Evaluate the Armitage model for chemical distributon in vitro. Takes input as data table or vectors of values. Outputs a data table. Updates over the model published in Armitage et al. (2014) include binding to plastic walls and lipid and protein compartments in cells.
armitage_eval(
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
casrn.vector = NA_character_,
nomconc.vector = 1,
this.well_number = 384,
this.FBSf = NA_real_,
tcdata = NA,
user_assay_parameters = NA,
this.sarea = NA_real_,
this.v_total = NA_real_,
this.v_working = NA_real_,
this.cell_yield = NA_real_,
this.Tsys = 37,
this.Tref = 298.15,
this.option.kbsa2 = FALSE,
this.option.swat2 = FALSE,
this.option.kpl2 = FALSE,
this.option.bottom = TRUE,
this.pseudooct = 0.01,
this.memblip = 0.04,
this.nlom = 0.05,
this.P_nlom = 0.035,
this.P_dom = 0.05,
this.P_cells = 1,
this.cell_pH = 7.4,
this.Anionic_VF = 0.175,
this.A_Prop_acid = 0.05,
this.A_Prop_base = 20,
this.Lyso_VF = 0.0068,
this.Lyso_Diam = 500,
this.Lyso_pH = 5.1,
this.csalt = 0.15,
this.celldensity = 1,
this.cellmass = 3,
this.f_oc = 1,
this.conc_ser_alb = 24,
this.conc_ser_lip = 1.9,
this.Vdom = 0,
this.pH = 7,
restrict.ion.partitioning = FALSE,
surface.area.switch = TRUE
)| Param | Description | Units |
| casrn | Chemical Abstracts Service Registry Number | character |
| nomconc | Nominal Concentration | uM=umol/L |
| well_number | Number of wells in plate (used to set default surface area) | unitless |
| sarea | Surface area of well | m^2 |
| v_total | Total volume of well | uL |
| v_working | Filled volume of well | uL |
| cell_yield | Number of cells | cells |
| assay_component_endpoint_name | link to invitro.assay.params table | character |
| gkow | The log10 octanol to water (PC) (logP) | log10 unitless ratio |
| logHenry | The log10 Henry's law constant ' | log10 unitless ratio |
| gswat | The log10 water solubility (logWSol) | log10 mg/L |
| MP_C | The chemical compound melting point | degrees Celcius |
| MP_K | The chemical compound melting point | degrees Kelvin |
| MW | The chemical compound molecular weight | g/mol |
| gkaw | The air to water PC | unitless ratio |
| duow | internal energy of phase change for octanol-water | J/mol |
| duaw | internal energy of phase change for air-water | J/mol |
| gkmw | The log10 membrane to water PC | log10 unitless ratio |
| gkcw | The log10 cell/tissue to water PC | log10 unitless ratio |
| gkbsa | The log10 bovine serum albumin to water PC | log10 unitless ratio |
| gkpl | The log10 plastic to water PC | log10 m2/m2 |
| ksalt | Setschenow constant | L/mol |
| Tsys | System temperature | degrees C |
| Tref | Reference temperature | degrees K |
| option.kbsa2 | Use alternative bovine-serum-albumin partitioning model | logical |
| option.swat2 | Use alternative water solubility correction | logical |
| option.kpl2 | Use alternative plastic-water partitioning model | logical |
| FBSf | Fraction fetal bovine serum | unitless |
| pseudooct | Pseudo-octanol cell storage lipid content | |
| memblip | Membrane lipid content of cells | unitless |
| nlom | Structural protein content of cells | unitless |
| P_nlom | Proportionality constant to octanol structural protein | unitless |
| P_dom | Proportionality constant to dissolved organic material (DOM) | unitless |
| P_cells | Proportionality constant to octanol storage lipid | unitless |
| Anionic_VF | Anionic phospholipid fraction | unitless |
| A_Prop_acid | Sorption to anionic lipids - acidic chemicals | unitless |
| A_Prop_base | Sorption to anionic lipids - basic chemicals | unitless |
| Lyso_VF | Lysosome volume fraction | unitless |
| Lyso_Diam | Diameter of lysosome | nm |
| Lyso_pH | pH of lysosome | unitless |
| csalt | Ionic strength of buffer | M=mol/L |
| celldensity | Cell density | kg/L, g/mL |
| cellmass | Mass per cell | ng/cell |
| f_oc | Indicates fraction of dissolved organic matter to be treated like proteins | unitless |
| cellwat | Fraction of the cell made up of water | unitless |
| Tcor | Temperature correction | |
| Vm | Volume of media | L |
| Vwell | Volume of medium (aqueous phase only) | L |
| Vair | Volume of head space | L |
| Vcells | Volume of cells/tissue | L |
| Valb | Volume of serum albumin | L |
| Vslip | Volume of serum lipids | L |
| Vdom | Volume of dissolved organic matter | L |
| F_ratio | Fugacity ratio | unitless |
| kmw | The membrane to water PC (i.e., 10^gkmow | unitless |
| kow | The octanol to water PC (i.e., 10^gkow) | unitless |
| kaw | The air to water PC (i.e., 10^gkaw) | unitless |
| swat | The intrinsic water solubility (i.e., 10^gswat) | mg/L |
| kpl | The plastic to water PC (i.e., 10^gkpl) | m3/m2 |
| kcw | The cell/tissue to water PC (i.e., 10^gkcw) | unitless |
| kbsa | The bovine serum albumin to water PC | unitless |
| swat_L | Water solubility limit used for Fugacity ratio calculation | |
| mtot | Total micromoles | umol |
| cwat | Total concentration in water | uM=umol/L |
| cwat_s | Dissolved concentration in water | uM=umol/L |
| csat | Is the solution saturated (1/0) | logical |
| activity | Chemical activity; indicates the potential for baseline toxicity to occur | |
| cair | Concentration in head space | uM=umol/L |
| calb | Concentration in serum albumin | uM=umol/L |
| cslip | Concentration in serum lipids | uM=umol/L |
| cdom | Concentration in dissolved organic matter | uM=umol/L |
| ccells | Concentration in cells | uM=umol/L |
| cplastic | Concentration in plastic | uM=umol/m^2 |
| mwat_s | Mass dissolved in water | umols |
| mair | Mass in air/head space | umols |
| mbsa | Mass bound to bovine serum albumin | umols |
| mslip | Mass bound to serum lipids | umols |
| mdom | Mass bound to dissolved organic matter | umols |
| mcells | Mass in cells | umols |
| mplastic | Mass bond to plastic | umols |
| mprecip | Mass precipitated out of solution | umols |
| xwat_s | Fraction dissolved in water | fraction |
| xair | Fraction in the air | fraction |
| xbsa | Fraction bound to bovine serum albumin | fraction |
| xslip | Fraction bound to serum lipids | fraction |
| xdom | Fraction bound to dissolved organic matter | fraction |
| xcells | Fraction within cells | fraction |
| xplastic | Fraction bound to plastic | fraction |
| xprecip | Fraction precipitated out of solution | fraction |
| eta_free | Effective availability ratio | fraction |
| cfree.invitro | Free concentration in the in vitro media (use for Honda1 and Honda2) | fraction |
A single or vector of Chemical Abstracts Service Registry Number(s) (CAS-RN) of desired chemical(s).
A single or vector of name(s)) of desired chemical(s).
A single or vector ofEPA's DSSTox Structure ID(s) (https://comptox.epa.gov/dashboard)
A deprecated argument specifying a single or vector of Chemical Abstracts Service Registry Number(s) (CAS-RN) of desired chemical(s).
For vector or single value, micromolar (uM = mol/L) nominal concentration (e.g. AC50 value)
For single value, plate format default is 384, used
if is.na(tcdata)==TRUE. This value chooses default surface area settings for
armitage_estimate_sarea based on the number of wells per plate.
Fraction fetal bovine serum, must be entered by user.
A data.table with casrn, nomconc, MP, gkow, gkaw, gswat, sarea,
v_total, v_working. Otherwise supply single values to this.params (e.g., this.sarea,
this.v_total, etc.). Chemical parameters are taken from
chem.physical_and_invitro.data.
option to fill in your own assay parameters (data table)
Surface area per well (m^2)
Total volume per well (uL)
Working volume per well (uL)
Number of cells per well
System temperature (degrees C)
Reference temperature (degrees K)
Use alternative bovine-serum-albumin partitioning model
Use alternative water solubility correction
Use alternative plastic-water partitioning model
Include the bottom of the well in surface area calculation
Pseudo-octanol cell storage lipid content
Membrane lipid content of cells
Structural protein content of cells
Proportionality constant to octanol structural protein
Proportionality constant to dissolve organic material
Proportionality constant to octanol storage lipid
7.4, pH of cell
Anionic phospholipid fraction
Sorption to anionic lipids - acidic chemicals
Sorption to anionic lipids - basic chemicals
lysosome volume fraction
diameter of lysosome (500 nm)
pH of lysosome (5.1)
Ionic strength of buffer (M = mol/L)
Cell density kg/L, g/mL
Mass per cell, ng/cell
Everything assumed to be like proteins
Mass concentration of albumin in serum (g/L)
Mass concentration of lipids in serum (g/L)
0 ml, the volume of dissolved organic matter (DOM)
pH of cell culture
FALSE, Should we restrict the chemical available to partition to only the neutral fraction?
TRUE, automatically calculates surface area, switch to FALSE if user provided
Greg Honda, Meredith Scherer adapted from code by James Armitage, Jon Arnot
armitage2014applicationhttk
honda2019usinghttk
library(httk)
# Check to see if we have info on the chemical:
"80-05-7" %in% get_cheminfo()
#We do:
temp <- armitage_eval(casrn.vector = c("80-05-7", "81-81-2"), this.FBSf = 0.1,
this.well_number = 384, nomconc = 10)
print(temp$cfree.invitro)
# Check to see if we have info on the chemical:
"793-24-8" %in% get_cheminfo()
# Since we don't have any info, let's look up phys-chem from dashboard:
cheminfo <- data.frame(
Compound="6-PPD",
CASRN="793-24-8",
DTXSID="DTXSID9025114",
logP=4.27,
logHenry=log10(7.69e-8),
logWSol=log10(1.58e-4),
MP= 99.4,
MW=268.404
)
# Add the information to HTTK's database:
chem.physical_and_invitro.data <- add_chemtable(
cheminfo,
current.table=chem.physical_and_invitro.data,
data.list=list(
Compound="Compound",
CAS="CASRN",
DTXSID="DTXSID",
MW="MW",
logP="logP",
logHenry="logHenry",
logWSol="logWSol",
MP="MP"),
species="Human",
reference="CompTox Dashboard 31921")
# Run the Armitage et al. (2014) model:
out <- armitage_eval(
casrn.vector = "793-24-8",
this.FBSf = 0.1,
this.well_number = 384,
nomconc = 10)
print(out)
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