Multimetal exposure: Challenges in diagnostics, prevention, and treatment.

Extensive use of heavy metals has posed a serious concern for ecosystem and human too. Heavy metals are toxic in nature and their accumulation in human body causes serious disorders such as neurological disease, cardiac disease, gastrointestinal problems, skin disorders, reproductive disease, lungs diseases, and so on. Furthermore, heavy metals not only affect the human health but also have a negative impact on the economy. In the current review, we have elaborated the impact of heavy metal exposure on human health and socioeconomics. We have discussed the molecular mechanism involved in the heavy metal-induced human disorders such as oxidative stress, neuroinflammation, and protein misfolding. Finally, we discussed the preventive measure and treatment strategy that could counter the negative effects of heavy metal intoxications. In conclusion, there is a substantial correlation between heavy metals and the onset and advancement of several health issues. Chelation treatment could be a useful tactic to lessen the toxic metal load and the difficulties that come with it.

Toxic Metal Species and 'Endogenous' Metalloproteins at the Blood-Organ Interface: Analytical and Bioinorganic Aspects.

Globally, human exposure to environmental pollutants causes an estimated 9 million deaths per year and it could also be implicated in the etiology of diseases that do not appear to have a genetic origin. Accordingly, there is a need to gain information about the biomolecular mechanisms that causally link exposure to inorganic environmental pollutants with distinct adverse health effects. Although the analysis of blood plasma and red blood cell (RBC) cytosol can provide important biochemical information about these mechanisms, the inherent complexity of these biological matrices can make this a difficult task. In this perspective, we will examine the use of metalloentities that are present in plasma and RBC cytosol as potential exposure biomarkers to assess human exposure to inorganic pollutants. Our primary objective is to explore the principal bioinorganic processes that contribute to increased or decreased metalloprotein concentrations in plasma and/or RBC cytosol. Furthermore, we will also identify metabolites which can form in the bloodstream and contain essential as well as toxic metals for use as exposure biomarkers. While the latter metal species represent useful biomarkers for short-term exposure, endogenous plasma metalloproteins represent indicators to assess the long-term exposure of an individual to inorganic pollutants. Based on these considerations, the quantification of metalloentities in blood plasma and/or RBC cytosol is identified as a feasible research avenue to better understand the adverse health effects that are associated with chronic exposure of various human populations to inorganic pollutants. Exposure to these pollutants will likely increase as a consequence of technological advances, including the fast-growing applications of metal-based engineering nanomaterials.

Chemical Hand Warmer Packet Ingestion: A Case of Elemental Iron Exposure.

For individuals who work outdoors in the winter or play winter sports, chemical hand warmers are becoming increasingly more commonplace because of their convenience and effectiveness. A 32-year-old woman with a history of chronic pain and bipolar disorder presented to the emergency department complaining of a "warm sensation" in her mouth and epigastrium after reportedly ingesting the partial contents of a chemical hand warmer packet containing between 5 and 8 g of elemental iron. She had been complaining of abdominal pain for approximately 1 month and was prescribed unknown antibiotics the previous day. The patient denied ingestion of any other product or medication other than what was prescribed. A serum iron level obtained approximately 6 hours after ingestion measured 235 micrograms/dL (reference range 40-180 micrograms/dL). As the patient demonstrated no new abdominal complaints and no evidence of systemic iron toxicity, she was discharged uneventfully after education. However, the potential for significant iron toxicity exists depending on the extent of exposure to this or similar products. Treatment for severe iron toxicity may include fluid resuscitation, whole bowel irrigation, and iron chelation therapy with deferoxamine. Physicians should become aware of the toxicity associated with ingestion of commercially available hand warmers. Consultation with a medical toxicologist is recommended.

Investigation and monitoring of heavy metal poisoning.

Historically, heavy metal measurement and interpretation has been a highly specialised area performed only in a handful of centres within the UK. However, recent years have seen a move to more local testing due to the repatriation of referred work into pathology networks and the increased availability of inductively coupled plasma mass spectrometry technology. While management of significant poisoning is still overseen by tertiary care poisoning specialists, management of milder cases may be undertaken locally.Non-specialist clinical scientists and clinicians need to know when heavy metal testing is appropriate, which samples are required (and any specific requirements around collection) and how to interpret and act on the results.This Best Practice article provides guidance on the investigation and monitoring of the toxic elements most frequently encountered in general medical practice; lead, mercury and arsenic. It is intended as a reference guide for the non-specialist and as a comprehensive summary for clinical toxicologists and clinical scientists.

Failure of chelator-provoked urine testing results to predict heavy metal toxicity in a prospective cohort of patients referred for medical toxicology evaluation.

INTRODUCTION: Provoked urine testing (PUT), involving chelating agent administration prior to measuring urine metal excretion levels, is used by some alternative health care practitioners to diagnose patients with heavy metal poisoning. Multiple medical societies have advised against this practice due to its presumed unreliability, expense, and lack of validation. However, no prospective study of the predictive value of PUT for heavy metal poisoning has been undertaken. METHODS: This study utilized the Toxicology Consortium's prospective case registry to evaluate the reliability of PUT for diagnosing heavy metal poisoning. Inclusion criteria were toxicology clinic patients with PUT results who were subsequently evaluated by a board-certified medical toxicologist and had a determination made regarding whether their signs and symptoms were likely related or unrelated to toxicologic exposures. The primary outcome was the positive predictive value of PUT for heavy metal toxicity as diagnosed by the evaluating medical toxicologist. Patients presenting to participating toxicology clinics without PUT served as a comparison group. RESULTS: 74 of 106 cases presenting with PUT results met inclusion criteria and were analyzed. 15 cases were determined by the examining toxicologist to be likely related to a toxicologic exposure. Only three cases were found to be related to heavy metal exposure, giving a positive predictive value of 4.3%. 20.2% of patients with PUT were found to have signs or symptoms related to any toxicologic exposure, compared to 14.3% of clinic patients without PUT. Demographics of toxicology clinic patients with and without PUT results were not significantly different except for age. DISCUSSION: Our results provide empiric support that PUT is an inaccurate predictor of a diagnosis of heavy metal poisoning by a board-certified medical toxicologist. Given the inability to properly interpret PUT results along with the increased cost burden and risk of false positives, PUT should not be performed.

Doc, can you test me for "toxic metals"? Challenges of testing for toxicants in patients with environmental concerns.

Laboratory testing is an important tool to assist clinicians in evaluation of patients with potential environmentally-related illness, however, it can be challenging to select or interpret the appropriate toxicological tests. Recent advances in analytical techniques and expanded consumer access to environmental laboratories led to a rise in laboratory testing for various environmental toxicants, including metals. However, most environmental tests have scant clinical evidence and are not validated for clinical use. While the tests themselves may not present direct harm to the patients, the results of inappropriately selected tests may lead to significant patient stress and unnecessary follow-up or treatment. Given the lack of environmental health content in medical training, pediatricians may feel ill-equipped to address most environmental issues they encounter in practice, including the interpretation of environmental toxicant lab results. This article provides an overview of how to approach a child and family with environmental health concerns about "toxic metals", select appropriate metal tests if indicated, and enlist the assistance of the Pediatric Environmental Health Specialty Units (PEHSU) for further management guidance.

Method validation for a multi-element panel in serum by inductively coupled plasma mass spectrometry (ICP-MS).

BACKGROUND: Laboratory testing for trace and toxic elements is important to diagnose metal toxicity and nutritional deficiency. There are several essential elements that are necessary for biological function and non-essential elements that can pose risk from exposure. Both essential and nonessential elements can be toxic if concentrations exceed a certain threshold. METHODS: An aliquot of serum was diluted in a diluent solution, which contained iridium (Ir) as the internal standard, gold (Au), 0.05% Triton X-100, and 1% nitric acid (HNO3). The diluted specimen was aspirated into an inductively coupled plasma-mass spectrometer for quantitative elemental analysis of chromium (Cr), cobalt (Co), copper (Cu), manganese (Mn), nickel (Ni), selenium (Se) and zinc (Zn). The sample was introduced into the instrument spray chamber to form aerosol droplets, then atomized and ionized in argon plasma. The ions exited the plasma, passed through the interface of the instrument, then arrived at the entrance of the collision cell where helium gas was introduced to remove polyatomic interferences by kinetic energy discrimination (KED). After exiting the collision cell, the ions were filtered by a quadrupole mass spectrometer. RESULTS: The analytical measurement range was determined specifically for each element. Imprecision was <20% CV for the lowest limit of quantification for each element and accuracy was within ±15%. CONCLUSIONS: This method was validated for the quantification of seven elements in serum to assess nutritional deficiency and toxicity. The multi-element panel by ICP-MS met the validation criteria for biological monitoring of trace and toxic elements in patient specimens.

Mean platelet volume mediated the relationships between heavy metals exposure and atherosclerotic cardiovascular disease risk: A community-based study.

BACKGROUND: Heavy metals were related to increased risk of atherosclerotic cardiovascular disease (ASCVD). However, potential mechanisms under such associations remain unclear. We aimed to investigate the mediating role of mean platelet volume in the associations between heavy metals exposure and 10-year ASCVD risk. METHOD: Urinary heavy metals and mean platelet volume were measured in 3081 adults from the Wuhan-Zhuhai cohort in China. The associations between urinary heavy metals, mean platelet volume and 10-year ASCVD risk were separately analyzed through generalized linear models and logistic regression models. Mediation analyses were conducted to assess the role of mean platelet volume in the associations between urinary heavy metals and 10-year ASCVD risk. RESULTS: After adjusting for potential confounders, 10-year ASCVD risk was positively associated with urinary iron (odds ratio (OR) = 1.142, 95% confidence interval (1.038-1.256)), copper (OR = 1.384 (1.197-1.601)), zinc (OR = 1.520 (1.296-1.783)), cadmium (OR = 1.153 (0.990, 1.342)) and antimony (OR = 1.452 (1.237-1.704)), and negatively related with urinary barium (OR = 0.905 (0.831-0.985)). Also, we found significant dose-response relationships between urinary iron, zinc, antimony and mean platelet volume, as well as between mean platelet volume and 10-year ASCVD risk (all pfor trends < 0.05). Furthermore, mediation analyses indicated that mean platelet volume mediated 17.55%, 6.15% and 7.38% of the associations between urinary iron, zinc, antimony and 10-year ASCVD risk, respectively (all pvalue < 0.05). CONCLUSIONS: Elevated concentrations of urinary iron, copper, zinc, cadmium and antimony were associated with increased risk of 10-year ASCVD. Mean platelet volume partially mediated the associations of urinary iron, zinc and antimony with 10-year ASCVD risk.

Clinical characteristics and treatment of thallium poisoning in patients with delayed admission in China.

Thallium is highly toxic and its effects are cumulative. The clinical symptoms of thallium poisoning are non-specific, thereby delaying admission and treatment. This study aimed to summarize the clinical features and treatment experience of patients with delayed admission who experience thallium poisoning.We conducted a retrospective descriptive analysis of patients in our hospital from 2008 to 2018 who had thallium poisoning and experienced a delay in hospital admission. The time from symptom onset to admission was assessed. The patients were divided into 3 groups and descriptive analyses of their clinical characteristics, including basic patient information, symptoms, laboratory test results, examination findings, treatment methods, outcomes, and follow-up information, were conducted.A total of 34 patients with thallium poisoning were included: 8 were admitted to the hospital early or with mild delay, 9 had a moderate delay, and 17 had a severely delayed admission. The time from illness onset to admission was 13 (interquartile range, 7.5-26) days. Some patients with delayed admission had significant symptoms associated with central nervous system damage, and changes in magnetic resonance images and electroencephalograms were also noted. After admission, all patients received Prussian blue treatment, and some patients with relatively high blood concentration received blood purification treatments. Following treatment, the blood and urine thallium concentrations of all patients decreased significantly, and their symptoms were alleviated.Our results show that delayed patient admission in cases of thallium poisoning is associated with greater risk of central nervous system damage. Use of Prussian blue combined with blood purification treatments might improve patients' conditions.

Unrecognized Elevations of Toxic Elements in Urine and Blood Highlight the Potential Need for a Broader Approach to Exposure Assessment.

Heavy metals testing remains an ongoing challenge for diagnosing acute or chronic exposure to heavy metals. In this study, we determined the positivity rates of single element and panel testing for toxic elements, and evaluated the potential utility of an expanded detection protocol for screening of toxic element exposures. The retrospective analysis included data from urine (n = 19,343) and blood (n = 196,019) specimens tested using inductively coupled plasma-mass spectrometry (ICP-MS) for arsenic, cadmium, lead and mercury (blood), and arsenic, cadmium, copper, lead, mercury and zinc (urine). Lead industrial monitoring in blood and cadmium exposure in blood and urine were included to represent directed single element ordering. The percent of positive results, defined as results greater than the upper limit of the reference interval was determined. For blood, the highest positivity was observed for lead occupational exposure monitoring (26.2%) whereas for urine, the highest positivity was observed for zinc testing (28.1%). Remarkably, reanalysis using an expanded panel, of 120 blood and 174 urine specimens originally negative identified 42% (50 of 120) of the blood specimens with at least one elevated result and 48% (83 of 174) of the urine specimens with at least one elevated result. Our results indicate that a broad elemental screening panel may help ensure easier identification of elemental exposure and may eliminate the need for additional follow-up sample collections.

Association of Typical Toxic Heavy Metals with Schizophrenia.

Toxic heavy metals (THMs) are contaminants commonly found in the environment. Although a large number of studies have demonstrated their damage to the biological functions of the human being, their potential associations with the risk of developing schizophrenia remain controversial. In this study, we investigated the associations between four THMs (chromium (Cr), cadmium (Cd), lead (Pb) and arsenic (As)) in serum and the risk of schizophrenia. In total, 95 patients with schizophrenia (cases) and 95 normal subjects (controls) were recruited from Hebei Province, China. The serum concentrations of the 4 THMs were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). A higher concentration of Pb was found significantly associated with an elevated risk of schizophrenia (OR = 3.146; 95%CI: 1.238-7.994, p = 0.016), while significant association for the other three THMs were not observed. Besides, significant correlations were found between the metabolic biomarkers and the concentrations of Pb and As, respectively. In order to further characterize the association between these THMs and schizophrenia with greater statistical power, we conducted meta-analysis by including 538 cases and 1040 controls from the current study and 5 available datasets published from 2002 to 2018. Using a random-effect model, Cr was significantly associated with schizophrenia (SMD = 0.3246; 95%CI: 0.0166-0.6326, p < 0.01). Overall, this study suggested that higher levels of Pb and Cr may be one of the factors associated with an elevated risk of schizophrenia.

Ingestion of bedding material as a cause of acute copper sulfate poisoning in turkey poults.

The article reports a case of acute copper sulfate (CuSO4) poisoning in 2-day-old turkeys. The first incidences were noticed 2 h after placing the animals in the poultry house, where turkeys were provided with wood shaving bedding. Post-mortem examination showed wood shavings present in gastric and intestinal contents and numerous lesions in the alimentary tract: dark green color of the koilin lining, and surface erosions, deep ulceration, and severe congestion of the gizzard. The copper (Cu) concentration in samples of the liver, kidney, heart, gizzard content, gizzard muscle, gizzard lining, and wood shavings from the bedding was determined. Our results showed that the level of Cu in the livers of affected birds was more than sevenfold higher than the recommended value and the Cu content in bedding material was above the value considered to be toxic to turkeys. Our investigation identified the bedding disinfected using a CuSO4 solution as a possible cause of turkey fatalities.

Metallosis in cemented titanium alloy total knee arthroplasty without apparent metal-on-metal articulation.

BACKGROUND: Metallosis is an uncommon phenomenon observed in late failures of cemented total knee arthroplasty (TKA), and it is rarely seen in the absence of metal-on-metal articulation. METHODS: We report the case of a TKA patient with cemented titanium-alloy components and a polyethylene patella that was revised for early loosening with intra-operative severe metallosis. RESULTS: We found that loosening and severe metallosis were associated with methacrylate particle abrasion on titanium alloy surfaces. CONCLUSION: Serum titanium ion level measurement may be helpful in the workup of a painful TKA with titanium-alloy components in order to establish a diagnosis.

Assessing exposure to metals using biomonitoring: Achievements and challenges experienced through surveys in low- and middle-income countries.

In this narrative account based on a keynote presentation on exposure biomonitoring of metals in low- and middle-income countries (LMIC), we first briefly address practical issues that have arisen from our experience during the conduct of various surveys in LMIC. These have included the statistical handling of multiple pollutants in the same subject, the problem of correctly adjusting for urinary flow in spot samples of urine, and the possible external contamination of samples when doing field surveys in challenging environments. We then review and present selected results from surveys conducted in the mining area of Katanga in the Democratic Republic of Congo (DR Congo), where we documented high urinary levels of cobalt and other trace metals (arsenic, uranium) in people living close (<3 km) to mining or smelting operations (Banza et al., 2009). Consumption of contaminated foodstuffs (maize, legumes, fish) and, especially among children, dust ingestion proved to be the main sources of exposure to cobalt (Cheyns et al., 2014). Urinary biomonitoring studies among artisanal workers involved in mining cobalt, craftsmen working malachite, and workers processing gold ore revealed high to extremely high values of cobalt (largely exceeding the Biological Exposure Index of 15 µg/L), as well as other trace metals such as uranium, manganese, lead or mercury, depending on the type of jobs. This abundant biomonitoring data has been valuable to argue for improved enforcement of legislation to protect workers and citizens against the hazards posed by the mining activities in the area. Epidemiological studies have been undertaken and are ongoing to assess the human health impact of this pollution.

Cobalt toxicity after revision total hip replacement due to fracture of a ceramic head. / Toxicidad por cobalto después de la revisión a una artroplastia total de cadera posterior a fractura de cabeza cerámica.

Symptomatic cobalt toxicity from a failed total hip replacement is a rare, but devastating complication. Potential clinical findings include cardiomyopathy, hypothyroidism, skin rash, visual and hearing impairment, polycythaemia, weakness, fatigue, cognitive impairment, and neuropathy. The case is presented of a 74year-old man in whom, after a ceramic-ceramic replacement and two episodes of prosthetic dislocation, it was decided to replace it with a polyethylene-metal total hip arthroplasty (THA). At 6months after the revision he developed symptoms of cobalt toxicity, confirmed by analytical determination (serum cobalt level=651.2µg/L). After removal of the prosthesis, the levels of chromium and cobalt in blood and urine returned to normal, with the patient currently being asymptomatic. It is recommended to use a new ceramic on ceramic bearing at revision, in order to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components.

Disparities of Selected Metal Levels in the Blood and Scalp Hair of Ischemia Heart Disease Patients and Healthy Subjects.

Imbalances in the concentrations of trace metals have become an increasingly recognized source of infirmity worldwide particularly in the development of ischemia heart disease (IHD). Present study is intended to analyze the concentrations of Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Pb, Sr, and Zn in the blood and scalp hair of the patients and counterpart controls by flame atomic absorption spectrometry after wet-acid digestion. On the average, Cd, Co, Cr, Fe, K, Li, Mn, Na, and Pb revealed significantly elevated concentrations in the blood of the patients compared with the controls (p < 0.05), whereas mean levels of Ca, Cd, Fe, K, Li, Pb, and Sr in the scalp hair were significantly higher in the patients than the controls (p < 0.05). Most of the metals exhibited noticeable disparities in their concentrations based on gender, abode, dietary/smoking habits, and occupations of both donor groups. The correlation study and multivariate statistical analyses revealed some significantly divergent associations and apportionment of the metals in both donor groups. Overall, comparative variations of the metal contents in blood/scalp hair of the patients were significantly different than the controls; thus, evaluation of trace metals status may be indicative of pathological disorders, such as IHD.