Metals in the environment: estimation, health impacts and toxicology
Meeting report by Leo Salter
Cornwall College
ECG Bulletin July 2005
Cornwall College
ECG Bulletin July 2005
The 2005 ECG Distinguished Guest Lecture and accompanying Symposium were held in the Council Room of the Royal Society of Chemistry, Burlington House on March 2nd. The theme for this well-attended meeting was “Metals in the environment: estimation, health impacts and toxicology.”
Dr Jörg Feldmann, from the Trace Element Speciation Laboratory Aberdeen, University of Aberdeen, opened the meeting with a review of arsenic metabolism. Dr Feldmann described the speciation of arsenic* and how the toxic effects of arsenic were related to its speciation. Although the acute toxicity of arsenic is well known, in recent years the effects of chronic toxicity linked to exposures to low concentrations of arsenic species have become more apparent. More than 70 million people worldwide are exposed to arsenic, and health effects such as hyperkeratosis and skin and bladder cancer have been observed in some regions. The precise mechanisms of arsenic toxicity are as yet unknown. Dr Feldmann contrasted arsenobetaine, which is present in fish and shellfish, but is not metabolised when ingested and is excreted unchanged in urine with no acute toxicity and no chronic effects, with arsenic III/V, which is present in water and vegetables, has a high acute toxicity, severe chronic effects, accumulates in hair, nails and skin, and is metabolised to DMA(III) & DMA(V) and MMA(III) & MMA(V) before excretion.
Identification of the arsenic species is particularly important when assessments of toxicity are made, and any analytical procedures need to have good speciation specificity. The range of arsenic metabolites (e.g. glutathione complexes, phytochelatins) demands access to a variety of species-discriminatory analytical methods. Dr Feldmann discussed the use of HPLC-ICP-MS and HPLC-ES(electrospray)-MS for the determination of arsenic species (with detection limits of around 1ng
mL-1), and the application of XAS (X-ray Absorption Spectroscopy) and XANES (X-ray Absorption Near Edge Spectroscopy) for in situ speciation of arsenic. These techniques were used to investigate the metabolism of arsenic sugar species in seaweed eaten by sheep in the Orkneys. Dr Feldmann commented that the identification and quantitative analysis of the wide range of arsenic-sulphur species that exists in biological systems will open a new chapter in arsenic speciation.
In the second presentation of the afternoon, Dr Andrew Smith (MRC Toxicology Unit, University of Leicester) spoke on “Toxicogenomic approaches to determine consequences of metal exposure”. He placed investigations of the chronic effects of arsenic and other metals in the frame of the current focus of toxicology. The traditional concerns of toxicologists in relation to drug responses and occupational exposures have been replaced by interests in carcinogenicity and neurotoxicity. In particular, the identification of neuronal effects and their influence on development were especially important for metals such as Mn, Fe, Ni, As, Pb, Hg and Cd where low concentrations produced low levels of neurotoxicity. For such effects the embryo and the very young were at greatest risk. Although mechanistic studies of such impacts had great intrinsic value, he pointed out that even if the identification of exact mechanisms of toxicity helped our understanding of the hazards of exposure to particular species, such investigations did not always assist in the quantification of risk.
New methodologies, including toxicogenomics, proteomics, and metabonomics (see ECG Bulletin, July 2004), provide new testing protocols for the toxicologist. These methods have an immense range of possibilities, but also produce large amounts of data with as yet no unified method of presentation. Examining how gene transcription, the nature and quantity of proteins, or the expression of metabolites varied after a toxicological insult might give an indication of occupational or environmental exposure. But the influence of variables such as diet (nutritional status), polymorphisms (individual genetic type) confounded the interpretation of results from such work. Dr Smith thought that metabolite expression might be the way ahead to link exposure to toxicity and gene function.
The closing session celebrated the work of Professor Jane Plant CBE (currently at Imperial College and ex-Chief Scientist at the British Geological Survey (BGS)). Her presentation was entitled “Chemicals in the Environment”. Professor Plant began by exploring the manner in which the evolution of man was linked to the increasingly sophisticated use of chemicals. This usage was changing with the introduction of new technologies that involve new modes of transport, communications, nanotechnology and similar. As man’s use of chemicals changes (and increases) so does the risk of health effects increase. Although many of the chemicals that are in the environment naturally or as a consequence of man’s activities are essential for life, the effects of metal deficiencies are apparent only at very low concentrations and exposure to a small excess of an essential element can easily produce chronic toxicity.
Professor Plant explored the way in which high resolution mapping of multi-element distributions in the UK could assist in estimates of metal bioavailability and subsequent health risks. She went on to argue that in the long term only the sustainable use of chemical resources could resolve the issues associated with the increasing redistribution of geologically ‘fixed’ chemicals by anthropogenic activity, and that the best way to address such sustainability issues was via Life Cycle Analysis (LCA).
The interlinking of toxicity studies (speciation, analysis, mechanisms, risk) with mapping of chemicals (spatial distribution, risk assessment) and efforts to mitigate hazards and risk (sustainable use, LCA) needs to be internationally targeted and prioritised.
The symposium ended with a series of questions, some of which reflected the concern of the delegates about the significant costs involved in accessing the BGS mapping data and the detrimental impact this has on education and research.
More detailed accounts of the three presentations from the ECG DGL 2005 will appear in the January 2006 issue of the ECG Bulletin.
Dr LEO SALTER,
Cornwall College,
Pool, Redruth, Cornwall
Dr Jörg Feldmann, from the Trace Element Speciation Laboratory Aberdeen, University of Aberdeen, opened the meeting with a review of arsenic metabolism. Dr Feldmann described the speciation of arsenic* and how the toxic effects of arsenic were related to its speciation. Although the acute toxicity of arsenic is well known, in recent years the effects of chronic toxicity linked to exposures to low concentrations of arsenic species have become more apparent. More than 70 million people worldwide are exposed to arsenic, and health effects such as hyperkeratosis and skin and bladder cancer have been observed in some regions. The precise mechanisms of arsenic toxicity are as yet unknown. Dr Feldmann contrasted arsenobetaine, which is present in fish and shellfish, but is not metabolised when ingested and is excreted unchanged in urine with no acute toxicity and no chronic effects, with arsenic III/V, which is present in water and vegetables, has a high acute toxicity, severe chronic effects, accumulates in hair, nails and skin, and is metabolised to DMA(III) & DMA(V) and MMA(III) & MMA(V) before excretion.
Identification of the arsenic species is particularly important when assessments of toxicity are made, and any analytical procedures need to have good speciation specificity. The range of arsenic metabolites (e.g. glutathione complexes, phytochelatins) demands access to a variety of species-discriminatory analytical methods. Dr Feldmann discussed the use of HPLC-ICP-MS and HPLC-ES(electrospray)-MS for the determination of arsenic species (with detection limits of around 1ng
mL-1), and the application of XAS (X-ray Absorption Spectroscopy) and XANES (X-ray Absorption Near Edge Spectroscopy) for in situ speciation of arsenic. These techniques were used to investigate the metabolism of arsenic sugar species in seaweed eaten by sheep in the Orkneys. Dr Feldmann commented that the identification and quantitative analysis of the wide range of arsenic-sulphur species that exists in biological systems will open a new chapter in arsenic speciation.
In the second presentation of the afternoon, Dr Andrew Smith (MRC Toxicology Unit, University of Leicester) spoke on “Toxicogenomic approaches to determine consequences of metal exposure”. He placed investigations of the chronic effects of arsenic and other metals in the frame of the current focus of toxicology. The traditional concerns of toxicologists in relation to drug responses and occupational exposures have been replaced by interests in carcinogenicity and neurotoxicity. In particular, the identification of neuronal effects and their influence on development were especially important for metals such as Mn, Fe, Ni, As, Pb, Hg and Cd where low concentrations produced low levels of neurotoxicity. For such effects the embryo and the very young were at greatest risk. Although mechanistic studies of such impacts had great intrinsic value, he pointed out that even if the identification of exact mechanisms of toxicity helped our understanding of the hazards of exposure to particular species, such investigations did not always assist in the quantification of risk.
New methodologies, including toxicogenomics, proteomics, and metabonomics (see ECG Bulletin, July 2004), provide new testing protocols for the toxicologist. These methods have an immense range of possibilities, but also produce large amounts of data with as yet no unified method of presentation. Examining how gene transcription, the nature and quantity of proteins, or the expression of metabolites varied after a toxicological insult might give an indication of occupational or environmental exposure. But the influence of variables such as diet (nutritional status), polymorphisms (individual genetic type) confounded the interpretation of results from such work. Dr Smith thought that metabolite expression might be the way ahead to link exposure to toxicity and gene function.
The closing session celebrated the work of Professor Jane Plant CBE (currently at Imperial College and ex-Chief Scientist at the British Geological Survey (BGS)). Her presentation was entitled “Chemicals in the Environment”. Professor Plant began by exploring the manner in which the evolution of man was linked to the increasingly sophisticated use of chemicals. This usage was changing with the introduction of new technologies that involve new modes of transport, communications, nanotechnology and similar. As man’s use of chemicals changes (and increases) so does the risk of health effects increase. Although many of the chemicals that are in the environment naturally or as a consequence of man’s activities are essential for life, the effects of metal deficiencies are apparent only at very low concentrations and exposure to a small excess of an essential element can easily produce chronic toxicity.
Professor Plant explored the way in which high resolution mapping of multi-element distributions in the UK could assist in estimates of metal bioavailability and subsequent health risks. She went on to argue that in the long term only the sustainable use of chemical resources could resolve the issues associated with the increasing redistribution of geologically ‘fixed’ chemicals by anthropogenic activity, and that the best way to address such sustainability issues was via Life Cycle Analysis (LCA).
The interlinking of toxicity studies (speciation, analysis, mechanisms, risk) with mapping of chemicals (spatial distribution, risk assessment) and efforts to mitigate hazards and risk (sustainable use, LCA) needs to be internationally targeted and prioritised.
The symposium ended with a series of questions, some of which reflected the concern of the delegates about the significant costs involved in accessing the BGS mapping data and the detrimental impact this has on education and research.
More detailed accounts of the three presentations from the ECG DGL 2005 will appear in the January 2006 issue of the ECG Bulletin.
Dr LEO SALTER,
Cornwall College,
Pool, Redruth, Cornwall
