Toxicity and risk assessment of mercury exposures from cinnabar and Baizi Yangxin Pills based on pharmacokinetic and tissue distribution studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Baizi Yangxin Pills (BZYXP), a popular cinnabar (α-HgS) contained Traditional Chinese Medicines (TCMs) is widely used in clinical trials. However, mercury is one of the most toxic elements. The adverse effects of cinnabar-containing TCMs have been occasionally reported in recent years, leading to the growing concerns about their toxicity and safety. AIM OF THE STUDY: The health risks of BZYXP and cinnabar related to the mercury exposures were evaluated through blood pharmacokinetic and tissue distribution studies in rats. MATERIALS AND METHODS: The distribution of absorbed mercury in rats' blood and tissues were measured by the developed cold-vapor atomic fluorescence spectrometric method. And the tissue damages were determined through the histopathological examinations. For single dose study, the low and high oral doses were equivalent to 1 and 10-fold therapeutic dose, respectively. The multiple doses study was conducted at low and high dose levels every 12 h for 30 consecutive days. RESULTS: Significant differences of mercury blood pharmacokinetic and tissue distribution characteristics were observed between the corresponding BZYXP and cinnabar groups. The herbal ingredients in BZYXP promoted the absorption of bio-accessible mercury of cinnabar and prolonged the elimination process, posing potential health risks. Although mercury was found easily accumulated in kidney, liver and brain tissues, kidney and liver didn't show obvious damages even after 30 days consecutive administration of BZYXP or cinnabar at 10-fold clinically equivalent doses. But brain did show some histopathological changes, and autonomic activities of rats decreased, pointing the potential neurotoxicity. CONCLUSIONS: Mercury tend to be accumulated especially when over-dose or prolonged medication with cinnabar-containing TCMs are given. The mercury exposures even at therapeutic doses of BZYXP or cinnabar do pose health risks from the neurotoxicity point of view.

[Mercury as a Global Pollutant and Mercury Exposure Assessment and Health Effects].

Mercury and its compounds are classified into three main groups: metallic mercury (Hg0), inorganic mercury (Hg2+), and organic mercury (methyl mercury: CH3Hg+, etc.). Metallic mercury is the only metal that is liquid at ambient temperature and normal pressure, which readily forms an amalgam with other metals. Therefore, mercury has long been used for refining various metals, and mercury amalgam has been used for dental treatment. Mercury has also been used in measuring instruments such as thermometers, barometers and blood pressure monitors, as well as electric appliances such as lighting equipment and dry batteries. Large amounts of metallic mercury are still used in other countries as a catalyst in the production of caustic soda by electrolysis. In addition, mercury compounds have been used in various chemicals such as mercurochrome, agricultural chemicals, and mildew-proofing agents. However, the use of mercury has also caused health problems for people. Minamata disease in Japan is a typical example. Also, since mercury is highly volatile, it is discharged as a product of industrial activities or derived from volcanoes, and it has been concluded on the basis of the findings of the United Nations Environment Program (UNEP) that it is circulating globally. Therefore, with the aim of establishing an internationally legally binding treaty for the regulation of mercury use to reduce risk, an intergovernmental negotiating committee was established in 2009. Japan actively contributed to this negotiation owing to its experience with Minamata disease, which led to the Convention on the regulation of mercury use being discharged as the "Minamata Convention on Mercury" and the treaty came into force on August 16, 2017. In this review, we introduce 1) the Global Mercury Assessment by UNEP; 2) mercury kinetics, exposure assessment and toxicity of different chemical forms; 3) large-scale epidemics of methylmercury poisoning; 4) methylmercury exposure assessment and health survey in whale-eating populations; 5) elemental mercury exposure assessment and health survey of mercury mine workers in China.

Bioaccessibility and health risk assessment of mercury in cinnabar containing Traditional Chinese Medicines.

Cinnabar (α-HgS), has been formulated in Traditional Chinese Medicines (TCMs) for thousands of years. Since the total Hg content was accepted widely as the toxicity criteria, the safety alerts have been issued about the cinnabar containing TCMs for exceeding Hg limits. However, cinnabar is almost insoluble in water, the oral absorption is extremely low. Hence, it is not suitable to use the total Hg content alone to evaluate the toxicity of cinnabar containing TCMs. In instead, the bioaccessible Hg is a much reasonable safety indicator. In this study, bioaccessible Hg contents of 29 cinnabar containing TCMs were determined by cold vapor-atomic fluorescence spectrometry after in vitro extractions with the simulated gastrointestinal fluids, while the total Hg contents were determined after acid digestion. According to the daily dosages, the bioaccessible Hg exposures of these TCMs were evaluated, and most of them were within the permitted daily exposure set by the International Council for Harmonisation, demonstrating that these TCMs are safe when administrated following the instructions. However, the obtained results also suggested that the Hg exposure could also be influenced by the herbal ingredients in TCMs and the bioactivities in gastrointestinal tract, indicating the possible health risks after excessive or long-term medication of cinnabar containing TCMs. Considering the influencing factors of the Hg intakes after oral administration of cinnabar containing TCMs, the bioaccessible Hg exposure should be considered as a more rational criterion for evaluating the health risks than the total Hg content. Furthermore, precautions should also be taken to ensure safe usages of cinnabar containing TCMs from both the cinnabar contents and the processing procedures points of view, as well as the daily dosage regimen, for all of them are directly related with the bioaccessible Hg exposures.

[Risk assessment for clinical external application of calomel].

Calomel is a common traditional Chinese medicine (TCM) containing mercury in clinical external application. Although the toxicity of calomel has attracted concern, there is no unified standard yet in clinical external application. Risk assessment is used for evaluating the potential health effects of hazardous substances. The purpose of this article was to evaluate the health risk of calomel in clinical external application on the basis of toxicity data, to ensure safe and rational application of TCM containing calomel. The toxicity data of transdermal administration of calomel or mercurous chloride were collected by searching the literature. The daily maximum exposure dosage of calomel in clinical external application was estimated by following the four procedures of risk assessment, and Margin of Safety (MOS) as an evaluation indicator was then calculated to evaluate the safety of calomel on clinical application. It has been reported that the adult in single transdermal administration of calomel at 1. 5 g was lethal. Based on the LOAEL of calomel for long-term transdermal exposure (1 month) in rats was 0.096 g · kg(-1) · d(-1), the NOAEL of calomel for patients (about 60 kg) by external application within 2 weeks was estimated to be 1.46 mg · kg(-1) · d(-1). When MOS value equals to 1, the daily maximum exposure of calomel in clinical external application within 2 weeks was calculated to be 1.1 g. The results suggest that daily single dose of calomel in clinical external application should be lower than 1.5 g for adults, and more attention should be paid to changes in hepatic and renal function of patients when repeated dose more than 1.1 g within 2 weeks. The approach of risk assessment could be helpful in rational application of TCM containing mercury.

Predicted no-effect concentrations for mercury species and ecological risk assessment for mercury pollution in aquatic environment.

Mercury (Hg) exists in different chemical forms presenting varied toxic potentials. It is necessary to explore an ecological risk assessment method for different mercury species in aquatic environment. The predicted no-effect concentrations (PNECs) for Hg(II) and methyl mercury (MeHg) in the aqueous phase, calculated using the species sensitivity distribution method and the assessment factor method, were 0.39 and 6.5×10(-3)µg/L, respectively. The partition theory of Hg between sediment and aqueous phases was considered, along with PNECs for the aqueous phase to conduct an ecological risk assessment for Hg in the sediment phase. Two case studies, one in China and one in the Western Black Sea, were conducted using these PNECs. The toxicity of mercury is heavily dependent on their forms, and their potential ecological risk should be respectively evaluated on the basis of mercury species.

Mercury exposure and children's health.

Acute or chronic mercury exposure can cause adverse effects during any period of development. Mercury is a highly toxic element; there is no known safe level of exposure. Ideally, neither children nor adults should have any mercury in their bodies because it provides no physiological benefit. Prenatal and postnatal mercury exposures occur frequently in many different ways. Pediatricians, nurses, and other health care providers should understand the scope of mercury exposures and health problems among children and be prepared to handle mercury exposures in medical practice. Prevention is the key to reducing mercury poisoning. Mercury exists in different chemical forms: elemental (or metallic), inorganic, and organic (methylmercury and ethyl mercury). Mercury exposure can cause acute and chronic intoxication at low levels of exposure. Mercury is neuro-, nephro-, and immunotoxic. The development of the child in utero and early in life is at particular risk. Mercury is ubiquitous and persistent. Mercury is a global pollutant, bio-accumulating, mainly through the aquatic food chain, resulting in a serious health hazard for children. This article provides an extensive review of mercury exposure and children's health.

Assessment of chronic mercury exposure within the U.S. population, National Health and Nutrition Examination Survey, 1999­2006.

The purpose of this study was to assess chronic mercury exposure within the US population. Time trends were analyzed for blood inorganic mercury (I-Hg) levels in 6,174 women, ages 18-49, in the NHANES, 1999-2006 data sets. Multivariate logistic regression distinguished a significant, direct correlation within the US population between I-Hg detection and years since the start of the survey (OR = 1.49, P < 0.001). Within this population, I-Hg detection rose sharply from 2% in 1999-2000 to 30% in 2005-2006. In addition, the population averaged mean I-Hg concentration rose significantly over that same period from 0.33 to 0.39 µ/L (Anova, P < 0.001). In a separate analysis, multivariate logistic regression indicated that I-Hg detection was significantly associated with age (OR = 1.02, P < 0.001). Furthermore, multivariate logistic regression revealed significant associations of both I-Hg detection and mean concentration with biomarkers for the main targets of mercury deposition and effect: the liver, immune system, and pituitary. This study provides compelling evidence that I-Hg deposition within the human body is a cumulative process, increasing with age and in the population over time, since 1999, as a result of chronic mercury exposure. Furthermore, our results indicate that I-Hg deposition is associated with the significant biological markers for main targets of exposure, deposition, and effect. Accumulation of focal I-Hg deposits within the human body due to chronic mercury exposure provides a mechanism which suggests a time dependent rise in the population risks for associated disease.

Neuropsychological function in school-age children with low mercury exposures.

The EPA reference dose for methylmercury (MeHg) was established using data from populations with greater exposures than those typical of the US. Few data are available on potential adverse health effects at lower levels. We examined relationships between hair mercury (Hg) levels and neuropsychological outcomes in a population of US children. This study included data from 355 children ages 6-10 enrolled in the New England Children's Amalgam Trial. Data on total hair Hg levels, sociodemographic information and neuropsychological function were collected. We evaluated associations between hair Hg and neuropsychological test scores with linear regression methods and used generalized additive models to determine the shape of associations that departed from linearity. Models controlled for relevant covariates, including the potential beneficial effects of consuming fish. In adjusted models, we observed no significant linear relationships between hair Hg level and any test score. Significant departures from linearity were identified for WIAT Math Reasoning and WRAMVA Visual-Motor Composite scores. The association was positive for hair Hg levels below 0.5 microg/g and negative for levels between 0.5 and 1.0 microg/g. Overall, test scores of children with hair Hg levels 1.0 microg/g appeared to be lower than those of children with levels < 1.0 microg/g, but few children had levels in this upper range and these differences did not reach statistical significance. Hair Hg levels below 1.0 microg/g in US school-age children were not adversely related to neuropsychological function.

Incorporating ethnographic methods in multidisciplinary approaches to risk assessment and communication: cultural and religious uses of mercury in Latino and Caribbean communities.

The potential risk from cultural and religious practices involving mercury in Latino and Caribbean communities raises central methodological and ethical questions for risk assessment and risk communication. Here, specific cultural practices unfamiliar to most risk professionals carry significant inherent risks in the eyes of those professionals but not necessarily in the eyes of practitioners. Practitioners' past experience and history as targets of religious suppression and anti-immigrant sentiment create a reluctance to engage with researchers or public health officials in risk assessment or preventive risk communication efforts. The potential for the risk--in this case mercury contamination in dwellings--to extend beyond the practicing community to future occupants adds to public health concern. Understanding the risks of these practices requires both an understanding of the cultural and political context, beliefs, and behaviors of mercury users and an understanding of the fate and transport of mercury in typical use scenarios. In this study, we employed ethnographic methods (interviews and participant observation) to understand beliefs and behavior about mercury use as well as quantitative modeling and measurement to estimate and assess potential exposures. This represents a new methodology tailored to situations in which traditional activities or observances that are integral components of cultural identity pose risks in and of themselves. Our findings indicate that there are different types of mercury use stemming from different cultural and religious traditions that result in different levels of exposure. Many of the mercury uses that can result in the highest exposures to mercury vapors have previously been attributed to the religious tradition of Santeria, but appear instead to have their roots outside of the religion.

Mercury use and exposure among Santeria practitioners: religious versus folk practice in Northern New Jersey, USA.

OBJECTIVE: To understand and characterize exposure to and use of elemental mercury among practitioners of Afro-Cuban religions in Hudson County, New Jersey, USA. DESIGN: Participant observation and open-ended interviews with 22 religious supply store employees and practitioners of Santeria, Espiritismo or Palo Mayombe probed respondents' knowledge and use of mercury, as well as their beliefs about its benefits and risks. Including a cultural and religious insider as part of the research team was crucial in working with this relatively closed community. RESULTS: Seventeen of the 21 practitioners reported using mercury or mercury compounds in various forms of practice and in services that they provide to clients. The contained nature of these uses suggests that accidental spills, as opposed to the practices themselves, emerge as the greatest exposure concern for this population. Mercury was never recommended to clients for individual use. This restriction appears to be rooted in the way the religion is practiced and in the way santeros receive compensation, not in a perception of mercury as hazardous. Most practitioners were aware that mercury can be hazardous, but were not familiar with the most significant exposure pathway, inhalation of mercury vapor. A climate of fear surrounds the use of mercury in this community, so that health concerns pale in comparison to fear of reprisal from authorities. Among those who sell or formerly sold mercury, several shared the erroneous belief that it was illegal to sell mercury in New Jersey. CONCLUSION: Despite widespread reported use, there were no reports of practices believed to result in the highest exposures. To reduce exposure in the community, interventions presenting general information on mercury hazards and instructions for cleaning up spills are recommended. To address insider-outsider dynamics and the climate of fear, educational materials should be accessible to the community and avoid any mention of religious practice.