Harvey Joseph Clewell III is a Principal Consultant with Ramboll who is located in North Carolina, USA. He has more than 40 years of experience in environmental quality research, toxicology research, chemical risk assessment, and hazardous materials management, and has authored more than 200 peer-reviewed scientific publications and book chapters. Dr. Clewell has gained an international reputation for his work on the incorporation of mechanistic data and mode of action information into chemical risk assessments, having played a seminal role in the first uses of physiologically based pharmacokinetic (PBPK) modeling in cancer and non-cancer assessments by the EPA, FDA, ATSDR, OSHA and Health Canada. He is also an expert in the use of cellular genomic response data to inform the mode of action for chemical toxicity and to determine alternative points of departure for risk assessments. Dr. Clewell served on the external peer review panels for the EPA guidelines on development of reference concentrations, cancer risk assessment, risk characterization, benchmark dose modeling, PBPK modeling and dermal absorption, and has also participated in many chemical-specific reviews conducted by the EPA Scientific Advisory Board and the FIFRA Scientific Advisory Panel. In 2007 the Society of Toxicology recognized Dr. Clewell with the Arnold J. Lehman Award for his major contributions to chemical safety and risk assessment. He has served as a member of the ECVAM Scientific Advisory Committee from 2012 to 2016, and as a member of the Chemical Assessment Advisory Committee of the EPA’s Scientific Advisory Board from 2019 to 2020.
Progress and difficulty in gaining regulatory acceptance of PBPK modeling and mechanism of toxicity in risk assessments
The practice of risk assessment, like the science of toxicology upon which it relies, is in a continuous process of evolution and refinement. As new experimental methods become available that show a potential to more accurately or efficiently characterize the toxicity of chemicals, they must be carefully evaluated by both scientists and regulatory officials to ensure they are an effective and reliable alternative to traditional approaches. Physiologically Based Kinetic (PBK) modeling is one of the more mature New Approach Methods, having been applied in regulatory decisions for nearly 40 years, and yet gaining regulatory agency acceptance of the use of a PBK model in a regulatory decision is still fraught with difficulty. This presentation will describe a number of recent modeling efforts that were conducted to foster the application of PBK in chemical risk assessments, and will discuss some of the factors that can make the regulatory acceptance of such applications so problematic.