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:

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.