Levels of organic and inorganic mercury in human blood predicted from measurements of total mercury.

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 co-exposure 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.

JEM spotlight: metal speciation related to neurotoxicity in humans.

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.

Biomonitoring of mercury in patients with complaints attributed to dental amalgam, healthy amalgam bearers, and amalgam-free subjects: a diagnostic study.

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.

Concentrations of the propylene metabolite propylene oxide in blood of propylene-exposed rats and humans--a basis for risk assessment.

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.

Manganese species from human serum, cerebrospinal fluid analyzed by size exclusion chromatography-, capillary electrophoresis coupled to inductively coupled plasma mass spectrometry.

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).

Speciation and toxicological relevance of manganese in humans.

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, enlightening 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.

Prognos in the diagnosis of amalgam hypersensitivity a diagnostic case-control study.

OBJECTIVE: We aimed to investigate whether the Prognos 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 amalgamfree 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 speciation in human cerebrospinal fluid using CZE coupled to inductively coupled plasma MS.

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, alpha-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-alpha-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 microg Mn/L. Interestingly, several other Mn species can be related to the citric acid cycle.

In-situ measurements of low-level mercury vapor exposure from dental amalgam with zeeman atomic absorption spectroscopy.

Alongside food, emissions from amalgam fillings are an essential contribution to man's mercury burden. Previous methods for the determination of intraoral mercury vapor (Hg degrees ) release used principally some form of preconcentration of Hg on gold (film or wool), allowing relatively few measurements with unknown precision and sensitivity at selected times. Recently available computer-controlled Hg detectors operating on Zeeman atomic absorption spectroscopy (ZAAS) facilitate the direct real-time measurement of Hg degrees concentrations. It was the aim to adapt this method for a comparative investigation of emission processes from fillings in situ and from amalgam specimens in vitro. In addition to the ZAAS instrument, the apparatus consisted of a pump, magnetic valves, an electronic flow controller and a handle with a disposable mouth piece for aspiration of oral air. A programmable timer integrated the computer-controlled instrument operation and the data collection into a standard sampling protocol. A fast exponential decay of the emission was found after stimulation of amalgam specimens and of fillings in situ (halftimes 8.6 and 10.7 min). Precision was evaluated by a series of measurements on a single patient which indicated a consistently low coefficient of variation between 18% and 25%. After insertion of a few new fillings, sensitivity was high enough to detect a significant increase in emission against the background emission from the majority of old fillings. Zeeman-AAS in connection with a semi-automated sampling protocol and data storage provides precise in-situ measurements of Hg degrees emission from dental amalgam with real-time resolution. This facilitates the detailed exploration of the Hg degrees release kinetics and the applicability to large-scale studies.