Adverse cardiovascular effects of exposure to cadmium and mercury alone and in combination on the cardiac tissue and aorta of Sprague-Dawley rats.

The aim of this study was to identify cardiovascular effects of relevant concentrations of Cd and Hg alone and in combination as a mixture in water. This was achieved by administering to male Sprague-Dawley rats via gavage 0.62 mg/kg Cd or 1.23 mg/kg Hg, or a combination of 0.62 mg/kg Cd and 1.23 mg/kg Hg in the co-exposure group for 28 days. Concentrations were the rat equivalence dosages of 1,000 times the World Health Organization's limits of 0.003 mg/L and 0.006 mg/L for Cd and Hg, respectively, for water. With termination, blood levels of the metals were increased. For all metal exposed groups, histological evaluation and transmission electron microscopy of the myocardium revealed myofibrillar necrosis, increased fibrosis, vacuole formation and mitochondrial damage. Cd caused the most mitochondrial damage while Hg to a greater degree induced fibrosis. In the aorta, both Cd and Hg also increased collagen deposition adversely altering the morphology of the fenestrated elastic fibers in the tunica media. Co-exposure resulted in increased cardiotoxicity with increased mitochondrial damage, fibrosis and distortion of the aortic wall as a result of increased collagen deposition, as well as altered elastin deposition, fragmentation and interlink formation. These are typical features of oxidative damage that correlates with a phenotype of premature ageing of the CVS that potentially can lead to hypertension and premature cardiac failure.

Exposure to Aluminum, Cadmium, and Mercury and Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis.

Autism spectrum disorder (ASD) is a complex neurobehavioral disorder that is believed to be multifactorial in origin. As the incidence of ASD is rising along with industrialization, and because certain metals have been linked to neurological problems, it is important to consider whether such metals may play a role in the development of ASD. Previously, we performed a meta-analysis of existing literature to examine the potential link between inorganic arsenic and lead exposure and ASD. This is a continuation of that study investigating the association of the exposure to aluminum (Al), cadmium (Cd), and mercury (Hg) and ASD. These metals were chosen because they are abundant in our environment, are known to cause neurological problems in humans, and have multiple published studies examining their potential links with ASD. Following the same approach as our previous paper, we conducted a systematic review of the existing literature and performed a meta-analysis to evaluate the current evidence regarding these metals and their potential relationship with autism. We reviewed 18 studies on Al, 18 on Cd, and 23 on Hg, and the individual studies showed inconsistent results. When the measurements were integrated into the meta-analysis, we found significant associations between all the metals and ASD, but the associations were not always in the same direction. Levels of Hg in hair, urine, and blood were all positively associated with ASD. Levels of Al in hair and urine were positively associated with ASD, while levels of Al in blood were negatively associated. In comparison, levels of Cd in hair and urine were negatively associated with ASD. These results imply that, while these metals are all neurotoxic, their impact on the development of ASD and their modes of action could be different. Further research is warranted to examine the longitudinal effects of these toxic metals on the risk of ASD, to assess the critical period when exposure may affect development, and to investigate potential factors that may enhance or ameliorate the effect of metals. Overall, these findings support policies that advocate limiting exposure to neurotoxic metals, particularly for pregnant women and young children, in order to help reduce the rising incidence of ASD.

Inyección subcutánea de mercurio elemental. Importancia de la remoción precoz / Subcutaneous injection of metallic mercury. The importance of early removal

La inyección subcutánea o intramuscular de mercurio elemental, sea accidental o intencional, es una forma poco frecuente de intoxicación. Presentamos el caso de un hombre de 22 años de edad, con antecedentes de rasgos psicóticos y lesiones autolíticas, que se inyectó mercurio elemental en el tejido celular subcutáneo del cuello, tórax y abdomen, tres meses antes de su internación. Las áreas afectadas fueron localizadas mediante el examen físico, radiografías y tomografías. Se realizó el dosaje de mercurio en sangre y orina. Se resecó quirúrgicamente el mercurio de las zonas comprometidas. La detección y remoción precoz del mercurio, mediante cirugía y eventual quelación, es necesaria para prevenir complicaciones a corto y largo plazo.

Accidental or intentional subcutaneous or intramuscular injection of metallic mercury is an uncommon form of intoxication. We present the case of a 22 year-old man, who had psychotic disorders and autoaggressive behavior, with a preceding history of self-injection of mercury into the soft tissues of the neck, thorax and abdomen. Clinical examination, radiographs, and computed tomography showed the affected area. Mercury was measured in blood and urine. The mercury was surgically resected from the affected areas. Early detection and removal of mercury from the body by physical removal or chelation is required to prevent short- and long-term toxicity.

Low levels of lead and glutathione markers of redox status in human blood.

Exposure to lead (Pb) is implicated in a plethora of health threats in both adults and children. Increased exposure levels are associated with oxidative stress in the blood of workers exposed at occupational levels. However, it is not known whether lower Pb exposure levels are related to a shift toward a more oxidized state. To assess the association between blood lead level (BLL) and glutathione (GSH) redox biomarkers in a population of healthy adults, BLL and four GSH markers (GSH, GSSG, GSH/GSSG ratio and redox potential E h ) were measured in the blood of a cross-sectional cohort of 282 avid seafood-eating healthy adults living on Long Island (NY). Additionally, blood levels of two other metals known to affect GSH redox status, selenium (Se) and mercury (Hg), and omega-3 index were tested for effect modification. Regression models were further adjusted for demographic and smoking status. Increasing exposure to Pb, measured in blood, was not associated with GSSG, but was associated with lower levels of GSH/GSSG ratio and more positive GSH redox potential E h , driven by its association with GSH. No effect modification was observed in analyses stratified by Hg, Se, omega-3 index, sex, age, or smoking. Blood Pb is associated with lower levels of GSH and the GSH/GSSG ratio in this cross-sectional study of healthy adults.

Dietary Intake of Cadmium, Lead and Mercury and Its Association with Bone Health in Healthy Premenopausal Women.

The bone is one of the relevant target organs of heavy metals, and heavy metal toxicity is associated with several degenerative processes, such osteoporosis and bone mineral alterations, that could lead to fractures. We aimed to study a presumed relationship between bone density, evaluated by quantitative bone ultrasound (QUS), dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) and the dietary intake of cadmium, lead and mercury in healthy premenopausal women. A total of 158 healthy, non-smoking, premenopausal women were incorporated into the study. A validated food frequency questionnaire (FFQ) was administered to assess intake during the preceding seven days. The median predicted dietary cadmium intake among the 158 women studied was 25.29 µg/day (18.62-35.00) and 2.74 µg/kg body weight/week (b.w./w) (1.92-3.83). Dietary lead intake was 43.85 µg/day (35.09-51.45) and 4.82 µg/kg b.w./w (3.67-6.13). The observed dietary mercury intake was 9.55 µg/day (7.18-13.57) and 1.02 µg/kg b.w./w (0.71-1.48). Comparisons, in terms of heavy metal intake, showed no significant results after further adjusting for energy intake. No statistically significant correlations between heavy metal intake and the QUS, DXA and pQCT parameters were observed. Levels of dietary exposure of cadmium, lead and mercury were mostly within the recommendations. We did not find associations between the QUS, DXA and pQCT parameters and the dietary intake of the studied heavy metals in healthy premenopausal women.

Characterization and risk of exposure to elements from artisanal gold mining operations in the Bolivian Andes.

Artisanal and small-scale gold mining (ASGM) offers low-skilled workers an opportunity to elevate themselves out of poverty. However, this industry operates with little to no pollution controls and the cost to the environment and human health can be large. The objectives of this study were to measure levels of arsenic (As), manganese (Mn), cobalt (Co), lead (Pb), and mercury (Hg) in the environment and characterize health risks to miners and residents in an area with active ASGM operations. An exposure assessment was conducted at two different mining sites and a nearby village in the Bolivian Anders. The resulting measurements were then used to quantify cancerous and noncancerous health risks to children and adults working at and living near ASGM areas. Soil concentrations of As were well above background levels and showed great variations between the village and mining area. Mercury vapor levels at the two mining sites were approximately 30 times larger than the EPA reference concentration. The risk of developing non-cancerous health effects were primarily due to exposure to As and Hg. The probability of individuals developing cancer was considerably increased with adult miners having a probability of 1.3 out of 100. Cancer potential was driven by exposure to As, with de minimus cancer risk from all other elements. Based on the environmental characterization of elements in soils and Hg vapors, the risk of developing cancerous and non-cancerous health outcomes were above a level of concern based on EPA risk assessment guidance. Personal protective equipment was not worn by workers and Hg amalgam is commonly heated in workers' homes. Better education of the risks of ASGM is needed as well as simple controls to reduce exposure.

Comparison of mercury sulfides with mercury chloride and methylmercury on hepatic P450, phase-2 and transporter gene expression in mice.

Zuotai (mainly ß-HgS) and Zhusha (also called as cinnabar, mainly α-HgS) are used in traditional medicines in combination with herbs or even drugs in the treatment of various disorders, while mercury chloride (HgCl2) and methylmercury (MeHg) do not have known medical values but are highly toxic. This study aimed to compare the effects of mercury sulfides with HgCl2 and MeHg on hepatic drug processing gene expression. Mice were orally administrated with Zuotai (ß-HgS, 30mg/kg), α-HgS (HgS, 30mg/kg), HgCl2 (33.6mg/kg), or MeHg (3.1mg/kg) for 7days, and the expression of genes related to phase-1 drug metabolism (P450), phase-2 conjugation, and phase-3 (transporters) genes were examined. The mercurials at the dose and duration used in the study did not have significant effects on the expression of cytochrome P450 1-4 family genes and the corresponding nuclear receptors, except for a slight increase in PPARα and Cyp4a10 by HgCl2. The expressions of UDP-glucuronosyltransferase and sulfotransferase were increased by HgCl2 and MeHg, but not by Zuotai and HgS. HgCl2 decreased the expression of organic anion transporter (Oatp1a1), but increased Oatp1a4. Both HgCl2 and MeHg increased the expression of multidrug resistance-associated protein genes (Mrp1, Mrp2, Mrp3, and Mrp4). Zuotai and HgS had little effects on these transporter genes. In conclusion, Zuotai and HgS are different from HgCl2 and MeHg in hepatic drug processing gene expression; suggesting that chemical forms of mercury not only affect their disposition and toxicity, but also affect their effects on the expression of hepatic drug processing genes.

Dose-response analysis indicating time-dependent neurotoxicity caused by organic and inorganic mercury-Implications for toxic effects in the developing brain.

A latency period preceding neurotoxicity is a common characteristic in the dose-response relationship induced by organic mercury. Latency periods have typically been observed with genotoxicants in carcinogenesis, with cancer being manifested a long time after the initiating event. These observations indicate that even a very small dose may cause extensive adverse effects later in life, so the toxicity of the genotoxic compound is dose and time-dependent. In children, methylmercury exposure during pregnancy (in utero) has been associated with delays in reaching developmental milestones (e.g., age at first walking) and decreases in intelligence, increasing in severity with increasing exposure. Ethylmercury exposure from thimerosal in some vaccines has been associated, in some studies, with autism and other neurological disorders in children. In this paper, we have examined whether dose-response data from in vitro and in vivo organic mercury toxicity studies fit the Druckrey-Küpfmüller equation c·t(n)=constant (c=exposure concentration, t=latency period), first established for genotoxic carcinogens, and whether or not irreversible effects are enhanced by time of exposure (n≥1), or else toxic effects are dose-dependent while time has only minor influence on the adverse outcome (n<1). The mode of action underlying time-dependent toxicity is irreversible binding to critical receptors causing adverse and cumulative effects. The results indicate that the Druckrey-Küpfmüller equation describes well the dose-response characteristics of organic mercury induced neurotoxic effects. This amounts to a paradigm shift in chemical risk assessment of mercurial compounds and highlights that it is vital to perform toxicity testing geared to investigate time-dependent effects.

Assessment of mercury and cadmium via seafood consumption in Italy: estimated dietary intake (EWI) and target hazard quotient (THQ).

Mercury (Hg) and cadmium (Cd) were quantified in fish, cephalopods and crustaceans from Italian supermarkets. Sample compliance with European dietary standards as well as human health risks according to provisional tolerable weekly intake (PTWI) and the methodology of target hazard quotient (THQ) were evaluated. Both element levels were under European legal limits, except for some fish having Hg and Cd contents exceeding or equal to critical values. Estimated weekly intakes (Hg: fish = 0.07-1.44 µg kg(-1) bw week(-1); cephalopods = 0.05-0.15 µg kg(-1) bw week(-1); crustaceans = 0.04-0.08 µg kg(-1) bw week(-1); and Cd: fish = 0.04-0.32 µg kg(-1) bw week(-1); cephalopods = 0.07-0.27 µg kg(-1) bw week(-1); crustaceans = 0.05-0.11 µg kg(-1) bw week(-1)) as well as THQ < 1 were within safe limits. Although there seems to be no important risks associated with seafood consumption, Hg exposure was in some cases close to safety margins and thus levels of this metal should be under frequent surveillance.

Tungíase atualidades clínicas / Tungiase clinical news

O objetivo deste artigo é revisar as características clínicas da tungíase. A Tunga penetrans é a menor das pulgas conhecidas, alcançando 1 milímetro de comprimento quando atinge a fase adulta. Os relatos antigos de surtos de tungíase são escassos em relação aos registros epidemiológicos. O diagnóstico da doença é realizado através da história epidemiológica e dos achados clínicos, aliados ao exame direto com visualização do parasita, após abertura da lesão com agulha estéril. A retirada da pulga é o tratamento preconizado, sendo a profilaxia a melhor alternativa para controlar o parasita. Os profissionais de saúde devem atentar para a importância de se orientar as populações de áreas endêmicas em relação à doença, a fim de reduzir o número de casos e de complicações.

The purpose of this article is to review the clinical features of tungiasis. Tunga penetrans is the smallest known flea, reaching a millimeter in length when fully grown. The earliest accounts of outbreaks of tungiasis are scarce in relation to epidemiological records. The diagnosis is made by history and clinical epidemiological findings, coupled with the direct examination with visualization of the parasite after opening the wound with a sterile needle. The removal of the flea is the recommended treatment, and prophylaxis the best way to control the parasite. Healthcare professionals should be aware as to the importance of educating the public in endemic areas for the disease in order to reduce the number of cases and complications.

Mercury-associated nephrotic syndrome: a case report and systematic review of the literature.

Kidney injury from mercury is known to cause dose-related tubular dysfunction and idiosyncratic nephrotic syndrome according to various case reports. Motivated by a patient with subacute-onset nephrotic syndrome, histologic features of secondary focal segmental glomerulosclerosis, and concurrent mercury toxicity, we conducted a systematic review to explore renal histologic changes in patients with toxic mercury exposures and nephrotic syndrome. Data were extracted from a patient's clinical record. MEDLINE/Ovid was searched from 1950 to November 2010 using a prespecified search strategy. Two nephrology textbooks and the UpToDate online database also were searched. Inclusion criteria were studies of humans with nephrotic syndrome, nephrotic-range proteinuria, or kidney biopsy results reported. There were no exclusion criteria. We identified 27 other reports of 42 patients with nephrotic syndrome or nephrotic-range proteinuria. Of the 26 individuals, including our patient, who underwent kidney biopsy, histology showed glomerular disease in 21. Of these 20 biopsies, 4 showed minimal change disease and 15 showed membranous glomerulonephritis. Mercury exposure can lead to various glomerular lesions; we emphasize the importance of a careful occupational and dietary history in elucidating a cause for the undetermined nephrotic syndrome.

Human exposure to lead, cadmium and mercury through fish and seafood product consumption in Italy: a pilot evaluation.

The presence of selected toxic heavy metals, such as cadmium (Cd), lead (Pb) and mercury (Hg), was investigated in fish and seafood products, namely, blue mussel, carpet shell clam, European squid, veined squid, deep-water rose shrimp, red mullet, European seabass, gilthead seabream, Atlantic cod, European hake, Atlantic bluefin tuna and swordfish so as to assess their human exposure through diet. Metals were detected by quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS) and hydride generation atomic absorption spectrometry (Hg-AAS). Measurements of Cd, Pb and Hg were performed by means of analytical methods validated in compliance with UNI CEI EN ISO/IEC 17025 [2005. General requirements for the competence of testing and calibration laboratories. Milano (Italy): UNI Ente Nazionale Italiano di Unificazione]. The exposure assessment was undertaken matching the levels of Cd, Pb and total Hg with consumption data related to fish and seafood products selected for this purpose. In order to establish human health implications, the estimated weekly intakes (EWIs) for Cd, Pb and Hg were compared with the standard tolerable weekly intakes (TWI) for Cd and provisional tolerable weekly intakes (PTWIs) for Pb and Hg stipulated by the European Food Safety Authority (EFSA) and the Food and Agriculture Organization/World Health Organization (FAO/WHO) Joint Expert Committee on Food Additives (JECFA). The found metal concentrations were largely below the maximum levels (MLs) established at the European Union level with the exception of Cd. This metal exceeded the MLs in squid, red mullet, European hake and Atlantic cod. Squid and blue mussel showed the highest Pb concentrations which accounted for 60% and 10% of the MLs, respectively. Highest Hg levels were found in predatory fish. The concentrations of Hg in swordfish, Atlantic bluefin tuna and red mullet accounted for 50%, 30% and 30% of the MLs, respectively. The EWIs for Cd, Pb and Hg related to the consumption of fish and seafood products by the median of the Italian total population accounted for 20%, 1.5% and 10% of the standard TWI for Cd as well as PTWIs for Pb and Hg, respectively. Furthermore, the EWIs estimated using consumption data concerning Italian consumers did not exceed the standard TWI and PTWIs, except for Cd at 95th percentile.

Human health risks from mercury exposure from broken compact fluorescent lamps (CFLs).

Human health risk to infants/toddlers and adults was evaluated based on two exposure scenarios from compact fluorescent lamp (CFL) breakage; first in a room with no ventilation and no clean-up, and second in a room with adequate ventilation and clean-up. Concentration data from multiple exposure scenarios tested in a study by Stahler et al. (2008) were compared to human toxicity benchmarks to calculate hazard quotients. For the no clean-up scenario, hazard quotients were generally less than 1, suggesting an unlikely health risk. When the room was ventilated and the broken CFL was cleaned-up, mercury concentrations were generally lower. A review of release scenarios, along with duration-adjusted toxicity benchmarks, indicated that few releases produced levels of concern, but some scenarios resulted in exceedance of risk targets and require further study. Uncertainties in this screening characterization include assumptions about room size, ventilation, age of lamp, the distribution of mercury in the room, and also the choice of the toxicity benchmarks used to develop the hazard quotients.

Reacción liquenoide en mucosa bucal asociada a restauración de amalgama: reporte de caso clínico / Lichenoid reaction in oral mucosa associated with amalgam restoration: case report

La reacción liquenoide en la mucosa bucal es una de las formas más frecuentes de las reacciones de hipersensibilidad retardada como respuesta inmune que puede estar relacionada al mercurio u otro componente de la amalgama. La reacción liquenoide es una lesión clínica e histológicamente indistinguible del liquen plano bucal. La única diferencia estriba en que desaparece al retirar el agente causante. Este trabajo tiene como objetivo presentar un caso de lesión liquenoide en mucosa bucal en una mujer de 34 años que solicito asistencia odontológica para diagnóstico y tratamiento de una lesión blanca en la mucosa yugal y encía vestibular derecha adyacente a los dientes 16 y 17 que presentaban restauración de amalgama. Se realizó una biopsia incisional y examen histopatológico teniendo un resultado compatible con el Liquen Plano. Con el consentimiento de la paciente las restauraciones de amalgama fueron substituidas por resina compuesta. Fue verificada la regresión continua de la lesión durante el seguimiento clínico del caso. El diagnóstico definitivo de lesiones liquenoides asociadas a la presencia de restauración de amalgama como factor etiológico es de suma relevancia porque de esta forma se obtiene un tratamiento basado en una intervención simplificada y local, diferente de la compleja actuación que ocurre en tratamientos que envuelven enfermedades auto-inmunes como el liquen plano.

Lichenoid reaction in the buccal mucosa is one of the most frequent forms of delayed hypersensitivity reaction as an immune response, which could be related to mercury or another amalgam component. It is a rare manifestation that is an important differential diagnosis in the group of buccal leucoplakias; and it is the reason of many controversies, particularly regarding lichen planus. The aim of this paper is to present a buccal mucosa lichenoid lesion case in a 34 year-old woman who requested odontologic assistance to be diagnosed and treated for a white lesion, located in the jugal mucosa and right vestibular gum, adjacent to teeth 16 and 17, which had amalgam restorations. An incisional biopsy and a histopatologic exam were made. The result was compatible with Liquen Planus. With the patient's consent the amalgam restorations were replaced with compound resin. A continuous regression of the lesion was verified during the clinical monitoring of the case. The final diagnosis of lichenoid lesions related to amalgam restorations as an etiologic factor is remarkable because by means of this a treatment based on a simplified and local intervention is obtained, which is different from the complicated procedure for treatments that involve auto-immune diseases like lichen planus.

Cutaneous mercury granuloma: a case report.

Cutaneous mercury (Hg) granuloma is a rare disorder caused by the traumatic introduction of elemental Hg into skin or soft tissue. Typically, cutaneous elemental Hg deposits cause limited systemic effects. Prominent systemic toxicity may, however, occasionally occur. Herein we report a case of cutaneous Hg granuloma resulting in chronic painful local wounds and systemic toxicity in the form of abdominal pain, visual disturbances, and psychiatric abnormalities. The related literature also is reviewed.

Auto-aggressive metallic mercury injection around the knee joint: a case report.

BACKGROUND: Accidental or intentional subcutaneous and/or intramuscular injection of metallic mercury is an uncommon form of poisoning. Although it does not carry the same risk as mercury vapour inhalation, it may cause destructive early and late reactions. CASE PRESENTATION: Herein we present the case of a 29-year-old male patient who developed an obsessive-compulsive disorder causing auto-aggressive behaviour with injection of elemental mercury and several other foreign bodies into the soft tissues around the left knee about 15 years before initial presentation. For clinical examination X-rays and a CT-scan of the affected area were performed. Furthermore, blood was taken to determine the mercury concentration in the blood, which showed a concentration 17-fold higher than recommended. As a consequence, the mercury depots and several foreign bodies were resected marginally. CONCLUSION: Blood levels of mercury will decrease rapidly following surgery, especially in combination with chelating therapy. In case of subcutaneous and intramuscular injection of metallic mercury we recommend marginal or wide excision of all contaminated tissue to prevent migration of mercury and chronic inflammation. Nevertheless, prolonged clinical and biochemical monitoring should be performed for several years to screen for chronic intoxication.

Influence of mercury bioaccessibility on exposure assessment associated with consumption of cooked predatory fish in Spain.

BACKGROUND: Predatory fish tend to accumulate high levels of mercury (Hg). Food safety assessment of these fish has been carried out on the raw product. However, the evaluation of the risk from Hg concentrations in raw fish might be modified if cooking and bioaccessibility (the contaminant fraction that solubilises from its matrix during gastrointestinal digestion and becomes available for intestinal absorption) were taken into account. Data on Hg bioaccessibility in raw predatory fish sold in Spain are scarce and no research on Hg bioaccessibility in cooked fish is available. The aim of the present study was to evaluate Hg bioaccessibility in various kinds of cooked predatory fish sold in Spain to estimate their health risk. RESULTS: Both Hg and bioaccessible Hg concentrations were analysed in raw and cooked fish (swordfish, tope shark, bonito and tuna). There were no changes in Hg concentrations during cooking. However, Hg bioaccessibility decreased significantly after cooking (42 ± 26% in raw fish and 26 ± 16% in cooked fish), thus reducing in swordfish and tope shark the Hg concentration to which the human organism would be exposed. CONCLUSION: In future, cooking and bioaccessibility should be considered in risk assessment of Hg concentrations in predatory fish.