P A Workshop Identified Research Needs V JAMES McKlNNEV AND RON ROGERS
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uman activities have measurably altered the global and regional cycles of most trace elements. The quantitative assessment of air, water, and soils worldwide indicates that the contamination of freshwater resources and accumulation of toxic metals in the human food chain are xcelerating. Lead and nickel are two examples of race metals showing human-induced mobilization .n the biosphere. Bioavailability studies, which attempt to define the factors that control uptake of a metal by the body qualitatively and quantitatively, lave become an important scientific research issue.
Among these metal contaminants, approximately 20 are under study or review by various EPA programs for their potential for increased human exposure and health risk. Many details about the origins, mechanisms, and routes of exposure to these metals and the risks they pose, however, remain sketchy. To address these data gaps and pertinent research needs, a twoday workshop was held in July 1990 at EPA’s Environmental Research Center [Research Triangle Park, NC) that focused on issues of bioavailability and disposal kinetics for 10 of the more important toxic trace metals. A major topic was the availability of metal-specific input parameters such as metabolic rate constants and organ-tissue partitioning properties needed to develop physiologically based pharmacokinetic models for assessing risk from exposure to metal compounds. Workshop discussions The hazards associated with exposure to metals vary. For example, dissolved metals C M exist as free hydrated ions or can form complexes with inorganic and organic ligands. The bioavailabilities of complexes and their disposition kinetics in biological systems can differ markedly from those of uncomplexed metals. This difference alone presents a major problem in determining the toxicokinetic properties of environmentally relevant forms or species of metals. Another problem is that forms of metal species examined in toxicological laboratories are not necessarily representative of their forms i n the environment. Often, the metal species studied in toxicological laboratories are chosen because they are convenient to examine (e.g., they are water soluble). The toxicological hazard from a metal often is considered to be less a property of the form of the metal administered than of the metal (ion) per se. Although the toxicity of different compounds of the same metal may be qualitatively similar, significant quantitative differences in the expression of this toxicity may be expected. These differences greatly increase the potential for uncertainty in risk assessments based on human exposures to metal compounds. Collaboration is needed Toxicologists and chemists need to coordinate research on the chemisby of metal speciation and on the
toxicological effects of metal species. Moreover, because some trace elements are vital to human nutrition, metal toxicologists and nutritional scientists need to work together to establish the levels above which intake of such metals constitutes intoxication rather than nutrition. Another need is improved analytical methodology. Its lack seriously hampers the investigation of the speciation of metals, and how metal species interact and transform in abiotic and biotic environments. The lack of suitable analytical standards for many metal species is a further setback to studies of metals in the environment and the food chain. For example, the chemical speciation of inorganic arsenic and its metabolites is particularly rele-
Because some trace elements are vital to human nutrition, metal toxicologists and nutritional scientists need to work together to establish the levels above which intake of such metals constitutes intoxication rather than nutrition. vant to the determination of factors that might account for the carcinogenic potential of exposures to this metalioid. It is increasinelv evident that the prooxidant actiGiiy of certain metals allows them to act as complete carcinogens-capable of producing tumors at or near the site of initial exposure. Prooxidant activity includes metal-induced overproduction or deregulation of oxidants needed for the normal functioning of cells. Valid analytical methodology is important for determining the metal chemistry that is responsible for the DNA-damaging, cell-trans-
W13-936Xi¶2/0926-1203.00/0 0 1992 American Chemical Society
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forming, and tumor-initiating and -promoting action of carcinogenic metals via direct or indirect oxidative interactions. Revisiting the problems A follow-up workshop on metal bioavailability will be held in Research Triangle Park in fall 1992. This workshop will focus on methods to conduct bioavailability studies with metal compounds. To prepare for this meeting, specific research needs that were identified during the 1990 workshop have been assembled in a set of proceedings. Topics include metal-specific research needs and background literature. Copies of the proceedings are available from James McKinney, Health Effects Research Laboratory, US. EPA, Mail Drop 74, Environmental Research Center, Research Triangle Park, NC 27711. James D. McKinney i s c h i e f of t h e Pharmacokinetics Branch of EPA’s Health Effects Laboratory. He received his Ph.D. in organic chemistry from the University of Geornia in 1966, with minors in biochemky and inorganic chemistry. His work has emphasized the use of structuml chemistry and chemical reactivity considemtions in understanding molecular mechanisms that underlie chemical toxicity.
Ron Rogers is a toxicologist with the Research Support Division of EPA’s Health Effects Laboratory. He received his M.S. degree in toxicology from N o r t h Carolina State University. Environ. Sci. Technol., VoI. 26, No. 7. 1992 1299
