R Under development (unstable) (2024-03-19 r86153 ucrt) -- "Unsuffered Consequences"
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> # R CMD BATCH --no-timing --no-restore --no-save ivive_test.R ivive_test.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 <- 10
> 
> # From Honda et al. (2019) (currently only use mean conc's because steady-state 
> # calculation does not give max):
> #
> # Default HTTK function arguments correspond to "Honda3"
> #
> #       in vivo Conc.	   Metabolic Clearance  In Vivo Conc.  In Vitro Conc.
> #Honda1	Veinous (Plasma) Restrictive	        Free           Free
> #Honda2	Veinous	         Restrictive	        Free	         Nominal
> #Honda3	Veinous	         Restrictive	        Total	         Nominal
> #Honda4	Target Tissue    Non-restrictive	    Total	         Nominal
> #
> # "Honda1" uses plasma concentration, restrictive clearance, and treats the 
> # unbound invivo concentration as bioactive. For IVIVE, any input nominal 
> # concentration in vitro should be converted to cfree.invitro using 
> # \code{\link{armitage_eval}}, otherwise performance will be the same as 
> # "Honda2". 
> #
> # Use \code{\link{show_honda.ivive()}} to print summary of Honda et al. (2019)
> # results.
> 
> # Default HTTK: 
> set.seed(12345)
> Css0 <- calc_mc_css(chem.name="bisphenol a",
+   output.units="uM",
+   samples=NSAMP)
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,  :
  Default value of 1.6 used for Caco2 permeability.
> set.seed(12345)
> # This should be the same as calc_mc_oral_equiv:
> signif(3/Css0,4) ==
+   calc_mc_oral_equiv(3.0,chem.name="bisphenol a",
+     samples=NSAMP)
Human plasma concentration returned in uM units for 0.95 quantile.
uM concentration converted to mgpkgpday dose for 0.95 quantile.
 95% 
TRUE 
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,  :
  Default value of 1.6 used for Caco2 permeability.
> 
> # Honda1:
> set.seed(12345)
> Css1 <- calc_mc_css(chem.name="bisphenol a",
+   calc.analytic.css.arg.list=list(
+     restrictive.clearance = TRUE,
+     bioactive.free.invivo = TRUE),
+   output.units="uM",
+   samples=NSAMP)
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,  :
  Default value of 1.6 used for Caco2 permeability.
> temp <- armitage_eval(
+   casrn.vector = c("80-05-7"), 
+   this.FBSf = 0.1,
+   this.well_number = 384, 
+   nomconc = 3)
> cfree <- temp$cfree.invitro
> set.seed(12345)
> # This should be the same as calc_mc_oral_equiv with IVIVE=="Honda1":
> signif(cfree/Css1,4) ==
+   calc_mc_oral_equiv(cfree,chem.name="bisphenol a",
+     calc.analytic.css.arg.list=list(IVIVE="Honda1"),
+     samples=NSAMP)
Human plasma concentration returned in uM units for 0.95 quantile.
uM concentration converted to mgpkgpday dose for 0.95 quantile.
 95% 
TRUE 
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,  :
  Default value of 1.6 used for Caco2 permeability.
4: In honda.ivive(method = IVIVE, tissue = tissue) :
  Argument method ="Honda1" uses plasma concentration, restrictive clearance, and treats the unbound invivo concentration as bioactive.
            For IVIVE, any input nominal concentration in vitro should be converted to cfree.invitro using armitage_eval(),
            otherwise performance will be the same as "Honda2". Use show_honda.ivive() to print summary of Honda et al. 2019 results.
> # Should be different from default:
> !(Css1 %in% c(Css0))
[1] TRUE
> 
> # Honda2:
> set.seed(12345)
> Css2 <- calc_mc_css(chem.name="bisphenol a",
+   calc.analytic.css.arg.list=list(
+     restrictive.clearance = TRUE,
+     bioactive.free.invivo = TRUE),
+   output.units="uM",
+   samples=NSAMP)
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,  :
  Default value of 1.6 used for Caco2 permeability.
> set.seed(12345)
> # This should be the same as calc_mc_oral_equiv with IVIVE=="Honda2":
> signif(3/Css2,4) ==
+   calc_mc_oral_equiv(3.0,chem.name="bisphenol a",
+     calc.analytic.css.arg.list=list(IVIVE="Honda2"),
+     samples=NSAMP)
Human plasma concentration returned in uM units for 0.95 quantile.
uM concentration converted to mgpkgpday dose for 0.95 quantile.
 95% 
TRUE 
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,  :
  Default value of 1.6 used for Caco2 permeability.
4: In honda.ivive(method = IVIVE, tissue = tissue) :
  Argument method ="Honda2" uses plasma concentration, restrictive clearance, and treats the unbound concentration as bioactive.
> # Should be different from previous:
> !(Css2 %in% c(Css0))
[1] TRUE
> 
> # Honda 3 (should be the same as degault HTTK):
> set.seed(12345)
> Css3 <- calc_mc_css(chem.name="bisphenol a",
+   calc.analytic.css.arg.list=list(
+     restrictive.clearance = TRUE,
+     bioactive.free.invivo = FALSE),
+   output.units="uM",
+   samples=NSAMP)
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,  :
  Default value of 1.6 used for Caco2 permeability.
> set.seed(12345)
> # This should be the same as calc_mc_oral_equiv with IVIVE=="Honda3":
> signif(3/Css3,4) ==
+   calc_mc_oral_equiv(3.0,chem.name="bisphenol a",
+     calc.analytic.css.arg.list=list(IVIVE="Honda3"),
+     samples=NSAMP)
Human plasma concentration returned in uM units for 0.95 quantile.
uM concentration converted to mgpkgpday dose for 0.95 quantile.
 95% 
TRUE 
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,  :
  Default value of 1.6 used for Caco2 permeability.
4: In honda.ivive(method = IVIVE, tissue = tissue) :
  Argument method ="Honda3" uses plasma concentration, restrictive clearance, and treats the total concentration as bioactive.
            This is equivalent to the default httk assumptions.
> # Should be same as default:
> Css0 == Css3
 95% 
TRUE 
> # Should be different from previous:
> !(Css3 %in% c(Css1, Css2))
[1] TRUE
> 
> # Honda4:
> set.seed(12345)
> Css4 <- calc_mc_css(chem.name="bisphenol a",
+   calc.analytic.css.arg.list=list(
+     tissue="liver",
+     restrictive.clearance = FALSE,
+     bioactive.free.invivo = FALSE),
+   model="pbtk",
+   output.units="uM",
+   samples=NSAMP)
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 available_rblood2plasma(chem.cas = chem.cas, species = species,  :
  Human in vivo measured Rblood2plasma used.
4: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
> set.seed(12345)
> # This should be the same as calc_mc_oral_equiv with IVIVE=="Honda4":
> signif(3/Css4,4) ==
+   calc_mc_oral_equiv(3.0,chem.name="bisphenol a",
+     calc.analytic.css.arg.list=list(IVIVE="Honda4"),
+     samples=NSAMP,
+     model="pbtk")
Human plasma concentration returned in uM units for 0.95 quantile.
uM concentration converted to mgpkgpday dose for 0.95 quantile.
 95% 
TRUE 
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 available_rblood2plasma(chem.cas = chem.cas, species = species,  :
  Human in vivo measured Rblood2plasma used.
4: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid,  :
  Default value of 1.6 used for Caco2 permeability.
5: In honda.ivive(method = IVIVE, tissue = tissue) :
  Argument method ="Honda4" uses target tissue (liver) concentration, non-restrictive clearance, and treats the total concentration as bioactive.
> # Should be different from previous:
> !(Css4 %in% c(Css0, Css1, Css2, Css3))
[1] TRUE
> 
> # Quit without saving or displaying messages:
> quit("no")
> proc.time()
   user  system elapsed 
  14.82    0.64   15.48