We Are Not Rodents: Environmental Toxicants and the Role of Human Studies

Speaker: Ernest Hodgson, PhD
North Carolina State University, Raleigh

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.

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 was produced by the Education Committee Undergraduate Subcommittee in conjunction with the Eminent Toxicologist Working Group.