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> # R CMD BATCH --no-timing --no-restore --no-save montecarlo_tests.R montecarlo_tests.Rout
> 
> # Get rid of anything in the workspace:
> rm(list=ls()) 
> 
> library(httk)
> 
> # Reduce the number of samples used by Monte Carlo to decrease runtime for
> # CRAN checks (never use predictions with only ten draws):
> NSAMP <- 5
> 
> #
> #
> # Test that the underlying PK models give the same answers:
> calc_analytic_css(chem.cas="15972-60-8")
Plasma concentration returned in uM units.
[1] 0.1784
Warning messages:
1: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) :
  Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu.
2: In calc_ma(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Membrane affintity (MA) predicted with method of Yun and Edginton (2013), see calc_ma.
3: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment,  :
  Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction.
4: In available_rblood2plasma(chem.cas = chem.cas, species = species,  :
  Human in vivo measured Rblood2plasma used.
5: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
> calc_analytic_css(chem.cas="15972-60-8",model="1compartment")
Human volume of distribution returned in units of L/kg BW.
Plasma concentration returned in uM units.
[1] 0.1784
Warning messages:
1: In calc_ma(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Membrane affintity (MA) predicted with method of Yun and Edginton (2013), see calc_ma.
2: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment,  :
  Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction.
3: In available_rblood2plasma(chem.cas = chem.cas, chem.name = chem.name,  :
  Human in vivo measured Rblood2plasma used.
> calc_analytic_css(chem.cas="15972-60-8",model="pbtk")
Plasma concentration returned in uM units.
[1] 0.1784
Warning messages:
1: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) :
  Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu.
2: In calc_ma(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Membrane affintity (MA) predicted with method of Yun and Edginton (2013), see calc_ma.
3: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment,  :
  Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction.
4: In available_rblood2plasma(chem.cas = chem.cas, species = species,  :
  Human in vivo measured Rblood2plasma used.
5: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
> calc_analytic_css(chem.cas="15972-60-8",model="3compartment")
Plasma concentration returned in uM units.
[1] 0.1784
Warning messages:
1: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) :
  Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu.
2: In calc_ma(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Membrane affintity (MA) predicted with method of Yun and Edginton (2013), see calc_ma.
3: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment,  :
  Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction.
4: In available_rblood2plasma(chem.cas = chem.cas, species = species,  :
  Human in vivo measured Rblood2plasma used.
5: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
> 
> 
> 
> #
> #
> # Now test Monte Carlo for a variety of chemicals:
> # Clint and Fup are distributions, clint is zero:
> set.seed(1234)
> uM <- calc_mc_css(chem.cas="50594-66-6",samples=NSAMP,output.units="uM")
Human plasma concentration returned in uM units for 0.95 quantile.
Warning messages:
1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas,  :
  Clint is provided as a distribution.
2: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas,  :
  Fraction unbound is provided as a distribution.
3: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Clint is provided as a distribution.
4: In (function (chem.name = NULL, chem.cas = NULL, dtxsid = NULL,  :
  calc_analytic_css deprecated argument daily.dose replaced with new argument dose, value given assigned to dose
> set.seed(1234)
> mgpL <- calc_mc_css(chem.cas="50594-66-6",samples=NSAMP,output.units="mg/L")
Human plasma concentration returned in mg/L units for 0.95 quantile.
Warning messages:
1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas,  :
  Clint is provided as a distribution.
2: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas,  :
  Fraction unbound is provided as a distribution.
3: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Clint is provided as a distribution.
4: In (function (chem.name = NULL, chem.cas = NULL, dtxsid = NULL,  :
  calc_analytic_css deprecated argument daily.dose replaced with new argument dose, value given assigned to dose
> # Test unit conversions, molecular weight of Acifluorfen is 361.66:
> signif(mgpL/uM*1000,3)
95% 
362 
> # Human.Clint.pvalue > 0.05, no measured Rblood2plasma
> set.seed(1234)
> calc_mc_css(chem.cas="116-06-3",samples=NSAMP)
Human plasma concentration returned in mg/L units for 0.95 quantile.
  95% 
1.494 
Warning messages:
1: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
2: In (function (chem.name = NULL, chem.cas = NULL, dtxsid = NULL,  :
  calc_analytic_css deprecated argument daily.dose replaced with new argument dose, value given assigned to dose
> # Human.Funbound.plasma is below LOD (0.005), can't do PBPK, can't predict
> # Rblood2plasma
> set.seed(1234)
> calc_mc_css(chem.cas="101-05-3",samples=NSAMP)
Human plasma concentration returned in mg/L units for 0.95 quantile.
  95% 
2.369 
Warning messages:
1: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas,  :
  Fraction unbound below limit of detection.
2: In (function (chem.cas = NULL, chem.name = NULL, dtxsid = NULL,  :
  Fraction unbound = 0, changed to 0.005.
3: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
4: In (function (chem.name = NULL, chem.cas = NULL, dtxsid = NULL,  :
  calc_analytic_css deprecated argument daily.dose replaced with new argument dose, value given assigned to dose
> # well-behaved chemical with a measured Rblood2plasma:
> set.seed(1234)
> calc_mc_css(chem.cas="15972-60-8",samples=NSAMP)
Human plasma concentration returned in mg/L units for 0.95 quantile.
   95% 
0.1355 
Warning messages:
1: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
2: In (function (chem.name = NULL, chem.cas = NULL, dtxsid = NULL,  :
  calc_analytic_css deprecated argument daily.dose replaced with new argument dose, value given assigned to dose
> # Chemical where median fup is 0 but upper 95th percentile is non-zero:
> set.seed(1234)
> calc_mc_css(dtxsid="DTXSID5041726",samples=NSAMP)
Human plasma concentration returned in mg/L units for 0.95 quantile.
 95% 
1901 
Warning messages:
1: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas,  :
  Fraction unbound is provided as a distribution.
2: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
3: In (function (chem.name = NULL, chem.cas = NULL, dtxsid = NULL,  :
  calc_analytic_css deprecated argument daily.dose replaced with new argument dose, value given assigned to dose
> 
> #
> #
> # Now test that MC works across different models:
> set.seed(1234)
> calc_mc_css(chem.cas="15972-60-8",model="3compartment",samples=NSAMP)
Human plasma concentration returned in mg/L units for 0.95 quantile.
   95% 
0.1354 
Warning messages:
1: In calc_ma(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Membrane affintity (MA) predicted with method of Yun and Edginton (2013), see calc_ma.
2: In available_rblood2plasma(chem.cas = chem.cas, species = species,  :
  Human in vivo measured Rblood2plasma used.
3: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
4: In (function (chem.name = NULL, chem.cas = NULL, dtxsid = NULL,  :
  calc_analytic_css deprecated argument daily.dose replaced with new argument dose, value given assigned to dose
> set.seed(1234)
> calc_mc_css(chem.cas="15972-60-8",model="1compartment",samples=NSAMP)
Human volume of distribution returned in units of L/kg BW.
Human plasma concentration returned in mg/L units for 0.95 quantile.
   95% 
0.1413 
Warning messages:
1: In calc_ma(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Membrane affintity (MA) predicted with method of Yun and Edginton (2013), see calc_ma.
2: In available_rblood2plasma(chem.cas = chem.cas, chem.name = chem.name,  :
  Human in vivo measured Rblood2plasma used.
3: In (function (chem.name = NULL, chem.cas = NULL, dtxsid = NULL,  :
  calc_analytic_css deprecated argument daily.dose replaced with new argument dose, value given assigned to dose
> set.seed(1234)
> calc_mc_css(chem.cas="15972-60-8",model="pbtk",samples=NSAMP)
Human plasma concentration returned in mg/L units for 0.95 quantile.
   95% 
0.1354 
Warning messages:
1: In calc_ma(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Membrane affintity (MA) predicted with method of Yun and Edginton (2013), see calc_ma.
2: In available_rblood2plasma(chem.cas = chem.cas, species = species,  :
  Human in vivo measured Rblood2plasma used.
3: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
4: In (function (chem.name = NULL, chem.cas = NULL, dtxsid = NULL,  :
  calc_analytic_css deprecated argument daily.dose replaced with new argument dose, value given assigned to dose
> 
> # Should be the same as the mean result:
> calc_analytic_css(chem.cas="90-43-7",model="pbtk",output.units="mg/L")
Plasma concentration returned in mg/L units.
[1] 8.353
Warning messages:
1: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) :
  Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu.
2: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment,  :
  Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction.
3: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment,  :
  Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction.
4: In calc_rblood2plasma(chem.cas = chem.cas, species = species, adjusted.Funbound.plasma = adjusted.Funbound.plasma,  :
  Rblood2plasma has been recalculated.
5: In available_rblood2plasma(chem.cas = chem.cas, species = species,  :
  Human Rblood2plasma calculated with calc_rblood2plasma.
6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
>                    
> quit("no")
> proc.time()
   user  system elapsed 
  49.71    1.32   51.06