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Using exposure prediction tools to link exposure and dosimetry for risk based decisions: a case study with phthalates
Moreau, M., J. Leonard, K. Phillips, J. Campbell, S. Pendse, C. Nicolas, M. Phillips, M. Yoon, C. Tan, S. Smith, H. Pudukodu, K. Isaacs, AND H. Clewell. Using exposure prediction tools to link exposure and dosimetry for risk based decisions: a case study with phthalates. 2017 SOT Annual Meeting, Baltimore, MD, March 12 - 16, 2017.
This case study highlights the utility of the reverse dosimetry module in the Population Life-course Exposure to Health Effects Modeling (PLETHEM) as an adaptable and flexible testing platform to evaluate linkages between exposure to environmental chemicals and human biomarkers
The Population Life-course Exposure to Health Effects Modeling (PLETHEM) platform being developed provides a tool that links results from emerging toxicity testing tools to exposure estimates for humans as defined by the USEPA. A reverse dosimetry case study using phthalates was conducted to demonstrate the utility of this platform in evaluating relationships between biomarker levels and human exposures. Data on mono-2-ethylhexyl phthalate (MEHP) and monobutyl phthalate (MBP) metabolites from NHANES (2011-2012) was converted to intake estimates for di-2-ethylhexyl (DEHP) and dibutyl (DBP) phthalates, respectively, using a reverse dosimetry approach. The previously developed physiologically based pharmacokinetic (PBPK) models for DEHP and DBP included their metabolites, MEHP and MBP for the current analysis. Daily estimated intakes corresponding to the 50th, 95th and 99th percentiles of mono-ester metabolites in urine from PBPK-reverse dosimetry were 0.73, 9.32 and 27.38 µg/kg-day and 0.089, 0.68 and 1.88 µg/kg-day for DEHP and DBP, respectively. Our PBPK-reverse dosimetry based exposure estimates were compared to predictions from two high throughput (HT) exposure models: the Stochastic Human Exposure and Dose Simulation (SHEDS-HT) and ExpoCast. For DEHP, our median is higher than the ExpoCast estimate (0.17 µg/kg-day), while the 95th percentile values are similar (12 µg/kg-day from ExpoCast). For DBP, our estimated median value is similar to that predicted by the ExpoCast, but our predicted value at the 95th percentile was lower than the predictions from ExpoCast and SHEDS-HT (6.13 and 13.7 µg/kg-day, respectively). Our predicted median intake for DEHP was also comparable to estimates from non-HT tools, ranging from 0.78 to 1.1 µg/kg-day. These comparisons provide insights into the different exposure prediction tools that can be incorporated into PLETHEM. This case study highlights the utility of the reverse dosimetry module in PLETHEM as an adaptable and flexible testing platform to evaluate linkages between exposure to environmental chemicals and human biomarkers (supported by ACC-LRI). Disclaimer: This abstract has been cleared by the EPA but solely expresses the view of the authors.