The Eminent Toxicologist Lectures are historically relevant, high-quality presentations appropriate for senior undergraduate students, graduate students, or the scientifically oriented general public. This series of lectures is produced by the SOT Undergraduate Subcommittee of the Education Committee in conjunction with the Eminent Toxicologist Working Group.
A bioassay was published in 1966 relying upon the respiratory reflex reactions due to stimulation of TNE during exposure to airborne chemicals, making it possible to measure the potency (abbreviated as RD50) of any airborne chemical as a sensory irritant. An excellent correlation between RD50 values and TLV values was demonstrated as the number of chemicals evaluated with this bioassay increased. In 2015, a QSAR was published using a database of RD50s for 145 chemicals, with excellent results. These updates should permit obtaining reliable estimates of TLVs for new chemicals prior to introducing them in the workplace, as well as for storing and transporting them.
Lecture Notes and Learning Objectives
“QSARs to Commemorate the Fiftieth Anniversary of the RD50” Recording
“QSARs to Commemorate the Fiftieth Anniversary of the 50” Slides
Table 1 2015 Update of the 1993 Schaper Database of RD50 and Their TLV
Table 2 2015 List of TLVs for Chemicals with URT Irritation Basis with No RD50 Values
Yves Alarie, PhD, DABT, ATS, is Professor Emeritus of the Environmental and Occupational Health Department, Graduate School of Public Health, University of Pittsburgh. In 1963 he received the PhD in Physiology from the Département de Physiologie, Faculté de Médecine, Université de Montréal. At the Hazleton Laboratories in Falls Church, Virginia, he developed the “mouse bioassay” or the “RD50 method” used to screen and evaluate the potency of airborne chemicals as sensory irritants. The method was widely used and tabulations of RD50 values are the largest published databases in inhalation toxicology. After joining the University of Pittsburgh in 1970 his research continued on the effects of inhaled chemicals at the surface of the respiratory tract, from the tip of the nose to the alveolar level. He published extensively on the use of animal models to estimate safe levels of exposure for airborne chemicals of industrial importance as well as investigating toxicity of smoke produced in fires and on the cause(s) of death in fire victims. He joined SOT in 1968 and received the SOT Achievement Award (1971), the Frank Blood Award (1974, 1981), the Enhancement of Animal Welfare Award (2000), and the Career Award from the Inhalation Section of SOT (2004).
This lecture examines my experience using quantitative models for understanding dose-response relationships, as well as touching on pharmacokinetics, pharmacodynamics, and new directions in cell pathway based models. Instead of postdoctoral work on shark hemoglobin, military service directed me to assess the toxicity of chemicals found onboard nuclear submarines. Training in modeling small and large molecule kinetics led me to question why probit analyses were used for dose response, why the logarithm of inhaled concentration is a measure of dose, and what is the relationship expected between inhaled concentration and chemical in tissue or between the amount of chemical and response? The main lessons of a long career are that models require us to state our ideas clearly and quantitatively and then to see if our ideas are correct or in need of revision. The use of these models repeatedly shows that it is even more important to know our ideas are wrong than simply to think they might be right.
Lecture Notes and Learning Objectives
“45 Years Modeling Dose-Response Relationships: An Unanticipated Career!” Recording
“45 Years Modeling Dose-Response Relationships: An Unanticipated Career!” Slides
Melvin Andersen, PhD, DABT, CIH, ATS, is Distinguished Research Fellow at ScitoVation LLC, Research Triangle Park, North Carolina. Previously, he was at The Hamner Institutes for Health Sciences. Over a 45-year career, he worked in government (US Navy, DoD, US EPA), industry (Chemical Industry Institute of Toxicology), academia (Colorado State University), and consulting (ICF Kaiser Consulting). Dr. Andersen introduced physiologically-based pharmacokinetic (PBPK) modeling. Other long-term interests include biologically realistic models of the uptake, distribution, metabolism, and biological effects of drugs and toxic chemicals and applying these models in safety assessments and quantitative health risk assessments. Dr. Andersen has mentored 13 graduate students and 13 postdoctoral researchers and served on an additional 11 graduate student research committees. He has served on or chaired many regulatory review panels, both domestic and international, regarding chemicals of environmental interest, including contributing to the 2007 National Academy of Sciences report “Toxicity Testing in the 21st Century: A Vision and a Strategy.” Author/co-author of 400 peer reviewed publications, 70 book chapters, and 30 technical reports, his work has more than 18,000 citations. He has received numerous SOT awards including the Frank Blood, Achievement, Arnold J. Lehman, Best Paper of the Year in Toxicological Sciences, and Merit.
John Doull, MD, PhD, FAACT, ATS, is Professor Emeritus of Pharmacology and Toxicology at the University of Kansas Medical School. A charter member of SOT, he was 1986–1987 President and has received numerous awards in recognition of his important and extensive contributions to toxicology. Among the SOT awards are the Merit Award (1993), the Founders Award (2008), and the John Doull Award (1992). He has also received the ATS Mildred Christian Achievement Award (2013), the Samuel Kuna Award (1989) from Rutgers University/Robert Wood Johnson Medical School, the International Achievement Award (1990) from the International Society for Regulatory Toxicology and Pharmacology, the Commanders Award for Public Service (1990) from the Department of the Army, the Distinguished Medical Alumnus Award (1992) from the University of Chicago, the Stockinger Award (1990)from the American Conference of Governmental Industrial Hygienists, the Founder's Award from CIIT (1996), the Meritorious Service Award from ACGIH, and the Distinguished Service Award from the American College of Toxicology.The founding co-editor of Casarett and Doull’s Toxicology: The Basic Science of Poisons, he has served on scientific advisory boards for Congress, the White House, NRC, NIH, EPA, NIOSH, and many others and consults with many organizations. He is a national associate of the National Academies.
For several decades mechanistic toxicology has relied on the use of surrogate animals with extrapolation to humans, an approach followed for many years by the author. However, new paradigms for human health risk assessment require biochemical and molecular studies carried out on human materials. Considering toxicity as a consequence of a cascade of events starting with exposure and ending with the expression of a toxic endpoint, it is clear that not only is gene expression an important endpoint but knowledge of metabolism and metabolic interactions are critical to understanding the entire process in humans. Metabolic studies utilizing human liver cell fractions were carried out on a number of agrochemicals, including insecticides such as chlorpyrifos, fonofos, and fipronil, as well as the repellent DEET and the diesel fuel component naphthalene. The most striking interaction based on inhibition is the inhibition of steroid hormone metabolism in hepatocytes by chlorpyriphos. Interactions based on induction included the induction of CYP isoforms by, for example, fipronil, DEET, and endosulfan. Effects on gene expression by DEET and fipronil were studied by microarray and RNAseq techniques. Throughout all of the studies human variation was studied by utilizing hepatocytes and hepatocyte fractions from different donors.
Lecture Notes and Learning Objectives
“We Are Not Rodents: Environmental Toxicants and the Role of Human Studies” Recording
“We Are Not Rodents: Environmental Toxicants and the Role of Human Studies” Slides
Ernest Hodgson, PhD, is Distinguished Professor Emeritus, Environmental and Molecular Toxicology and the Department of Applied Ecology, North Carolina State University, Raleigh. He received his PhD from Oregon State University and his postdoctoral research was at the University of Wisconsin, Madison. He is renowned for research in the metabolism of toxicants in the human liver, especially human metabolism of agrochemicals. In addition to editing and part-authoring two textbooks of toxicology and contributing to a variety of review books, dictionaries, and electronic databases, Dr. Hodgson is editor of the Journal of Biochemical and Molecular Toxicology. He has contributed to the education of numerous toxicologists; former students and postdocs are distributed among a variety of academic, industrial, and government positions. He serves on advisory committees and review panels. Significant recognition at his own institution is his being named to the prestigious endowed William Neal Reynolds Professorship. Recognition from the Society of Toxicology includes the Education (1984), Merit (1994), and Distinguished Toxicology Scholar (2012) Awards. Other major awards include the Baxter, Burdick & Jackson International Award and Sterling Hendricks Award (American Chemical Society, 1989, 1997) and the Frederick J. DiCarlo International Service Award (International Society for the Study of Xenobiotics , 2004).
Curtis D. Klaassen, PhD, DABT, ATS, was a Distinguished Professor at the University of Kansas Medical Center and was instrumental in establishing his department as one of the top departments for research and training in toxicology in the world. Dr. Klaassen’s research interests have centered on how we adapt to chemicals in the environment. His studies have included the hepatobiliary disposition of xenobiotics, the toxicity of cadmium, the hepatotoxicity of chemicals, and mechanisms of chemical-induced thyroid tumors. Dr. Klaassen is editor of Casarett and Doull’s Toxicology: The Basic Science of Poisons, considered the premier textbook in the field. He has twice been named a “Highly Cited Researcher” (2002, 2007) by the Institute for Scientific Information, a designation held by less than one half of one percent of all researchers. He has been elected to 27 different positions in professional organizations, including President of SOT from 1990–1991 and President of IUTOX 1992–1995. An SOT member since 1969, his Society recognition includes the Achievement Award, Merit Award, Education Award, the Burroughs Welcome Toxicology Scholar Award, the Women in Toxicology Mentoring Award, and numerous Regional Chapter and Specialty Section awards.
Dr. Nancy Monteiro-Riviere introduces the exciting field of nanotechnology which has been transforming many aspects of everyday life, ranging from cosmetics and sunscreens to new electronics and nanomedicines. Nanomaterials are substances less than 100nm in size that exhibit physical, chemical, and /or biological characteristics associated with the nanostructure. This lecture focuses on how the safety of these novel nanomaterials is vastly different from traditional chemicals and drugs. Because the skin is the major route of exposure where many nanomaterials interact with the body, her research focuses on this organ. The role of the physicochemical parameters that modify cellular uptake and lead to biomolecular corona formation and interactions with cells are discussed. Having worked in this field since its inception now over a decade ago, she tracks how the latest techniques in cell culture, in vitro absorption systems, biomarkers, electron microscopy, analytical chemistry, and animal model development have been applied to this problem with varied levels of success.
Nancy Monteiro-Riviere, PhD, ATS, is the Regents Distinguished Research Scholar and University Distinguished Professor and Director of the Nanotechnology Innovation Center of Kansas State. Previously she was Professor of Investigative Dermatology and Toxicology at North Carolina State University (NCSU), Professor in the Joint Department of Biomedical Engineering at UNC-Chapel Hill/NCSU, and Research Adjunct Professor of Dermatology at UNC-Chapel Hill School of Medicine. Her research interests involve in vivo and in vitro studies of skin absorption, penetration, and toxicity of chemicals, nanoparticles, biocorona uptake, and cellular responses. Editor of three books and author of 300 manuscripts, she appears on Thomson Reuters’s 2014 list of the top 1% most highly cited researchers in pharmacology and toxicology. Dr. Montiero-Riviere serves on national and international expert review panels as well as having editorial duties for eight journals. Her awards include the Purdue University Inaugural Distinguished Women Scholars Award and KSU Woman of Distinction. SOT service includes the Nomination Committee (2001–2002), the Board of Publications, and President of Dermal (2004–2005) and In Vitro (2001–2002) Specialty Sections. Dr. Monteiro-Riviere is a Fellow in The Academy of Toxicological Sciences and elected to its Board of Directors.
Lecture Notes and Learning Objectives
“Environmental Epigenomics: The Developmental Origins of Health and Disease” Recording
“Environmental Epigenomics: The Developmental Origins of Health and Disease” Slides