Toxicology of Metals

Metals and their compounds have long been recognized as important toxic agents, causing acute and chronic poisoning cases in occupational settings and in environmental high-exposure situations. In recent years it has been demonstrated in epidemiological studies that exposures in the general environment to low levels of toxic metals may make an important contribution to the global burden of disease. Furthermore, deficient intakes of essential metals through food give rise to a considerable burden of disease from a global perspective. There is an obvious need for preventive action to decrease this global burden of disease. It is also important to address current concerns for possible increases of metal exposures. This chapter highlights such concerns in relation to the current status of the scientific understanding of the metals included and discussed fully in the relevant chapters of this Handbook. Furthermore, it draws attention to future directions for generating new knowledge to fill gaps in the continued quest to assemble the knowledge base necessary for the protection of human health from adverse consequences related to exposure to metals

Risk Assessment

Risk assessment for metallic substances usually follows the generally accepted framework format for risk assessment for all toxic substances, which involves (1) exposure assessment, (2) hazard identification, (3) assessment of dose-response relationships, and (4) risk characterization. The importance of risk communication is also addressed. Risk assessment/risk communication is of particular relevance for metals and metalloids because all living organisms are exposed to these elements. Lead, cadmium, mercury, and the metalloid arsenic have been responsible for many human poisonings and even deaths. It is, hence, imperative that readers of this Handbook have a firm perspective on the exposure levels of metallic substances that produce adverse health effects and the various risk assessment approaches that have been used and are evolving to protect the health and well-being of living organisms. Because of the increasing use of nanomaterials, a recent concern is the dose metric for inhaled metallic nanoparticles. Regardless of exposure route, the following risk assessment considerations are important: biomonitoring approaches, identification of the mode of action for toxicity of metallic species for hazard identification, determining dose-effect relationships, the construction of dose-response curves, and the development of benchmark doses for various metallic species, which are discussed in relation to protecting sensitive subpopulations because not all individuals within a general population are at equal risk for toxicity. Risk characterization using modern biomarkers that are capable of detecting early cellular effects to low-dose exposures to metallic substances will play an increasingly important role in assessing risk from exposure to this class of toxic substances on an individual or mixture basis. The issue of metal-/metalloid-induced carcinogenesis is of ever increasing importance because many of the elements associated with this cellular outcome produce a number of early cellular effects, including the formation of reactive oxygen species, modification of apoptosis, and methylation of DNA. Finally, the issue of risk communication/risk management is of great importance because these issues are critical to addressing the health concerns of exposed populations and the practical, ethical, and financial issues related to reducing hazardous exposures to metallic substances.</p