Selenosis in Ruminants.

Selenium (Se) is a metalloid that exists as a red amorphous powder, reddish crystal, silver-gray crystal, or brown-black solid. Its potency as a nutrient and a toxicant is such that few people have seen the pure element. It is easy to lose sight of the narrow margin between too little and too much. The most common cause of selenosis is accidental or intentional overuse of supplements. Many target organs and effects of Se toxicity are similar to those of Se deficiency, so laboratory confirmation is necessary. Prevention consists of minimizing exposure to seleniferous feedstuffs and optimizing dietary factors that might aggravate selenosis.

Chemical Speciation of Selenium and Mercury as Determinant of Their Neurotoxicity.

The antagonism of mercury toxicity by selenium has been well documented. Mercury is a toxic metal, widespread in the environment. The main target organs (kidneys, lungs, or brain) of mercury vary depending on its chemical forms (inorganic or organic). Selenium is a semimetal essential to mammalian life as part of the amino acid selenocysteine, which is required to the synthesis of the selenoproteins. This chapter has the aim of disclosing the role of selenide or hydrogen selenide (Se-2 or HSe-) as central metabolite of selenium and as an important antidote of the electrophilic mercury forms (particularly, Hg2+ and MeHg). Emphasis will be centered on the neurotoxicity of electrophile forms of mercury and selenium. The controversial participation of electrophile mercury and selenium forms in the development of some neurodegenerative disease will be briefly presented. The potential pharmacological use of organoseleno compounds (Ebselen and diphenyl diselenide) in the treatment of mercury poisoning will be considered. The central role of thiol (-SH) and selenol (-SeH) groups as the generic targets of electrophile mercury forms and the need of new in silico tools to guide the future biological researches will be commented.

Evaluation of the Content of Antimony, Arsenic, Bismuth, Selenium, Tellurium and Their Inorganic Forms in Commercially Baby Foods.

Baby foods, from the Spanish market and prepared from meat, fish, vegetables, cereals, legumes, and fruits, were analyzed to obtain the concentration of antimony (Sb), arsenic (As), bismuth (Bi), and tellurium (Te) as toxic elements and selenium (Se) as essential element. An analytical procedure was employed based on atomic fluorescence spectroscopy which allowed to obtain accurate data at low levels of concentration. Values of 14 commercial samples, expressed in nanograms per gram fresh weight, ranged for Sb 0.66-6.9, As 4.5-242, Te 1.35-2.94, Bi 2.18-4.79, and Se 5.4-109. Additionally, speciation studies were performed based on data from a non-chromatographic screening method. It was concluded that tellurium and bismuth were mainly present as inorganic forms and selenium as organic form, and antimony and arsenic species depend on the ingredients of each baby food. Risk assessment considerations were made by comparing dietary intake of the aforementioned elements through the consumption of one baby food portion a day and recommended or tolerable guideline values.

Modulation of urinary siderophores by the diet, gut microbiota and inflammation in mice.

Mammalian siderophores are believed to play a critical role in maintaining iron homeostasis. However, the properties and functions of mammalian siderophores have not been fully clarified. In this study, we have employed Chrome Azurol S (CAS) assay which is a well-established method for bacterial siderophores study, to detect and quantify mammalian siderophores in urine samples. Our study demonstrates that siderophores in urine can be altered by diet, gut microbiota and inflammation. C57BL/6 mice, fed on plant-based chow diets which contain numerous phytochemicals, have more siderophores in the urine compared to those fed on purified diets. Urinary siderophores were up-regulated in iron overload conditions, but not altered by other tested nutrients status. Further, germ-free mice displayed 50% reduced urinary siderophores, in comparison to conventional mice, indicating microbiota biotransformation is critical in generating or stimulating host metabolism to create more siderophores. Altered urinary siderophores levels during inflammation suggest that host health conditions influence systemic siderophores level. This is the first report to measure urinary siderophores as a whole, describing how siderophores levels are modulated under different physiological conditions. We believe that our study opens up a new field in mammalian siderophores research and the technique we used in a novel manner has the potential to be applied to clinical purpose.

Selenium Health Benefit Values: Updated Criteria for Mercury Risk Assessments.

Selenium (Se)-dependent enzymes (selenoenzymes) protect brain tissues against oxidative damage and perform other vital functions, but their synthesis requires a steady supply of Se. High methylmercury (CH3Hg) exposures can severely diminish Se transport across the placenta and irreversibly inhibit fetal brain selenoenzymes. However, supplemental dietary Se preserves their activities and thus prevents pathological consequences. The modified Se health benefit value (HBVSe) is a risk assessment criterion based on the molar concentrations of CH3Hg and Se present in a fish or seafood. It was developed to reflect the contrasting effects of maternal CH3Hg and Se intakes on fetal brain selenoenzyme activities. However, the original equation was prone to divide-by-zero-type errors whereby the calculated values increased exponentially in samples with low CH3Hg contents. The equation was refined to provide an improved index to better reflect the risks of CH3Hg exposures and the benefits provided by dietary Se. The HBVSe provides a biochemically based perspective that confirms and supports the FDA/EPA advice for pregnant and breast-feeding women regarding seafoods that should be avoided vs. those that are beneficial to consume. Since Se can be highly variable between watersheds, further evaluation of freshwater fish is needed to identify locations where fish with negative HBVSe may arise and be consumed by vulnerable subpopulation groups.

Methods of Selenium Supplementation: Bioavailability and Determination of Selenium Compounds.

Selenium, a "dual-surface" element, maintains a very thin line between a level of necessity and harmfulness. Because of this, a deficiency or excess of this element in an organism is dangerous and causes health-related problems, both physically and mentally. The main source of selenium is a balanced diet, with a proper selection of meat and plant products. Meanwhile, the proper assimilation of selenium into these products depends on their bioavailability, bioaccessibility, and/or bioactivity of a given selenium compound. From the time when it was discovered that selenium and its compounds have a significant influence on metabolic processes and in many countries throughout the world, a low quantity of selenium was found in different parts of the environment, pressure was put upon an effective and fast method of supplementing the environment with the help of selenium. This work describes supplementation methods applied with the use of selenium, as well as new ideas for increasing the level of this element in various organisms. Based on the fact that selenium appears in the environment at trace levels, the determination of total amount of selenium or selenium speciation in a given sample demands the selection of appropriate measurement methods. These methods are most often comprised of a sample preparation technique and/or a separation technique as well as a detection system. The work presents information on the subject of analytical methods used for determining selenium and its compounds as well as examples in literature of their application.

Teratogenic effects and monetary cost of selenium poisoning of fish in Lake Sutton, North Carolina.

Selenium pollution from coal ash wastewater was investigated in Lake Sutton, NC. This lake has been continuously used as a cooling pond for a coal-fired power plant since 1972. Historic and recent levels of contamination in fish tissues (14-105µg Se/g dry weight in liver, 24-127 in eggs, 4-23 in muscle, 7-38 in whole-body) exceeded toxic thresholds and teratogenic effects were observed in fish collected in 2013. A high proportion (28.9 percent) of juvenile Lepomis spp. exhibited spinal and craniofacial malformations that were consistent with selenium poisoning. Teratogenic Deformity Index values indicated population-level impacts on the fishery. The partially monetized cost of resultant fishery losses was calculated at over $US 8.6 million annually, and over $US 217 million for the entire period of damage, which dates back to 1987 when chemical and biological monitoring began.

Selenium toxicity from a misformulated dietary supplement, adverse health effects, and the temporal response in the nail biologic monitor.

Use of dietary supplements in the U.S. has increased steadily over the last 25 years. While misformulation is uncommon, the consequences can be serious. A March 2008 voluntary market recall removed supplement products responsible for the most serious selenium toxicity outbreak that has occurred in the U.S. We quantified selenium concentrations in the misformulated supplement products, measured the temporal response in the nail biologic monitor, and associated exposure to self-reported selenosis symptoms. Subjects recruited through state health departments and referrals provided samples of the misformulated supplement products, exposure information, monthly toenail and or fingernail clippings or onycholysitic nail fragments, and listed their newly onset adverse health effects attributed to selenium toxicity. Ninety-seven subjects enrolled and submitted at least one test sample. Peak selenium concentrations (up to 18.3 and 44.1 µg/g for toenails and fingernails, respectively) were measured. Multiple samples (52 total) of all six recalled supplement lots were analyzed ranging from 22,300 to 32,200 µg selenium per daily dose. Average consumption was 30.9 ± 13.9 doses; 73 subjects provided follow-up data on selenosis symptoms at 2.50 ± 0.14 years. Nail samples accurately reflect exposure in this selenium toxicity outbreak, which resulted in long-term/permanent adverse health effects.

The bioavailability of selenium and risk assessment for human selenium poisoning in high-Se areas, China.

Enshi prefecture of Hubei Province is well known for human selenium (Se) poisoning in the early 1960s in China. Sporadic cases of Se poisoning in livestocks are still being found. In this study, Se levels in water, cropland soils and various crops from high-Se areas of Enshi were measured to investigate the distribution and bioavailability of Se in the environments, as well as probable daily intake (PDI) of Se for local residents. The total Se in surface water ranged from 2.0 to 519.3µg/L with a geometric mean of 46.0±127.8 µg/L (n=48), 70.5-99.5% of which was present in the form of Se(VI). The soil Se concentration varied from 2.89 to 87.3 µg/g with a geometric mean of 9.36±18.6 µg/g (n=45), and most of Se was associated with organic matter (OM-Se). The total Se in rice, corn, and vegetable samples were 2.11±2.87 µg/g (n=21), 3.76±11.6 µg/g (n=16), and 2.09±3.38 µg/g (n=25), respectively. Stream water Se is likely leached from carbonaceous shale and mine wastes, leading to Se accumulation in paddy soils. OM-Se may play an important role in Se uptake by rice plant in high-Se area of Enshi. The PDI of Se is approximately 2144 µg/day, and Se concentration in blood is estimated at about 3248 µg/L, posing a potential chronic Se poisoning risk to local residents. Cereal consumption (48.5%) makes a great contribution to human daily Se intake, followed by vegetables (36.6%), meats (8.5%), and drinking water (6.4%). However, when assessing health risk on human in high-Se areas, the contribution of drinking water to daily Se intake cannot be ignored due to high Se content and dominant Se(VI) species. Local inhabitants should be advised not to grow crops in high-Se lands or irrigate using high-Se water. If possible, they should drink pipe water and consume foods mixed with those from outside the high-Se areas.

[Re-evaluation of the fundamentals of trace elements].

The roles of trace elements have been extensively studied for decades. However, recent advances in both molecular and epidemiological studies on trace elements have provided new information and concepts on the actions of trace elements. Some of our fundamental knowledge on the roles of trace elements based on classical data should be replaced by new concept based on new findings. This series of "Re-evaluation of the Fundamentals of Trace Elements" aims to provide new fundamentals on trace elements by reviewing rapidly advancing knowledge in this study area. The first article is a critical review on the role of chromium in human nutrition.

T-2 toxin contamination in grains and selenium concentration in drinking water and grains in Kaschin-Beck disease endemic areas of Qinghai Province.

It has been strongly suggested that two factors are involved in the development of Kaschin-Beck Disease (KBD), namely grains contamination with T-2 toxin and selenium deficiency. So our team undertook a survey about grains and drinking water in three rural KBD endemic villages and one non-KBD village in Qinghai Province. The level of T-2 toxin contamination in 364 grain samples was assayed using an ELISA kit. The selenium concentration in these grains and 15 drinking water samples from three KBD endemic villages were determined using the 2,3-diaminonaphthalene fluorometric assay. The results revealed that the level of T-2 toxin contamination in the samples from three KBD endemic villages was relatively high with an average level of 78.91 ng/g in wheat and 47.47 ng/g in flour. The T-2 toxin level in samples from the non-KBD village (12.23 ng/g) was significantly lower than that of local grains from the three KBD endemic villages. The average selenium content in wheat and flour from KBD areas was 0.0045 and 0.0067 µg/g, respectively. The selenium concentration in local grain samples was significantly lower than that in samples from the non-KBD village (0.0604 µg/g). In addition, the selenium concentration in drinking water from three KBD endemic villages was also low (0.156 µg/L). These results support a potential role of T-2 toxin contamination and selenium deficiency in KBD. Compared with non-KBD endemic areas, health hazards in grains and in the environment of KBD endemic areas were observed.

Toxicokinetics and pathology of plant-associated acute selenium toxicosis in steers.

Sixteen of approximately 500 yearling steers died of acute selenium (Se) toxicosis after grazing on a Se-contaminated range for only a few days. Field studies and chemical analyses identified the predominant toxic plant as western aster (Symphyotrichum ascendens, previously Aster ascendens), which contained over 4,000 ppm Se (dry weight). Several dead animals that were necropsied had acute severe myocardial necrosis characterized by edema and myocyte swelling, with hypereosinophilia, clumping, and coagulation of myocardial proteins. Whole blood from 36 surviving steers was collected and analyzed, and 10 steers with elevated Se concentrations were selected for close monitoring and clinical evaluations. Each steer was weighed, and serum, blood, liver, skeletal muscle, and hair were regularly collected after removal from the Se-contaminated range. One animal that died 18 days after exposure was necropsied and exhibited severe multifocal myocardial fibrosis with extensive hepatic congestion, degeneration, and hemosiderosis. At 180 days postexposure, 2 of the 10 steers were euthanized, and tissue samples were collected. Both steers had rare, small fibrotic foci in their hearts. The Se elimination half-lives from serum, whole blood, liver, and muscle of the recovering steers were 40.5 ± 8.2, 115.6 ± 25.1, 38.2 ± 5.0, and 98.5 ± 19.1 days, respectively. The Se concentration in hair reached a peak of 11.5 ± 5.3 ppm at 22 days postexposure. The findings indicate that cattle are sensitive to acute Se toxicosis caused by ingestion of Se-accumulator plants, with myocardial necrosis as the primary lesion. Some poisoned animals may develop congestive heart failure weeks after the toxic exposure, and in the current study, Se was slowly excreted requiring a relatively long withdrawal time.

Case series of selenium toxicity from a nutritional supplement.

INTRODUCTION: Selenium is an essential trace element, but can be toxic in excess. In May 2008, US FDA reported 201 individuals with adverse reactions to liquid nutritional supplements containing excess selenium and chromium resulting in the largest epidemic of selenosis in the history of the United States. OBJECTIVE: To describe the clinical features, biomonitoring data of selenium levels, and the estimated total dose of selenium ingestions of nine patients with selenium toxicity who presented after use of a liquid dietary supplement with a formulation error. METHODS: A retrospective observational case series was performed on nine patients presenting to our medical toxicology clinic between March 2008 and May 2008 with symptoms of selenosis after consuming a nutritional supplement. Institutional IRB approval was obtained for this case series. RESULTS: Supplement testing revealed almost 200 times the reported amount of selenium. There were 5 males and 4 females and their ages ranged from 15 to 57 years (median 46 years, mean 44.2 years). The mean estimated cumulative dose of selenium ingested in our patients was 1.3 gram over a mean period of 37.5 days (10-60 days). In each case, the symptoms of selenium toxicity manifested within 1 week from the start of ingestion. Initial symptoms included alopecia, dystrophic fingernail changes, GI symptoms, and memory difficulties. The initial whole blood selenium concentrations ranged from 150 to 732 mcg/L (reference mean range 123-193 mcg/L) at an average of 27 days post cessation of the formula. The urinary selenium concentrations ranged from 41 to 220 mcg/g Creat (reference < 25 mcg/g Creatinine). None of the patients required more than supportive care for symptoms and none required hospitalization. CONCLUSION: Selenium is an essential element, which can result in significant toxicity if ingested in large amounts.

Selenium fractions in organic matter from Se-rich soils and weathered stone coal in selenosis areas of China.

A high degree of association between Selenium (Se) and organic matter has been demonstrated in natural environments, but Se fractions and speciation in organic matter is unclear. In this study, a method for quantifying organic matter associated with Se (OM-Se) was developed to investigate Se fractions in organic matter in Se-rich soils and weathered stone coal from Enshi, China, where Se poisoning of humans and livestock has been documented. Initially, Se was extracted using water and a phosphate buffer. Subsequently, OM-Se was extracted using NaOH, and then speciated into Se associated with fulvic acids (FA-Se) and humic acids (HA-Se). Both FA-Se and HA-Se were further speciated into the weakly bound and strongly bound fractions using a customized hydride generation reactor. The results show that FA-Se (1.91-479 mg kg(-1)) is the predominant form of Se in all Se-rich soils and the weathered stone coal samples, accounting for more than 62% of OM-Se (3.07-484 mg kg(-1)). Weakly bound FA-Se (1.33-450 mg kg(-1)) was prevalent in the total FA-Se, while weakly bound HA-Se (0.62-26.2 mg kg(-1)) was variable in the total HA-Se (1.15-32.5 mg kg(-1)). These data indicate that OM-Se could play a significant source and sink role in the biogeochemical cycling of Se in the supergene environment. Weakly bound FA-Se seems to act as a potential source for bioavailable Se, whereas strongly bound HA-Se is a possible OM-Se sink which is not readily transformed into bioavailable Se.

No evidence of selenosis from a selenium-rich diet in the Brazilian Amazon.

Selenium (Se) is an essential element and a well-known anti-oxidant. In the Lower Tapajós River region of the Brazilian Amazon, biomarkers of Se range from normal to very high. The local traditional diet includes important Se sources such as Brazil nuts, chicken, game meat and certain fish species. Some studies have reported alterations in keratin structure, gastrointestinal problems and paresthesia in populations with high Se intake. The objective of the present study was to evaluate cutaneous and garlic odor of the breath signs and sentinel symptoms of Se toxicity (selenosis) in relation to Se status in communities along the Tapajós River. Participants (N=448), aged 15-87 years, were recruited from 12 communities. Se concentrations were measured in blood (B-Se) and plasma (P-Se) by ICP-MS. A nurse performed an examination of the hair, nails, skin and breath for signs of Se toxicity. Interview-administered questionnaires were used to collect information on socio-demographics, medical history and possible symptoms of Se toxicity. In this population, the median levels of B-Se and P-Se were 228.4 µg/L (range 103.3-1500.2 µg/L) and 134.8 µg/L (range 53.6-913.2 µg/L) respectively. Although B-Se and P-Se surpassed concentrations considered toxic (B-Se: 1000 µg/L (U.S. EPA, 2002)), no dermal or breath signs or symptoms of Se toxicity were associated with the biomarkers of Se status. In the present study population, where Se intake is mostly from traditional diet, there is no evidence of selenosis. These findings support the need to re-assess Se toxicity considering factors such as the chemical form of Se exposure, route of exposure (inhaled versus ingested), co-exposures to toxic elements such as mercury. Considering the current food transition towards a western diet in the Amazon, further studies should address the possible association between high Se status and cardiometabolic health in this study population.

Selenium levels in breads from Sakarya, Turkey.

Selenium (Se) is an important trace element for human and animal health. It accumulates in wheat and corn, which is consumed mostly as bread. The Turkish population consumes mainly white wheat, whole wheat (brown bread) and corn breads. In this study, samples of these breads were collected from six different bakeries in the city of Sakarya, and their selenium levels were determined by ICP-OES after a chemical digestion. It was found that average selenium levels in white wheat, whole wheat and corn breads were 1149, 1204 and 2023 µg/kg, respectively. The results are compared with daily recommended intake and upper tolerable levels for selenium.

Acute selenium toxicosis in polo ponies.

Just prior to an international polo event, 21 horses from one team exhibited clinical signs of central nervous system disturbance, hyperexcitability, sweating, ataxia, tachycardia, dyspnea, pyrexia, and rapid death. The suspected cause of this peracute onset of illness and death included intentional contamination of feed or iatrogenic administration of performance-enhancing drugs resulting in a severe adverse reaction. Six horses were submitted to the Bronson Animal Disease Diagnostic Laboratory for necropsy and toxicological examination. The clinical signs and sudden death, the similarity to earlier work by the lead author of selenium toxicosis in calves, as well as published reports, prompted investigators to focus on selenium testing. Sixty-four hours following receipt, the laboratory detected toxic selenium concentrations in the tissues of these animals. Following further investigation of the case by regulatory officials, it was determined that all affected horses had received an intravenous injection of a compounded "vitamin/mineral" supplement just prior to the onset of signs. The compounded supplement contained toxic levels of selenium. The present report illustrates the in-depth laboratory investigation of the cause of acute death in 6 polo ponies due to selenium toxicosis. In addition to solving this high profile case, the toxic levels of selenium found in livers (6.13 ± 0.31 mg/kg wet weight), kidneys (6.25 ± 0.3 mg/kg wet weight), and sera (1.50 ± 0.11 µg/ml) of these affected animals may provide important diagnostic criteria for future interpretations of selenium concentrations in tissues of horses.

Selenium toxicosis in a white-tailed deer herd.

Chronic selenium (Se) toxicosis was found in a herd of white-tailed deer showing signs of anorexia, weight loss, and lameness. Concentration of Se in the liver ranged from 2.7 to 8.97 mg/kg wet weight. Myocardial necrosis, mineralization, and fibroplasia were seen histologically. This is the first report of this toxicosis in white-tailed deer.