Table 1.

Test cases using PBPK modeling

Case Study Chemicals	Species	Modeling Purposes
Test Case 1: Hypothetical chemical A	Rat	Evaluate the internal to external (IEC) relationship for the parent assuming a wide range of: tissue:blood partition coefficients (Figure 2) metabolism parameters (maximum rate, half maximal constant) (Figures 3A–C) parameters for saturable fraction of oral absorption (Figure 3D)
Test Case 2: Hypothetical chemicals A, B	Rat	Simulate the IEC relationships for both the parent and the metabolite, assuming: metabolism of the parent as first-order or saturable (Figures 4A, B) urinary excretion of the parent as first-order or saturable (Figures 4C, D) urinary excretion of the metabolite as first-order or saturable (Figures 4E, F) both metabolism of the parent and urinary excretion of the metabolite as saturable (Figure 5)
Test Case 3: Hypothetical chemicals C, D	Rat	Simulate the IEC relationships for both the parent and the metabolite, assuming first-order or saturable oral absorption (Figure 6)
Test Case 4: Styrene	Rat	Compare the IEC relationships across: species (Figure 7A) oral and inhalation routes (Figure 7B) exposure frequency (number of doses per day) (Figure 7C)
	Human	Compare the IEC relationships across: species (Figure 7A) exposure duration (hours of inhalation exposure per day) (Figure 7D) Compare the estimated air concentrations with the simulated IEC relationship
Test Case 5: Caffeine	Human	Compare the IEC relationships between oral and dermal exposures (Figure 8) Compare the estimated human exposures to caffeine with the simulated IEC relationship
Test Case 6: 2,4-D	Rat	Analyze the proportionality of the IEC relationship based on plasma AUCs measured at multiple external concentrations (Figure 9)