Cancer Risk Assessment: Chemical Carcinogenesis, Hazard Evaluation, and Risk Quantification

Article excerpt

Humans can be exposed to a panoply of agents and actions including chemicals, nanomaterials, metals, and complex mixtures. The link between these exposures and possible clinical sequelae including cancer is often poorly understood. Historically, regulators have addressed such uncertainty by applying linear low-dose defaults when establishing cancer risk estimates for suspected or known carcinogens. However, in recent years, cancer risk assessments have become increasingly sophisticated. An important component of this increased sophistication is the relatively new ability to consider the mode of action by which a substance might exert procarcinogenic, anticarcinogenic, or neutral effects. Knowledge regarding the mode of action can elucidate the relevance to human health associated with the particular exposure. In addition, technological advances in molecular biology and computational analyses increasingly contribute to screening for the potential for substances to cause cancer, or to inform particular areas of risk assessments. Cancer Risk Assessment provides an excellent synthesis of the aforementioned topics, as well as others essential for students becoming acquainted with the field or practitioners struggling to stay abreast of the rapid pace of emerging concepts in the literature.

This carefully edited book represents a multiauthor compilation of chapters contributed by well-known experts in the field. The author roster is well-balanced across all sectors of the scientific community, with primary contributions from academia, consulting companies, and government agencies. The book is divided into six major parts presented in a logical format and amenable to the classroom setting or individual study.

A historical and current overview of cancer risk assessment is provided in Part I. The science and regulatory processes that lead to policy decisions are discussed, along with shaping chemical-control frameworks such as the European Commission's Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation.

Part II begins with a historical account of cancer, followed by advances in the cell biology of cancers. The classic and mechanistically groundbreaking studies on polycyclic aromatic hydrocarbons (PAHs) are used to convey critical concepts on multistage carcinogenesis, including initiation, promotion, and progression. From there, specific types of dose--response relationship, such as the sometimes controversial hormesis mechanism and always controversial biological thresholds for genotoxic carcinogens, are discussed, thereby supplementing the understanding of these latter critical concepts.

Part III focuses on specific types of genotoxicity testing. Although methodological and analytical aspects of this topic have been addressed extensively in available books, Cancer Risk Assessment provides the finest presentation I have seen on regulatory aspects of genotoxicity, specific genotoxicity assays, and interpretative guidance for the various assays. The wealth of information conveyed on this important topic alone justifies purchasing this book.

In Part IV, the reader is introduced to a specific framework for analyzing mode of action and human relevance of chemical-induced tumors. Specific examples are discussed, including PPAR-[alpha] and liver tumors, [[alpha].sub.2u]-globulin nephropathy, chronic progressive nephropathy, and urinary tract calculi and bladder tumors. …