The toxicologically relevant mercury species inorganic and organic Hg in blood are frequently determined by separate measurements of total Hg and of inorganic Hg, with their difference indicating organic Hg It is shown that the different partition of inorganic and organic Hg between erythrocytes and plasma (e/p ratio) can be used to calculate the concentrations of either Hg species in either blood constituent from measurement of total Hg only This was tested on the blood of different groups of volunteers The calculated concentrations of inorganic and organic Hg in cells and plasma were then compared by linear regression with their previously measured counterparts An accurate prediction has been found for individual levels of inorganic Hg in plasma and organic Hg in cells These calculated levels were little affected by variations of the e/p ratios The coincidence between calculated and measured levels of inorganic Hg in cells and organic Hg in plasma was more sensitive to alterations of the e/p ratios In conclusion, the relevant concentrations of inorganic Hg in plasma and organic Hg in cells can reliably be calculated from measurements of total Hg and from assumed e/p ratios This means a sizeable reduction of analytical work, and also provides specific information in cases of low-level coexposure to both Hg species Besides the possibility to introduce automated analyses of total Hg in mercury speciation in blood, the proposed calculation scheme has the potential to easily enlarge the data base in epidemiological and toxicological surveys of mercury exposure Copyright (C) 2010 John Wiley & Sons, Ltd

Improved living conditions have led to a steady increase in the life expectancy of humans in most countries. However, this is accompanied by an increased probability of suffering from neurodegenerative diseases like Alzheimer's disease or Parkinson's disease. Unfortunately, the therapeutic possibilities for curing these diseases are very limited up to now. Many studies indicate that a variety of environmental factors contribute to the initiation and promotion of neurodegenerative diseases. For example, the role of metal exposure and disturbance of metal homeostasis in the brain is discussed in this respect. However, most studies focus on the neurological and toxicological aspects but not on a detailed characterisation of the species of the involved metals. Therefore, this review summarizes the neurotoxic effects of selected metals on humans and focuses on contributions from trace element speciation analysis with relevance to neuroscientific research. In spite of the advance in instrumentation and methodology of speciation analysis there are few applications for matrices like cerebrospinal fluid which is due to limited access to these samples and analytical challenges caused by matrix interferences, low concentrations and limited stability of many trace element species of interest. The most relevant neurotoxic metals aluminium, lead, manganese and mercury are reviewed in detail while further metals like cadmium, arsenic, bismuth and tin are briefly discussed. Current results indicate that knowledge on trace element speciation can contribute to a better understanding of the transport of metals across the neural barriers and potentially of their role in diseased human brains.

Die Langzeit-Resorption sehr kleiner Quecksilber-(Hg-) Dosen aus Amalgamfüllungen führt zu einem leicht erhöhten Verteilungsgleichgewicht von Quecksilber im Organismus und entsprechend zu geringfügig erhöhten Konzentrationen in Blut und Urin. Viele unabhängige Untersuchungen haben auf Gruppenbasis bestätigt, dass die erhöhten Werte weit unter den regulatorischen Richt- und Grenzwerten, bzw. unter den humantoxikologisch minimal wirksamen Werten liegen. Es hat sich ebenfalls zweifelsfrei bestätigt, dass das Entfernen der Füllungen eine rasche signifikante Abnahme der Hg-Werte in Blut und Urin und damit der inneren Hg-Belastung des Organismus bewirkt. Eine Gabe von Hg-spezifischen Antidoten ist nicht notwendig. Eine Hg-Entlastung durch Amalgamentfernung ist zur Besserung eines hohen psychosomatischen, auf Amalgam bezogenen, Leidensdrucks (sog. Amalgamkrankheit) nicht zwingend nötig, da sich dieser Symptomenkomplex auch bei erhaltenen Füllungen durch psychotherapeutische Maßnahmen bessern lässt.

This chapter contains sections titled: Persistent Polyhalogenated Aromatic Hydrocarbons Metals Toxicology of Fibers and Particles Xenoestrogens and Xenoantiandrogens Toxicology of Solvents Noxious Gases Animal and Plant Toxins References For Further Reading Further Reading Reference

OBJECTIVE:To investigate the suitability of measurements of mercury (Hg) concentration as a means of identifying patients with health complaints attributed to dental amalgam.METHODS:Hg in erythrocytes, plasma, urine, and saliva was determined in 27 patients complaining about health problems attributed to amalgam, 27 healthy volunteers with amalgam fillings, and 27 healthy amalgam-free volunteers.RESULTS:Concentrations of inorganic mercury in blood and of total mercury in urine and saliva differed significantly between individuals with amalgam fillings and amalgam-free volunteers, but not between symptomatic patients and healthy volunteers with amalgam fillings. Urine Hg levels tended to be better correlated with blood than with saliva data. Levels of organic Hg were equal in all groups.CONCLUSION:Concentrations of total and inorganic mercury in body fluids do not distinguish between asymptomatic amalgam bearers and those who suffer from a poorly defined syndrome of multiple nonspecific symptoms.

Propylene (PE) was not carcinogenic in long-term studies in rodents. However, its biotransformation to propylene oxide (PO) raises questions about a carcinogenic risk. PO alkylates macromolecules, is a direct mutagen, and caused tumors in rodents at high concentrations. In order to acquire knowledge on the species-specific PO concentrations in blood resulting from PE exposure, we exposed male Fischer 344/N rats in closed exposure chambers to constant PE concentrations, between 20.1 and 3000 ppm (7 h at least), and four male volunteers to mean constant PE concentrations of 9.82 and 23.4 ppm (180 min) in inhaled air. In the animal experiments, PE and PO were measured in the chamber atmosphere, PE by gas chromatography with flame ionization detection (GC/FID), PO by GC/FID or GC with mass-selective detection (GC/MSD). In the human studies, PE was measured in inhaled and exhaled air by GC/FID. PO was quantified by GC/MSD from exhaled breath collected in gasbags. Blood concentrations of PO were calculated based on the measured PO concentrations in air using the blood-to-air partition coefficients of 60 (rat) and 66 (human). In rats, PO blood concentrations ranged from 53 nmol/l at 20.1 ppm PE to 1750 nmol/l at 3000 ppm PE. In humans, mean blood concentrations of PO were 0.44 and 0.92 nmol/l at mean PE concentrations of 9.82 and 23.4 ppm, respectively. These findings should be taken into consideration when estimating the carcinogenic risk of PE to humans based on carcinogenicity studies in PE- or PO-exposed rats.

Mercury vapor (Hg0) emission from plants contributes to the atmospheric Hg cycle. Young barley (Hordeum vulgare L.) plants grown on a hydroponic cultivation medium containing Hg(II) have previously been shown to increase their Hg0 emission significantly by reduction of Hg(II) with endogenous ascorbic acid. Regarding the potential contribution to the Hg cycle from the vast forest-covered areas, it was important to investigate this mechanism in trees. The increase in Hg0 emission from young European beech plants cultivated on a HgCl2 medium exceeded that from controls by ca. tenfold and was proportional to the Hg(II) concentration. From these experiments, a flux of 12.8μg Hg0/h/m2 was estimated at an exposure of the roots to 20μM Hg(II). Mercury vapor release from homogenates of Norway spruce needles exceeded that from European beech leaves by a factor of 2.3–4, i.e. in proportion to the reported AA concentrations; the reduction was maximal at alkaline pH which is typical for AA. The 8.4-fold difference in Hg0 release between homogenates from wild-type Arabidopsis thaliana and from its AA-deficient mutant vtc 1-1 also paralleled the reported difference in AA levels of both species. It is concluded that the phytoreduction and vaporization of Hg by AA is an important mechanism as much for Hg detoxification in trees as for Hg emission to the atmosphere. The efficiency of this process seems to result from the optimal coordination of transfer and biochemical transformation of mercuric ions and Hg vapor. There is no evidence for a relevant difference in the mechanisms of biogenic Hg(II) reduction between grass plants and trees.

Although manganese is an essential trace element, concerns are rising about the Mn exposure of humans being related to neurotoxic effects. This review summarizes several aspects of this topic to provide updated information on Mn related investigations, including chemical speciation of Mn-compounds. The paper starts with some chemical aspects of Mn and its compounds, enlighting oxidation states in general and in biological matrices. This is followed by considerations on natural sources of human exposure, on occupational sources and on anthropogenically caused environmental sources, for example from the use of methylcyclopentadienyl manganese tricarbonyl (MMT). Next, the paper deals with Mn levels in the human organism, showing normal Mn concentrations in various tissues or body fluids, and continues with the toxicology of Mn, i.e. absorption, distribution and excretion. Of specific concern is the transfer of Mn to the brain which is the relevant neurotoxic target. In this context, parallels and differences between primary and Mn-dependent Parkinsonism are discussed, concluding with a risk assessment and a consideration of susceptible groups. The main part of this review focuses on recent investigations on Mn speciation. Analytical problems and their solutions are also described for correct identification of relevant Mn-compounds in matrices of human origin. Finally, future needs are discussed, such as further investigations on those Mn-species which may overcome neural barrier control, on disease-modulated barrier control, on susceptibility to certain Mn-species, and on the interaction of Mn with Fe-homeostasis in the brain.

The neurotoxic effects of manganese (Mn) at elevated concentrations are well known. This raises the question, which of the Mn species can cross neural barriers and appear in cerebrospinal fluid (CSF). CSF is the last matrix in a living human organism available for analysis before a compound reaches the brain cells and therefore it is assumed to reflect best the internal exposure of brain tissue to Mn species. A previously developed CE method was modified for separation of albumin, histidine, tyrosine, cystine, fumarate, malate, inorganic Mn, oxalacetate, α‐keto‐glutarate, nicotinamide‐dinucleotide (NAD), citrate, adenosine, glutathione, and glutamine. These compounds are supposed in the literature to act as potential Mn carriers. In a first attempt, these compounds were analyzed by CZE‐UV to check whether they are present in CSF. The CZE‐UV method was simpler than the coupled CZE‐inductively coupled plasma (ICP)‐dynamic reaction cell (DRC)‐MS method and it was therefore chosen to obtain a first overview information. In a second step, the coupled method (CZE‐ICP‐DRC‐MS) was used to analyze, in detail, which of the compounds found in CSF by CZE‐UV were actually bound to Mn. Finally, 13 Mn species were monitored in CSF samples, most of them being identified: Mn‐histidine, Mn‐fumarate, Mn‐malate, inorganic Mn, Mn‐oxalacetate, Mn‐α‐keto glutarate, Mn‐carrying NAD, Mn‐citrate and Mn‐adenosine. By far the most abundant Mn species was Mn‐citrate showing a concentration of 0.7 ± 0.13 µg Mn/L. Interestingly, several other Mn species can be related to the citric acid cycle.

Objective: We aimed to investigate whether the Prognos (R) device might be a useful tool in the diagnosis of disorders suspected to be due to dental amalgam fillings. Participants and Methods: A diagnostic case-control study was performed in 27 patients who complained about health problems attributed to amalgam ( cases), 27 healthy volunteers with amalgam fillings ( controls I), and 27 healthy amalgam-free volunteers ( controls II). All participants were tested before and after application of 300 mg DMPS (2.3-dimercapto-1-propanesulfonic acid) with Prognos, a diagnostic device for the energetic measurement of Traditional Chinese Medicine meridians. In addition, mercury was measured in blood, urine, and saliva, and a lymphocyte transformation test (LTT) was performed. Results: Diagnoses derived from the first and second Prognos testing did not agree above chance (Cohen's Kappa = -0.11, 95% confidence interval -0.33 to 0.10; p = 0.30). Agreement for secondary outcome measures was poor, too. Prognos measurements did not differ between cases and controls. Correlations with measurements in urine, blood and saliva were low. Conclusion: In this study Prognos could not be shown to be a useful tool in the diagnosis of disorders suspected to be due to dental amalgam fillings.

Manganese (Mn) at high concentrations can have adverse effects on health, mainly because of its toxicity to the central nervous system. Health impacts of Mn are known mostly from occupational health studies, but the exact mechanisms how Mn, being bound to transferrin (TF) in the blood, enters the brain--are unknown. Mn speciation at the neural barriers can help to obtain more information about the pathways and carriers. This paper summarizes investigations on the size distribution of Mn carriers (e.g. proteins, peptides, carbonic acids) in serum before the neural barriers and in cerebrospinal fluid (CSF) behind them as a first characterization step of the Mn carriers being involved in moving Mn across the neural barriers. Further identification of Mn-species in CSF was successfully achieved by CZE-inductively coupled plasma (ICP)-dynamic reaction cell (DRC)-mass spectrometry (MS). Serum samples showed Mn mean concentrations of 1.7+/-0.8 microg L(-1). The size distribution of Mn-carriers showed a main peak in the TF/albumin size fitting to the known physiological ligands. However, also an increasing Mn peak at 700 Da with increasing total Mn concentration was seen. Samples of CSF showed Mn mean concentrations of 2.6 microg L(-1)=48 nM. In CSF Mn was found to be mostly bound to low-molecular-mass (LMM)-Mn carriers in the range of 640-680 Da. This is similar to the LMM compound in serum and to Mn-citrate complexes suggested to be present in body fluids. Citrate concentration was 573 microM, thus being in huge excess compared to Mn. CSF was further analyzed by CZE-ICP-DRC-MS. Several Mn-species were monitored and mostly identified. The most abundant Mn-species was Mn-citrate at a concentration of around 0.7 microg Mn L(-1).

Manganese, at excess concentrations, can have adverse effects on health. Mn is a neurotoxicant. The health impacts of Mn are known mostly from occupational health studies, but the exact mechanisms by which Mn can enter the brain without transferrin-receptor mediated transport is unknown. Mn speciation at the neural barriers can help to obtain more information about the pathways and carriers. This paper therefore investigates the size distribution of Mn carriers ( e. g., proteins, peptides, carbonic acids) in serum before the neural barriers and in cerebrospinal fluid behind them, as a first step in characterization of the Mn carriers involved in moving Mn across the neural barriers. Serum samples showed Mn concentrations between 1.5 - 2.5 mu g L-1 (mean 1.7 +/- 0.8 mg L-1), the lower figure being fully in the physiological range, the higher being slightly elevated. The size distribution of Mn corresponding to the carriers showed a main peak in the transferrin/albumin size fitting to the known physiological ligands. However, preliminary results also indicated an increasing Mn peak at 700 Da with increasing total Mn concentration. This finding could point to excess Mn being transported by a low molecular mass (LMM) carrier. Samples of cerebrospinal fluid (CSF) showed Mn concentrations between 1.8 - 6.7 mu g L-1 (mean 2.66 mu g L-1, = 48 nM). Only sparse values have been published with which our results could be compared. The lower concentrations seem to be in the physiological range, whilst the higher ones are clearly elevated. In cerebrospinal fluid Mn was found to be nearly exclusively bound to LMM Mn carriers. The major fraction is in the range of 640 - 680 Da, which is similar to the LMM compound in serum and to Mn - citrate complexes suggested to be present in body fluids. Therefore, citrate was additionally determined in CSF. The concentration ranged from 420 - 713 mu M ( mean 573 mu M), proving that citrate is in huge excess compared with Mn (ratio 1:12 000). This finding makes a Mn - citrate complex in CSF likely.

The article contains sections titled: 1. Introduction 2. Properties 2.1. Physical Properties 2.2. Chemical Properties 3. Resources and Raw Materials 3.1. Deposits 3.2. Secondary Sources 4. Production 4.1. Extraction from Primary Sources 4.1.1. Dressing 4.1.2. Processing to Metallic Mercury 4.1.3. Furnace Systems 4.2. Extraction from Secondary Sources 4.3. Condensation of Mercury from Furnace Off-Gas 4.4. Treatment of the Stupp 5. Environmental Protection 5.1. Natural Distribution of Mercury 5.1.1. Mercury in Soil, Plants, and Animals 5.1.2. Mercury in Food 5.2. Mercury Emissions 5.2.1. Gas Purification 5.2.2. Water Purification 6. Quality Specifications 7. Chemical Analysis 8. Storage and Transportation 9. Uses 10. Mercury Alloys 10.1. General 10.2. Production of Amalgams 11. Mercury Compounds 11.1. Inorganic Compounds 11.1.1. Mercury Chalconides 11.1.2. Mercury Halides 11.1.3. Mercury Pseudohalides 11.1.4. Acetates, Nitrates, Sulfates 11.1.5. Mercury - Nitrogen Compounds 11.1.6. Analysis, Storage, and Transportation; Protective Measures 11.2. Organic Compounds 11.2.1. Production 11.2.2. Compounds of the Type R1−Hg−R2 11.2.3. Compounds of the Type R−Hg−X 11.2.4. Analysis 12. Economic Aspects 13. Toxicology and Occupational Health 13.1. Chemical Forms and Mechanism of Action 13.2. Exposure 13.3. Metabolism 13.3.1. Mercury Vapor and Inorganic Mercury 13.3.2. Organic Mercury Compounds 13.4. Toxic Effects 13.4.1. Mercury Vapor and Inorganic Mercury 13.4.1.1. Acute Toxicity 13.4.1.2. Chronic Toxicity 13.4.2. Organic Mercury Compounds 13.4.3. Dental Amalgam Fillings 13.4.4. Carcinogenicity 13.5. Indicator Media and Reference Values 13.5.1. Mercury Vapor and Inorganic Mercury 13.5.2. Methylmercury 13.6. Critical Levels, Risk Assessment

In May 1999,the Bundesinstitut fur gesundheitlichen Verbraucher-schutz und Veterinarmedizin (BgVV) (Federal Institute of consumer health protection and veterinary medicine) recommended that pregnant women should nor consume certain species of fish because of neurotoxic effects of methyl mercury on the development of the fetal brain. Evaluation of two studies not mentioned in the BgVV's warning has shown, however, that, from the toxicological point of view, there is no reason to restrict the recommendation by the German Society for Nutrition advising pregnant women in Central Europe to eat one to two fish meals per week.

InvestigatiOn of the toxicokinetics of mercury upon inhalation of the vapor (Hg-degrees) requires an exposure system characterized by rapid development and stability of preselected Hg-degrees concentrations, continuous operation over variable exposure times, easy monitoring of Hg-degrees concentration in air, and ready determination of Hg in organs and carcasses. This can be realized by generating Hg-degrees from the reduction of Hg2+ labeled with radioactive Hg-203(2+). Since the commonly used reducing agents stannous chloride (SnCl2) or sodium borohydride (NaBH4) gave unsatisfactory results, the reducing properties of hypophosporous acid (HPH2O2) were tested. Continuous measurement with atomic absorption spectrometry (AAS) showed that rise time of Hg-degrees concentration was below 10 min and that the plateau was stable and higher than with the other reductants. The concentration of Hg-degrees in air was linearly correlated to that of Hg2+ in solution. Concentrations of Hg-203 in the wasted solution were below 5% of that of the initial Hg2+ solution, i.e., vaporization of Hg was nearly complete. The time to attain 90% of the steady-state Hg-degrees concentration in the exposure chamber can be calculated to be 3.7 min, which is in accordance with 4.6 min actually measured. Body burden and organ distribution of Hg were determined after exposure to 0.5, 1.0, and 2.0 mg Hg-degrees/m3 for 1. 2, and 3 h. Under these conditions Hg uptake was linearly correlated to exposure time or concentration.

Lipophilicity is suggested to modulate the diffusion and the cytotoxic effects of mercury compounds. To investigate this, the positive inotropic effect of four Hg compounds (HgCl2, CH3HgCl, chlormerodrin, bromomercurihydroxypropane) was studied in catecholamine-depleted isolated heart muscle preparations. The rate of development of the positive effect was inversely correlated to the concentration in the case of HgCl2 and chlormerodrin, i.e. the product of concentration (c) and time to halfmaximal effect (t50) remained constant. This was in accordance with the assumption of a permeation-controlled rate of action, as was shown earlier forp-chloromercuriphenylsulfonic acid. In addition, the c×t50 values of the individual mercurials decreased hyperbolically with the increase in lipophilicity as measured by the octanol/water partition. The results support the view that the toxicity of mercurials increases with their lipid solubility. In conjunction with the previously reported negative inotropic effect of Hg compounds, a model is proposed allocating thiol groups responsible for the negative inotropic action to lipid compartments within the cell membrane, while SH groups conveying the increase in contraction force are thought to be situated at the internal surface of the sarcolemma.