{"text_format":"1","workbook":"xlsx","n_sheets":15,"sheets":["introduction","compound input data","organism input data","BMF","k1","k2 - lung","k2 - hepatic biotransf","k2 - lung biotransf","k2 - GIT biotransf","k2 - kidney biotransf","k2 - feces","k2 - urine","references","glossary","Tabelle1"],"not_rendered":{"charts":0,"images":3,"macros":1,"external_links":0,"defined_names":114,"comments":1,"pivot_tables":0},"unopened":[],"bounds":{"document_bytes":16777216,"sheet_cells":100000,"rows_first":2000,"rows_last":500,"rows_between":2000,"halvings":0,"cell_chars":16384,"cell_head_chars":4096},"cells_cut":0,"cells_raw":0,"read":"whole","date_system":"1900"}

{"sheet":"introduction","index":0,"n_rows":33,"n_cols":2,"rows_kept":33,"cut":false,"hidden":false,"merged":[]}
[]
[null,"For correct functioning of this sheet, support of Visual Basic for Applications is required."]
[null,"So please confirm 'enable macros' when a safety warning pops up."]
[null,"For more details on the application of 'B-compass rat', please refer to the manual:"]
[]
[]
[null,"B-compass rat, version 1.0 (September 2022):"]
[null,"This file represents a tool for calculation of rat biomagnification factors (BMFs). For the calculation, two BMF"]
[null,"model variants are implemented: "]
[null,"          - a simple one-compartment model "]
[null,"          - and a more complex steady state multi-compartment model."]
[null,"Both models calculate the BMF from uptake and elimination rate constants. The uptake rate constant k1 reflects "]
[null,"the uptake of the chemical via diet, the elimination is a combination of elimination via ventilation, fecal"]
[null,"egestion and biotransformation."]
[null,"For the calculation, information on the chemical's partition properties are required. The partition properties of"]
[null,"a chemical are estimated from KOW- and KOA-correlations."]
[]
[]
[null,"For the user, the following three sheets are most essential:"]
[null," - compound input data sheet (partition information & in vitro biotranformation data need to be entered)"]
[null," - organism input data sheet (bodyweight of modeled rat needs to be entered)"]
[null," - BMF sheet (presents results of the calculations & supporting graphs)"]
[]
[null,"All background calculations (i.e. how the required rate constants are calculated from the given input data)"]
[null,"are shown in the additional sheets so that interested users can understand the calculation methods. These"]
[null,"sheets require no modification by the user."]
[null,"Finally there is a reference and a glossary sheet summarizing the used variable names."]
[]
[]
[]
[null,"Note: Users may modify this sheet according to their needs. We thus recommend that new users do not accept this file "]
[null,"from third parties, but always download it as an original copy from www.ufz.de/b-compass-rat. "]
[null,"Feel free to share any problems, suggestions, wishes or success with us!"]

{"sheet":"compound input data","index":1,"n_rows":103,"n_cols":13,"rows_kept":103,"cut":false,"hidden":false,"merged":[[2,1,2,4],[9,1,10,1],[9,2,10,2],[4,1,4,2]]}
[null,"INPUT PARAMETERS"]
[]
[null,"compound-specific input cells that need to be entered by the user are marked with orange colour"]
[]
[null,"compound name",null,"b(a)p"]
[null,"chemical concentration in food Cfood [gchemical/gfood]",null,0.1," assumed value"]
[]
[null,"1) log KOW and log KOA of the chemical"]
[]
[null,"log KOW [LH2O/Loctanol]","log KOA [Lair/Loctanol]"]
[]
[null,8,10]
[]
[]
[null,"2) Information from in vitro biotransformation assay"]
[]
[null,"Select the type of in vitro information (S9, cell or microsome assay) you want to use and insert the required input data. In case biotrans-"]
[null,"formation data is not available for all tissues, select 'N/A' for the cases where information is missing."]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[null,"a) hepatic biotransformation",null,null,null,"b) lung biotransformation",null,null,"c) GIT biotransformation",null,null,"d) kidney biotransformation"]
[]
[null,"Please tick as appropriate:",null,null,null,"Please tick as appropriate:",null,null,"Please tick as appropriate:",null,null,"Please tick as appropriate:"]
[]
[]
[]
[]
[]
[]
[null," - liver S9-Assay",null,null,null," - lung S9-Assay ",null,null," - GIT S9-Assay ",null,null," - kidney S9-Assay "]
[null,"kassay [1/h]",{"$f":"0.022*60","v":1.3199999999999998},null,null,"kassay [1/h]",5,null,"kassay [1/h]",1,null,"kassay [1/h]",1]
[null,"CS9 in assay [mgS9/mLassay]",1.2,null,null,"CS9 in assay [mgS9/mLassay]",1,null,"CS9 in assay [mgS9/mLassay]",1,null,"CS9 in assay [mgS9/mLassay]",1]
[null,"Vassay [mLassay]",1,null,null,"Vassay [mLassay]",1,null,"Vassay [mLassay]",1,null,"Vassay [mLassay]",1]
[]
[null," - hepatocyte assay",null,null,null," - cell assay",null,null," - cell assay",null,null," - cell assay"]
[null,"kassay [1/h]",50,null,null,"kassay [1/h]",0.1,null,"kassay [1/h]",0.1,null,"kassay [1/h]",0.1]
[null,"Cviable cells in assay \n[* 106 cells/mLassay]",2,null,null,"Cviable cells in assay \n[* 106 cells/mLassay]",2,null,"Cviable cells in assay                    [* 106 cells/mLassay]",2,null,"Cviable cells in assay                    [* 106 cells/mLassay]",2]
[null,"viability",0.85,null,null,"viability",0.85,null,"viability",0.85,null,"viability",0.85]
[null,"Vassay [mLassay]",1,null,null,"Vassay [mLassay]",1,null,"Vassay [mLassay]",1,null,"Vassay [mLassay]",1]
[]
[null," - microsome assay",null,null,null," - microsome assay",null,null," - microsome assay",null,null," - microsome assay"]
[null,"kassay [1/h]",{"$f":"0.022*60","v":1.3199999999999998},null,null,"kassay [1/h]",5,null,"kassay [1/h]",{"$f":"0.022*60","v":1.3199999999999998},null,"kassay [1/h]",{"$f":"0.022*60","v":1.3199999999999998}]
[null,"Cmicrosomes in assay [mgmic/mLassay]",1.2,null,null,"Cmicrosomes in assay [mgmic/mLassay]",2,null,"Cmicrosomes in assay [mgmic/mLassay]",1.2,null,"Cmicrosomes in assay [mgmic/mLassay]",1.2]
[null,"Vassay [mLassay]",1,null,null,"Vassay [mLassay]",1,null,"Vassay [mLassay]",1,null,"Vassay [mLassay]",1]
[]
[]
[]
[null,"CALCULATED PARAMETERS - no changes by the user required"]
[]
[null,"Water contents in assay"]
[null,"a) hepatic assay",null,null,null,"a) lung assay",null,null,"a) intestinal assay",null,null,"a) renal assay"]
[null,"S9 volume present in assay VS9 [mL]",{"$f":"(C50*(CliverSnine/1000))/'organism input data'!D109","v":9.2680705748434831E-4}," = (Vassay * CS9/1000) / ρS9",null,"S9 volume present in assay VS9 [mL]",{"$f":"(G50*(G49/1000))/'organism input data'!D109","v":7.7233921457029028E-4},null,"S9 volume present in assay VS9 [mL]",{"$f":"(J50*(J49/1000))/'organism input data'!D109","v":7.7233921457029028E-4},null,"S9 volume present in assay VS9 [mL]",{"$f":"(M50*(M49/1000))/'organism input data'!D109","v":7.7233921457029028E-4}]
[null,"S9-assay water content wassay",{"$f":"(C50-C69)/C50","v":0.99907319294251562}," = (Vassay - VS9)) / Vassay",null,"S9-assay water content wassay",{"$f":"(G50-G69)/G50","v":0.99922766078542968},null,"S9-assay water content wassay",{"$f":"(J50-J69)/J50","v":0.99922766078542968},null,"S9-assay water content wassay",{"$f":"(M50-M69)/M50","v":0.99922766078542968}]
[null,"total hepatocyte volume present in assay Vhep [mLhep]",{"$f":"(Chep*10^6*C56)/C55*1/6*PI()*dhep^3","v":1.4033217184233815E-2}," = (Cviable cells * 106 * Vhepassay)/viability * Vsinglecell ",null,"total cell volume present in assay Vlungcells [mLcells]",{"$f":"('compound input data'!G54*10^6*'compound input data'!G56)/'compound input data'!G55*(1/6*PI()*'organism input data'!D89^3)","v":0.51974878460125251},null,"total cell volume present in assay Vgutcells [mLcells]",{"$f":"('compound input data'!J54*10^6*'compound input data'!J56)/'compound input data'!J55*(1/6*PI()*'organism input data'!D91^3)","v":3.3263922214480164E-2},null,"total cell volume present in assay Vkidneycells [mLcells]",{"$f":"('compound input data'!M54*10^6*'compound input data'!M56)/'compound input data'!M55*(1/6*PI()*'organism input data'!D94^3)","v":3.3263922214480164E-2}]
[null,"hep-assay water content wassay",{"$f":"(C56-Vhep)/C56","v":0.98596678281576622}," = (Vassay - Vhep ) / Vassay",null,"lung-assay water content wassay",{"$f":"('compound input data'!G56-G71)/'compound input data'!G56","v":0.48025121539874749},null,"gut assay water content wassay",{"$f":"('compound input data'!J56-J71)/'compound input data'!J56","v":0.96673607778551984},null,"kidney assay water content wassay",{"$f":"('compound input data'!M56-M71)/'compound input data'!M56","v":0.96673607778551984}]
[null,"microsome volume present in assay Vmic [mL]",{"$f":"C61*C60/1000","v":1.1999999999999999E-3},null,null,"microsome volume present in assay Vmic [mL]",{"$f":"G61*G60/1000","v":2E-3},null,"microsome volume present in assay Vmic [mL]",{"$f":"J61*J60/1000","v":1.1999999999999999E-3},null,"microsome volume present in assay Vmic [mL]",{"$f":"M61*M60/1000","v":1.1999999999999999E-3}]
[null,"microsome assay water content wassay",{"$f":"(C61-C73)/C61","v":0.99880000000000002},null,null,"microsome assay water content wassay",{"$f":"(G61-G73)/G61","v":0.998},null,"microsome assay water content wassay",{"$f":"(J61-J73)/J61","v":0.99880000000000002},null,"microsome assay water content wassay",{"$f":"(M61-M73)/M61","v":0.99880000000000002}]
[]
[]
[null,"Partition information"]
[]
[null,"Korganism/W [LH2O/LOrg]",{"$f":"lipidorganism*10^logKow+'organism input data'!C32*0.05*10^logKow+worganism","v":8355000.6979499999}," = proteinorganism * 0.05 * KOW+ lipidorganism * KOW + worganism"]
[null,"Kblood/W [LH2O/Lblood]",{"$f":"('organism input data'!C28+'organism input data'!D28)*0.05*10^logKow+'organism input data'!E28*10^logKow+'organism input data'!F28*(0.3*10^logKow+0.7)+wblood","v":2840000.8254}," = proteinblood * 0.05 * KOW + n.lipidblood * KOW + ph.lipidblood * (0.3 * KOW + 0.7) + wblood               from Lee et al. 2017"]
[null,"Khep/W [LH2O/Lhep]",{"$f":"'organism input data'!C36*0.05*10^logKow+'organism input data'!D36*10^logKow+'organism input data'!E36*(0.3*10^logKow+0.7)+whep","v":3543500.7262100005}," = proteinhep * 0.05 * KOW + n.lipidhep * KOW + ph.liphep* (0.3 * KOW + 0.7) + whep                       from Lee et al. 2017"]
[null,"Klungcell/W [LH2O/Llungcell]",{"$f":"'organism input data'!C40*Kpw+'organism input data'!D40*10^logKow++'organism input data'!E40*(0.3*10^logKow+0.7)+wlung","v":3480500.7998000002}," = proteinlung * 0.05 * KOW + n.lipidlung * KOW + ph.liplung* (0.3 * KOW + 0.7) + wlung                     "]
[null,"Kgutcell/W [LH2O/Lgutcell]",{"$f":"'organism input data'!C44*Kpw+'organism input data'!D44*10^logKow+'organism input data'!E4*(0.3*10^logKow+0.7)+wgut","v":3960000.7489999998}," = proteingut * 0.05 * KOW + n.lipidgut * KOW + ph.lipgut* (0.3 * KOW + 0.7) + wgut                      "]
[null,"Kkidneycell/W [LH2O/Lkidneycell]",{"$f":"'organism input data'!C48*Kpw+'organism input data'!D48*10^logKow+'organism input data'!E48*(0.3*10^logKow+0.7)+wkidney","v":3023500.7908800002}," = proteinkidney * 0.05 * KOW + n.lipidkidney * KOW + ph.lipkidney* (0.3 * KOW + 0.7) + wkidney                      "]
[null,"Krestbody/W [LH2O/Lrestbody]",{"$f":"(Vhepliver/mbody*Khepw+Vgut/mbody*Kgutcellw+Vlung/mbody*Klungcellw+Vkidney/mbody*Kkidneycellw-Korganismw)/(-(mbody-Vhepliver-Vgut-Vlung-Vkidney)/mbody)","v":8530460.5130574387}," = (Vliver/Vbody * Khep/W + Vgut/Vbody * Kgutcell/W + Vlung/Vbody * Klungcell/W + Vkidney/mbody*Kkidneycellw - Korganism/W) / (-Vrestbody/Vbody))"]
[null,"Kprotein/w [Lw/Lprotein]",{"$f":"0.05*10^logKow","v":5000000}," = 0.05 * 10logKow"]
[null,"Kwater/air [Lair/LH2O]",{"$f":"1/(10^logKow)*10^logKoa","v":100}," = KOA / KOW"]
[null,"Korganism/air [Lair/Lorg]",{"$f":"Korganismw*C87","v":835500069.79499996}," = Korganism/water * Kwater/air"]
[null,"Kfood/water [LH2O/Lfood]",{"$f":"'organism input data'!D60*10^logKow+'organism input data'!C60*0.05*10^logKow+('organism input data'!E60*0.7*10^logKow+'organism input data'!E60*0.3*1)+(1-'organism input data'!D60-'organism input data'!C60-'organism input data'!E60)","v":15900000.67}," = n.lipidfood * KOW + proteinfood * 0.05 * KOW + n.lipidkidney * KOW + ph.lipkidney* (0.3 * KOW + 0.7) + wkidney                      "]
[null,"Kfood/air [Lair/Lfood]",{"$f":"C89*Kwaterair","v":1590000067}," = Kfood/water * Kwater/air"]
[null,"fu,blood",{"$f":"wblood/Kbloodw","v":2.8521118471362262E-7}," = wblood / Kblood/H2O"]
[null,"fu,liverS9-assay",{"$f":"wliverS9assay/((C69*'organism input data'!B52)/C50*0.05*10^logKow+(C69*'organism input data'!C52)/C50*10^logKow+wliverS9assay)","v":3.593997772284604E-5}," = wliverS9assay / ( proteinliverS9assay * 0.05 * KOW + lipidliverS9assay * KOW + wliverS9assay )         from Lee et al. 2017"]
[null,"fu,hep-assay",{"$f":"whepassay/((C71*'organism input data'!C36)/Vhepassay*0.05*10^logKow+(C71*'organism input data'!D36)/Vhepassay*10^logKow+(C71*'organism input data'!E36)/Vhepassay*(0.3*10^logKow+0.7)+whepassay)","v":1.9827318661189689E-5}," = whepassay / ( proteinhepassay * 0.05 * KOW + lipidhepassay * KOW + whepassay )                        from Lee et al. 2017"]
[null,"fu,liver mic-assay",{"$f":"wlivermicassay/((C73*'organism input data'!B56)/C61*Kpw+(C73*'organism input data'!C56)/C61*10^logKow+wlivermicassay)","v":2.775049115013123E-5}," = wmicassay / ( proteinmicassay * 0.05 * KOW + lipidmicassay * KOW + wmicassay )                       "]
[null,"fu,lungS9-assay",{"$f":"wlungS9assay/((G69*'organism input data'!B52)/G50*0.05*10^logKow+(G69*'organism input data'!C52)/G50*10^logKow+wlungS9assay)","v":4.3134330995423301E-5}," = wlungS9assay / ( proteinlungS9assay * 0.05 * KOW + lipidlungS9assay * KOW + wlungS9assay )              from Lee et al. 2017"]
[null,"fu,lungcell-assay",{"$f":"wlungcellassay/((G71*'organism input data'!C36)/G56*0.05*10^logKow+(G71*'organism input data'!D36)/G56*10^logKow+(G71*'organism input data'!E36)/G56*(0.3*10^logKow+0.7)+wlungcellassay)","v":2.6076087954843829E-7}," = wlungcellassay / ( proteinlungcellassay * 0.05 * KOW + lipidlungcellassay * KOW + wlungcellassay )          from Lee et al. 2017"]
[null,"fu,lung mic-assay",{"$f":"wlungmicassay/((G73*'organism input data'!B56)/G61*Kpw+(G73*'organism input data'!C56)/G61*10^logKow+wlungmicassay)","v":1.6637143348276209E-5}," = wmicassay / ( proteinmicassay * 0.05 * KOW + lipidmicassay * KOW + wmicassay )                       "]
[null,"fu,gutS9-assay",{"$f":"wgutS9assay/((J69*'organism input data'!B52)/J50*0.05*10^logKow+(J69*'organism input data'!C52)/J50*10^logKow+wgutS9assay)","v":4.3134330995423301E-5}," = wgutS9assay / ( proteingutS9assay * 0.05 * KOW + lipidgutS9assay * KOW + wgutS9assay )              from Lee et al. 2017"]
[null,"fu,gutcell-assay",{"$f":"wgutcellassay/((J71*'organism input data'!C36)/J56*0.05*10^logKow+(J71*'organism input data'!D36)/J56*10^logKow+(J71*'organism input data'!E36)/J56*(0.3*10^logKow+0.7)+wgutcellassay)","v":8.2015978067129047E-6}," = wgutcellassay / ( proteingutcellassay * 0.05 * KOW + lipidgutcellassay * KOW + wgutcellassay )          from Lee et al. 2017"]
[null,"fu,gut mic-assay",{"$f":"wgutmicassay/((J73*'organism input data'!B56)/J61*Kpw+(J73*'organism input data'!C56)/J61*10^logKow+wgutmicassay)","v":2.775049115013123E-5}," = wmicassay / ( proteinmicassay * 0.05 * KOW + lipidmicassay * KOW + wmicassay )                       "]
[null,"fu,kidneyS9-assay",{"$f":"wkidneyS9assay/((M69*'organism input data'!B52)/M50*0.05*10^logKow+(M69*'organism input data'!C52)/M50*10^logKow+wkidneyS9assay)","v":4.3134330995423301E-5}," = wkidneyS9assay / ( proteinkidneyS9assay * 0.05 * KOW + lipidkidneyS9assay * KOW + wkidneyS9assay )"]
[null,"fu,kidneycell-assay",{"$f":"wkidneycellassay/((M71*'organism input data'!C36)/M56*0.05*10^logKow+(M71*'organism input data'!D36)/M56*10^logKow+(M71*'organism input data'!E36)/M56*(0.3*10^logKow+0.7)+wkidneycellassay)","v":8.2015978067129047E-6}," = wgutcellassay / ( proteinkidneycellassay * 0.05 * KOW + lipidkidneycellassay * KOW + wkidneycellassay )"]
[null,"fu,kidney mic-assay",{"$f":"wkidneymicassay/((M73*'organism input data'!B56)/M61*Kpw+(M73*'organism input data'!C56)/M61*10^logKow+wkidneymicassay)","v":2.775049115013123E-5}," = wmicassay / ( proteinmicassay * 0.05 * KOW + lipidmicassay * KOW + wmicassay )                       "]

{"sheet":"organism input data","index":2,"n_rows":132,"n_cols":6,"rows_kept":132,"cut":false,"hidden":false,"merged":[[114,1,114,2],[119,1,119,2],[129,1,129,2],[131,1,131,2],[128,1,128,2],[126,1,126,2],[127,1,127,2],[130,1,130,2],[125,1,125,2],[124,1,124,2],[121,1,121,2],[123,1,123,2],[116,1,116,2],[117,1,117,2],[118,1,118,2],[113,1,113,2],[111,1,111,2],[112,1,112,2],[110,1,110,2],[108,1,108,2],[63,1,63,2],[68,1,68,2],[73,1,73,2],[78,1,78,2],[93,1,93,2],[84,1,84,2],[66,1,66,2],[70,1,70,2],[79,1,79,2],[80,1,80,2],[81,1,81,2],[64,1,64,2],[75,1,75,2],[85,1,85,2],[65,1,65,2],[69,1,69,2],[71,1,71,2],[98,1,98,2],[103,1,103,2],[74,1,74,2],[76,1,76,2],[91,1,91,2],[88,1,88,2],[90,1,90,2],[102,1,102,2],[94,1,94,2],[97,1,97,2],[99,1,99,2],[86,1,86,2],[100,1,100,2],[101,1,101,2]]}
[null,"INPUT PARAMETERS"]
[]
[null,"organism-specific input cells that need to be entered by the user are marked with blue colour"]
[]
[null,"bodyweight mbody [grat]",200]
[]
[]
[]
[null,"Additionally, physiological information is required. Typical default values for all required parameters are provided (see below)"]
[null,"so that no further information needs to be entered by the user. If desired, however, the user can of course modify the"]
[null,"parameter values."]
[]
[null,"For the one-compartment model, only information on the composition (lipid, protein and water contents) and scaling factors"]
[null,"(e.g. S9 content of the liver) are needed."]
[null,"The multi-compartment model additionally requires information on blood flow rates (cardiac output, organ flow rates) and"]
[null,"organ volumes."]
[]
[]
[]
[null,"Below is a list of the used default values for the required physiological parameters (for rat) and their corresponding"]
[null,"references."]
[]
[null,"Required Physiological Parameters"]
[]
[null,"1) Compositions"]
[null,"composition blood (volume fractions, values between 0 - 1!) - from Endo et al. 2013"]
[null,"water wblood ","albumin","non-albumin protein","storage lipid ","membrane lipid"]
[null,0.81,1.6E-2,0.16,1.2999999999999999E-2,2.1999999999999999E-2]
[]
[null,"composition organism (volume fractions, values between 0 - 1!) - lipid calculated from bodyweight (Brown et al. 1997), protein from Lee et al. 2017"]
[null,"water worganism ","protein ","total lipid"]
[null,{"$f":"1-C32-D32","v":0.69795000000000007},0.23,{"$f":"(0.035*mbody+0.205)/100","v":7.2050000000000003E-2}]
[]
[null,"composition hepatocyte (volume fractions, values between 0 - 1!) - from Lee et al. 2017 "]
[null,"water whep","protein ","storage lipid","membrane lipid"]
[null,0.70499999999999996,{"$f":"1-whep-D36-E36","v":0.25090000000000007},1.38E-2,3.0300000000000001E-2]
[]
[null,"composition lung cells (volume fractions, values between 0 - 1!)  - from Lee et al. 2017 "]
[null,"water wlung","protein ","storage lipid","membrane lipid"]
[null,0.79,{"$f":"1-wlung-D40-E40","v":0.17409999999999995},2.1899999999999999E-2,1.4E-2]
[]
[null,"composition intestinal cells (volume fractions, values between 0 - 1!)  - from Lee et al. 2017 "]
[null,"water wgut","protein ","storage lipid","membrane lipid"]
[null,0.749,{"$f":"1-wgut-D44-E44","v":0.20799999999999999},2.92E-2,1.38E-2]
[]
[null,"composition kidney cells (volume fractions, values between 0 - 1!)  - from Lee et al. 2017 "]
[null,"water wkidney","protein ","storage lipid","membrane lipid"]
[null,0.77100000000000002,{"$f":"1-wkidney-D48-E48","v":0.18829999999999997},1.23E-2,2.8400000000000002E-2]
[]
[null,"composition S9 fraction (volume fractions, values between 0 - 1!) - value for trout S9 used"]
[null,"protein","lipid"]
[null,{"$f":"(2/1.4)/(2/1.4+0.51/1)","v":0.73691967575534267},{"$f":"(0.51/1)/(2/1.4+0.51/1)","v":0.26308032424465733}]
[]
[null,"composition microsomes (volume fractions, values between 0 - 1!) - value for trout S9 used"]
[null,"protein","lipid"]
[null,{"$f":"(2/1.4)/(2/1.4+0.51/1)","v":0.73691967575534267},{"$f":"(0.51/1)/(2/1.4+0.51/1)","v":0.26308032424465733}]
[]
[null,"composition rat food (volume fractions, values between 0 - 1!) - from Vento et al. 2008 "]
[null,"water wfood","protein ","storage lipid","membrane lipid"]
[null,{"$f":"1-C60-D60","v":0.67},0.18,0.15,0]
[null,"Note: typical ratons for laboratory rats often contain up to 0.15 lipid (Canadian Council on Animal Care), the minimum lipid content for laboratory rat food is 0.05 acc. to Keenan et al. 2000"]
[]
[null,"2) Scaling factors"]
[null,"liver microsomal protein content Lmic [mg/gliver]",null,35," from Punt et al. 2008"]
[null,"liver S9 protein content LS9 [mg/gliver]",null,143," from Punt et al. 2008"]
[null,"liver hepatocyte content LHEP [106 cells/gliver]",null,117," from Sohlenius-Sternbeck 2006"]
[null,"fractional liver weight LFBW [gliver/grat]",null,3.6600000000000001E-2," from Brown et al .1997"]
[]
[null,"lung microsomal protein content Lungmic [mg/glung]",null,20," from Punt et al. 2008"]
[null,"lung S9 content LungS9 [mg/glung]",null,75.8," from Behera et al. 2008 (organ protein content)"]
[null,"alveolar cell content Lungcells [106 cells/glung]",null,{"$f":"79/(325*D72)","v":48.615384615384613}," from Crapo et al. 1996 (alveolar type I cells)"]
[null,"fractional lung weight LungFBW [glung/grat]",null,5.0000000000000001E-3," from Brown et al .1997"]
[]
[null,"gut microsomal protein content Gutmic [mg/ggut]",null,{"$f":"(15.1+25.9)/2","v":20.5}," from Hatley et al. 2017"]
[null,"S9 content in gut, GutS9 [mg/gGIT]",null,37.1," from Behera et al. 2008 (organ protein content)"]
[null,"cell content in gut, Gutcells [106 cells/gGIT]",null,40," from Koster et al. 1983"]
[null,"fractional intestine weight GutFBW [ggut/grat]",null,{"$f":"0.0046+0.014+0.0084","v":2.6999999999999996E-2}," from Brown et al .1997"]
[]
[null,"kidney microsomal protein content Kmic [mg/gkidney]",null,7," from Punt et al. 2008"]
[null,"S9 content in kidney, KS9 [mg/gkidney]",null,112.8," from Behera et al. 2008 (organ protein content)"]
[null,"cell content in kidney, Kcells [106 cells/gkidney]",null,{"$f":"31764*674*2/(215*D82)/10^6","v":27.281218222363808}," from Bertram et al. 1992 (calculated from glomeruli number and multiplied by 2)"]
[null,"fractional kidney weight KFBW [gkidney/grat]",null,7.3000000000000001E-3," from Brown et al .1997"]
[]
[null,"3) Blood flow and volume information"]
[null,"total liver blood flow as fraction of cardiac output QHFRAC [unitless]",null,{"$f":"D86+D92","v":0.17399999999999999}," = QHFRAC,arterial + QGFRAC"]
[null,"arterial liver blood flow as fraction of cardiac output QHFRAC,arterial [unitless]",null,{"$f":"0.021","v":2.1000000000000001E-2}," from Brown et al .1997"]
[null,"hepatocyte diameter dhep [cm]",null,{"$f":"22.5/10000","v":2.2499999999999998E-3}," from Klinger et al. 1988"]
[]
[null,"lung cell diameter dlung [cm]",null,{"$f":"75/10000","v":7.4999999999999997E-3}," from Gonzalez et al. 2009"]
[]
[null,"gut cell diameter dgut [cm]",null,3.0000000000000001E-3," assumed"]
[null,"intestinal blood flow as fraction of cardiac output QGFRAC [unitless]",null,{"$f":"0.153","v":0.153}," from Brown et al .1997"]
[]
[null,"kidney cell diameter dkidney [cm]",null,3.0000000000000001E-3," assumed"]
[null,"kidney blood flow as fraction of cardiac output QKFRAC [unitless]",null,0.14099999999999999," from Brown et al .1997"]
[]
[null,"4) Uptake and excretion"]
[null,"feeding rate kfeed [kgfood/kgrat/d]",null,{"$f":"0.0276/0.364","v":7.5824175824175818E-2}," from Lee et al. 2017 (assuming food density of 1 kg/L)"]
[null,"uptake efficiency for chemical [unitless]",null,1," assumed"]
[null,"assimilation efficiency for lipid",null,0.97," from Lee et al. 2017"]
[null,"assimilation efficiency for protein",null,0.96," from Lee et al. 2017"]
[null,"assimilation efficiency for water ",null,0.85," from Lee et al. 2017"]
[null,"urination rate [L/d/kgrat]",null,{"$f":"0.0064*(mbody)^0.82/1000*24/(mbody/1000)","v":5.9184204755973586E-2}," = (0.0064* mbody0.82) /1000 * 24  / (mbody/1000)      from Roth et al. 1993 eq. (4)"]
[null,"alveolar ventilation rate kalveolar [L/kgrat/d]",null,{"$f":"0.117*60*24/0.25","v":673.92000000000007}," = 0.117 L/min * 60 min/h * 24 h/d  / 0.25 kgrat          from Arms 1988 table 4-14"]
[]
[]
[null,"Calculated Physiological Parameters - no changes by the user required"]
[]
[null,"S9 density ρS9 [g/mL]",null,{"$f":"(2.51/(2/1.4+0.51/1))","v":1.294767870302137}]
[]
[null,"liver weight mliver [gliver]",null,{"$f":"D67*mbody","v":7.32}," = LFBW * mbody"]
[null,"lung weight mlung [glung]",null,{"$f":"D72*mbody","v":1}," = lungFBW * mbody"]
[null,"intestine weight mgut [ggut]",null,{"$f":"0.0124*mbody","v":2.48}," = GutFBW * mbody"]
[null,"kidney weight mkidney [gkidney]",null,{"$f":"D82*mbody","v":1.46}," = KFBW * mbody"]
[null,"volume rest of body Vrestbody [mL]",null,{"$f":"mbody-Vgut-Vlung-Vhepliver-Vkidney","v":192.90511525809634}]
[]
[null,"hepatocyte volume in the liver Vhepliver [mL]",null,{"$f":"Lhep * 10^6 * mliver * 1/6 * PI() *dhep^3","v":5.107908623237714}," = Lhep * 10^6 * mliver * Vsinglecell         (Vsinglecell = 1/6 * π * dhep3  because spherical shape assumed)"]
[null,"lung cell volume  Vlung [mL]",null,{"$f":"Acells* 10^6 * mlung * ((D89/2)^2*PI()*0.1/10000)","v":2.1477619006753296E-2}," = Acells * 10^6 * mlung * Vsinglecell         (Vsinglecell = dlung/22 * π * 0.1/10000 because flat cylinder shape assumed from Yang et al. 2016)"]
[null,"gut cell volume Vgut [mL]",null,{"$f":"gutcells * 10^6 * mgut * 1/6 * PI() *D91^3","v":1.4024069605624836}," = Gutcells * 10^6 * mgut * Vsinglecell         (Vsinglecell = 1/6 * π * dgut3  because spherical shape assumed)"]
[null,"kidney cell volume Vkidney [mL]",null,{"$f":"Kcells * 10^6 * mkidney * 1/6 * PI() *D94^3","v":0.56309153909671295}," = Kcells * 10^6 * mkidney * Vsinglecell         (Vsinglecell = 1/6 * π * dgut3  because spherical shape assumed)"]
[]
[null,"cardiac output QC [L/d/kgrat]",null,{"$f":"(0.235*(mbody/1000)^0.75)*60*24/(mbody/1000)","v":506.02602756526107}," = (0.235 * mbody/1000)0.74) * 60 * 24  / (mbody/1000)      from Brown 1997"]
[]
[null,"arterial liver blood flow per bodyweight Qliver,bodyweight [mL/h/grat]",null,{"$f":"D122*D86*1000/1000/24","v":0.44277277411960347}," = QC * QHFRAC,arterial"]
[null,"arterial liver blood flow Qliver [mL/h]",null,{"$f":"D124*mbody","v":88.554554823920697}," = Qliver,bodyweight / 24 * mbody"]
[null,"lung blood flow rate per bodyweight Qlung, bodyweight [mLblood/h/grat] ",null,{"$f":"'organism input data'!D122*1000/1000/24","v":21.084417815219211}," assumed as 100% of cardiac output "]
[null,"lung blood flow rate  Q [mLblood/h]",null,{"$f":"D126*mbody","v":4216.8835630438425}," = Qlung,bodyweight * mbody"]
[null,"gut blood flow rate [mLblood/h/grat] Qgut, bodyweight",null,{"$f":"D122*D92*1000/1000/24","v":3.2259159257285392}," = QC * QGFRAC"]
[null,"gut blood flow rate  Qgut [mLblood/h]",null,{"$f":"D128*mbody","v":645.18318514570785}," = Qgut,bodyweight * mbody"]
[null,"total liver blood flow Qliver-total [mLblood/h]",null,{"$f":"(D122*D85*1000/1000)/24*mbody","v":733.73773996962859}," = QC * QHFRAC / 24 * mbody"]
[null,"kidney blood flow rate  Qkidney [mLblood/h]",null,{"$f":"D122*D95*1000/1000/24*mbody","v":594.5805823891817}," = QC * QKFRAC / 24 * mbody"]
[null,"blood flow rate to rest body Qbody [mLblood/h]",null,{"$f":"('organism input data'!D122*1000/1000/24*mbody)-Qliver-Qgut-Qkidney","v":2888.5652406850322}," = QC / 24 * mbody - Qgut - Qliver - Qkidney"]

{"sheet":"BMF","index":3,"n_rows":55,"n_cols":23,"rows_kept":55,"cut":false,"hidden":false,"merged":[[9,1,9,2],[8,1,8,2],[30,1,30,2],[54,1,54,2],[13,14,13,15],[14,14,14,17],[46,1,46,2],[45,1,45,2],[49,1,49,2],[50,1,50,2]]}
[]
[null,{"$f":"\"Calculation of the BMF for \"&'compound input data'!D5","v":"Calculation of the BMF for b(a)p"}]
[]
[null,{"$f":"\"Info: You are currently using a log Kow of \"&'compound input data'!B12&\" and a log Koa of \"&'compound input data'!C12&\".\"","v":"Info: You are currently using a log Kow of 8 and a log Koa of 10."}]
[]
[null,"1) kinetic BMFs "]
[]
[null,"  a) Classical one-compartment model (no flow limitations):"]
[null,"kinetic BMFone-compartment [unitless]",null,{"$f":"kone/(kV+kBLIVER+kE+kBLUNG+kBGIT+kBKIDNEY+kU)*(1/Korganismair)/(1/Kfoodair)","v":9.3561567817954851E-3}," = k1 /(kV+kB,LIVER+kE+kB,LUNG+kB,GIT+kB,KIDNEY+kU) * Kair/organism / Kair/food"]
[null,"freely dissolved steady-state concentration in body-water [g/mL]",null,{"$f":"(kone/(kV+kBLIVER+kE+kBLUNG+kBGIT+kBKIDNEY+kU)*Cfood)/Korganismw","v":5.8843750865046234E-11}]
[]
[null,"  b) Multi-compartment model:"]
[null,"    The multi-compartment model distinguishes the five compartments lung, liver, GIT, kidney and",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"in g/d","% of uptake"]
[null,"    rest of the body. By this, the model can represent the potential first-pass effect in the GIT & liver",null,null,null,null,null,null,null,null,null,null,null,null,"chemical mass taken up",null,{"$f":"kone*Cfood*mbody","v":1.5164835164835164},{"$f":"Q14/Q14","v":1}]
[null,"    and the direct blood flow from GIT to liver.",null,null,null,null,null,null,null,null,null,null,null,null,"one-compartment model",null,null,null,null,"multi-compartment model",null,"in g/d","% of uptake"]
[null,"    For every compartment, a mass balance is set up containing all uptake and elimination",null,null,null,null,null,null,null,null,null,null,null,null,"mass eliminated via ventilation",null,{"$f":"kV*D46*Cfood*mbody","v":3.9655980582971963E-7},{"$f":"Q16/$Q$14","v":2.6149958210510495E-7},null,"mass eliminated via ventilation",null,{"$f":"klungventilation*B28*Vlung","v":3.9484380856917285E-7},{"$f":"V16/$Q$14","v":2.6036801869416473E-7}]
[null,"    processes applying to the respective compartment. This linear system of equations is ",null,null,null,null,null,null,null,null,null,null,null,null,"mass transformed in lung",null,{"$f":"D46*kBLUNG*Cfood*mbody","v":1.2399157621199483E-2},8.1762561125300944E-3,null,"mass transformed in lung",null,{"$f":"klungbiotransf*B28*Vlung","v":1.2345503871630617E-2},8.140875741437582E-3]
[null,"    then solved via the Gaussian elimination method.",null,null,null,null,null,null,null,null,null,null,null,null,"mass transformed in liver",null,{"$f":"kBLIVER*D46*Cfood*mbody","v":1.5036502766957651},0.99153750129938134,null,"mass transformed in liver",null,{"$f":"kliverbiotransf*C28*Vhepliver","v":1.5034517686075048},0.99140660103828226]
[null,"The linear system of equations is written into the following 5x5-matrix:",null,null,null,"Clung","Cliver","CGIT","Ckidney","Crestbody",null,null,null,null,"mass transformed in GIT",null,{"$f":"D46*kBGIT*Cfood*mbody","v":0},0,null,"mass transformed in kidney",null,{"$f":"D28*kGITbiotransf*Vgut","v":0},0]
[null,null,null,null,"I",{"$f":"kbodyin*Vlung","v":56567.912306679355},0,0,0,{"$f":"-kbodyout*mrestbody","v":-23080.191711226562},0,null,null,null,"mass transformed in kidney",null,{"$f":"kBKIDNEY*D46*Cfood*mbody","v":0},0,null,"mass transformed in GIT",null,{"$f":"E28*kkidneybiotransf*Vkidney","v":0},0]
[null,null,null,null,"II",{"$f":"kkidneyin*Vlung","v":11643.906036849326},0,0,{"$f":"-(kkidneybiotransf+kkidneyout+kkidneyurine)*Vkidney","v":-13403.874213669897},0,0,null,null,null,"mass eliminated via feces",null,{"$f":"kE*D46*Cfood*mbody","v":4.3368491022164002E-4},2.8598062920412497E-4,null,"mass eliminated via feces",null,{"$f":"kGITfeces*D28*Vgut","v":6.8584846706160052E-4},4.5226239494641773E-4]
[null,null,null,null,"III",{"$f":"kliverin*Vlung","v":1734.1987714456445},{"$f":"-((kliverbiotransf+kliverout)*Vhepliver)","v":-21324.914292751535},{"$f":"kGITout*Vgut","v":11104.972313820203},0,0,0,null,null,null,"mass eliminated via urine",null,{"$f":"kU*D46*Cfood*mbody","v":6.9652411996127889E-10},4.5930213707591579E-10,null,"mass eliminated via urine",null,{"$f":"kkidneyurine*E28*Vkidney","v":6.9351011414295404E-10},4.5731464048557119E-10]
[null,null,null,null,"IV",{"$f":"kGITin*Vlung","v":12634.876763389695},0,{"$f":"-(kGITbiotransf+kGITfeces+kGITout)*Vgut","v":-11106.833452329323},0,0,{"$f":"-kone*Cfood*mbody","v":-1.5164835164835164},null,null,null,null,null,null,null,null,"blood flows:","lung-to-body",{"$f":"1-V24-V25-V26","v":0.68499999999999994}]
[null,null,null,null,"V",{"$f":"-(klungventilation+klungbiotransf+kbodyin+kliverin+kGITin+kkidneyin)*Vlung","v":-82641.436884990035},{"$f":"kliverout*Vhepliver","v":14113.607631420351},0,{"$f":"kkidneyout*Vkidney","v":13403.874209754951},{"$f":"kbodyout*mrestbody","v":23080.191711226562},0,null,null,null,null,null,null,null,null,null,"lung-to-GIT ",{"$f":"'organism input data'!D92","v":0.153}]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"lung-to-liver",{"$f":"'organism input data'!D86","v":2.1000000000000001E-2}]
[null,"    Solution of the mass balance equations yields the following steady state-concentrations in lung, liver, GIT, kidney and rest body:",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"lung-to-kidney",{"$f":"'organism input data'!D95","v":0.14099999999999999}]
[null,"Clung [g/mL]","Cliver [g/mL]","CGIT [g/mL]","Ckidney [g/mL]","Crestbody [g/mL]"]
[null,{"$f":"TRANSPOSE(MMULT(MINVERSE(F20:J24),K20:K24))","v":2.0391948473425393E-4},2.0848534658349601E-4,3.6851016928649108E-4,1.7714425556954565E-4,4.9979218866104869E-4]
[]
[null,"    Combination of the steady state-concentrations in the four compartments yields the BMF:"]
[null,"kinetic BMFmulti-compartment [unitless]",null,{"$f":"(B28*Vlung+D28*Vgut+C28*Vhepliver+E28*Vkidney+F28*mrestbody)/mbody /Cfood*(1/Korganismair)/(1/Kfoodair)","v":9.3343104407398875E-3}," =(Clung*Vlung + Cliver*Vliver + CGIT*VGIT + Ckidney*Vkidney + Crestbody*Vrestbody) / mbody / Cfood * Kair/organism / Kair/food"]
[]
[]
[]
[]
[]
[null,"By combining the steady state concentrations with the respective tissue-water partition coefficients, one can "]
[null,"calculate the corresponding aqueous concentrations to see whether there is equilibrium between the tissues."]
[null,"C in lung-water [g/mL]","C in liver-water [g/mL]","C in GIT-water [g/mL]","C in kidney-water [g/mL]","C in restbody-water [g/mL]"]
[null,{"$f":"B28/Klungcellw","v":5.8589121641911922E-11},{"$f":"C28/Khepw","v":5.8835982462598322E-11},{"$f":"D28/Kgutcellw","v":9.3058105956052959E-11},{"$f":"E28/Kkidneycellw","v":5.8589121624799442E-11},{"$f":"F28/Krestorganismw","v":5.8589121641911922E-11}]
[]
[]
[null,"2) steady state-concentration ratios rat/food"]
[]
[null,"  a) Classical one-compartment model (no flow limitations):"]
[null,"Crat/Cfood [kgfood/kgrat]",null,{"$f":"kone/(kV+kBLIVER+kE+kBLUNG+kBGIT+kBKIDNEY+kU)","v":4.9163957954745721E-3}," = k1 /(kV+kB,LIVER+kE+kB,LUNG+kB,GIT+kB,KIDNEY+kU)"]
[null,"lipid-normalised kinetic BMFone-compartment [kglipid/kglipid]",null,{"$f":"D46*'organism input data'!D60/lipidorganism","v":1.0235383335477943E-2}]
[]
[null,"  b) Multi-compartment model:"]
[null,"Crat/Cfood [kgfood/kgrat]",null,{"$f":"(B28*Vlung+D28*Vgut+C28*Vhepliver+E28*Vkidney+F28*mrestbody)/mbody /Cfood","v":4.9049161610672885E-3}," =(Clung*Vlung + Cliver*Vliver + CGIT*VGIT + Ckidney*Vkidney + Crestbody*Vrestbody) / mbody / Cfood "]
[null,"lipid-normalised kinetic BMFmulti-compartment [kglipid/kglipid]",null,{"$f":"D50*'organism input data'!D60/lipidorganism","v":1.0211484027204624E-2}]
[]
[]
[null,"3) whole-body elimination constant as an alternative endpoint:"]
[null,"whole-body elimination rate constant k2 [1/d]",null,{"$f":"kV+kBLIVER+kE+kBLUNG+kBGIT+kBKIDNEY+kU","v":15.422715944466921}," = kV+kB,LIVER+kE+kB,LUNG+kB,GIT+kB,KIDNEY+kU"]

{"sheet":"k1","index":4,"n_rows":19,"n_cols":7,"rows_kept":19,"cut":false,"hidden":false,"merged":[[98,1,98,3],[99,1,99,3],[78,1,78,3],[63,5,63,6],[65,1,65,3],[65,5,65,6],[66,1,66,3],[66,5,66,6],[47,1,47,3],[48,1,48,3],[75,1,75,3],[76,1,76,3],[77,1,77,3],[67,1,67,3],[63,1,63,3]]}
[]
[null,{"$f":"\"Calculation of the GIT uptake rate constant for \"&'compound input data'!D5","v":"Calculation of the GIT uptake rate constant for b(a)p"}]
[]
[null,{"$f":"\"Info: You are currently using a log Kow of \"&'compound input data'!B12&\" and a log Koa of \"&'compound input data'!C12&\".\"","v":"Info: You are currently using a log Kow of 8 and a log Koa of 10."}]
[]
[]
[]
[]
[null,"GIT uptake rate constant k1 [kg/kg/d]",null,null,{"$f":"kGITuptake*'organism input data'!D99","v":7.5824175824175818E-2},null," = kfeed * uptake efficiency"]
[]
[]
[]
[]
[]
[]
[null,"Insert the k1 value you want to use for final BMF calculation here:"]
[]
[]
[null,"GIT uptake rate constant k1 [kg/kg/d]",null,null,{"$f":"E9","v":7.5824175824175818E-2}]

{"sheet":"k2 - lung","index":5,"n_rows":16,"n_cols":6,"rows_kept":16,"cut":false,"hidden":false,"merged":[[45,1,45,3],[15,1,15,3]]}
[]
[null,{"$f":"\"Calculation of the ventilation elimination rate constant for \"&'compound input data'!D5","v":"Calculation of the ventilation elimination rate constant for b(a)p"}]
[]
[null,{"$f":"\"Info: You are currently using a log Kow of \"&'compound input data'!B12&\" and a log Koa of \"&'compound input data'!C12&\".\"","v":"Info: You are currently using a log Kow of 8 and a log Koa of 10."}]
[]
[null,"whole-body ventilation elimination rate constant kV [1/d]",null,null,{"$f":"(kalveolar)/(Korganismw*Kwaterair*mbody/1000)","v":4.03303377440384E-6}," = kventilation / (Korganism/W * Kw/air)      Lee 2012 eq. S5"]
[]
[]
[null,"The above calculated ventilation rate constant kV refers to whole-body concentration and is used in the"]
[null,"one-compartment model. "]
[null,"For the multi-compartment model (that represents the lung as an extra compartment), this kV cannot be "]
[null,"used. Instead, a ventilation rate constant that refers to chemical concentration in the lung (and not to "]
[null,"whole-body concentration) is required."]
[null,"This required ventilation rate constant klung,ventilation is calcuated from the above kV via adjusting the"]
[null,"normalization as follows:"]
[null,"\"lung-based\" ventilation rate constant klung,ventilation [1/d]",null,null,{"$f":"kV*Korganismw/Klungcellw*mbody/Vlung","v":9.0153060186285452E-2}," = kV * Korganism/w / Klungcells/w * Vorganism / Vlungs"]

{"sheet":"k2 - hepatic biotransf","index":6,"n_rows":64,"n_cols":4,"rows_kept":64,"cut":false,"hidden":false,"merged":[[45,21,45,22],[113,3,113,5],[134,3,134,4],[23,3,23,4],[36,3,36,4]]}
[]
[null,{"$f":"\"Calculation of the hepatic biotransformation rate constant for \"&'compound input data'!D5","v":"Calculation of the hepatic biotransformation rate constant for b(a)p"}]
[]
[null,{"$f":"\"Info: You are currently using a log Kow of \"&'compound input data'!B12&\" and a log Koa of \"&'compound input data'!C12&\".\"","v":"Info: You are currently using a log Kow of 8 and a log Koa of 10."}]
[]
[null,"in vitro-in vivo extrapolation of liver S9 assay data"]
[]
[]
[null,"assay clearance CLin vitro [mLassay/h/mgS9]",{"$f":"kliverS9assay/CliverSnine","v":1.0999999999999999}," = kassay / CS9"]
[]
[null,"hepatocyte clearance CLhep [mLhep/h]",{"$f":"CLS9assay*1/fuliverS9assay*LSnine*mliver*wliverS9assay/Khepw","v":9.0328912192994295}," = 1/fu,liverS9assay * CLin vitro * LS9  * mliver * wassay/Khepw "]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,liver [mLblood/h]",{"$f":"fublood/fuliverS9assay*CLS9assay*LSnine*mliver*wliverS9assay/wblood","v":11.270439187585552}," = fu,blood/fu,liverS9assay * CLin vitro * LS9 * mliver* wassay/wblood"]
[null,"blood clearance incl. flow lim. \nCLblood,liver [mLblood/h]",{"$f":"(Qlivertotal*fublood/fuliverS9assay*CLS9assay*LSnine*mliver*wliverS9assay/wblood)/(Qlivertotal+fublood/fuliverS9assay*CLS9assay*LSnine*mliver*wliverS9assay/wblood)","v":11.099940657455644}," = (Qliver * fu,blood/fu,liverS9assay * CLin vitro * LS9 * mliver* wassay/wblood) / (Qliver + fu,blood/fu,liverS9assay * CLin vitro * LS9 * mliver* wassay/wblood)"]
[]
[null,"Whole-body biotransformation rate constant kB,LIVER [1/d] (w/o flow lim.)",{"$f":"(C13*Kbloodw/Korganismw)/mbody*24","v":0.45972070264291465}," = (CLblood w/o flowlim,liver * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[null,"in vitro-in vivo extrapolation of hepatocyte assay data"]
[]
[]
[null,"assay clearance CLin vitro [mLassay/h/106hep]",{"$f":"khepassay/Chep","v":25}," = kassay / Chep"]
[]
[null,"hepatocyte clearance CLhep [mLhep/h]",{"$f":"CLhepassay*1/fuhepassay*(Lhep*mliver)*whepassay/Khepw","v":300.47111088879922}," = 1/fu,hep-assay * CLin vitro * Lhep  * mliver * wassay/Khepw "]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,liver [mLblood/h]",{"$f":"fublood/fuhepassay*CLhepassay*Lhep*mliver*whepassay/wblood","v":374.90115851977799}," = fu,blood/fu,hep-assay * CLin vitro * LHep * mliver* wassay/wblood"]
[null,"blood clearance incl. flow lim. CLblood,liver [mLblood/h]",{"$f":"(Qlivertotal*fublood/fuhepassay*CLhepassay*Lhep*mliver*whepassay/wblood)/(Qlivertotal+fublood/fuhepassay*CLhepassay*Lhep*mliver*whepassay/wblood)","v":248.12328805990015}," = (Qliver * fu,blood/fu,hep-assay * CLin vitro * LHep * mliver* wassay/wblood) / (Qliver + fu,blood/fu,hep-assay * CLin vitro * LHep * mliver* wassay/wblood)"]
[]
[null,"Whole-body biotransformation rate constant kB,LIVER (w/o flow lim.) [1/d]",{"$f":"(C26*Kbloodw/Korganismw)/mbody*24","v":15.292201230826862}," = (CLblood w/o flowlim,liver * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[]
[null,"in vitro-in vivo extrapolation of liver microsome assay data"]
[]
[null,"assay clearance CLin vitro [mLassay/h/mgmic]",{"$f":"'compound input data'!C59/'compound input data'!C60","v":1.0999999999999999}," = kassay / Cmicrosomes"]
[]
[null,"hepatocyte clearance CLhep [mLhep/h]",{"$f":"C35*1/fulivermicassay*(Lmic*mliver)*wlivermicassay/Khepw","v":2.8625108673897905}," = 1/fu,mic-assay * CLin vitro * Lmic  * mliver * wassay/Khepw "]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,liver [mLblood/h]",{"$f":"fublood/fulivermicassay*CLhepassay*Lmic*mliver*wlivermicassay/wblood","v":81.172426291549584}," = fu,blood/fu,mic-assay * CLin vitro * Lmic * mliver* wassay/wblood"]
[null,"blood clearance incl. flow lim. CLblood,liver [mLblood/h]",{"$f":"(Qlivertotal*fublood/fulivermicassay*CLhepassay*Lmic*mliver*wlivermicassay/wblood)/(Qlivertotal+fublood/fulivermicassay*CLhepassay*Lmic*mliver*wlivermicassay/wblood)","v":73.086918142489026}," = (Qliver * fu,blood/fu,mic-assay * CLin vitro * Lmic * mliver* wassay/wblood) / \n    (Qliver + fu,blood/fu,mic-assay * CLin vitro * Lmic * mliver* wassay/wblood)"]
[]
[null,"Whole-body biotransformation rate constant kB,LIVER (w/o flow lim.) [1/d]",{"$f":"(C39*Kbloodw/Korganismw)/mbody*24","v":3.3110195821903603}," = (CLblood w/o flowlim,liver * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[null,"The following value for kB,LIVER is used for final BMF calculation:"]
[]
[null,"whole-body hepatic biotransformation rate constant kB,LIVER (w/o flow lim.) [1/d]",{"$f":"C29","v":15.292201230826862}]
[]
[]
[null,"The above calculated hepatic biotransformation rate constant kB,LIVER refers to whole-body concentration and"]
[null,"is used in the one-compartment model. "]
[null,"For the multi-compartment model (that represents the liver as an extra compartment), this kB,LIVER cannot be "]
[null,"used. Instead, a hepatic biotransformation rate constant that refers to chemical concentration in the liver (and "]
[null,"not to whole-body concentration) is required."]
[null,"This required liver biotransformation rate constant kliver,biotransf is calcuated from the above kB,LIVER via adjusting"]
[null,"the normalization as follows:"]
[null,"liver biotransformation rate constant kliver,biotransf [1/d]",{"$f":"kBLIVER*Korganismw/Khepw*mbody/Vhepliver","v":1411.7924170617214}," = kB,LIVER * Korganismw / Khepw * Vbody / Vhepliver"]
[]
[null,"When the liver is considered as an extra compartment, rate constants describing transport from liver to lung"]
[null,"and vice versa (\"kliver,out\" and \"kliver,in\") are required. When no limitations due to slow permeation kinetics are"]
[null,"assumed, this transport should solely depend on the liver blood flow rate."]
[null,"The rate constants can then be calculated from liver blood flow rate as follows:"]
[null,"liver-to-body rate constant kliver,out [1/d]",{"$f":"Qlivertotal*Kbloodw/Khepw*1/Vhepliver*24","v":2763.0892939651412}," = Qlivertotal * Kbloodw/Khepw *1/Vhepliver *24"]
[null,"body-to-liver rate constant kliver,in [1/d]",{"$f":"Qliver*Kbloodw/Klungcellw*1/Vlung*24","v":80744.461055033767}," = Qliver * Kbloodw/Klungcellsw * 1/Vlung * 24"]

{"sheet":"k2 - lung biotransf","index":7,"n_rows":64,"n_cols":4,"rows_kept":64,"cut":false,"hidden":false,"merged":[]}
[]
[null,{"$f":"\"Calculation of the lung biotransformation rate constant for \"&'compound input data'!D5","v":"Calculation of the lung biotransformation rate constant for b(a)p"}]
[]
[null,{"$f":"\"Info: You are currently using a log Kow of \"&'compound input data'!B12&\" and a log Koa of \"&'compound input data'!C12&\".\"","v":"Info: You are currently using a log Kow of 8 and a log Koa of 10."}]
[]
[]
[null,"in vitro - in vivo extrapolation of lung S9 assay data:"]
[]
[null,"assay clearance CLin vitro [mLassay/h/mgS9]",{"$f":"'compound input data'!G48/'compound input data'!G49","v":5}," = kassay / CS9"]
[]
[null,"lung cell clearance CLlung [mLlung/h]",{"$f":"1/fulungS9assay*C9*lungSnine*mlung*wlungS9assay/Klungcellw","v":2.5225445980389365}," = 1/fu,lungS9-assay * CLin vitro  * LungS9 * mlung * wassay/Klungcell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,lung [mLblood/h]",{"$f":"fublood/fulungS9assay*C9*lungSnine*mlung*wlungS9assay/wblood","v":3.0914492744096682}," = fu,blood/fu,lungS9-assay * CLin vitro * LungS9 * mlung * wassay/wblood"]
[null,"blood clearance incl. flow lim. \nCLblood,lung [mLblood/h]",{"$f":"(QL*fublood/fulungS9assay*C9*lungSnine*mlung*wlungS9assay/wblood)/(QL+fublood/fulungS9assay*C9*lungSnine*mlung*wlungS9assay/wblood)","v":3.0891845551664625}," = (Qlung * fu,blood/fu,lungS9-assay * CLin vitro * LungS9 * mlung* wassay/wblood) / \n(Qlung + fu,blood/fu,lung-assay * CLin vitro * LungS9 * mlung* wassay/wblood)"]
[]
[null,"whole-body lung biotransformation rate constant kB,LUNG (w/o flow lim.) [1/d]",{"$f":"(C13*Kbloodw/Korganismw)/mbody*24","v":0.12610007551276303}," = (CLblood w/o flowlim,lung * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[]
[null,"in vitro - in vivo extrapolation of lung cell assay data:"]
[]
[null,"assay clearance CLin vitro [mLassay/h/106cells]",{"$f":"'compound input data'!G53/'compound input data'!G54","v":0.05}," = kassay / Ccells,assay"]
[]
[null,"lung cell clearance CLlung [mLlung/h]",{"$f":"1/fulungcellassay*C22*Acells*mlung*'compound input data'!G72/Klungcellw","v":1.2862578189863771}," = 1/fu,lungcell-assay * CLin vitro  * Lungcells * mlung * wassay/Klungcell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,lung [mLblood/h]",{"$f":"fublood/fulungcellassay*C22*Acells*mlung*wlungcellassay/wblood","v":1.5763450938788204}," = fu,blood/fu,lungcell-assay * CLin vitro * Lungcells * mlung * wassay/wblood"]
[null,"blood clearance incl. flow lim. \nCLblood,lung [mLblood/h]",{"$f":"(QL*fublood/fulungcellassay*C22*Acells*mlung*wlungcellassay/wblood)/(QL+fublood/fulungcellassay*C22*Acells*mlung*wlungcellassay/wblood)","v":1.5757560486089575}," = (Qlung * fu,blood/fu,lungcell-assay * CLin vitro * Lungcells * mlung* wassay/wblood) / \n(Qlung + fu,blood/fu,lungcell-assay * CLin vitro * Lungcells * mlung* wassay/wblood)"]
[]
[null,"whole-body lung biotransformation rate constant kB,LUNG (w/o flow lim.) [1/d]",{"$f":"(C26*Kbloodw/Korganismw)/mbody*24","v":6.4299044793562243E-2}," = (CLblood w/o flowlim,lung * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[]
[null,"in vitro - in vivo extrapolation of lung microsome assay data:"]
[]
[null,"assay clearance CLin vitro [mLassay/h/mgmic]",{"$f":"'compound input data'!G59/'compound input data'!G60","v":2.5}," = kassay / Cmicrosomes"]
[]
[null,"lung cell clearance CLlung [mLlung/h]",{"$f":"1/fulungmicassay*C35*lungmic*mlung*wlungmicassay/Klungcellw","v":0.86174753371600832}," = 1/fu,lungmic-assay * CLin vitro  * Lungmic * mlung * wassay/Klungcell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,lung [mLblood/h]",{"$f":"fublood/fulungmicassay*C35*lungmic*mlung*wlungmicassay/wblood","v":1.0560958128953384}," = fu,blood/fu,lungmic-assay * CLin vitro * Lungmic * mlung * wassay/wblood"]
[null,"blood clearance incl. flow lim. \nCLblood,lung [mLblood/h]",{"$f":"(QL*fublood/fulungmicassay*C35*lungmic*mlung*wlungmicassay/wblood)/(QL+fublood/fulungmicassay*C35*lungmic*mlung*wlungmicassay/wblood)","v":1.0558313856023416}," = (Qlung * fu,blood/fu,lungmic-assay * CLin vitro * Lungmic * mlung* wassay/wblood) / \n(Qlung + fu,blood/fu,lungmic-assay * CLin vitro * Lungmic * mlung* wassay/wblood)"]
[]
[null,"whole-body lung biotransformation rate constant kB,LUNG (w/o flow lim.) [1/d]",{"$f":"(C39*Kbloodw/Korganismw)/mbody*24","v":4.3078100248060962E-2}," = (CLblood w/o flowlim,lung * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[null,"The following value for kB,LUNG is used for final BMF calculation:"]
[]
[null,"whole-body lung biotransformation rate constant kB,LUNG (w/o flow lim.) [1/d]",{"$f":"C16","v":0.12610007551276303}]
[]
[]
[null,"The above calculated lung biotransformation rate constant kB,LUNG refers to whole-body concentration and"]
[null,"is used in the one-compartment model. "]
[null,"For the multi-compartment model (that represents the lung as an extra compartment), this kB,LUNG cannot be "]
[null,"used. Instead, a lung biotransformation rate constant that refers to chemical concentration in the lung (and "]
[null,"not to whole-body concentration) is required."]
[null,"This required lung biotransformation rate constant klung,biotransf is calcuated from the above kB,LUNG via adjusting"]
[null,"the normalization as follows:"]
[null,"lung biotransformation rate constant klung,biotransf [1/d]",{"$f":"kBLUNG*Korganismw/Klungcellw*mbody/Vlung","v":2818.7980396662365}," = kB,LUNG * Korganismw / Klungcellw * Vbody / Vlung"]
[]
[null,"When the lung is considered as an extra compartment, rate constants describing transport from lung to rest"]
[null,"body (i.e. body without lung, liver, GIT and kidney) and vice versa are required (\"kbody,in\" and \"kbody,out\"). When no limi-"]
[null,"tations due to slow permeation kinetics are assumed, this transport should solely depend on the blood flow rate."]
[null,"The rate constants can then be calculated from blood flow as follows:"]
[null,"body-to-lung rate constant kbody,out [1/d]",{"$f":"'organism input data'!D132*Kbloodw/Krestorganismw*1/mrestbody*24","v":119.64530686678032}," = Qbody * Kblood/w / Krestorganism/w * 1/mrestbody * 24"]
[null,"lung-to-body rate constant kbody,in [1/d]",{"$f":"'organism input data'!D132*Kbloodw/Klungcellw*1/Vlung*24","v":2633807.4201284824}," = Qbody * Kblood/w / Klungcells/w * 1/Vlung * 24"]

{"sheet":"k2 - GIT biotransf","index":8,"n_rows":64,"n_cols":4,"rows_kept":64,"cut":false,"hidden":false,"merged":[]}
[]
[null,{"$f":"\"Calculation of the GIT biotransformation rate constant for \"&'compound input data'!D5","v":"Calculation of the GIT biotransformation rate constant for b(a)p"}]
[]
[null,{"$f":"\"Info: You are currently using a log Kow of \"&'compound input data'!B12&\" and a log Koa of \"&'compound input data'!C12&\".\"","v":"Info: You are currently using a log Kow of 8 and a log Koa of 10."}]
[]
[]
[null,"in vitro - in vivo extrapolation of gut S9 assay data:"]
[]
[null,"assay clearance CLin vitro\n[mLassay/h/mgS9]",{"$f":"'compound input data'!J48/'compound input data'!J49","v":1}," = kassay / CS9"]
[]
[null,"gut cell clearance CLgut [mLgut/h]",{"$f":"1/fugutS9assay*C9*gutSnine*mgut*wgutS9assay/Kgutcellw","v":0.5382347126484005}," = 1/fu,gutS9-assay * CLin vitro  * gutS9 * mgut * wassay/Kgutcell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,GIT [mLblood/h]",{"$f":"fublood/fugutS9assay*C9*gutSnine*mgut*wgutS9assay/wblood","v":0.7504962132978491}," = fu,blood/fu,gutS9-assay * CLin vitro  * gutS9 * mgut * wassay/wblood"]
[null,"blood clearance incl. flow lim. \nCLblood,GIT [mLblood/h]",{"$f":"(Qgut*fublood/fugutS9assay*C9*gutSnine*mgut*wgutS9assay/wblood)/(Qgut+fublood/fugutS9assay*C9*gutSnine*mgut*wgutS9assay/wblood)","v":0.74962422816620322}," = (Qgut * fu,blood/fu,gutS9-assay * CLin vitro * gutS9 * mgut * wassay/wblood) / \n    (Qgut + fu,blood/fu,gutS9-assay * CLin vitro * gutS9* mgut * wassay/wblood)"]
[]
[null,"Whole-body GIT biotransformation rate constant kB,GIT (w/o flow lim.) [1/d]",{"$f":"(C13*Kbloodw/Korganismw)/mbody*24","v":3.0612706458517942E-2}," = (CLblood w/o flowlim,GIT * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[]
[null,"in vitro - in vivo extrapolation of gut cell assay data:"]
[]
[null,"assay clearance CLin vitro\n[mLassay/h/106cells]",{"$f":"'compound input data'!J53/'compound input data'!J54","v":0.05}," = kassay / Ccells,assay"]
[]
[null,"gut cell clearance CLgut [mLgut/h]",{"$f":"1/fugutcellassay*C22*gutcells*mgut*'compound input data'!J72/Kgutcellw","v":0.14763722258344841}," = 1/fu,gutcell-assay * CLin vitro  * gutcells * mgut * wassay/Kgutcell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,GIT [mLblood/h]",{"$f":"fublood/fugutcellassay*C22*gutcells*mgut*'compound input data'!J72/wblood","v":0.20586033172310486}," = fu,blood/fu,gutcell-assay * CLin vitro  * gutcells * mgut * wassay/wblood"]
[null,"blood clearance incl. flow lim. \nCLblood,GIT [mLblood/h]",{"$f":"(Qgut*fublood/fugutcellassay*C22*gutcells*mgut*'compound input data'!J72/wblood)/(Qgut+fublood/fugutcellassay*C22*gutcells*mgut*'compound input data'!J72/wblood)","v":0.20579466826557624}," = (Qgut * fu,blood/fu,gutcell-assay * CLin vitro * gutcells * mgut * wassay/wblood) / (Qgut + fu,blood/fu,gutcell-assay * CLin vitro * gutcells* mgut * wassay/wblood)"]
[]
[null,"Whole-body GIT biotransformation rate constant kB,GIT (w/o flow lim.) [1/d]",{"$f":"(C26*Kbloodw/Korganismw)/mbody*24","v":8.3970335823553184E-3}," = (CLblood w/o flowlim,GIT * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[]
[null,"in vitro - in vivo extrapolation of gut microsome assay data:"]
[]
[null,"assay clearance CLin vitro\n[mLassay/h/mgmic]",{"$f":"'compound input data'!J59/'compound input data'!J60","v":1.0999999999999999}," = kassay / Cmicrosomes"]
[]
[null,"gut cell clearance CLgut [mLgut/h]",{"$f":"1/fugutmicassay*C35*gutmic*mgut*wgutmicassay/Kgutcellw","v":0.50828912581598007}," = 1/fu,gutmic-assay * CLin vitro  * gutmic * mgut * wassay/Kgutcell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,GIT [mLblood/h]",{"$f":"fublood/fugutmicassay*C35*gutmic*mgut*wgutmicassay/wblood","v":0.7087411035017358}," = fu,blood/fu,gutmic-assay * CLin vitro  * gutmic * mgut * wassay/wblood"]
[null,"blood clearance incl. flow lim. \nCLblood,GIT [mLblood/h]",{"$f":"(Qgut*fublood/fugutmicassay*C35*gutmic*mgut*wgutmicassay/wblood)/(Qgut+fublood/fugutmicassay*C35*gutmic*mgut*wgutmicassay/wblood)","v":0.70796339761723892}," = (Qgut * fu,blood/fu,gutmic-assay * CLin vitro * gutmic * mgut * wassay/wblood) / (Qgut + fu,blood/fu,gutmic-assay * CLin vitro * gutmic* mgut * wassay/wblood)"]
[]
[null,"Whole-body GIT biotransformation rate constant kB,GIT (w/o flow lim.) [1/d]",{"$f":"(C39*Kbloodw/Korganismw)/mbody*24","v":2.8909517426137961E-2}," = (CLblood w/o flowlim,GIT * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[null,"The following value for kB,GIT is used for final BMF calculation:"]
[]
[null,"whole-body GIT biotransformation rate constant kB,GIT (w/o flow lim.) [1/d]",0]
[]
[]
[null,"The above calculated GIT biotransformation rate constant kB,GIT refers to whole-body concentration and"]
[null,"is used in the one-compartment model. "]
[null,"For the multi-compartment model (that represents the GIT as an extra compartment), this kB,GIT cannot be "]
[null,"used. Instead, a GIT biotransformation rate constant that refers to chemical concentration in the GIT (and "]
[null,"not to whole-body concentration) is required."]
[null,"This required GIT biotransformation rate constant kGIT,biotransf is calcuated from the above kB,GIT via adjusting"]
[null,"the normalization as follows:"]
[null,"GIT biotransformation rate constant kGIT,biotransf [1/d]",{"$f":"kBGIT*Korganismw/Kgutcellw*mbody/Vgut","v":0}," = kB,GIT * Korganismw / Kgutcellw * Vbody / Vgut "]
[]
[null,"When the GIT is considered as an extra compartment, rate constants describing transport from GIT to lung"]
[null,"and vice versa (\"kGIT,out\" and \"kGIT,in\") are required. When no limitations due to slow permeation kinetics are"]
[null,"assumed, this transport should solely depend on the blood flow rate."]
[null,"The rate constants can then be calculated from blood flow as follows:"]
[null,"GIT-to-liver rate constant kGIT,out [1/d]",{"$f":"Qgut*Kbloodw/Kgutcellw*1/Vgut*24","v":7918.5091247451965}," = Qgut * Kblood/w / Kgutcells/w * 1/Vgut * 24"]
[null,"body-to-GIT rate constant kGIT,in [1/d]",{"$f":"Qgut*Kbloodw/Klungcellw*1/Vlung*24","v":588281.0734009603}," = Qgut * Kblood/w / Klung/w * 1/Vlung * 24"]

{"sheet":"k2 - kidney biotransf","index":9,"n_rows":64,"n_cols":4,"rows_kept":64,"cut":false,"hidden":false,"merged":[]}
[]
[null,{"$f":"\"Calculation of the kidney biotransformation rate constant for \"&'compound input data'!D5","v":"Calculation of the kidney biotransformation rate constant for b(a)p"}]
[]
[null,{"$f":"\"Info: You are currently using a log Kow of \"&'compound input data'!B12&\" and a log Koa of \"&'compound input data'!C12&\".\"","v":"Info: You are currently using a log Kow of 8 and a log Koa of 10."}]
[]
[]
[null,"in vitro - in vivo extrapolation of kidney S9 assay data:"]
[]
[null,"assay clearance CLin vitro\n[mLassay/h/mgS9]",{"$f":"'compound input data'!M48/'compound input data'!M49","v":1}," = kassay / CS9"]
[]
[null,"kidney cell clearance CLkidney [mLkidney/h]",{"$f":"1/fukidneyS9assay*C9*KSnine*mkidney*wkidneyS9assay/Kkidneycellw","v":1.261807922922155}," = 1/fu,kidneyS9-assay * CLin vitro  * KS9 * mkidney * wassay/Kkidneycell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,kidney [mLblood/h]",{"$f":"fublood/fukidneyS9assay*C9*KSnine*mkidney*wkidneyS9assay/wblood","v":1.343336670459049}," = fu,blood/fu,kidneyS9-assay * CLin vitro  * KS9 * mkidney * wassay/wblood"]
[null,"blood clearance incl. flow lim. \nCLblood,kidney [mLblood/h]",{"$f":"(Qkidney*fublood/fukidneyS9assay*C9*KSnine*mkidney*wkidneyS9assay/wblood)/(Qkidney+fublood/fukidneyS9assay*C9*KSnine*mkidney*wkidneyS9assay/wblood)","v":1.3403085097283174}," = (Qkidney * fu,blood/fu,kidneyS9-assay * CLin vitro * KS9 * mkidney * wassay/wblood) / \n    (Qkidney + fu,blood/fu,kidneyS9-assay * CLin vitro * KS9* mkidney * wassay/wblood)"]
[]
[null,"Whole-body kidney biotransformation rate constant kB,KIDNEY (w/o flow lim.) [1/d]",{"$f":"(C13*Kbloodw/Korganismw)/mbody*24","v":5.4794641783762317E-2}," = (CLblood w/o flowlim,kidney * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[]
[null,"in vitro - in vivo extrapolation of kidney cell assay data:"]
[]
[null,"assay clearance CLin vitro\n[mLassay/h/106cells]",{"$f":"'compound input data'!M53/'compound input data'!M54","v":0.05}," = kassay / Ccells,assay"]
[]
[null,"kidney cell clearance CLkidney [mLkidney/h]",{"$f":"1/fukidneycellassay*C22*Kcells*mkidney*wkidneycellassay/Kkidneycellw","v":7.7640083024264298E-2}," = 1/fu,kidneycell-assay * CLin vitro  * Kcells * mkidney * wassay/Kkidneycell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,kidney [mLblood/h]",{"$f":"fublood/fukidneycellassay*C22*Kcells*mkidney*wkidneycellassay/wblood","v":8.2656614156015037E-2}," = fu,blood/fu,kidneycell-assay * CLin vitro  * Kcells * mkidney * wassay/wblood"]
[null,"blood clearance incl. flow lim. \nCLblood,kidney [mLblood/h]",{"$f":"(Qkidney*fublood/fukidneycellassay*C22*Kcells*mkidney*wkidneycellassay/wblood)/(Qkidney+fublood/fukidneycellassay*C22*Kcells*mkidney*wkidneycellassay/wblood)","v":8.2645125105716255E-2}," = (Qkidney * fu,blood/fu,kidneycell-assay * CLin vitro * Kcells * mkidney * wassay/wblood) / (Qkidney + fu,blood/fu,kidneycell-assay * CLin vitro * Kcells* mkidney * wassay/wblood)"]
[]
[null,"Whole-body kidney biotransformation rate constant kB,KIDNEY (w/o flow lim.) [1/d]",{"$f":"(C26*Kbloodw/Korganismw)/mbody*24","v":3.3715595377812402E-3}," = (CLblood w/o flowlim,kidney * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[]
[null,"in vitro - in vivo extrapolation of kidney microsome assay data:"]
[]
[null,"assay clearance CLin vitro\n[mLassay/h/mgmic]",{"$f":"'compound input data'!M59/'compound input data'!M60","v":1.0999999999999999}," = kassay / Cmicrosomes"]
[]
[null,"kidney cell clearance CLkidney [mLkidney/h]",{"$f":"1/fukidneymicassay*C35*Kmic*mkidney*wkidneymicassay/Kkidneycellw","v":0.13382626401757766}," = 1/fu,kidneymic-assay * CLin vitro  * Kmic * mkidney * wassay/Kkidneycell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,kidney [mLblood/h]",{"$f":"fublood/fukidneymicassay*C35*Kmic*mkidney*wkidneymicassay/wblood","v":0.14247313292265421}," = fu,blood/fu,kidneymic-assay * CLin vitro  * Kmic * mkidney * wassay/wblood"]
[null,"blood clearance incl. flow lim. \nCLblood,kidney [mLblood/h]",{"$f":"(Qkidney*fublood/fukidneymicassay*C35*Kmic*mkidney*wkidneymicassay/wblood)/(Qkidney+fublood/fukidneymicassay*C35*Kmic*mkidney*wkidneymicassay/wblood)","v":0.14243900175283267}," = (Qkidney * fu,blood/fu,kidneymic-assay * CLin vitro * Kmic * mkidney * wassay/wblood) / (Qkidney + fu,blood/fu,kidneymic-assay * CLin vitro * Kmic* mkidney * wassay/wblood)"]
[]
[null,"Whole-body kidney biotransformation rate constant kB,KIDNEY (w/o flow lim.) [1/d]",{"$f":"(C39*Kbloodw/Korganismw)/mbody*24","v":5.8114726218554289E-3}," = (CLblood w/o flowlim,kidney * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[null,"The following value for kB,KIDNEY is used for final BMF calculation:"]
[]
[null,"whole-body kidney biotransformation rate constant kB,KIDNEY (w/o flow lim.) [1/d]",0]
[]
[]
[null,"The above calculated kidney biotransformation rate constant kB,KIDNEY refers to whole-body concentration and"]
[null,"is used in the one-compartment model. "]
[null,"For the multi-compartment model (that represents the kidney as an extra compartment), this kB,KIDNEY cannot be "]
[null,"used. Instead, a kidney biotransformation rate constant that refers to chemical concentration in the kidney (and "]
[null,"not to whole-body concentration) is required."]
[null,"This required kidney biotransformation rate constant kkidney,biotransf is calcuated from the above kB,KIDNEY via adjusting"]
[null,"the normalization as follows:"]
[null,"renal biotransformation rate constant kkidney,biotransf [1/d]",{"$f":"C47*Korganismw/Kkidneycellw*mbody/Vkidney","v":0}]
[]
[null,"When the kidney is considered as an extra compartment, rate constants describing transport from kidney to lung"]
[null,"and vice versa (\"kkidney,out\" and \"kkidney,in\") are required. When no limitations due to slow permeation kinetics are"]
[null,"assumed, this transport should solely depend on the blood flow rate."]
[null,"The rate constants can then be calculated from blood flow as follows:"]
[null,"lung-to-kidney rate constant kkidney,in [1/d]",{"$f":"Qkidney*Kbloodw/Klungcellw*1/Vlung*24","v":542141.38136951241}," = Qkidney * Kblood/w / Klungcells/w * 1/Vlung* 24"]
[null,"kidney-to-lung rate constant kkidney,out [1/d]",{"$f":"Qkidney*Kbloodw/Kkidneycellw*1/Vkidney*24","v":23804.076742578774}," = Qkidney * Kblood/w / Kkidneycells/w * 1/Vkidney * 24"]

{"sheet":"k2 - feces","index":10,"n_rows":16,"n_cols":5,"rows_kept":16,"cut":false,"hidden":false,"merged":[[5,1,5,2]]}
[]
[null,{"$f":"\"Calculation of the fecal egestion rate constant for \"&'compound input data'!D5","v":"Calculation of the fecal egestion rate constant for b(a)p"}]
[]
[null,{"$f":"\"Info: You are currently using a log Kow of \"&'compound input data'!B12&\" and a log Koa of \"&'compound input data'!C12&\".\"","v":"Info: You are currently using a log Kow of 8 and a log Koa of 10."}]
[]
[null,"Fecal egestion rate constant kE [1/d]",null,{"$f":"kGITuptake*('organism input data'!C60*(1-'organism input data'!D101)*Kpw/Korganismw+'organism input data'!D60*(1-'organism input data'!D100)*10^logKow/Korganismw)","v":4.4105980098351405E-3}," = kFEED* (proteincontentfood *(1-EP)*KPW/Korganism/W + lipcontentfood *(1-EL)*KOW/Korganism/W )"]
[]
[]
[null,"The above calculated fecal egestion rate constant kE refers to whole-body concentration and is used "]
[null,"in the one-compartment model. "]
[null,"For the multi-compartment model (that represents the GIT as an extra compartment), this kE cannot be "]
[null,"used. Instead, a fecal egestion rate constant that refers to chemical concentration in the GIT (and not to"]
[null,"whole-body concentration) is required."]
[null,"This required fecal egestion rate constant kGIT,feces is calcuated from the above kE via adjusting the"]
[null,"normalization as follows:"]
[null,"GIT fecal egestion rate constant kGIT,feces [1/d]",null,{"$f":"kE*Korganismw/Kgutcellw*mbody/Vgut","v":1.3271030174964473}," = kE * Korganism/w / Kgutcell/w * Vbody / Vgut"]

{"sheet":"k2 - urine","index":11,"n_rows":16,"n_cols":5,"rows_kept":16,"cut":false,"hidden":false,"merged":[[5,1,5,2],[15,1,15,2]]}
[]
[null,{"$f":"\"Calculation of the urinary excretion rate constant for \"&'compound input data'!D5","v":"Calculation of the urinary excretion rate constant for b(a)p"}]
[]
[null,{"$f":"\"Info: You are currently using a log Kow of \"&'compound input data'!B12&\" and a log Koa of \"&'compound input data'!C12&\".\"","v":"Info: You are currently using a log Kow of 8 and a log Koa of 10."}]
[]
[null,"Urinary excretion rate constant kU [1/d]",null,{"$f":"'organism input data'!D103/Korganismw","v":7.0836863928084579E-9}," = urination rate / Korganism/water"]
[]
[]
[null,"The above calculated urinary excretion egestion rate constant kU refers to whole-body concentration and is used "]
[null,"in the one-compartment model. "]
[null,"For the multi-compartment model (that represents the kidney as an extra compartment), this kU cannot be "]
[null,"used. Instead, a urinary exrection rate constant that refers to chemical concentration in the kidney (and not to"]
[null,"whole-body concentration) is required."]
[null,"This required fecal egestion rate constant kkidney,urine is calcuated from the above kU via adjusting the"]
[null,"normalization as follows:"]
[null,"\"kidney-based\" urinary excretion rate constant kkidney,urine [1/d]",null,{"$f":"kU*Korganismw/Kkidneycellw*mbody/Vkidney","v":6.9525916712573821E-6}]

{"sheet":"references","index":12,"n_rows":23,"n_cols":2,"rows_kept":23,"cut":false,"hidden":false,"merged":[]}
[]
[null,"References"]
[]
[null,"Arms AD, Travis CC (1988) Reference physiological parameters in pharmacokinetic modeling. Washington, US: EPA, 1988"]
[null,"Behera D, Damre A, Varghese A, Addepalli V (2008) In vitro evaluation of hepatic and extra-hepatic metabolism of coumarins using rat subcellular fractions: Correlation of in vitro clearance with in vivo data. Drug metabolism and drug interactions 23(3-4):329-350 "]
[null,"Bertram JF, Soosaipillai MC, Ricardo SD, Ryan GB (1992) Total numbers of glomeruli and individual glomerular cell types in the normal rat kidney. Cell and Tissue Research 270(1):37-45 doi:10.1007/bf00381877"]
[null,"Brown RP, Delp MD, Lindstedt SL, Rhomberg LR, Beliles RP (1997) Physiological Parameter Values for Physiologically Based Pharmacokinetic Models. Toxicology and Industrial Health 13(4):407-484 doi:10.1177/074823379701300401"]
[null,"Canadian Council on Animal Care, Guideline for animal ethics and care - rat."]
[null,"Crapo JD, Barry BE, Foscue HA, Shelburne J (1980) Structural and Biochemical Changes in Rat Lungs Occurring During Exposures to Lethal and Adaptive Doses of Oxygen. American Review of Respiratory Disease 122(1):123-143 doi:10.1164/arrd.1980.122.1.123"]
[null,"Endo S, Brown TN, Goss K-U (2013) General model for estimating partition coefficients to organisms and their tissues using the biological compositions and polyparameter linear free energy relationships. Environmental Science & Technology 47(12):6630-6639 doi:10.1021/es401772m"]
[null,"Gonzalez RF, Allen L, Dobbs LG (2009) Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro. American Journal of Physiology-Lung Cellular and Molecular Physiology 297(6):L1045-L1055 doi:10.1152/ajplung.90389.2008"]
[null,"Hatley OJD, Jones CR, Galetin A, Rostami-Hodjegan A (2017) Optimization of intestinal microsomal preparation in the rat: A systematic approach to assess the influence of various methodologies on metabolic activity and scaling factors. Biopharmaceutics & Drug Disposition 38(3):187-208 doi:10.1002/bdd.2070"]
[null,"Keenan KP, Ballam GC, Haught DG, Laroque P (2000) Chapter 5 - Nutrition. In: Krinke GJ (ed) The Laboratory Rat. Academic Press, London, p 57-75"]
[null,"Klinger W, Devereux T, Fouts J (1988) Separation and characterization of hepatocytes from immature and adult rats into distinct subpopulations by centrifugal elutriation. Experimental pathology 33(4):213-222 doi:https://doi.org/10.1016/S0232-1513(88)80075-6"]
[null,"Koster AS, Noordhoek J (1983) Glucuronidation in the rat intestinal wall: Comparison of isolated mucosal cells, latent microsomes and activated microsomes. Biochemical pharmacology 32(5):895-900 doi:https://doi.org/10.1016/0006-2952(83)90594-4"]
[null,"Krause S, Goss K-U (2018) In Vitro–in Vivo Extrapolation of Hepatic Metabolism for Different Scenarios-a Toolbox. Chemical Research in Toxicology 31(11):1195-1202 doi:10.1021/acs.chemrestox.8b00187"]
[null,"Lee Y-S, Otton SV, Campbell DA, Moore MM, Kennedy CJ, Gobas FAPC (2012) Measuring In Vitro Biotransformation Rates of Super Hydrophobic Chemicals in Rat Liver S9 Fractions Using Thin-Film Sorbent-Phase Dosing. Environmental Science & Technology 46(1):410-418 doi:10.1021/es203338h"]
[null,"Lee Y-S, Lo JC, Otton SV, Moore MM, Kennedy CJ, Gobas FAPC (2017) In vitro to in vivo extrapolation of biotransformation rates for assessing bioaccumulation of hydrophobic organic chemicals in mammals. Environmental Toxicology and Chemistry 36(7):1934-1946 doi:10.1002/etc.3718"]
[null,"Punt A, Freidig AP, Delatour T, et al. (2008) A physiologically based biokinetic (PBBK) model for estragole bioactivation and detoxification in rat. Toxicology and Applied Pharmacology 231(2):248-259 doi:https://doi.org/10.1016/j.taap.2008.04.011"]
[null,"Roth WL, Freeman RA, Wilson AG (1993) A physiologically based model for gastrointestinal absorption and excretion of chemicals carried by lipids. Risk Analysis 13(5):531-543 "]
[null,"Sohlenius-Sternbeck A-K (2006) Determination of the hepatocellularity number for human, dog, rabbit, rat and mouse livers from protein concentration measurements. Toxicology in Vitro 20(8):1582-1586 doi:https://doi.org/10.1016/j.tiv.2006.06.003"]
[null,"Vento PJ, Swartz ME, Martin LBE, Daniels D (2008) Food Intake in Laboratory Rats Provided Standard and Fenbendazole-supplemented Diets. Journal of the American Association for Laboratory Animal Science 47(6):46-50 "]
[null,"Yang J, Hernandez BJ, Martinez Alanis D, et al. (2016) The development and plasticity of alveolar type 1 cells. Development 143(1):54-65 doi:10.1242/dev.130005"]

{"sheet":"glossary","index":13,"n_rows":106,"n_cols":3,"rows_kept":106,"cut":false,"hidden":false,"merged":[]}
[]
[null,"Explanation of the used colours"]
[]
[null,"compound specific input data"]
[null,"organism specific input data"]
[null,"values used for final BMF calculation",1234]
[null,"interim results shown for information purposes only",1234]
[null,"IVIVE for cell assay in vitro data"]
[null,"IVIVE for S9 in vitro data"]
[]
[]
[]
[]
[null,"Explanation of the used variables"]
[]
[]
[null,"CLblood,lung","blood clearance due to lung biotransformation incl. flow limitation  [mLblood/h]"]
[null,"Clung","chemical steady state-concentration in lungs [g/mLlung]"]
[null,"CGIT","chemical steady state-concentration in GIT [g/mLGIT]"]
[null,"CLblood w/o flowlim,lung ","blood clearance due to lung biotransformation without flow limitation  [mLblood/h]"]
[null,"CLblood w/o flowlim,GIT ","blood clearance due to biotransformation in GITwithout flow limitation [mLblood/h]"]
[null,"CLblood w/o flowlim,liver","blood clearance due to hepatic biotransformation without flow limitation  [mLblood/h]"]
[null,"CLblood,GIT ","blood clearance due to biotransformation in GIT incl. flow limitation [mLblood/h]"]
[null,"CLblood,liver","blood clearance due to hepatic biotransformation incl. flow limitation  [mLblood/h]"]
[null,"CLlung","lung cell clearance [mLlung/h]"]
[null,"CLgut","gut cell clearance [mLgut/h]"]
[null,"CLhep ","hepatocyte clearance [mLhep/h]"]
[null,"CLin vitro ","assay clearance [mLassay/h/mgS9 or mLassay/h/106 cells]"]
[null,"Cliver","chemical steady state-concentration in liver [g/mLliver]"]
[null,"Crestbody","chemical steady state-concentration in restbody [g/mLrestbody]"]
[null,"CS9 in assay ","S9 concentration in assay [mgS9/mLassay]"]
[null,"Cviable cells in assay ","concentration of viable cells in assay [* 106 cells/mLassay]"]
[]
[]
[null,"dlungcell","lung cell diameter [cm]"]
[null,"dgutcell","gut cell diameter [cm]"]
[null,"dhep","hepatocyte diameter [cm]"]
[null,"fu,blood","unbound fraction in blood [unitless]"]
[]
[null,"fu,lungcell-assay","unbound fraction in lungcell assay"]
[null,"fu,lungS9-assay","unbound fraction in lung S9 assay [unitless]"]
[null,"fu,gutcell-assay","unbound fraction in gutcell assay"]
[null,"fu,gutS9-assay","unbound fraction in gut S9 assay [unitless]"]
[null,"fu,hep-assay","unbound fraction in hepatocyte assay [unitless]"]
[null,"fu,liverS9-assay","unbound fraction in liver S9 assay [unitless]"]
[null,"Gcells","cell content in lungs [106 cells/glungs]"]
[null,"GFBW","fractional lung weight [glung/grat]"]
[null,"GS9","lung S9 protein content [mg/glung]"]
[null,"Gutcells","cell content in gut [106 cells/gGIT]"]
[null,"GutFBW ","fractional intestine weight [ggut/grat]"]
[null,"GutS9","gut S9 protein content [mg/ggut]"]
[null,"k1","lung uptake rate constant [L/kg/d]"]
[null,"kassay","first-order biotransformation rate constant determined in assay [1/h]"]
[null,"kB,LUNG","whole-body lung biotransformation rate constant [1/d]"]
[null,"kB,GIT","whole-body GIT biotransformation rate constant [1/d]"]
[null,"kB,LIVER ","whole-body biotransformation rate constant [1/d]"]
[null,"Kblood/W","blood-water partition coefficient [LH2O/Lblood]"]
[null,"kE","fecal egestion rate constant [1/d]"]
[null,"kFEED","feeding rate [kgfood/d/kgrat]"]
[null,"Klungcells/W ","lung cell-water partition coefficient [LH2O/Llungcell]"]
[null,"klung,biotransf","lung biotransformation rate constant referring to lung concentration [1/d]"]
[null,"kbody,in","rate constant describing transport from lungs to gibody [1/d]"]
[null,"kbody,out","rate constant describing transport from body to lungs rate constant [1/d]"]
[null,"klung,ventilation","\"lung-based\" ventilation rate constant [1/d]"]
[null,"kGIT,feces ","GIT fecal egestion rate constant [1/d]"]
[null,"kGIT,in","rate constant describing transport from body to GIT [1/d]"]
[null,"kGIT,out","rate constant describing transport from GIT to body rate constant [1/d]"]
[null,"Kgutcells/W","gut cell-water partition coefficient [LH2O/Lgutcell]"]
[null,"Khep/W ","hepatocyte-water partition coefficient [LH2O/Lhep]"]
[null,"kliver,biotransf","liver biotransformation rate constant referring to liver concentration [1/d]"]
[null,"kliver,in","rate constant describing transport from body to liver [1/d]"]
[null,"kliver,out","rate constant describing transport from liver to body rate constant [1/d]"]
[null,"Korganism/W ","organism-water partition coefficient [LH2O/LOrg]"]
[null,"KOW ","octanol-water partition coefficient [LH2O/Loctanol]"]
[null,"Krestbody/W [LH2O/Lrestbody]","rest body-water partition coefficient [LH2O/Lrestbody]"]
[null,"kV","whole-body ventilation elimination rate constant [1/d]"]
[null,"LFBW","fractional liver weight [gliver/grat]"]
[null,"LHEP ","liver hepatocyte content [106 cells/gliver]"]
[null,"lipidhepassay (or lipidblood or lipidhep …)","lipid content of hepatocyte assay (or blood or hepatocytes …)"]
[null,"LS9","liver S9 protein content [mg/gliver]"]
[null,"mbody ","bodyweight [grat]"]
[null,"mlungs","lung weight [glung]"]
[null,"mgut","gut weight [ggut]"]
[null,"mliver","liver weight [gliver]"]
[null,"proteinhepassay (or proteinblood or proteinhep …)","protein content of hepatocyte assay (or blood or hepatocytes …) "]
[null,"QC","cardiac output [L/d/kgrat]"]
[null,"QGFRAC","intestinal blood flow as fraction of cardiac output [unitless]"]
[null,"Qlung","lung blood flow rate [mLblood/h]"]
[null,"Qlung, bodyweight","lung blood flow rate per bodyweight [mLblood/h/grat]"]
[null,"Qgut","gut blood flow rate [mLblood/h]"]
[null,"Qgut, bodyweight","gut blood flow rate per bodyweight [mLblood/h/grat]"]
[null,"QHFRAC","liver blood flow as fraction of cardiac output [unitless]"]
[null,"Qliver ","arterial liver blood flow [mL/h]"]
[null,"Qliver,bodyweight","liver blood flow per bodyweight [L/d/kgrat]"]
[null,"Qliver-total","total liver blood flow [mL/h]"]
[null,"Vassay","total assay volume [mLassay]"]
[null,"Vlungcells","total cell volume present in lung cell assay [mLcells]"]
[null,"Vlung","lung volume [mLlung]"]
[null,"Vgut","gut volume Vgut in [mLgut]"]
[null,"Vgutcells","total cell volume present in gutcell assay [mLcells]"]
[null,"Vhep","total hepatocyte volume present in assay  [mLhep]"]
[null,"Vorganism = mbody","volume of body [mLbody], density of 1 assumed!"]
[null,"Vrestbody","volume of restbody [mLrestbody]"]
[null,"VS9 ","S9 volume present in assay [mL]"]
[null,"whepassay (or wblood or whep …)","water content of assay (or blood or hepatocytes …)"]
[null,"ρS9","S9 density [g/mL]"]

{"sheet":"Tabelle1","index":14,"n_rows":60,"n_cols":7,"rows_kept":60,"cut":false,"hidden":false,"merged":[]}
[]
[]
[]
[]
[]
[]
[]
[]
[]
[null,null,"Crestbody","Cliver","CGIT","Cgills"]
[null,"I",{"$f":"-kbodyout*mrestbody","v":-23080.191711226562},0,0,{"$f":"kbodyin*Vlung","v":56567.912306679355},0]
[null,"II",0,{"$f":"-((kliverbiotransf+kliverout)*Vhepliver)","v":-21324.914292751535},{"$f":"kGITout*Vgut","v":11104.972313820203},{"$f":"kliverin*Vlung","v":1734.1987714456445},0]
[null,"III",0,0,{"$f":"-(kGITbiotransf+kGITfeces+kGITout)*Vgut","v":-11106.833452329323},{"$f":"kGITin*Vlung","v":12634.876763389695},0]
[null,"IV",{"$f":"kbodyout*mrestbody","v":23080.191711226562},{"$f":"kliverout*Vhepliver","v":14113.607631420351},0,{"$f":"-(klungventilation+klungbiotransf+kbodyin+kliverin+kGITin)*Vlung","v":-70997.530848140712},{"$f":"-kone*mbody*Cwfree","v":0}]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[null,"Kontrolle"]
[]
[]
[null,"  --> ( IV * Crestbody-I )  - ( I * Crestbody-IV ):"]
[null,null,"Crestbody","Cliver","CGIT","Cgills"]
[null,"I",{"$f":"-kbodyout*mrestbody","v":-23080.191711226562},0,0,{"$f":"kbodyin*Vlung","v":56567.912306679355},0]
[null,"II",0,{"$f":"-((kliverbiotransf+kliverout)*Vhepliver)","v":-21324.914292751535},{"$f":"kGITout*Vgut","v":11104.972313820203},{"$f":"kliverin*Vlung","v":1734.1987714456445},0]
[null,"III",0,0,{"$f":"-(kGITbiotransf+kGITfeces+kGITout)*Vgut","v":-11106.833452329323},{"$f":"kGITin*Vlung","v":12634.876763389695},0]
[null,"IV",{"$f":"C14*C11-C11*C14","v":0},{"$f":"D14*C11-D11*C14","v":-325744769.87021196},{"$f":"E14*C11-E11*C14","v":0},{"$f":"F14*C11-F11*C14","v":333038362.25679755},{"$f":"G14*C11-G11*C14","v":0}]
[]
[null,"  --> ( IV * Cliver-II )  - ( II * Cliver-IV):"]
[null,null,"Crestbody","Cliver","CGIT","Cgills"]
[null,"I",{"$f":"-kbodyout*mrestbody","v":-23080.191711226562},0,0,{"$f":"kbodyin*Vlung","v":56567.912306679355},0]
[null,"II",0,{"$f":"-((kliverbiotransf+kliverout)*Vhepliver)","v":-21324.914292751535},{"$f":"kGITout*Vgut","v":11104.972313820203},{"$f":"kliverin*Vlung","v":1734.1987714456445},0]
[null,"III",0,0,{"$f":"-(kGITbiotransf+kGITfeces+kGITout)*Vgut","v":-11106.833452329323},{"$f":"kGITin*Vlung","v":12634.876763389695},0]
[null,"IV",0,{"$f":"D35*D33-D33*D35","v":0},{"$f":"E35*D33-E33*D35","v":3617386650780.437},{"$f":"F35*D33-F33*D35","v":-6537108351610.7803},{"$f":"G35*D33-G33*D35","v":0}]
[]
[null,"  --> ( IV * CGIT-III )  - ( III * CGIT-IV):"]
[null,null,"Crestbody","Cliver","CGIT","Cgills"]
[null,"I",{"$f":"-kbodyout*mrestbody","v":-23080.191711226562},0,0,{"$f":"kbodyin*Vlung","v":56567.912306679355},0]
[null,"II",0,{"$f":"-((kliverbiotransf+kliverout)*Vhepliver)","v":-21324.914292751535},{"$f":"kGITout*Vgut","v":11104.972313820203},{"$f":"kliverin*Vlung","v":1734.1987714456445},0]
[null,"III",0,0,{"$f":"-(kGITbiotransf+kGITfeces+kGITout)*Vgut","v":-11106.833452329323},{"$f":"kGITin*Vlung","v":12634.876763389695},0]
[null,"IV",0,0,{"$f":"E42*E41-E41*E42","v":0},{"$f":"F42*E41-F41*E42","v":2.69013391830302E+16},{"$f":"G42*E41-G41*E42","v":0}]
[]
[null,"From the triangular form of the matrix the steady state - concentrations in the four compartments"]
[null,"can be calculated:"]
[]
[null,"Cgills",{"$f":"G49/F49","v":0}]
[null,"CGIT",{"$f":"(G48-C54*F48)/E48","v":0}]
[null,"Cliver",{"$f":"(G47-F47*C54-E47*C55)/D47","v":0}]
[null,"Crestbody",{"$f":"(G46-F46*C54-E46*C55-D46*C56)/C46","v":0}]
[]
[null,"Combination of the steady state-concentrations in the compartments finally yields the BCF:"]
[null,"BCF",{"$f":"(C55*Vgut+C56*Vhepliver+C54*Vlung+C57*mrestbody)/mbody/ 'compound input data'!$D$116","v":{"$error":"#DIV/0!"}}]