Mercury Toxicokinetics Research Articles

Genetic factors of toxic effects development in pollution liquidators of the former factory with mercury electrolysis technology

Introduction. According to genetic factors, it is possible to determine the degree of manifestation of the toxic effects of mercury. The latter justifies the assessment of the genetic status of the exposed contingent in order to identify hypersensitive individuals in whom adverse health effects can be realized when exposed to relatively low levels of the toxicant. The study aims to research the distribution of genotypes of some polymorphic variants of genes of the xenobiotic biotransformation system, heat shock proteins and tumor necrosis factor in the contingent involved in liquidation measures, as well as to identify individuals with a high prognostic risk of toxic effects due to exposure to mercury. Materials and methods. We conducted genotyping of 231 people (men only): 193 employees of the Ministry of Emergency Situations (MES) of Russia in the Irkutsk Region and 38 employees of the Federal Environmental Operator (FEO) involved in the elimination of mercury pollution at the industrial site of the mercury electrolysis plant and adjacent facilities on the territory of a former chemical plant in Eastern Siberia. The researchers used real-time PCR and PCR-RFLP methods to study polymorphic variants of the genes CYP1A1 (rs1048943), GSTP1 (rs1695 and rs1138272), TNF-α (rs1800629) and HSPA1B (rs1061581). Results. For the polymorphism of the GSTP1 gene (rs1695), we have identified an increase in the frequency of AG genotypes (p=0.043) and a decrease in the frequency of GG genotypes (p=0.048) in employees of the MES compared to those from the FEO group. The researchers didn’t detect carriers of the TT genotype for the polymorphic locus GSTP1 (rs1138272) in both examined groups. There was the carriage of the rare GG-CYP1A1 homozygote only in one MES employee. We found that 33 MES employees and 3 examined from the FEO group who are carriers of the GG-HSPA1B (+1267A/G) genotype have a high predictive risk of developing toxic effects due to mercury exposure. The experts discussed the data obtained with the results of genotyping of former mercury electrolysis shop workers who were chronically exposed to metallic mercury vapor. The experts have reviewed the data obtained from the results of genotyping of former employees of the mercury electrolysis shop who were chronically exposed to metallic mercury vapor Limitations. The limitations, first of all, should include the number of examined individuals in the FEO group, as well as the lack of data on deletion polymorphisms of the GSTT1 and GSTM1 genes, potentially having a significant role in the toxicokinetics of mercury. Conclusion. The study has revealed 36 carriers of the GG genotype of the polymorphic locus +1267A/G of the HSPA1B gene associated with a high prognostic risk of toxic effects associated with exposure to mercury among the employees of the Ministry of Emergency Situations (MES) and the FEO involved in liquidation work. Taking into account the forthcoming volume and duration of work related to the demercurization of the territory of the former factory with mercury electrolysis technology and the surrounding area it is advisable to take into account the results obtained when monitoring the health status of the liquidators. Ethics. We have received voluntary informed consent, approved by the Committee on Biomedical Ethics (Protocol No. 6 of 10.03.2020), from each employee being examined.

Sexual dimorphism in inorganic mercury toxicokinetics and the attendant lipotoxic and non-lipotoxic dyslipidemia in the rat

The influence of variability in the biology of living organisms is poorly appreciated in toxicology. However, multiple lines of evidence indicate that sex-differences modulate toxicokinetics and toxicodynamics from cellular/molecular to whole animal levels resulting in different toxic responses of living organisms to xenobiotics exposure. In order to investigate the influence of sex in inorganic mercury (Hg) exposure, male and female Wistar rats were exposed to 0.5, 1.0 and 1.5 mg Hg/kg body weight orally as HgCl2 twice a week for 12 weeks. Higher Hg levels in the females (except heart) as compared to males were observed in the animals. At the highest dose of inorganic Hg, female renal Hg content was 3.3 times higher than that of the males. Mixed sexual dimorphism characterised circulating-lipid- and organ-lipid lipotoxic and non-lipotoxic dyslipidemia. The highest dose of inorganic Hg, induced hypercholesterolemia in the males as opposed to hypocholesterolemia in the female. Plasma and erythrocyte free fatty acids increased in both sexes, although the increase was more pronounced in the male. Reverse cholesterol transport was inhibited in the male at the highest dose of Hg, whereas female HDL became enriched with cholesterol. Female erythrocytes had all their lipids increased, whereas only male erythrocyte triglyceride increased. Brain cholesterol and phospholipids, and splenic phospholipids were depleted in both sexes. Our findings indicate that inorganic Hg exposure appears to affect Hg and lipid kinetics differently in both sexes, thus underscoring the need to develop sex-tailored approaches in the treatment of metal toxicosis and its metabolic outcomes.

Genetic Polymorphism of Delta Aminolevulinic Acid Dehydratase (ALAD) Gene and Symptoms of Chronic Mercury Exposure in Munduruku Indigenous Children within the Brazilian Amazon.

Genetic polymorphisms involved in mercury toxicokinetics and toxicodynamics may be associated with severe mercury toxicity. This study aimed to investigate the impact of an ALAD polymorphism on chronic mercury exposure and the health situation of indigenous children from the Brazilian Amazon. One-hundred-and-three indigenous children (under 15 years old) were included and genotyped (rs1800435) using a TaqMan validated assay. The mean age was 6.6 ± 4.5 years old, 60% were female, 49% presented with anemia, and the mean hair mercury concentration was 7.0 ± 4.5 (1.4–23.9) µg/g, with 49% exceeding the reference limit (≥6.0 µg/g). Only two children were heterozygous ALAD, while the others were all wild type. Minor allele frequency (ALAD G) and heterozygous genotype (ALAD CG) were 1% and 2%, respectively. The two children (12 and 14 years old) with the ALAD polymorphism had mercury levels above the average as well as had neurological symptoms related to chronic mercury exposure, such as visual field alterations, memory deficit, distal neuropathy, and toe amyotrophy. Both children also reported frequent consumption of fish in the diet, at least three times a week. In conclusion, our data confirm that an ALAD polymorphism can contribute to mercury half-life time, harmful effects, and neuropsychological disorders in indigenous children with chronic mercury exposure to gold mining activity.

Effect of lactic acid bacteria on mercury toxicokinetics

The capacity of two LAB strains to inhibit inorganic [Hg(II)] and organic (methyl-Hg; MeHg) mercury translocation through monolayers of co-cultures of NCM460 and HT29-MTX colonic cells was evaluated. Lactobacillus casei BL23 and Lactobacillus acidophilus ATCC4356 reduced the permeability of Hg(II) and MeHg from aqueous solutions through NCM460/HT29-MTX monolayers (20–94% reduction). However, assays using the bioaccessible (soluble) Hg fraction obtained by in vitro gastrointestinal digestion of Hg-contaminated swordfish only showed a reduction (42%) with the BL23 strain. In vivo experiments carried out in mice receiving an acute dose of Hg(II) or MeHg (0.5 mg/kg body weight/day) with or without lactobacilli resulted in significant decreases of the bioavailability of MeHg with both strains and increased excretion of Hg in feces after treatment with the lactobacilli. However, Hg(II) bioavailability or excretion was not affected. Hg accumulation in liver and kidney remained similar in LAB-treated or non-treated animals. This is the first study of the impact of LAB on Hg(II) and MeHg toxicokinetics and shows that some LAB strains have potential to diminish MeHg bioavailability. Furthermore, it has established the basis for new studies on the protective effect of LAB under conditions resembling subchronic and chronic Hg exposures.

Transplant Experiments as a Tool for Evaluating the Suitability of Sessile Organisms as Biomonitor Species in Tropical Coastal Waters: The Case of the Brown Mussel Perna perna (Linnaeus, 1758) in Rio de Janeiro State, Brazil

The present study evaluates mercury (Hg) toxicokinetics in Perna perna (L.) mussels from tropical bays through transplantation experiments. The mussels were transplanted from Guanabara Bay (GB) to Ilha Grande Bay (IGB). The experiments were carried out in December 2008 (experiment 1) and June 2009 (experiment 2). Both experiments lasted one month. In the experiment 2, the transplanted animals (77±8 µg.kg -1 ) showed a significant increase in Hg concentrations and exhibited significantly higher Hg concentrations than the animals that remained in GB (41±4 µg.kg -1 ). Despite this increase in mercury levels, the transplanted animals have not achieved the Hg concentrations of IGB resident animals (100±11 µg.kg -1 ). These results suggest that individuals of this species rapidly incorporated Hg in tropical estuaries. DOI: http://dx.doi.org/10.17807/orbital.v10i4.1069

Mercury toxicokinetics of the healthy human term placenta involve amino acid transporters and ABC transporters.

The capacity of the human placenta to handle exogenous stressors is poorly understood. The heavy metal mercury is well-known to pass the placenta and to affect brain development. An active transport across the placenta has been assumed. The underlying mechanisms however are virtually unknown. Uptake and efflux transporters (17 candidate proteins) assumed to play a key role in placental mercury transfer were examined for expression, localization and function in human primary trophoblast cells and the trophoblast-derived choriocarcinoma cell line BeWo. To prove involvement of the transporters, we used small interfering RNA (siRNA) and exposed cells to methylmercury (MeHg). Total mercury contents of cells were analyzed by Cold vapor-atomic fluorescence spectrometry (CV-AFS). Localization of the proteins in human term placenta sections was determined via immunofluorescence microscopy. We found the amino acid transporter subunits L-type amino acid transporter (LAT)1 and rBAT (related to b(0,+) type amino acid transporter) as well as the efflux transporter multidrug resistance associated protein (MRP)1 to be involved in mercury kinetics of trophoblast cells (t-test P<0.05). The amino acid transporters located at the apical side of the syncytiotrophoblast (STB) manage uptake of MeHg. Mercury conjugated to glutathione (GSH) is effluxed via MRP1 localized to the basal side of the STB. The findings can well explain why mercury is transported primarily towards the fetal side.

Effect of Gene-Mercury Interactions on Mercury Toxicokinetics and Neurotoxicity.

Individuals differ in susceptibility to mercury neurotoxicity, in part, due to underlying genetic differences. This review aims to evaluate the state-of-the-art of the effect of (1) genetics on mercury toxicokinetics and (2) gene-mercury interactions on neurodevelopment and neurotoxicity. We conducted a PubMed search in September 2014 and retrieved 14 studies on the influence of genetics on mercury toxicokinetics and ten on neurological effects of gene-mercury interactions. Genes frequently studied for their influence on mercury toxicokinetics were mainly related to the metabolism of glutathione, but the results were contradictory for most of the genes. The gene-mercury interactions on child neurodevelopment and adult neurotoxicity reported were too few to draw any definite conclusion. So far, candidate gene approaches have not identified any major gene/s modifying the kinetics or toxicity of mercury, suggesting that these might be polygenic traits. More research is highly warranted to clarify if there are vulnerable subgroups to mercury neurotoxicity in humans.

Alteration of placental type 2 11β-hydroxysteroid dehydrogenase expression and activity by lead

Alteration of placental type 2 11β-hydroxysteroid dehydrogenase expression and activity by lead

In Vitro Study of Bisphenol A (BPA) in the early human placenta

In Vitro Study of Bisphenol A (BPA) in the early human placenta

The importance of mercury determination and speciation to the health of the general population

It is well known that the toxicokinetics (i.e. absorption, distribution, metabolism and excretion) of mercury is highly dependent on the form of mercury to which a receptor has been exposed. The aim of this paper is to summarize the available health effects information for mercury and mercury compounds in the international scientific literature (1940-2003) and to point to the need for increased Hg control of water and food, including mercury speciation, especially in Mediterranean countries.

Mercury distribution and speciation in different brain regions of beluga whales (Delphinapterus leucas)

The toxicokinetics of mercury (Hg) in key species of Arctic ecosystem are poorly understood. We sampled five brain regions (frontal lobe, temporal lobe, cerebellum, brain stem and spinal cord) from beluga whales (Delphinapterus leucas) harvested in 2006, 2008, and 2010 from the eastern Beaufort Sea, Canada, and measured total Hg (HgT) and total selenium (SeT) by inductively coupled plasma mass spectrometry (ICP-MS), mercury analyzer or cold vapor atomic absorption spectrometry, and the chemical forms using a high performance liquid chromatography ICP-MS. At least 14% of the beluga whales had HgT concentrations higher than the levels of observable adverse effect (6.0mgkg−1 wet weight (ww)) in primates. The concentrations of HgT differed between brain regions; median concentrations (mgkg−1 ww) were 2.34 (0.06 to 22.6, 81) (range, n) in temporal lobe, 1.84 (0.12 to 21.9, 77) in frontal lobe, 1.84 (0.05 to 16.9, 83) in cerebellum, 1.25 (0.02 to 11.1, 77) in spinal cord and 1.32 (0.13 to 15.2, 39) in brain stem. Total Hg concentrations in the cerebellum increased with age (p<0.05). Between 35 and 45% of HgT was water-soluble, of which, 32 to 41% was methyl mercury (MeHg) and 59 to 68% was labile inorganic Hg. The concentration of MeHg (range: 0.03 to 1.05mgkg−1 ww) was positively associated with HgT concentration, and the percent MeHg (4 to 109%) decreased exponentially with increasing HgT concentration in the spinal cord, cerebellum, frontal lobe and temporal lobe. There was a positive association between SeT and HgT in all brain regions (p<0.05) suggesting that Se may play a role in the detoxification of Hg in the brain. The concentration of HgT in the cerebellum was significantly associated with HgT in other organs. Therefore, HgT concentrations in organs that are frequently sampled in bio-monitoring studies could be used to estimate HgT concentrations in the cerebellum, which is the target organ of MeHg toxicity.

Toxicokinetics of mercury in blood compartments and hair of fish-fed sled dogs

BackgroundUnderstanding mercury (Hg) distribution in blood and the importance of hair as an excretory pathway is critical for evaluating risk from long term dietary Hg exposure. The major objective of this study was to characterize changes in total Hg concentrations in specific blood compartments and hair over time due to long term piscivory.MethodsEight sled dogs (Canis lupus familiaris) were fed either a fish and kibble diet (n = 4), or a fish-free control diet (n = 4) for 12 weeks. Concentrations of Hg were monitored throughout the exposure period, and for 10 weeks post exposure, until Hg concentrations in all blood compartments of one of the exposed dogs dropped below detection limit. Additionally, foreleg hair was sampled during acclimation and weeks 0 and 12.ResultsHg was detected primarily in whole blood and packed cells, although it was sporadically detected at low concentrations in plasma and serum in two of the fish fed dogs. Dogs ingested an estimated average of 13.4 ± 0.58 μg Hg per kg body weight per day. Hg was detectable in whole blood and packed cells within a week of exposure. Detected concentrations continued to rise until plateauing at approximately 3-6 weeks of exposure at a mean of 9.2 ± 1.97 ng/g (ppb) in whole blood. Hg concentration decreased post exposure following 1st order elimination. The mean half-life (t1/2) in whole blood for Hg was 7 weeks. Mean Hg in hair for the fish-fed dogs at week 12 was 540 ± 111 ppb and was significantly greater (about 7-fold) than the Hg hair concentration for the control dogs. The hair to blood ratio for Hg in fish-fed dogs was 59.0 ± 7.6:1.ConclusionsThis study found the sled dog model to be an effective method for investigating and characterizing blood Hg distribution (whole blood, serum, plasma, packed cells) and toxicokinetics associated with a piscivorous diet, especially for Hg-exposed fur bearing mammals (such as polar bears). Although hair excretion and hair to blood Hg ratios were not similar to human concentrations and ratios, the sled dog toxicokinetics of Hg in blood, was more similar to that of humans than traditional laboratory animals (such as the rat).

Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n = 515), and total mercury content was measured. Average urine (1.06 ± 1.24 ug/L) and hair mercury levels (0.49 ± 0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels ( GSTT1 deletion), hair mercury levels ( GSTP1-105, GSTP1-114, GSS 5′), or both ( SEPP1 3′UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption).

Ethyl mercury toxicokinetics in humans after long-term repeated vaccine administration

Ethyl mercury toxicokinetics in humans after long-term repeated vaccine administration

Toxicokinetics of Mercury after Long-Term Repeated Exposure to Thimerosal-Containing Vaccine

The preservative thimerosal contains ethyl mercury (EtHg). Concerns over possible toxicity have re-emerged recently due to its presence in (swine and other) flu vaccines. We examined the potential accumulation of mercury in adults given repeated injections of a thimerosal-preserved vaccine for many years. Fifteen female patients were recruited from an outpatient clinic running a clinical trial with repeated injections (1 ml every 3-4 weeks) of a staphylococcus toxoid vaccine containing 0.01% thimerosal to treat chronic fatigue syndrome. Fifteen untreated female patients with the same diagnoses served as controls. Blood samples were taken before injecting the vaccine, 1 day later, about 2 weeks later, and just before the next injection. In the 15 controls, samples were taken twice. Blood was analyzed for total mercury and EtHg. The toxicokinetics were assessed for each patient separately as well as with a population-based pharmacokinetic model. Total mercury in blood increased on Day 1 in all treated patients (median: 0.33, range: 0.17-1.3 μg/l), as did EtHg (median: 0.14 μg/l, range: 0.06-0.43 μg/l). After a few weeks, levels were back to normal and similar to those in controls. Levels of methyl mercury (MeHg; from fish consumption) were much higher than those of EtHg. After exclusion of an outlier, the mean half-life in a population-based model was 5.6 (95% CI: 4.8-6.3) days. The results indicate that mercury from thimerosal is not accumulated in blood in adults. This is in accordance with short half-lives and rapid metabolism of EtHg to inorganic mercury.

The relevance of the individual genetic background for the toxicokinetics of two significant neurodevelopmental toxicants: Mercury and lead

The heavy metals mercury and lead are well-known and significant developmental neurotoxicants. This review summarizes the genetic factors that modify their toxicokinetics. Understanding toxicokinetics (uptake, biotransformation, distribution, and elimination processes) is a key precondition to understanding the individual health risks associated with exposure. We selected candidate susceptibility genes when evidence was available for (1) genes/proteins playing a significant role in mercury and lead toxicokinetics, (2) gene expression/protein activity being induced by these metals, and (3) mercury and lead toxicokinetics being affected by gene knockout/knockdown or (4) by functional gene polymorphisms. The genetic background is far better known for mercury than for lead toxicokinetics. Involved are genes encoding L-type amino acid transporters, organic anion transporters, glutathione (GSH)-related enzymes, metallothioneins, and transporters of the ABC family. Certain gene variants can influence mercury toxicokinetics, potentially explaining part of the variable susceptibility to mercury toxicity. Delta-aminolevulinic acid dehydratase (ALAD), vitamin D receptor (VDR) and hemochromatosis (HFE) gene variants are the only well-established susceptibility markers of lead toxicity in humans. Many gaps remain in our knowledge about the functional genomics of this issue. This calls for studies to detect functional gene polymorphisms related to mercury- and lead-associated disease phenotypes, to demonstrate the impact of functional polymorphisms and gene knockout/knockdown in relation to toxicity, to confirm the in vivo relevance of genetic variation, and to examine gene-gene interactions on the respective toxicokinetics. Another crucial aspect is knowledge on the maternal-fetal genetic background, which modulates fetal exposure to these neurotoxicants. To completely define the genetically susceptible risk groups, research is also needed on the genes/proteins involved in the toxicodynamics, i.e., in the mechanisms causing adverse effects in the brain. Studies relating the toxicogenetics to neurodevelopmental disorders are lacking (mercury) or very scarce (lead). Thus, the extent of variability in susceptibility to heavy metal-associated neurological outcomes is poorly characterized.

Mercury toxicokinetics during larval and juvenile stages in rainbow trout

Mercury toxicokinetics during larval and juvenile stages in rainbow trout

Mercury toxicokinetics—dependency on strain and gender

Mercury (Hg) exposure from dental amalgam fillings and thimerosal in vaccines is not a major health hazard, but adverse health effects cannot be ruled out in a small and more susceptible part of the exposed population. Individual differences in toxicokinetics may explain susceptibility to mercury. Inbred, H-2-congenic A.SW and B10.S mice and their F1- and F2-hybrids were given HgCl 2 with 2.0 mg Hg/L drinking water and traces of 203Hg. Whole-body retention (WBR) was monitored until steady state after 5 weeks, when the organ Hg content was assessed. Despite similar Hg intake, A.SW males attained a 20–30% significantly higher WBR and 2- to 5-fold higher total renal Hg retention/concentration than A.SW females and B10.S mice. A selective renal Hg accumulation but of lower magnitude was seen also in B10.S males compared with females. Differences in WBR and organ Hg accumulation are therefore regulated by non-H-2 genes and gender. Lymph nodes lacked the strain- and gender-dependent Hg accumulation profile of kidney, liver and spleen. After 15 days without Hg A.SW mice showed a 4-fold higher WBR and liver Hg concentration, but 11-fold higher renal Hg concentration, showing the key role for the kidneys in explaining the slower Hg elimination in A.SW mice. The trait causing higher mercury accumulation was not dominantly inherited in the F1 hybrids. F2 mice showed a large inter-individual variation in Hg accumulation, showing that multiple genetic factors influence the Hg toxicokinetics in the mouse. The genetically heterogeneous human population may therefore show a large variation in mercury toxicokinetics.

Genetic background of lead and mercury metabolism in a group of medical students in Austria

Information on the impact of genetic predisposition on metal toxicokinetics in the human body is limited. There is increasing evidence that certain genetic polymorphisms modify lead and mercury toxicokinetics. This called for analysis of further candidate genes. Medical students (N=324) were examined in order to detect potential associations between lead exposure and polymorphisms in HFE, VDR, ALAD, and MT genes, as well as between mercury exposure and GSTT1, GSTM1, GSTA1, GSTP1, GCLC, and MT polymorphisms. The levels of lead and mercury exposure of students were determined by blood, urine, and hair analyses (ICP-MS, CV-AAS). Genotyping of common polymorphisms was examined by MALDI-TOF MS and the TaqMan methodology. Associations between lead and mercury exposures and genetic background were examined by bivariate analysis, and by categorical regression analysis (CATREG) controlled by metal- and matrix-specific variables. Lead and mercury levels in urine, blood, and hair indicated low exposures. VDR polymorphism and joint presence of VDR/ALAD polymorphisms were significantly and independently associated with urine lead concentrations (CATREG P<0.05). Polymorphisms in GSTP1-114 and MT4 genes as well as dual gene combinations including GSTP1, GCLC, GSTT1, and GSTM1 polymorphisms were independent variables related to mercury body burdens (CATREG P<0.05). GSTP1-114/GSTT1 and GSTP1-105/GCLC combinations showed synergistic effects on hair mercury levels compared to single-gene variants. We found evidence that certain genetic backgrounds were associated with lead and mercury metabolism, suggesting gene-environment and gene-gene-environment interactions. The modes of interaction remain to be evaluated.

Whole blood mercury and selenium concentrations in a selected Austrian population: Does gender matter?

Data on mercury exposure of the Austrian population were inadequate. This study was performed to determine the causal factors underlying mercury exposure and selenium concentrations, and to estimate the gender-related health impacts. Venous blood samples of 78 women and 81 men were drawn at the Austrian Red Cross, Vienna. Mercury contents in acid-digested whole blood samples were measured after amalgam enrichment by CV-AAS, and selenium by AAS (heated quartz-cell) after hydrid formation. The average total mercury blood content of Austrians was low (2.38+/-1.55 microgL(-1); N=152). Mercury and selenium concentrations were not different between the genders (P>0.05) but we observed discrepancies regarding the causal factors. Mercury levels in men were influenced not only by fish consumption but also by age, education level, and amalgam fillings, whereas in women, only the diet (fish/seafood, red wine consumption) determined blood mercury (P<0.05). Moreover, only the males indicated a depressive effect of dental amalgam on hematocrit (P<0.05). Regarding selenium, age and alcohol consumption led to lower concentrations in men, whereas a high-level education had the opposite effect; no determinant was found for women. For the whole study group, a significant effect of chronic disease on selenium levels could be detected (P<0.05). 18% of women and 13% of men showed marginal selenium deficiency (blood selenium<65 microgL(-1)). Selenium and mercury concentrations were not correlated. Our results indicate the need to evaluate and integrate gender-related findings in metal toxicology and trace element research, because different causal factors require different preventive measures to reduce mercury exposure and the risk of low selenium concentrations. Future research is needed on the gender- and age-related differences in fish/seafood consumption habits, the modifications of mercury toxicokinetics through sex hormones, the selenium supply in Austria, and the clinical relevance of a low selenium status.