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 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 188 Exposure routes (forcings)
Id	Description	Unit
Dietary	Dietary exposure	nmoles
Oral	Oral exposure	nmoles
Dermal	Dermal exposure	nmoles
Inhalation	Inhalation exposure	nmoles

Table 189 Model outputs
Id	Description	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 190 Model parameters
Id	Description	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		Other
gender	gender		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 191 Exposure routes (forcings)
Id	Description	Unit
Dietary	Dietary exposure	nmoles
Oral	Oral exposure	nmoles
Dermal	Dermal exposure	nmoles
Inhalation	Inhalation exposure	nmoles

Table 192 Model outputs
Id	Description	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 193 Model parameters
Id	Description	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		Other
gender	gender		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 194 Exposure routes (forcings)
Id	Description	Unit
Dietary	Dietary exposure	mmoles
Dermal	Dermal exposure	mmoles
Inhalation	Inhalatory exposure	mmoles

Table 195 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 196 Model parameters
Id	Description	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 197 Exposure routes (forcings)
Id	Description	Unit
Dietary	Dietary exposure	mmoles
Dermal	Dermal exposure	mmoles
Inhalation	Inhalatory exposure	mmoles

Table 198 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 199 Model parameters
Id	Description	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

Note

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