Exposição humana ao mercúrio e seus efeitos hematológicos: uma revisão sistemática

Vianna, Angélica dos Santos; Matos, Elisabete Pedra de; Jesus, Iracina Maura de; Asmus, Carmen Ildes Rodrigues Fróes; Câmara, Volney de Magalhães

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REVIEW • Cad. Saúde Pública 35 (2) • 2019 • https://doi.org/10.1590/0102-311X00091618 copiar

Exposição humana ao mercúrio e seus efeitos hematológicos: uma revisão sistemática

Autoria SCIMAGO INSTITUTIONS RANKINGS

O mercúrio é um metal que pode ser encontrado naturalmente no meio ambiente e através de fontes antropogênicas. É altamente tóxico para ecossistemas e seres vivos. A maior parte da exposição humana provém da ingestão de pescados contaminados, da liberação de gases da amálgama dentária ou da exposição ocupacional (p.ex.: extração de ouro). Vastas populações são expostas ao mercúrio, tornando-se uma questão de saúde pública muito importante. Efeitos adversos à saúde são comumente observados no sistema nervoso, mas todos os órgãos são alvos em potencial, como a medula óssea. O principal objetivo do estudo foi avaliar as evidências disponíveis sobre a exposição humana ao mercúrio e seus efeitos hematológicos. Uma estratégia de busca foi realizada, incluindo termos chave (palavras-chave, palavras do texto e equivalentes), para pesquisar dois repositórios de dissertações de mestrado e teses de doutorado (Fiocruz/ARCA e Universidade de São Paulo) e quatro bases de dados eletrônicas: BVS/LILACS, MEDLINE/PubMed, Scopus e TOXLINE/NIH (artigos publicados de 1950 até fevereiro de 2018). Não houve restrições de linguagem e uma ferramenta (EPHPP) foi utilizada para avaliar a qualidade dos estudos incluídos. De acordo com os critérios pré-estabelecidos, foram encontrados 80 estudos, todos observacionais (48 relatos de caso, 24 estudos transversais, 6 séries de casos e 2 coortes), que compreendiam 9.284 pessoas. Apesar do fato de que as pessoas mais expostas (6.012) tinham contagens de células sanguíneas normais, e os efeitos hematológicos do mercúrio não pareciam muito comuns (1.914 casos, 14 graves e 29 mortes), três estudos relataram a associação de (β) anemia, linfopenia, neutrofilia e basofilia. Concluímos que as informações coletadas indicam efeitos hematotóxicos do mercúrio, alguns dos quais podem ser muito graves e até fatais.

Palavras-chave:
Intoxicação por Mercúrio; Intoxicação por Metais Pesados; Mercúrio; Contagem de Células Sanguíneas

Hematological effect	Exposure	Cases
Anemia	Non-occupational	547
Anemia	Occupational	328
Polycythemia	Non-occupational	0
Polycythemia	Occupational	48
Leukopenia	Non-occupational	84
Leukopenia	Occupational	22
Leukocytosis	Non-occupational	23
Leukocytosis	Occupational	3
Basopenia	Non-occupational	80
Basopenia	Occupational	0
Basophilia	Non-occupational	191
Basophilia	Occupational	0
Eosinophilia	Non-occupational	30
Eosinophilia	Occupational	7
Neutropenia	Non-occupational	26
Neutropenia	Occupational	0
Neutrophilia	Non-occupational	199
Neutrophilia	Occupational	5
Lymphopenia	Non-occupational	273
Lymphopenia	Occupational	33
Lymphocytosis	Non-occupational	102
Lymphocytosis	Occupational	259
Monocytopenia	Non-occupational	56
Monocytopenia	Occupational	0
Monocytosis	Non-occupational	24
Monocytosis	Occupational	0
Thrombocytopenia	Non-occupational	19
Thrombocytopenia	Occupational	2
Thrombocytosis	Non-occupational	2
Thrombocytosis	Occupational	0
Pancytopenia	Non-occupational	5
Pancytopenia	Occupational	1
Other (alteration of hematocrit and leukocytes)	Non-occupational	0
Other (alteration of hematocrit and leukocytes)	Occupational	7
Total		2,376

Study (year)	Country	Study characteristics [design/number/exposure]	Population [age/sex]	Mercury level	Hemtologic effect	Statistical analysis	EPHPP tool
Bender et al. ²⁷27. Bender CE, Hoxsey RJ, DeMarsh QB. Neutropenia in a patient treated with a mercurial diuretic and its response to BAL. Ann Intern Med 1950; 33:1285-90. (1950)	USA	Case report; n = 1; non-occupational (medicine)/chronic	Female (61y)	NI	Anemia = 1, leukopenia = 1, neutropenia = 1	NA	3
Butt & Simonsen ⁴¹41. Butt EM, Simonsen DG. Mercury and lead storage in human tissue. Am J Clin Pathol 1950; 20:716-23. (1950)	USA	Cross-sectional; n = 134, no control (occupational = 1, non-occupational = 55, NI = 78); non-occupational (medicine + environment + maternal exposure)	Female = 22, male = 42, NI = 69 (< 1-81y)	High	Thrombocytopenia = 12	ND	3
Doolan et al. ⁷³73. Doolan PD, Hess WC, Kyle LH. Acute renal insufficiency dure to biclhoride of mercury - observations on gastrointestinal hemorrhage and Bal. N Engl J Med 1953; 249:273-6. (1953)	USA	Case report; n = 1; non-occupational (suicide)/chronic	Female (28y)	NI	Anemia = 1	NA	3
Portwich & Maron ²⁸28. Portwich F, Maron H. Fatal allergic thrombopenia after influenza prophylaxis with phenylmercuric borate (merfen). Arztl Wochensch 1959; 14:65-6. (1959)	Germany	Case report; n = 1; non-occupational (medicine)/chronic	Female (64y)	NI	Thrombocytopenia = 1	NA	3
Larsen et al. ⁸²82. Larsen RR, Sawyer KC, Sawyer RB, Saliba NS. Mercury granuloma complicating gastrointestinal tube decompression. Surgery 1963; 54:442-7. (1963)	USA	Case report; n = 2; non-occupational (medicine)/acute	Female = 1, male = 1 (55y, 69y)	NI	Leukocytosis = 1, normal = 1	NA	3
Ross ⁸³83. Ross AT. Mercuric polyneuropathy with albumin-cytologic dissociation and eosinophilia. JAMA 1964; 188:830-1. (1964)	USA	Case report; n = 1; non-occupational (medicine)/chronic	Male (4y)	High	Leukocytosis = 1	NA	3
Wilson ²⁹29. Wilson DR. Mercurial poisoning and aplastic anaemia. BMJ 1966; 2:1534. (1966)	UK	Case report; n = 1; non-occupational (medicine)/chronic	Male (77y)	High	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Johnson et al. ³⁰30. Johnson KG, Evanger A, van Meter W. Elemental mercury poisoning manifest by acrodynia and neutropenia. Vet Human Toxicol 1978; 20:404-9. (1978)	USA	Case report; n = 1; non-occupational (medicine)/chronic	Female (3y)	High	Anemia = 1, leukopenia = 1, neutropenia = 1	NA	3
Hannigan ⁸⁴84. Hannigan BG. Self-administration of metallic mercury by intravenous injection. BMJ 1978; 2:933. (1978)	UK	Case report; n = 1; non-occupational (suicide)/chronic	Male (34y)	High	Normal = 1	NA	3
Murphy et al. ³¹31. Murphy MJ, Culliford EJ, Parsons V. A case of poisoning with mercuric chloride. Resuscitation 1979; 7:35-44. (1979)	UK	Case report; n = 1; non-occupational (medicine)/acute	Male (35y)	High	Anemia = 1, leukocytosis = 1, neutrophilia = 1, thrombocytopenia = 1	NA	3
Slee et al. ³²32. Slee PH, den Ottolander GJ, de Wolff FA. A case of merbromin (mercurochrome) intoxication possibly resulting in aplastic anemia. Acta Med Scand 1979; 205:463-6. (1979)	Netherlands	Case report; n = 1; non-occupational (medicine)/acute	Female (59y)	High	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Wright et al. ⁸⁵85. Wright N, Yeoman WB, Carter GF. Massive oral ingestion of elemental mercury without poisoning. Lancet 1980; 1:206. (1980)	UK	Case report; n = 1; non-occupational (suicide)/acute	Male (17y)	NI	Normal = 1	NA	3
Lien et al. ⁸⁶86. Lien DC, Todoruk DN, Rajani HR, Cook DA, Herbert FA. Accidental inhalation of mercury vapour: respiratory and toxicologic consenquences. Can Med Assoc J 1983; 129:591-5. (1983)	Canada	Case series; n = 7 (occupational = 1, non-occupational = 6); non-occupational (home)/acute	Female = 1, male = 2, NI = 3 (< 2-28y)	High = 6	Leukocytosis = 6	NA	3
McNeil et al. ⁸⁷87. McNeil NI, Issler HC, Olver RE, Wrong OM. Domestic metallic mercury poisoning. Lancet 1984; 1:269-71. (1984)	UK	Case series; n = 4; non-occupational (home)/chronic	Female = 2, male = 2 (10-41y)	High	Normal = 4	NA	3
Foulds et al. ⁸⁸88. Foulds DM, Copeland KC, Franks RC. Mercury poisoning and acrodynia. Am J Dis Child 1987; 141:124-5. (1987)	USA	Case report; n = 1; non-occupational (home)/chronic	Female (< 3y)	High	Normal = 1	NA	3
Lauwerys et al. ²⁵25. Lauwerys R, Bonnier C, Evrad P, Gennart JP, Bernard A. Prenatal and early postnatal intoxication by inorganic mercury resulting from the maternal use of mercury containing soap. Hum Toxicol 1987; 6:253-6. (1987)	Belgium	Case report; n = 1; non-occupational (aesthetic/maternal exposure)/chronic	Male (< 1y)	High	Anemia = 1, leukocytosis = 1, lymphocytosis = 1	NA	3
Oliveira et al. ⁸⁹89. Oliveira DB, Foster G, Savill J, Syme PD, Taylor A. Membranous nephropathy caused by mercury containing skin lightening cream. Postgrad Med J 1987; 63:303-4. (1987)	UK	Case report; n = 1; non-occupational (aesthetic)/chronic	Female (46y)	High	Anemia = 1	NA	3
Tunnessen et al. ⁷⁸78. Tunnessen WW, McMahon KJ, Baser M. Acrodynia: exposure to mercury from fluorescente light bulbs. Pediatrics 1987; 79:786-9. (1987)	USA	Case report; n = 1; non-occupational (school)/chronic	Male (< 2y)	High	Leukocytosis = 1, Eosinophilia = 1, thrombocytosis = 1	NA	3
Murray & Hedgepeth ⁹⁰90. Murray KM, Hedgepeth JC. Intravenous self-administration of elemental mercury: efficacy of dimercaprol therapy. Drug Intell Clin Pharm 1988; 22:972-5. (1988)	USA	Case report; n = 1; non-occupational (suicide)/chronic	Male (25y)	High	Anemia = 1, neutrophilia = 1	NA	3
Oluwole et al. ⁴²42. Oluwole AF, Asubiojo OI, Adekile AD, Filby RH, Bragg A, Grimm CI. Trace element distribution in the hair of some sickle cell anemia patients and controls. Biol Trace Elem Res 1990; 26-27:479-84. (1989)	Nigeria	Cross-sectional; n = 21 (no control); non-occupational (environment)/chronic	Male = 21 (3-12y)	High = 1, normal = 20	Anemia = 10, normal = 11	t-test, no mean difference, p < 0.05	3
Siblerud ⁴³43. Siblerud RL. The relationship between mercury from dental amalgam and the cardiovascular system. Sci Total Environ 1990; 99:23-35. (1990)	USA	Cross-sectional; n = 101 (exposed = 50, not exposed = 51); non-occupational (amalgam)/chronic	Female = 60, male = 41 (exposed x = 22y, not exposed x = 23y)	NI	Anemia = 15, normal = 86	Mean difference, p = 0.016; Pearson r = -0.4208, p = 0.003	3
Montoya-Cabrera et al. ²⁶26. Montoya-Cabrera MA, Rubio-Rodríguez S, Velázquez-González E, Avila SM. Intoxicación mercurial causada por un medicamento homeopático. Gac Méd Méx 1991; 127:260-70. (1991)	Mexico	Case report; n = 1; non-occupational (medicine)/acute	Female = 1 (< 1y)	High	Anemia = 1, lymphocytosis = 1	NA	3
Schwartz et al. ⁸¹81. Schwartz JG, Snider TE, Montiel MM. Toxicity of a family from vaccumed mercury. Am J Emerg Med 1992; 10:258-61. (1992)	USA	Case series; n = 4; non-occupational (home)/acute	Female = 1, male = 3 (< 4y-adults)	High	Anemia = 1, leukopenia = 1, thrombocytopenia = 1, normal = 3	NA	3
Pavithran ³³33. Pavithran K. Mercury and aplastic anemia. Natl Med J India 1994; 7:252. (1994)	India	Case report; n = 1; non-occupational (medicine)/chronic	Female (29y)	ND	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Alvarado et al. ³⁴34. Alvarado EV, Ramírez JA, Nilsman M, Bonilla R. Intoxicación sistemática por mercurio elemental depositado en el organismo. Medicina Legal 1995; 12:36-40. (1995)	Costa Rica	Case report; n = 2 (occupational = 1, non-occupational = 1); non-occupational (medicine)/chronic	Male (25y)	NI	Leukocytosis = 1, neutrophilia = 1	NA	3
Fuortes et al. ³⁹39. Fuortes LJ, Weismann DN, Graeff ML, Bale JF, Tannous R, Peters C. Immune thrombocytopenia and elemental mercury poisoning. Clin Toxicol (Phila) 1995; 33:449-55. (1995)	USA	Case report; n = 3; non-occupational (home)/chronic	Female = 1, male = 2 (10y, 12y, 17y)	High	Anemia = 1, leukocytosis = 1, eosinophilia = 2, thrombocytopenia = 2, normal = 1	NA	3
Dell’Omo et al. ⁹¹91. Dell'Omo M, Muzi G, Bernard A, Filiberto S, Lauwerys RR, Abbritti G. Long term pulmonar and systemic toxicity following intravenous mercury injection. Arch Toxicol 1997; 72:59-62. (1997)	Italy	Case report; n = 1; non-occupational (suicide)/chronic	Male (34y)	High	Normal = 1	NA	3
Dada et al. ³⁵35. Dada MA, Jogessar V, Ramdial PK. Membranous fat necrosis and aplastic anaemia due to mercury poisoning. J Pathol 1999; 189 Suppl S:22A. (1999)	South Africa	Case report; n = 1; non-occupational (medicine)/acute	Male (21y)	NI	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Chodorowski & Anand ⁹²92. Chodorowski Z, Anand JS. Intravenous self-administration of metallic mercury by two alcohol abusers. Przegl Lek 2000; 57:585-7. (2000)	Poland	Case report; n = 2; non-occupational (suicide)/acute	Male = 2 (19-59y)	High	Normal = 2	NA	3
Tschanz & Prins ⁷⁷77. Tschanz C, Prins C. Drug rash with eosinophilia and systemic symptoms caused by topical application of mercury. Dermatology 2000; 201:381-2. (2000)	Switzerland	Case report; n = 1; non-occupational (medicine)/acute	Female (29y)	NI	Leukocytosis = 1, eosinophilia = 1	NA	3
González et al. ⁹³93. González R, Rodulfo A, Botero M. Púrpura de Henoch-Schönlein secundaria a hipersensibilidad por mercurio en un preescolar: a propósito de un caso. Arch Venez Pueric Pediatr 2001; 64:156-62. (2001)	Venezuela	Case report; n = 1; non-occupational (medicine)/acute	Female (3y)	Normal	Anemia = 1, leukocytosis = 1, neutrophilia = 1, thrombocytosis = 1	NA	3
Deschamps et al. ⁹⁴94. Deschamps F, Strady C, Deslee G, Menciere-Faroy B, Deschamps S. Five years of follow-up after elemental mercury self-poisoning. Am J Forensic Med Pathol 2002; 23:170-2. (2002)	France	Case report; n = 1; non-occupational (suicide)/chronic	Male (41y)	High	Normal = 1	NA	3
Langworth et al. ⁹⁵95. Langworth S, Björkman L, Elinder CG, Järup L, Savlin P. Multidisciplinary examination of patitens with illness attributes to dental fillings. J Oral Rehabil 2002; 29:705-13. (2002)	Sweden	Cross-sectional; n = 379 (no control); non-occupational (amalgam)/chronic	Female = 263, male = 116 (x = 46y)	High	Anemia = 6, normal = 373	ND	3
Winkler et al. ⁹⁶96. Winkler R, Schaffer AW, Komaris C, Barth A, Giovanoli P, Osterode W, et al. Health consequences of intravenous injection of metallic mercury. Int Arch Occup Environ Health 2002; 75:581-6. (2002)	Austria	Case report; n = 1; non-occupational (suicide)/acute	Male (22y)	High	Anemia = 1	NA	3
Kouyn et al. ⁹⁷97. Koyun M, Akman S, Güven AG. Mercury intoxication resulting from school barometers in three unrelated adolescents. Eur J Pediatr 2004; 163:131-4. (2004)	Turkey	Case report; n = 3; non-occupational (home)/chronic	Female = 1, male = 2 (11y, 13y, 16y)	Normal = 1, high = 2	Normal = 3	NA	3
Glezos et al. ⁹⁸98. Glezos JD, Albrecht JE, Gair RD. Pneumonitis after inhalation of mercury vapours. Can Respir J 2006; 13:150-2. (2006)	Canada	Case report; n = 1; non-occupational (home)/acute	Male (43y)	High	Anemia = 1	NA	3
Maramba et al. ⁷⁶76. Maramba NPC, Reyes JP, Francisco-Rivera AT, Panganiban LCR, Dioquino C, Dando N, et al. Environmental and human exposure assessment monitoring of communities near an abandoned mercury mine in the Philippines: a toxic legacy. J Environ Manage 2006; 81:135-45. (2006)	Philippines	Cross-sectional; n = 140 (exposed = 100, not exposde = 40); non-occupational (gold minig = food)/chronic	Female = 70, NI = 70 (35 < 1y, 35 < 2y, 70 x = 28y)	Normal, high *	Anemia = 140, eosinophilia = ?	ND	3
Frisk et al. ⁴⁶46. Frisk P, Danersund A, Hudecek R, Lindh U. Changed clinical chemistry pattern in blood after removal of dental amalgam and other metal alloys supported by antioxidant therapy. Biol Trace Elem Res 2007; 120:163-70. (2007)	Sweden	Cross-sectional; n = 46 (exposed = 24, not exposed = 22); non-occupational (amalgam)/acute	Adults = 46	Normal	Leukopenia = 24, neutropenia = 24, basopenia = 24, lymphopenia = 24, eosinophilia = 24, monocytosis = 24, normal = 22	Wilcoxon’s sign rank, mean difference, p < 0.05	3
Matushita et al. ⁹⁹99. Matushita JPK, Peixoto RMA, Leão Filho HM, Missiaggia GC, Dias RS, Tavares Junior WC, et al. Embolismo por mercúrio metálico: relato de caso. Radiol Bras 2007; 40:217-9. (2007)	Brazil	Case report; n = 1; non-occupational (suicide)/chronic	Male (29y)	High	Normal = 1	NA	3
Bamonti et al. ¹⁰⁰100. Bamonti F, Guzzi G, Ferrero E. Cracked mercury dental amalgam as possible cause of fever of unknown origin: a case report. J Med Case Rep 2008; 2:72. (2008)	Italy	Case report; n = 1; non-occupational (amalgam)/acute	Female (63y)	Normal	Anemia = 1, leukocytosis = 1, neutrophilia = 1, lymphopenia = 1	NA	3
Girault et al. ¹⁰¹101. Girault PY, Rey P, Veran Y. Acute hepatitis after cutaneous application of an artisanal topical ointment with mercury. Gastroenterol Clin Biol 2008; 32:819-23. (2008)	France	Case report; n = 1; non-occupational (medicine)/acute	Female (66y)	High	Neutrophilia = 1, lymphopenia = 1	NA	3
Berrouet Mejía et al. ¹⁰²102. Berrouet Mejía MC, Escobar Toledo IE, González Ramírez DM. Toxicidad sistémica asociada con la inyección intramuscular de mercúrio metálico: reporte de un caso. Iatreia 2008; 21:420-5. (2008)	Colombia	Case report; n = 1; non-occupational (suicide)/chronic	Female (16y)	High	Anemia = 1, leukocytosis = 1, neutrophilia = 1	NA	3
De Palma et al. ³⁶36. De Palma G, Mariotti O, Lonati D, Goldoni M, Catalani S, Mutti A, et al. Toxicokinetics and toxicodynamics of elemental mercury following self-administration. Clin Toxicol (Phila) 2008; 46:869-76. (2008)	Italy	Case report; n = 1; non-occupational (suicide)/acute	Female (30y)	High	Anemia = 1, leukocytosis = 1	NA	3
Erkek et al. ⁴⁰40. Erkek N, Senel S, Sarac A, Ertan U, Karacan CD. Being alive after a severe inorganic mercury intoxication. Eur J Pediatr 2010; 169:625-8. (2010)	Turkey	Case report; n = 1; non-occupational (environment)/acute	Female (10y)	High	Anemia = 1	NA	3
Sarikaya et al. ¹⁰³103. Sarikaya S, Karcioglu O, Ay D, Cetin A, Aktas C, Serinken M. Acute poisoning: a case report. BMC Emerg Med 2010; 10:7. (2010)	Turkey	Case report; n = 1; non-occupational (school)/acute	Female (36y)	NI	Normal = 1	NA	3
Al-Sinani et al. ⁷⁹79. Al-Sinani S, Al-Rawas A, Dhawan A. Mercury as a cause of fulminant hepatic failure in a child: case report and literature review. Clin Res Hepatol Gastroenterol 2011; 35:580-2. (2011)	Oman	Case report; n = 1; non-occupational (medicine)/chronic	Female (12y)	High	Leukocytosis = 1, eosinophilia = 1	NA	3
Plante et al. ⁴⁹49. Plante C, Blanchet C, Rochette L, O'Brien HT. Prevalence of anemia among inuit women in Nunavik, Canada. Int J Circumpolar Health 2011; 70:154-65. (2011)	Canada	Cross-sectional; n = 466 (no control); non-occupational (food)/chronic	Female = 466 (20-54y)	High	Anemia = 200, normal = 266	Previous data not shown. Pearson r = 0.04, p-value not informed	3
Yildrim et al. ³⁷37. Yildrim R, Erdem F, Gündogdu M, Bilen Y, Koca E, Yillikoglu Y, et al. Mercury toxicity: a family case report. Turk J Hematol 2012; 29:76-9. (2012)	Turkey	Case series; n = 5; non-occupational (home)/acute	Female = 3, male = 2 (20-54y)	High	Anemia = 2, leukopenia = 2, thrombocytopenia = 2, normal = 2	NA	3
Priya et al. ¹¹11. Priya N, Nagaprabhu VN, Kurian G, Seethalakshmi N, Rao GG, Unni VN. Aplastic anemia and membranous nephropathy induced by intravenous mercury. Indian J Nephrol 2012; 22:451-4. (2012)	India	Case report; n = 1; non-occupational (suicide)/acute	Female (19y)	High	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Khoury et al. ¹⁰⁴104. Khoury EDT, Souza GS, Silveira LCL, Costa CA, Araújo AA, Pinheiro MCN. Manifestações neurológicas em ribeirinhos de áreas expostas ao mercúrio na Amazônia brasileira. Cad Saúde Pública 2013; 29:2307-18. (2013)	Brazil	Cross-sectional; n = 157 (exposed = 108, not exposed = 49); non-occupational (gold mining + food)/chronic	NI = 157 (13-53y)	Normal = 49, high = 108	NI	ND	3
Kim et al. ⁵⁰50. Kim JH, Lee KH, Hong SC, Lee HS, Lee J, Kang JW. Association between serum mercury concentration and leukocyte differential count in children. Pediatr Hematol Oncol 2013; 32:109-14. (2013)	Korea	Cross-sectional; n = 311 (no control); non-occupational (food)/chronic	Female = 141, male = 170 (5-12y)	High = 7	Lymphocytosis = 100, normal = 211	Spearman r = 0.121, p = 0.049	3
Wu et al. ⁷²72. Wu ML, Deng JF, Lin KP, Tsai WJ. Lead, mercury na arsenic poisoning due to topical use of traditional chinese medicines. Am J Med 2013; 126:451-54. (2013)	Taiwan	Case report; n = 1; non-occupational (medicine)/acute	Male (51y)	Normal	Anemia = 1	NA	3
Beasley et al. ¹⁰⁵105. Beasley DM, Schep LJ, Slaughter RJ, Temple WA, Michel JM. Full recovery from a potentially lethal dose of mercuric chloride. J Med Toxicol 2014; 10:40-4. (2014)	New Zealand	Case report; n = 1; non-occupational (suicide)/acute	Female (19y)	High	Leukocytosis = 1, neutrophilia = 1	NA	3
Brázdová et al. ⁴⁷47. Brázdová ZD, Pomerleau J, Fiala J, Vorlová L, Müllerová D. Heavy metals in hair samples: a pilot study of anaemic children in Kazakhstan, Kyrgyzstan and Uzbekistan. Cent Eur J Public Health 2014; 22:273-6. (2014)	Kazakhstan, Kyrgyzstan, Uzbeskistan	Cross-sectional; n = 60; non-occupational (environment)/chronic	Female = 27, male = 33 (1-15y)	Normal	Anemia = 60	Bonferroni’s test, mean difference, p < 0.05	3
Dardamanis et al. ¹⁰⁶106. Dardamanis M, Balta L, Zacharopoulos V, Tatsi V, Tzima H. An unexpected foreign body (a thermometer) in the bladder: a case report. Urol Case Rep 2014; 2:65-6. (2014)	Greece	Case report; n = 1; non-occupational (thermometer)/acute	Female (48y)	NI	Anemia = 1	NA	3
Cicek-Senturk et al. ¹⁰⁷107. Cicek-Senturk G, Altay FA, Ulu-Klilic A, Gurbuz Y, Tutuncu E, Sencan I. Acute mercury poisoning presenting as fever of unknown origin in an adult woman: a case report. J Med Case Rep 2014; 8:266. (2014)	Turkey	Case report; n = 3; non-occupational (home)/chronic	Female = 1, male = 2 (14y, 52y, NI)	High	Anemia = 1, leukocytosis = 3	NA	3
Mathee et al. ⁴⁸48. Mathee A, Naicker N, Kootbodien T, Muluma T, Nkomo P, Naik I, et al. A cross sectional analytical study of geophagia practices and blood metal concentrations in pregnant women in Johannesburg, South Africa. S Afr Med J 2014; 104:568-70. (2014)	South Africa	Cross-sectional; n = 307 (exposed = 60, not exposed = 247); non-occupational (geophagia)/chronic	Female = 307 (18-46y)	Normal	Anemia = 52, normal = 255	No association (OR not informed), no mean difference, p = 0.183	2
Kim et al. ⁵¹51. Kim KN, Bae S, Park HY, Kwon HJ, Hong YC. Low-level mercury exposure and risk of asthma in school-age children. Epidemiology 2015; 26:733-9. (2015)	Korea	Cohort; n = 4,350 (no control); non-occupational (food)/chronic	Female = 2,175, male = 2,175 (7y)	High	Basophilia = 191, neutrophilia = 191, lymphopenia = 191, normal = 4,159	Linear mixed model, β = 1.38 (95%CI: 0.11; 2.65)	2
Oulhote et al. ⁵²52. Oulhote Y, Shamim Z, Kielsen K, Weihe P, Grandjean P, Ryder LP, et al. Children's white blood cell counts in relation to developmental exposures to methylmercury and persistente organic pollutants. Reprod Toxicol 2017; 68:207-14. (2017)	Denmark	Cohort; n = 56 (no control); non-occupational (food)/chronic	Female = 33, male = 22, NI = 1 (7-12y)	Normal, high *	Leukopenia = 56, basopenia = 56, lymphopenia = 56, monocytopenia = 56	Structural equation, β = -0.23 (95%CI: -043; -0.04), p = 0.02	2
Weinhouse et al. ⁵³53. Weinhouse C, Ortiz EJ, Berky AJ, Bullins P, Hare-Grogg J, Rogers L, et al. Hair mercury level is associated with anemia and micronutrients status in children living near artisanal ans small-scale gold mining in the Peruvian Amazon. Am J Trop Med Hyg 2017; 97:1886-97. (2017)	Peru	Cross-sectional; n = 83 (no control); non-occupational (gold mining + food)/chronic	Female = 44, male = 38, NI = 1 (< 12y)	Normal = 35, high = 48	Anemia = 41, normal = 42	Multivariate linear, regression model, β = -0.14g/dL, p = 0.04	2

Study (year)	Country	Study characteristics [design/number/exposure]	Population [age/sex]	Mercury level	Hemtologic effect	Statistical analysis	EPHHP tool
Butt & Simonsen ⁴¹41. Butt EM, Simonsen DG. Mercury and lead storage in human tissue. Am J Clin Pathol 1950; 20:716-23. (1950)	USA	Cross-sectional; n = 134, no control (occupational = 1, non-occupational = 55, NI = 78); occupational (fur cleaning plant)/chronic	Female (49y)	High	Thrombocytopenia = 1	ND	3
Devlin & Sudlow ¹⁰⁸108. Devlin HH, Sudlow M. Peripheral mercury embolization ocurring during arterial blood sampling. BMJ 1967; 1:347-8. (1967)	UK	Case report; n = 1; occupational (laboratory)/chronic	Male (32y)	High	Leukopenia = 1, thrombocytopenia = 1	NA	3
Takamatsu et al. ¹⁰⁹109. Takamatsu M, Maeda H, Inuzuka T, Futatsuka M, Arimatsu Y. Health hazards of workers engaged in the laboratory of a fungicide factory. Journal of the Kumamoto Medical Society 1969; 43:93-8. (1969)	Japan	Case series; n = 5; occupational (agriculture)/chronic	Male = 5 (adults = 5)	High = 5	Leukopenia = 5	NA	3
Ryrie et al. ³⁸38. Ryrie DR, Toghill PJ, Tanna MK, Galan GN. Marrow suppression from mercury poisoning? BMJ 1970; 1:499. (1970)	UK	Case report; n = 1; occupational (thermometer fabric)/acute	Male (59y)	High	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Gys & Fadeev ⁸⁰80. Gys YF, Fadeev AP. Clinical aspects of occupational intoxications by organic mercury toxic chemicals among agricultural workers in the Chelyabinsk region. Scientific Transactions of Leningrad Postgraduate Medical Institute 1971; 8:127-33. (1971)	USSR	Cross-sectional; n = 103 (no control); occupational (agriculture)/chronic	NI (adults = 103)	ND	Leukopenia = ?	ND	3
Nizov & Shestakov ¹¹⁰110. Nizov AA, Shestakov HM. Contribution to the clinical aspects of granosan poisoning. Sov Med 1971; 11:150-2. (1971)	USSR	Case series; n = 10; occupational (agriculture)/acute	NI (adults = 10)	ND	Anemia = 10, leukopenia = 10	NA	3
Jung & Aaronson ¹¹¹111. Jung RC, Aaronson J. Death following inhalation of mercury vapor at home. West J Med 1980; 132:539-43. (1980)	USA	Case report; n = 1; occupational (gold mining)/acute	Male (53y)	High	Polycythemia = 1; leukocytosis = 1; neutrophilia = 1	NA	3
Lien et al. ⁸⁶86. Lien DC, Todoruk DN, Rajani HR, Cook DA, Herbert FA. Accidental inhalation of mercury vapour: respiratory and toxicologic consenquences. Can Med Assoc J 1983; 129:591-5. (1983)	Canada	Case series; n = 7 (occupational = 1, non-occupational = 6); occupational (gold mining)/acute	Male = 1 (28y)	High = 1	Leukocytosis = 1	NA	3
Kanamaru et al. ⁷⁵75. Kanamaru M, Suzuki H, Katoh M, Nishikawa T, Ohyama Y, Noda H. Effects of agricultural chemicals on rural inhabitants in Miye prefecture: a report on the findings of health examinations. Journal of the Japanese Association of Rural Medicine 1984; 33:159-66. (1984)	Japan	Cross-sectional; n = 1,164 (no control); occupational (agriculture)/chronic	Female = 397, male = 767 (adults = 1,164)	Female x = 2.97, male x = 5.35	Anemia = 197, normal = 967	ND	3
Langworth et al. ⁴⁴44. Langworth S, Elinder EG, Sundqvist KG. Minor effects of low exposure to inorganic mercury on the human immune system. Scand J Work Environ Health 1993; 19:405-13. (1993)	Sweden	Cross-sectional; n = 110 (exposed = 71, not exposed = 39); occupational (chlor-alkali fabric/lamp facgtory/dentist office)/chronic	Female 75, male = 35 (exposed x = 49y, not exposed x = 40y)	Exposed x = 4.3, not exposed x = 3.9	Normal = 110	t-test, no mean difference, Pearson r not informed, no correlation	3
Torresani et al. ¹¹²112. Torresani C, Caprari E, Manara GC. Contact urticaria syndrome due to phenylmercuric acetate. Contact Dermatitis 1993; 29:282-3. (1993)	Italy	Case report; n = 1; occupational (agriculture)/chronic	Female (54y)	ND	Eosinophilia = 1	NA	3
Zavariz & Glina ¹³13. Zavariz C, Glina DMR. Efeitos da exposição ocupacional ao mercúrio em trabalhadores de uma indústria de lâmpadas elétricas localizada em Santo Amaro, São Paulo, Brasil. Cad Saúde Pública 1993; 9:117-29. (1993)	Brazil	Cross-sectional; n = 91 (no control); occupational (lamp fabric)/chronic	Female = 8, male = 83 (20-65y)	High = 54, normal = 32, NI = 42	Anemia = 1, leukopenia = 6, lymphocytosis = 6, eosinophilia = 5, neutrophilia = 4, normal = 69	ND	3
Moszczyński & Slowiński ²²22. Moszczynski P, Slowinski S. The behaviour of T-cell subpopulations in the blood of workers exposed to mercury. Med Lav 1994; 85:239-41. (1994)	Poland	Cross-sectional; n = 91 (exposed = 55, not exposed = 36); occupational (chlor-alkali fabric)/chronic	Male = 91 (28-55y)	High = 55, normal = 36	Lymphocytosis = 55, normal = 36	t-test, no mean difference, Pearson r = 0.3405, p < 0.05	3
Alvarado et al. ³⁴34. Alvarado EV, Ramírez JA, Nilsman M, Bonilla R. Intoxicación sistemática por mercurio elemental depositado en el organismo. Medicina Legal 1995; 12:36-40. (1995)	Costa Rica	Case report; n = 2 (occupational = 1, non-occupational = 1); occupational (compressor)/chronic	Male (30y)	High	Normal = 1	NA	3
Moszczyński et al. ²³23. Moszczynski P, Slowinski S, Rutkowski J, Bem S, Jakus-Stoga D. Lymphocytes, T and NK cells, in men occupationally exposed to mercury vapours. Int J Occup Med Environ Health 1995; 8:49-56. (1995)	Poland	Cross-sectional; n = 117 (exposed = 81, not exposed = 36); occupational (chlor-alkali fabric)/chronic	Male = 117 (21-60y)	Exposed x = 54	Lymphocytosis = 81, normal = 36	t-test, no mean difference, Pearson r = -0.11, 0.10, no correlation	3
Queiroz & Dantas ¹²12. Queiroz MLS, Dantas DCM. B lymphocytes in mercury-exposed workers. Pharmacol Toxicol 1997; 81:130-3. (1997)	Brazil	Cross-sectional; n = 41 (exposed = 33, not exposed = 8); occupational (chlor-alkali fabric)/chronic	NI (19-46y)	Normal = 41	Lymphopenia = 33, normal = 8	Mann-Whitney’s U, mean difference, p < 0.05, Pearson r = -0.077, no correlation	3
Melo et al. ¹¹³113. Melo B, Cortes B, Mujica G, Acosta M, Cortez A, Bourg D, et al. Exposición mercurial y estado de salud del personal que labora en el servicio de odontología del IPASME Barquisímeto. Acta Odontol Venez 2000; 38:24-31. (2000)	Venezuela	Cross-sectional; n = 47 (no control); occupational (dentist office)/chronic	NI	NI	Hemoglobin alteration = 4, leukocyte alteration = 3, normal = 40	ND	3
Zabiński et al. ⁴⁵45. Zabinski Z, Dabrowski Z, Moszczynski P, Rutowski J. The activity of erythrocyte enzymes and basic indices of peripheral blood erythrocytes from workers chronically exposed to mercury vapours. Toxicol Ind Health 2000; 16:58-64. (2000)	Poland	Cross-sectional; n = 81 (exposed = 46, not exposed = 35); occupational (chlor-alkali fabric)/chronic	NI (20-56y)	x = 77.44 ± 48.15 (exposed/not exposed)	Polycythemia = 46, normal = 35	t-test, mean difference, 47.89% vs. 46.1%, p < 0.05	3
Soleo et al. ²⁴24. Soleo L, Colosio C, Alinovi R, Guarnieri D, Russo A, Lovreglio F, et al. Immunological effects of exposure to low exposure to inorganic mercury. Med Lav 2002; 93:225-32. (2002)	Italy	Cross-sectional; n = 289 (exposed = 117, not exposed = 172); occupational (lamp fabric)/chronic	NI (adults = 289)	Normal = 289	Lymphocytosis = 117, normal = 172	t-test, no mean difference, Pearson r = 0.184, positive correlation	3
Campbell et al. ⁷⁴74. Campbell G, Leitch D, Lewington AJP, Dargan PI, Baker RJ. Minimal change nephrotic syndrome due to ocupational mercury vapor inhalation. Clin Nephrol 2009; 3:216-9. (2009)	UK	Case report; n = 1; occupational (lamp fabric)/acute	Male (25y)	High	Polycythemia = 1	NA	3
Rodríguez et al. ¹¹⁴114. Rodríguez EA, Tubio FPM, Ferrera JMD. Enfermedades de los trabajadores de las minas de Almadén y Almadenejos (España, 1883-1887). Salud Trabaj (Maracay) 2011; 19:147-59. (2002)	Spain	Cross-sectional; n = 26 (no control); occupational (gold mining)/chronic	NI	ND	Anemia = 26	NA	3
Alhamad et al. ¹¹⁵115. Alhamad T, Rooney J, Nwosu A, Maccombs J, Kim YS, Shukla V. Lessons learned from a fatal case of mercury intoxication. Int Urol Nephrol 2012; 44:647-51. (2011)	USA	Case report; n = 1; occupational (thermometer fabric)/acute	Male = (36y)	High	Leukocytosis = 1, eosinophilia = 1	NA	3
Douine et al. ⁵⁴54. Douine M, Mosnier E, Le Hingrat Q, Charpentier C, Corlin F, Hureau L, et al. Illegal gold miners in French Guiana: a neglected population with poor health. BMC Public Health 2017; 18:1-20. (2018)	Guyana/Suriname	Cross-sectional; n = 421 (exposed = 202, not exposed = 219); occupational (gold mining)/chronic	Female = 124, male = 297 (x = 37y)	ND	Anemia = 93, normal = 328	Prevalence 22% (95%CI: 18.0; 25.9)	2

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[1] Correspondence A. S. Vianna Instituto de Estudos de Saúde Coletiva, Universidade Federal do Rio de Janeiro. Av. Horácio Macedo s/n, Rio de Janeiro, RJ 21941-598, Brasil. angelica@iesc.ufrj.br