Using human data to protect the public's health

The value of using human data in the assessment and management of risk is evaluated. Although the use of such data has a long and successful history with environmental contaminants and the development of drugs and commercial chemicals, recent deliberations within the Environmental Protection Agency (EPA) have questioned this practice in part. Specifically, we evaluate the degree to which reference doses (RfDs) and reference concentrations (RfCs) derived from human data on EPA's Integrated Risk Information System (IRIS) differ with RfDs and RfCs that we estimate from experimental animal data. We also use several minimal risk levels of the Agency for Toxic Substances and Disease Registry (ATSDR) and tolerable intakes of Health Canada in this comparison. Human-based RfDs are more than threefold lower than the corresponding animal-based RfDs for 23% of the comparisons. Human- based RfDs or RfCs are lower than corresponding animal-based RfDs or RfCs for 36% of the comparisons. Furthermore, for 10 of 43 possible comparisons, insufficient experimental animal data are readily available or data are inappropriate to estimate either RfDs or RfCs. We also discuss human pharmacokinetic data from volunteer studies and mechanistic studies with human tissues in vitro and demonstrate through a series of case discussions that utilization of such data is important when making decisions to protect exposed individuals. Moreover, physiologically based pharmacokinetic (PBPK) modeling evaluates critical information in assessing interindividual variability and identifying at-risk populations. Within the limits of our analysis, we conclude that the direct use and interpretation of human data, in conjunction with data gathered from experimental animals, are public health protective policies that should be encouraged.