal prenatal blood mercury levels in the ALSPAC birth cohort study. Environ Health Perspect 121:1214–1218PubMedPubMedCentralGoogle Scholar
  46. 46.
    Miller LL, Scharf JM, Mathews CA et al (2014) Tourette syndrome and chronic tic disorder are associated with lower socio-economic status: findings from the Avon Longitudinal Study of Parents and Children cohort. Dev Med Child Neurol 56:157–163PubMedCrossRefGoogle Scholar
  47. 47.
    Ben-Shlomo Y, Scharf JM, Miller LL et al (2016) Parental mood during pregnancy and post-natally is associated with offspring risk of Tourette syndrome or chronic tics: prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Eur Child Adolesc Psychiatry 25:373–381PubMedCrossRefGoogle Scholar
  48. 48.
    Kadesjö B, Gillberg C (2000) Tourette’s disorder: epidemiology and comorbidity in primary school children. J Am Acad Child Adolesc Psychiatry 39:548–555PubMedCrossRefGoogle Scholar
  49. 49.
    Sealey LA, Hughes BW, Sriskanda AN et al (2016) Environmental factors in the development of autism spectrum disorders. Environ Int 88:288–298PubMedCrossRefGoogle Scholar
  50. 50.
    Kalkbrenner AE, Schmidt RJ, Penlesky AC (2014) Environmental chemical exposures and autism spectrum disorders: a review of the epidemiological evidence. Curr Probl Pediatr Adolesc Health Care 44:277–318PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Kern JK, Geier DA, Sykes LK et al (2016) The relationship between mercury and autism: a comprehensive review and discussion. J Trace Elem Med Biol 37:8–24PubMedCrossRefGoogle Scholar
  52. 52.
    Zerbo O, Qian Y, Yoshida C et al (2017) Association between influenza infection and vaccination during pregnancy and risk of autism spectrum disorder. JAMA Pediatr 171(1):e163609PubMedCrossRefGoogle Scholar
  53. 53.
    Geier DA, Geier MR (2005) A two-phased population epidemiological study of the safety of thimerosal-containing vaccines: a follow-up analysis. Med Sci Monit 11:CR160–C170PubMedGoogle Scholar
  54. 54.
    Young HA, Geier DA, Geier MR (2008) Thimerosal exposure in infants and neurodevelopmental disorders: an assessment of computerized medical records in the Vaccine Safety Datalink. J Neurol Sci 271:110–118PubMedCrossRefGoogle Scholar
  55. 55.
    Geier DA, Hooker BS, Kern JK et al (2014) A dose-response relationship between organic mercury exposure from thimerosal-containing vaccines and neurodevelopmental disorders. Int J Env iron Res Public Health 11:9156–9170CrossRefGoogle Scholar
  56. 56.
    Geier DA, Kern JK, Hooker BS et al (2016) Thimerosal-preserved hepatitis B vaccination and hyperkinetic syndrome of childhood. Brain Sci 6(1):9PubMedCentralCrossRefGoogle Scholar
  57. 57.
    Geier DA, Mumper E, Gladfelter B et al (2008) Neurodevelopmental disorders, maternal Rhnegativity, and Rho(D) immune globulins: a multi-center assessment. Neuro Endocrinol Lett 29(2):27280Google Scholar
  58. 58.
    Verstraeten T, Davis RL, DeStefano F, Vaccine Safety Datalink Team et al (2003) Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases. Pediatrics 112:1039–1048PubMedCrossRefGoogle Scholar
  59. 59.
    Geier DA, Kern JK, Homme KG et al (2016) Thimerosal-containing hepatitis B vaccine exposure is highly associated with childhood obesity: a case-control study using the Vaccine Safety Datalink. N Am J Med Sci 8(7):297–306PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Geier DA, Kern JK, Homme KG et al (2017) Thimerosal exposure and disturbance of emotions specific to childhood and adolescence: a case-control study in the Vaccine Safety Datalink (VSD) database. Brain Inj 31:1–7CrossRefGoogle Scholar
  61. 61.
    Geier DA, Geier MR (2006) A meta-analysis epidemiological assessment of neurodevelopmental disorders following vaccines administered from 1994 through 2000 in the United States. Neuroendocrinol Lett 27(4):401–413PubMedGoogle Scholar
  62. 62.
    Geier DA, Young HA, Geier MR (2010) Thimerosal exposure & increasing trends of premature puberty in the vaccine safety datalink. Indian J Med Res 131:500–507PubMedGoogle Scholar
  63. 63.
    Geier DA, Kern JK, Hooker BS et al (2014) Thimerosal containing hepatitis B vaccination and the risk for diagnosed specific delays in development in the United States: a case-control study in the vaccine safety datalink. N Am J Med Sci 6:519–531PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Geier DA, Kern JK, Hooker BS et al (2016) A longitudinal cohort study of the relationship between Thimerosal-containing hepatitis B vaccination and specific delays in development in the United States: assessment of attributable risk and lifetime care costs. J Epidemiol Glob Health 6(2):10518CrossRefGoogle Scholar
  65. 65.
    Geier DA, Kern JK, King PG et al (2014) The risk of neurodevelopmental disorders following a Thimerosal-preserved DTaP formulation in comparison to its Thimerosal-reduced formulation in the Vaccine Adverse Event Reporting System (VAERS). J Biochem Pharmacol Res 2:64–73Google Scholar
  66. 66.
    Gallagher C, Goodman M (2008) Hepatitis B triple series vaccine and developmental disability in US children aged 1–9 years. Toxicol Environ Chem 90:997–1008CrossRefGoogle Scholar
  67. 67.
    Geier DA, Geier MR (2006) An assessment of downward trends in neurodevelopmental disorders in the United States following removal of Thimerosal from childhood vaccines. Med Sci Monit 12(6):CR231–C9PubMedGoogle Scholar
  68. 68.
    Geier DA, Geier MR (2005) A two-phased population epidemiological study of the safety of Thimerosal-containing vaccines: a follow-up analysis. Med Sci Monit 11:CR160–CR170PubMedGoogle Scholar
  69. 69.
    Geier DA, Geier MR (2006) An evaluation of the effects of thimerosal on neurodevelopmental disorders reported following DTP and Hib vaccines in comparison to DTPH vaccine in the United States. J Toxicol Environ Health A 69(15):1481–1495PubMedCrossRefGoogle Scholar
  70. 70.
    Yoshimasu K, Kiyohara C, Takemura S et al (2014) A meta-analysis of the evidence on the impact of prenatal and early infancy exposures to mercury on autism and attention deficit/hyperactivity disorder in the childhood. Neurotoxicology 44:121–131PubMedCrossRefGoogle Scholar
  71. 71.
    Fombonne E, Zakarian R, Bennett A et al (2006) Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations. Pediatrics 118:e139–e150PubMedCrossRefGoogle Scholar
  72. 72.
    Meilleur AA, Fombonne E (2009) Regression of language and non-language skills in pervasive developmental disorders. J Intellect Disabil Res 53:115–124PubMedCrossRefGoogle Scholar
  73. 73.
    Lazoff T, Zhong L, Piperni T et al (2010) Prevalence of pervasive developmental disorders among children at the English Montreal School Board. Can J Psychiatry 55:715–720PubMedCrossRefGoogle Scholar
  74. 74.
    Grønborg TK, Schendel DE, Parner ET (2013) Recurrence of autism spectrum disorders in full- and half-siblings and trends over time: a population-based cohort study. JAMA Pediatr 167:947–953PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Dórea JG, Donangelo CM (2006) Early (in uterus and infant) exposure to mercury and lead. Clin Nutr 25:369–376PubMedCrossRefGoogle Scholar
  76. 76.
    Rebelo FM, Caldas ED (2016) Arsenic, lead, mercury and cadmium: toxicity, levels in breast milk and the risks for breastfed infants. Environ Res 151:671–688PubMedCrossRefGoogle Scholar
  77. 77.
    Claus Henn B, Coull BA, Wright RO (2014) Chemical mixtures and children’s health. Curr Opin Pediatr 26:223–229PubMedCrossRefGoogle Scholar
  78. 78.
    von Stackelberg K, Guzy E, Chu T et al (2015) Exposure to mixtures of metals and neurodevelopmental outcomes: a multidisciplinary review using an adverse outcome pathway framework. Risk Anal 35:971–1016CrossRefGoogle Scholar
  79. 79.
    Zaręba M, Sanecki PT, Rawski R (2016) Simultaneous determination of thimerosal and aluminum in vaccines and pharmaceuticals with the use of HPLC method. Acta Chromatogr 28:299–311CrossRefGoogle Scholar
  80. 80.
    Marques RC, Abreu L, Bernardi JV et al (2016) Neurodevelopment of Amazonian children exposed to ethylmercury (from Thimerosal in vaccines) and methylmercury (from fish). Environ Res 149:259–265PubMedCrossRefGoogle Scholar
  81. 81.
    Dórea JG, Bezerra VL, Fajon V et al (2011) Speciation of methyl- and ethyl-mercury in hair of breastfed infants acutely exposed to thimerosal-containing vaccines. Clin Chim Acta 412:1563–1566PubMedCrossRefGoogle Scholar
  82. 82.
    Mrozek-Budzyn D, Majewska R, Kiełtyka A (2015) Early exposure to thimerosal-containing vaccines and children’s cognitive development. A 9-year prospective birth cohort study in Poland. Eur J Pediatr 174:383–391PubMedCrossRefGoogle Scholar
  83. 83.
    Marques RC, Dórea JG, McManus C et al (2011) Hydroelectric reservoir inundation (Rio Madeira Basin, Amazon) and changes in traditional lifestyle: impact on growth and neurodevelopment of pre-school children. Public Health Nutr 14:661–669PubMedCrossRefGoogle Scholar
  84. 84.
    Marques RC, Bernardi JV, Dórea JG et al (2008) Principal component analysis and discrimination of variables associated with pre- and post-natal exposure to mercury. Int J Hyg Environ Health 211:606–614PubMedCrossRefGoogle Scholar
  85. 85.
    Marques RC, Dórea JG, Bernardi JVE (2010) Thimerosal exposure (from tetanus-diphtheria vaccine) during pregnancy and neurodevelopment of breastfed infants at six months. Acta Paediatr 99:1–6Google Scholar
  86. 86.
    Marques RC, Dórea JG, Manzatto AG et al (2007) Time of perinatal immunization, thimerosal exposure and neurodevelopment at 6 months in breastfed infants. Acta Paediatr 96:864–868PubMedCrossRefGoogle Scholar
  87. 87.
    Marques RC, Bernardi JV, Cunha MP et al (2016) Impact of organic mercury exposure and home delivery on neurodevelopment of Amazonian children. Int J Hyg Environ Health 219:498–502PubMedCrossRefGoogle Scholar
  88. 88.
    Marques RC, Abreu L, Bernardi JV et al (2016) Traditional living in the Amazon: extended breastfeeding, fish consumption, mercury exposure and neurodevelopment. Ann Hum Biol 43:360–370PubMedCrossRefGoogle Scholar
  89. 89.
    Marques R, Dórea JG, Bernardi JVE et al (2009) Prenatal and postnatal mercury exposure, breastfeeding and neurodevelopment during the first 5 years. Cogn Behav Neurol 22:134–141PubMedCrossRefGoogle Scholar
  90. 90.
    Mrozek-Budzyn D, Majewska R, Kieltyka A et al (2012) Neonatal exposure to Thimerosal from vaccines and child development in the first 3 years of life. Neurotoxicol Teratol 34:592–597PubMedCrossRefGoogle Scholar
  91. 91.
    Dόrea JG, Souza JR, Marques RC et al (2012) Neurodevelopment of Amazonian infants: antenatal and postnatal exposure to methyl-and ethylmercury. J Biomed Biotechnol 2012:132876. doi: 10.1155/2012/132876 CrossRefGoogle Scholar
  92. 92.
    Dórea JG, Marques RC, Abreu L (2014) Milestone achievement and neurodevelopment of rural Amazonian toddlers (12 to 24 months) with different methylmercury and ethylmercury exposure. J Toxicol Environ Health A 77:1–13PubMedCrossRefGoogle Scholar
  93. 93.
    Marques RC, Dórea JG, Leão RS et al (2012) Role of methylmercury exposure (from fish consumption) on growth and neurodevelopment of children under 5 years of age living in a transitioning (tin-mining) area of the western Amazon, Brazil. Arch Environ Contam Toxicol 62:341–350PubMedCrossRefGoogle Scholar
  94. 94.
    Marques RC, Bernardi JV, Abreu L et al (2015) Neurodevelopment outcomes in children exposed to organic mercury from multiple sources in a tin-ore mine environment in Brazil. Arch Environ Contam Toxicol 68:432–441PubMedCrossRefGoogle Scholar
  95. 95.
    Lee BE, Ha EH (2012) Response to commentary “Co-exposure and confounders during neurodevelopment: we need them in the bigger picture of secondhand smoke exposure during pregnancy”. Environ Res 112:235PubMedCrossRefGoogle Scholar
  96. 96.
    Bellinger DC (2004) What is an adverse effect? A possible resolution of clinical and epidemiological perspectives on neurobehavioral toxicity. Environ Res 95:394–405PubMedCrossRefGoogle Scholar
  97. 97.
    Dórea JG (2007) Exposure to mercury during the first six months via human milk and vaccines: modifying risk factors. Am J Perinatol 24:387–400PubMedCrossRefGoogle Scholar
  98. 98.
    Pichichero M, Cernichiari E, Lopreiato J et al (2002) Mercury concentrations and metabolism in infants receiving vaccines containing thiomersal: a descriptive study. Lancet 360:1737–1741PubMedCrossRefGoogle Scholar
  99. 99.
    Pichichero ME, Gentile A, Giglio N et al (2009) Mercury levels in premature and low birth weight newborn infants after receipt of thimerosal containing vaccines. J Pediatr 155:495–499PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Barregard L, Rekić D, Horvat M et al (2011) Toxicokinetics of mercury after long-term repeated exposure to thimerosal-containing vaccine. Toxicol Sci 120:499–506PubMedCrossRefGoogle Scholar
  101. 101.
    Wohrl S, Hemmer W, Focke M et al (2003) Patch testing in children, adults, and the elderly: influence of age and sex on sensitization patterns. Pediatr Dermatol 20:119–123PubMedCrossRefGoogle Scholar
  102. 102.
    Fernández Vozmediano JM, Armario Hita JC (2005) Allergic contact dermatitis in children. J Eur Acad Dermatol Venereol 19:42–46PubMedCrossRefGoogle Scholar
  103. 103.
    Goon AT, Goh CL (2006) Patch testing of Singapore children and adolescents: our experience over 18 years. Pediatr Dermatol 23:117–120PubMedCrossRefGoogle Scholar
  104. 104.
    Zug KA, McGinley-Smith D, Warshaw EM et al (2008) Contact allergy in children referred for patch testing: North American Contact Dermatitis Group data, 2001–2004. Arch Dermatol 144:1329–1336PubMedCrossRefGoogle Scholar
  105. 105.
    Kuljanac I, Knežević E, Cvitanović H (2011) Epicutaneous patch test results in children and adults with allergic contact dermatitis in Karlovac county: a retrospective survey. Acta Dermatovenerol Croat 19:91–97PubMedGoogle Scholar
  106. 106.
    Warshaw EM, Nelsen DD, Sasseville D et al (2010) Positivity ratio and reaction index: patch-test quality-control metrics applied to the North American contact dermatitis group database. Dermatitis 21:91–97PubMedGoogle Scholar
  107. 107.
    Geier DA, Kern JK, Homme KG et al (2017) Abnormal Brain connectivity spectrum disorders following Thimerosal administration: a prospective longitudinal case–control assessment of medical records in the vaccine safety datalink. Dose-Response 15(1):1559325817690849PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Geier DA, Kern JK, Hooker BS et al (2015) Thimerosal exposure and increased risk for diagnosed tic disorder in the United States: a case-control study. Interdiscip Toxicol 8:68–76PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Leslie DL, Kobre RA, Richmand BJ et al (2017) Temporal association of certain neuropsychiatric disorders following vaccination of children and adolescents: a pilot case-control study. Front. Psychiatry 8:3. doi: 10.3389/fpsyt.2017.00003 PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Lloret PS, Rey MV, Rascol O et al (2013) Drugs related to Tourette-like syndrome: a case/non-case study in the French Pharmacovigilance Database and a comparison with cases reported in the Literature. Fundam Clin Pharmacol 27:112Google Scholar
  111. 111.
    U.S. Department of Health and Human Services. U.S. Food & Drug Administration. Vaccines, blood biologics. Thimerosal in vaccines. http://www.fda.gov/biologicsbloodvaccines/safetyavailability/vaccinesafety/ucm096228.htm#t1. Accessed 27 Sep 2016

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Professor Emeritus, Faculty of Health SciencesUniversidade de BrasíliaBrasíliaBrazil

Personalised recommendations