{"text_format":"1","workbook":"xlsx","n_sheets":13,"sheets":["introduction","compound input data","organism input data","BCF","k1","k2 - gills","k2 - hepatic biotransf","k2 - gill biotransf","k2 - GIT biotransf","k2 - feces","references","glossary","BAF"],"not_rendered":{"charts":0,"images":7,"macros":1,"external_links":0,"defined_names":84,"comments":4,"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":32,"n_cols":2,"rows_kept":32,"cut":false,"hidden":false,"merged":[[30,1,30,6]]}
[]
[null,"For correct functioning of this document, 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 fish', please refer to the manual:"]
[]
[null,"B-compass fish, version 1.2 (April 2021):"]
[null,"This file represents a tool for calculation of fish bioconcentration factors (BCFs). For the calculation, two BCF"]
[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 BCF from uptake and elimination rate constants. The uptake rate constant k1 reflects "]
[null,"the uptake of the chemical via the gills, 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 can either be estimated from KOW-correlations or via poly-parameter free energy relationships"]
[null,"(ppLFERs), we thus offer two versions of this file. This version is the one that uses ppLFERs."]
[]
[null,"For the user, the following three sheets are most essential:"]
[null," - compound input data sheet (partition information & in vitro biotransformation data need to be entered)"]
[null," - organism input data sheet (bodyweight of modeled fish and temperature need to be entered)"]
[null," - BCF 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,"Furthermore, there is a sheet that also allows calculation of bioaccumulation factors (BAFs)."]
[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-fish."]
[null,"Feel free to share any problems, suggestions, wishes or success with us!"]

{"sheet":"compound input data","index":1,"n_rows":120,"n_cols":10,"rows_kept":120,"cut":false,"hidden":false,"merged":[[101,1,101,2],[119,1,119,2],[77,3,77,7],[2,1,2,4],[72,4,73,4],[72,3,73,3],[72,5,73,5],[72,1,73,1],[72,2,73,2],[98,1,98,2],[8,1,8,4],[101,4,101,9],[138,4,138,6],[115,1,115,2],[116,1,116,2],[118,1,118,2],[139,1,139,2],[135,1,135,2],[118,4,118,6]]}
[null,"INPUT PARAMETERS"]
[]
[null,"Input cells that need to be entered by the user are marked with orange colour!!"]
[]
[null,"compound name","benzo[a]pyrene"]
[]
[]
[null,"1) ppLFER descriptors of the chemical"]
[null,"  - the required physico-chemical parameters can be retrieved from the LSER database"]
[null,"  - enter the chemical's physico-chemical parameters requested from the LSER database here:"]
[]
[null,"E","S","A","B","V","L"]
[null,3.63,1.98,0,0.44,1.9536,11.736000000000001]
[]
[null,"System Parameters:"]
[null,null,"s","a","b","v","l","c"]
[null,"muscle protein-water",-0.59,0.21,-3.17,2.13,0.33,-0.94]
[null,"membrane lipid-water",-0.93,-0.18,-3.75,1.73,0.49,0.53]
[null,"storage lipid-water",-1.62,-1.93,-4.1500000000000004,1.99,0.57999999999999996,0.55000000000000004]
[null,"bovine serum albumin-water",-0.46,0.2,-3.18,1.84,0.28000000000000003,0.48]
[null,"wet 1-octanol-water",-1.41,-0.18,-3.45,2.41,0.43,0.34]
[null,"Pahokee Peat-water (0.1 to 100 mmol/kgoc)",-0.98,-0.42,-3.34,1.2,0.54,0.02]
[null,"Suwannee River FA-water",-0.69,0.02,-2.4300000000000002,1.54,0.34,-0.82]
[]
[null,"For estimation of the unbound fraction in the exposure media, DOC-water and POC-water partition coefficients are needed:"]
[null,"log KPOC [LH2O/kgPOC]",{"$f":"H22+C22*C$13+D22*D$13+E22*E$13+F22*F$13+G22*G$13","v":5.2917600000000009}]
[null,"log KDOC [LH2O/kgDOC]",{"$f":"H23+C23*C$13+D23*D$13+E23*E$13+F23*F$13+G23*G$13","v":3.7433840000000007}]
[null,"For estimation of the rate constants k1 and kE, a KOW is needed. The KOW calculated from physico-chemical parameters is:"]
[null,"log KOW [LH2O/Loctanol]",{"$f":"H21+C21*C$13+D21*D$13+E21*E$13+F21*F$13+G21*G$13","v":5.7848559999999996}]
[]
[]
[]
[null,"2) Information from in vitro biotransformation assay"]
[]
[null,"Select the type of in vitro information (S9 or cell assay) you want to use and insert the required input data. In case biotransformation data is"]
[null,"not available for all tissues, select 'N/A' for the cases where information is missing."]
[null,"The extrapolation procedure will be adapted automatically according your selection (in sheets 'k2 - hepatic biotransf', 'k2 - gill biotransf' and 'k2 - GIT biotransf')."]
[null,"a) hepatic biotransformation",null,null,null,"b) gill biotransformation",null,null,"c) GIT biotransformation"]
[]
[null,"Please tick as appropriate:",null,null,null,"Please tick as appropriate:",null,null,"Please tick as appropriate:"]
[]
[]
[]
[]
[]
[]
[null," - liver S9-Assay",null,null,null," - gill S9-Assay ",null,null," - GIT S9-Assay "]
[null,"kassay [1/h]",20.98,null,null,"kassay [1/h]",5,null,"kassay [1/h]",8]
[null,"CS9 in assay [mgS9/mLassay]",1,null,null,"CS9 in assay [mgS9/mLassay]",1,null,"CS9 in assay [mgS9/mLassay]",1]
[null,"VL-S9assay [mLassay]",1,null,null,"Vgillassay [mLassay]",1,null,"Vgutassay [mLassay]",1]
[]
[null," - hepatocyte assay",null,null,null," - cell assay",null,null," - cell assay"]
[null,"kassay [1/h]",5,null,null,"kassay [1/h]",1,null,"kassay [1/h]",10]
[null,"Cviable cells in assay                    [* 106 cells/mLassay]",2,null,null,"Cviable cells in assay                    [* 106 cells/mLassay]",2,null,"Cviable cells in assay                    [* 106 cells/mLassay]",2]
[null,"viability",0.85,null,null,"viability",0.85,null,"viability",0.85]
[null,"Vhepassay [mLassay]",1,null,null,"Vgillassay [mLassay]",1,null,"Vgutassay [mLassay]",1]
[]
[]
[]
[]
[null,"CALCULATED PARAMETERS - no changes by the user required"]
[]
[null,"Water contents in assay"]
[null,"a) hepatic assay",null,null,null,"a) gill assay",null,null,"a) gut assay"]
[null,"S9 volume present in assay VS9 [mL]",{"$f":"C50*(CliverSnine/1000)/'organism input data'!D79","v":7.7233921457029028E-4}," = (Vassay * CS9/1000) / ρS9",null,"S9 volume present in assay VS9 [mL]",{"$f":"(G50*(G49/1000))/'organism input data'!D79","v":7.7233921457029028E-4},null,"S9 volume present in assay VS9 [mL]",{"$f":"(J50*(J49/1000))/'organism input data'!D79","v":7.7233921457029028E-4}]
[null,"S9-assay water content wassay",{"$f":"(C50-C65)/C50","v":0.99922766078542968}," = (Vassay - VS9)) / Vassay",null,"S9-assay water content wassay",{"$f":"(G50-G65)/G50","v":0.99922766078542968},null,"S9-assay water content wassay",{"$f":"(J50-J65)/J50","v":0.99922766078542968}]
[null,"total hepatocyte volume present in assay Vhep [mLhep]",{"$f":"(Chep*10^6*C56)/C55*1/6*PI()*dhep^3","v":2.8984420061817767E-3}," = (Cviable cells * 106 * Vhepassay)/viability * Vsinglecell ",null,"total cell volume present in assay Vgillcells [mLcells]",{"$f":"('compound input data'!G54*10^6*'compound input data'!G56)/'compound input data'!G55*(1/6*PI()*'organism input data'!D70^3)","v":4.241705713046915E-3},null,"total cell volume present in assay Vgutcells [mLcells]",{"$f":"('compound input data'!J54*10^6*'compound input data'!J56)/'compound input data'!J55*(1/6*PI()*'organism input data'!D72^3)","v":6.3789324272811691E-3}]
[null,"hep-assay water content wassay",{"$f":"(C56-Vhep)/C56","v":0.99710155799381828}," = (Vhepassay - Vhep ) / Vhepassay",null,"gill-assay water content wassay",{"$f":"('compound input data'!G56-G67)/'compound input data'!G56","v":0.99575829428695306},null,"gut assay water content wassay",{"$f":"('compound input data'!J56-J67)/'compound input data'!J56","v":0.99362106757271884}]
[]
[]
[null,"Partition information:"]
[null,"        - as interim result the following partition coefficients to different biological phases are calculated:"]
[null,"log KWW [LH2O/LH2O]","log KPW [LH2O/LProtein]","log KMW\n [LH2O/Lmembrane lip]","log KSW [LH2O/Lstorage lip]","log KAW [LH2O/Lalbumin]"]
[]
[null,0,{"$f":"H17+C17*C$13+D17*D$13+E17*E$13+F17*F$13+G17*G$13","v":4.5310480000000002},{"$f":"H18+C18*C$13+D18*D$13+E18*E$13+F18*F$13+G18*G$13","v":6.1689680000000005},{"$f":"H19+C19*C$13+D19*D$13+E19*E$13+F19*F$13+G19*G$13","v":6.2109439999999987},{"$f":"H20+C20*C$13+D20*D$13+E20*E$13+F20*F$13+G20*G$13","v":5.0507040000000005}]
[]
[null,"Korganism/W [LH2O/LOrg]",{"$f":"worganism*10^logKww+'organism input data'!C32*10^logKpw+'organism input data'!D32*10^logKsw+'organism input data'!E32*10^logKmw","v":85885.715783484644}," = worganism * KWW + proteincontentorganism * KPW + membrlipcontentorganism * KMW + storlipcontentorganism * KSW"]
[null,"Kblood/W [LH2O/Lblood]",{"$f":"wblood*10^logKww+'organism input data'!C28*10^logKaw+'organism input data'!D28*10^logKpw+'organism input data'!E28*10^logKsw+'organism input data'!F28*10^logKmw","v":26199.078867155666}," = wblood * KWW + albumincontentblood * KAW + proteincontentblood * KPW + storlipidpcontentblood * KSW +\n     membrlipcontentblood * KMW"]
[null,"Khep/W [LH2O/Lhep]",{"$f":"whep*10^logKww+'organism input data'!C36*10^logKpw+'organism input data'!D36*10^logKsw+'organism input data'!E36*10^logKmw","v":105722.76068389899}," = whep * KWW + proteincontenthep * KPW + membrlipcontenthep * KMW + storlipcontenthep * KSW"]
[null,"Kgillcell/W [LH2O/Lgillcell]",{"$f":"Khepw","v":105722.76068389899}," taken from hepatocyte data"]
[null,"Kgutcell/W [LH2O/Lgutcell]",{"$f":"Khepw","v":105722.76068389899}," taken from hepatocyte data"]
[null,"Krestbody/W [LH2O/Lrestbody]",{"$f":"(Vhepliver/mbody*Khepw+Vgut/mbody*Kgutcellw+Vgills/mbody*Kgillcellw-Korganismw)/(-(mbody-Vhepliver-Vgut-Vgills)/mbody)","v":84918.645780877618}," = (Vliver/Vbody * Khep/W + Vgut/Vbody * Kgutcell/W + Vgills/Vbody * Kgillcell/W - Korganism/W) / (-Vrestbody/Vbody))"]
[null,"fu,blood",{"$f":"wblood/Kbloodw","v":3.3945468255180386E-5}," = wblood / Kblood/H2O"]
[null,"fu,liverS9-assay",{"$f":"1/(1+'compound input data'!C92*C65/(C50-C65))","v":3.1210857392394379E-3}," = 1/(1+ KS9/W* VS9 / (VliverS9assay-VS9) )"]
[null,"fu,hep-assay",{"$f":"1/(1+Khepw*Vhep/(Vhepassay-Vhep))","v":3.2433619779663968E-3}," = 1/(1+ Khep/W *  Vhep / (Vhepassay- Vhep) )"]
[null,"fu,gillS9-assay",{"$f":"1/(1+'compound input data'!C92*G65/(G50-G65))","v":3.1210857392394379E-3}," = 1/(1+ KS9/W* VS9 / (VgillS9assay-VS9) )"]
[null,"fu,gillcell-assay",{"$f":"1/(1+Kgillcellw*G67/(G56-G67))","v":2.215550403134257E-3}," = 1/(1+ Kgillcell/W *  Vgillcells / (Vgillassay- Vgillcells )"]
[null,"fu,gutS9-assay",{"$f":"1/(1+'compound input data'!C92*J65/(J50-J65))","v":3.1210857392394379E-3}," = 1/(1+ KS9/W* VS9 / (VgutS9assay-VS9) )"]
[null,"fu,gutcell-assay",{"$f":"1/(1+Kgutcellw*J67/(J56-J67))","v":1.4711769096941818E-3}," = 1/(1+ Kgutcell/W *  Vgutcells / (Vgutassay- Vgutcells )"]
[]
[]
[null,"KS9/H2O [LH2O/LS9]=",{"$f":"'organism input data'!B40*10^logKpw+'organism input data'!C40*10^logKmw","v":413231.16940918739},"The required KS9/W is calculated as KS9/W = proteincontentS9 * KPW + lipidcontentS9 * KMW"]
[]
[]
[]
[]
[]
[]
[]
[null,"Information for comparison of the predicted BCF with a measured in vivo BCF"]
[]
[null,"freely dissolved chemical concentration in fish exposure media Cw,free [g/mL]",null,1,"Note: The exact concentration value is not relevant for the resulting BCF (or BAF), because BCF and BAF reflect concentration ratios.\nPer default, we entered 1 g/mL because with this, interpretation of the steady-state concentrations in the supporting graphs (see BCF sheet) is straight forward."]
[]
[null,"Per definition, the BCF is given by the chemical concentration in fish and the freely dissolved chemical concentration "]
[null,"in surrounding water. When dissolved organic carbon (DOC) or particulate organic carbon (POC) are present in"]
[null,"water during a BCF study, binding of the chemical to DOC and POC occurs. Accordingly, the freely dissolved chemical"]
[null,"concentration needs to be measured explicitly to allow a correct BCF calculcation."]
[null,"For practical reasons, however, in vivo BCFs are often calculated on basis of total water concentration instead of the"]
[null,"freely dissolved water concentration. To enable comparison of the here calculated modeling results with such a \"BCF "]
[null,"on total concentration basis\", chemical binding to DOC and POC need to be accounted for in the model. For this purpose,"]
[null,"information on the DOC and POC concentrations are required."]
[null,"Default values for DOC and POC concentrations derived from the maximum acceptable value given in the OECD 305 test guideline are "]
[null,"provided below, the user may adjust them if desired. In version 1.0 and 1.1 of B-compass fish, higher values were implemented as "]
[null,"defaults (form Nichols et al. 2013). With the new defaults, the predicted BCFs change partucilarly for highly hydrophobic chemicals."]
[]
[null,"dissolved organic carbon concentration CDOC [kg/L]",null,1.5999999999999999E-6,"derived from the maximum acceptable value for total organic carbon indicated in OECD "]
[null,"particulate organic carbon concentration CPOC [kg/L]",null,3.9999999999999998E-7,"TG 305 (TOC=2 mg/L) assuming that TOC consists of 80% DOC and 20 % DOC"]
[]
[null,"fraction unbound in exposure media\nfu,exposure media",null,{"$f":"1/(1+D116*10^'compound input data'!C27+D117*10^'compound input data'!C26)","v":0.91981771245857957}," =  1/(1 + CDOC *  KDOC/W + CPOC  * KPOC/W)"]
[null,"total chemical concentration in fish exposure media \nCw [g/mL]",null,{"$f":"Cwfree/D119","v":1.0871719324985614}," = Cw,free / fu, exposure media"]

{"sheet":"organism input data","index":2,"n_rows":99,"n_cols":6,"rows_kept":99,"cut":false,"hidden":false,"merged":[[85,1,85,2],[86,1,86,2],[87,1,87,2],[83,1,83,2],[51,1,51,2],[52,1,52,2],[80,1,80,2],[67,1,67,2],[53,1,53,2],[69,1,69,2],[82,1,82,2],[82,8,82,9],[78,1,78,2],[55,1,55,2],[59,1,59,2],[66,1,66,2],[77,8,77,9],[78,8,78,9],[65,1,65,2],[76,8,76,9],[75,1,75,2],[71,1,71,2],[2,1,2,4],[98,1,98,2],[95,1,95,2],[96,1,96,2],[97,1,97,2],[56,1,56,2],[89,1,89,2],[91,1,91,2],[92,1,92,2],[94,1,94,2],[57,1,57,2],[81,1,81,2],[93,1,93,2],[60,1,60,2],[61,1,61,2],[72,1,72,2]]}
[null,"INPUT PARAMETERS"]
[]
[null,"Input cells that need to be entered by the user are marked with orange colour!!"]
[]
[null,"bodyweight mbody [gfish]",10]
[null," temperature [°C]",15,"Note: Currently only kE and the cardiac output are temperature-adjusted!"]
[null,"lipid content of fish\n(value between 0 - 1!)",0.05]
[]
[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 rainbow trout) and their corresponding"]
[null,"references."]
[]
[null,"Required Physiological Parameters"]
[]
[null,"1) Compositions"]
[null,"composition fish blood (volume fractions, values between 0 - 1!) - from Bertelsen et al. 1998 and Manera & Britti 2006"]
[null,"water wblood ","albumin","non-albumin protein","storage lipid ","membrane lipid"]
[null,{"$f":"0.839*1.06/1","v":0.88934000000000002},{"$f":"0.0138*0.7/1.4","v":6.899999999999999E-3},{"$f":"1-(wblood+C28+E28+F28)","v":8.9398709677419252E-2},{"$f":"0.007*1.06/0.93","v":7.9784946236559143E-3},{"$f":"(0.014-E28)*1.06/1","v":6.3827956989247316E-3}]
[]
[null,"composition rainbow trout (volume fractions, values between 0 - 1!) "]
[null,"water worganism ","protein ","storage lipid (calculated from above)","membrane lipid (calculated from above)"]
[null,{"$f":"1-C32-C7","v":0.79199999999999993},0.158,{"$f":"lipidorganism*0.9","v":4.5000000000000005E-2},{"$f":"lipidorganism*0.1","v":5.000000000000001E-3}]
[]
[null,"composition hepatocyte (volume fractions, values between 0 - 1!) - from Endo & Brown & Goss 2013"]
[null,"water whep","protein ","storage lipid","membrane lipid"]
[null,0.73,{"$f":"1-whep-D36-E36","v":0.20500000000000002},1.9E-2,4.5999999999999999E-2]
[]
[null,"composition S9 fraction (volume fractions, values between 0 - 1!) - from Escher et al. 2011"]
[null,"protein","lipid"]
[null,{"$f":"(2/1.4)/(2/1.4+0.51/1)","v":0.73691967575534267},{"$f":"(0.51/1)/(2/1.4+0.51/1)","v":0.26308032424465733}]
[]
[null,"composition gill cells (volume fractions, values between 0 - 1!)"]
[null,"assumed to be equal to hepatocytes"]
[]
[]
[null,"composition intestinal cells (volume fractions, values between 0 - 1!)"]
[null,"assumed to be equal to hepatocytes"]
[]
[]
[]
[null,"2) Scaling factors"]
[null,"liver S9 protein content LS9 [mg/gliver]",null,163," from Nichols et al. 2013"]
[null,"liver hepatocyte content LHEP [106 cells/gliver]",null,510," from Nichols et al. 2013"]
[null,"fractional liver weight LFBW [gliver/gfish]",null,1.4999999999999999E-2," from Schultz et al. 1999 "]
[]
[null,"gill S9 content GS9 [mg/ggills]",null,163," assumed!"]
[null,"gill cell content Gcells [106 cells/ggills]",null,556," from Stadnicka et al. 2018"]
[null,"fractional gill weight GFBW [ggills/gfish]",null,2.47E-2," from Nichols et al. 1990"]
[]
[null,"cell content in gut, Gutcells [mg/gGIT]",null,229," from Saunders et al. 2020"]
[null,"S9 content in gut, Gutcells [106 cells/gGIT]",null,366," from Stadnicka et al. 2018"]
[null,"fractional intestine weight GutFBW [ggut/gfish]",null,1.24E-2," from Barron et al. 1987"]
[]
[]
[null,"3) Blood flow and volume information"]
[null,"total liver blood flow as fraction of cardiac output QHFRAC [unitless]",null,0.25900000000000001," from Nichols et al. 1990"]
[null,"arterial liver blood flow as fraction of cardiac output QHFRAC,arterial [unitless]",null,{"$f":"0.06/2.07","v":2.8985507246376812E-2}," from Nichols et al. 1991"]
[null,"hepatocyte diameter dhep [cm]",null,1.33E-3," from Arnold et al. 1995"]
[]
[null,"gill cell diameter dgill [cm]",null,1.5100000000000001E-3," from Stadnicka et al. 2018"]
[]
[null,"gut cell diameter dgut [cm]",null,1.73E-3," from Stadnicka et al. 2018"]
[null,"intestinal blood flow as fraction of cardiac output QGFRAC [unitless]",null,{"$f":"D66-D67","v":0.23001449275362321}," = QHFRAC - QHFRAC,arterial"]
[]
[]
[]
[null,"Calculated Physiological Parameters - no changes by the user required"]
[]
[null,"S9 density ρS9 [g/mL]",null,{"$f":"(2.51/(2/1.4+0.51/1))","v":1.294767870302137}]
[]
[null,"liver weight mliver [gliver]",null,{"$f":"D54*mbody","v":0.15}," = LFBW * mbody"]
[null,"gill weight mgills [ggills]",null,{"$f":"D58*mbody","v":0.247}," = GFBW * mbody"]
[null,"intestine weight mgut [ggut]",null,{"$f":"0.0124*mbody","v":0.124}," = GutFBW * mbody"]
[null,"weight rest of body mrestbody [g]",null,{"$f":"mbody-Vgut-Vgills-Vhepliver","v":9.5351544600118636}]
[]
[null,"hepatocyte volume in the liver Vhepliver [mL]",null,{"$f":"Lhep*10^6*mliver*1/6*PI()*dhep^3","v":9.4235595725985014E-2}," = Lhep * 10^6 * mliver * Vsinglecell         (Vsinglecell = 1/6 * π * dhep3  because spherical shape assumed)"]
[null,"gill cell volume  Vgills [mL]",null,{"$f":"Gcells*10^6*mgills*(1/6*PI()*D70^3)","v":0.24757181981826754}," = Gcells * 10^6 * mgills * Vsinglecell         (Vsinglecell = 1/6 * π * dgill3  because spherical shape assumed)"]
[null,"gut cell volume Vgut [mL]",null,{"$f":"gutcells*10^6*mgut*(1/6*PI()*D72^3)","v":0.12303812444388464}," = Gutcells * 10^6 * mgut * Vsinglecell         (Vsinglecell = 1/6 * π * dgut3  because spherical shape assumed)"]
[]
[null,"temperature adjusted cardiac output QC [L/d/kgfish]",null,{"$f":"((((0.23*T)-0.78)*(mbody/500)^-0.1)*24)","v":94.758789355142355}," = (((0.23 * T) - 0.78) * (mbody/500)-0.1) * 24        from Erickson & McKim 1990"]
[]
[null,"arterial liver blood flow per bodyweight Qliver,bodyweight [L/d/kgfish]",null,{"$f":"D90*D67","v":2.7466315755113726}," = QC * QHFRAC"]
[null,"arterial liver blood flow Qliver [mL/h]",null,{"$f":"(D92*1000/1000)/24*mbody","v":1.1444298231297387}," = Qliver,bodyweight / 24 * mbody"]
[null,"gill blood flow rate per bodyweight Qgills, bodyweight [mLblood/h/gfish] ",null,{"$f":"'organism input data'!D90*1000/1000/24","v":3.9482828897975977}," assumed as 100% of cardiac output "]
[null,"gill blood flow rate  Qgills [mLblood/h]",null,{"$f":"D94*mbody","v":39.482828897975978}," = Qgills,bodyweight * mbody"]
[null,"gut blood flow rate [mLblood/h/gfish] Qgut, bodyweight",null,{"$f":"D90*D73","v":21.795894867470498}," = QC * QGFRAC"]
[null,"gut blood flow rate  Qgut [mLblood/h]",null,{"$f":"(D96*1000/1000)/24*mbody","v":9.081622861446041}," = Qgut,bodyweight * mbody"]
[null,"total liver blood flow Qliver-total [mL/h]",null,{"$f":"(D90*D66*1000/1000)/24*mbody","v":10.22605268457578}," = QC * QHFRAC / 24 * mbody"]
[null,"blood flow rate to rest body Qbody [mL/h]",null,{"$f":"('organism input data'!D90*1000/1000/24*mbody)-Qliver-Qgut","v":29.256776213400194}," = QC / 24 * mbody - Qgut - Qliver"]

{"sheet":"BCF","index":3,"n_rows":265,"n_cols":19,"rows_kept":265,"cut":false,"hidden":false,"merged":[[1,10,1,11],[4,10,4,13],[61,21,61,22],[194,6,194,7],[197,6,197,7],[6,1,6,2],[46,1,46,2],[49,1,49,2],[183,1,183,2],[189,1,189,2],[194,1,194,2],[197,1,197,2],[13,1,13,2],[33,1,33,2],[70,1,70,2],[91,1,91,2],[53,1,53,2]]}
[null,null,null,null,null,null,null,null,null,null,null,null,"in g/d","% of uptake"]
[null,{"$f":"\"Calculation of the BCF for \"&'compound input data'!C5","v":"Calculation of the BCF for benzo[a]pyrene"},null,null,null,null,null,null,null,null,"chemical mass taken up",null,{"$f":"kone*Cwfree*mbody","v":2488.8764800777194},{"$f":"M2/M2","v":1}]
[]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"in g/d","% of uptake"]
[null,null,null,null,null,null,null,null,null,null,"one-compartment model",null,null,null,null,"multi-compartment model"]
[null,"1) Partitioning based BCF (without biotransformation):",null,null,null,null,null,null,null,null,"mass eliminated via ventilation",null,{"$f":"kV*D47*Cwfree*mbody","v":2.0888297914102796},{"$f":"M6/$M$2","v":8.3926615407810528E-4},null,"mass eliminated via ventilation",null,{"$f":"kgillsventilation*B31*Vgills","v":2.2852428118566479},{"$f":"R6/$M$2","v":9.1818249324501929E-4}]
[null,"partitioning based BCF (corresponds to the organism-water partition coefficient)\n [Lwater/Lfish]",null,{"$f":"Korganismw","v":85885.715783484644},null,null,null,null,null,null,"mass transformed in gills",null,{"$f":"D47*kBGILLS*Cwfree*mbody","v":1298.148157814685},{"$f":"M7/$M$2","v":0.52157998526875393},null,"mass transformed in gills",null,{"$f":"kgillsbiotransf*B31*Vgills","v":1420.2132498158501},{"$f":"R7/$M$2","v":0.57062423996690326}]
[null,null,null,null,null,null,null,null,null,null,"mass transformed in liver",null,{"$f":"kBLIVER*D47*Cwfree*mbody","v":1184.2853814309769},{"$f":"M8/$M$2","v":0.47583132024052699},null,"mass transformed in liver",null,{"$f":"kliverbiotransf*C31*Vhepliver","v":1061.6187824863068},{"$f":"R8/$M$2","v":0.42654538744050324}]
[null,null,null,null,null,null,null,null,null,null,"mass transformed in GIT",null,{"$f":"D47*kBGIT*Cwfree*mbody","v":0},{"$f":"M9/$M$2","v":0},null,"mass transformed in GIT",null,{"$f":"D31*kGITbiotransf*Vgut","v":0},{"$f":"R9/$M$2","v":0}]
[null,"2) Kinetic BCFs calculated on based on the total chemical concentration in",null,null,null,null,null,null,null,null,"mass eliminated via feces",null,{"$f":"kE*D47*Cwfree*mbody","v":4.3541110406473855},{"$f":"M10/$M$2","v":1.7494283366410457E-3},null,"mass eliminated via feces",null,{"$f":"kGITfeces*D31*Vgut","v":4.7592049637055833},{"$f":"R10/$M$2","v":1.912190099348349E-3}]
[null,"    fish cultivation media:",null,null,null,null,null,null,null,null,null,null,null,null,null,"blood flows:","gill-to-body",{"$f":"1-R12-R13","v":0.74099999999999999}]
[null,"    (i.e. consistent with BCFs determined according OECD TG 305)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"gills-to-GIT ",{"$f":"'organism input data'!D73","v":0.23001449275362321}]
[null,"  a) Classical one-compartment model (no mass transfer limitations):",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"gills-to-liver",{"$f":"'organism input data'!D67","v":2.8985507246376812E-2}]
[null,"kinetic BCFone-compartment [Lwater/kgfish]",null,{"$f":"kone*'compound input data'!D119/(kV+kBLIVER+kE+kBGILLS+kBGIT)","v":66.301356962180193}," = (k1 * fu,exposure media)/(kV+kB,LIVER+kE+kB,GILLS+kB,GIT)",null,null,null,null,null,"steady state Cfree in fish",null,{"$f":"(D47*Cwfree)/Korganismw","v":8.3926615407810539E-4}]
[]
[null,"  b) Multi-compartment model:"]
[null,"    The multi-compartment model distinguishes the four compartments gills, liver, GIT and"]
[null,"    rest of the body. By this, the model can represent the potential first pass effect in the gills"]
[null,"    and the direct blood flow from GIT to liver."]
[null,"    For every compartment, a mass balance is set up containing all uptake"]
[null,"    and elimination processes applying to the respective compartment. This linear system of"]
[null,"    equations is then solved via the Gaussian elimination method."]
[null,"The linear system of equations is written into the following 4x4-matrix:",null,null,null,"Cgills","Cliver","CGIT","Crestbody"]
[null,null,null,null,"I",{"$f":"kbodyin*Vgills","v":174.00240004069349},0,0,{"$f":"-kbodyout*mrestbody","v":-216.63103466575529},0]
[null,null,null,null,"II",{"$f":"kliverin*Vgills","v":6.806407324246261},{"$f":"-((kliverbiotransf+kliverout)*Vhepliver)","v":-74.165791055409201},{"$f":"kGITout*Vgut","v":54.012245321556208},0,0]
[null,null,null,null,"III",{"$f":"kGITin*Vgills","v":54.012245321556208},0,{"$f":"-(kGITbiotransf+kGITfeces+kGITout)*Vgut","v":-54.061317043306332},0,0]
[null,null,null,null,"IV",{"$f":"-(kgillsventilation+kgillsbiotransf+kbodyin+kliverin+kGITin)*Vgills","v":-249.47498940730492},{"$f":"kliverout*Vhepliver","v":60.818652645802473},0,{"$f":"kbodyout*mrestbody","v":216.63103466575529},{"$f":"-kone*mbody*Cwfree","v":-2488.8764800777194}]
[]
[null,"    Solution of the linear systems of equations yield the steady state - concentrations in the four compartments:"]
[null,"Cgills","Cliver","CGIT","Crestbody"]
[null,{"$f":"TRANSPOSE(MMULT(MINVERSE(F24:I27),J24:J27))","v":97.072787997488859},79.539055481899936,96.984674553299072,77.970813906076842]
[]
[null,"    Combination of the steady state-concentrations in the compartments yields the BCF:"]
[null,"kinetic BCFmulti-compartment [Lwater/kgfish]",null,{"$f":"(D31*Vgut+C31*Vhepliver+B31*Vgills+E31*mrestbody)/mbody /Cwtotal","v":72.38270598761558}," =(Cgills*Vgills + Cliver*Vliver + CGIT*VGIT + Crestbody*Vrestbody) / mbody / Cw"]
[]
[null,"By combining the steady state concentrations with the respective tissue-water partition coefficients, one can "]
[null,"calculate the corresponding aqueous concentrations to see whether there is equilibrium between the tissues."]
[null,"C in gill-water [g/mL]","C in liver-water [g/mL]","C in GIT-water [g/mL]","C in restbody-water [g/mL]"]
[null,{"$f":"B31/Kgillcellw","v":9.1818249324501918E-4},{"$f":"C31/Khepw","v":7.5233615701461067E-4},{"$f":"D31/Kgutcellw","v":9.173490545075155E-4},{"$f":"E31/Krestorganismw","v":9.1818249324501918E-4}]
[]
[]
[null,"Other results:"]
[]
[null,"3) Kinetic BCFs calculated based on freely dissolved chemical concentration in"]
[null,"    fish cultivation media (BCFfd):"]
[null,"  a) Classical one-compartment model (no flow limitations):"]
[null,"kinetic BCFone-compartment,fd [Lwater/kgfish]",null,{"$f":"kone/(kV+kBLIVER+kE+kBGILLS+kBGIT)","v":72.080974375850388}," = k1 /(kV+kB,LIVER+kE+kB,GILLS+kB,GIT)"]
[]
[null,"  b) Multi-compartment model:"]
[null,"kinetic BCFmulti-compartment,fd [Lwater/kgfish]",null,{"$f":"(D31*Vgut+C31*Vhepliver+B31*Vgills+E31*mrestbody)/mbody / Cwfree","v":78.692446348031226}," =(Cgills*Vgills + Cliver*Vliver + CGIT*VGIT + Crestbody*Vrestbody) / mbody / Cw,free"]
[]
[]
[null,"4) whole-body elimination constant as an alternative endpoint:"]
[null,"whole-body elimination rate constant [1/d]",null,{"$f":"kV+kBLIVER+kE+kBGILLS+kBGIT","v":3.4528896170298982}," = kV+kB,LIVER+kE+kB,GILLS+kB,GIT"]
[]
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[null,"a) with hepatic biotransformation only:"]
[null," Classical one-compartment model (no mass transfer limitations):"]
[null,"kinetic BCF [Lwater/kgfish]",null,{"$f":"kone*'compound input data'!D119/(kV+kBLIVER+kE)","v":138.58399506848639}," =(k1 * fu,exposure media)/(kV+kB,LIVER+kE)"]
[]
[]
[]
[null,"2) with hepatic & gill biotransformation (as whole-body elimination processes):"]
[null,"    For this purpose, the extrapolated whole-body gill biotransformation rate constant kB,gills is used."]
[null,"kinetic BCF [Lwater/kgfish]",null,null,null,{"$f":"kone*'compound input data'!D119/(kV+kBLIVER+kE+kBGILLS)","v":66.301356962180193}," = (k1 * fu,exposure media)/(kV+kB,LIVER+kE+kB,GILLS)"]
[]
[null,"3) with hepatic and gill biotransformation (representing first pass-effect in gills):"]
[null,"   For this purpose, a different equation for BCF calculation and the gill-based gill biotransformation "]
[null,"   rate constant kgills,biotransf has to be used."]
[null,"kinetic BCFfirst-pass [Lwater/kgfish]",null,null,null,{"$f":"(kone*kbodyout*'compound input data'!D119)/((kbodyin+kBLIVER+kE)*(kgillsventilation+kgillsbiotransf+kbodyout)-kbodyout*kbodyin)","v":0.12461867470485251}," =(kgills,out * k1 * fu,exposure media) /\n  ((kgills,in+kB,LIVER+kE) * (kgills,ventilation+kgills,biotrans+kgills,out) - kgills,in kgills,out)"]
[]
[null,"4) with hepatic & gill & GIT biotransformation (as whole-body elimination processes):"]
[null,"kinetic BCF [Lwater/kgfish]",null,null,null,{"$f":"(kone*kbodyout*'compound input data'!D119)/((kbodyin+kBLIVER+kBGIT+kE)*(kgillsventilation+kgillsbiotransf+kbodyout)-kbodyout*kbodyin)","v":0.12461867470485251}," =(kgills,out * k1 * fu,exposure media) /\n  ((kgills,in+kB,LIVER+kBGIT+kE) * (kgills,ventilation+kgills,biotrans+kgills,out) - kgills,in kgills,out)"]
[]
[null,"steady state-concentrations:"]
[null,"chemical concentration in fish exposure medium",null,1]
[null,"state state concentration in rest of body",null,{"$f":"F198*D201","v":0.12461867470485251},null,null,null,null,{"$f":"Khepw","v":105722.76068389899}]
[null,"steady state-concentration in gills",null,{"$f":"(kone*D201*mbody+kbodyin*(mbody-mgills)*F198)/(mgills*(kgillsventilation+kgillsbiotransf+kbodyout))","v":165.24080412514084},null,null,null,null,{"$f":"(Vhepliver/mbody*Khepw-Korganismw)/(-(mbody-Vhepliver)/mbody)","v":85697.00185214715}]
[null,"fugacity in rest of body",null,{"$f":"D202/Korganismw","v":1.4509825477732819E-6},null,null,null,"restbody vertlgskoeff",{"$f":"(kone*mbody/(mbody-Vhepliver))/I202","v":2.3765494422405076E-3}]
[null,"fugacity in gills",null,{"$f":"D203/Khepw","v":1.5629633870344641E-3},null,null,null,null,{"$f":"Qliver*Kbloodw/Krestorganismw*1/mrestbody*24","v":0.88870093758489799}]
[null,null,null,null,null,null,null,"kV rest body",{"$f":"Qliver*Kbloodw/I202*1/(mbody-Vhepliver)*24","v":0.68711580918576254}]
[null,null,null,null,null,null,null,"body-to-liver rate constant kliver,in [1/d]"]
[]
[]
[null,null,null,null,null,null,null,null,"\"falsches\" 2-Kompartment","\"korrektes\" 2-Kompartment-Modell:","d.h. Abzug von Sorptionskapazität und Volumen der Leber vom Gesamtkörper,"]
[null,null,null,null,null,null,null,null,{"$f":"kone/(-(kliverout)*(kliverin)/(kliverout+('k2 - hepatic biotransf'!C24)*1/Vhepliver*24)+(kliverin)+kV+kE)","v":50.213234482016617},{"$f":"(L212*(mbody-Vhepliver)+L213*Vhepliver)/mbody/D201","v":1878.7006341042156},"anschließendes Aufsummieren der Massen in Leber und Restkörper:"]
[null,null,null,null,null,null,null,"(Quasi-)1-Kompartment"," =k1 / (-kliver,out * kliver,in / (kliver,out+kliver,biotransf) + kliver,in + kV + kE)","aus den steady-state konz in leber und restkörper berechnet","steadystate konz in restkörper",{"$f":"(D201*kone*mbody/(mbody-Vhepliver))/(-kliverout*BCF!I206/(kliverout+'k2 - hepatic biotransf'!C24/Vhepliver*24)+BCF!I206+kV+kE)","v":1894.9187366567373}]
[null,null,null,null,null,null,null,{"$f":"kone/(kV+kBLIVER+kE)","v":150.66462973197744},null,null,"steadystate konz in leber",{"$f":"BCF!I206/(kliverout+'k2 - hepatic biotransf'!C24/Vhepliver*24)*L212*(mbody-Vhepliver)/Vhepliver","v":173.90212636437892}]
[null,null,null,null,null,null,null," =(k1)/(kV+kB,LIVER+kE)",{"$f":"kone/(-(kliverout)*(kliverin)/(kliverout+('k2 - hepatic biotransf'!C24)*1/Vhepliver*24)+(kliverin)+kV+0)","v":50.274503581382731},{"$f":"(L214*(mbody-Vhepliver)+L215*Vhepliver)/mbody/D201","v":1968.3736195278511},null,{"$f":"(D201*kone*mbody/(mbody-Vhepliver))/(-kliverout*BCF!I206/(kliverout+'k2 - hepatic biotransf'!C24/Vhepliver*24)+BCF!I206+kV+0)","v":1985.3658345959011}]
[null,null,null,null,null,null,null,null," =k1 / (-kliver,out * kliver,in / (kliver,out+kliver,biotransf) + kliver,in + kV)",null,null,{"$f":"BCF!I206/(kliverout+'k2 - hepatic biotransf'!C24/Vhepliver*24)*L214*(mbody-Vhepliver)/Vhepliver","v":182.20271590990151}]
[null,null,null,null,null,null,null,{"$f":"kone/(kV+kBLIVER)","v":151.21758386866179}]
[null,null,null,null,null,null,null," =(k1)/(kV+kB,LIVER)"]
[]
[]
[]
[null,"für Stadnicka:"]
[null,"\"no biotransformation BCF\" [Lwater/kgfish]",{"$f":"kone*'compound input data'!D119/(kV+kE)","v":25611.889390532666}," =(k1 * fu,exposure media)/(kV+kE)"]
[]
[]
[null,"a) zum Vergleich Ergebnisse der Modellvereinfachung - nur Ventilation und Kiemenbiotransformation"]
[]
[]
[]
[]
[null,"Kiemenbiotransformation auf Kiemenkonzentration (\"first-pass\"):"]
[null,"kinetic BCFfirst-pass [Lwater/kgfish]",{"$f":"(kone*kbodyout)/(kbodyin*(kgillsventilation+kgillsbiotransf+kbodyout)-kbodyout*kbodyin)","v":0.13592181109479648}," =(kgills,out * k1 ) /(kgills,in * (kgills,ventilation+kgills,biotrans+kgills,out) - kgills,in kgills,out)"]
[]
[]
[null,"b) zum Vergleich nur Ventilation, Kiemenbiotransformation und ein weiterer Eliminationspfad:"]
[]
[null,"Nur Ventilation, Kiemenbiotransformation und feces:",null,null,null,"Nur Ventilation, Kiemenbiotransformation und hepatische Biotransformation:"]
[]
[null,"kinetic BCF [Lwater/kgfish]",{"$f":"kone/(kV+kE)","v":27844.527283644798}," = k1/(kV+kE)",null,"kinetic BCF [Lwater/kgfish]",{"$f":"kone/(kV+kBLIVER)","v":151.21758386866179}," = k1/(kV+kB)"]
[]
[null,"kinetic BCF [Lwater/kgfish]",{"$f":"kone/(kV+kE+kBGILLS)","v":137.5148442843369}," = k1/(kV+kE+kB,GILLS)",null,"kinetic BCF [Lwater/kgfish]",{"$f":"kone/(kV+kBLIVER+kBGILLS)","v":72.207295865349451}," = k1/(kV+kB+kgills,body)"]
[]
[null,"kinetic BCFfirst-pass [Lwater/kgfish]",{"$f":"(kone*kbodyout)/((kbodyin+kE)*(kgillsventilation+kgillsbiotransf+kbodyout)-kbodyout*kbodyin)","v":0.13592019453487669}," =(kgills,out * k1 ) /((kgills,in +kE) * (kgills,ventilation+kgills,biotrans+kgills,out) - kgills,in kgills,out)",null,"kinetic BCFfirst-pass [Lwater/kgfish]",{"$f":"(kone*kbodyout)/((kbodyin+kBLIVER)*(kgillsventilation+kgillsbiotransf+kbodyout)-kbodyout*kbodyin)","v":0.13548353155588666}," =(kgills,out * k1 ) /((kgills,in + kB,LIVER) * (kgills,ventilation+kgills,biotrans+kgills,out) - kgills,in kgills,out)"]
[]
[]
[]
[null,"c) zum Vergleich nur Ventilation und ein weiterer Ganzkörper-Eliminationspfad (dh ohne Kiemenbiotransformation):"]
[]
[null,"Nur Ventilation und feces:"]
[]
[null,"kinetic BCF [Lwater/kgfish]",{"$f":"kone/(kV+kE)","v":27844.527283644798}," = k1/(kV+kE)"]
[]
[null,"kinetic BCFfirst-pass [Lwater/kgfish]",{"$f":"(kone*kbodyout)/((kbodyin+kE)*(kgillsventilation+kbodyout)-kbodyout*kbodyin)","v":84.433346628043182}," =(kin * k1) /((kout+kE) * (kV,gills+kin) - kin kout)"]
[]
[null," -> liefert nicht das gleiche Ergebnis, wie BCF ohne first-pass!! Das müsste doch aber so sein?"]
[null," -> Problem scheint der Kiemen-zu-Körperblutfluss zu sein: Wenn dieser zu langsam ist, limitiert"]
[null,"      er die nachfolgenden kinetischen Schritte?"]
[]
[null,"bisher verwendeter Qgills [mL/h]",{"$f":"Qgills","v":39.482828897975978}]
[null,"nun folgenden Qgills verwenden:",100000]
[null,"ergibt folgendes kin und kout:"]
[null,"gill-to-body rate constant kin [1/d]",{"$f":"C259*Kbloodw/Kgillcellw*1/Vgills*24","v":2402301.7618584326}," = Qgills * Kblood/w / Kgills/w * 1/Vgills * 24"]
[null,"body-to-gills rate constant kout [1/d]",{"$f":"C259*Kbloodw/Korganismw*1/mbody*24","v":73210.99755364054}," = Qgills * Kblood/w / Korganism/w * 1/mbody * 24"]
[null,"damit kinetic BCFfirst-pass berechnen:"]
[null,"kinetic BCFfirst-pass [Lwater/kgfish]",{"$f":"(kone*C261)/((C262+kE)*(kgillsventilation+C261)-C261*C262)","v":27844.526548942526}," =(kin * k1) /((kout+kE) * (kV,gills+kin) - kin kout)"]
[null," -> nun stimmt das Ergebnis mit obigem Ergebnis (BCF ohne first-pass nur Ventilation & feces, Zelle C59) überein! "]

{"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,{"$f":"\"Calculation of the gill uptake rate constant for \"&'compound input data'!C5","v":"Calculation of the gill uptake rate constant for benzo[a]pyrene"}]
[]
[]
[]
[null,"Comparison of two variants for calculation of the gill uptake rate constant"]
[]
[null,"1) Sijm-Method"]
[null,"Gill uptake rate constant k1 [L/kg/d]",null,null,{"$f":"520*mbody^-0.32","v":248.88764800777193},null," = 520*mbody-0.32     from Sijm et al. 1995"]
[]
[null,"2) Arnot&Gobas-Method"]
[]
[null,"Gill uptake rate constant k1 [L/kg/d]",null,null,{"$f":"1/((0.01+1/(10^logKow))*(mbody/1000)^0.4)","v":630.85381292630586},null," = 1/((0.01 + 1/KOW)*(mbody/1000)0.4)      from Arnot & Gobas 2003"]
[]
[]
[null,"Insert the k1 value you want to use for final BCF calculation here:"]
[null,"(either one from above or one from your own sources)"]
[]
[null,"Gill uptake rate constant k1 [L/kg/d]",null,null,{"$f":"E9","v":248.88764800777193}]

{"sheet":"k2 - gills","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,{"$f":"\"Calculation of the ventilation elimination rate constant for \"&'compound input data'!C5","v":"Calculation of the ventilation elimination rate constant for benzo[a]pyrene"}]
[]
[]
[]
[null,"whole-body ventilation elimination rate constant kV [1/d]",null,null,{"$f":"kone/Korganismw","v":2.8978933893409045E-3}," = k1 / Korganism/W       from Arnot & Gobas 2003"]
[]
[]
[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 gills as an extra compartment), this kV cannot be "]
[null,"used. Instead, a ventilation rate constant that refers to chemical concentration in the gills (and not to "]
[null,"whole-body concentration) is required."]
[null,"This required ventilation rate constant kgills,ventilation is calcuated from the above kV via adjusting the"]
[null,"normalization as follows:"]
[null,"\"gill-based\"  ventilation rate constant kgills,ventilation [1/d]",null,null,{"$f":"kV*Korganismw/Kgillcellw*mbody/Vgills","v":9.5089735524924335E-2}," = kV * Korganism/w / Kgills/w * Vbody / Vgills"]

{"sheet":"k2 - hepatic biotransf","index":6,"n_rows":52,"n_cols":5,"rows_kept":52,"cut":false,"hidden":false,"merged":[[32,21,32,22],[100,3,100,5],[121,3,121,4],[23,3,23,4]]}
[]
[null,{"$f":"\"Calculation of the hepatic biotransformation rate constant for \"&'compound input data'!C5","v":"Calculation of the hepatic biotransformation rate constant for benzo[a]pyrene"}]
[]
[]
[]
[null,"in vitro-in vivo extrapolation of liver S9 assay data"]
[]
[]
[null,"assay clearance CLin vitro [mLassay/h/mgS9]",{"$f":"kliverS9assay/CliverSnine","v":20.98}," = kassay / CS9"]
[]
[null,"hepatocyte clearance CLhep [mLhep/h]",{"$f":"CLS9assay*1/fuliverS9assay*LSnine*mliver*wliverS9assay/Khepw","v":1.5533688811593165}," = 1/fu,liverS9assay * CLin vitro * LS9  * mliver * wassay/Khepw "]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,liver [mLblood/h]",{"$f":"fublood/fuliverS9assay*CLS9assay*LSnine*mliver*wliverS9assay/wblood","v":6.2684053630031986}," = fu,blood/fu,liverS9assay * CLin vitro * LS9 * mliver* wassay/wblood"]
[null,"blood clearance incl. flow lim. CLblood,liver [mLblood/h]",{"$f":"(Qlivertotal*fublood/fuliverS9assay*CLS9assay*LSnine*mliver*wliverS9assay/wblood)/(Qlivertotal+fublood/fuliverS9assay*CLS9assay*LSnine*mliver*wliverS9assay/wblood)","v":3.8862170133414398}," = (Qliver * fu,blood/fu,liverS9assay * CLin vitro * LS9 * mliver* wassay/wblood) / (Qliver + fu,blood/fu,liverS9assay * CLin vitro * LS9 * mliver* wassay/wblood)"]
[]
[null,"Whole-body biotransformation rate constant kB,LIVER [1/d] (w/o flow lim.)",{"$f":"(C13*Kbloodw/Korganismw)/mbody*24","v":4.5891620969605427}," = (CLblood,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]",{"$f":"khepassay/Chep","v":2.5}," = kassay / Chep"]
[]
[null,"hepatocyte clearance CLhep [mLhep/h]",{"$f":"CLhepassay*1/fuhepassay*(Lhep*mliver)*whepassay/Khepw","v":0.55613076706694697}," = 1/fu,hep-assay * CLin vitro * Lhep  * mliver * wassay/Khepw "]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,liver [mLblood/h]",{"$f":"fublood/fuhepassay*CLhepassay*Lhep*mliver*whepassay/wblood","v":2.2441888241071291}," = fu,blood/fu,hep-assay * CLin vitro * LHep * mliver* wassay/wblood"]
[null,"blood clearance incl. flow lim. CLblood,liver [mLblood/h]",{"$f":"(Qlivertotal*fublood/fuhepassay*CLhepassay*Lhep*mliver*whepassay/wblood)/(Qlivertotal+fublood/fuhepassay*CLhepassay*Lhep*mliver*whepassay/wblood)","v":1.8403166557340824}," = (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]",{"$f":"(C26*Kbloodw/Korganismw)/mbody*24","v":1.642993025116144}," = (CLblood,liver * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[null,"The following value for kB,LIVER is used for final BCF calculation:"]
[]
[null,"whole-body hepatic biotransformation rate constant kB,LIVER (w/o flow lim.) [1/d]",{"$f":"C29","v":1.642993025116144}]
[]
[]
[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]",{"$f":"kBLIVER*Korganismw/Khepw*mbody/Vhepliver","v":141.63584690881638}," = kB,LIVER * Korganismw / Khepw * Vbody / Vhepliver"]
[]
[null,"For consideration of the liver as an extra compartment,  rate constants describing transport from"]
[null,"liver to body and vice versa (\"kliver,out\" and \"kliver,in\") are required. When no limitations due to slow "]
[null,"permeation kinetics are assumed, this transport should solely depend on the liver blood flow rate."]
[null,"The rate constants can be calculated from liver blood flow rate as follows:"]
[null,"liver-to-body rate constant kliver,out [1/d]",{"$f":"Qlivertotal*Kbloodw/Khepw*1/Vhepliver*24","v":645.38937942992197}," = Qlivertotal * Kbloodw/Khepw *1/Vhepliver *24"]
[null,"body-to-liver rate constant kliver,in [1/d]",{"$f":"Qliver*Kbloodw/Kgillcellw*1/Vgills*24","v":27.492657804279055}," = Qliver * Kbloodw/Kgillcellsw * 1/Vgills * 24","      "]
[null,null,null,null,"    "]

{"sheet":"k2 - gill biotransf","index":7,"n_rows":71,"n_cols":4,"rows_kept":71,"cut":false,"hidden":false,"merged":[]}
[]
[null,{"$f":"\"Calculation of the gill biotransformation rate constant for \"&'compound input data'!C5","v":"Calculation of the gill biotransformation rate constant for benzo[a]pyrene"}]
[]
[]
[]
[]
[null,"in vitro - in vivo extrapolation of gill S9 assay data:"]
[]
[null,"assay clearance CLin vitro [mLassay/h/106cells]",{"$f":"'compound input data'!G48/'compound input data'!G49","v":5}," = kassay / Ccells,assay"]
[]
[null,"gill cell clearance CLgills [mLgills/h]",{"$f":"1/fugillS9assay*C9*GSnine*mgills*wgillS9assay/Kgillcellw","v":0.60959979924745966}," = 1/fu,gillS9-assay * CLin vitro  * GS9 * mgills * wassay/Kgillcell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,gills [mLblood/h]",{"$f":"fublood/fugillS9assay*C9*GSnine*mgills*wgillS9assay/wblood","v":2.4599557112516521}," = fu,blood/fu,gillS9-assay * CLin vitro * GS9 * mgills * wassay/wblood"]
[null,"blood clearance incl. flow lim. CLblood,gills [mLblood/h]",{"$f":"(Qgills*fublood/fugillS9assay*C9*GSnine*mgills*wgillS9assay/wblood)/(Qgills+fublood/fugillS9assay*C9*GSnine*mgills*wgillS9assay/wblood)","v":2.315678640530213}," = (Qgills * fu,blood/fu,gillS9-assay * CLin vitro * GS9 * mgills* wassay/wblood) / \n(Qgills + fu,blood/fu,gillS9-assay * CLin vitro * GS9 * mgills* wassay/wblood)"]
[]
[null,"whole-body gill biotransformation rate constant kB,GILLS (w/o flow lim.) [1/d]",{"$f":"(C13*Kbloodw/Korganismw)/mbody*24","v":1.8009581155850873}," = (CLblood w/o flowlim,gills * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[]
[null,"in vitro - in vivo extrapolation of gill cell assay data:"]
[]
[null,"assay clearance CLin vitro [mLassay/h/106cells]",{"$f":"'compound input data'!G53/'compound input data'!G54","v":0.5}," = kassay / Ccells,assay"]
[]
[null,"gill cell clearance CLgills [mLgills/h]",{"$f":"1/fugillcellassay*C22*Gcells*mgills*'compound input data'!G68/Kgillcellw","v":0.29190770071607897}," = 1/fu,gillcell-assay * CLin vitro  * Gcells * mgills * wassay/Kgillcell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,gills [mLblood/h]",{"$f":"fublood/fugillcellassay*C22*Gcells*mgills*'compound input data'!G68/wblood","v":1.1779531693109375}," = fu,blood/fu,gillcell-assay * CLin vitro * Gcells * mgills * wassay/wblood"]
[null,"blood clearance incl. flow lim. CLblood,gills [mLblood/h]",{"$f":"(Qgills*fublood/fugillcellassay*C22*Gcells*mgills*'compound input data'!G68/wblood)/(Qgills+fublood/fugillcellassay*C22*Gcells*mgills*'compound input data'!G68/wblood)","v":1.143827567230941}," = (Qgills * fu,blood/fu,gillcell-assay * CLin vitro * Gcells * mgills* wassay/wblood) / \n(Qgills + fu,blood/fu,gillcell-assay * CLin vitro * Gcells * mgills* wassay/wblood)"]
[]
[null,"whole-body gill biotransformation rate constant kB,GILLS (w/o flow lim.) [1/d]",{"$f":"(C26*Kbloodw/Korganismw)/mbody*24","v":0.86239126596726157}," = (CLblood w/o flowlim,gills * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[null,"The following value for kB,GILLS is used for final BCF calculation:"]
[]
[null,"whole-body gill biotransformation rate constant kB,GILLS (w/o flow lim.) [1/d]",{"$f":"C16","v":1.8009581155850873}]
[]
[]
[null,"The above calculated gill biotransformation rate constant kB,GILLS refers to whole-body concentration and"]
[null,"is used in the one-compartment model. "]
[null,"For the multi-compartment model (that represents the gills as an extra compartment), this kB,GILLS cannot be "]
[null,"used. Instead, a gill biotransformation rate constant that refers to chemical concentration in the gills (and "]
[null,"not to whole-body concentration) is required."]
[null,"This required gill biotransformation rate constant kgills,biotransf is calcuated from the above kB,GILLS via adjusting"]
[null,"the normalization as follows:"]
[null,"gill biotransformation rate constant kgills,biotransf [1/d]",{"$f":"kBGILLS*Korganismw/Kgillcellw*mbody/Vgills","v":59.095559392335574}," = kB,gills * Korganismw / Kgillcellw * Vbody / Vgills "]
[]
[null,"When the gills are considered as an extra compartment, rate constants describing transport from gills to rest"]
[null,"body (i.e. body without gills, liver and GIT) and vice versa are required (\"kbody,in\" and \"kbody,out\"). When no limi-"]
[null,"tations due to slow permeation kinetics are assumed, this transport should solely depend on the blood flow rate."]
[null,"The rate constants can then be calculated from blood flow as follows:"]
[null,"body-to-gill rate constant kbody,out [1/d]",{"$f":"'organism input data'!D99*Kbloodw/Krestorganismw*1/mrestbody*24","v":22.719195118889115}," = Qbody * Kblood/w / Krestorganism/w * 1/mrestbody * 24"]
[null,"gill-to-body rate constant kbody,in [1/d]",{"$f":"'organism input data'!D99*Kbloodw/Kgillcellw*1/Vgills*24","v":702.83605043749174}," = Qbody * Kblood/w / Kgillcells/w * 1/Vgills * 24"]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[null,"body-to-gills rate constant kgills,in [1/d], corrected for sorption capacities & volumes",{"$f":"Qgills*Kbloodw/Krestorganismw*1/mrestbody*24","v":30.660182346678972}]

{"sheet":"k2 - GIT biotransf","index":8,"n_rows":51,"n_cols":4,"rows_kept":51,"cut":false,"hidden":false,"merged":[]}
[]
[null,{"$f":"\"Calculation of the GIT biotransformation rate constant for \"&'compound input data'!C5","v":"Calculation of the GIT biotransformation rate constant for benzo[a]pyrene"}]
[]
[]
[]
[]
[null,"in vitro - in vivo extrapolation of gut S9 assay data:"]
[]
[null,"assay clearance CLin vitro\n[mLassay/h/106cells]",{"$f":"'compound input data'!J48/'compound input data'!J49","v":8}," = kassay / Ccells,assay"]
[]
[null,"gut cell clearance CLgut [mLgut/h]",{"$f":"1/fugutS9assay*C9*gutSnine*mgut*wgutS9assay/Kgutcellw","v":0.68791916343581594}," = 1/fu,gutS9-assay * CLin vitro  * gutS9 * mgut * wassay/Kgutcell/w"]
[]
[null,"blood clearance w/o flow limitation \nCLblood w/o flowlim,GIT [mLblood/h]",{"$f":"fublood/fugutS9assay*C9*gutSnine*mgut*wgutS9assay/wblood","v":2.7760026775967583}," = fu,blood/fu,gutS9-assay * CLin vitro  * gutS9 * mgut * wassay/wblood"]
[null,"blood clearance incl. flow lim. CLblood,GIT [mLblood/h]",{"$f":"(Qgut*fublood/fugutS9assay*C9*gutSnine*mgut*wgutS9assay/wblood)/(Qgut+fublood/fugutS9assay*C9*gutSnine*mgut*wgutS9assay/wblood)","v":2.1261094219318086}," = (Qgut * fu,blood/fu,gutS9-assay * CLin vitro * gutS9 * mgut * wassay/wblood) / (Qgut + fu,blood/fu,gutS9-assay * CLin vitro * gutS9* mgut * wassay/wblood)"]
[]
[null,"Whole-body GIT biotransformation rate constant kB,GIT (w/o flow lim.) [1/d]",{"$f":"(C13*Kbloodw/Korganismw)/mbody*24","v":2.0323392523843582}," = (CLblood,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]",{"$f":"'compound input data'!J53/'compound input data'!J54","v":5}," = kassay / Ccells,assay"]
[]
[null,"gut cell clearance CLgut [mLgut/h]",{"$f":"1/fugutcellassay*C22*gutcells*mgut*'compound input data'!J68/Kgutcellw","v":1.4496400233283324}," = 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]",{"$f":"fublood/fugutcellassay*C22*gutcells*mgut*'compound input data'!J68/wblood","v":5.8498218979857519}," = fu,blood/fu,gutcell-assay * CLin vitro  * gutcells * mgut * wassay/wblood"]
[null,"blood clearance incl. flow lim. CLblood,GIT [mLblood/h]",{"$f":"(Qgut*fublood/fugutcellassay*C22*gutcells*mgut*'compound input data'!J68/wblood)/(Qgut+fublood/fugutcellassay*C22*gutcells*mgut*'compound input data'!J68/wblood)","v":3.5579863261776397}," = (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]",{"$f":"(C26*Kbloodw/Korganismw)/mbody*24","v":4.2827129666266774}," = (CLblood,GIT * Kblood/water / Korganism/water) / Vorganism * 24"]
[]
[]
[null,"The following value for kB,GIT is used for final BCF calculation:"]
[]
[null,"whole-body GIT biotransformation rate constant kB,GIT (w/o flow lim.) [1/d]",0]
[]
[]
[null,"The above calculated GIT biotransformation rate constant kB,GIT refers to whole-body concentration and"]
[null,"is used in the one-compartment model. "]
[null,"For the multi-compartment model (that represents the GIT as an extra compartment), this kB,GIT cannot be "]
[null,"used. Instead, a GIT biotransformation rate constant that refers to chemical concentration in the GIT (and "]
[null,"not to whole-body concentration) is required."]
[null,"This required GIT biotransformation rate constant kGIT,biotransf is calcuated from the above kB,GIT via adjusting"]
[null,"the normalization as follows:"]
[null,"GIT biotransformation rate constant kGIT,biotransf [1/d]",{"$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 body"]
[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-body rate constant kGIT,out [1/d]",{"$f":"Qgut*Kbloodw/Kgutcellw*1/Vgut*24","v":438.98787929094425}," = Qgut * Kblood/w / Kgutcells/w * 1/Vgut * 24"]
[null,"body-to-GIT rate constant kGIT,in [1/d]",{"$f":"Qgut*Kbloodw/Kgillcellw*1/Vgills*24","v":218.16798600585645}," = Qgut * Kblood/w / Kgillcells/w * 1/Vgills * 24"]

{"sheet":"k2 - feces","index":9,"n_rows":16,"n_cols":5,"rows_kept":16,"cut":false,"hidden":false,"merged":[]}
[]
[null,{"$f":"\"Calculation of the fecal egestion rate constant for \"&'compound input data'!C5","v":"Calculation of the fecal egestion rate constant for benzo[a]pyrene"}]
[]
[]
[]
[null,"Fecal egestion rate constant kE [1/d]",null,{"$f":"0.125*(0.02*(mbody/1000)^-0.15*EXP(0.06*T))/(0.000000051*10^logKow+2)","v":6.0405829393257518E-3}," = 0.125*(0.02 * (mbody/1000)-0.15 * e(0.06*T)) / (0.000000051 * KOW + 2)        from Arnot & Gobas 2003"]
[]
[]
[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":0.39883346704055295}," = kE * Korganism/w / Kgut/w * Vbody / Vgut"]

{"sheet":"references","index":10,"n_rows":30,"n_cols":2,"rows_kept":30,"cut":false,"hidden":false,"merged":[]}
[]
[null,"References"]
[]
[null,"Arnold H, Pluta H-J, Braunbeck T (1995) Simultaneous exposure of fish to endosulfan and disulfoton in vivo: ultrastructural, stereological and biochemical reactions in hepatocytes of male rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology 33(1):17-43 doi:https://doi.org/10.1016/0166-445X(95)00006-P"]
[null,"Arnot JA, Gobas FAPC (2003) A Generic QSAR for Assessing the Bioaccumulation Potential of Organic Chemicals in Aquatic Food Webs. QSAR & Combinatorial Science 22(3):337-345 doi:10.1002/qsar.200390023"]
[null,"Barron MG, Tarr BD, Hayton WL (1987) Temperature-dependence of cardiac output and regional blood flow in rainbow trout, Salmo gairdneri Richardson. Journal of Fish Biology 31(6):735-744 doi:10.1111/j.1095-8649.1987.tb05276.x"]
[null,"Bertelsen SL, Hoffman AD, Gallinat CA, Elonen CM, Nichols JW (1998) Evaluation of log KOW and tissue lipid content as predictors of chemical partitioning to fish tissues. Environmental Toxicology and Chemistry 17(8):1447-1455 doi:10.1002/etc.5620170803"]
[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,"Erickson RJ, McKim JM (1990) A model for exchange of organic chemicals at fish gills: flow and diffusion limitations. Aquatic Toxicology 18(4):175-197"]
[null,"Escher BI, Cowan-Ellsberry CE, Dyer S, et al. (2011) Protein and lipid binding parameters in rainbow trout (Oncorhynchus mykiss) blood and liver fractions to extrapolate from an in vitro metabolic degradation assay to in vivo bioaccumulation potential of hydrophobic organic chemicals. Chemical Research in Toxicology 24(7):1134-43 "]
[null,"Fitzsimmons PN, Fernandez JD, Hoffman AD, Butterworth BC, Nichols JW (2001) Branchial elimination of superhydrophobic organic compounds by rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology 55(1–2):23-34 doi:https://doi.org/10.1016/S0166-445X(01)00174-6"]
[null,"Gingerich WH, Pityer RA, Rach JJ (1987) Estimates of plasma, packed cell and total blood volume in tissues of the rainbow trout (Salmo gairdneri). Comparative Biochemistry and Physiology Part A: Physiology 87(2):251-256 doi:https://doi.org/10.1016/0300-9629(87)90119-8"]
[null,"Gobas FAPC, Lee Y-S (2019) Growth-Correcting the Bioconcentration Factor and Biomagnification Factor in Bioaccumulation Assessments. Environmental Toxicology and Chemistry 38(9):2065-2072 doi:10.1002/etc.4509"]
[null,"Hampton JA, Lantz RC, Hinton DE (1989) Functional units in rainbow trout (Salmo gairdneri, Richardson) liver: III. Morphometric analysis of parenchyma, stroma, and component cell types. American Journal of Anatomy 185(1):58-73 doi:10.1002/aja.1001850107"]
[null,"Han X, Nabb DL, Mingoia RT, Yang C-H (2007) Determination of xenobiotic intrinsic clearance in freshly isolated hepatocytes from rainbow trout (Oncorhynchus mykiss) and rat and its application in bioaccumulation assessment. Environmental Science & Technology 41(9):3269-3276 doi:10.1021/es0626279"]
[null,"Han X, Nabb DL, Yang C-H, Snajdr SI, Mingoia RT (2009) Liver microsomes and S9 from rainbow trout (Oncorhynchus mykiss): Comparison of basal-level enzyme activities with rat and determination of xenobiotic intrinsic clearance in support of bioaccumulation assessment. Environmental Toxicology and Chemistry 28(3):481-488 doi:10.1897/08-269.1"]
[null,"Krause S, Goss K-U (2018b) In Vitro–in Vivo Extrapolation of Hepatic Metabolism for Different Scenarios-a Toolbox. Chemical research in toxicology "]
[null,"Lee, Y.-S., et al., In vitro to in vivo extrapolation of biotransformation rates for assessing bioaccumulation of hydrophobic organic chemicals in mammals. Environmental Toxicology and Chemistry, 2017. 36(7): p. 1934-1946."]
[null,"Manera M, Britti D (2006) Assessment of blood chemistry normal ranges in rainbow trout. Journal of Fish Biology 69(5):1427-1434 doi:doi:10.1111/j.1095-8649.2006.01205.x"]
[null,"Nichols J, Fitzsimmons P, Whiteman F, Kuehl D, Butterworth B, Jenson C (2001) Dietary uptake kinetics of 2, 2′, 5, 5′-tetrachlorobiphenyl in rainbow trout. Drug metabolism and disposition 29(7):1013-1022 "]
[null,"Nichols JW, Huggett DB, Arnot JA, Fitzsimmons PN, Cowan-Ellsberry CE (2013) Toward improved models for predicting bioconcentration of well-metabolized compounds by rainbow trout using measured rates of in vitro intrinsic clearance. Environmental Toxicology and Chemistry 32(7):1611-22 doi:10.1002/etc.2219"]
[null,"Nichols JW, McKim JM, Andersen ME, Gargas ML, Clewell HJ, Erickson RJ (1990) A physiologically based toxicokinetic model for the uptake and disposition of waterborne organic chemicals in fish. Toxicology and Applied Pharmacology 106(3):433-447 doi:http://dx.doi.org/10.1016/0041-008X(90)90338-U"]
[null,"OECD Test No. 305: Bioaccumulation in Fish: Aqueous and Dietary Exposure. OECD Publishing"]
[null,"Schultz IR, Hayton WL (1999) Interspecies scaling of the bioaccumulation of lipophilic xenobiotics in fish: An example using trifluralin. Environmental Toxicology and Chemistry 18(7):1440-1449 doi:10.1002/etc.5620180714"]
[null,"Sijm DTHM, Verberne ME, Dejonge WJ, Part P, Opperhuizen A (1995) Allometry in the uptake of hydrophobic chemicals determined in vivo and in isolated perfused gills. Toxicology and Applied Pharmacology 131(1):130-135 doi:http://dx.doi.org/10.1006/taap.1995.1054"]
[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,"Stadnicka-Michalak J, Weiss FT, Fischer M, Tanneberger K, Schirmer K (2018) Biotransformation of benzo[a]pyrene by three rainbow trout (Onchorhynchus mykiss) cell lines and extrapolation to derive a fish bioconcentration factor. Environmental Science & Technology 52(5):3091-3100 doi:10.1021/acs.est.7b04548"]
[null,"Ulrich N, Endo S., Brown T. N., Watanabe N., Bronner G., Abraham M. H., Goss K. U. (2017) UFZ-LSER database v 3.2 http://www.ufz.de/lserd "]
[null,"Valentin J (2002) Basic anatomical and physiological data for use in radiological protection: reference values: ICRP Publication 89. Annals of the ICRP 32(3–4):1-277 doi:https://doi.org/10.1016/S0146-6453(03)00002-2"]
[null,"Yamamoto T, Shima T, Furuita H, Suzuki N (2002) Influence of feeding diets with and without fish meal by hand and by self-feeders on feed intake, growth and nutrient utilization of juvenile rainbow trout (Oncorhynchus mykiss). Aquaculture 214(1):289-305 doi:http://dx.doi.org/10.1016/S0044-8486(02)00035-2"]

{"sheet":"glossary","index":11,"n_rows":111,"n_cols":3,"rows_kept":111,"cut":false,"hidden":false,"merged":[]}
[]
[null,"Explanation of the used colours"]
[]
[null,"input data"]
[null,"values used for final BCF calculation",1234]
[null,"interim results shown for information purposes only",1234]
[null,"IVIVE for hepatocyte in vitro data"]
[null,"IVIVE for S9 in vitro data"]
[]
[]
[]
[]
[null,"Explanation of the used variables"]
[]
[null,"CLblood,gills ","blood clearance due to gill biotransformation incl. flow limitation  [mLblood/h]"]
[null,"Cgills","chemical steady state-concentration in gills [g/mLgills]"]
[null,"CGIT","chemical steady state-concentration in GIT [g/mLGIT]"]
[null,"CLblood w/o flowlim,gills ","blood clearance due to gill 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,"CLgills","gill cell clearance [mLgills/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,"CW","total chemical concentration in fish tank water (in BCF study)"]
[null,"CW,free","freely dissolved chemical concentration in fish tank water (in BCF study)"]
[null,"dgillcell","gill cell diameter [cm]"]
[null,"dgutcell","gut cell diameter [cm]"]
[null,"dhep","hepatocyte diameter [cm]"]
[null,"fu,blood","unbound fraction in blood [unitless]"]
[null,"fu,exposure media","unbound fraction in fish exposure media (i.e. in fish tank water) [unitless]"]
[null,"fu,gillcell-assay","unbound fraction in gillcell assay"]
[null,"fu,gillS9-assay","unbound fraction in gill 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 gills [106 cells/ggills]"]
[null,"GFBW","fractional gill weight [ggills/gfish]"]
[null,"GS9","gill S9 protein content [mg/ggill]"]
[null,"Gutcells","cell content in gut [106 cells/gGIT]"]
[null,"GutFBW ","fractional intestine weight [ggut/gfish]"]
[null,"GutS9","gut S9 protein content [mg/ggut]"]
[null,"k1","gill uptake rate constant [L/kg/d]"]
[null,"kassay","first-order biotransformation rate constant determined in assay [1/h]"]
[null,"KAW","albumin-water partition coefficient [LH2O/Lalbumin]"]
[null,"kB,GILLS","whole-body gill biotransformation rate constant kB,GILLS [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/kgfish]"]
[null,"Kgillcells/W ","gill cell-water partition coefficient [LH2O/Lgillcell]"]
[null,"kgills,biotransf","gill biotransformation rate constant referring to gill concentration [1/d]"]
[null,"kgills,in","rate constant describing transport from body to gills [1/d]"]
[null,"kgills,out","rate constant describing transport from gills to body rate constant [1/d]"]
[null,"kgills,ventilation","\"gill-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,"KMW","membrane lipid-water partition coefficient [LH2O/Lmembrane lip]"]
[null,"Korganism/W ","organism-water partition coefficient [LH2O/LOrg]"]
[null,"KOW ","octanol-water partition coefficient [LH2O/Loctanol]"]
[null,"KPW ","protein-water partition coefficient [LH2O/LProtein]"]
[null,"Krestbody/W [LH2O/Lrestbody]","rest body-water partition coefficient [LH2O/Lrestbody]"]
[null,"KS9/H2O","S9-water partition coefficient [LH2O/LS9]"]
[null,"KSW","storage lipid-water partition coefficient [LH2O/Lstorage lip]"]
[null,"kV","whole-body ventilation elimination rate constant [1/d] (also called branchial elimination rate constant)"]
[null,"KWW","water-water partition coefficient (always = 1) [LH2O/LH2O]"]
[null,"LFBW","fractional liver weight [gliver/gfish]"]
[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 [gfish]"]
[null,"mgills","gill weight [ggills]"]
[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,"Qbody","blood flow rate to rest of body [mLblood/h]"]
[null,"QC","temperature adjusted cardiac output [L/d/kgfish]"]
[null,"QGFRAC","intestinal blood flow as fraction of cardiac output [unitless]"]
[null,"Qgills","gill blood flow rate [mLblood/h]"]
[null,"Qgills, bodyweight","gill blood flow rate per bodyweight [mLblood/h/gfish]"]
[null,"Qgut","gut blood flow rate [mLblood/h]"]
[null,"Qgut, bodyweight","gut blood flow rate per bodyweight [mLblood/h/gfish]"]
[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/kgfish]"]
[null,"Qliver-total","total liver blood flow [mL/h]"]
[null,"Vassay","total assay volume [mLassay]"]
[null,"Vgillcells","total cell volume present in gill cell assay [mLcells]"]
[null,"Vgills","gill volume Vgills [mLgills]"]
[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":"BAF","index":12,"n_rows":53,"n_cols":18,"rows_kept":53,"cut":false,"hidden":false,"merged":[[1,10,1,11],[2,10,2,11],[4,10,4,13],[4,15,4,18],[10,1,10,2],[49,1,49,2],[52,1,52,2],[17,1,17,2],[37,1,37,2]]}
[null,null,null,null,null,null,null,null,null,null,null,null,"in g/d","% of total uptake"]
[null,{"$f":"\"Calculation of the BAF for \"&'compound input data'!C5","v":"Calculation of the BAF for benzo[a]pyrene"},null,null,null,null,null,null,null,null,"chemical mass taken up - ventilation",null,{"$f":"kone*Cwfree*mbody","v":2488.8764800777194},{"$f":"M2/(M2+M3)","v":0.12655720506978557}]
[null,null,null,null,null,null,null,null,null,null,"chemical mass taken up - food",null,{"$f":"kGITuptake*Cfood*mbody","v":17177.14315669693},{"$f":"M3/(M2+M3)","v":0.87344279493021437}]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"in g/d","% of uptake"]
[null,"In case chemical uptake from the diet should also be considered, i.e. the BAF instead of the BCF",null,null,null,null,null,null,null,null,"one-compartment model",null,null,null,null,"multi-compartment model"]
[null,"should be calculated, additional input data is required:",null,null,null,null,null,null,null,null,"mass eliminated via ventilation",null,{"$f":"kV*D50*Cwfree*mbody","v":16.505024666580358},{"$f":"M6/($M$2+$M$3)","v":8.3926615407810528E-4},null,"mass eliminated via ventilation",{"$f":"kgillsventilation*B35*Vgills","v":15.20691485362636},{"$f":"Q6/($M$2+$M$3)","v":7.7325839872497901E-4}]
[null,"feeding rate kFEED [kgfood/kgfish/d]",null,0.02," from OECD Guideline 305 (Annex 7)",null,null,null,null,null,"mass transformed in gills",null,{"$f":"D50*kBGILLS*Cwfree*mbody","v":10257.402232443947},{"$f":"M7/($M$2+$M$3)","v":0.52157998526875393},null,"mass transformed in gills",{"$f":"kgillsbiotransf*B35*Vgills","v":9450.6639959169406},{"$f":"Q7/($M$2+$M$3)","v":0.48055804735619129}]
[null,null,null,null,null,null,null,null,null,null,"mass transformed in liver",null,{"$f":"kBLIVER*D50*Cwfree*mbody","v":9357.7080876426098},{"$f":"M8/($M$2+$M$3)","v":0.47583132024052693},null,"mass transformed in liver",{"$f":"kliverbiotransf*C35*Vhepliver","v":10152.887305915565},0.5162654921248061]
[null,"For simplicity, we assume the fish food to be of identical composition like the fish, i.e. we predict",null,null,null,null,null,null,null,null,"mass transformed in GIT",null,{"$f":"D50*kBGIT*Cwfree*mbody","v":0},0,null,"mass transformed in GIT",{"$f":"D35*kGITbiotransf*Vgut","v":0},0]
[null,"the BAF for a predatory fish and we assume an uptake efficiency of 100%.",null,null,null,null,null,null,null,null,"mass eliminated via feces",null,{"$f":"kE*D50*Cwfree*mbody","v":34.404292021512816},1.7494283366410457E-3,null,"mass eliminated via feces",{"$f":"kGITfeces*D35*Vgut","v":47.261420088514967},2.4032021202774582E-3]
[null,"Kfood/water [mLw/gfood]",null,{"$f":"Korganismw","v":85885.715783484644}]
[null,"chemical concentration in fish food Cfood [gchemical/gfood]",null,{"$f":"Cwfree*D11","v":85885.715783484644},null,null,null,null,null,null,"steady state Cfree in fish",null,{"$f":"(D50*Cwfree)/Korganismw","v":6.6315161876032355E-3}]
[null,"    Note that the assumption of thermodynamic equilibrium between food and surrounding water represents"]
[null,"    a worst-case estimation (biotransformation in the prey is neglected)."]
[]
[null,"Kinetic BAFs based on total chemical concentration in fish exposure water: "]
[null,"  a) Classical one-compartment model (no flow limitations):"]
[null,"kinetic BAFone-compartment [Lwater/kgfish]",null,{"$f":"((kone+kGITuptake*Cfood/Cwfree)*'compound input data'!D119)/(kV+kBLIVER+kE+kBGILLS+kBGIT)","v":523.88449101432514}," = ((k1 + kFEED *Cfood/CW,free) * fu,exposure media)/(kV+kB,LIVER+kE+kB,GILLS+kB,GIT)"]
[]
[null,"  b) Multi-compartment model:"]
[null,"    The multi-compartment model distinguishes the four compartments gills, liver, GIT and"]
[null,"    rest of the body. By this, the model can represent the potential first pass effect in the gills"]
[null,"    and the direct blood flow from GIT to liver."]
[null,"    For every compartment, a mass balance is set up containing all uptake"]
[null,"    and elimination processes applying to the respective compartment. This linear system of"]
[null,"    equations is then solved via the Gaussian elimination method."]
[null,"The linear system of equations is written into the following 4x4-matrix:",null,null,null,"Cgills","Cliver","CGIT","Crestbody"]
[null,null,null,null,"I",{"$f":"kbodyin*Vgills","v":174.00240004069349},0,0,{"$f":"-kbodyout*mrestbody","v":-216.63103466575529},0]
[null,null,null,null,"II",{"$f":"kliverin*Vgills","v":6.806407324246261},{"$f":"-((kliverbiotransf+kliverout)*Vhepliver)","v":-74.165791055409201},{"$f":"kGITout*Vgut","v":54.012245321556208},0,0]
[null,null,null,null,"III",{"$f":"kGITin*Vgills","v":54.012245321556208},0,{"$f":"-(kGITbiotransf+kGITfeces+kGITout)*Vgut","v":-54.061317043306332},0,{"$f":"-kGITuptake*mbody*Cfood","v":-17177.14315669693}]
[null,null,null,null,"IV",{"$f":"-(kgillsventilation+kgillsbiotransf+kbodyin+kliverin+kGITin)*Vgills","v":-249.47498940730492},{"$f":"kliverout*Vhepliver","v":60.818652645802473},0,{"$f":"kbodyout*mrestbody","v":216.63103466575529},{"$f":"-kone*mbody*Cwfree","v":-2488.8764800777194}]
[]
[null,"    Solution of the mass balance equations yields the steady state-concentrations in gills, liver, GIT and rest body:"]
[null,"Cgills","Cliver","CGIT","Crestbody"]
[null,{"$f":"TRANSPOSE(MMULT(MINVERSE(F28:I31),J28:J31))","v":645.9609517303827},760.67895561852652,963.10906572985562,518.84881640841354]
[]
[null,"    Combination of the steady state-concentrations in the four compartments yields the BCF:"]
[null,"kinetic BAFmulti-compartment [Lwater/kgfish]",null,{"$f":"(D35*Vgut+C35*Vhepliver+B35*Vgills+E35*mrestbody)/mbody / Cwtotal","v":487.26492502861208}," =(Cgills*Vgills + Cliver*Vliver + CGIT*VGIT + Crestbody*Vrestbody) / mbody / Cw"]
[]
[]
[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 gill-water [g/mL]","C in liver-water [g/mL]","C in GIT-water [g/mL]","C in restbody-water [g/mL]"]
[null,{"$f":"B35/Kgillcellw","v":6.1099516088285342E-3},{"$f":"C35/Khepw","v":7.1950349262339484E-3},{"$f":"D35/Kgutcellw","v":9.1097608452493997E-3},{"$f":"E35/Krestorganismw","v":6.1099516088285333E-3}]
[]
[null,"Kinetic BAFs based on freely dissolved chemical concentration in "]
[null,"fish exposure water:"]
[]
[null,"  a) Classical one-compartment model (no mass transfer limitations):"]
[null,"kinetic BAFone-compartment [Lwater/kgfish]",null,{"$f":"(kone+kGITuptake*Cfood/Cwfree)/(kV+kBLIVER+kE+kBGILLS+kBGIT)","v":569.55251450206913}," = (k1+kFEED * Cfood/CW,free) /(kV+kB,LIVER+kE+kB,GILLS+kB,GIT)"]
[]
[null,"  b) Multi-compartment model:"]
[null,"kinetic BAFmulti-compartment [Lwater/kgfish]",null,{"$f":"(D35*Vgut+C35*Vhepliver+B35*Vgills+E35*mrestbody)/mbody / Cwfree","v":529.74075018212284}," =(Cgills*Vgills + Cliver*Vliver + CGIT*VGIT + Crestbody*Vrestbody) / mbody / Cw"]