Risk Assessment for Human Metal Exposures: Mode of Action and Kinetic Approaches examines the current principles of risk assessment in human metal exposures, with a focus on Mode of Action(MOA), Toxicokinetic and Toxicodynamic (TKTD) considerations, and computer models. Derived from the highly respected Handbook on the Toxicology of Metals, Fourth Edition (2014), the book summarizes principles and methods and provides examples of how MOA –TKTD can be used. In addition, it presents tactics on how information generated by such methods can be confirmed by epidemiological data. Furthermore, it demonstrates how epidemiological data can be confirmed and evaluated by the examined models and considerations. This resource uniquely integrates several important topics, such as risk assessment, characterization, management and communication—the classic risk assessment paradigm—with mode of action, TKTD, and epidemiology, all topics related to human exposure. Written by pioneers in the field, this book is an essential reference for researchers, students and technicians in toxicology and risk assessment. Covers fundamental risk assessment concerns for the effects of metals on human health Provides an easy-to-use structure to quickly locate specific methods Uses case studies to illustrate the methods and theories described Written to be understood by students, researchers and industry workers who need to conduct risk assessment in metals and human health

Heavy metals and metalloids, singly or in combination, induce toxic manifestations either through acute or chronic pathology. In particular, long-term chronic exposure to diverse heavy metals and metalloids to humans and animals can lead to numerous physical, muscular, neurological, nephrological, and diverse degenerative diseases and dysfunctions, including multiple sclerosis, muscular dystrophy, Parkinson’s and Alzheimer’s diseases, cardiovascular disorders, and several others. Recognized heavy metals such as lead, mercury, arsenic, cadmium, thallium, and hexavalent chromium are known for enormous toxicity. The immediate vital signs of acute heavy metal exposure include nausea, vomiting, diarrhea, and acute abdominal pain. Mercury has been identified as the most toxic heavy metal, and mercury poisoning is known as acrodynia or pink disease. Similarly, lead, another toxic heavy metal, was at one time an integral part of painting. Metal Toxicology Handbook further explains and discusses the varying attributes of metals, discussing toxicity, safety, and proper human utilization of metals. Beginning with a broad overview of metals, metalloids, redox biology, and neurodegeneration and going further into the roles, benefits, and toxicity of metals with each section, the text contains 28 chapters from eminent researchers and scientists in their respective fields and is a must-have for anyone researching the potential toxicity in metals. Key Features Discusses the pathology of metal toxicity Highlights the benefits of metals Explains the mechanism and salient features of restoring metabolic homeostasis Highlights dose-dependent beneficial and adverse effects of vanadium safety and toxicity The initial introductory section provides a broad overview of metals, metalloids, redox biology, and neurodegeneration. The second section discusses the pathology of metal toxicity in two chapters, while the third section highlights the mechanism and salient features of restoring metabolic homeostasis in two chapters. The fourth section demonstrates the aspect of radionuclides toxicity. In a change of pace, the fifth section discusses the benefits of metals in four chapters. The sixth section, titled "Toxic Manifestations by Diverse Heavy Metals and Metalloids," provides fourteen chapters that discuss the toxicological mechanism and manifestation of individual metals. The editors have crafted a commentary titled "A Treatise on Metal Toxicity" and summarized a vivid scenario of metal toxicity and its consequences.

An insight into new advances of current interest in metal toxicology, such as mechanisms important in risk-assessment for human health. The book also has chapters on emerging conceptual problems including resistance to metal toxicity effects on gene expression, alongside principles regarding drug-chelation of metals, the potential use of prophyrins as indicators of metal exposure and toxicity. The toxicology of specific metals of major public health concern are discussed in depth, such as mercury, aluminum, arsenic, chromium, and cadmium. Of interest to basic scientists as well as public health administrators.

Generally, the assessment of hazard and risk to humans that might arise from exposure to chemical substances is based on the extrapolation from data generated in studies with experimental animals. The assumption is made that the effects observed in the animals would also be expressed in humans and, to account for uncertainties including intra- and interspecies variability, and more recently susceptible human subpopulations, assessment factors are applied in deriving 'safe' exposures for humans. This is usually done without testing the hypothesis in humans, as the default approach allows for humans to be more sensitive than the most susceptible animal species. However, for those substances where humans are not sensitive to the effects seen in the animal studies, this approach is conservative and may result in risk management measures being taken that are totally unwarranted. An alternative approach is proposed in this report for the evaluation of such substances. The view has been expressed by many leading researchers and regulatory organisations that an understanding of the molecular and cellular processes underlying toxicity and carcinogenicity allows a more scientifically-based risk assessment and, where such information is available and adequate, this should replace default approaches in assessing human risk. All mechanisms of toxicity can be described in terms of a sequence of events, each of which is critical to the manifestation of the toxic endpoint. To elucidate such a mechanism requires rigorous investigation to obtain a complete and detailed understanding of the process leading to a toxic effect. However, the complete elucidation of all the events leading to the effect is not essential for evaluating the species differences in sensitivity to a toxicant. To achieve this we can restrict our understanding to selected key events within the complete sequence of events. This concept, termed the 'mode of action' can be used for the evaluation of species specificity including human susceptibility. If it could be shown that one or more of the key events could not occur in humans, or could only occur to a much lesser extent, it could be assumed that the mode of action of the substance in question was not relevant to the assessment of human risk. In such cases departure from the default approach would be justified. This philosophy is illustrated by a number of well-studied examples for which the modes of action and corresponding key events have been established for effects that are not relevant to humans. A structured two-step 'mode of action' approach was developed to guide the evaluation of substances expressing toxicity suspected as being species-specific and of questionable relevance to humans. Advice is given on how to identify the key events in the mode of action of the toxicological effect, how to test the strength of the data on which the mode of action hypothesis is based and how to establish its relevance to humans. The extent to which new data will be required to associate a substance with an established mechanism of toxicity or mode of action will vary, depending on the existing knowledge of the role of toxicokinetics and toxicodynamics and of the understanding already available within that class of chemicals. The use of this approach to identify those substances which express toxicity in experimental animals via a mode of action that is not relevant to humans will enable a more scientifically objective assessment of risk in humans. Furthermore, adopting a 'mode of action' approach should considerably speed up the risk assessment process and avoid unnecessary animal experimentation. [Editor]