In 2000 OpdenKamp Registration & Notification organized a two-day symposium in The Hague, The Netherlands, on `The Practical Applicability of Toxicokinetic Models in the Risk Assessment of Chemicals'. Several speakers from Europe and the United States were invited to present the different aspects. A vast range of areas was discussed in relation to toxicological modeling and risk assessment, such as occupational toxicology and biomonitoring, exposure to organic solvents and crop protection products, dose-response relations in carcinogenicity, regulatory toxicology, estimation of dermal penetration, uptake and disposition of organic chemicals in fish, the possibilities of in vitro methods in hazard and risk assessment, and the extrapolation between animal and human species. Based on their presentations, the speakers prepared comprehensive papers for this symposium book, reflecting the state of the art of modeling and toxicological risk assessment at the beginning of the third millennium.

Toxicokinetics in Risk Assessment discusses the noncancer risk assessment process and its reliance on uncertainty factors in order to facilitate the continued study and refinement of the scientific basis for health risk assessment. This text clearly demonstrates the application of physiologically-based pharmacokinetic (PBPK) modeling in human healt

Unlike many existing books on toxicology that cover either toxicity of a particular substance or toxicity of chemicals on particular organ systems, Toxicological Risk Assessment of Chemicals: A Practical Guide lays out the principle activities of conducting a toxicological risk assessment, including international approaches and methods for the risk

The book contains the contributions at the NATO Study Institute on Exposure and Risk Assessment of Chemical Pollution – Contemporary Methodology, which took place in Sofia – Borovetz, Bulgaria, July 1–10, 2008. Rapid advances in mathematics, computer science and molecular biology and chemistry have lead to the development in of a new branch of toxicology called Computational Toxicology. This emerging field is addressing the estimation and prediction of exposure risk and effects of chemicals based on experimental data, measured concentration and biological mechanisms and computational models of biological systems. Mathematical models are also being used to predict the fate and transport of substances in the environment. Because this area is still in its infancy, there has been limited application from governmental agencies to regulating controllable processes, such as registration of new chemicals, determination of estimated exposure and risk based limits and maximum acceptable concentrations in different compartments of the environment – ambient air, waters, soil and food products. However, this is soon to change as the ability to collect, analyze and interpret the required information is becoming increasingly more efficient and cost effective. Full implementation of the new processes have to involve education on both part of the experimentalists who are generating the data and the models, and the risk assessors who will use them to better protect human health and the environment.

This thesis presents the development, evaluation, and application of a generalized toxicokinetic model for mixtures of chemicals. Humans are exposed to mixtures of chemicals that are found together in multiple exposure media (soil, food, and air), and at levels that have been shown to cause adverse effects due to toxic interactions. Although several physiologically based toxicokinetic (PBTK) models exist for different environmental chemicals, using them in assessing risks to co-occurring contaminants is often impractical. This is especially true for the case of toxic metals, where half-lives in the human body span days (e.g. arsenic), months (e.g. methylmercury), and decades (e.g. lead, cadmium). Several differences in the formulation of these models exist with respect to (a) physiological structure (e.g. body tissue volumes and blood flow ratios), (b) general modeling assumptions (e.g. for transport and transformation of the chemicals within the body), and (c) exposure-relevant parameters. Since assumptions made for one metal or metal compound can be incompatible with the assumptions made for another metal, current formulations are inadequate for use in assessing health risks from mixtures of toxic metals. Further complications arise when assessing risks of both metals and nonmetals, which also interact at the toxicokinetic and toxicodynamic levels. The issues of consistent representation of physiology and chemical interactions across different classes of chemicals such as mixtures of metals and mixtures of metals and organics are addressed through the development of a Generalized Toxicokinetic Model for Mixtures of chemicals (GTMM). The GTMM resolves inconsistencies by standardizing the physiology across all models, and by allowing simulations of different models to be done simultaneously. It has been implemented as a set of modules in Matlab and as a user-oriented graphical interface in Matlab-Simulink. The GTMM has been evaluated with multiple existing PBTK models for individual chemicals, and the results demonstrate that the GTMM produces identical results as the original published formulations. Subsequently, the GTMM has been applied to different problems relevant to population risk assessment.

In 2007, the National Research Council envisioned a new paradigm in which biologically important perturbations in key toxicity pathways would be evaluated with new methods in molecular biology, bioinformatics, computational toxicology, and a comprehensive array of in vitro tests based primarily on human biology. Although some considered the vision too optimistic with respect to the promise of the new science, no one can deny that a revolution in toxicity testing is under way. New approaches are being developed, and data are being generated. As a result, the U.S. Environmental Protection Agency (EPA) expects a large influx of data that will need to be evaluated. EPA also is faced with tens of thousands of chemicals on which toxicity information is incomplete and emerging chemicals and substances that will need risk assessment and possible regulation. Therefore, the agency asked the National Research Council to convene a symposium to stimulate discussion on the application of the new approaches and data in risk assessment. The symposium was held on May 11-13, 2009, in Washington, DC, and included presentations and discussion sessions on pathway-based approaches for hazard identification, applications of new approaches to mode-of-action analyses, the challenges to and opportunities for risk assessment in the changing paradigm, and future directions.

Risk management is especially important for military forces deployed in hostile and/or chemically contaminated environments, and on-line or rapid turn-around capabilities for assessing exposures can create viable options for preventing or minimizing incapaciting exposures or latent disease or disability in the years after the deployment. With military support for the development, testing, and validation of state-of-the-art personal and area sensors, telecommunications, and data management resources, the DOD can enhance its capabilities for meeting its novel and challenging tasks and create technologies that will find widespread civilian uses. Strategies to Protect the Health of Deployed U.S. Forces assesses currently available options and technologies for productive pre-deployment environmental surveillance, exposure surveillance during deployments, and retrospective exposure surveillance post-deployment. This report also considers some opportunities for technological and operational advancements in technology for more effective exposure surveillance and effects management options for force deployments in future years.