Health risk assessment for human mercury exposure from Cinnabaris-containing Baizi Yangxin Pills in healthy volunteers Po administration.

BACKGROUND: Cinnabaris (α-HgS), a mineral traditional Chinese material medica, has been used in combination with other herbs manifesting some definite therapeutic effects for thousands of years. But the currently reported mercury poisoning incidents raised the doubts about the safety of Cinnabaris-containing traditional Chinese medicines (TCMs). Baizi Yangxin Pills (BZYXP) is a Cinnabaris-containing TCM widely used in clinical practice. This study evaluated the health risk of mercury exposure from BZYXP in healthy volunteers based on the total mercury and mercury species analysis of blood and urine after single and multiple doses of BZYXP. METHODS: Blood pharmacokinetics and urinary excretion studies of mercury were compared between single (9 g, once daily) and multiple doses (9 g, twice daily, continued for 7 days) of BZYXP. The whole blood and urine samples were collected at the specific points or periods after the administration of BZYXP. The total mercury and mercury species in blood and urine samples were determined by cold vapor-atomic fluorescence spectrometry (CV-AFS) and HPLC-CV-AFS, respectively. RESULTS: The mercury was excreted slowly and accumulated obviously after continuous exposure of BZYXP. Moreover, the well-known neurotoxin methylmercury (MeHg) was detected in blood samples after 7 days' administration of BZYXP. In the urine samples, only Hg(II) was detected. Therefore, long-term use of BZYXP will cause mercury poisoning due to mercury's high accumulative properties and MeHg formation. CONCLUSION: Cinnabaris-containing TCMs such as BZYXP should be restricted to cases in which alternatives are available, and the blood mercury species profile should be monitored during the long-term clinical medication.

The use of CytoSorb in acute oral mercuric chloride poisoning at a potentially lethal dose.

INTRODUCTION: The study aims to present a case of acute mercuric chloride poisoning treated successfully with continuous renal replacement therapy using the CytoSorb filter. CASE DESCRIPTION: A 21-year-old female patient after a suicide attempt by intentional ingestion of mercuric chloride, was admitted to the hospital with features of multiple organ damage for specific treatment. The performed laboratory tests confirmed high levels of mercury in the blood (1051 µg/L) and urine (22,960 µg/L). Due to acute renal failure, continuous renal replacement therapy (CRRT) CVVHD Ci-Ca was initiated; the procedure was then converted to CVVHDF Ci-Ca with ultrafiltration to optimise therapy, and CytoSorb was added to the artificial kidney system on day 3. Specific antidote therapy (DMPS) was administered concurrently. The ongoing treatment resulted in a reduction in subjective complaints, a decrease in blood mercury levels to 580 µg/L, and an improvement in parenchymal organ function. CONCLUSION: In the event of poisoning with inorganic mercury compounds (mercuric chloride), continuous renal replacement therapy using the CytoSorb filter as an extracorporeal blood purification method may be considered.

Synchrotron speciation of umbilical cord mercury and selenium after environmental exposure in Niigata.

The insidious and deadly nature of mercury's organometallic compounds is informed by two large scale poisonings due to industrial mercury pollution that occurred decades ago in Minamata and Niigata, Japan. The present study examined chemical speciation for both mercury and selenium in a historic umbilical cord sample from a child born to a mother who lived near the Agano River in Niigata. The mother had experienced mercury exposure leading to more than 50 ppm mercury measured in her hair and was symptomatic 9 years prior to the birth. We sought to determine the mercury and selenium speciation in the child's cord using Hg Lα1 and Se Kα1 high-energy resolution fluorescence detected X-ray absorption spectroscopy, the chemical speciation of mercury was found to be predominantly organometallic and coordinated to a thiolate. The selenium was found to be primarily in an organic form and at levels higher than those of mercury, with no evidence of mercury-selenium chemical species. Our results are consistent with mercury exposure at Niigata being due to exposure to organometallic mercury species.

Pathology of human organic mercury poisoning: Lessons from an autopsy case.

We had an opportunity to perform a general autopsy of a case with chronic organic mercury toxicosis in 2017. He had been engaged in synthesizing a variety of organic mercury compounds throughout the four years from 1966 and developed chronic organic mercury poisoning in 1969. Almost forty years on, he still remained to complain of persistent paresthesia at finger tips and tongue, and of narrowed visual field. Neurological examinations clarified a rise of two-point discrimination thresholds, a systemic increase of touch thresholds, constriction of the visual field caused by general visual depression, and sensorineural hearing loss while primary modalities of his somatic, visual, and auditory sensations were preserved. These symptoms and signs are characteristic of human organic mercury poisoning. Furthermore, he had difficulty in processing a lot of visual and auditory information at a time. His two-point discrimination thresholds and systemic elevation of touch thresholds were comparable to those of mild organic mercury poisoning cases. He had slight sensory ataxia, but not cerebellar ataxia. Brain [18F]-2-fluorodeoxyglucose positron emission tomography analysis exhibited marked hypometabolism at bilateral postcentral gyrus, striate cortex, and superior temporal gyrus, but not the cerebellum. Histopathological studies revealed considerable decrease of granular neurons and neuronal networks in bilateral primary somatosensory, visual, and auditory cortices. Those characteristic brain lesions fairly explain increase of thresholds of somatic, visual, and auditory sensations, and degradation of integrating sensory information. It is noted that damages to the peripheral nervous system and the cerebellum were not detected and that his intellectual faculties were preserved.

Thrombocytopenia Associated with Elemental Mercury Poisoning in Two Siblings - Connecticut, July 2022.

Two siblings aged 5 and 15 years from Connecticut were hospitalized with petechial rash, oral mucositis, and severe thrombocytopenia approximately 10 days after they played with a jar of elemental mercury they found in their home. Before the mercury exposure was disclosed, the siblings were treated with platelet transfusions, intravenous immune globulin (IVIG) for possible immune thrombocytopenic purpura, and antibiotics for possible infectious causes. When their conditions did not improve after 6 days, poison control facilitated further questioning about toxic exposures including mercury, testing for mercury, and chelation with dimercaptosuccinic acid. The older sibling soon recovered, but the younger child required a prolonged hospitalization for severe thrombocytopenia, ultimately receiving repeated doses of IVIG, steroids, and romiplostim, a thrombopoietin receptor agonist. Close collaboration among multiple agencies was required to identify the extent of mercury contamination, evaluate and treat the other family members, and decontaminate the home. These cases demonstrate the importance of ongoing public health outreach to promote early detection of elemental mercury toxicity, and the need to evaluate for environmental exposures when multiple close contacts experience similar signs and symptoms.

Acute mercuric chloride poisoning at a potentially lethal dose ended with survival: symptoms, concentration in cerebrospinal fluid, treatment.

This study aims to present a case of acute mercuric chloride poisoning at a potentially lethal dose treated with the antidote - 2,3-dimercapto- 1-propanesulfonic acid (DMPS) and continuous renal replacement therapy (CRRT) combined with CytoSorb. A 21-year-old woman was admitted to a hospital with abdominal pain, vomiting, and suspected gastrointestinal bleeding after taking 5000 mg of mercuric chloride for suicidal purposes. Due to the patient deteriorating general condition and multiple organ damage, on the third day she was transported to the Clinic of Anaesthesiology and Intensive Care (CAaIC), Lódz, Poland. Laboratory tests confirmed features of acute kidney injury and high mercury levels in the blood (1051 µg/l) and urine (22 960 µg/l) - DMPS therapy and CRRT combined with CytoSorb were instituted. Due to nervous system complaints (headache, dizziness), a lumbosacral puncture was performed - the mercury concentration in the cerebrospinal fluid (CSF) was 5.45 µg/l. During a colonoscopy, significant diagnostic abnormalities revealed features of colonic mucosal necrosis. The treatment resulted in a decrease in subjective complaints, decreased mercury levels in biological material, and improved parenchymal organ function. On the 15th day of therapy, the patient was transferred to the primary care center for further treatment. The case confirms the possibility of improvement of patient condition following ingestion of a potentially lethal dose (5 g) as a result of the initiation of appropriate therapy even on the third day. The presence of mercury in CSF confirms that inorganic mercury compounds (mercuric chloride) can pass through the blood-brain barrier after oral ingestion. Int J Occup Med Environ Health. 2023;36(5):685-92.

Clinical Spectrum of Mercury Poisoning in India: Case-series from a Poison Control Center.

BACKGROUND: Mercury is a naturally occurring heavy metal that finds wide application in industrial and household settings. It exists in three chemical forms which include elemental (Hg0 ), inorganic mercurous (Hg+) or mercuric (Hg++) salts, and organic compounds. All forms are highly toxic, particularly to the nervous, gastrointestinal, and renal systems. Common circumstances of exposure include recreational substance use, suicide or homicide attempts, occupational hazards, traditional medicines, and endemic food ingestions as witnessed in the public health disasters in Minamata Bay, Japan and in Iraq. Poisoning can result in death or long-term disabilities. Clinical manifestations vary with chemical form, dose, rate, and route of exposure. AIMS AND OBJECTIVES: To summarize the incidence of mercury poisoning encountered at an Indian Poison Center and use three cases to highlight the marked variations observed in clinical manifestations and long-term outcomes among poisoned patients based on differences in chemical forms and routes of exposure to mercury. MATERIALS AND METHODS: A structured retrospective review of the enquiry-database of the Poison Information Center and medical records of patients admitted between August 2019 and August 2021 in a tertiary care referral center was performed. All patients with reported exposure to mercury were identified. We analyzed clinical data and laboratory investigations which included heavy metal (arsenic, mercury, and lead) estimation in whole blood and urine samples. Additionally, selected patients were screened for serum voltage-gated potassium ion channels (VGKC)- contactin-associated protein-like 2 (CASPR2) antibodies. Three cases with a classical presentation were selected for detailed case description. RESULTS: Twenty-two cases were identified between August 2019 and August 2021. Twenty (91%) were acute exposures while two (9%) were chronic. Of these, three representative cases have been discussed in detail. Case 1 is a 3.5-year-old girl who was ought to the emergency department with suspected elemental-mercury ingestion after biting a thermometer. Clinical examination was unremarkable. Chest and abdominal radiography revealed radiodense material in the stomach. Subsequent serial radiographs documented distal intestinal transit of the radiodense material. The child remained asymptomatic. This case exemplifies the largely nontoxic nature of elemental mercury ingestion as it is usually not absorbed from the gastrointestinal tract. Case 2 is a 27-year-old lady who presented with multiple linear nodules over both upper limbs after receiving a red intravenous injection for anemia. Imaging revealed metallic-density deposits in viscera and bones. Nodular biopsy was suggestive of mercury granulomas. A 24-hour urine mercury levels were elevated. She was advised chelation therapy with oral dimercaptosuccinic acid (DMSA). Case 3 is a 22-year-old lady who presented with acrodynia, neuromyotonia, tremulousness, postural giddiness, tachycardia, and hypertension for 2 months, associated with intractable, diffuse burning pain over the buttocks and both lower limbs, 1 month after completing a 3-week course of traditional medications for polycystic ovarian syndrome. A 24-hour urine normetanephrine levels and mercury levels were markedly elevated. Serum anti-VGKC antibodies were present. She was treated with glucocorticoids and oral DMSA with a favorable clinical response. CONCLUSIONS: The clinical manifestations of mercury toxicity are highly variable depending on the source, form, and route of mercury exposure and are related to its toxicokinetics.

Mercurial risk from dental amalgam use in a population of Moroccan dentists: A latent class regression approach.

BACKGROUND: Dentists using dental amalgam are chronically exposed to low doses of elemental mercury. The complex toxico-kinetics of this systemic toxicant results in polymorphic and variable clinical phenotypes. In this context, adapted statistical methods are required to highlight potential adverse effects of occupational mercury exposure on dentists' health. OBJECTIVE: The present study aims to analyze the distribution of self-reported subjective symptoms, commonly associated with chronic mercury poisoning, according to occupational mercury exposure in a population of Moroccan liberal dentists. METHODS: In order to achieve the defined objectives, a three-step latent class regression was fitted. First a latent class analysis was performed to cluster the studied population according to their declared symptoms. Dentists were then classified in the defined latent classes based on their posterior probabilities. Finally, a logistic regression is fitted to identify predictors associated with the latent classes' membership. RESULTS: The final obtained model showed acceptable calibration and discrimination. Its interpretation revealed that the increase of the frequency of amalgam use was associated with significant higher odds of belonging to the high risk latent class. CONCLUSIONS: The present study represents an initial step towards the development of diagnosis model that predict clinical profiles according to occupational mercury exposure.

Proteasome and p62/SQSTM1 are involved in methylmercury toxicity mitigation in mouse embryonic fibroblast cells.

Methylmercury (MeHg), an environmental pollutant, disrupts and impairs cellular function. MeHg binds to various cellular proteins, causing dysfunction and misfolding, which are considered underlying causes of MeHg toxicity. The p62 protein, also termed SQSTM1, is a ubiquitin-binding protein that targets ubiquitinated substrates to undergo autophagy and plays a key role in ameliorating MeHg toxicity. p62 also delivers ubiquitinated substrates to proteasomes. However, the role of these degradation systems in mitigating MeHg toxicity remains unknown. Herein, we explored the impact of the proteasome inhibitor MG132 on MeHg toxicity and examined the toxicity of co-treatment with MG132 and MeHg in p62KO mouse embryonic fibroblasts (MEFs) by analyzing cell viability, immunoblotting, mRNA levels, immunofluorescence, and the mercury content. The proteasome inhibitor MG132 enhanced MeHg-induced cytotoxicity while reducing intracellular mercury levels in MEFs. Co-treatment with MG132 and MeHg markedly increased levels of p62 and ubiquitinated proteins. Furthermore, co-treatment with MG132 and MeHg reduced p62KO MEF viability compared to that of wild-type MEFs. Our findings suggest that the proteasome participates in mitigating MeHg cytotoxicity, while p62 may play an important role in transporting MeHg-induced ubiquitinated proteins to the proteasome, as well as in autophagy. Collectively, these results imply that p62, and proteasome, and autophagy are vital for cytoprotection against MeHg toxicity.

Monitoring Hg2+ and MeHg+ poisoning in living body with an activatable near-infrared II fluorescence probe.

Noninvasively imaging mercury poisoning in living organisms is critical to understanding its toxicity and treatments. Especially, simultaneous fluorescence imaging of Hg2+ and MeHg+in vivo is helpful to disclose the mysteries of mercury poisoning. The key limitation for mercury imaging in vivo is the low imaging signal-to-background ratio (SBR) and limited imaging depth, which may result in unreliable detection results. Here, we designed and prepared a near-infrared II (NIR II) emissive probe, NIR-Rh-MS, leveraging the "spirolactam ring-open" tactic of xanthene dyes for in situ visualization of mercury toxicity in mice. The probe produces a marked fluorescence signal at 1015 nm and displays good linear responses to Hg2+ and MeHg+ with excellent sensitivity, respectively. The penetration experiments elucidate that the activated NIR-II fluorescence signal of the probe penetrates to a depth of up to 7 mm in simulated tissues. Impressively, the probe can monitor the toxicity of Hg2+ in mouse livers and the accumulation of MeHg+ in mouse brains via intravital NIR-II imaging for the first time. Thus, we believe that detecting Hg2+ and MeHg+ in different organs with a single NIR-II fluorescence probe in mice would assuredly advance the toxicologic study of mercury poisoning in vivo.

[Report on a case of significant increase in urine mercury due to excessive mercury in cosmetics].

Mercury is highly toxic and can be absorbed through skin contact. From December 5, 2020 to February 16, 2021, occupational disease laboratory of the First People's Hospital of Baiyin received 30 urine mercury test samples from a beauty salon in Lanzhou City. The test results showed that 28 samples exceeded the normal value (normal value: 4 µg/g Cr) . 15 patients were treated with sodium dimertopropyl sulfonate for mercury removal and tiopron for liver protection, and the prognosis was good.

Suicidal intoxication with mercury chloride.

PURPOSE: Poisoning with elemental metals and metallic compounds was much more frequent in the past, and was related, among other things, to lifestyle and the lack of appropriate toxicological diagnostics. One example is mercury, which is being gradually eliminated but still has many different applications as a pure metal or in the form of various compounds. The paper presents a case of suicidal poisoning with mercury chloride (corrosive sublimate). METHODS: Forensic and toxicological tests including inductively coupled plasma mass spectrometry (ICP-MS) were at the Department of Forensic Medicine, PMU in Szczecin. RESULTS: The patient before death had a range of symptoms such as epigastric pain, vomiting of the stomach contents, central cyanosis with tachycardia, tremors, severe shortness of breath with wheezing, difficulty swallowing, slurred speech, rales in the lungs, and diarrhea. The concentration of mercury measured by ICP-MS was 191 mg/L for a blood sample collected antemortem, and 147 mg/L for a blood sample collected at autopsy. Both concentrations of mercury are regarded as lethal. The post-mortem examination revealed signs of extensive thrombotic necrosis in some internal organs. CONCLUSIONS: Mercuric chloride has an estimated human fatal dose of between 1 and 4 g. It can produce a range of toxic effects, including corrosive injury, severe gastrointestinal disturbances, acute renal failure, circulatory collapse, and eventual death. The presented case of fatal poisoning with mercury chloride, due to the type of agent used, is now interesting in toxicological practice.

Characteristics, Treatment, and Prognosis of Elemental Mercury Intoxication in Children: A Single-Center Retrospective Study.

OBJECTIVES: Mercury exposure is common and can be toxic, especially in children. Children are often drawn to elemental mercury because of its density, color, and proclivity to form beads. METHODS: We present data on 49 children with mercury intoxication (MI) and 60 children with mercury exposure from Turkey. RESULTS: The most common source of mercury was broken thermometer in schools. Inhaling mercury vapor was the most common route of exposure. The median exposure time was 6 (6-16) hours in the MI group, and the time to 1st symptoms was 10 (0-24) hours. In the MI group, the median blood mercury level was 21 µg/L (13-32.3), the median spot urine mercury level was 40 µg/L (7.66-78), and the median 24-hour urine mercury level was 25.8 µg/L (11-64). The most common symptoms in patients with MI were malaise, muscle pain, muscle cramps, abdominal pain, nausea, headache, and decreased appetite. The patients were treated with n-acetyl cysteine, 2,3-dimercaptopropane sulfonic acid, D-penicillamine, and meso 2,3-dimercaptosuccinic acid. A positive correlation was found between exposure time and urinary mercury level in the MI group (r = 0.793, P < 0.001). A positive moderate correlation was found between exposure time and blood level in the mercury exposure group (r = 0.535, P < 0.00). The neurological and systemic examinations of patients were all normal at the 1st follow-up visit 1 month after discharge. CONCLUSIONS: Diagnosis, removal of the exposure source, and use of chelation therapy can result in complete resolution of the signs and symptoms of MI.

Non-essential heavy metals and protective effects of selenium against mercury toxicity in endangered Australian sea lion (Neophoca cinerea) pups with hookworm disease.

The endangered Australian sea lion, Neophoca cinerea, faces ongoing population decline. Identification of key threats to N. cinerea population recovery, including disease and pollutants, is an objective of the species' recovery plan. Previous studies have identified Uncinaria sanguinis, an intestinal nematode, as a significant cause of disease and mortality in N. cinerea pups. Given the impact of heavy metals on the immune response, investigation of these pollutants is critical. To this end, the concentrations of arsenic (As), total mercury (Hg), cadmium (Cd), chromium (Cr), lead (Pb) and selenium (Se) were determined in blood collected from N. cinerea pups sampled during the 2017/18, 2019 and 2020/21 breeding seasons at Seal Bay Conservation Park, South Australia. Significant differences (p < 0.05) in Hg, As, Cr, and Se concentrations and molar ratio of Se:Hg were seen between breeding seasons. Pup age, maternal parity and inter-individual foraging behaviour were considered factors driving these differences. The concentrations of Hg (357, 198 and 241 µg/L) and As (225, 834 and 608 µg/L) were high in 2017/18, 2019 and 2020/21 respectively with Hg concentrations in the blood of N. cinerea pups above toxicological thresholds reported for marine mammals. The concentration of Se (1332, 647, 763 µg/L) and molar ratio of Se:Hg (9.47, 7.98 and 6.82) were low compared to other pinniped pups, indicating potential vulnerability of pups to the toxic effects of Hg. Significant (p < 0.05) negative associations for Pb and Cd with several red blood cell parameters suggest they could be exacerbating the anaemia caused by hookworm disease. Temporal (age-related) changes in element concentrations were also seen, such that pup age needs to be considered when interpreting bioaccumulation patterns. Further investigation of the role of elevated heavy metal concentrations on N. cinerea pup health, disease and development is recommended, particularly with respect to immunological impacts.

Serum hsa-circ-0025244 as a biomarker in Chinese occupational mercury-exposed population and mediate apoptosis through JNK/p38 MAPK signaling pathway.

BACKGROUND: circRNAs have been recognized as biomarkers of numerous diseases. We would like to explore the expression pattern and molecular mechanisms of circRNAs in the Chinese occupational mercury-exposed population. METHODS: The workers from a thermometer manufacturing plant and lamp factory in Jiangsu province of China were recruited in 2016. Blood samples were collected from the subjects with chronic mercury poisoning group, mercury absorption group, and the healthy controls. The differentially expressed circRNAs (DECRs) between the three groups were screened from serum samples using a circRNA microarray. The significant DECRs were validated by qRT-PCR, and their respective diagnostic values for mercury poisoning and mercury absorption were analyzed by receiver operating characteristic (ROC) curves. For in vitro experiments, 293T cells were treated with different doses of HgCl2 to determine the half-lethal concentration. The cells were transfected with the siRNA construct or expression plasmid of circRNA. The expression levels of JNK, p38, and caspase family proteins were analyzed by Western blotting. RESULTS: hsa_circ_0025244 was up-regulated in the mercury poisoning and absorption groups compared to the control group (P < 0.05), and positively correlated with the urine mercury levels (P < 0.05). The area under the ROC curve (AUC) of hsa_circ_0025244 for diagnosing occupational mercury poisoning was 0.748, indicating moderate accuracy (P < 0.001). Moreover, the diagnostic accuracy of occupational mercury absorption was high (P < 0.001) with an AUC of 0.918. Knockdown of hsa_circ_0025244 in 293T cells significantly reduced the expression levels of JNK/p38, and caspase family proteins compared to that in the control cells (P < 0.01), and its overexpression led to opposite effects (P < 0.05). CONCLUSIONS: hsa_circ_0025244 is a potential biomarker for mercury exposure and mediates mercury-induced apoptosis in 293T cells by activating the JNK/p38 MAPK signaling pathway.