Figure 5.

Chemical-specific EAD predictions compared with oral LELs. EAD values (mg/kg/d) were predicted from ${\text{ACC}}_{\text{ER}}$ using ${\text{GP}}_{\text{oral}}$ (square), ${\text{HT}3\mathrm{C}}_{\text{oral}}$ (triangle) and PPK models (circle) with EF or ${\mathrm{f}}_{\mathrm{u}}$ adjustments were plotted against the median or mean (if only two studies), highest, and lowest LELs (mg/kg/d) from uterotrophic oral studies for 8 chemicals. The dashed line highlights the range from lowest ( “$+$”) to highest (“x”) LELs of all guideline-like uterotrophic oral studies. The chemicals are ordered from left to right based on their median or mean (if only two studies) LEL values, from low to high. Data for this figure are provided in Excel Table S1. ${\text{ACC}}_{\text{ER}}$, pseudo median activity concentration at cutoff from estrogen receptor pathway model; ${\text{CL}}_{\text{int}}$, intrinsic clearance ($\mathrm{L}/\mathrm{h}$); EAD, equivalent administered dose; EF, enrichment factor; ${\mathrm{f}}_{\mathrm{u}}$, fraction of chemical unbound to plasma protein; LEL, lowest effect level; ${\text{GP}}_{\text{oral}}$, PBPK model built using GastroPlus™ software simulating oral exposure; ${\text{HT}3\mathrm{C}}_{\text{oral}}$, the httk “3compartment” model simulating oral route of exposure; PPK, one-compartment population-based pharmacokinetic model.