Evaluation of the Relationship Between Exposure Estimates and Measured Biomarkers forPersistent Lipophilic Chemicals, Non-Persistent Chemicals and Cumulative Exposures
Jerry Campbell, Harvey J. Clewell, III, Barbara A. Wetmore, and Cory Strope. ScitoVation.
Risk assessors have traditionally addressed exposure to health outcomes separately with a reliance on conservative default assumptions often leading to an overestimation of exposure. A tool that allows correlation of an exposure assessment with biomonitoring data will provide a scientifically defendable assessment that reduces uncertainty in the estimation of risk from exposure, transitioning regulators away from a reliance on default assumptions and standard modifying factors. The Population Life-course Exposure to Health EffectsModel (PLETHEM) software platform will allow the incorporation of in silico, in vitro and population based biomonitoring data along with the physiological changes that occur throughout life to provide a realistic assessment of the relationship between contact with chemicals in our environment and target tissue dosimetry in addressing potential for adverse outcome.
This project ispart of the initial development ofthe Population Life-course Exposure to Health EffectsModel (PLETHEM) software platform (see abstract for project IP-I) that will allow quantitative source to outcome assessmentof chemicals. This project was developed to support collaboration between ScitoVation and U.S. Environmental Protection Agency (EPA) personnel in developing and validating the platform. Currently, there is an ongoing effort to collectthe information necessary to generate the exposure estimates based on the interpretation ofpopulation biomonitoring data. Additionally, one of the current topics under investigation is the most appropriate method for scalingurinary excretion within a population. Recently published data indicates that traditional body weight scaling of urinary production might not provide the most accurate picture of mass excreted asurine flow rates and bodyweight adjusted urinary flow rates exhibit systematic variations withage/ sex/ race/ethnicity as well as body mass index(Hays et al., 2015). The impact ofthis analysis will beimportant as we move forward with the reverse dosimetry of short and intermediate half-lifecompounds.
Implications:Without a tool to aid in the evaluation of exposure to health outcome, uncertainty in risk assessment will remain firmly rooted in the 20th century and fail to adapt to NexGen approaches. As data from in vitro testing efforts gains acceptance, an accompanying strategy that facilitates the incorporation of target tissue kinetics and reverse dosimetry with in vitro datasets is required. Such a quantitative and translational tool will allow us to bridge the gap between the nominal in vitro assay concentrations and ultimate prediction of potential risk to a population.
Collaborations: USEPA – National Exposure Research Laboratory and National Center for Computational Toxicology; ACC LRI-funded ExpoDat investigators
Key words:PLETHEM, lifestage model, reverse dosimetry
Projectstartandend dates:January 2015 – December 2016
Peer-reviewed publication(s): None to date
Otherpublication(s): None to date
Abstractcreationdate:February 2016
This abstract was prepared by the principal investigator for the project. Please see for more information about the LRI.