A Brazilian Minamata disease? Neurologists must be aware of mercury exposure and intoxication

Abstract

Mercury intoxication poses a significant challenge and growing threat to public health, particularly in the Amazon region. Despite a known history of neurological damage, as evidenced by Japan's Minamata disease, mercury intoxication remains underdiagnosed in Brazil. This review underscores the need for increased clinical awareness among neurologists, as mercury exposure has been linked to over 250 neurological symptoms, including cognitive impairment, cerebellar ataxia, peripheral neuropathy, and psychiatric disturbances. The Indigenous and riverside populations in the Amazon present a high prevalence of cognitive and motor deficits, tremors, and sensory disturbances, which are associated with mercury body burdens. Diagnosis relies on a combination of clinical suspicion, environmental exposure history, and biomonitoring through hair and urine analyses. Given the widespread environmental contamination and potential long-term health consequences, neurologists must be vigilant in recognizing and managing mercury-related neurotoxicity, particularly in vulnerable Brazilian populations.

 

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Keywords

Mercury - Mercury Poisoning, Nervous System

THE USE OF MERCURY IN BRAZIL: AN ENVIRONMENTAL AND PUBLIC HEALTH TRAGEDY

The Amazon rainforest encompasses the world's largest river system, enormous biodiversity, and mineral resources that have been exploited for centuries.[1] Gold mining has been uncontrolled, increasing by almost 495% in Indigenous lands in the last decade.[2] [3] Mining sites, known as garimpo, largely and illegally use mercury for gold extraction.[4] Currently, this is a large-scale activity that frequently uses heavy machinery, rather than “artisanal” or “small-scale” as described in international reports.[5] [6] More than directly linked to deforestation, this process disrupts fishing, poisons the water, and can harm human health.[4] Consequently, mercury concentrations exceed permissible limits across multiple matrices, ranging from commercial fish to the hair of riverside populations.[7] [8]

Beyond these issues, there are also other ongoing public health concerns. The World Health Organization (WHO) has been supporting the phase-down use of mercury in dental care for more than 10 years.[9] Despite this, the use of encapsulated mercury-containing amalgams continues in Brazil.[10] Dental amalgams, even the encapsulated, have the potential of increasing the mercury concentration in blood, brain, and urine, which is linked to a high risk of infertility, inflammatory diseases, neurodevelopmental disorders, as well as Alzheimer's and Parkinson's diseases.[11] [12] [13] [14] [15] [16] [17] Inorganic mercury is also frequently detected in noncontrolled imported cosmetics,[18] [19] which is a great problem, as Brazil is one of the world's largest beauty product consumers.

Responsible for a myriad of health issues, mercury intoxication has already been linked to different neurological symptoms. Considering the ongoing environmental tragedy, the use of mercury-containing amalgams and cosmetics, and the underdiagnosis of mercury intoxication in Brazil,[5] [20] this review aims to alert neurologists to its clinical suspicion and differential diagnosis.

 

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NEUROLOGICAL ASPECTS

The Japanese Minamata basin tragedy was the first great awareness of methylmercury (MeHg) poisoning. Children exposed in utero and diagnosed with congenital Minamata disease had intellectual disabilities, cerebellar ataxia, failure to thrive, limb deformities, epilepsy, strabismus, and an increased prevalence of cerebral palsy.[21] [22] Later, homemade bread prepared with grain treated with MeHg as a fungicide caused a severe outbreak of cases in Iraq.[21] In the face of these enormous public health issues, researchers and politicians started to debate the acute and chronic aspects of mercury neurotoxicity.

Although less widespread and resolutive than necessary, this discussion currently exists in Brazil. In 15 years, the Latin America's largest country registered more than 600 cases of mercury intoxication,[20] [23] and most specialists assert the real number is even higher, due to underdiagnosis and notification problems.[5] [20] As shown in [Figure 1], only 15.6% of officially notified cases occurred in the Amazon region, despite it harboring 92% of the country's gold mining activities.[20] This discrepancy suggests an alarming under-reporting of mercury intoxication in this region. Indeed, notwithstanding hundreds of cases in other Brazilian regions, there are no consistent published papers regarding intoxication's neurological symptoms or assessment.

Figure 1 Distribution of reported cases in Brazil from 2007 to 2022. Source: Modified from Crespo-Lopez et al.[20]. The figure was elaborated using Datawrapper.

Despite its pulmonary, urinary, dermatological, and gastrointestinal effects,[24] this review will attain the neurological aspects of mercury intoxication, focusing on the national perspectives, particularly in the Amazon population, due to the underreported issues mentioned above ([Figure 2]).

Figure 2 Map of the Amazon region. Geographical distribution of the clinical assessments reported in this review.

From bench to clinics

Mercury can be found in three main species: the highly volatile elemental mercury (Hg⁰), inorganic mercury (as found in mercury salts used in some cosmetics), and organic mercury (mainly MeHg). Elemental mercury has numerous uses in industry, such as fluorescent lamps, dental amalgams, and gold recovery, among others. The Hg⁰ vapor, released into the air by these anthropogenic sources, is scattered by precipitation to soil and water (Hg²⁺).[5] A bacterial biomagnification process transforms the inorganic mercury into MeHg, introducing it into the food chain.[5] Therefore, mercury reaches humans mainly by air (Hg⁰ vapor) and food (MeHg intake), as well as by direct dermal contact (inorganic mercury and Hg⁰), to a lesser degree. The main food contaminated with MeHg is seafood. The elemental species are mainly absorbed by the lungs, but also through the skin to a lesser extent.[21]

Around 95% of the ingested MeHg is absorbed by the human body.[25] Once in the bloodstream, it is carried by hemoglobin and Hg⁰ by cysteine/albumin/glutathione to the organs[25] and actively transported to the brain by the blood–brain barrier.[26] Furthermore, MeHg is slowly excreted, mainly by bile and feces, despite being detected in small amounts in human milk and urine.[21] It can also rapidly cross the placenta and transfer to the fetus.[21] All species of mercury are neurotoxic due to acute and/or chronic exposure.[21] However, this review will focus on the main ones (MeHg and Hg⁰) responsible for the neurological outcomes of human intoxication.[27]

The exposure pathway is relevant in addition to quantity. For example, inhaled Hg⁰ rapidly crosses the blood–brain barrier when compared with the other mercury species and can lead to severe acute intoxication.[21] However, lower MeHg concentrations lead to worse outcomes, making it more neurotoxic than Hg⁰.

It is important to highlight that humans can be exposed to more than one mercury species simultaneously, through different pathways. For example, a garimpo worker can be exposed by inhalation during work, eating contaminated fish, and having their teeth repaired with mercury-containing amalgam. Gender, nutritional aspects, and other intraindividual factors, such as genetic polymorphisms and the microsomal system, could explain different physiopathological processes in the same population and interfere with the poisoning response.[21] [28] [29]

Mercury's neurotoxicity arises through multiple mechanisms, including the induction of oxidative stress, impairment of mitochondrial function, and disruption of neurotransmitter homeostasis.[30] In the peripheral nervous system, MeHg binds to the myelin sheath, damaging preferentially sensory neurons and dorsal root ganglia.[31] Additionally, there is documented evidence of degeneration in the granule and Purkinje cell layers of the cerebellum,[32] cerebral cortex,[33] and hippocampus ([Figure 3]).[34]

Figure 3 Illustration of the main molecular mechanisms of mercury neurotoxicity.

 

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Central nervous system

Exposure to MeHg in adults provokes focal central nervous system (CNS) impairment, while the developing brain is more susceptible to severe and global injury.[21] Congenital Minamata disease due to alimentary MeHg exposure is the most well-known neurological damage in children. All the affected newborns had intellectual disability, cerebellar ataxia, difficulty thriving, and limb deformities.[22] Most of them had epilepsy (82%), strabismus (77%), and pyramidal signs (75%), rather than the almost five times increased cerebral palsy prevalence.[21] [22] Regarding national perspectives, studies are urgently needed to assess the real prevalence of congenital diseases among Brazilian children.

Cognitive impairment has also been proven in adults. Even basal mercury levels (1–2 ppm of hair mercury) due to chronic MeHg exposure have been significantly associated with worse results on rapid-processing cognitive tasks.[35] This diminished cognitive performance was correlated with a lower gray matter volume in the thalamus and hippocampus, as well as widespread reduced white matter volume, especially in the right basal ganglia and both frontal lobes.[35]

Executive function involvement has already been confirmed in the Amazonian vulnerable populations.[27] In the Yanomami indigenous population living in the Northwest Amazon, there was a 95.9% higher prevalence of reduced cognitive performance among individuals with MeHg levels > 6.0 mcg/g in comparison to those with lower levels.[36] Also, Munduruku individuals of the Tapajós river basin with over 10 ppm of hair mercury have presented a 2-fold higher risk of alterations in the brief cognitive screening battery (BCSB) and verbal fluency (VF) test than those with lower MeHg levels.[37] Additionally, other vulnerable Amazonian populations, such as riverside communities, have registered cognitive alterations. In the Madeira river basin, children and adolescents with high mercury levels had lower scores in estimated intelligence quotient (IQ), visuospatial working memory, semantic knowledge, and phonological verbal fluency.[38]

Behavioral abnormalities are other classic descriptions of acute or chronically intoxicated patients. Erethism (historically known as Mad Hatter syndrome) is the name given to increased excitability, emotional lability, and irritability related to mercury poisoning (especially Hg⁰).[39] Other frequent neurological symptoms in acute Hg⁰ poisoning are headache, nausea, abdominal pain, and distal limb paresthesia, as described in 179 pediatric Turkish cases.[40]

Acute and chronic mercury exposure is also associated with several types of movement disorders. Cerebellar ataxia and dysarthria with cerebellar features are the most described findings.[41] Furthermore, tremors, cortical myoclonus, chorea, and Parkinsonism were reported worldwide.[42] In the Brazilian Amazon, a study involving gold traders detected a high frequency (6,6–10 Hz) of appendicular tremor.[43] In another interesting national investigation, chronically exposed gold miners were detected with higher rates of appendicular ataxia, nystagmus, and tremors.[44]

 

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Visual system

Ophthalmological issues are pivotal in Minamata disease. Bilateral visual field constriction associated with visual acuity impairment was largely related to MeHg intoxication,[41] encompassing the classical description of the disorder. A possible explanation is the atrophy of calcarine fissures (primary visual cortex), which spares occipital poles, preserving the central vision.[45] [46] [47]

In the Amazon population, impairment in color discrimination has been described as the main ophthalmologic finding, being associated with chronic MeHg contamination in adults[48] and children.[49] Additionally, there is a positive correlation between MeHg levels and the magnitude of the visual impairment,[49] diminished contrast sensitivity,[50] and reduced peripheral visual fields.[51]

 

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Peripheral nervous system

Mercury serum levels are higher in patients diagnosed with idiopathic axonal neuropathy. However, the required damaging concentration and duration of exposure are still unknown.[52] Although electrophysiologic studies revealed consistent axonal polyneuropathy involving both motor and sensory fibers in a patient exposed to chronic inorganic mercury,[53] sensory disturbance (numbness and paresthesia), especially in Minamata's patients, is more attributable to sensory cortex damage than to peripheral nerve lesions.[54]

Damaged afferent proprioceptive pathways could explain the higher prevalence of postural instability[55] and gait deviation with closed eyes in MeHg-contaminated individuals.[56] There is also a higher impairment in tactile sensation, two-point discrimination, and vibration in almost all body parts.[57] However, more neurophysiological assessments are necessary to analyze and discriminate large- and small-fiber involvement.

For instance, in the Yanonami population, it is estimated that approximately 30.3% of those with high levels of MeHg have some degree of peripheral neuropathy, mainly those with mercury levels above 6 µg/g.[36] In another Brazilian cohort, hand grip, manual dexterity, and muscular fatigue were also correlated with high MeHg levels.[58] These findings underscore the need for comprehensive national evaluations of mercury-associated peripheral neuropathy, employing a methodologically rigorous approach. Accurate diagnosis requires the exclusion of differential etiologies through the application of standardized diagnostic criteria for peripheral neuropathy, complemented by neurophysiological assessments. Such evaluations are essential to underly pathophysiological mechanisms and characterize patterns of nerve injury.

Despite rarity, subacute mercury poisoning due to skin-lightening creams and products from traditional Chinese medicine has already been related to complex neuromuscular findings.[59] A case series described patients presenting subacute fasciculation, cramps, myokymia, and neuromyotonia as a differential diagnosis of hyperexcitability disorders (Isaacs and Morvan syndromes). Motor neuron disease in an isolated form[60] [61] was already described as associated with presynaptic myasthenic involvement, mimicking an overlap between amyotrophic lateral sclerosis and Lambert-Eaton syndrome.[59] Additionally, there is a report of vacuolar myopathy related to dental amalgams,[62] however, further descriptions in the literature concerning myopathy secondary to mercury intoxication are still scarce.

 

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Cardiovascular risk

According to the most robust evidence (systematic review and meta-analyses), more than 2 ppm of mercury in hair is associated with a 59% increase in the relative risk of hypertension and a significant increase in the risk of fatal and nonfatal outcomes related to cardiovascular diseases.[63] This is alarming considering that current chronic exposure to MeHg in Brazil can be 15 to 100 times higher (∼30 μg/L of blood mercury)[64] [65] than reported in some international cohorts.[66] [67] [68]

In specific Brazilian Munduruku Indigenous villages, a positive correlation between mercury intoxication and high blood pressure in pregnant women was reported.[69] Cross-sectional studies[64] found dyslipidemia and high/moderate cardiovascular risk correlated with hair mercury levels in chronically exposed riverside populations in the Amazon. Furthermore, a high prevalence of hypertension, metabolic syndrome, and a high risk of acute myocardial infarction have been registered in exposed populations of different Amazonian basins.[70] [71] Neurologists need to be alerted to the early screening of these patients due to the increased risk of stroke.

 

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Miscellaneous findings

Bilateral hearing impairment was described and, despite cochlear involvement, some pathological studies found that the primary auditory area of the temporal lobe was affected, which is probably the main etiology.[54] A perioral sensory disturbance, described as an “onion peel,” is common, indicating somatosensory cortical involvement instead of peripheral damage.[41]

Other documented symptoms in exposed individuals living in the Amazon were insomnia, depression, anxiety, limb pain,[72] and partial hearing loss.[44] However, to this date, these findings lack a statistically significant correlation with mercury levels and differential diagnosis.

 

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Neuroimaging

Brain magnetic resonance imaging (MRI) may show gray matter volume reduction in cerebellum, calcarine fissure, and thalamus.[73] Exposure time is associated with different patterns, with the thalamic atrophy being most evident in fetuses (contaminated since the intrauterine life), while cerebellar and calcarine fissure abnormalities are more commonly observed in those affected during childhood or adult life.[73] Some case reports showed reversible, subcortical, white matter T2-hyperintense lesions in acutely intoxicated children.[74] [75] Nonetheless, the main neuroimaging application in mercury intoxication is helping to rule out the differential diagnoses.

 

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WHEN TO SUSPECT

Neurologists should always raise suspicion when consulting a patient presenting the constellation of symptoms mentioned above ([Table 1]) reporting previous exposure to a potential source of mercury (such as high intake of fish, presence of dental amalgams, use of imported cosmetics, work in garimpos, use of thermometers and batteries) given special attention to the Amazon populations.[7] [8] [76] Another interesting point is that neurological symptoms could appear at least 20 years after exposure, as described in the classical Minamata disease[21] and the anamnesis is hugely important at this moment to establish causal correlation. Child neurologists should screen for mercury intoxication in patients presenting CNS lesions (cerebral-palsy-like) without the most prevalent acquired and genetic causes. A careful investigation into patients' history is needed, questioning the mothers about environmental/occupational exposure.

Table 1 Main neurological findings in chronic mercury intoxication described in this review

	Signs and symptoms	References
Cognition and behavioral	Reduced performance in BCSB and the verbal fluency test, and erethism (increased excitability, emotional lability, and irritability).	[37] [39]
Ophthalmological	Bilateral visual constriction, color discrimination deficit, and reduced contrast sensitivity.	[41] [48] [50]
Neuromuscular	Sensory axonal neuropathy with preserved deep tendon reflexes, numbness, and paresthesia.	[36] [41] [57]
Movement disorders	High-frequency tremor (6.6–10 Hz), cerebellar ataxia. Others (see text, less frequent).	[41] [43] [44]
Miscellanea	Bilateral hearing impairment, “onion peel” perioral paresthesia.	[41] [44] [54]
Neurodevelopmental and congenital disease	Intellectual disability, failure to thrive, limb deformities, epilepsy, strabismus, pyramidal signs, cerebral palsy-like.	[22]

Abbreviations: BCSB, brief cognitive screening battery; Hz, Hertz.

No case of mercury poisoning from drinking contaminated water has ever been described because it is hardly found in sufficient quantities, and direct gastrointestinal absorption of inorganic mercury (as mainly found in water) is low. However, any presence of mercury in water influences the contamination of the food chain.[7] [76] Higher levels of mercury are currently found in the riverside population living near the Tucuruí hydroelectric dam (in the Tocantins river region, which is not influenced by gold mining).[29] [64] [71]

It is worth noting that the consequences of mining can extend far beyond the extraction site, and clinical suspicion should not be restricted to people living closer to mining areas or in the Amazon region. Any Brazilian inhabitant who frequently consumes fish and seafood may be exposed to organic mercury. Almost all Brazilian states have already registered confirmed or suspected cases of acute or chronic exposure/intoxication ([Figure 1]).[5] [20] Thus, this should concern all Brazilian health professionals who work with neurological diseases.

 

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DIAGNOSIS

There is no pathognomonic test. The suspected cases must be analyzed from the cluster of symptoms ([Table 1]),[21] previous personal exposure, analyses of mercury body burden, and correlation analysis of risk factors and differential diagnosis. The 1977 Diagnostic Criteria of Minamata Disease may be used, but its accuracy is debated[77] and there is no validation data in the Brazilian population. After the initial suspicion, the physician must fill in a compulsory notification form alerting the regional health secretary. Then, local authorities are officially obligated to investigate epidemiological risks and perform laboratory analyses.[78]

Urinary mercury is indicative of exposure mainly to Hg⁰, as a significant part is transformed into inorganic mercury and eliminated in the urine. Otherwise, hair mercury indicates exposure primarily to MeHg, as approximately 10% of this species is deposited in the hair, which is directly correlated with the brain load.

Unlike blood analysis, both urinary and hair analyses are noninvasive and informative methods. Blood mercury is from any pathway of exposure, being therefore nonspecific). As such, mercury analysis in hair is less expensive and has good correlations, as MeHg is slowly accumulated over time.[79] The hair from the initial 0.5 cm next to the scalp represents, on average, MeHg exposure during the 3 weeks before the collection date (Supplementary Material – available at https://www.arquivosdeneuropsiquiatria.org/wp-content/uploads/2025/06/ANP-2025.0161-Supplementary-Material.docx).

For the diagnosis and interpretation of laboratory results, it is essential to understand that, in chronic mercury exposure, the levels fluctuate over time, increasing when a new load received and subsequently decreasing through metabolism and the metal's clearance.[79] Therefore, considering the coexposure risk, patients should be assessed using both urinary and hair analyses. Those with negative levels and high clinical suspicion must be followed by the doctor and have their laboratory reassessed later. Another essential point is that mercury levels do not necessarily correlate with symptoms, considering the latency since the start of exposure (sometimes of decades, as described before). Therefore, patients presenting high levels of mercury without evident signs or symptoms must also be monitored.

The WHO recommends a provisional tolerable weekly intake (PTWI) for MeHg of 1.6 µg/Kg body weight (see Supplementary References), which is approximately equivalent to 2.3 mg/Kg of hair mercury.[7] Other agencies such as the Environmental Protection Agency of the United States (USEPA) and the National Institute for Public Health and the Environment of the Netherlands (NIPHE) are more cautious, and they recommend a PTWI of 0.7 µg/Kg body weight (equivalent to 1.0 mg/Kg of hair mercury).[8] Despite these recommendations, it is crucial to be aware of the individual factors (genetic, nutritional, occupational, coexposure, etc.) influencing the neurological outcomes. Therefore, any mercury concentration has the potential to be neurotoxic, requiring a case-by-case analysis (see Supplementary References).

 

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TREATMENT

In acute poisoning, patients require inpatient evaluation and emergency care. Gastric lavage and activated charcoal are possible prescriptions, but their value has been challenged and lacks clinical evidence (see Supplementary References). Hemodialysis could be a helpful strategy for severely ill patients (see Supplementary References). Special attention to pulmonary complications must be offered for those with acute Hg⁰ vapor exposure by inhalation (see Supplementary References).

To date, no controlled clinical study has demonstrated the efficacy of the treatment with chelation agents in mercury intoxication (see Supplementary References). Due to the high adverse effects of the use of these agents, the risk-benefit therapeutic index must be carefully evaluated in each case. Chelating agents with thiol groups (dimercaptosuccinic acid, DMSA, and N-acetyl-D-L-penicillamine) have already been used for acute intoxication, but their real effect has been questioned, and more studies are needed (see Supplementary References). Furthermore, chelation therapy can only decrease the mercury level in blood, without any direct impact on symptoms already established, especially neurological outcomes. The availability of these agents in the Brazilian health system are another challenge.

For chronic intoxication, it must be highlighted that chelation therapy is not recommended, as there is no clinical evidence of efficacy. Furthermore, the presence of side effects was noted. Indeed, the main therapy remains to remove the patient from the source of exposure and provide them with health support. Chronic patients with cognitive, psychiatric, and neurological sequelae can be treated with psychotropic and relief medications. Unfortunately, there is no therapy to reduce neuronal damage after long exposure.[41]

 

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IS THERE A BRAZILIAN MINAMATA DISEASE?

Especially on Amazon, numerous epidemiological studies[27] have suggested neurological outcomes associated with mercury exposure and intoxication. Considering the spread of this pollutant, a national assessment is urgent, with Hg⁰ remaining airborne for a long time and travel long distances, and fish with MeHg being sold in national and international markets. There is an enormous lack of information owing to underdiagnosis and unawareness among the population and doctors. The number of exposed people is higher than official records, as demonstrated in the Amazon by comparing Brazilian government data[5] with that of scientific literature.[27] Unfortunately, there are newborns and elderly people struggling with neurological conditions without knowing the name of their disease.

Adult and child neurologists must raise their suspicions and contribute to case notification. More patients must be tested for mercury exposure inside and outside the Amazon river basin. At the same time, the population should be enlightened about the symptoms and the disease progression. All patients presenting with acute or chronic suggestive features ([Table 1]) and potential exposure (Amazonian populations, consumption of contaminated fish and seafood, dental amalgams, and illegal cosmetics) with no other common/clear etiology for the symptoms must be notified and tested for mercury exposure.

Despite all the alerts from toxicologists, politicians continue to turn a blind eye to this issue. As health professionals, we cannot do the same. Initiatives must be supported, such as the bill proposal n° 1011/2023 for the implementation of National Policies to Prevent Mercury Exposure in Brazil, engaging collaborative efforts of Amazonian public institutions, especially universities, to increase mercury monitoring and prevention strategies. It is important to engage in collaborative efforts and increase mercury monitoring, enhance diagnosis, and raise prevention strategies. Then, the course of this announced tragedy might change.

Additional references are available in the “Supplementary References” section provided online.

 

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Conflict of Interest

The authors have no conflict of interest to declare.

Acknowledgments

We thank the National Council for Scientific and Technological Development (CNPQ) for the scholarship awarded to JLMN (314004/2023 -8 /2024). We also thank CNPq for the grant numbers 313406/2021 -9 and 406442/2022 -3, Fundação Amazônia de Amparo a Estudos e Pesquisas (FAPESPA, grant number 040/2023), and the Brazilian Ministry of Public Security (Termo de Execuç ão Descentralizada- MJSP n° 08/2023 (26068571). We also thank Datawrapper for being a tool to map development. [Figure 3] was created in BioRender (Alves, GM (2025), https://BioRender.com/26n9elm).

Authors' Contributions

Conceptualization: GMA, ELSD, MECL, JLMN; Formal analysis: GMA, ELSD; Funding acquisition: MECL, JLMN; Investigation: GMA, ELSD; Validation: GMA, ELSD; Writing – original draft: GMA, ELSD; Writing – review & editing: GMA, ELSD MECL, JLMN.

Data Availability Statement

All data supporting the findings of the present study are available on paper.

Editor-in-Chief: Ayrton Roberto Massaro's https://orcid.org/0000-0002-0487-5299.

Associate Editor: Orlando G. P. Barsottini's https://orcid.org/0000-0002-0107-0831.

• References

• 1 Putzer H. The geological evolution of the Amazon basin and its mineral resources. In: Sioli H. ed The Amazon: Limnology and landscape ecology of a mighty tropical river and its basin. Dordrecht: Springer Nature; 1984: 15-46 10.1007/978-94-009-6542-3_2
• 2 MapBiomas Brasil. . Área ocupada pela mineração no Brasil cresce mais de 6 vezes entre 1985 e 2020. Accessed March 11, 2025. https://brasil.mapbiomas.org/2021/08/30/area-ocupada-pela-mineracao-no-brasil-cresce-mais-de-6-vezes-entre-1985-e-2020/
• 3 Ellwanger JH, Chies JAB. Brazil's heavy metal pollution harms humans and ecosystems. Sci One Health 2023; 2: 100019
• 4 Ferreira Neto LC, Diniz CG, Maretto RV, Persello C, Pinheiro MLS, Castro MC. et al. Uncontrolled Illegal Mining and Garimpo in the Brazilian Amazon. Nat Commun 2024; 15 (01) 9847
• 5 Crespo-Lopez ME, Arrifano GdP, Augusto-Oliveira M, Araújo AL, Sacramento LdS, Barthelemy JL, Souza CBAd. Mineração e Mercúrio na Amazônia: principais perguntas e respostas. In: Loureiro SMS, Souza Filho EC, Badr E. (orgs.). Mineração de Ouro Artesanal e em Pequena Escala na Amazônia - Grandes Impactos Socioambientais e Violações Multidimensionais de Direitos Humanos. Manaus: UEA, 2023: 15-70
• 6 Crespo-Lopez ME, Arrifano GP, Augusto-Oliveira M, Macchi BM, Lima RR, do Nascimento JLM, de Souza CBA. Mercury in the Amazon: The danger of a single story. Ecotoxicol Environ Saf 2023; 256: 114895
• 7 Martín-Doimeadios RCR, Nevado JJB, Bernardo FJG, Moreno MJ, Arrifano GPF, Herculano AM. et al. Comparative study of mercury speciation in commercial fishes of the Brazilian Amazon. Environ Sci Pollut Res Int 2014; 21 (12) 7466-7479
• 8 Crespo-Lopez ME, Augusto-Oliveira M, Lopes-Araújo A, Santos-Sacramento L, Takeda PY, Macchi BdM. et al. Mercury: What can we learn from the Amazon?. Environ Int 2021; 146: 106223
• 9 World Health Organization. . Future use of materials for dental restoration: Report of the meeting at WHO Headquarters, Geneva, Switzerland, 16–17 November 2009. Geneva: World Health Organization, 2011. . 65 p
• 10 ANVISA. . Agência Nacional de Vigilância Sanitária. Resolução da Diretoria Colegiada – RDC No 879, de 28 de Maio de 2024 . Brazil (2024)
• 11 World Health Organization. . Mercury and health. World Health Organization (WHO)
• 12 Geier DA, Geier MR. Dental Amalgams and the Incidence Rate of Arthritis among American Adults. Clin Med Insights Arthritis Musculoskelet Disord 2021; 14: 11 795441211016261.
• 13 Geier DA, Geier MR. Reported asthma and dental amalgam exposure among adults in the United States: An assessment of the National Health and Nutrition Examination Survey. SAGE Open Med 2021; 9: 20 503121211048677.
• 14 Geier DA, Geier MR. Dental amalgam fillings and mercury vapor safety limits in American adults. Hum Exp Toxicol 2022; 41: 9603271221106341 10.1177/09603271221106341
• 15 Zhu F, Chen C, Zhang Y, Chen S, Huang X, Li J. et al. Elevated blood mercury level has a non-linear association with infertility in U.S. women: Data from the NHANES 2013-2016. Reprod Toxicol 2020; 91: 53-58
• 16 Tibau A, Grube B. Alarming Findings on Mercury Dental Amalgam – Latest Research Using the National Health and Nutrition Examination Survey (NHANES) Database: A Mini-Review. Oral Health Dental Sci 2022; 6 (02) 1-6
• 17 Mutter J. Is dental amalgam safe for humans? The opinion of the scientific committee of the European Commission. J Occup Med Toxicol 2011; 6 (01) 2
• 18 Zero Mercury Wotking Group (ZMWG). . Skin Lighteners Still Online Despite Mercury Findings. 2022. https://www.zeromercury.org/skin-lighteners-still-online-despite-mercury-findings/
• 19 Crespo-Lopez ME, Augusto-Oliveira M, Lopes-Araújo A, Santos-Sacramento L, Souza-Monteiro JR, da Rocha FF, Arrifano GdP. Mercury neurotoxicity in gold miners. Adv Neurotoxicol 2022; 7: 283-314
• 20 Crespo-Lopez ME, Lopes-Araújo A, Basta PC, Soares-Silva I, de Souza CBA, Leal-Nazaré CG. et al. Environmental pollution challenges public health surveillance: the case of mercury exposure and intoxication in Brazil. Lancet Reg Health Am 2024; 39: 100880
• 21 National Research Council (US) Committee on the Toxicological Effects of Methylmercury. . Chemistry, exposure, toxicokinetics, and toxicodynamics. In: Toxicological Effects of Methylmercury. Washington: National Academies Press; 2000. Accessed March 11, 2025. https://www.ncbi.nlm.nih.gov/books/NBK225779
• 22 Harada M. Minamata disease: methylmercury poisoning in Japan caused by environmental pollution. Crit Rev Toxicol 1995; 25 (01) 1-24
• 23 Ministério da Saúde. . Boletim Epidemiológico. Secretaria de Vigilância em Saúde e Ambiente, Brasil. 2023;54(02)
• 24 Kim KH, Kabir E, Jahan SA. A review on the distribution of Hg in the environment and its human health impacts. J Hazard Mater 2016; 306: 376-385
• 25 Bradley MA, Barst BD, Basu N. A Review of Mercury Bioavailability in Humans and Fish. Int J Environ Res Public Health 2017; 14 (02) 169
• 26 Kerper LE, Ballatori N, Clarkson TW. Methylmercury transport across the blood-brain barrier by an amino acid carrier. Am J Physiol 1992; 262 (5 Pt 2): R761-R765
• 27 Santos-Sacramento L, Arrifano GP, Lopes-Araújo A, Augusto-Oliveira M, Albuquerque-Santos R, Takeda PY. et al. Human neurotoxicity of mercury in the Amazon: A scoping review with insights and critical considerations. Ecotoxicol Environ Saf 2021; 208: 111686
• 28 Arrifano GP, Augusto-Oliveira M, Sealey-Bright M, Zainal J, Imbiriba L, Fernandes LMP. et al. Contributing to Understand the Crosstalk between Brain and Periphery in Methylmercury Intoxication: Neurotoxicity and Extracellular Vesicles. Int J Mol Sci 2021; 22 (19) 10855
• 29 Arrifano GPF, Martín-Doimeadios RCR, Jiménez-Moreno M, Fernández-Trujillo S, Augusto-Oliveira M, Souza-Monteiro JR. et al. Genetic susceptibility to neurodegeneration in Amazon: Apolipoprotein E genotyping in vulnerable populations exposed to mercury. Front Genet 2018; 9: 285
• 30 Kang B, Wang J, Guo S, Yang L. Mercury-induced toxicity: Mechanisms, molecular pathways, and gene regulation. Sci Total Environ 2024; 943: 173577
• 31 Nakano T, Yoshida E, Sasaki Y, Kazama S, Katami F, Aoki K. et al. Mechanisms Underlying Sensory Nerve-Predominant Damage by Methylmercury in the Peripheral Nervous System. Int J Mol Sci 2024; 25 (21) 11672
• 32 Bittencourt LO, Chemelo VS, Aragão WAB, Puty B, Dionizio A, Teixeira FB. et al. From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats. Int J Mol Sci 2021; 23 (01) 111
• 33 Teixeira FB, de Oliveira ACA, Leão LKR, Fagundes NCF, Fernandes RM, Fernandes LMP. et al. Exposure to inorganic mercury causes oxidative stress, cell death, and functional deficits in the motor cortex. Front Mol Neurosci 2018; 11: 125 10.3389/fnmol.2018.00125
• 34 Teixeira FB, Fernandes RM, Farias-Junior PMA, Costa NMM, Fernandes LMP, Santana LNS. et al. Evaluation of the effects of chronic intoxication with inorganic mercury on memory and motor control in rats. Int J Environ Res Public Health 2014; 11 (09) 9171-9185
• 35 Takeuchi H, Shiota Y, Yaoi K, Taki Y, Nouchi R, Yokoyama R. et al. Mercury levels in hair are associated with reduced neurobehavioral performance and altered brain structures in young adults. Commun Biol 2022; 5 (01) 529
• 36 Rebouças BH, Kubota GT, Oliveira RAA, Pinto BD, Cardoso RM, Vasconcellos ACS, Basta PC. Long-Term Environmental Methylmercury Exposure Is Associated with Peripheral Neuropathy and Cognitive Impairment among an Amazon Indigenous Population. Toxics 2024; 12 (03) 212
• 37 Oliveira RAAd, Pinto BD, Rebouças BH, de Andrade DC, Vasconcellos ACSd, Basta PC. Neurological Impacts of Chronic Methylmercury Exposure in Munduruku Indigenous Adults: Somatosensory, Motor, and Cognitive Abnormalities. Int J Environ Res Public Health 2021; 18 (19) 10270
• 38 Santos-Lima Cd, Mourão DdS, Carvalho CFd, Souza-Marques B, Vega CM, Gonçalves RA. et al. Neuropsychological Effects of Mercury Exposure in Children and Adolescents of the Amazon Region, Brazil. Neurotoxicology 2020; 79: 48-57
• 39 Ozuah PO. Mercury poisoning. Curr Probl Pediatr 2000; 30 (03) 91-99
• 40 Carman KB, Tutkun E, Yilmaz H, Dilber C, Dalkiran T, Cakir B. et al. Acute mercury poisoning among children in two provinces of Turkey. Eur J Pediatr 2013; 172 (06) 821-827
• 41 Jackson AC. Chronic Neurological Disease Due to Methylmercury Poisoning. Can J Neurol Sci 2018; 45 (06) 620-623
• 42 Ganguly J, Kulshreshtha D, Jog M. Mercury and Movement Disorders: The Toxic Legacy Continues. Can J Neurol Sci 2022; 49 (04) 493-501
• 43 Biernat H, Ellias SA, Wermuth L, Cleary D, Santos ECdO, Jørgensen PJ. et al. Tremor frequency patterns in mercury vapor exposure, compared with early Parkinson's disease and essential tremor. Neurotoxicology 1999; 20 (06) 945-952
• 44 Corbett CEP, El Khouri M, Costa AN, Gyuricza JV, Corbett JF, Frizzarini R. et al. Health evaluation of gold miners living in a mercury-contaminated village in Serra Pelada, Pará, Brazil. Arch Environ Occup Health 2007; 62 (03) 121-128
• 45 Hunter D, Russell DS. Focal cerebellar and cerebellar atrophy in a human subject due to organic mercury compounds. J Neurol Neurosurg Psychiatry 1954; 17 (04) 235-241
• 46 Korogi Y, Takahashi M, Okajima T, Eto K. MR findings of Minamata disease--organic mercury poisoning. J Magn Reson Imaging 1998; 8 (02) 308-316
• 47 Yorifuji T, Tsuda T, Takao S, Harada M. Long-term exposure to methylmercury and neurologic signs in Minamata and neighboring communities. Epidemiology 2008; 19 (01) 3-9
• 48 Feitosa-Santana C, Souza GdS, Sirius EVP, Rodrigues AR, Cortes MIT, Silveira LCdL, Ventura DF. Color vision impairment with low-level methylmercury exposure of an Amazonian population - Brazil. Neurotoxicology 2018; 66: 179-184
• 49 Freitas JdS, Lacerda EMdCB, Martins ICVdS, Rodrigues Jr D, Bonci DMO, Cortes MIT. et al. Cross-sectional study to assess the association of color vision with mercury hair concentration in children from Brazilian Amazonian riverine communities. Neurotoxicology 2018; 65: 60-67
• 50 Rodrigues AR, Souza CRB, Braga AM, Rodrigues PSS, Silveira AT, Damin ETB. et al. Mercury toxicity in the Amazon: contrast sensitivity and color discrimination of subjects exposed to mercury. Braz J Med Biol Res 2007; 40 (03) 415-424
• 51 Lebel J, Mergler D, Lucotte M, Amorim M, Dolbec J, Miranda D. et al. Evidence of early nervous system dysfunction in Amazonian populations exposed to low-levels of methylmercury. Neurotoxicology 1996; 17 (01) 157-167
• 52 Latov N, Kumar G, Vo ML, Chin RL, Carey BT, Langsdorf JA, Feuer NT. Elevated blood mercury levels in idiopathic axonal neuropathy. JAMA Neurol 2015; 72 (04) 474-475
• 53 Chu CC, Huang CC, Ryu SJ, Wu TN. Chronic inorganic mercury induced peripheral neuropathy. Acta Neurol Scand 1998; 98 (06) 461-465
• 54 Ekino S, Susa M, Ninomiya T, Imamura K, Kitamura T. Minamata disease revisited: an update on the acute and chronic manifestations of methyl mercury poisoning. J Neurol Sci 2007; 262 (1-2): 131-144
• 55 Benefice E, Luna-Monrroy S, Lopez-Rodriguez R. Fishing activity, health characteristics and mercury exposure of Amerindian women living alongside the Beni River (Amazonian Bolivia). Int J Hyg Environ Health 2010; 213 (06) 458-464
• 56 Khoury EDT, Souza GdS, Silveira LCdL, Costa CA, Araújo AA, Pinheiro MdCN. Neurological manifestations in riverine populations from areas exposed to mercury in the Brazilian Amazon [Manifestações neurológicas em ribeirinhos de áreas expostas ao mercúrio na Amazônia brasileira]. Cad Saude Publica 2013; 29 (11) 2307-2318
• 57 Khoury EDT, Souza GdS, Costa CAd, de Araújo AAK, Oliveira CSBd, Silveira LCdL, Pinheiro MdCN. Somatosensory Psychophysical Losses in Inhabitants of Riverside Communities of the Tapajós River Basin, Amazon, Brazil: Exposure to Methylmercury Is Possibly Involved. PLoS One 2015; 10 (12) e0144625
• 58 Lebel J, Mergler D, Branches F, Lucotte M, Amorim M, Larribe F, Dolbec J. Neurotoxic effects of low-level methylmercury contamination in the Amazonian Basin. Environ Res 1998; 79 (01) 20-32
• 59 Zhou Z, Zhang X, Cui F, Liu R, Dong Z, Wang X, Yu S. Subacute motor neuron hyperexcitability with mercury poisoning: a case series and literature review. Eur Neurol 2014; 72 (3-4): 218-222
• 60 Singh D, Lal V. Mercury masquerading as motor neuron disease. J Neurol Sci 2021; 429: 119389
• 61 Pamphlett R, Jew SK. Heavy metals in locus ceruleus and motor neurons in motor neuron disease. Acta Neuropathol Commun 2013; 12: 1-81
• 62 Akbal A, Yılmaz H, Tutkun E, Köş DM. Aggravated neuromuscular symptoms of mercury exposure from dental amalgam fillings. J Trace Elem Med Biol 2014; 28 (01) 32-34
• 63 Hu XF, Lowe M, Chan HM. Mercury exposure, cardiovascular disease, and mortality: A systematic review and dose-response meta-analysis. Environ Res 2021; 193: 110538
• 64 Lopes-Araújo A, Arrifano GP, Macchi BM, Augusto-Oliveira M, Santos-Sacramento L, Martín-Doimeadios RCR. et al. Hair mercury is associated with dyslipidemia and cardiovascular risk: An anthropometric, biochemical and genetic cross-sectional study of Amazonian vulnerable populations. Environ Res 2023; 229: 115971
• 65 Castro NSSd, Lima MdO. Hair as a Biomarker of Long Term Mercury Exposure in Brazilian Amazon: A Systematic Review. Int J Environ Res Public Health 2018; 15 (03) 500
• 66 Sun Y, Liu B, Rong S, Zhang H, Du Y, Xu G. et al. Association of Seafood Consumption and Mercury Exposure with Cardiovascular and All-Cause Mortality Among US Adults. JAMA Netw Open 2021; 4 (11) e2136367
• 67 Chen C, Xun P, McClure LA, Brockman J, MacDonald L, Cushman M. et al. Serum mercury concentration and the risk of ischemic stroke: The REasons for Geographic and Racial Differences in Stroke Trace Element Study. Environ Int 2018; 117: 125-131
• 68 Golding J, Hibbeln JR, Gregory SM, Iles-Caven Y, Emond A, Taylor CM. Maternal prenatal blood mercury is not adversely associated with offspring IQ at 8 years provided the mother eats fish: A British prebirth cohort study. Int J Hyg Environ Health 2017; 220 (07) 1161-1167
• 69 Basta PC, Viana PVS, Vasconcellos ACS, Périssé ARS, Hofer CB, Paiva NS. et al. Mercury Exposure in Munduruku Indigenous Communities from Brazilian Amazon: Methodological Background and an Overview of the Principal Results. Int J Environ Res Public Health 2021; 18 (17) 9222
• 70 Machado CLR, Crespo-Lopez ME, Augusto-Oliveira M, Arrifano GdP, Macchi BdM, Lopes-Araújo A. et al. Eating in the Amazon: Nutritional Status of the Riverine Populations and Possible Nudge Interventions. Foods 2021; 10 (05) 1015
• 71 Arrifano GPF, Alvarez-Leite JI, Souza-Monteiro JR, Augusto-Oliveira M, Paraense R, Macchi BM. et al. In the Heart of the Amazon: Noncommunicable Diseases and Apolipoprotein E4 Genotype in the Riverine Population. Int J Environ Res Public Health 2018; 15 (09) 1957
• 72 Costa JMF, Lima AADS, Rodrigues Junior D, Khoury EDT, Souza GdS, Silveira LCdL, Pinheiro MdCN. Emotional and motor symptoms in riverside dwellers exposed to mercury in the Amazon [Manifestações emocionais e motoras de ribeirinhos expostos ao mercúrio na Amazônia]. Rev Bras Epidemiol 2017; 20 (02) 212-224
• 73 Hirai T, Abe O, Nakamura M, Inui S, Uetani H, Ueda M, Azuma M. Brain structural changes in patients with chronic methylmercury poisoning in Minamata. Brain Res 2023; 15: 1805-148278
• 74 Benz MR, Lee SH, Kellner L, Döhlemann C, Berweck S. Hyperintense lesions in brain MRI after exposure to a mercuric chloride-containing skin whitening cream. Eur J Pediatr 2011; 170 (06) 747-750
• 75 Abbaslou P, Zaman T. A Child with elemental mercury poisoning and unusual brain MRI findings. Clin Toxicol (Phila) 2006; 44 (01) 85-88
• 76 Basta PC, Vasconcellos ACSd, Hallwass G, Yokota D, Pinto DODR, Aguiar DSd. et al. Risk Assessment of Mercury-Contaminated Fish Consumption in the Brazilian Amazon: An Ecological Study. Toxics 2023; 11 (09) 800
• 77 Yorifuji T, Tsuda T, Inoue S, Takao S, Harada M, Kawachi I. Critical appraisal of the 1977 diagnostic criteria for Minamata disease. Arch Environ Occup Health 2013; 68 (01) 22-29
• 78 Ministério da Saúde; Secretaria de Vigilância em Saúde; Departamento de Saúde Ambiental do Trabalhador e de Vigilância das Emergências em Saúde Pública. . Orientações Para a Notificação de Intoxicações por Mercúrio. Brasília: Ministério da Saúde, 2021. https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/svsa/vigilancia-ambiental/orientacoes-para-notificacao-intoxicacao-por-mercurio/view
• 79 Al-Shahristani H, Shihab K, Al-Haddad IK. Mercury in hair as an indicator of total body burden. Bull World Health Organ 1976; 53 (Suppl): 105-112
• 80 Nuttall KL. Interpreting Hair Mercury Levels in Individual Patients. Ann Clin Lab Sci 2006; 36 (03) 248-261
• 81 World Health Organization. . Guidance for identifying populations at risk from mercury exposure. Geneva: UNEP DTIE Chemicals Branch and WHO Department of Food Safety, Zoonoses and Foodborne Diseases, 2008 . Available from: https://www.who.int/foodsafety/publications/chem/mercuryexposure.pdf . Last accessed March 2025
• 82 Sue Y. Mercury. In: Hoffman RS, Howland M, Lewin NA. et al. eds. Goldfrank's Toxicologic Emergencies. 10th ed.. Colombus: McGraw-Hill; 2015
• 83 Agocs M. . Case studies in environmental medicine: Mercury toxicity. Agency for Toxic Substances and Disease Registry; US Department of Health & Human Services, 1992
• 84 Ye BJ, Kim BG, Jeon MJ, Kim SY, Kim HC, Jang TW. et al. Evaluation of mercury exposure level, clinical diagnosis and treatment for mercury intoxication. Ann Occup Environ Med 2016; 28 (01) 5
• 85 Elinder CG, Friberg L, Kjellström T, Nordberg GF, Oberdoerster G. World Health Organization. Biological monitoring of metals. Geneva: Chemical Safety Monographs International Program, 1994. 78 p

Publication History

Received: 29 April 2025

Accepted: 21 June 2025

Article published online:
08 September 2025