Accumulation properties of inorganic mercury and organic mercury in the red-crowned crane Grus japonensis in east Hokkaido, Japan.

The red-crowned (Japanese) crane Grus japonensis is native to east Hokkaido, Japan, in contrast to the East Asia mainland. Previously, we reported that red-crowned cranes in Hokkaido were highly contaminated with mercury in the 1990s and that the contamination rapidly decreased to a moderate level in the 2000s. In the present study, we determined levels of organic mercury (O-Hg) in the liver and kidney of cranes in east Hokkaido in comparison with levels of total mercury (T-Hg). T-Hg levels in the kidneys were higher than those in the livers in adults but not in subadults and juveniles; however, the reverse was the case for O-Hg even for adults. The ratio of O-Hg to T-Hg in both the liver and kidney decreased as T-Hg increased in the three developmental stages. While the ratios of O-Hg to T-Hg in the liver and kidney of adults were significantly lower than those of juveniles, the ratios were similar for adults and juveniles in a lower range of T-Hg. The ratio of selenium (Se) to T-Hg decreased as T-Hg increased in both the liver and kidney, irrespective of stages. Mercury burdens in feathers were about 59% and 67% of the total body burdens for juveniles and adults, respectively. Furthermore, ratios of carbon and nitrogen stable isotopes to T-Hg varied greatly, with no relation to mercury level in the liver. The results suggest slow accumulation of inorganic mercury in the kidney of red-crowned cranes in east Hokkaido, Japan.

Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level.

Using synchrotron x-ray fluorescence mapping, we have examined the uptake and localization of organic mercury in zebrafish larvae. Strikingly, the greatest accumulation of methyl and ethyl mercury compounds was highly localized in the rapidly dividing lens epithelium, with lower levels going to brain, optic nerve, and various other organs. The data suggest that the reported impairment of visual processes by mercury may arise not only from previously reported neurological effects, but also from direct effects on the ocular tissue. This novel approach is a powerful tool for directly investigating the molecular toxicology of heavy metals, and should be equally applicable to the study of a wide range of elements in developing embryos.

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

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

Hepatobiliary transport of the anionic organomercury compound (mersalyl) is carrier mediated.

The hepatobiliary excretion of the anionic organic mercury compound (mersalyl) was studied in the isolated perfused rat liver and in isolated rat liver plasma membrane vesicles. In the isolated perfused liver, mersalyl is immediately taken up from the perfusion medium and concentratively excreted into bile. Uptake is characterized by saturation kinetics (S)0.5 = 20 microM, Vmax = 117 nmoles/min/g liver, cooperatively of mersalyl binding sites, stimulation by extracellular sodium and temperature dependence. Uptake of mersalyl into basolateral membrane vesicles also exhibits characteristics of a carrier mediated transport: saturation kinetics (S)0.5 = 28 microM, Vmax = 1.6 nmoles/min/mg protein, dependence on extravesicular sodium, cooperativity of mersalyl binding sites, temperature dependence and transstimulation by intravesicular non-radioactive mersalyl. Uptake was inhibited by alpha-naphthylacetic acid and mercapto group reagents, indicating involvement of mercapto groups on the carrier and a binding site for carboxylic anions. Data from the isolated perfused liver and from isolated basolateral vesicles indicate that mersalyl uptake into the liver is carrier mediated. Uptake mechanism and driving forces appear analogous to those for the uptake of chemically related compounds such as taurocholic acid. Therefore it is speculated that mersalyl may be transported by carrier molecules which apparently accept numerous chemically unrelated compounds.

Neurotoxicity of organomercurial compounds.

Mercury is a ubiquitous contaminant, and a range of chemical species is generated by human activity and natural environmental change. Elemental mercury and its inorganic and organic compounds have different toxic properties, but all them are considered hazardous in human exposure. In an equimolecular exposure basis, organomercurials with a short aliphatic chain are the most harmful compounds and they may cause irreversible damage to the nervous system. Methylmercury (CH(3)Hg(+)) is the most studied following the neurotoxic outbreaks identified as Minamata disease and the Iraq poisoning. The first description of the CNS pathology dates from 1954. Since then, the clinical neurology, the neuropathology and the mechanisms of neurotoxicity of organomercurials have been widely studied. The high thiol reactivity of CH(3)Hg(+), as well as all mercury compounds, has been suggested to be the basis of their harmful biological effects. However, there is clear selectivity of CH(3)Hg(+) for specific cell types and brain structures, which is not yet fully understood. The main mechanisms involved are inhibition of protein synthesis, microtubule disruption, increase of intracellular Ca(2+) with disturbance of neurotransmitter function, oxidative stress and triggering of excitotoxicity mechanisms. The effects are more damaging during CNS development, leading to alterations of the structure and functionality of the nervous system. The major source of CH(3)Hg(+) exposure is the consumption of fish and, therefore, its intake is practically unavoidable. The present concern is on the study of the effects of low level exposure to CH(3)Hg(+) on human neurodevelopment, with a view to establishing a safe daily intake. Recommendations are 0.4 micro g/kg body weight/day by the WHO and US FDA and, recently, 0.1 micro g/kg body weight/day by the US EPA. Unfortunately, these levels are easily attained with few meals of fish per week, depending on the source of the fish and its position in the food chain.

In vitro cyto- and genotoxicity of organomercurials to cells in culture.

The sequence of cytotoxic effects for a series of mercury compounds to the BG/F epithelioid cells derived from fin tissue of bluegill sunfish was phenyl mercuric chloride greater than methyl mercuric chloride greater than ethyl mercuric chloride much greater than mercuric chloride. This sequence of in vitro cytotoxicity was similar to that observed in a 48-h LC50 in vivo acute toxicity assay with rainbow trout. Using induction of micronuclei as an indicator of genetic damage, the organomercurials, but not mercuric chloride, were noted to be clastogenic to the BG/F cells.

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.

Mercury as a potential hazard for the dental practitioner.

Mercury has been used for centuries for medical, chemical, metallurgical and electrical applications. It is an element of mystery, which in its metallic form is an enticing silvery liquid that can be as fascinating as it is dangerous. Its use in dental amalgam has a potential for continuous occupational exposure of dental practitioners to mercury vapor. It is imperative that the dental practitioner understands the hazards associated with the use of mercury, and controls exposures to prevent the development of any untoward effects. This article provides an overview of the toxicology of the different forms of mercury to which human exposure occurs and addresses safety issues associated with mercury vapor, the primary form of mercury encountered in the practice of dentistry.

Organomercurial removal from vaccine production wastewaters in a supported liquid membrane bioreactor.

Vaccine production effluents are strongly polluted with thiomersal, a highly toxic organomercurial compound, for which there is presently no remediation technology available. This work describes a new remediation process based on the extraction of thiomersal from the wastewater to a biological compartment, where it is degraded by a microbial strain. The selective extraction of thiomersal is achieved by using an ionic liquid immobilized in a porous membrane. In the biological compartment, thiomersal is degraded to metallic mercury, under aerobic conditions, by a Pseudomonas putida strain. The utilization of ionic liquids in supported liquid membranes for thiomersal transport, and the kinetics of thiomersal biodegradation by a Pseudomonas putida strain are presented and discussed.

Factors involved in absorption of organic mercuric compounds from rat small intestine: comparative study with mercuric chloride in situ.

A correlation between absorption of organic mercuric compounds and their molecular weight or lipophilicity was investigated by the perfusion of rat small intestine. The intestine was perfused for 1.0 hr at different osmolarity and different pH with buffers containing 10(-4) M organic mercuric compounds, methyl mercuric chloride (MMC), phenyl mercuric chloride (PMC), p-chloromercuribenzoic acid (PCMB) and p-chloromercuriphenylsulfonic acid (PCMBS). The order of absorption of these compounds at several osmolarities and pHs (MMC greater than PMC greater than PCMB greater than PCMBS) was inversely correlated to their molecular weight. The increase in pH decreased markedly the absorption and n-octanol/water partition coefficient of PCMB, and it decreased scarcely those of MMC, PMC and PCMBS. The order of the coefficients at each pH was as follows; PMC greater than MMC greater than PCMB greater than PCMBS, in disagreement with the order of absorption. These results suggest that the molecular weight is more important factor in the intestinal absorption of organic mercuric compounds than the lipophilicity.

Toxicity and transport of three synthesized mercury-thiol-complexes in isolated rabbit renal proximal tubule suspensions.

Previous work has suggested that endogenous sulfhydryls, such as glutathione (GSH) and cysteine, are involved in the uptake and toxicity of HgCl2. To study this possibility, uptake and toxicity of synthesized Hg(SG)2, Hg(cysteinylglycine)2 [Hg(CYS-GLY)2] and Hg(CYS)2 were investigated in rabbit renal proximal tubule suspensions (RPT). The intracellular K+ was used as a toxicity indicator, and the mercury content in the tubules was measured by proton induced x-ray emission analysis. The toxicity rank order of the three synthesized mercury-thiol-complexes from the highest to the lowest was: Hg(CYS)2 > Hg(CYS-GLY)2 > Hg(SG)2. However, no significant difference among the mercury contents in the tubules exposed to these synthesized mercury-thiol-complexes was detected. Acivicin (0.25 mM), an inhibitor of gamma-glutamyltranspeptidase (GGT), decreased the toxicity of Hg(SG)2 in a manner that did not decrease the uptake of mercury in the tubules. This suggests that the toxicity of Hg(SG)2 requires processing to Hg(CYS-GLY)2 or Hg(CYS)2, while Hg(SG)2 may be taken up by the tubules via Na(+)-dependent GSH transporter since 10 mM acivicin, an inhibitor of this transporter dramatically decreased the uptake of Hg(SG)2. Organic anion transporter plays a minor role, if any, in the toxicity and uptake of Hg(SG)2 and Hg(CYS)2 since p-aminohippuric acid (PAH), an inhibitor of organic anion transporter, did not have significant effect on their uptake and toxicity. L-phenylalanine, an inhibitor of the neutral amino acid decreased the uptake of mercury, but to a lesser extent. This suggested that neutral amino acid transporter seemed to play a role, in part, in the toxicity and uptake of synthesized Hg(CYS)2. In summary, the data suggested that basolateral transport is important for the toxicity of the three synthesized mercury-thiol-complexes, and a variety of mechanisms are involved in the toxicity and uptake of these complexes in isolated rabbit RPT.

Human organic anion transporter 1 mediates cellular uptake of cysteine-S conjugates of inorganic mercury.

BACKGROUND: The epithelial cells lining the renal proximal tubule have been shown to be the primary cellular targets where mercuric ions gain entry, accumulate, and induce pathologic effects in vivo. Recent data have implicated at least one of the organic anion transport systems in the basolateral uptake of inorganic mercury (Hg(2+)). METHODS: Using a line of Madin-Darby canine kidney (MDCK) II cells transfected stably with the human organic anion transporter 1 (hOAT1), and oocytes from Xenopus laevis microinjected with cRNA for hOAT1, we tested the hypothesis that hOAT1 can transport biologically relevant mercuric conjugates of cysteine (Cys). RESULTS: Indeed, MDCK II cells expressing a functional form of hOAT1 gained the ability to transport the mercuric conjugate 2-Amino-3-(2-amino-2-carboxy-ethylsulfanyl-mercuricsulfanyl)-propionic acid (Cys-S-Hg-S-Cys), but not the corresponding di-glutathione S-conjugate of Hg(2+) (G-S-Hg-S-G). Moreover, p-aminohippurate (PAH), adipate, and glutarate (but not succinate or malonate) inhibited individually the uptake of Cys-S-Hg-S-Cys in a dose-dependent manner. Uptake of Cys-S-Hg-S-Cys, but not G-S-Hg-S-G, was also documented in Xenopus oocytes expressing hOAT1. CONCLUSION: These data represent ostensibly the most direct line of evidence implicating a specific membrane protein (i.e., hOAT1) in the transport of a biologically relevant molecular species of Hg(2+) in a mammalian cell. Moreover, these data indicate that the organic anion transporter(s) likely play a prominent role in the basolateral transport of mercuric ions by proximal tubular cells and in the nephropathy induced by Hg(2+).