International Symposium on Selenium–Mercury Interactions Session Summary from the SETAC North America 2010 Annual Meeting
Laura Raymond (Energy and Environmental Research Center)
Selenium (Se) is an essential trace element that is required by enzymes (selenoenzymes) that protect brain tissues from oxidative damage. Methylmercury (MeHg) covalently binds to the Se present at the active sites of these enzymes and is, by biochemical definition, a highly specific, irreversible selenoenzyme inhibitor. When insufficient dietary Se is available to replace Se lost to binding with Hg, increased oxidative damage is expected to occur. This expectation is consistent with the adverse effects of high maternal MeHg exposures observed among children whose mothers were exposed to MeHg from shark and pilot whale meats that contained many times more MeHg than Se. However, when maternal dietary Se intakes have been in molar excess of MeHg, no harmful consequences have been observed. Increasing dietary Se intakes throughout the nutritionally relevant range of concentrations normally encountered in foods is increasingly protective against MeHg toxicity. Selenium has been recognized as an effective means of counteracting Hg toxicity since 1967, but its role in the Hg issue has been largely overlooked and widely misunderstood. Human and animal studies confirm that exposures to MeHg in molar excess of Se is harmful; however, the most recent, largest, and most thorough human studies indicate that when Se is more abundant than MeHg, the beneficial effects of improved Se, omega-3, and vitamin D nutritional status results in substantial benefits to children. Instead of causing adverse effects, maternal consumption of typical varieties of ocean fish has resulted in developmental benefits in these children.
Since ocean fish are among the richest sources of dietary Se, it is important to consider their Se contents when performing MeHg risk assessments and establishing seafood safety criteria. Use of parameters that integrate Hg:Se molar relationships also make it easy to understand the distinctions between the findings of maternal MeHg exposure studies that have been performed. Development of criteria for evaluating Hg:Se interactions will enhance environmental protection and improve public safety. Ignoring the importance of Se may also result in misunderstanding and substantial underestimation of risks associated with MeHg exposure from freshwater fish. Freshwater fish in North American lakes are expected to have sufficient Se to prevent adverse effects from MeHg exposures in most cases, but exceptions may be more hazardous than is currently recognized. Restoring Se levels to adequate levels in low-Se lakes can diminish MeHg bioaccumulation and toxicity associated with the fish. Therefore, MeHg risk assessment needs to consider dietary Se and Hg:Se molar ratios present in fish to accurately assess both the risks and benefits of maternal fish consumption by humans and wildlife. Regulatory policies that ignore the role of Se in the Hg issue fail to protect and may cause harm to children. Therefore, improved public health policies require clear understanding of Hg–Se interactions.
The platform presentations and posters focused on the importance of measuring Hg and Se molar ratios when considering MeHg exposure risks. Group discussions in the session highlighted the fact that Se’s binding affinity with Hg results in the formation of an inert HgSe complex that plays a crucial role in mitigating MeHg toxicity. This inert complex formation is proposed to result in the phenomenon of a selenoenzyme deficiency due to Se’s unavailability to participate in selenocysteine synthesis, a crucial selenoenzyme required for neurodevelopment and other important physiological functions.
Dr. Phil Whanger, professor emeritus from Oregon State University, gave an informative summary of the history of Se research leading to the discovery of Se’s protective effects against MeHg toxicity. He further discussed two postulations for Se’s effect of decreased MeHg toxicity: one being the formation of the inert HgSe complex that is not biochemically available and the other possibility of Se causing a diversion from MeHg binding of low molecular tissue proteins to larger molecular weight proteins that are not critically involved in metabolism. Likewise, Dr. Chiho Watanabe, University of Tokyo, gave an overview illustrating the importance of consideration for the chemical forms of Se regarding the Hg–Se interactions and suggested that the influence of MeHg on selenoprotein functions is just one of the possible pathways through which these elements can interact. He further emphasized that Se should be regarded as an item in the list of the many nutrients that may have relevance to MeHg toxicity and that the importance of Se may be influenced by regional and population variability.
Evidence was also presented illustrating the misunderstanding of MeHg consumption advisories, leading to unintended harm during fetal development resulting from limiting fish consumption during pregnancy. Since MeHg advisories and reference dose levels were determined from MeHg assessments alone, the advisories negate consideration for the beneficial nutrients also present in fish. Therefore the importance of refined advisories and risk assessments are needed. The Selenium Health Benefit Value (Se-HBV) criterion was presented as a method to assess dose-effect relationships between MeHg exposures and Se intakes through fish consumption. Fish with negative Se-HBVs predict relative risks while positive values predict benefits of seafood consumption. Predictions based on dietary Se-HBVs coincide with observed effects noted in epidemiological studies and MeHg poisoning incidents. Therefore, in the context of risk assessment, Hg:Se molar ratios need to be considered when determining toxicity risk in order to ensure the benefits of fish consumption can be obtained while minimizing MeHg risks.
Highlights from Specific Studies Presented:
- Fish tissue analysis from samples taken at sites influenced by fly ash exposure from power plants provided indirect evidence that elevated Se in tissues of aquatic biota antagonistically regulate the bioaccumulation of MeHg. A significant inverse relationship between whole body MeHg and Se concentration was observed. Among each species analyzed, the ratios of molar Se to molar Hg concentrations were consistently higher at high-exposure sites.
- Fish tissue samples from 50 Idaho lakes and 45 northeastern U.S. lakes were assessed to compare MeHg concentration risk criteria with molar ratio risk measurements. The mean filet fish tissue MeHg concentrations exceeded the human consumption criterion of 0.3 ug/g in 25% of the Idaho lakes and 47% of the northeastern U.S. lakes. However, fish tissue Se:Hg molar ratios for all fish were <1:1 in only 17% of the Idaho lakes and 25% of the northeastern U.S. lakes. Among fish species common to both western and northeastern lakes, bass presented the greatest potential MeHg toxicity risk to consumers based on their higher MeHg content and reduced Se:Hg molar ratios. In Idaho lakes that contained bass, their filets had a Se:Hg molar ratio <1:1 in 36% of the lakes. In northeastern U.S. lakes that contained bass, the fish filets had a Se:Hg molar ratio <1:1 in 14% of the lakes.
- Further fish analysis was performed on 468 fish from 137 sites in 11 states. The mean Hg concentrations in all piscivore fish groups exceeded 0.1 µg Hg/g, however 97.5% of the fish had Se:Hg molar ratios >1. Despite 33% of piscivorous stream fish exceeding the human health Hg protective criterion, approximately 94% of them had Se:Hg molar ratios >1.
- Analysis of three neuroendocrine tissues (brain, pituitary, and thyroid) and six somatic tissues (liver, kidney, heart, skeletal muscle, blubber, and skin) were performed from 11 beluga whales. The Se and Hg present in these tissues were analyzed, and their molar concentrations and chemical structures were compared. Other than skeletal muscle, Se occurred in excess of Hg in all tissues studied. Analysis at the Stanford synchrotron indicated the bulk of Hg present in pituitary and liver was present as HgSe (the other tissues were not assessed).
- Dietary Se intakes at levels that reflect the nutritionally relevant ranges were shown to protect against MeHg toxicity in rats. Hair and blood Hg levels were shown to accurately reflect MeHg exposure but not toxicity risk. MeHg toxicity was only apparent with Se-deficient diets. However, the increased molar excess of Hg:Se indicated toxicity. The study further indicated that reinstating dietary Se could avert the declining symptoms of MeHg toxicity irrespective of MeHg remaining present in the diet.
- Plants that are known to hyperaccumulate Se were evaluated to assess their potential to accentuate Hg uptake. Preliminary studies indicated that Hg uptake by terrestrial plants was accentuated when the soil was enriched with Se. High uptake of Hg and Se occurred in the assessed plant species, suggesting the potential for HgSe formation in plant tissues.
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