The Irrawaddy dolphin, Orcaella brevirostris from the Mekong river Cambodia: Preliminary health and toxicological investigations.

The subpopulation of the Irrawaddy dolphin (Orcaella brevirostris) living in the Mekong River, Cambodia, is considered to be critically endangered. The aim of the investigation was to gain information about the genetic variation, health status and exposure to toxic compounds of these dolphins. Tissue samples from 27 Irrawaddy river dolphins found dead along the Mekong River between 2004 and 2009 were analysed with regards to genetics, pathology and ecotoxicology. Genetic maternal lineage detection, based on polymorphisms of the mitochondrial d-loop sequences, was performed. Data indicate a genetic separation of the Mekong dolphins from both the coastal population and the Mahakam dolphins. Pathological investigations revealed acute moderate multifocal suppurative bronchopneumonia, moderate periportal hepatic lipidosis, moderate diffuse hepatic atrophy and acute severe diffuse suppurative leptomeningitis. Residue levels of organochlorines and polybrominated diphenyl ethers in Irrawaddy dolphins from the Mekong River were lower than the concentrations reported for other cetaceans in the coastal and riverine waters of Asia, except for Dichlorodiphenyltrichloroethane. A high percentage of organic mercury compared to the immuno-toxic methylmercury was observed. Due to numerous confounding factors, it is not possible to relate levels of pollutants to observed morphological lesions. However, it is likely that chemical contaminants do adversely impact on the health of the Irrawaddy dolphins at present, and have also affected previous generations.

Revision of reciprocal action of mercury and selenium.

Diverse forms of mercury (Hg) have various effects on animals and humans because of a variety of routes of administration. Inorganic mercury (iHg) binds to thiol groups of proteins and enzymes in one's body or is methylated by microorganisms. Organic form of Hg, contrary to the iHg, is more stable but may be demethylated to Hg2+ in the tissue of intestinal flora. Selenium (Se) also occurs in a variety of chemical forms in one's body but both of these elements behave very differently from one another. Mercury binding to selenide or Se-containing ligands is a primary molecular mechanism that reduces toxicity of Hg. Complexes formed in such a way are irreversible, and thus, biologically inactive. Se deficiency in a human body may impair normal synthesis of selenoproteins and its expression because expression of mRNA may be potentially regulated by the Se status. This paper provides a comprehensive review concerning Hg-Se reciprocal action as a potential mechanism of protective action of Se against Hg toxicity as well as a potential detoxification mechanism. Although interactions between Hg-Se have been presented in numerous studies concerning animals and humans, we have focused mainly on animal models so as to understand molecular mechanisms responsible for antagonism better. The review also investigates what conclusions have been drawn by researchers with respect to the chemical species of Se and Hg (and their relationship) in biological systems as well as genetic variations and expression and/or activity of selenoproteins related to the thioredoxin (thioredoxin Trx/TrxR) system and glutathione metabolism. Int J Occup Med Environ Health 2018;31(5):575-592.

The aging kidney and the nephrotoxic effects of mercury.

Owing to advances in modern medicine, life expectancies are lengthening and leading to an increase in the population of older individuals. The aging process leads to significant alterations in many organ systems, with the kidney being particularly susceptible to age-related changes. Within the kidney, aging leads to ultrastructural changes such as glomerular and tubular hypertrophy, glomerulosclerosis, and tubulointerstitial fibrosis, which may compromise renal plasma flow (RPF) and glomerular filtration rate (GFR). These alterations may reduce the functional reserve of the kidneys, making them more susceptible to pathological events when challenged or stressed, such as following exposure to nephrotoxicants. An important and prevalent environmental toxicant that induces nephrotoxic effects is mercury (Hg). Since exposure of normal kidneys to mercuric ions might induce glomerular and tubular injury, aged kidneys, which may not be functioning at full capacity, may be more sensitive to the effects of Hg than normal kidneys. Age-related renal changes and the effects of Hg in the kidney have been characterized separately. However, little is known regarding the influence of nephrotoxicants, such as Hg, on aged kidneys. The purpose of this review was to summarize known findings related to exposure of aged and diseased kidneys to the environmentally relevant nephrotoxicant Hg.

Mechanisms involved in the transport of mercuric ions in target tissues.

Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are taken up by and accumulate in numerous organs, including brain, intestine, kidney, liver, and placenta. In order to understand the toxicological effects of exposure to mercury, a thorough understanding of the mechanisms that facilitate entry of mercuric ions into target cells must first be obtained. A number of mechanisms for the transport of mercuric ions into target cells and organs have been proposed in recent years. However, the ability of these mechanisms to transport mercuric ions and the regulatory features of these carriers have not been characterized completely. The purpose of this review is to summarize the current findings related to the mechanisms that may be involved in the transport of inorganic and organic forms of mercury in target tissues and organs. This review will describe mechanisms known to be involved in the transport of mercury and will also propose additional mechanisms that may potentially be involved in the transport of mercuric ions into target cells.

Organic and inorganic mercurials have distinct effects on cellular thiols, metal homeostasis, and Fe-binding proteins in Escherichia coli.

The protean chemical properties of the toxic metal mercury (Hg) have made it attractive in diverse applications since antiquity. However, growing public concern has led to an international agreement to decrease its impact on health and the environment. During a recent proteomics study of acute Hg exposure in E. coli, we also examined the effects of inorganic and organic Hg compounds on thiol and metal homeostases. On brief exposure, lower concentrations of divalent inorganic mercury Hg(II) blocked bulk cellular thiols and protein-associated thiols more completely than higher concentrations of monovalent organomercurials, phenylmercuric acetate (PMA) and merthiolate (MT). Cells bound Hg(II) and PMA in excess of their available thiol ligands; X-ray absorption spectroscopy indicated nitrogens as likely additional ligands. The mercurials released protein-bound iron (Fe) more effectively than common organic oxidants and all disturbed the Na(+)/K(+) electrolyte balance, but none provoked efflux of six essential transition metals including Fe. PMA and MT made stable cysteine monothiol adducts in many Fe-binding proteins, but stable Hg(II) adducts were only seen in CysXxx(n)Cys peptides. We conclude that on acute exposure: (a) the distinct effects of mercurials on thiol and Fe homeostases reflected their different uptake and valences; (b) their similar effects on essential metal and electrolyte homeostases reflected the energy dependence of these processes; and (c) peptide phenylmercury-adducts were more stable or detectable in mass spectrometry than Hg(II)-adducts. These first in vivo observations in a well-defined model organism reveal differences upon acute exposure to inorganic and organic mercurials that may underlie their distinct toxicology.

[History of ignorance of methylmercury toxicity and intoxication in Japan in relation to Minamata disease].

The first reports of methylmercury intoxication appeared in 1865 and 1866. These reports had sensational effects in European countries, and were introduced not only in journals but also in newspapers. These two reports were referable in Japan at the latest in 1927. The formation of organic mercury in the production of acetoaldehyde was also referable in 1906 in Japan. In 1931 (one year before the start of acetoaldehyde production in Minamata) these important reports cited above were referable in Kumamoto University, and there were warnings about the toxicity of organic mercury and environmental pollution prior to the start of acetoaldehyde production. However, not only the plant, authorities (Ministry of Welfare), and Kumamoto Prefectural Office, but also the scientists completely ignored these reports. Waste was dumped into the environment without any treatment. Serious pollution of the environment by organic mercury started, which resulted in the outbreak of Minamata disease (=methylmercury intoxication).

Risks associated with the transfer of toxic organo-metallic mercury from soils into the terrestrial feed chain.

Although the transfer of organo-metallic mercury (OrgHg) in aquatic food webs has long been studied, it has only been recently recognized that there is also accumulation in terrestrial systems. There is still however little information about the exposure of grazing animals to OrgHg from soils and feed as well as on risks of exposure to animal and humans. In this study we collected 78 soil samples and 40 plant samples (Lolium perenne and Brassica juncea) from agricultural fields near a contaminated industrial area and evaluated the soil-to-plant transfer of Hg as well as subsequent trophic transfer. Inorganic Hg (IHg) concentrations ranged from 0.080 to 210mgkg(-1) d.w. in soils, from 0.010 to 84mgkg(-1) d.w. in roots and from 0.020 to 6.9mgkg(-1) d.w. in shoots. OrgHg concentrations in soils varied between 0.20 and 130µgkg(-1) d.w. representing on average 0.13% of the total Hg (THg). In root and shoot samples OrgHg comprised on average 0.58% (roots) and 0.66% (shoots) of THg. Average bioaccumulation factors (BAFs) for OrgHg in relation to soil concentrations were 3.3 (for roots) and 1.5 (for shoots). The daily intake (DI) of THg in 33 sampling sites exceeded the acceptable daily intake (ADI) of THg of both cows (ADI=1.4mgd(-1)) and sheep (ADI=0.28mgd(-1)), in view of food safety associated with THg in animal kidneys. Estimated DI of OrgHg for grazing animals were up to 220µgd(-1) (for cows) and up to 33µgd(-1) (for sheep). This study suggested that solely monitoring the levels of THg in soils and feed may not allow to adequately taking into account accumulation of OrgHg in feed crops and properly address risks associated with OrgHg exposure for animals and humans. Hence, the inclusion of limits for OrgHg in feed quality and food safety legislation is advised.

In vivo effects of traditional Ayurvedic formulations in Drosophila melanogaster model relate with therapeutic applications.

BACKGROUND: Ayurveda represents the traditional medicine system of India. Since mechanistic details of therapy in terms of current biology are not available in Ayurvedic literature, modern scientific studies are necessary to understand its major concepts and procedures. It is necessary to examine effects of the whole Ayurvedic formulations rather than their "active" components as is done in most current studies. METHODS: We tested two different categories of formulations, a Rasayana (Amalaki Rasayana or AR, an herbal derivative) and a Bhasma (Rasa-Sindoor or RS, an organo-metallic derivative of mercury), for effects on longevity, development, fecundity, stress-tolerance, and heterogeneous nuclear ribonucleoprotein (hnRNP) levels of Drosophila melanogaster using at least 200 larvae or flies for each assay. RESULTS: A 0.5% (weight/volume) supplement of AR or RS affected life-history and other physiological traits in distinct ways. While the size of salivary glands, hnRNP levels in larval tissues, and thermotolerance of larvae/adult flies improved significantly following feeding either of the two formulations, the median life span and starvation resistance improved only with AR. Feeding on AR or RS supplemented food improved fecundity differently. Feeding of larvae and adults with AR increased the fecundity while the same with RS had opposite effect. On the contrary, feeding larvae on normal food and adults on AR supplement had no effect on fecundity but a comparable regime of feeding on RS-supplemented food improved fecundity. RS feeding did not cause heavy metal toxicity. CONCLUSIONS: The present study with two Ayurvedic formulations reveals formulation-specific effects on several parameters of the fly's life, which seem to generally agree with their recommended human usages in Ayurvedic practices. Thus, Drosophila, with its very rich genetic tools and well-worked-out developmental pathways promises to be a very good model for examining the cellular and molecular bases of the effects of different Ayurvedic formulations.

Fish consumption and risk of contamination by mercury---considerations on the definition of edible parts based on the case study of European sea bass.

In the present study, the risk to humans by consuming European sea bass (Dicentrarchus labrax), captured at three sites along a Hg contamination gradient, was evaluated by comparing muscle and kidney total Hg (T-Hg) levels with the European regulations for marketed fish. Moreover, T-Hg and organic Hg (O-Hg) levels in muscle were compared with the Provisional Tolerable Weekly Intake (PTWI) and the Reference Dose (RfD). Although T-Hg levels in muscle were below the European value allowable for marketed fish, kidney's levels were higher than the set value, stressing the importance of redefining the concept of edible tissue and which tissues should be considered. Mercury weekly ingestion in the contaminated areas was higher than the PTWI, and O-Hg daily ingestion rates were higher than the RfD in all sampling sites. Thus, populations consuming sea bass from the contaminated sites may be at risk, with particular relevance for children and pregnant women.

[Bibliographical study of the toxicity of organic mercury compounds].

OBJECTIVES: The aim of this study is to correct the misunderstanding that the toxicity of organic mercury compounds is unknown at the time of the outbreak of Minamata disease (May 1, 1956). RESULTS AND DISCUSSION: Two case reports of organic mercury (methylmercury) intoxication were published already in 1865 and 1866. The conversion of inorganic mercury added in acetoaldehyde synthesis was already pointed out in 1921. In 1930 several cases of organic mercury poisoning among workers engaged in acetoaldehyde production were reported. Many reports on not only in occupational exposure but a oral exposure via the ingestion of flour made from grains treated with organic mercurials were available at the time of the outbreak of Minamata disease (May 1, 1956). These reports pointed out the toxic effects of organic mercury on the central nervous system, and indicated cleary that the causal substance of Minamata disease must be the organic mercury compounds (methylmercury) from the Chisso plant. The identification of methylmercury as the causal substance by the authority was presented in 1968 when acetoaldehyde production in the Chisso plant was closed. Most of these reports except that of (Hunter et al.) were not referred to in the study of Minamata disease . Inadequate referencing should be pointed out. CONCLUSION: Several reports indicated that the causal substance of Minamata disease must be methylmercury from the Chisso Plant. However, most of these reports were not referred to during the study of Minamata disease. Inadequate referencing of literatures should be pointed out.

Organic and total mercury levels in bigeye tuna, Thunnus obesus, harvested by Taiwanese fishing vessels in the Atlantic and Indian Oceans.

Muscle samples of 121 and 110 bigeye tuna (Thunnus obesus) caught by Taiwanese long-line fishing vessels in the Atlantic and Indian Oceans, respectively, were used to analyze total mercury (THg) and organic mercury (OHg) content. The overall THg and OHg concentrations were 0.786 ± 0.386 (0.214-3.133) and 0.595 ± 0.238 (0.143-2.222) mg kg⁻¹ wet weight, respectively, similar to the results of previous studies. Our findings, however, reflected the highest THg and OHg concentrations for the species in each ocean among the published data. Mean THg and OHg concentrations in Atlantic tuna were significantly (p < 0.05) higher than those in Indian tuna. Two of 121 samples of tuna from the Atlantic Ocean, but no samples from the Indian Ocean, had levels of OHg above 2 mg kg⁻¹ wet weight set by the Department of Health Taiwan, and 13 of 121 samples of tuna from the Atlantic Ocean and three of 110 samples from the Indian Ocean had levels of OHg above 1 mg kg⁻¹ wet weight set by US FDA and WHO. Accordingly, for adult Taiwanese men and women with average body weight of 65 and 55 kg, respectively, the maximum allowable weekly intake of bigeye tuna is suggested to be 170 and 145 g, respectively.

Scopoli's work in the field of mercurialism in light of today's knowledge: past and present perspectives.

The Idrija Mercury Mine (1490-1994) appointed its first physician, Joannes Antonius Scopoli, in 1754. Most of his descriptions of mercurialism are still relevant today. This study highlights Scopoli's observations on the interaction between elemental mercury (Hg degrees ) and alcohol, on the appearance of lung impairment, insomnia, and depressive mood in mercurialism. This presentation is based on Scopoli's experiences presented in his book, De Hydrargyro Idriensi Tentamina (1761), current knowledge, and our own experience acquired through health monitoring of occupational Hg degrees exposure. Some studies have confirmed Scopoli's observation that alcohol enhances mercurialism and his hypothesis that exposure to high Hg degrees concentrations causes serious lung impairment. Neurobiological studies have highlighted the influence of Hg degrees on sleep disorder and depressive mood observed by Scopoli. Although today's knowledge provides new perspectives of Scopoli's work on mercurialism, his work is still very important and can be considered a part of occupational medicine heritage.

Detoxification of mercury in the environment.

In this study, a "green chemistry" approach was developed as an option for remediation of toxic mercury in the environment. Twenty mercury compounds were treated with an environmentally friendly agent cyclodextrin to produce stable non-toxic mercury in soil and water. The binding efficiency was determined using high performance liquid chromatography with diode-array detection. The stability of the cyclodextrin mercury complexes toward environmental microorganisms in water was estimated under OECD guidelines using gas chromatography-mass spectrometry. The toxicity of the cyclodextrin mercury compounds to terrestrial organisms was investigated by use of internationally recognized toxicity methods using mercuric acetate as a model contaminant. Key process conditions, for example pH, temperature, and amount of detoxifying agent were investigated and found to have significant effects on the toxicity of mercury. It was found that organic and inorganic mercury pollutants could be mineralized in the environment with cyclodextrins. The bound mercury compounds resisted biodegradation and were found to be non-toxic to environmental microorganisms under laboratory conditions.

Inverse relationship between bioconcentration factor and exposure concentration for metals: implications for hazard assessment of metals in the aquatic environment.

The bioconcentration factor (BCF) and bioaccumulation factor (BAF) are used as the criteria for bioaccumulation in the context of identifying and classifying substances that are hazardous to the aquatic environment. The BCF/BAF criteria, while developed as surrogates for chronic toxicity and/or biomagnification of anthropogenic organic substances, are applied to all substances including metals. This work examines the theoretical and experimental basis for the use of BCF/BAF in the hazard assessment of Zn, Cd, Cu, Pb, Ni, and Ag. As well, BCF/BAFs for Hg (methyl and inorganic forms) and hexachlorobenzene (HCB) were evaluated. The BCF/BAF data for Zn, Cd, Cu, Pb, Ni, and Ag were characterized by extreme variability in mean BCF/BAF values and a clear inverse relationship between BCF/BAF and aqueous exposure. The high variability persisted when even when data were limited to an exposure range where chronic toxicity would be expected. Mean BCF/BAF values for Hg were also variable, but the inverse relationship was equivocal, in contrast with HCB, which conformed to the BCF model. This study illustrates that the BCF/BAF criteria, as currently applied, are inappropriate for the hazard identification and classification of metals. Furthermore, using BCF and BAF data leads to conclusions that are inconsistent with the toxicological data, as values are highest (indicating hazard) at low exposure concentrations and are lowest (indicating no hazard) at high exposure concentrations, where impacts are likely. Bioconcentration and bioaccumulation factors do not distinguish between essential mineral nutrient, normal background metal bioaccumulation, the adaptive capabilities of animals to vary uptake and elimination within the spectrum of exposure regimes, nor the specific ability to sequester, detoxify, and store internalized metal from metal uptake that results in adverse effect. An alternative to BCF, the accumulation factor (ACF), for metals was assessed and, while providing an improvement, it did not provide a complete solution. A bioaccumulation criterion for the hazard identification of metals is required, and work directed at linking chronic toxicity and bioaccumulation may provide some solutions.

Organic mercury compounds: human exposure and its relevance to public health.

Humans may be exposed to organic forms of mercury by either inhalation, oral, or dermal routes, and the effects of such exposure depend upon both the type of mercury to which exposed and the magnitude of the exposure. In general, the effects of exposure to organic mercury are primarily neurologic, while a host of other organ systems may also be involved, including gastrointestinal, respiratory, hepatic, immune, dermal, and renal. While the primary source of exposure to organic mercury for most populations is the consumption of methylmercury-contaminated fish and shellfish, there are a number of other organomercurials to which humans might be exposed. The antibacterial and antifungal properties of organomercurials have resulted in their long use as topical disinfectants (thimerosal and merbromin) and preservatives in medical preparations (thimerosal) and grain products (both methyl and ethyl mercurials). Phenylmercury has been used in the past in paints, and dialkyl mercurials are still used in some industrial processes and in the calibration of certain analytical laboratory equipment. The effects of exposure to different organic mercurials by different routes of exposure are summarized in this article.