Table 2: Anatomical, physiological, and kinetic constants and parameters used in the PBPK model.


Molecular mass m-xylene (g/mol)MWxyl106.17
Molecular mass MHA (g/mol) MWMHA193.2
Body mass (kg)BWNormal BW~N(76.2, (8.73)2)
Vascularised tissue (proportion of body mass)VT0.91
Cardiac output (L h−1 BW−0.75)QCCNormal QCC~N(13.8, (2.5)2)
Metabolism (Liver)
In vitro Michaelis constant (mMol L−1)KMNormal KM ~N(11.8, (1.4)2)
In vitro maximum rate of metabolism (pmol min−1 mg−1
 microsomal protein)
𝑉 m a x Normal 𝑉 m a x N (895, (68)2)
 Microsomal protein yield per gram wet weight liver (mg g−1)MPYLognormal ln (MPY)~N(3.7, (2.9)2)
Gas exchange
 Respiratory rate (L h−1)QPC Normal QPC~N(390.4, (54.9)2)
 Respiratory dead space (proportion respiratory rate)DS0.3
Partition coefficient
 Blood : air partition coefficientPbaNormal Pba~N(18.5, (4.9)2)
 Rapidly perfusedPrpdaUniform Prpda~U(50–150)
 Slowly perfusedPspdaUniform Pspda~U(40–80)
 AdiposePfaa Uniform Pfaa~U(1400–2200)
 LiverPliaUniform Plia~U(150–350)
Tissue blood flow as a fraction of cardiac output
 Rapidly perfusedQrpdC0.48
 Slowly perfusedQspdC0.22Uniform QspdC~U(0.2–0.35)
 AdiposeQfaC0.05Normal QfaC~N(0.053,(0.003)2)
 LiverQliC0.25Normal QliC~N(0.271,(0.01)2)
Tissue mass as a fraction of body mass
 Rapidly perfusedVrpdC0.09
 Slowly perfusedVspdC0.604
 AdiposeVfaC0.19Lognormal ln(VfaC)~N(−1.59,(−2.88)2)
 LiverVliC0.0257Normal VliC~N(0.036,(0.01)2)
Bladder compartment
 Rate of urine production (L h−1) Rurine0.07Normal R u r i n e N (0.083,(0.021)2)
 Urinary creatinine concentration (mmol L−1)CRE12.5Normal CRE~N(12.5,(2.7)2)
 First-order elimination rate constant (h−1)K1Uniform K1~U(5–20)