Available kinetic models

Physiologically based kinetic (PBK) models, or kinetic models for short, are mathematical representations of the animal or human body aimed at describing and predicting the time course distribution of chemicals in tissues and organs. Those internal dose metrics can usefully replace external exposure dose in the derivation of the quantitative dose-response relationships and following risk assessments. PBK models can simulate both internal doses from exposure scenarios (forward dosimetry) and external dose from biomonitoring data (reverse dosimetry).

The following generic PBK models are currently implemented in MCRA:

• EuroMix generic PBK model (Tebby et al. (2020)).

• bisphenol PBK model ETHZ (Karrer et al. (2019)).

The MCRA interface allows to run PBK models for any number of days and supplies an option to skip an initial number of days (build-up phase PBK model) in the calculation of the internal exposure.

In the original bisphenol PBK model of Karrer et al. (2019), doses were applied on fixed time points and only for the first four days. For oral exposure, three dosings per day with t = 0, 6 and 12 h, for dermal exposure to PCPs and TP, two dosings per day with t = 0 and 12 h. The steady state was reached after dosing on four consecutive days. Therefore, the bisphenol PBK model described in Karrer et al. should be run for four days to reached steady state and the number of initial days to be skipped should be set to 0. Note, no dosing is applied from day 5th onwards.

These restrictions were relaxed in a new implementation of the bisphenol PBK model (General Model BPA Re-implementation). In this new version the number of days is unlimited. Dosings are specified through the user interface including the definition on the non-stationary period, see settings kinetic models.

EuroMix Generic PBK (v1)

EuroMix Generic PBK model based on SBML modelling language

Model aliases: EuroMixGenericPbk, EuroMixGenericPbk_V1, Euromix_SBML.

Table 255 Exposure routes (forcings)

Id	Description	Unit

Table 256 Model outputs

Id	Description	ScalingFactor	MultiplicationFactor	Unit

Table 257 Model parameters

Id	Description	Default	Unit	Type

EuroMix Bisphenols PBPK model (v1)

EuroMix Bisphenols PBPK model by Karrer et al. (23 July 2018).

Model aliases: EuroMix_Bisphenols_PBPK_model_V1, PBPKModel_BPA.

Table 258 Exposure routes (forcings)

Id	Description	Unit
Dietary	Dietary exposure	nmoles
Oral	Oral exposure	nmoles
Dermal	Dermal exposure	nmoles
Inhalation	Inhalation exposure	nmoles

Table 259 Model outputs

Id	Description	ScalingFactor	MultiplicationFactor	Unit
CPlasmaOut	Concentration in plasma			nmol/L
CGonadOut	Concentration in gonads			nmol/L
AurinebpaOut	Cumulative excretion of BPA in urine			nmoles
AurinegOut	Cumulative excretion of BPA-g in urine			nmoles
AurineTotalOut	Cumulative excretion of BPA and metabolites in urine			nmoles

Table 260 Model parameters

Id	Description	Default	Unit	Type
BW	Bodyweight		kg	Physiological
QCC	Cardiac output		L/min	Physiological
QgonadC	Fractional blood flow to gonads			Physiological
QliverC	Fractional blood flow to liver			Physiological
QfatC	Fractional blood flow to fat tissue			Physiological
QbrainC	Fractional blood flow to brain			Physiological
QskinC	Fractional blood flow to skin			Physiological
QmuscleC	Fractional blood flow to gonads			Physiological
VplasmaC	Fractional volume of plasma			Physiological
VfatC	Fractional volume of fat tissue			Physiological
VliverC	Fractional volume of liver tissue			Physiological
VbrainC	Fractional volume of brain tissue			Physiological
VskinC	Fractional volume of skin tissue			Physiological
VgonadC	Fractional volume of gonads			Physiological
VmuscleC	Fractional volume of muscle tissue			Physiological
VrichC	Fractional volume of richly perfused tissue			Physiological
VbodygC	Distribution volume of BPA-g			Physiological
VbodysC	Distribution volume of BPA-s			Other
MW	Molecular weight		g/mol	ChemicalProperty
pliver	Partition coefficient liver to blood			PartitionCoefficient
pfat	Partition coefficient fat to blood			PartitionCoefficient
pslow	Partition coefficient slowly perfused tissue to blood			PartitionCoefficient
prich	Partition coefficient richly perfused tissue to blood			PartitionCoefficient
pgonad	Partition coefficient gonads to blood			PartitionCoefficient
pbrain	Partition coefficient brain to blood			PartitionCoefficient
pskin	Partition coefficient skin to blood			PartitionCoefficient
geC	Gastric emptying		1/h/kg bw^-0.25	Metabolic
k0C	Oral uptake from the stomach into the liver		1/h/kg bw^-0.25	Metabolic
k1C	Oral uptake from the small intestine into the liver		1/h/kg bw^-0.25	Metabolic
k4C	Fecal elimination from small intestine after oral administration		1/h/kg bw^-0.25	Metabolic
kGIingC	Transport of glucuronide from enterocytes into serum		1/h/kg bw^-0.25	Metabolic
kGIinsC	Transport of sulfate from enterocytes into serum		1/h/kg bw^-0.25	Metabolic
kmgutg	Km of Glucuronidation in the gut		nM	Metabolic
vmaxgutgC	Vmax of Glucuronidation in the gut		nmol/h/kg bw	Metabolic
fgutg	Correction factor of glucuronidation in the gut			Metabolic
kmguts	Km of Sulfation in the gut		nM	Metabolic
vmaxgutsC	Vmax of Sulfation in the gut		nmol/h/kg bw	Metabolic
fguts	Correction factor of sulfation in the gut			Metabolic
met1g	Fraction of glucuronide in the liver taken up directly into serum (the rest undergoes EHR)			Metabolic
met1s	Fraction of sulfate in the liver taken up directly into serum			Metabolic
enterocytes	Sum of enterocytes weights in duodenum, jejunum and ileum		L	Metabolic
kmliver	Km of Glucuronidation in the liver		nM	Metabolic
vmaxliverC	Vmax of Glucuronidation in the liver		nmol/h/g liver	Metabolic
fliverg	Correction factor of glucuronidation in the liver			Metabolic
kmlivers	Km of Sulfation in the liver		nM	Metabolic
vmaxliversC	Vmax of Sulfation in the liver		nmol/h/g liver	Metabolic
flivers	Correction factor of sulfation in the liver			Metabolic
EHRtime	Time until EHR occurs		h	Metabolic
EHRrateC	EHR of glucuronide		1/h/kg bw^-0.25	Metabolic
k4C_IV	Fecal elimination of glucuronide from the EHR compartment		1/h/kg bw^-0.25	Metabolic
kurinebpaC	Clearance, urine excretion of parent compound		L/h/kg bw^0.75	Metabolic
kurinebpagC	Clearance, urine excretion of glucuronide		L/h/kg bw^0.75	Metabolic
kurinebpasC	Clearance, urine excretion of sulfate		L/h/kg bw^0.75	Metabolic
vreabsorptiongC	Vmax for renal reabsorption of glucuronide		nmol/h/kg bw^0.75	Metabolic
vreabsorptionsC	Vmax for renal reabsorption of sulfate		nmol/h/kg bw^0.75	Metabolic
kreabsorptiong	Km for renal reabsorption of glucuronide		nM	Metabolic
kreabsorptions	Km for renal reabsorption of sulfate		nM	Metabolic
kenterobpagC	EHR of parent compound due to biliary excretion of glucuronide		1/h/kg bw^-0.25	Metabolic
kenterobpasC	EHR of parent compound due to biliary excretion of sulfate		1/h/kg bw^-0.25	Metabolic
D_o	oral dose		ng/kg bw/dosing	Other
dose_O	oral dose		nmol/kg bw/dosing	Other
EoA_O	Extent of oral absorption			Physiological
uptake_O	amount of oral uptake		nmol/dosing	Other
period_O	uptake period		h	Other
koa	uptake rate		nmol/h	Other
t0_O	time point at which dosing starts		h	Other
t1_O	time point at which dosing ends		h	Other
D_d	dermal dose from thermal paper (TP)		ng/kg bw/dosing	Other
EoA_D	Extent of dermal absorption from TP			Physiological
dose_D	dermal dose from TP		nmol/kg bw/dosing	Other
aHL_D	Half-life for dermal penetration		h	Other
uptake_D	amount of dermal uptake from TP		nmol/dosing	Other
period_D	Uptake period dermal exposure from TP		h	Other
kda	Uptake rate of dermal exposure from TP		nmol/h	Other
t0_D	Time points at which dermal dosing from TP starts		h	Other
t1_D	Time points at which dermal dosing from TP ends		h	Other
D_d2	Dermal dose from PCPs		ng/kg bw/dosing	Other
EoA_D2	Extent of dermal absorption from PCPs			Physiological
dose_D2	Dermal dose from PCPs		nmol/kg bw/dosing	Other
aHL_D2	Half-life for dermal penetration from PCPs		h	Other
uptake_D2	amount of dermal uptake from PCPs		nmol/dosing	Other
period_D2	Uptake period dermal exposure from PCPs		h	Other
kda2	uptake rate of dermal exposure from PCPs		nmol/h	Other
t0_D2	Time points at which dermal dosing from PCPs starts		h	Other
t1_D2	time points at which dermal dosing from TP ends		h	Other
QC	Cardiac output		L/h	Other
Qfat	Blood flow to the fat tissue		L/h	Other
Qliver	Blood flow to the liver tissue		L/h	Other
Qgonad	Blood flow to the gonads		L/h	Other
Qbrain	Blood flow to the brain		L/h	Other
Qskin	Blood flow to the skin tissue		L/h	Other
Qslow	Blood flow to the slowly perfused tissue		L/h	Other
Qrich	Blood flow to the richly perfused tissue		L/h	Other
Vliver	Volume of the liver		L	Other
Vfat	Volume of the fat tissue		L	Other
Vgonad	Volume of the gonads		L	Other
Vplasma	Volume of the plasma		L	Other
Vbrain	Volume of the brain		L	Other
Vskin	Volume of the skin		L	Other
Vslow	Volume of the slowly perfused tissue		L	Other
Vrich	richly perfused tissue		L	Other
Vbodyg	Volume of the distribution for BPAG		L	Other
Vbodys	Volume of the distribution for BPAS		L	Other
BW075	BW^0.75		kg^0.75	Other
BW025	BW^0.25		kg^0.25	Other
vmaxliversCnew	scaled Vmax of Sulfation of BPA in the liver		nmol/h/kg bw^0.75	Other
vmaxliverCnew	scaled Vmax of Glucuronidation of BPA in the liver		nmol/h/kg bw^0.75	Other
vmaxgutgCnew	scaled Vmax of Glucuronidation of BPA in the gut		nmol/h/kg bw^0.75	Other
vreabsorptiong	scaled vmax of renal resorption of BPAG		nmol/h	Other
vreabsorptions	scaled vmax of renal resorption of BPAS		nmol/h	Other
EHRrate	scaled EHR of BPAG		1/h	Other
k0	scaled Uptake of BPA from the stomach into the liver		1/h	Other
ge	scaled Gastric emptying of BPA		1/h	Other
k1	scaled Uptake of BPA from small intestine into the liver		1/h	Other
k4	scaled Fecal excretion of BPA after oral administration from small intestine		1/h	Other
k4_IV	scaled Fecal excretion of BPAG from the EHR compartment		1/h	Other
vmaxliver	rescaled and corrected vmax of BPA glucuronidation in the liver		nmol/h	Other
kGIing	scaled Uptake of BPAG from small intestine into serum		1/h	Other
met2g	Fraction of BPAG formed subject to EHR			Other
met2s	Fraction of BPAS formed subject to EHR			Other
kurinebpa	scaled Clearance of BPA via urine		L/h	Other
kurinebpag	scaled Clearance of BPAg via urine		L/h	Other
kurinebpas	scaled Clearance of BPAs via urine		L/h	Other
vmaxlivers	rescaled and corrected vmax of BPA sulfation in the liver		nmol/h	Other
kGIins	scaled Uptake of BPAS from small intestine into serum		1/h	Other
vmaxgutg	rescaled and corrected vmax of BPA glucuronidation in the gut		nmol/h	Other
vmaxguts	rescaled and corrected vmax of BPA sulfation in the gut		nmol/h	Other
kenterobpag	scaled EHR of BPA due to biliary excretion of BPAG		1/h	Other
kenterobpas	scaled EHR of BPA due to biliary excretion of BPAS		1/h	Other
t0_D1_day1	time points at which dermal dosing from Thermal paper starts		h	Other
t0_D2_day1	time points at which dermal dosing from Thermal paper starts		h	Other
t0_D1_day2	time points at which dermal dosing from Thermal paper starts		h	Other
t0_D2_day2	time points at which dermal dosing from Thermal paper starts		h	Other
t0_D1_day3	time points at which dermal dosing from Thermal paper starts		h	Other
t0_D2_day3	time points at which dermal dosing from Thermal paper starts		h	Other
t0_D1_day4	time points at which dermal dosing from Thermal paper starts		h	Other
t0_D2_day4	time points at which dermal dosing from Thermal paper starts		h	Other
t0_D21_day1	time points at which dermal dosing from PCPs starts		h	Other
t0_D22_day1	time points at which dermal dosing from PCPs starts		h	Other
t0_D21_day2	time points at which dermal dosing from PCPs starts		h	Other
t0_D22_day2	time points at which dermal dosing from PCPs starts		h	Other
t0_D21_day3	time points at which dermal dosing from PCPs starts		h	Other
t0_D22_day3	time points at which dermal dosing from PCPs starts		h	Other
t0_D21_day4	time points at which dermal dosing from PCPs starts		h	Other
t0_D22_day4	time points at which dermal dosing from PCPs starts		h	Other
t0_O1_day1	time points at which oral dosing starts		h	Other
t0_O2_day1	time points at which oral dosing starts		h	Other
t0_O3_day1	time points at which oral dosing starts		h	Other
t0_O1_day2	time points at which oral dosing starts		h	Other
t0_O2_day2	time points at which oral dosing starts		h	Other
t0_O3_day2	time points at which oral dosing starts		h	Other
t0_O1_day3	time points at which oral dosing starts		h	Other
t0_O2_day3	time points at which oral dosing starts		h	Other
t0_O3_day3	time points at which oral dosing starts		h	Other
t0_O1_day4	time points at which oral dosing starts		h	Other
t0_O2_day4	time points at which oral dosing starts		h	Other
t0_O3_day4	time points at which oral dosing starts		h	Other
ksiLiver	Ksi of glucuronidation in liver		nM	Other
ksiGut	Ksi of glucuronidation in gut		nM	Other
age	age	30		Other
gender	gender	0		Other
QCC_adult_f	QCC_adult_f			Other
QgonadC_adult_f	QgonadC_adult_f			Other
QliverC_adult_f	QliverC_adult_f			Other
QfatC_adult_f	QfatC_adult_f			Other
QbrainC_adult_f	QbrainC_adult_f			Other
QskinC_adult_f	QskinC_adult_f			Other
QmuscleC_adult_f	QmuscleC_adult_f			Other
VplasmaC_adult_f	VplasmaC_adult_f			Other
VfatC_adult_f	VfatC_adult_f			Other
VliverC_adult_f	VliverC_adult_f			Other
VbrainC_adult_f	VbrainC_adult_f			Other
VskinC_adult_f	VskinC_adult_f			Other
VgonadC_adult_f	VgonadC_adult_f			Other
VmuscleC_adult_f	VmuscleC_adult_f			Other
VrichC_adult_f	VrichC_adult_f			Other
VbodygC_adult_f	VbodygC_adult_f			Other
VbodysC_adult_f	VbodysC_adult_f			Other
QCC_adult_m	QCC_adult_m			Other
QgonadC_adult_m	QgonadC_adult_m			Other
QliverC_adult_m	QliverC_adult_m			Other
QfatC_adult_m	QfatC_adult_m			Other
QbrainC_adult_m	QbrainC_adult_m			Other
QskinC_adult_m	QskinC_adult_m			Other
QmuscleC_adult_m	QmuscleC_adult_m			Other
VplasmaC_adult_m	VplasmaC_adult_m			Other
VfatC_adult_m	VfatC_adult_m			Other
VliverC_adult_m	VliverC_adult_m			Other
VbrainC_adult_m	VbrainC_adult_m			Other
VskinC_adult_m	VskinC_adult_m			Other
VgonadC_adult_m	VgonadC_adult_m			Other
VmuscleC_adult_m	VmuscleC_adult_m			Other
VrichC_adult_m	VrichC_adult_m			Other
VbodygC_adult_m	VbodygC_adult_m			Other
VbodysC_adult_m	VbodysC_adult_m			Other
QCC_adolescent_f	QCC_adolescent_f			Other
QgonadC_adolescent_f	QgonadC_adolescent_f			Other
QliverC_adolescent_f	QliverC_adolescent_f			Other
QfatC_adolescent_f	QfatC_adolescent_f			Other
QbrainC_adolescent_f	QbrainC_adolescent_f			Other
QskinC_adolescent_f	QskinC_adolescent_f			Other
QmuscleC_adolescent_f	QmuscleC_adolescent_f			Other
VplasmaC_adolescent_f	VplasmaC_adolescent_f			Other
VfatC_adolescent_f	VfatC_adolescent_f			Other
VliverC_adolescent_f	VliverC_adolescent_f			Other
VbrainC_adolescent_f	VbrainC_adolescent_f			Other
VskinC_adolescent_f	VskinC_adolescent_f			Other
VgonadC_adolescent_f	VgonadC_adolescent_f			Other
VmuscleC_adolescent_f	VmuscleC_adolescent_f			Other
VrichC_adolescent_f	VrichC_adolescent_f			Other
VbodygC_adolescent_f	VbodygC_adolescent_f			Other
VbodysC_adolescent_f	VbodysC_adolescent_f			Other
QCC_adolescent_m	QCC_adolescent_m			Other
QgonadC_adolescent_m	QgonadC_adolescent_m			Other
QliverC_adolescent_m	QliverC_adolescent_m			Other
QfatC_adolescent_m	QfatC_adolescent_m			Other
QbrainC_adolescent_m	QbrainC_adolescent_m			Other
QskinC_adolescent_m	QskinC_adolescent_m			Other
QmuscleC_adolescent_m	QmuscleC_adolescent_m			Other
VplasmaC_adolescent_m	VplasmaC_adolescent_m			Other
VfatC_adolescent_m	VfatC_adolescent_m			Other
VliverC_adolescent_m	VliverC_adolescent_m			Other
VbrainC_adolescent_m	VbrainC_adolescent_m			Other
VskinC_adolescent_m	VskinC_adolescent_m			Other
VgonadC_adolescent_m	VgonadC_adolescent_m			Other
VmuscleC_adolescent_m	VmuscleC_adolescent_m			Other
VrichC_adolescent_m	VrichC_adolescent_m			Other
VbodygC_adolescent_m	VbodygC_adolescent_m			Other
VbodysC_adolescent_m	VbodysC_adolescent_m			Other
QCC_child_f	QCC_child_f			Other
QgonadC_child_f	QgonadC_child_f			Other
QliverC_child_f	QliverC_child_f			Other
QfatC_child_f	QfatC_child_f			Other
QbrainC_child_f	QbrainC_child_f			Other
QskinC_child_f	QskinC_child_f			Other
QmuscleC_child_f	QmuscleC_child_f			Other
VplasmaC_child_f	VplasmaC_child_f			Other
VfatC_child_f	VfatC_child_f			Other
VliverC_child_f	VliverC_child_f			Other
VbrainC_child_f	VbrainC_child_f			Other
VskinC_child_f	VskinC_child_f			Other
VgonadC_child_f	VgonadC_child_f			Other
VmuscleC_child_f	VmuscleC_child_f			Other
VrichC_child_f	VrichC_child_f			Other
VbodygC_child_f	VbodygC_child_f			Other
VbodysC_child_f	VbodysC_child_f			Other
QCC_child_m	QCC_child_m			Other
QgonadC_child_m	QgonadC_child_m			Other
QliverC_child_m	QliverC_child_m			Other
QfatC_child_m	QfatC_child_m			Other
QbrainC_child_m	QbrainC_child_m			Other
QskinC_child_m	QskinC_child_m			Other
QmuscleC_child_m	QmuscleC_child_m			Other
VplasmaC_child_m	VplasmaC_child_m			Other
VfatC_child_m	VfatC_child_m			Other
VliverC_child_m	VliverC_child_m			Other
VbrainC_child_m	VbrainC_child_m			Other
VskinC_child_m	VskinC_child_m			Other
VgonadC_child_m	VgonadC_child_m			Other
VmuscleC_child_m	VmuscleC_child_m			Other
VrichC_child_m	VrichC_child_m			Other
VbodygC_child_m	VbodygC_child_m			Other
VbodysC_child_m	VbodysC_child_m			Other

EuroMix Bisphenols PBPK model (v2)

EuroMix Bisphenols PBPK model by Karrer et al. (2019).

Model aliases: EuroMix_Bisphenols_PBPK_model_V2, PBPKModel_BPA_Reimplementation.

Table 261 Exposure routes (forcings)

Id	Description	Unit
Dietary	Dietary exposure	nmoles
Oral	Oral exposure	nmoles
Dermal	Dermal exposure	nmoles
Inhalation	Inhalation exposure	nmoles

Table 262 Model outputs

Id	Description	ScalingFactor	MultiplicationFactor	Unit
CPlasmaOut	Concentration in plasma			nmol/L
CGonadOut	Concentration in gonads			nmol/L
AurinebpaOut	Cumulative excretion of BPA in urine			nmoles
AurinegOut	Cumulative excretion of BPA-g in urine			nmoles
AurineTotalOut	Cumulative excretion of BPA and metabolites in urine			nmoles

Table 263 Model parameters

Id	Description	Default	Unit	Type
BW	Bodyweight		kg	Physiological
QCC	Cardiac output		L/min	Physiological
QgonadC	Fractional blood flow to gonads			Physiological
QliverC	Fractional blood flow to liver			Physiological
QfatC	Fractional blood flow to fat tissue			Physiological
QbrainC	Fractional blood flow to brain			Physiological
QskinC	Fractional blood flow to skin			Physiological
QmuscleC	Fractional blood flow to gonads			Physiological
VplasmaC	Fractional volume of plasma			Physiological
VfatC	Fractional volume of fat tissue			Physiological
VliverC	Fractional volume of liver tissue			Physiological
VbrainC	Fractional volume of brain tissue			Physiological
VskinC	Fractional volume of skin tissue			Physiological
VgonadC	Fractional volume of gonads			Physiological
VmuscleC	Fractional volume of muscle tissue			Physiological
VrichC	Fractional volume of richly perfused tissue			Physiological
VbodygC	Distribution volume of BPA-g			Physiological
VbodysC	Distribution volume of BPA-s			Other
pliver	Partition coefficient liver to blood			PartitionCoefficient
pfat	Partition coefficient fat to blood			PartitionCoefficient
pslow	Partition coefficient slowly perfused tissue to blood			PartitionCoefficient
prich	Partition coefficient richly perfused tissue to blood			PartitionCoefficient
pgonad	Partition coefficient gonads to blood			PartitionCoefficient
pbrain	Partition coefficient brain to blood			PartitionCoefficient
pskin	Partition coefficient skin to blood			PartitionCoefficient
geC	Gastric emptying		1/h/kg bw^-0.25	Metabolic
k0C	Oral uptake from the stomach into the liver		1/h/kg bw^-0.25	Metabolic
k1C	Oral uptake from the small intestine into the liver		1/h/kg bw^-0.25	Metabolic
k4C	Fecal elimination from small intestine after oral administration		1/h/kg bw^-0.25	Metabolic
kGIingC	Transport of glucuronide from enterocytes into serum		1/h/kg bw^-0.25	Metabolic
kGIinsC	Transport of sulfate from enterocytes into serum		1/h/kg bw^-0.25	Metabolic
kmgutg	Km of Glucuronidation in the gut		nM	Metabolic
vmaxgutgC	Vmax of Glucuronidation in the gut		nmol/h/kg bw	Metabolic
fgutg	Correction factor of glucuronidation in the gut			Metabolic
kmguts	Km of Sulfation in the gut		nM	Metabolic
vmaxgutsC	Vmax of Sulfation in the gut		nmol/h/kg bw	Metabolic
fguts	Correction factor of sulfation in the gut			Metabolic
met1g	Fraction of glucuronide in the liver taken up directly into serum (the rest undergoes EHR)			Metabolic
met1s	Fraction of sulfate in the liver taken up directly into serum			Metabolic
enterocytes	Sum of enterocytes weights in duodenum, jejunum and ileum		L	Metabolic
kmliver	Km of Glucuronidation in the liver		nM	Metabolic
vmaxliverC	Vmax of Glucuronidation in the liver		nmol/h/g liver	Metabolic
fliverg	Correction factor of glucuronidation in the liver			Metabolic
kmlivers	Km of Sulfation in the liver		nM	Metabolic
vmaxliversC	Vmax of Sulfation in the liver		nmol/h/g liver	Metabolic
flivers	Correction factor of sulfation in the liver			Metabolic
EHRtime	Time until EHR occurs		h	Metabolic
EHRrateC	EHR of glucuronide		1/h/kg bw^-0.25	Metabolic
k4C_IV	Fecal elimination of glucuronide from the EHR compartment		1/h/kg bw^-0.25	Metabolic
kurinebpaC	Clearance, urine excretion of parent compound		L/h/kg bw^0.75	Metabolic
kurinebpagC	Clearance, urine excretion of glucuronide		L/h/kg bw^0.75	Metabolic
kurinebpasC	Clearance, urine excretion of sulfate		L/h/kg bw^0.75	Metabolic
vreabsorptiongC	Vmax for renal reabsorption of glucuronide		nmol/h/kg bw^0.75	Metabolic
vreabsorptionsC	Vmax for renal reabsorption of sulfate		nmol/h/kg bw^0.75	Metabolic
kreabsorptiong	Km for renal reabsorption of glucuronide		nM	Metabolic
kreabsorptions	Km for renal reabsorption of sulfate		nM	Metabolic
kenterobpagC	EHR of parent compound due to biliary excretion of glucuronide		1/h/kg bw^-0.25	Metabolic
kenterobpasC	EHR of parent compound due to biliary excretion of sulfate		1/h/kg bw^-0.25	Metabolic
koa	uptake rate		nmol/h	Other
EoA_D	Extent of dermal absorption from TP			Physiological
aHL_D	Half-life for dermal penetration		h	Other
kda	Uptake rate of dermal exposure from TP		nmol/h	Other
EoA_D2	Extent of dermal absorption from PCPs			Physiological
aHL_D2	Half-life for dermal penetration from PCPs		h	Other
kda2	Uptake rate of dermal exposure from PCPs		nmol/h	Other
QC	Cardiac output		L/h	Other
Qfat	Blood flow to the fat tissue		L/h	Other
Qliver	Blood flow to the liver tissue		L/h	Other
Qgonad	Blood flow to the gonads		L/h	Other
Qbrain	Blood flow to the brain		L/h	Other
Qskin	Blood flow to the skin tissue		L/h	Other
Qslow	Blood flow to the slowly perfused tissue		L/h	Other
Qrich	Blood flow to the richly perfused tissue		L/h	Other
Vliver	Volume of the liver		L	Other
Vfat	Volume of the fat tissue		L	Other
Vgonad	Volume of the gonads		L	Other
Vplasma	Volume of the plasma		L	Other
Vbrain	Volume of the brain		L	Other
Vskin	Volume of the skin		L	Other
Vslow	Volume of the slowly perfused tissue		L	Other
Vrich	richly perfused tissue		L	Other
Vbodyg	Volume of the distribution for BPAG		L	Other
Vbodys	Volume of the distribution for BPAS		L	Other
vreabsorptiong	scaled vmax of renal resorption of BPAG		nmol/h	Other
vreabsorptions	scaled vmax of renal resorption of BPAS		nmol/h	Other
EHRrate	scaled EHR of BPAG		1/h	Other
k0	scaled Uptake of BPA from the stomach into the liver		1/h	Other
ge	scaled Gastric emptying of BPA		1/h	Other
k1	scaled Uptake of BPA from small intestine into the liver		1/h	Other
k4	scaled Fecal excretion of BPA after oral administration from small intestine		1/h	Other
k4_IV	scaled Fecal excretion of BPAG from the EHR compartment		1/h	Other
vmaxliver	rescaled and corrected vmax of BPA glucuronidation in the liver		nmol/h	Other
kGIing	scaled Uptake of BPAG from small intestine into serum		1/h	Other
met2g	Fraction of BPAG formed subject to EHR			Other
met2s	Fraction of BPAS formed subject to EHR			Other
kurinebpa	scaled Clearance of BPA via urine		L/h	Other
kurinebpag	scaled Clearance of BPAg via urine		L/h	Other
kurinebpas	scaled Clearance of BPAs via urine		L/h	Other
vmaxlivers	rescaled and corrected vmax of BPA sulfation in the liver		nmol/h	Other
kGIins	scaled Uptake of BPAS from small intestine into serum		1/h	Other
vmaxgutg	rescaled and corrected vmax of BPA glucuronidation in the gut		nmol/h	Other
vmaxguts	rescaled and corrected vmax of BPA sulfation in the gut		nmol/h	Other
kenterobpag	scaled EHR of BPA due to biliary excretion of BPAG		1/h	Other
kenterobpas	scaled EHR of BPA due to biliary excretion of BPAS		1/h	Other
ksiLiver	Ksi of glucuronidation in liver		nM	Other
ksiGut	Ksi of glucuronidation in gut		nM	Other
age	age	30		Other
gender	gender	0		Other
QCC_adult_f	QCC_adult_f			Other
QgonadC_adult_f	QgonadC_adult_f			Other
QliverC_adult_f	QliverC_adult_f			Other
QfatC_adult_f	QfatC_adult_f			Other
QbrainC_adult_f	QbrainC_adult_f			Other
QskinC_adult_f	QskinC_adult_f			Other
QmuscleC_adult_f	QmuscleC_adult_f			Other
VplasmaC_adult_f	VplasmaC_adult_f			Other
VfatC_adult_f	VfatC_adult_f			Other
VliverC_adult_f	VliverC_adult_f			Other
VbrainC_adult_f	VbrainC_adult_f			Other
VskinC_adult_f	VskinC_adult_f			Other
VgonadC_adult_f	VgonadC_adult_f			Other
VmuscleC_adult_f	VmuscleC_adult_f			Other
VrichC_adult_f	VrichC_adult_f			Other
VbodygC_adult_f	VbodygC_adult_f			Other
VbodysC_adult_f	VbodysC_adult_f			Other
QCC_adult_m	QCC_adult_m			Other
QgonadC_adult_m	QgonadC_adult_m			Other
QliverC_adult_m	QliverC_adult_m			Other
QfatC_adult_m	QfatC_adult_m			Other
QbrainC_adult_m	QbrainC_adult_m			Other
QskinC_adult_m	QskinC_adult_m			Other
QmuscleC_adult_m	QmuscleC_adult_m			Other
VplasmaC_adult_m	VplasmaC_adult_m			Other
VfatC_adult_m	VfatC_adult_m			Other
VliverC_adult_m	VliverC_adult_m			Other
VbrainC_adult_m	VbrainC_adult_m			Other
VskinC_adult_m	VskinC_adult_m			Other
VgonadC_adult_m	VgonadC_adult_m			Other
VmuscleC_adult_m	VmuscleC_adult_m			Other
VrichC_adult_m	VrichC_adult_m			Other
VbodygC_adult_m	VbodygC_adult_m			Other
VbodysC_adult_m	VbodysC_adult_m			Other
QCC_adolescent_f	QCC_adolescent_f			Other
QgonadC_adolescent_f	QgonadC_adolescent_f			Other
QliverC_adolescent_f	QliverC_adolescent_f			Other
QfatC_adolescent_f	QfatC_adolescent_f			Other
QbrainC_adolescent_f	QbrainC_adolescent_f			Other
QskinC_adolescent_f	QskinC_adolescent_f			Other
QmuscleC_adolescent_f	QmuscleC_adolescent_f			Other
VplasmaC_adolescent_f	VplasmaC_adolescent_f			Other
VfatC_adolescent_f	VfatC_adolescent_f			Other
VliverC_adolescent_f	VliverC_adolescent_f			Other
VbrainC_adolescent_f	VbrainC_adolescent_f			Other
VskinC_adolescent_f	VskinC_adolescent_f			Other
VgonadC_adolescent_f	VgonadC_adolescent_f			Other
VmuscleC_adolescent_f	VmuscleC_adolescent_f			Other
VrichC_adolescent_f	VrichC_adolescent_f			Other
VbodygC_adolescent_f	VbodygC_adolescent_f			Other
VbodysC_adolescent_f	VbodysC_adolescent_f			Other
QCC_adolescent_m	QCC_adolescent_m			Other
QgonadC_adolescent_m	QgonadC_adolescent_m			Other
QliverC_adolescent_m	QliverC_adolescent_m			Other
QfatC_adolescent_m	QfatC_adolescent_m			Other
QbrainC_adolescent_m	QbrainC_adolescent_m			Other
QskinC_adolescent_m	QskinC_adolescent_m			Other
QmuscleC_adolescent_m	QmuscleC_adolescent_m			Other
VplasmaC_adolescent_m	VplasmaC_adolescent_m			Other
VfatC_adolescent_m	VfatC_adolescent_m			Other
VliverC_adolescent_m	VliverC_adolescent_m			Other
VbrainC_adolescent_m	VbrainC_adolescent_m			Other
VskinC_adolescent_m	VskinC_adolescent_m			Other
VgonadC_adolescent_m	VgonadC_adolescent_m			Other
VmuscleC_adolescent_m	VmuscleC_adolescent_m			Other
VrichC_adolescent_m	VrichC_adolescent_m			Other
VbodygC_adolescent_m	VbodygC_adolescent_m			Other
VbodysC_adolescent_m	VbodysC_adolescent_m			Other
QCC_child_f	QCC_child_f			Other
QgonadC_child_f	QgonadC_child_f			Other
QliverC_child_f	QliverC_child_f			Other
QfatC_child_f	QfatC_child_f			Other
QbrainC_child_f	QbrainC_child_f			Other
QskinC_child_f	QskinC_child_f			Other
QmuscleC_child_f	QmuscleC_child_f			Other
VplasmaC_child_f	VplasmaC_child_f			Other
VfatC_child_f	VfatC_child_f			Other
VliverC_child_f	VliverC_child_f			Other
VbrainC_child_f	VbrainC_child_f			Other
VskinC_child_f	VskinC_child_f			Other
VgonadC_child_f	VgonadC_child_f			Other
VmuscleC_child_f	VmuscleC_child_f			Other
VrichC_child_f	VrichC_child_f			Other
VbodygC_child_f	VbodygC_child_f			Other
VbodysC_child_f	VbodysC_child_f			Other
QCC_child_m	QCC_child_m			Other
QgonadC_child_m	QgonadC_child_m			Other
QliverC_child_m	QliverC_child_m			Other
QfatC_child_m	QfatC_child_m			Other
QbrainC_child_m	QbrainC_child_m			Other
QskinC_child_m	QskinC_child_m			Other
QmuscleC_child_m	QmuscleC_child_m			Other
VplasmaC_child_m	VplasmaC_child_m			Other
VfatC_child_m	VfatC_child_m			Other
VliverC_child_m	VliverC_child_m			Other
VbrainC_child_m	VbrainC_child_m			Other
VskinC_child_m	VskinC_child_m			Other
VgonadC_child_m	VgonadC_child_m			Other
VmuscleC_child_m	VmuscleC_child_m			Other
VrichC_child_m	VrichC_child_m			Other
VbodygC_child_m	VbodygC_child_m			Other
VbodysC_child_m	VbodysC_child_m			Other

EuroMix Generic PBTK model (v5)

Cosmos version 5 (adapted 9/11/2018)

Model aliases: EuroMix_Generic_PBTK_model_V5, CosmosV4, CosmosV5.

Table 264 Exposure routes (forcings)

Id	Description	Unit
Dietary	Dietary exposure	mmoles
Dermal	Dermal exposure	mmoles
Inhalation	Inhalatory exposure	mmoles

Table 265 Model outputs

Id	Description	ScalingFactor	MultiplicationFactor	Unit
CVen	Venous blood	scVBlood	0.66667	mM
CArt	Arterial blood	scVBlood	0.33333	mM
CFat	Fat tissues	scVFat		mM
CPoor	Muscle tissues			mM
CRich	Viscera	scVRich		mM
CLiver	Liver	scVLiver		mM
CSkin_u	Viable skin, unexposed			mM
CSkin_e	Viable skin, exposed	BSA, Height_vs, fsA_exposed		mM
CSkin_sc_u	Skin stratum corneum, unexposed			mM
CSkin_sc_e	Skin stratum corneum, exposed	BSA, Height_vs, fsA_exposed		mM

Table 266 Model parameters

Id	Description	Default	Unit	Type
BM	Body mass		kg	Physiological
BSA	Body skin surface area		dm2	Physiological
scVFat	Fat as fraction of total body volume			Physiological
scVRich	Richly perfused tissues (viscera) as fraction of total body volume			Physiological
scVLiver	Liver as fraction of total body volume			Physiological
scVBlood	Blood as fraction of total body volume			Physiological
Height_sc	Skin thickness		decimeter	Physiological
Height_vs	Viable skin			Physiological
scFBlood	Total blood flow per unit mass		L/h/kg	Physiological
scFFat	Fat fraction of total blood flow going to compartments			Physiological
scFPoor	Poorly perfused tissues (muscles) fraction of total blood flow going to compartments			Physiological
scFLiver	Liver fraction of total blood flow going to compartments			Physiological
scFSkin	Skin fraction of total blood flow going to compartments			Physiological
Falv	Alveolar ventilation rate		L/h	Physiological
mic	Microsomal proteins content		mg/gr liver	Physiological
PCAir	Partition coefficient: blood over air			PartitionCoefficient
log_PCFat	Scaled parameter, partition coefficient: fat over blood			PartitionCoefficient
log_aPoor	Scaled parameter, partition coefficient: muscle over blood (poorly perfused tissue)			PartitionCoefficient
log_aRich	Scaled parameter, partition coefficient: viscera over blood (richly perfused tissue)			PartitionCoefficient
log_aLiver	Scaled parameter, partition coefficient: liver over blood			PartitionCoefficient
log_aSkin	Scaled parameter, partition coefficient: viable skin / blood			PartitionCoefficient
log_aSkin_sc	Scaled parameter, partition coefficient: viable skin / stratum corneum			PartitionCoefficient
Kp_sc_vs	Diffusion rate from stratum corneum to viable skin		decimeter/h	Metabolic
Ke	Renal excretion rate		L/h	Metabolic
Michaelis	Flag for Michaelis-Menten vs linear metabolism (0 = linear)			Metabolic
Vmax	Maximum rate of metabolism		mmoles/h/L liver	Metabolic
Km	Michaelis-Menten constant		mM	Metabolic
CLH	Hepatic clearance			Metabolic
fup	Unbound fraction in blood			Metabolic
Frac	Fraction absorbed by the gut			Metabolic
kGut	Oral 1st order absorption rate constant		1/h	Metabolic
Cinh	Inhalation			Other
Tinh	Inhalation duration			Other
OralDose			mmol	Other
DermalDose			mmol	Other
fSA_exposed	Fraction of skin surface area actually exposed			Metabolic
FBlood	Blood flow			Other
FFat	Scaled parameters			Other
FPoor	Scaled parameters			Other
FRich	Scaled parameters			Other
FLiver	Scaled parameters			Other
FSkin	Scaled parameters			Other
VFat	Scaled parameters			Other
VRich	Scaled parameters			Other
VLiver	Scaled parameters			Other
VSkin_e	Scaled parameters			Other
VSkin_u	Scaled parameters			Other
VSkin_sc_e	Scaled parameters			Other
VSkin_sc_u	Scaled parameters			Other
VBlood	Scaled parameters			Other
VPoor	Scaled parameters			Other
VArt	Scaled parameters			Other
VVen	Scaled parameters			Other
FSkin_e	Scaled parameters			Other
FSkin_u	Scaled parameters			Other
PCFat	Partition coefficient: fat over blood			PartitionCoefficient
PCPoor	Partition coefficient: muscle over blood (poorly perfused tissue)			PartitionCoefficient
PCRich	Partition coefficient: viscera over blood (richly perfused tissue)			PartitionCoefficient
PCLiver	Partition coefficient: liver over blood			PartitionCoefficient
PCSkin	Partition coefficient: viable skin / blood			PartitionCoefficient
PCSkin_sc	Partition coefficient: viable skin / stratum corneum			PartitionCoefficient
ResampledPCFat	Resampled value PCFat			PartitionCoefficient

EuroMix Generic PBTK model (v6)

Cosmos version 6 (received 3/27/2019)

Model aliases: EuroMix_Generic_PBTK_model_V6, CosmosV6.

Table 267 Exposure routes (forcings)

Id	Description	Unit
Dietary	Dietary exposure	mmoles
Dermal	Dermal exposure	mmoles
Inhalation	Inhalatory exposure	mmoles

Table 268 Model outputs

Id	Description	ScalingFactor	MultiplicationFactor	Unit
CTotal	Total concentration			mM
CVen	Venous blood concentration	scVBlood	0.66667	mM
CArt	Arterial blood concentration	scVBlood	0.33333	mM
CFat	Fat (adipose) tissue concentration	scVFat		mM
CPoor	Poorly perfused tissue (muscle) concentration			mM
CRich	Richly perfused tissue (viscera) concentration	scVRich		mM
CLiver	Liver concentration	scVLiver		mM
CSkin_u	Viable unexposed skin concentration			mM
CSkin_e	Viable exposed skin concentration	BSA, Height_vs, fsA_exposed		mM
CSkin_sc_u	Skin unexposed stratum corneum concentration			mM
CSkin_sc_e	Skin exposed stratum corneum concentration	BSA, Height_vs, fsA_exposed		mM

Table 269 Model parameters

Id	Description	Default	Unit	Type
BM	Body mass		kg	Physiological
BSA	Body surface area (internally scaled by an allometric scaling factor s = 70/BM^0.3)		dm2	Physiological
scVFat	Fat as fraction of total body volume			Physiological
scVRich	Richly perfused tissues (viscera) as fraction of total body volume			Physiological
scVLiver	Liver as fraction of total body volume			Physiological
scVBlood	Blood as fraction of total body volume			Physiological
Height_sc	Skin thickness		decimeter	Physiological
Height_vs	Viable skin			Physiological
scFBlood	Total blood flow per unit mass		L/h/kg	Physiological
scFFat	Fat fraction of total blood flow going to compartments			Physiological
scFPoor	Poorly perfused tissues (muscles) fraction of total blood flow going to compartments			Physiological
scFLiver	Liver fraction of total blood flow going to compartments			Physiological
scFSkin	Skin fraction of total blood flow going to compartments			Physiological
Falv	Alveolar ventilation rate		L/h	Physiological
mic	Microsomal proteins content		mg/gr liver	Physiological
PCAir	Partition coefficient: blood over air			PartitionCoefficient
log_PCFat	Scaled parameter, partition coefficient: fat over blood			PartitionCoefficient
log_aPoor	Scaled parameter, partition coefficient: muscle over blood (poorly perfused tissue)			PartitionCoefficient
log_aRich	Scaled parameter, partition coefficient: viscera over blood (richly perfused tissue)			PartitionCoefficient
log_aLiver	Scaled parameter, partition coefficient: liver over blood			PartitionCoefficient
log_aSkin	Scaled parameter, partition coefficient: viable skin over blood			PartitionCoefficient
log_aSkin_sc	Scaled parameter, partition coefficient: viable skin stratum corneum over blood			PartitionCoefficient
Kp_sc_vs	Diffusion rate from stratum corneum to viable skin		decimeter/h	Metabolic
Ke	Renal excretion rate		L/h	Metabolic
Michaelis	Flag for Michaelis-Menten vs linear metabolism (0 = linear)			Metabolic
Vmax	Maximum rate of metabolism		mmoles/h/L liver	Metabolic
Km	Michaelis-Menten constant for metabolism		mM	Metabolic
CLH	Hepatic metabolic clearance			Metabolic
fub	Unbound fraction in blood			Metabolic
Frac	Fraction absorbed by the gut			Metabolic
kGut	Oral 1st order absorption rate constant		1/h	Metabolic
Cinh	Inhalation			Other
Tinh	Inhalation duration			Other
OralDose			mmol	Other
DermalDose			mmol	Other
fSA_exposed	Fraction of skin surface area actually exposed			Metabolic
FBlood	Blood flow			Other
FFat	Scaled parameters, blood flow to the fat			Other
FPoor	Scaled parameters, blood flow to poorly perfused tissues			Other
FRich	Scaled parameters, blood flow to richly perfused tissues			Other
FLiver	Scaled parameters, blood flow to the liver			Other
FSkin	Scaled parameters, blood flow to the skin			Other
VFat	Scaled parameters			Other
VRich	Scaled parameters, richly perfused tissue volume			Other
VLiver	Scaled parameters, liver volume			Other
VSkin_e	Scaled parameters, exposed skin volume			Other
VSkin_u	Scaled parameters, unexposed skin volume			Other
VSkin_sc_e	Scaled parameters, stratum corneum exposed skin volume			Other
VSkin_sc_u	Scaled parameters, stratum corneum unexposed skin volume			Other
VBlood	Scaled parameters, blood volume			Other
VPoor	Scaled parameters, poorly perfused tissue volume			Other
VArt	Scaled parameters, arterial blood volume			Other
VVen	Scaled parameters, venous blood volume			Other
FSkin_e	Scaled parameters, blood flow to exposed skin			Other
FSkin_u	Scaled parameters, blood flow to unexposed skin			Other
PCFat	Partition coefficient: fat over blood			PartitionCoefficient
PCPoor	Partition coefficient: muscle over blood (poorly perfused tissue)			PartitionCoefficient
PCRich	Partition coefficient: viscera over blood (richly perfused tissue)			PartitionCoefficient
PCLiver	Partition coefficient: liver over blood			PartitionCoefficient
PCSkin	Partition coefficient: viable skin over blood			PartitionCoefficient
PCSkin_sc	Partition coefficient: viable skin / stratum corneum			PartitionCoefficient
ResampledPCFat	Resampled value PCFat			PartitionCoefficient

PBK model chlorpyrifos (v1)

PBK model chlorpyrifos (v1)

Model aliases: PBK_Chlorpyrifos_V1.

Table 270 Exposure routes (forcings)

Id	Description	Unit
Dietary	Dietary exposure	umoles

Table 271 Model outputs

Id	Description	ScalingFactor	MultiplicationFactor	Unit
O_CV	Venous blood	VVc		uM
O_CP	Plasma from whole blood	VVc	0.6	uM
O_CU	Uterus tissue	VUc		uM
O_ACL	Cleared renally		0.03	umoles
O_CS	Slowly perfused tissue			umoles
O_CR	Richly perfused tissue			umoles
O_CF	Fat	VFc		umoles
O_CL	Liver	VLc		umoles
O_CK	Kidney	VKc		umoles
O_CM	Muscle	VMc		umoles
O_CH	Heart	VHc		umoles
O_CLu	Lung	VLuc		umoles
O_CBrb	Brain blood	VBrc	0.05	umoles
O_CBrt	Brain tissue	VBrc	0.95	umoles
O_CBr	Brain total	VBrc		umoles
O_CA	Arterial blood	VAc		umoles

Table 272 Model parameters

Id	Description	Default	Unit	Type
VLc	Fraction liver tissue of BW	0.0257		Physiological
VFc	Fraction fat tissue of BW	0.2142		Physiological
VLuc	Fraction lung tissue of BW	0.0076		Physiological
VAc	Fraction arterial blood of BW (0.074*1/4)	0.0198		Physiological
VVc	Fraction venous blood of BW (0.074*3/4)	0.0593		Physiological
VKc	Fraction kidney tissue of BW	0.004		Physiological
VMc	Fraction muscle tissue of BW	0.04		Physiological
VUc	Fraction uterus tissue of BW	0.0018		Physiological
VBrc	Fraction brain tissue of BW	0.02		Physiological
VHc	Fraction heart tissue of BW	0.0047		Physiological
QLc	Fraction of blood flow to liver	0.227		Physiological
QFc	Fraction of blood flow to fat	0.052		Physiological
QKc	Fraction of blood flow to kidneys	0.175		Physiological
QMc	Fraction of blood flow to muscle	0.12		Physiological
QUc	Fraction of blood flow to uterus	0.2		Physiological
QBrc	Fraction of blood flow to brain	0.114		Physiological
QHc	Fraction of blood flow to heart	0.04		Physiological
MWP	Molecular weight	350.59	g/mol	PhysicoChemical
MWM1	Molecular weight	334.52	g/mol	PhysicoChemical
MWM2	Molecular weight	198.43	g/mol	PhysicoChemical
LogPP	Octanol/water partition coefficient	4.784		PartitionCoefficient
LogPM1	Octanol/water partition coefficient	3.894		PartitionCoefficient
LogPM2	Octanol/water partition coefficient	1.856		PartitionCoefficient
Fa	Fraction absorbed. Obtained from Nolan 1984	0.7		Metabolic
KaS	Absorption constant stomach. Obtained from Timchalk et al. 2002 (stomach; /h)	0.00000733	/h	Metabolic
KaI	Absorption constant intestine. Obtained from Timchalk et al. 2002 (intestine; /h)	1.00033	/h	Metabolic
KsI	Absorption constant (transfer stomach to intestine). Obtained from Timchalk et al. 2002 (transfer stomach to intestine; /h)	0.967749	/h	Metabolic
fuP	Unbound fraction in plasma. Obtained from SimCyp	0.021		Metabolic
fuM1	Unbound fraction in plasma. Obtained from SimCyp	0.15		Metabolic
fuM2	Unbound fraction in plasma. Obtained from SimCyp	0.082		Metabolic
BPP	B/P ratio obtained from Hsu, 2013. If no data available, set to 1	1.3		Metabolic
BPM1	B/P ratio obtained from Hsu, 2013. If no data available, set to 1	2.7		Metabolic
BPM2	B/P ratio obtained from Hsu, 2013. If no data available, set to 1	1		Metabolic
KurineP	Urinary excretion rate constant (/h)	0	/h	Metabolic
KurineM1	Urinary excretion rate constant (/h)	0	/h	Metabolic
KurineM2	Urinary excretion rate constant (/h)	0.026	/h	Metabolic
CYPabundanceCYP1A2	CYP1A2 abundance (pmolCYP/mg protein) ;(calculated based on database in Simcyp; sum of EM, PM and UM)	52		Metabolic
CYPabundanceCYP2B6	CYP2B6 abundance (pmolCYP/mg protein) ;(calculated based on database in Simcyp; sum of EM, PM and UM)	15.8		Metabolic
CYPabundanceCYP2C19	CYP2C19 abundance (pmolCYP/mg protein) ;(calculated based on database in Simcyp; sum of EM, PM and UM)	5.4		Metabolic
CYPabundanceCYP3A4	CYP3A4 abundance (pmolCYP/mg protein) ;(calculated based on database in Simcyp; sum of EM, PM and UM)	137		Metabolic
ISEFCYP1A2	Scaling factor CYP1A2 ISEF (Vmax) (non compound-specific) (calculated based on probe incubation, lab specific)	0.072		Metabolic
ISEFCYP2B6	Scaling factor CYP2B6 ISEF (Vmax) (non compound-specific) (calculated based on probe incubation, lab specific)	0.476		Metabolic
ISEFCYP2C19	Scaling factor CYP2C19 ISEF (Vmax) (non compound-specific) (calculated based on probe incubation, lab specific)	0.209		Metabolic
ISEFCYP3A4	Scaling factor CYP3A4 ISEF (Vmax) (non compound-specific) (calculated based on probe incubation, lab specific)	0.107		Metabolic
MPL	Scaling factor of human liver microsome in mg to gram liver (mg microsomal protein /g liver) (Al-Malahmeh, A. J et al., 2017) (Barter et al., 2007)	32	mg/g	Metabolic
VMaxCYP1A2mP1	Vmax of CYP1A2 at supersome level (pmol/min/pmol CYP) (Experimentally determined using supersomes, Chen et al., 2022)	3.963		Metabolic
VMaxCYP2B6mP1	Vmax of CYP2B6 at supersome level (pmol/min/pmol CYP) (Experimentally determined using supersomes, Chen et al., 2022)	7.755		Metabolic
VMaxCYP2C19mP1	Vmax of CYP2C19 at supersome level (pmol/min/pmol CYP) (Experimentally determined using supersomes, Chen et al., 2022)	2.744		Metabolic
VMaxCYP3A4mP1	Vmax of CYP3A4 at supersome level (pmol/min/pmol CYP) (Experimentally determined using supersomes, Chen et al., 2022)	17.78		Metabolic
KmCYP1A2P1	Affinity constant of CYP1A2 (umoles/L) (Experimentally determined using supersomes, Chen et al., 2022)	0.61	umoles/L	Metabolic
KmCYP2B6P1	Affinity constant of CYP2B6 (umoles/L) (Experimentally determined using supersomes, Chen et al., 2022)	0.14	umoles/L	Metabolic
KmCYP2C19P1	Affinity constant of CYP2C19 (umoles/L) (Experimentally determined using supersomes, Chen et al., 2022)	1.89	umoles/L	Metabolic
KmCYP3A4P1	Affinity constant of CYP3A4 (umoles/L) (Experimentally determined using supersomes, Chen et al., 2022)	29.77	umoles/L	Metabolic
VMaxCYP1A2mP2	Vmax of CYP1A2 at supersome level (pmol/min/pmol CYP) (Experimentally determined using supersomes, Chen et al., 2022)	2.957		Metabolic
VMaxCYP2B6mP2	Vmax of CYP2B6 at supersome level (pmol/min/pmol CYP) (Experimentally determined using supersomes, Chen et al., 2022)	5.492		Metabolic
VMaxCYP2C19mP2	Vmax of CYP2C19 at supersome level (pmol/min/pmol CYP) (Experimentally determined using supersomes, Chen et al., 2022)	17.51		Metabolic
VMaxCYP3A4mP2	Vmax of CYP3A4 at supersome level (pmol/min/pmol CYP) (Experimentally determined using supersomes, Chen et al., 2022)	23.86		Metabolic
KmCYP1A2P2	Affinity constant of CYP1A2 (umoles/L) (Experimentally determined using supersomes, Chen et al., 2022)	1.25	umoles/L	Metabolic
KmCYP2B6P2	Affinity constant of CYP2B6 (umoles/L) (Experimentally determined using supersomes, Chen et al., 2022)	1.28	umoles/L	Metabolic
KmCYP2C19P2	Affinity constant of CYP2C19 (umoles/L) (Experimentally determined using supersomes, Chen et al., 2022)	1.37	umoles/L	Metabolic
KmCYP3A4P2	Affinity constant of CYP3A4 (umoles/L) (Experimentally determined using supersomes, Chen et al., 2022)	18.13	umoles/L	Metabolic
VMax3c	Maximum velocity constant (nmol/min/ml plasma) (Experimentally determined using microsomes, Chen et al., 2022)	37.98	nmoles/min/ml	Metabolic
Km3	Affinity constant (umoles/L) (Experimentally determined)	627.9		Metabolic
VMax4c	Maximum velocity constant (nmol/min/ml plasma) (Experimentally determined using microsomes, Chen et al., 2022)	1844	nmoles/min/ml	Metabolic
Km4	Affinity constant (umoles/L) (Experimentally determined)	289.8	umoles/L	Metabolic
BW		70	kg	Physiological

Note

Additional kinetic models can be implemented, please contact the MCRA administrator.