Atrazine PBPK Model Brief Instructions
This document provides additional information on the atrazine PBPK model developed by Syngenta.  The model is written in ACSL and has a number of m-files provided to run. Notes written by Paul Hinderliter 16Oct2018.
The main model file is named "Lifestage.csl". Locate m-files in the attachments for this document. For posting to the docket, ".txt" was added to the file extension. This ".txt" has to be removed for the files to run in acslX. 
Data and parameters files - these only load data or parameters, they do not execute a run:
data.m : Loads mouse and rat pharmacokinetic data.
mouse.m : Loads mouse parameters.
Ratp.m : Loads rat parameters.
monkey.m : Loads monkey parameters.
human.m : Loads human parameters.
growth.m : Sets human physiology at given age.

Files for conducting specific runs:
pod.m : Runs lifestage model at various ages and doses to calculate the point of departure.
lssensetup.m : Sets parameters to run sensitivity analysis.
SYNRatdiAT.m : Model simulation of Syngenta 4 day diet of atrazine in rat.
SYNRatgaAT.m : Model simulation of Syngenta 4 day gavage of atrazine in rat.
SYNsngleORHum.m : Syngenta human simulation - single gavage dose of 0.1 mg/kg.

The m-files for running the various human points of departures (PoD): 
PoDdermgolf.m
PoDdermmow.m
PoDdermocc.m
PoDdermturf.m
PoDdiet.m
PoDdietacute.m
PoDdw.m
PoDdwacute.m
PoDinh.m
PoDinhbys.m
PoDinhbysacute.m
PoDinhocc.m
PoDinhturf.m
PoDoralturf.m

The matrix for the human PoDs is derailed in the table below. Please see the comments in each m-file for additional documentation. All of the m-files are included at the end of this document for reference. 

Additionally, the model can be run for simazine and propazine.
For propazine, set metabolism to DIA to zero by setting VMAXCATRA_ISO and KMETATRA_ISO_OR2C = 0.
For simazine, set metabolism to DEA to zero by setting VMAXCATRA_ETHYL and KMETATRA_ETHYL_OR2C = 0.


File Key for the PBPK model to run scenarios
Run ratpod.m to verify the rat PoD
                                    RA Type
                               Exposure Pathway
                         (all triazines unless noted)
                                    Infants
                                Young Children
                                   Children
                                    Youths
                                    Females
                                       
                                       
                                 Steady State
                                 Steady State
                                 Steady State
                                 Steady State
                               Acute - Atrazine
                               Acute - Simazine
                               Acute - Propazine
                                 Steady State
                                    Dietary
                                Drinking Water
                                     PoDdw
                                     PoDdw
                                     PoDdw
                                     PoDdw
                                  PoDdwacute
                                  PoDdwacute
                                  PoDdwacute
                                     PoDdw
                                       
                                     Food
                                    PoDdiet
                                    PoDdiet
                                    PoDdiet
                                    PoDdiet
                                 PoDdietacute
                                 PoDdietacute
                                 PoDdietacute
                                    PoDdiet
                             Residential Handlers
                                    Dermal
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                  PoDdermmow
                                       
                                  Inhalation
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                    PoDinh
                             Residential (Golfers)
                                    Dermal
                                       
                                       
                                  PoDdermgolf
                                  PoDdermgolf
                                       
                                       
                                       
                                  PoDdermgolf
                             Residential (Mowing)
                                    Dermal
                                       
                                       
                                       
                                  PoDdermmow
                                       
                                       
                                       
                                  PoDdermmow
                      Residential (Other Turf Scenarios)
                                    Dermal
                                       
                                  PoDdermturf
                                       
                                       
                                       
                                       
                                       
                                  PoDdermturf
                                       
                                     Oral
                                       
                                  PoDoralturf
                                       
                                       
                                       
                                       
                                       
                                  PoDoralturf
                                       
                                  Inhalation
                                       
                                  PoDinhturf
                                       
                                       
                                       
                                       
                                       
                                  PoDinhturf
                             Residential Bystander
                                  Inhalation
                                       
                                   PoDinhbys
                                       
                                       
                                PoDinhbysacute
                                PoDinhbysacute
                                PoDinhbysacute
                                   PoDinhbys
                        Non-Occupational (Spray Drift)
                                    Dermal
                                       
                                  PoDdermturf
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                     Oral
                                       
                                  PoDoralturf
                                       
                                       
                                       
                                       
                                       
                                  PoDoralturf
                                 Occupational
                                    Dermal
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                  PoDdermocc
                                       
                                  Inhalation
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                   PoDinhocc




Additional comments:
The PoD was calculated as the average daily blood AUC for total triazines for the last 4 days (of 365 days of exposure). For humans, steady state is achieved in 2 days. Therefore 21 days was the simulation time for all of the steady state simulations

For acute scenarios, the single day AUC was used for the PoD.

All of the simulations had the lifestage growth model turned on.

Exposure scenarios were run independently (e.g. occupational dermal and inhalation were run separately).

General: 
 Assume 4-day average residues since 4-day time to effect
 Have to first run the PBPK model for the rat oral dosing study to calculate the systemic dose corresponding to the NOAEL oral dose received by the rat  -  this is the target NOAEL/POD
 Each input in table reflects the exposure required to reach the internal dose causing LH surge attenuation measured in the rat study
 Since we're using the same endpoint for all 3 triazines, running these PODs will cover all 3  -  we can pick and choose which scenarios are appropriate for each chemical.  

Body Weights
For each exposure scenario, the appropriate body weight for each age group or sex was modeled as identified from the Exposure Factors Handbook (USEPA, 2011) for occupational and residential exposures and from the NHANES/What We Eat in America (WWEIA) Survey for dietary exposures.  All body weights used are consistent with those assumed for dietary, occupational and residential exposure assessments.  

Infants birth to < 1 year old:  4.8 kg
Children 1-2 years old:  12.6 kg for dietary exposures; 11 kg for residential exposures
Female adults:  72.9 kg for dietary exposures; 69 kg for residential exposures
Dietary children 6-12 years old (37.1 kg) / residential children 6-11 (32 kg) years old (combine for aggregate)
Dietary youths 13-19 years old (67.3 kg)/ residential 11-16 years old (57 kg)  (combine for aggregate)

Dietary Consumption
Dietary exposure was estimated for 7 days/week.  

Drinking water:
0.688557 L/day for infants, children between 1-2 year old, and children 6-12 years old; 
1.71062 L/day for youths 13-19 years old and female adults.  
Infants and children were assumed to consume water six times a day; youths and female adults were assumed to consume water four times a day.  

Food:
For food, the eating event was set to one meal per day. 
Residential
Handler (Adult only)
Residential dermal exposures, the fraction of skin in contact with triazines was set to 50%.  
Contact time with turf assumed to be 1.0 hours.
A daily shower was assumed following exposure.  
All residential exposures were set to be continuous for 21 days.  
Breathing Rate: adults - 0.64 m[3]/hr 

Golfer (Adult, Children 6 to 11, Youth 11 to 16)
Residential dermal exposures, the fraction of skin in contact with triazines was set to 50%.  
Daily exposure time is assumed to be 4 hours/day
All golfer exposures were set to be continuous for 21 days

Mowing (Adults and Children 11 to 16)
Residential dermal exposures, the fraction of skin in contact with triazines was set to 50%.  
Daily exposure time is assumed to be 1.0 hours/day
All exposures were set to be continuous for 21 days

Other Turf Activities (Children 1 to < 2, and Adults)
Residential dermal exposures, the fraction of skin in contact with triazines was set to 50%.  
Daily exposure time is assumed to be 1.5 hours/day
All exposures were set to be continuous for 21 days
For oral exposures 4 replenishments per hour, and 6 replenishments per day.

Residential Bystander  -  Inhalation assessment (Acute and Steady State) 
Exposure time is assumed to be 24 hours 
Breathing rates: Children 1 to < 2 - 0.33 m[3]/hr, adults - 0.64 m[3]/hr 

Non-Occupational Spray Drift (Adults and Children 1 to < 2)
 Skin contact 50%
 Assume 1.5 hrs/day exposure
 Body weight: adults 69 kg, children 1 to < 2 years old  -  11 kg 


Occupational
 Dermal exposures for workers assumed even distribution across the entire body surface area
 A daily shower (i.e., washing off the triazines) was assumed following exposure
 The worker was assumed to be a female adult between the ages of 13 to 49, and had a body weight of 69 kg
 The worker is exposed to either via inhalation or skin for 8 hours/day, 5 days/week, for a total of 21 days
 Breathing rates: mixer/loader  -  1 m[3]/hr, applicator  -  0.5 m[3]/hr, and PHED combo  -  7.3 m[3]/hr.  

Data and parameter M-files
data.m

%Lin etal 2010 Mouse Data - Plasma (uM), Urine (accumulated umole)
load @File='data\MousePlasma5.txt' @Format='Ascii' @Separator='Tab'
load @File='data\MousePlasma25.txt' @Format='Ascii' @Separator='Tab'
load @File='data\MousePlasma125.txt' @Format='Ascii' @Separator='Tab'
load @File='data\MousePlasma250.txt' @Format='Ascii' @Separator='Tab'
load @File='data\MouseUrine5.txt' @Format='Ascii' @Separator='Tab'
load @File='data\MouseUrine25.txt' @Format='Ascii' @Separator='Tab'
load @File='data\MouseUrine125.txt' @Format='Ascii' @Separator='Tab'
load @File='data\MouseUrine250.txt' @Format='Ascii' @Separator='Tab'

%Syngenta Rat data
%Gavage study (1 to 4 day dosing) at 3, 10 and 50 mg/kg
%Individual Animal Data
load @File='data\SYNatraORaeid3.txt' @Format='Ascii' @Separator='Tab'
load @File='data\SYNatraORaeid10.txt' @Format='Ascii' @Separator='Tab'
load @File='data\SYNatraORaeid50.txt' @Format='Ascii' @Separator='Tab'

%Average Data Single Gavage Dose
load @File='data\gasingleatra.txt' @Format='Ascii' @Separator='Tab'
load @File='data\gasingledact.txt' @Format='Ascii' @Separator='Tab'
load @File='data\gasingleethyl.txt' @Format='Ascii' @Separator='Tab'
load @File='data\gasingleiso.txt' @Format='Ascii' @Separator='Tab'

%Average Data Multiple Gavage Dose
load @File='data\gamultiatra.txt' @Format='Ascii' @Separator='Tab'
load @File='data\gamultidact.txt' @Format='Ascii' @Separator='Tab'
load @File='data\gamultiethyl.txt' @Format='Ascii' @Separator='Tab'
load @File='data\gamultiiso.txt' @Format='Ascii' @Separator='Tab'

%Syngenta Rat data
%Single dietary study
%Individual Animal Data
load @File='data\SYNdiet30.txt' @Format='Ascii' @Separator='Tab'
load @File='data\SYNdiet100.txt' @Format='Ascii' @Separator='Tab'
load @File='data\SYNdiet500.txt' @Format='Ascii' @Separator='Tab'


%Syngenta Human data
%Single gavage study 0.1 mg/kg
%Blood data for one individual BW - 96 kg
load @File='data\DIAHumanWholeBlood01.txt' @Format='Ascii' @Separator='Tab'
load @File='data\DACTHumanWholeBlood01.txt' @Format='Ascii' @Separator='Tab'
load @File='data\SynHumUrnExcr.txt' @Format='Ascii' @Separator='Tab'
load @File='data\SynHumUrnExcravg.txt' @Format='Ascii' @Separator='Tab'

%Individual Urine data (cummulative excretion in micromoles)
load @File='data\SynHumUrnExcrindda.txt' @Format='Ascii' @Separator='Tab'
load @File='data\SynHumUrnExcrinddi.txt' @Format='Ascii' @Separator='Tab'
load @File='data\SynHumUrnExcrindde.txt' @Format='Ascii' @Separator='Tab'
load @File='data\SynHumUrnExcrindtct.txt' @Format='Ascii' @Separator='Tab'


%Syngenta Monkey data
%Single iv study 0.26 mg
%Plasma data for four subjects 
load @File='data\ATRAMnkyPlasmaIV.txt' @Format='Ascii' @Separator='Tab'
load @File='data\ATRAMnkyUrineIVed.txt' @Format='Ascii' @Separator='Tab'
load @File='data\ATRAMnkyUrineTCTIV.txt' @Format='Ascii' @Separator='Tab'


%Syngenta Monkey data
%Single oral capsule study 1, 10, 100 mg
%Plasma data for four subjects per dose 
load @File='data\ATRAMnkyPlasmaCap.txt' @Format='Ascii' @Separator='Tab'

%Syngenta Monkey data (2011) 
%Single oral dose study 0.5 mg/kg
%Plasma data for 5 subjects per dose 
%Phase 1 - CMC as dosing vehicle
load @File='data\m1107784.txt' @Format='Ascii' @Separator='Tab'
load @File='data\m1107785.txt' @Format='Ascii' @Separator='Tab'
load @File='data\m1107786.txt' @Format='Ascii' @Separator='Tab'
load @File='data\m1107787.txt' @Format='Ascii' @Separator='Tab'
load @File='data\m1107788.txt' @Format='Ascii' @Separator='Tab'
load @File='data\m1107789.txt' @Format='Ascii' @Separator='Tab'

%Phase 2 - ethanol as dosing vehicle
load @File='data\m2107784.txt' @Format='Ascii' @Separator='Tab'
load @File='data\m2107785.txt' @Format='Ascii' @Separator='Tab'
load @File='data\m2107786.txt' @Format='Ascii' @Separator='Tab'
load @File='data\m2107787.txt' @Format='Ascii' @Separator='Tab'
load @File='data\m2107788.txt' @Format='Ascii' @Separator='Tab'
load @File='data\m2107789.txt' @Format='Ascii' @Separator='Tab'

%Syngenta Monkey Data (5 phases)
%Plasma
MonkeyPhase1Data
MonkeyPhase2Data
MonkeyPhase3Data
MonkeyPhase4Data
MonkeyPhase5Data
MonkeyPhase6Data
%Cummulative Urine
load @File='data\nhpph1cu.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph2cu.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph3cu.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph4cu.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph5cu.txt' @Format='Ascii' @Separator='Tab'

load @File='data\nhpph1cudea.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph2cudea.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph3cudea.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph4cudea.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph5cudea.txt' @Format='Ascii' @Separator='Tab'

load @File='data\nhpph1cudia.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph2cudia.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph3cudia.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph4cudia.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph5cudia.txt' @Format='Ascii' @Separator='Tab'

load @File='data\nhpph1cudact.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph2cudact.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph3cudact.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph4cudact.txt' @Format='Ascii' @Separator='Tab'
load @File='data\nhpph5cudact.txt' @Format='Ascii' @Separator='Tab'


mouse.m

%Constants to simulate mouse

%Physiological Parameters						
		BW	=	0.035	;	 %body weight(kg)
		VLC	=	0.055	;	 %volume of liver (L/kg)
		VBRC	=	0.017	;	%volume of brain (L/kg)
		VPITC	=	0.0000082	;	%volume of pitituary (L/kg)
		VHTLC	=	0.0000145	;	%volume of hypothalmus (L/kg)
		VFC	=	0.07	;	%volume of fat (L/kg)
		VMAC	=	0.01	;	%volume mammary tissue (L/kg) (Gentry etal 2002, IPA Model, O'Fhaherty etal 1992)
		VROC	=	0.0063	;	%Set to rat value
		VADC	=	0.0002	;	%volume adrenal tissue (L/kg) scaled from human value
		VRPC	=	0.25	;	%volume rapidly perfused tissue (L/kg)
		VSPC	=	0.91	;	%volume slowly perfused tissue (L/kg)
		VBLC = 0.049	;		 %volume of blood (L/kg)
  	VOLUC = 57.0 ;		%Volume Urine per day (ml/kg/day, rat)

		QCC	=	10.4	;	 %cardiac output (L/hr/kg**0.75)
		QLC	=	0.162	;	 %fraction of blood flow to liver
		QBRC	=	0.033	;	 %fraction of blood flow to brain
		QPITC	=	1.59E-05	;	 %fraction of blood flow to pituitary (based on QBR)
		QHTLC	=	2.81E-05	;	 %fraction of blood flow to hypothalmus (based on QBR)
		QFC	=	0.07	;	 %fraction of blood flow to fat
		QMAC	=	0.002	;		%fraction of blood flow to mammary O'Flaherty etal 1992
		QROC	=	0.0005	;	 %fraction of blood flow to testes (0.0005)/ovaries (0.0002) tissue (L/kg) ICRP 2003
		QADC	=	0.003	;		%fraction of blood flow to adrenals (scaled from human value)
		QSPC	=	0.19	;	 %fraction of blood flow to slowly perfused
		QRPC	=	1.0	;	 %fraction of blood flow to rapidly perfused (less all other tissues)
						
%ATRA Specific Parameters						
		MWATRA	=	215.0	;	 %molecular weight of atra (mg/mmol)
		KELIMATRAC	=	41.01	;	 %rate of "other" clearance process of ATRA (/hr-Kg BW**0.25)
		VMAXCATRA_ISO	=	202.5 ;	 %Maximum velocity of metabolism of ATRA to DIA (umol/hr/kg**0.75)
		VMAXCATRA_ETHYL	=	236.3	; %Maximum velocity of metabolism of ATRA to DEA (umol/hr/kg**0.75)
		KMATRA	=	30.0	;	 %Micaelis-Menten for ATRA to DIA or DEA (umol/L)
		PLATRA	=	0.7	;	%2.36	;	 %liver:plasma partition coefficient
		PBRATRA	=	0.7	;	%1.93	;	 %brain:plasma partition coefficient
		PPITATRA	=	0.7	;	%1.93	;	 %pituitary:plasma partition coefficient
		PHTLATRA	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFATRA	=	0.7	;	 %fat:plasma partition coefficient
		PMAATRA	=	0.7	;	 %mammary:plasma partition coefficient
		PADATRA	= 0.7		;		%adrenal:plasma partition coefficient
		PROATRA	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPATRA	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPATRA	=	0.7	;	 %slowly perfused:plasma partition coefficient
						
%ISOPROPYL Specific Parameters						
		KELIMISOC	=	48.4	;	 %rate  of "other" clearance process of iso (/hr-Kg BW**0.25)
		VMAXCISO = 13.5	;	 %max velocity of enzyme for metab of iso to DACT (umol/hr/kg**0.75)
		KMISO = 13.0	;			%M-M for iso to dact
		PLISO	=	0.7	;	 %Liver:blood partition coefficient for isopropyl
		PBRISO	=	0.7	;	 %brain:plasma partition coefficient
		PPITISO	=	0.7	;	 %pituitary:plasma partition coefficient
		PHTLISO	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFISO	=	0.7	;	 %fat:plasma partition coefficient
		PMAISO	=	0.7	;	 %mammary:plasma partition coefficient
		PADISO	= 0.7		;		%adrenal:plasma partition coefficient
		PROISO	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPISO	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPISO	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWISO	=	187.0	;	%molecular weight of iso (mg/mmol)
						
%ETHYL Specific Parameter						
		KELIMETHYLC	=	7.071	;	%rate  of "other" clearance process of ethyl (/hr-Kg BW**0.25)
		VMAXCETHYL = 25.3	; 	%max velocity of enzyme for metab of ethyl to DACT (umol/hr/kg**0.75)
		KMETHYL = 13.0	;			%M-M for ethyl - DACT
		PLETHYL	=	0.7	;	%QSAR estimated liver:blood partition coefficent for ethyl
		PBRETHYL	=	0.7	;	 %brain:plasma partition coefficient
		PPITETHYL	=	0.7	;	 %pituitary:plasma partition coefficient
		PHTLETHYL	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFETHYL	=	0.7	;	 %fat:plasma partition coefficient
		PMAETHYL	=	0.7	;	 %mammary:plasma partition coefficient
		PADETHYL	= 0.7		;		%adrenal:plasma partition coefficient
		PROETHYL	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPETHYL	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPETHYL	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWETHYL	=	173.0	;	%molecular weight of ethyl (mg/mmol)
						
%DACT specific Parameters						
		KELIMDAC	=	1.191	;	%rate  of "other"clearance process of DACT (/hr-Kg BW**0.25)
		PLDA	=	0.7	;	  %liver:plasma partition coefficient
		PBRDA	=	0.7	;	 %brain:plasma partition coefficient
		PPITDA	=	0.7	;	%pituitary:plasma partition coefficient
		PHTLDA	=	0.7	;	%hypothalmus:plasma partition coefficient
		PFDA	=	0.7	;	  %fat:plasma partition coefficient
		PMADA	=	0.7	;	 %mammary:plasma partition coefficient
		PADDA	= 0.7		;		%adrenal:plasma partition coefficient
		PRODA	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPDA	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPDA	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWDACT	=	145.0	;	%molecular weight of dact

%Urinary Clearance Constants (L/hr/BW**0.75)

	  CLRISOC = 0.0016 ;
	  CLRETHYLC = 0.0053 ;
  	CLRDAC = 0.0521 ;

%Parameters for oral absorption
		SOLORDOSE	=	2400.0	;			%soluble portion of dose ug/kg
		KMETATRA_ISO_OR2C = 0.9	;
		KMETATRA_ETHYL_OR2C = 0.3	;

		KOR1_OR2ATRAC	=	0.181	;	 %transfer of atra from Oral 1 to Oral 2
		KAOR2ATRAC	=	0.09	;			 %absorption of atra from Oral 2
		KAOR2ISOC	=	0.8	;			 %absorption of iso from Oral 2
		KAOR2ETHYLC	=	0.6	;			 %absorption of ethyl from Oral 2
		KAOR2DAC	=	0.6	;			 %absorption of dact from Oral 2

    DIETSTUDY = 0	;						%Binary to turn on Dietary study in rat (0 off 1 on)
    DIETCON = 0		;						%Set diet concentration for dietary study in rat (30, 100, 500)

%Plasma Binding to DACT (to describe the for 14C study)
	  KALBC = 0.00	;		%Elimination rat for serum albumin in rat (based on 46 hr t1/2)
  	KDAALBC =  0.00 ;	%rate of DACT to serum albumin covalent binding

Ratp.m

%Constants to simulate rat

%Physiological Parameters						
		BW	=	0.25	;	 %body weight(kg)
		VLC	=	0.034	;	 %volume of liver (L/kg) Brown etal 1997
		VBRC	=	0.006	;	%volume of brain (L/kg) Brown etal 1997
		VPITC	=	0.0000082	;	%volume of pitituary (L/kg) (Human value)
		VHTLC	=	0.0000145	;	%volume of hypothalamus (L/kg) Used human value
		VFC	=	0.07	;	%volume of fat (L/kg)  Brown etal 1997
		VMAC	=	0.01	;	%volume mammary tissue (L/kg) (Gentry etal 2002, IPA Model, O'Fhaherty etal 1992)
		VROC	=	0.0063	;	% Table 1 - Adkins et al. (1982)
		VADC	=	0.0002	;	%volume adrenal tissue (L/kg) set human value
		VRPC	=	0.25	;	%volume rapidly perfused tissue (L/kg)
		VSPC	=	0.91	;	%volume slowly perfused tissue (L/kg)
		VBLC = 0.074	;		 %volume of blood (L/kg)
  	VOLUC = 57.0 ;		%Volume Urine per day (ml/kg/day, rat)

		QCC	=	18.7	;	 %cardiac output (L/hr/kg**.75) for 0.25 kg rat Brown et al. 1997
		QLC	=	0.174	;	 %fraction of blood flow to liver  Brown etal 1997
		QBRC	=	0.02	;	 %fraction of blood flow to brain  Brown etal 1997
		QPITC	=	2.73e-05  ;	 %fraction of blood flow to pituitary (based on QBR)
		QHTLC	=	4.83e-05	;	 %fraction of blood flow to hypothalmus (based on QBR)
		QFC	=	0.07	;	 %fraction of blood flow to fat  Brown etal 1997
		QMAC	=	0.002	;		%fraction of blood flow to mammary O'Flaherty etal 1992
		QROC	=	0.0005	;	 %fraction of blood flow to testes (0.0005)/ovaries (0.0002) tissue set to human 
		QADC	=	0.003	;		%fraction of blood flow to adrenals (set to human)
		QSPC	=	0.19	;	 %fraction of blood flow to slowly perfused
		QRPC	=	1.0	;	 %fraction of blood flow to rapidly perfused (less all other tissues)
						
%ATRA Specific Parameters						
		MWATRA	=	215.0	;	 %molecular weight of atra (ug/umol)
		KELIMATRAC	=	41.01	;	 %rate of "other" clearance process of ATRA (/hr-Kg BW**0.25)
		VMAXCATRA_ISO	=	202.5 ;	 %Maximum velocity of metabolism of ATRA to DIA (umol/hr/kg**0.75)
		VMAXCATRA_ETHYL	=	236.3 ;	 %Maximum velocity of metabolism of ATRA to DEA (umol/hr/kg**0.75)
		KMATRA	=	30.0	;	 %Micaelis-Menten for ATRA to DIA or DEA (umol/L)
		PLATRA	=	0.7	;	%2.36	;	 %liver:plasma partition coefficient
		PBRATRA	=	0.7	;	%1.93	;	 %brain:plasma partition coefficient
		PPITATRA	=	0.7	;	%1.93	;	 %pituitary:plasma partition coefficient
		PHTLATRA	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFATRA	=	0.7	;	 %fat:plasma partition coefficient
		PMAATRA	=	0.7	;	 %mammary:plasma partition coefficient
		PADATRA	= 0.7		;		%adrenal:plasma partition coefficient
		PROATRA	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPATRA	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPATRA	=	0.7	;	 %slowly perfused:plasma partition coefficient

%ISOPROPYL Specific Parameters						
		KELIMISOC	=	48.4	;	 %rate  of "other" clearance process of iso (/hr-Kg BW**0.25)
		VMAXCISO = 13.5	;	 %max velocity of enzyme for metab of iso to DACT (umol/hr/kg**0.75)
		KMISO = 13.0	;			%M-M for iso to dact
		PLISO	=	0.7	;	 %Liver:blood partition coefficient for isopropyl
		PBRISO	=	0.7	;	 %brain:plasma partition coefficient
		PPITISO	=	0.7	;	 %pituitary:plasma partition coefficient
		PHTLISO	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFISO	=	0.7	;	 %fat:plasma partition coefficient
		PMAISO	=	0.7	;	 %mammary:plasma partition coefficient
		PADISO	= 0.7		;		%adrenal:plasma partition coefficient
		PROISO	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPISO	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPISO	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWISO	=	187.0	;	%molecular weight of iso (ug/umol)

%ETHYL Specific Parameter						
		KELIMETHYLC	=	7.071	;	%rate  of "other" clearance process of ethyl (/hr-Kg BW**0.25)
		VMAXCETHYL = 25.3	; 	%max velocity of enzyme for metab of ethyl to DACT (umol/hr/kg**0.75)
		KMETHYL = 13.0	;			%M-M for ethyl - DACT
		PLETHYL	=	0.7	;	%QSAR estimated liver:blood partition coefficent for ethyl
		PBRETHYL	=	0.7	;	 %brain:plasma partition coefficient
		PPITETHYL	=	0.7	;	 %pituitary:plasma partition coefficient
		PHTLETHYL	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFETHYL	=	0.7	;	 %fat:plasma partition coefficient
		PMAETHYL	=	0.7	;	 %mammary:plasma partition coefficient
		PADETHYL	= 0.7		;		%adrenal:plasma partition coefficient
		PROETHYL	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPETHYL	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPETHYL	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWETHYL	=	173.0	;	%molecular weight of ethyl (ug/umol)

%DACT specific Parameters						
		KELIMDAC	=	1.191	;	%rate  of "other"clearance process of DACT (/hr-Kg BW**0.25)
		PLDA	=	0.7	;	  %liver:plasma partition coefficient
		PBRDA	=	0.7	;	 %brain:plasma partition coefficient
		PPITDA	=	0.7	;	%pituitary:plasma partition coefficient
		PHTLDA	=	0.7	;	%hypothalmus:plasma partition coefficient
		PFDA	=	0.7	;	  %fat:plasma partition coefficient
		PMADA	=	0.7	;	 %mammary:plasma partition coefficient
		PADDA	= 0.7		;		%adrenal:plasma partition coefficient
		PRODA	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPDA	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPDA	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWDACT	=	145.0	;	%molecular weight of dact

%Urinary Clearance Constants (L/hr/BW**0.75)

  	CLRISOC = 0.0016 ;
	  CLRETHYLC = 0.0053 ;
	  CLRDAC = 0.0521 ;

%Parameters for oral absorption
		SOLORDOSE	=	2400.0	;			%soluble portion of dose ug/kg
		KMETATRA_ISO_OR2C = 0.917	;   %metabolosim of atra to iso in Oral 2 (kg BW^0.25/L)
		KMETATRA_ETHYL_OR2C = 0.393	; %metabolosim of atra to ethyl in Oral 2 (kg BW^0.25/L)

		KOR1_OR2ATRAC	=	0.181	;	 %transfer of atra from Oral 1 to Oral 2
		KAOR2ATRAC	=	0.09	;			 %absorption of atra from Oral 2
		KAOR2ISOC	=	0.8	;			 %absorption of iso from Oral 2
		KAOR2ETHYLC	=	0.6	;			 %absorption of ethyl from Oral 2
		KAOR2DAC	=	0.6	;			 %absorption of dact from Oral 2

    DIETSTUDY = 0	;						%Binary to turn on Dietary study in rat (0 off 1 on)
    DIETCON = 0		;						%Set diet concentration for dietary study in rat (30, 100, 500)

%Plasma Binding to DACT (to describe the for 14C study)
	KALBC = 0.016	;		%Elimination rat for serum albumin in rat (based on 46 hr t1/2)
	KDAALBC =  0.01 ;	%rate of DACT to serum albumin covalent binding

%1st order reaction rate (used directly)
		KELIMATRAC	=	56.892	;	 
		KELIMISOC	=	67.144	;	 
		KELIMETHYLC	=	9.809	;	
		KELIMDAC	=	1.652	;	

%turn off GST-pi for rat
    CLGSTPI = 0.0 ; %			0.07 for up to  2 yr old and 0.01 for >than 2 yr %0.07*{L/min}*(0.01/1000){ug}*CPPGL*liver weight_25yr{g}

monkey.m

%Constants to simulate monkey

%Physiological Parameters						
		BW	=	5.0	;	 %body weight(kg)
		VLC	=	0.027	;	 %volume of liver (L/kg) Davies and Morris 1993
		VBRC	=	0.018	;	%volume of brain (L/kg)Davies and Morris 1993
		VPITC	=	0.0000082	;	%volume of pitituary (L/kg) ICRP, Pub 89, 2002, set to human
		VHTLC	=	0.0000145	;	%volume of hypothalamus (L/kg) (Human value)
		VFC	=	0.199	;	%volume of fat (L/kg) Raman et al. 2005
		VMAC	=	0.00034	;	%volume mammary tissue (L/kg) set to male human
		VROC	=	0.0007	;	%volume testes (0.0007)/ovaries (0.0027) Plowchalk and Teeguarden (2002)
		VADC	=	0.00024	;	%volume adrenal tissue (L/kg) Davies and Morris 1993
		VRPC	=	0.25	;	%volume rapidly perfused tissue (L/kg)
		VSPC	=	0.91	;	%volume perfused tissue (L/kg)
		VBLC = 0.0734	;		 %volume of blood (L/kg) set to human (similar plasma volume to human Davies and Morris, 1993)
	 VOLUC = 75.0 ;		%Volume Urine per day (ml/kg/day) Davies and Morris (1993)

		QCC	=	18.96	;	 %cardiac output (L/hr/kg**.75) Forsyth et al. (1970)
		QLC	=	0.2	;	 %fraction of blood flow to liver Davies and Morris (1993)
		QBRC	=	0.066	;	 %fraction of blood flow to brain Davies and Morris (1993)
		QPITC	=	3.01E-05	;	 %fraction of blood flow to pituitary (based on QBR)
		QHTLC	=	5.32E-05	;	 %fraction of blood flow to hypothalmus (based on QBR)
		QFC	=	0.018	;	 %fraction of blood flow to fat Forsyth et al. (1968, 1971)
		QMAC	=	0.0016	;		%fraction of blood flow to mammary set to human
		QROC	=	0.0012	;	 %fraction of blood flow to testes - human value used
		QADC	=	0.003	;		%fraction of blood flow to adrenals set to human
		QSPC	=	0.19	;	 %fraction of blood flow to slowly perfused
		QRPC	=	1.0	;	 %fraction of blood flow to rapidly perfused (less all other tissues)

%ATRA Specific Parameters						
		MWATRA	=	215.0	;	 %molecular weight of atra (ug/umol)
		KELIMATRAC	=	41.01	;	 %rate of "other" clearance process of ATRA (/hr-Kg BW**0.25)
		VMAXCATRA_ISO	=	202.53 ;%135.87	;	%388.2;	 %Maximum velocity of metabolism of ATRA to DIA (umol/hr/kg**0.75)
		VMAXCATRA_ETHYL	=	236.3 ;%252.33	;	%0.127	;	 %Maximum velocity of metabolism of ATRA to DEA (umol/hr/kg**0.75)
		KMATRA	=	30.0	;	 %Micaelis-Menten for ATRA to DIA or DEA (umol/L)
		PLATRA	=	0.7	;	%2.36	;	 %liver:plasma partition coefficient
		PBRATRA	=	0.7	;	%1.93	;	 %brain:plasma partition coefficient
		PPITATRA	=	0.7	;	%1.93	;	 %pituitary:plasma partition coefficient
		PHTLATRA	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFATRA	=	0.7	;	 %fat:plasma partition coefficient
		PMAATRA	=	0.7	;	 %mammary:plasma partition coefficient
		PADATRA	= 0.7		;		%adrenal:plasma partition coefficient
		PROATRA	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPATRA	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPATRA	=	0.7	;	 %slowly perfused:plasma partition coefficient
						
%ISOPROPYL Specific Parameters						
		KELIMISOC	=	48.4	;	 %rate  of "other" clearance process of iso (/hr-Kg BW**0.25)
		VMAXCISO = 13.5	;	 %max velocity of enzyme for metab of iso to DACT (umol/hr/kg**0.75)
		KMISO = 13.0	;			%M-M for iso to dact
		PLISO	=	0.7	;	 %Liver:blood partition coefficient for isopropyl
		PBRISO	=	0.7	;	 %brain:plasma partition coefficient
		PPITISO	=	0.7	;	 %pituitary:plasma partition coefficient
		PHTLISO	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFISO	=	0.7	;	 %fat:plasma partition coefficient
		PMAISO	=	0.7	;	 %mammary:plasma partition coefficient
		PADISO	= 0.7		;		%adrenal:plasma partition coefficient
		PROISO	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPISO	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPISO	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWISO	=	187.0	;	%molecular weight of iso (ug/umol)
						
%ETHYL Specific Parameter						
		KELIMETHYLC	=	7.071	;	%rate  of "other" clearance process of ethyl (/hr-Kg BW**0.25)
		VMAXCETHYL = 25.3	; 	%max velocity of enzyme for metab of ethyl to DACT (umol/hr/kg**0.75)
		KMETHYL = 13.0	;			%M-M for ethyl - DACT
		PLETHYL	=	0.7	;	%QSAR estimated liver:blood partition coefficent for ethyl
		PBRETHYL	=	0.7	;	 %brain:plasma partition coefficient
		PPITETHYL	=	0.7	;	 %pituitary:plasma partition coefficient
		PHTLETHYL	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFETHYL	=	0.7	;	 %fat:plasma partition coefficient
		PMAETHYL	=	0.7	;	 %mammary:plasma partition coefficient
		PADETHYL	= 0.7		;		%adrenal:plasma partition coefficient
		PROETHYL	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPETHYL	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPETHYL	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWETHYL	=	173.0	;	%molecular weight of ethyl (ug/umol)
						
%DACT specific Parameters						
		KELIMDAC = 3.55	;	%rate  of "other"clearance process of DACT (/hr-Kg BW**0.25)
		PLDA	=	0.7	;	  %liver:plasma partition coefficient
		PBRDA	=	0.7	;	 %brain:plasma partition coefficient
		PPITDA	=	0.7	;	%pituitary:plasma partition coefficient
		PHTLDA	=	0.7	;	%hypothalmus:plasma partition coefficient
		PFDA	=	0.7	;	  %fat:plasma partition coefficient
		PMADA	=	0.7	;	 %mammary:plasma partition coefficient
		PADDA	= 0.7		;		%adrenal:plasma partition coefficient
		PRODA	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPDA	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPDA	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWDACT	=	145.0	;	%molecular weight of dact
						
%Urinary Clearance Constants (L/hr/BW**0.75)
%Fit to monkey urine data
  	CLRISOC = 0.010 ;
	  CLRETHYLC = 0.053 ;
	  CLRDAC = 0.014 ;

%Parameters for oral absorption
		SOLORDOSE	=	10000.0	;	%all of monkey dose was soluble	%soluble portion of dose ug/kg
		KMETATRA_ISO_OR2C = 0.317	;
		KMETATRA_ETHYL_OR2C = 0.693	;

		KOR1_OR2ATRAC	=	0.181	;	 %transfer of atra from Oral 1 to Oral 2
		KAOR2ATRAC	=	0.09	;			 %absorption of atra from Oral 2
		KAOR2ISOC	=	0.8	;			 %absorption of iso from Oral 2
		KAOR2ETHYLC	=	0.6	;			 %absorption of ethyl from Oral 2
		KAOR2DAC	=	0.6	;			 %absorption of dact from Oral 2

    DIETSTUDY = 0	;						%Binary to turn on Dietary study in rat (0 off 1 on)
    DIETCON = 0		;						%Set diet concentration for dietary study in rat (30, 100, 500)

%Plasma Binding to DACT (to describe the for 14C study)
	KALBC = 0.0	;		%Elimination rat for serum albumin in rat (based on 46 hr t1/2)
	KDAALBC =  0.0 ;	%rate of DACT to serum albumin covalent binding

human.m

%Constants to simulate human

%Physiological Parameters						
		BW	=	73.0	;	 %body weight(kg)
		VLC	=	0.026	;	 %volume of liver (L/kg) Brown et al. (1997)
		VBRC	=	0.02	;	%volume of brain (L/kg) Brown et al. (1997)
		VPITC	=	0.0000082	;	%volume of pitituary (L/kg) ICRP 2003
		VHTLC	=	0.0000145	;	%volume of hypothalmus (L/kg) Young and Stanton (1991)
		VFC	=	0.21	;	%volume of fat (L/kg)
		VMAC	=	0.00034	;	%volume mammary tissue (L/kg) MALE VALUE (0.0083 FOR FEMALE) ICRP 2003
		VROC	=	0.00048	;	%volume testes ovaries (0.00018) tissue (L/kg) ICRP 2003
		VADC	=	0.0002	;	%volume adrenal tissue (L/kg) (0.00023 female) ICRP 2003
		VRPC	=	0.25	;	%volume rapidly perfused tissue (L/kg)
		VSPC	=	0.91	;	%volume slowly perfused tissue (L/kg)
		VBLC = 0.079	;		 %volume of blood (L/kg) Brown et al. (1997)
  	VOLUC = 21.92 ;		%Volume Urine per day (ml/kg/day, rat)

		QCC	=	15.6	;	 %cardiac output (L/hr/kg**.75) ICRP 2003
		QLC	=	0.25	;	 %fraction of blood flow to liver  Brown et al. (1997)
		QBRC	=	0.114	;	 %fraction of blood flow to brain  Brown et al. (1997)
		QPITC	=	4.67e-05	;	 %fraction of blood flow to pituitary (based on QBR) 
		QHTLC	=	8.27e-05	;	 %fraction of blood flow to hypothalmus (based on QBR)
		QFC	=	0.05	;	 %fraction of blood flow to fat  Brown et al. (1997)
		QMAC	=	0.00016	;		%fraction of blood flow to mammary (0.004 female volume ratio adjusted to male) ICRP 2003
		QROC	=	0.0005	;	 %fraction of blood flow to testes (0.0012 male)/uterus intact (0.02) tissue (L/kg) Plowchalk and Teeguarden (2002)
		QADC	=	0.003	;		%fraction of blood flow to adrenals ICRP 2003 male and female
		QSPC	=	0.19	;	 %fraction of blood flow to slowly perfused
		QRPC	=	1.0	;	 %fraction of blood flow to rapidly perfused (less all other tissues)
						
%ATRA Specific Parameters						
		MWATRA	=	215.0	;	 %molecular weight of atra (ug/umol)
		KELIMATRAC	=	41.01	;	 %rate of "other" clearance process of ATRA (/hr-Kg BW**0.25)
		VMAXCATRA_ISO	=	188.16	;		 %Maximum velocity of metabolism of ATRA to DIA (umol/hr/kg**0.75)
		VMAXCATRA_ETHYL	=	752.64	;	 %Maximum velocity of metabolism of ATRA to DEA  (umol/hr/kg**0.75)
		KMATRA	=	30.0	;	 %Micaelis-Menten for ATRA to iso and ethyl (umol/L)
		PLATRA	=	0.7	;	%2.36	;	 %liver:plasma partition coefficient
		PBRATRA	=	0.7	;	%1.93	;	 %brain:plasma partition coefficient
		PPITATRA	=	0.7	;	%1.93	;	 %pituitary:plasma partition coefficient
		PHTLATRA	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFATRA	=	0.7	;	 %fat:plasma partition coefficient
		PMAATRA	=	0.7	;	 %mammary:plasma partition coefficient
		PADATRA	= 0.7		;		%adrenal:plasma partition coefficient
		PROATRA	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPATRA	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPATRA	=	0.7	;	 %slowly perfused:plasma partition coefficient
						
%ISOPROPYL Specific Parameters						
		KELIMISOC	=	48.4	;	 %rate  of "other" clearance process of iso (/hr-Kg BW**0.25)
		VMAXCISO = 25.1	;	 %max velocity of enzyme for metab of iso to DACT (umol/hr/kg**0.75)
		KMISO = 13.0	;			%M-M for iso to dact
		PLISO	=	0.7	;	 %Liver:blood partition coefficient for isopropyl
		PBRISO	=	0.7	;	 %brain:plasma partition coefficient
		PPITISO	=	0.7	;	 %pituitary:plasma partition coefficient
		PHTLISO	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFISO	=	0.7	;	 %fat:plasma partition coefficient
		PMAISO	=	0.7	;	 %mammary:plasma partition coefficient
		PADISO	= 0.7		;		%adrenal:plasma partition coefficient
		PROISO	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPISO	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPISO	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWISO	=	187.0	;	%molecular weight of iso (ug/umol)
						
%ETHYL Specific Parameter						
		KELIMETHYLC	=	7.071	;	%rate  of "other" clearance process of ethyl (/hr-Kg BW**0.25)
		VMAXCETHYL = 25.1	; 	%max velocity of enzyme for metab of ethyl to DACT (umol/hr/kg**0.75)
		KMETHYL = 13.0	;			%M-M for ethyl - DACT
		PLETHYL	=	0.7	;	%QSAR estimated liver:blood partition coefficent for ethyl
		PBRETHYL	=	0.7	;	 %brain:plasma partition coefficient
		PPITETHYL	=	0.7	;	 %pituitary:plasma partition coefficient
		PHTLETHYL	=	0.7	;	 %hypothalmus:plasma partition coefficient
		PFETHYL	=	0.7	;	 %fat:plasma partition coefficient
		PMAETHYL	=	0.7	;	 %mammary:plasma partition coefficient
		PADETHYL	= 0.7		;		%adrenal:plasma partition coefficient
		PROETHYL	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPETHYL	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPETHYL	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWETHYL	=	173.0	;	%molecular weight of ethyl (ug/umol)
						
%DACT specific Parameters						
		KELIMDAC	=	20.6	;	%rate  of "other"clearance process of DACT (/hr-Kg BW**0.25)
		PLDA	=	0.7	;	  %liver:plasma partition coefficient
		PBRDA	=	0.7	;	%brain:plasma partition coefficient
		PPITDA	=	0.7	;	%pituitary:plasma partition coefficient
		PHTLDA	=	0.7	;	%hypothalmus:plasma partition coefficient
		PFDA	=	0.7	;	  %fat:plasma partition coefficient
		PMADA	=	0.7	;	 %mammary:plasma partition coefficient
		PADDA	= 0.7		;		%adrenal:plasma partition coefficient
		PRODA	=	0.7	;	 %testes/ovaries:plasma partition coefficient
		PRPDA	=	0.7	;	 %rapidly perfused:plasma partition coefficient
		PSPDA	=	0.7	;	 %slowly perfused:plasma partition coefficient
		MWDACT	=	145.0	;	%molecular weight of dact
						
%Urinary Clearance Constants (L/hr/BW**0.75)
%Fit to human study URINE DATA
  	CLRISOC = 0.2 ;
	  CLRETHYLC = 0.2 ;
	  CLRDAC = 0.069 ;

%Parameters for oral absorption
		SOLORDOSE	=	10000.0	;			%soluble portion of dose ug/kg
		KMETATRA_ISO_OR2C = 1.05	;	 %metabolosim of atra to ISO in Oral 2
		KMETATRA_ETHYL_OR2C = 0.26	;	 %metabolosim of atra to ETHYL in Oral 2

		KOR1_OR2ATRAC	=	0.181	;		%transfer of atra from Oral 1 to Oral 2
		KAOR2ATRAC	=	0.09	;			 %absorption of atra from Oral 2
		KAOR2ISOC	=	0.8	;			 %absorption of iso from Oral 2
		KAOR2ETHYLC	=	0.6	;			 %absorption of ethyl from Oral 2
		KAOR2DAC	=	0.6	;			 %absorption of dact from Oral 2

    DIETSTUDY = 0	;						%Binary to turn on Dietary study in rat (0 off 1 on)
    DIETCON = 0		;						%Set diet concentration for dietary study in rat (30, 100, 500)

%Plasma Binding to DACT (to describe the for 14C study in rat)
	KALBC = 0.0	;
	KDAALBC =  0.0 ;


		KELIMATRAC	=	14.178	;	 
		KELIMISOC	=	16.733	;	 
		KELIMETHYLC	=	2.445	;	
		KELIMDAC	=	7.122	;	


      CPPGL = 80.7  ;       %mg cytosolic protein per gram liver
    CLGSTPI = 0.0 ; %			0.07 for up to  2 yr old and 0.01 for >than 2 yr %0.07*{L/min}*(0.01/1000){ug}*CPPGL*liver weight_25yr{g}
   KMSCALER = 1  ;       %1 for 0.01 km and 10 for 0.1 km
       UGPI = 0.21 ;  %ug pi/1000 ug protein 0.21 for infant; 0.01 for adult


growth.m

% File to calculate lifestage physiology
% Reference: Smith JN, Hinderliter PM, Timchalk C, Bartels MJ, Poet TS. (2014)
%         A human life-stage physiologically based pharmacokinetic and pharmacodynamic
%         model for chlorpyrifos: development and validation.
%         Regul Toxicol Pharmacol. 69(3):580-97.

% Gender neutral or male specific values, except for female BTW and fat available
% Set sex=1 to access female parameters

% To adjust copartments, set the AGE0:
%AGE0=50.;

BWSW=1;
SPECIES=1;
SEX=0;

% Gompertz BWT Parameters (Luecke 2007)
B1=3.42826;B2=2.188189;B3=1.506303;B5=34.35453;B6=0.179781;B7=0.221175;
B4=2.462428;B8=-0.0911;
AGE1=2.949004;AGE2=11;AGE3=21.66022;
if (SEX==1)
% set Female BWT Parameters
B1=3.4;B2=2.07402;B3=1.504154;B5=34.8806;B6=0.2120837;B7=0.443786;
B4=2.672665;B8=0.31127;
AGE1=2.949004;AGE2=11;AGE3=21.86533;
end

% Dynamic organ volumes
% VBC Parameters (Refit Valentine 2002 & Young 2009)
VB6=0;VB5=0;VB4=5.132e-22;VB3=-2.463e-16;VB2=4.354e-11;
VB1=-3.465e-6;VB0=1.216e-1;
% VHC (Refit Valentine 2002 & Young 2009)
VH4=1.869E-22;VH3=-8.016E-17;VH2=1.155E-11;VH1=-7.058E-07;VH0=3.939E-02;
% VBL (Young 2009)
VBL2=6.54E-13;VBL1=-3.50E-7;VBL0=8.97E-2;
% VFC (Refit, JNS w/ Valentin 2002 & Lafortuna 2005)
VF6=-2.036e-30;VF5=1.203e-24;VF4=-2.718e-19;VF3=2.892e-14;VF2=-1.422e-09;
VF1=2.803e-05;VF0=3.484e-02;
if(SEX==1)
% set Female VFC
VF6=-1.273e-30;VF5=7.249e-25;VF4=-1.558e-19;VF3=1.540e-14;VF2=-6.787e-10;
VF1=1.401e-05;VF0=9.217e-02;
end
% VAC (Fit, JNS w/ Valentin 2002 & Lafortuna 2005 fat/.8)
VA6=-2.353e-30;VA5=1.387e-24;VA4=-3.116e-19;VA3=3.268e-14;VA2=-1.542e-9;VA1=2.617e-05;
VA0=2.044e-01;
% VLC (Young 2009)
VL2=0;VL1=-4.55e-8;VL0=1.86e-2;
% VKC (Young 2009)
VK2=3.33e-13;VK1=-6.69e-8;VK0=7.26e-3;
% VSPC (Young 2009)
VSP2=0;VSP1=-5.57e-9;VSP0=3.12e-3;
% VGIC (Brown 1997, sum of stom and both intestines)
VGI3=0;VGI2=0;VGI1=0;VGI0=0.0165;
% VMC (Refit, JNS w/ Valentin 2002 & Janssen 2000)
VM4=-5.061e-21;VM3=2.052e-15;VM2=-2.865e-10;VM1=1.436e-5;VM0=1.268e-1;
% VSKC (Young 2009)
VSK5=-1.1e-27;VSK4=8.62e-22;VSK3=-2.58e-16;VSK2=3.68e-11;
VSK1=-2.56e-6;VSK0=1.03e-1;

% Age dependent B4 & B8 for humans (Luecke 2007)
if AGE0 >= AGE1 & AGE0 < AGE2 & SPECIES == 1
B4x=B4;B8x=0;
elseif AGE0 >= AGE3 & SPECIES == 1
B4x=0;B8x=B8;
else
B4x=0;B8x=0;
end

% BWT (kg) (Luecke 2007)
if (AGE0 >= AGE2)
BWT=B5*exp((B6/B7)*(1-exp(-B7*(AGE0-AGE2))))+B8x*(AGE0-AGE3);
else
BWT=B1*exp((B2/B3)*(1-exp(-B3*AGE0)))+B4x*(AGE0-AGE1);
end
BWTG=BWT*1000;			% BWT kg to grams for compartment vol calcs

if (SPECIES == 0)	% Log of BWT for rat brain calc
LBWT=log(BWT);
else
LBWT=BWT*1000.;
end


% compartment volumes (frac of BWT)
VBRC=VB0+(VB1*LBWT)+(VB2*LBWT^2)+(VB3*LBWT^3)+(VB4*LBWT^4)+(VB5*LBWT^5)+(VB6*LBWT^6);
								% Brain
VLC=VH0+(VH1*BWTG)+(VH2*BWTG^2)+(VH3*BWTG^3)+(VH4*BWTG^4);	% Liver
VBLC=VBL0+(VBL1*BWTG)+(VBL2*BWTG^2);				% Blood
VFC=VF0+(VF1*BWTG)+(VF2*BWTG^2)+(VF3*BWTG^3)+(VF4*BWTG^4)+(VF5*BWTG^5)+(VF6*BWTG^6);
								% Fat
VAC=VA0+(VA1*BWTG)+(VA2*BWTG^2)+(VA3*BWTG^3)+(VA4*BWTG^4)+(VA5*BWTG^5)+(VA6*BWTG^6);
								% Adipose
VKC=VK0+(VK1*BWTG)+(VK2*BWTG^2);				% Kidney (in rapid)
VSPC=VSP0+(VSP1*BWTG)+(VSP2*BWTG^2) ;				% Spleen (in rapid)
VLC=VL0+(VL1*BWTG)+(VL2*BWTG^2);				% Lung (in rapid)
VGIC=VGI0+(VGI1*BWTG)+(VGI2*BWTG^2)+(VGI3*BWTG^3);		% GI, both stomach and intestines (in rapid)
VMC=VM0+(VM1*BWTG)+(VM2*BWTG^2)+(VM3*BWTG^3)+(VM4*BWTG^4);			% Muscle (in slow)
VSKC=VSK0+(VSK1*BWTG)+(VSK2*BWTG^2)+(VSK3*BWTG^3)+(VSK4*BWTG^4)+(VSK5*BWTG^5);
								% Skin (in slow)


BW=BWT;


Files for conducting specific runs:
pod.m

%Calculate POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing

%rat POD should output:
%rat POD should output:
% ddd= 2.6234e+000 ---> average plasma TCT

prepare @clear @all
output @clear


WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

%Dose should be input in ug/kg or ug/kg/day
DOSEC	=	0.0	;
DOSEISOC	=	0.0	;
DOSEETHYLC	=	0.0	;
DOSEIVC	=	0.0	;
DIETC	=	0.	;

TSTOP	=	365.*24.;
CINT = 0.2 ; %Model runs in 0.1 hour or 6 minute increments

% use scientific notation, so the small quantities are not displayed at zeros
format shorte

ATRAIN   = zeros(1,17521);
DEAIN    = zeros(1,17521);
DIAIN    = zeros(1,17521);
DACTIN   = zeros(1,17521);

ratp
BW = 0.270; % 270 g rat
BWSW=0;

DOSES0 = 2.42; % DOSE WILL BE CONVERTED TO UG/KG/DAY IN CSL FILE
for ii = 1:365;
  TT(ii)       = (ii-1.)*24.;
  ATRAIN(ii)  = DOSES0;
end

start @nocallback

cvtct = _cvatra+_cviso+_cvethyl+_cvda;

ddd=mean(_cvatra+_cviso+_cvethyl+_cvda)


%___________________________________________________________________________________________

% Run human model to match rat POD
% Runs requested by USEPA on 16-July-2015
% Exposure scenarios: daily oral exposure to atrazine, same doses every day for 365 days.
% Body weights: 4.8 7 11 32 57 70 80 kg
% Both lifestage and static body weights

prepare @clear @all
output @clear


WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

outera=[]; outerm=[]; outerp=[]; ee=[]; ee2=[]; dm=[];

%Dose should be input in ug/kg or ug/kg/day
DOSEC	=	0.0	;
DOSEISOC	=	0.0	;
DOSEETHYLC	=	0.0	;
DOSEIVC	=	0.0	;
DIETC	=	0.	;

CINT = 0.2 ; %Model runs in 0.1 hour or 6 minute increments

target = 2.6234e+000; % average TCT from rat POD above
STARTDOSE = 2.42   ;
check = 0;
toltgt = .02;
% use scientific notation, so the small quantities are not displayed at zeros
format shorte

ATRAIN   = zeros(1,17521);
DEAIN    = zeros(1,17521);
DIAIN    = zeros(1,17521);
DACTIN   = zeros(1,17521);


BWS0 = [4.8 7. 11.0 32.0 57.0 70.0 80.0]; %kg
AGES0 = [0.175 0.449 1.077 9.99 15.41 20.425 40.0]; % Ages corresponding to BW requested

for ii = 1:365;
  TT(ii)       = (ii-1.)*24.;
  ATRAIN(ii)  = 1.;
end

TSTOP = 365*24.;
tic

for bwswi = 1:2 % run for LS and static
   BWSWx=bwswi-1

for bwi = 1:size(AGES0,2)  %run for each of the BWs in BWS0
   growth
   human
   BW=BWS0(bwi);
   AGE0 = AGES0(bwi)
   BWSW=BWSWx
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:365;
         ATRAIN(ii)  = DOSES0;
      end
      ATRAIN(1)

      start @nocallback

      meantct = mean(_cvatra+_cviso+_cvethyl+_cvda)

      if(abs((meantct-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/meantct);
      end
   end
   dm = [dm; BWS0(bwi) BWSW meantct DOSES0]
   check = 0;
   DOSES0 = STARTDOSE;
end
end

dm

lssensetup.m

%___________________________________________________________________________________________

% Run human model to match rat POD
% Runs requested by USEPA on 16-July-2015
% Exposure scenarios: daily oral exposure to atrazine, same doses every day for 365 days.
% Body weights: 4.8 7 11 32 57 70 80 kg
% Both lifestage and static body weights

prepare @clear 
%@all
output @clear


WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

outera=[]; outerm=[]; outerp=[]; ee=[]; ee2=[]; dm=[];

%Dose should be input in ug/kg or ug/kg/day
DOSEC	=	0.0	;
DOSEISOC	=	0.0	;
DOSEETHYLC	=	0.0	;
DOSEIVC	=	0.0	;
DIETC	=	0.	;

CINT = 0.2 ; %Model runs in 0.1 hour or 6 minute increments

target = 2.6234e+000; % average TCT from rat POD above

check = 0;
toltgt = 0.002;
% use scientific notation, so the small quantities are not displayed at zeros
format shorte

ATRAIN   = zeros(1,17521);
DEAIN    = zeros(1,17521);
DIAIN    = zeros(1,17521);
DACTIN   = zeros(1,17521);


BWS0 = [4.8 7. 11.0 32.0 57.0 70.0 80.0]; %kg
AGES0 = [0.175 0.449 1.077 9.99 15.41 20.425 40.0]; % Ages corresponding to BW requested
STARTDOSE = 2.5   ;
for ii = 1:365;
  TT(ii)       = (ii-1.)*24.;
  ATRAIN(ii)  = 1.;
end

TSTOP = 365*24.;
tic

%for bwswi = 2 ;	%1:2 % run for LS and static
   BWSWx= 1 ; 		%bwswi-1 ;

for bwi = 3 ; 		%1:size(AGES0,2)  %run for each of the BWs in BWS0
   growth
   human
   BW = BWS0(bwi);
   AGE0 = AGES0(bwi) ;
   BWSW=BWSWx ;
   DOSES0 = STARTDOSE
  % while (check==0)  %run until check is met
      for ii = 1:365;
         ATRAIN(ii)  = DOSES0;
      end
      ATRAIN(1) ;

 end

SYNRatdiAT.m

%Model simulation of Syngenta dietary exposure to atrazine in rat
%Dose - input as a rate based on measured food consumption ug/kg/hr as a table function
%Table functions are linearly interpolated in acslx
%See .csl file for the table matrix
%Food consumption was measured dirunally - light cycle is 14 hr on 10 hr off.


prepare @clear @all
output @clear


WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

ratp


DOSEC	=	0.0	;
DOSEISOC	=	0.0	;
DOSEETHYLC	=	0.0	;
DOSEDAC = 0.0 ;
DOSEIVC	=	0.0	;
DIETC	=	0.	;

TSTOP	=	169.0	;
TSTART	=	0.0	;

TINF	=	24.0	;
CINT	=	0.01	;

DSTOP	=	96.0	;

 DIETSTUDY = 1	;						%Binary to turn on Dietary study in rat (0 off 1 on)
 DIETCON = 30		;						%Set diet concentration for dietary study in rat (30, 100, 500)
DIETTAB(1,1:18) = [0.00,10.00,10.05,24.00,24.05,34.00,34.05,48.00,48.05,58.00,58.05,72.00,72.05,82.00,82.05,96.00,96.05,169.00];
DIETTAB(2,1:18) = [41.667,41.667,83.333,83.333,41.667,41.667,83.333,83.333,41.667,41.667,83.333,83.333,41.667,41.667,83.333,83.333,0.0,0.0];

 BW	=	0.268	;
    
start @nocallback

t1 = _t ;
cvatra1 = _cvatra ;
cvethyl1 = _cvethyl ;
cviso1 = _cviso ;
cvda1 = _cvda ;
aor1atra1 = _aor1atra ;
aor2atra1 = _aor2atra ;
aucvatra1 = AUCVATRA ;
aucvethyl1 = AUCVETHYL ;
aucviso1 = AUCVISO ;
aucvda1 = AUCVDA ;
%mass1 = _mass;

 DIETSTUDY = 1	;						%Binary to turn on Dietary study in rat (0 off 1 on)
 DIETCON = 100		;						%Set diet concentration for dietary study in rat (30, 100, 500)
DIETTAB(1,1:18) = [0.00,10.00,10.05,24.00,24.05,34.00,34.05,48.00,48.05,58.00,58.05,72.00,72.05,82.00,82.05,96.00,96.05,169.00];
DIETTAB(2,1:18) = [166.667,166.667,250.000,250.000,125.000,125.000,208.333,208.333,125.000,125.000,250.000,250.000,125.000,125.000,250.000,250.000,0.0,0.0];
 BW	=	0.277	;
start @nocallback
t2 = _t ;
cvatra2 = _cvatra ;
cvethyl2 = _cvethyl ;
cviso2 = _cviso ;
cvda2 = _cvda ;
aor1atra2 = _aor1atra ;
aor2atra2 = _aor2atra ;
aucvatra2 = AUCVATRA ;
aucvethyl2 = AUCVETHYL ;
aucviso2 = AUCVISO ;
aucvda2 = AUCVDA ;
%mass2 = _mass;

 DIETSTUDY = 1	;						%Binary to turn on Dietary study in rat (0 off 1 on)
 DIETCON = 500		;						%Set diet concentration for dietary study in rat (30, 100, 500)
DIETTAB(1,1:18) = [0.00,10.00,10.05,24.00,24.05,34.00,34.05,48.00,48.05,58.00,58.05,72.00,72.05,82.00,82.05,96.00,96.05,169.00];
DIETTAB(2,1:18) = [750.000,750.000,916.667,916.667,541.667,541.667,1125.000,1125.000,666.667,666.667,1458.333,1458.333,666.667,666.667,1375.000,1375.000,0.0,0.0];
 BW	=	0.255	;
start @nocallback
t3 = _t ;
cvatra3 = _cvatra ;
cvethyl3 = _cvethyl ;
cviso3 = _cviso ;
cvda3 = _cvda ;
aor1atra3 = _aor1atra ;
aor2atra3 = _aor2atra ;
aucvatra3 = AUCVATRA ;
aucvethyl3 = AUCVETHYL ;
aucviso3 = AUCVISO ;
aucvda3 = AUCVDA ;
%mass3 = _mass;

loqatra = [0.0	0.0047
169.0	0.0047];

loqda = [0.0	0.069
169.0	0.069];



plot(t1,cvatra1,t2,cvatra2,t3,cvatra3,SYNdiet30(:,1),SYNdiet30(:,2),SYNdiet100(:,1),SYNdiet100(:,2),SYNdiet500(:,1),SYNdiet500(:,2),loqatra(:,1),loqatra(:,2), 'diatraind.aps');
plot(t1,cvda1,t2,cvda2,t3,cvda3,SYNdiet30(:,1),SYNdiet30(:,5),SYNdiet100(:,1),SYNdiet100(:,5),SYNdiet500(:,1),SYNdiet500(:,5),loqda(:,1),loqda(:,2), 'didactind.aps');
plot(t1,cvethyl1,t2,cvethyl2,t3,cvethyl3,SYNdiet30(:,1),SYNdiet30(:,3),SYNdiet100(:,1),SYNdiet100(:,3),SYNdiet500(:,1),SYNdiet500(:,3),loqatra(:,1),loqatra(:,2), 'diethylind.aps');
plot(t1,cviso1,t2,cviso2,t3,cviso3,SYNdiet30(:,1),SYNdiet30(:,4),SYNdiet100(:,1),SYNdiet100(:,4),SYNdiet500(:,1),SYNdiet500(:,4),loqatra(:,1),loqatra(:,2), 'diisoind.aps');


SYNRatgaAT.m

%Model simulation of Syngenta single gavage of atrazine in rat
%Dose - 3, 10 and 50 mg/kg input as ug/kg


prepare @clear @all
output @clear


WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

ratp


DOSEC	=	3000.0	;
DOSEISOC	=	0.0	;
DOSEETHYLC	=	0.0	;
DOSEIVC	=	0.0	;
DIETC	=	0.0	;
TSTOP	=	96.0	;
TSTART	=	0.0	;
DSTOP	=	0.8	;
TINF	=	0.05	;
CINT	=	0.01	;

start @nocallback

t1 = _t ;
cvatra1 = _cvatra ;
cvethyl1 = _cvethyl ;
cviso1 = _cviso ;
cvda1 = _cvda ;
aor1atra1 = _aor1atra ;
aor2atra1 = _aor2atra ;

DOSEC	=	10000.0	;
start @nocallback
t2 = _t ;
cvatra2 = _cvatra ;
cvethyl2 = _cvethyl ;
cviso2 = _cviso ;
cvda2 = _cvda ;
aor1atra2 = _aor1atra ;
aor2atra2 = _aor2atra ;


DOSEC	=	50000.0	;
start @nocallback
t3 = _t ;
cvatra3 = _cvatra ;
cvethyl3 = _cvethyl ;
cviso3 = _cviso ;
cvda3 = _cvda ;
aor1atra3 = _aor1atra ;
aor2atra3 = _aor2atra ;

loqatra = [0.0	0.0047
24.0	0.0047];

loqda = [0.0	0.069
24.0	0.069];

plot(t1,cvatra1,t2,cvatra2,t3,cvatra3,gasingleatra(:,1),gasingleatra(:,2),gasingleatra(:,1),gasingleatra(:,3),gasingleatra(:,1),gasingleatra(:,4),loqatra(:,1),loqatra(:,2), 'gaatraavg.aps');
plot(t1,cvda1,t2,cvda2,t3,cvda3,gasingledact(:,1),gasingledact(:,2),gasingledact(:,1),gasingledact(:,3),gasingledact(:,1),gasingledact(:,4),loqda(:,1),loqda(:,2), 'gadactavg.aps');
plot(t1,cvethyl1,t2,cvethyl2,t3,cvethyl3,gasingleethyl(:,1),gasingleethyl(:,2),gasingleethyl(:,1),gasingleethyl(:,3),gasingleethyl(:,1),gasingleethyl(:,4),loqatra(:,1),loqatra(:,2), 'gaethylavg.aps');
plot(t1,cviso1,t2,cviso2,t3,cviso3,gasingleiso(:,1),gasingleiso(:,2),gasingleiso(:,1),gasingleiso(:,3),gasingleiso(:,1),gasingleiso(:,4),loqatra(:,1),loqatra(:,2), 'gaisoavg.aps');


%plot(t1,aor1atra1,t1,aor2atra1, 'amtor1satra.aps')
%plot(t2,aor1atra2,t2,aor2atra2, 'amtor1satra.aps')
%plot(t3,aor1atra3,t3,aor2atra3, 'amtor1satra.aps')


SYNsngleORHum.m

%Syngenta human simulation - single gavage dose of 0.1 mg/kg

prepare @clear @all
output @clear


WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

human
%Dose should be input in ug/kg or ug/kg/day

DOSEC	=	100.0	;
DOSEISOC	=	0.0	;
DOSEETHYLC	=	0.0	;
DOSEDAC = 0.0 ;
DOSEIVC	=	0.0	;
TSTOP	=	48.0	;
TSTART	=	0.0	;
DSTOP	=	0.1	;
TINF	=	0.05	;
BW	=	96.0	;

start @nocallback


plot(_t,_cvatra,_t,_cvda,_t,_cviso,_t,_cvethyl,DACTHumanWholeBlood01(:,1),DACTHumanWholeBlood01(:,2),DIAHumanWholeBlood01(:,1),DIAHumanWholeBlood01(:,2), 'syngorhum.aps')


M-files for PoD calculations

ratpod.m
%Calculate POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing

%rat POD should output:
%rat POD should output:
% ddd= 2.6234e+000 ---> average plasma TCT

prepare @clear @all
output @clear


WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

%Dose should be input in ug/kg or ug/kg/day
DOSEC	=	0.0	;
DOSEISOC	=	0.0	;
DOSEETHYLC	=	0.0	;
DOSEIVC	=	0.0	;
DIETC	=	0.	;

TSTOP	=	365.*24.;
CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

% use scientific notation, so the small quantities are not displayed at zeros
format shorte

ATRAIN   = zeros(1,17521);
DEAIN    = zeros(1,17521);
DIAIN    = zeros(1,17521);
DACTIN   = zeros(1,17521);

ratp
BW = 0.270; % 270 g rat
BWSW=0;

DOSES0 = 2.42; % DOSE WILL BE CONVERTED TO UG/KG/DAY IN CSL FILE
for ii = 1:365;
  TT(ii)       = (ii-1.)*24.;
  ATRAIN(ii)  = DOSES0;
end

start @nocallback

cvtct = _cvatra+_cviso+_cvethyl+_cvda;

ddd=mean(_cvatra+_cviso+_cvethyl+_cvda)
ddd2=(_aucpltri(87601)-_aucpltri(86641))/4.

PoDdw.m

%Drinking water:
%0.688557 L/day for infants, children between 1-2 year old, and children 6-12 years old; 
%1.71062 L/day for youths 13-19 years old and female adults.  
%Infants and children were assumed to consume water six times a day; youths and female adults were assumed to consume water four times a day.  
%Dietary exposure was estimated for 7 days/week.  


% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];

CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above
STARTDOSE = 2.42   ;
check = 0;
toltgt = 0.002;

% use scientific notation, so the small quantities are not displayed at zeros
format shorte

ATRAIN   = zeros(1,17521);
TT       = zeros(1,17521);


BWS0 = [4.8 11.0 32.0 57.0 69.0]; %kg
AGES0 = [0.175 1.077 9.99 15.41 20.425]; % Ages corresponding to BW requested
DWV0 = [0.688667 0.688667 0.688667 1.71062 1.71062] ; %L of drinking water /day
DPD0 = [6. 6. 6. 4. 4.] % number of drinks per day
EXPDW=1

TSTOP = 21*24.;
tic


for bwi = 1:size(AGES0,2)  %run for each of the BWs in BWS0

% Set the DW exposure schedule
for ix = 1:21;
  if(DPD0(bwi)==4)  % split into 4 doses per day for youth and adult
    TT((ix-1)*4+1) = 7.+(ix-1)*24.;
    TT((ix-1)*4+2) = 12.+(ix-1)*24.;
    TT((ix-1)*4+3) = 17.+(ix-1)*24.;
    TT((ix-1)*4+4) = 22.+(ix-1)*24.;
    ATRAIN((ix-1)*4+1) = 1./4.;
    ATRAIN((ix-1)*4+2) = 1./4.;
    ATRAIN((ix-1)*4+3) = 1./4.;
    ATRAIN((ix-1)*4+4) = 1./4.;
  else              % split into 6 doses per day for infants and children
    TT((ix-1)*6+1) = 7.+(ix-1)*24.;
    TT((ix-1)*6+2) = 10.+(ix-1)*24.;
    TT((ix-1)*6+3) = 13.+(ix-1)*24.;
    TT((ix-1)*6+4) = 16.+(ix-1)*24.;
    TT((ix-1)*6+5) = 19.+(ix-1)*24.;
    TT((ix-1)*6+6) = 22.+(ix-1)*24.;
    ATRAIN((ix-1)*6+1) = 1./6.;
    ATRAIN((ix-1)*6+2) = 1./6.;
    ATRAIN((ix-1)*6+3) = 1./6.;
    ATRAIN((ix-1)*6+4) = 1./6.;
    ATRAIN((ix-1)*6+5) = 1./6.;
    ATRAIN((ix-1)*6+6) = 1./6.;
  end
end
 TOTDWE = ix*DPD0(bwi); %Total number of exposures

   growth
   human
   BW=BWS0(bwi);
   AGE0 = AGES0(bwi)
   BWSW=1
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:TOTDWE;
         ATRAIN(ii)  = DOSES0/DPD0(bwi); %divide by number of drinking events
      end
      ATRAIN(1)

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
   dm = [dm; BWS0(bwi) aucpod DOSES0]
   check = 0;
   DOSES0 = STARTDOSE;
end

dmm=[];

% ATRAIN is in mg/kg
% convert to ppb
for iz=1:size(AGES0,2)
 dmm = [dmm; BWS0(iz) dm(iz,3)*BWS0(iz)/DWV0(iz)*1000];
end
% Output final doses
"    BW           DW (ppb)"
dmm

PoDdiet.m

%Drinking water:
%0.688557 L/day for infants, children between 1-2 year old, and children 6-12 years old; 
%1.71062 L/day for youths 13-19 years old and female adults.  
%Infants and children were assumed to consume water six times a day; youths and female adults were assumed to consume water four times a day.  
%Dietary exposure was estimated for 7 days/week.  


% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];

CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above
STARTDOSE = 2.42   ;
check = 0;
toltgt = 0.002;

% use scientific notation, so the small quantities are not displayed at zeros
format shorte

ATRAIN   = zeros(1,17521);
TT       = zeros(1,17521);


BWS0 = [4.8 11.0 32.0 57.0 69.0]; %kg
AGES0 = [0.175 1.077 9.99 15.41 20.425]; % Ages corresponding to BW requested
DWV0 = [0.688667 0.688667 0.688667 1.71062 1.71062] ; %L of drinking water /day
DPD0 = [6. 6. 6. 4. 4.] % number of drinks per day
EXPDW=1

TSTOP = 21*24.;
tic


for bwi = 1:size(AGES0,2)  %run for each of the BWs in BWS0

% Set the DW exposure schedule
for ix = 1:21;
  if(DPD0(bwi)==4)  % split into 4 doses per day for youth and adult
    TT((ix-1)*4+1) = 7.+(ix-1)*24.;
    TT((ix-1)*4+2) = 12.+(ix-1)*24.;
    TT((ix-1)*4+3) = 17.+(ix-1)*24.;
    TT((ix-1)*4+4) = 22.+(ix-1)*24.;
    ATRAIN((ix-1)*4+1) = 1./4.;
    ATRAIN((ix-1)*4+2) = 1./4.;
    ATRAIN((ix-1)*4+3) = 1./4.;
    ATRAIN((ix-1)*4+4) = 1./4.;
  else              % split into 6 doses per day for infants and children
    TT((ix-1)*6+1) = 7.+(ix-1)*24.;
    TT((ix-1)*6+2) = 10.+(ix-1)*24.;
    TT((ix-1)*6+3) = 13.+(ix-1)*24.;
    TT((ix-1)*6+4) = 16.+(ix-1)*24.;
    TT((ix-1)*6+5) = 19.+(ix-1)*24.;
    TT((ix-1)*6+6) = 22.+(ix-1)*24.;
    ATRAIN((ix-1)*6+1) = 1./6.;
    ATRAIN((ix-1)*6+2) = 1./6.;
    ATRAIN((ix-1)*6+3) = 1./6.;
    ATRAIN((ix-1)*6+4) = 1./6.;
    ATRAIN((ix-1)*6+5) = 1./6.;
    ATRAIN((ix-1)*6+6) = 1./6.;
  end
end
 TOTDWE = ix*DPD0(bwi); %Total number of exposures

   growth
   human
   BW=BWS0(bwi);
   AGE0 = AGES0(bwi)
   BWSW=1
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:TOTDWE;
         ATRAIN(ii)  = DOSES0/DPD0(bwi); %divide by number of drinking events
      end
      ATRAIN(1)

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
   dm = [dm; BWS0(bwi) aucpod DOSES0]
   check = 0;
   DOSES0 = STARTDOSE;
end

dmm=[];

% ATRAIN is in mg/kg
% convert to ppb
for iz=1:size(AGES0,2)
 dmm = [dmm; BWS0(iz) dm(iz,3)*BWS0(iz)/DWV0(iz)*1000];
end
% Output final doses
"    BW           DW (ppb)"
dmm

PoDdietacute.m

% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];

CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above
STARTDOSE = 2.42   ;
check = 0;
toltgt = 0.002;
% use scientific notation, so the small quantities are not displayed at zeros
format shorte

TT       = zeros(1,17521);
ATRAIN   = zeros(1,17521);

for ii = 1:1;
  TT(ii)       = (ii-1.)*24.;
  ATRAIN(ii)  = 1.;
end

  TSTOP = 24.;


for ix = 1:3  %run for each of the parent compounds
   growth
   human
 	if(ix==2)
  	VMAXCATRA_ISO = 0.;	 %For propazine, set metabolism to DIA = 0
   elseif(ix==3)
		VMAXCATRA_ETHYL = 0.;	 %For simazine , set metabolism to DEA = 0
   end
   BW=69.0;
   AGE0 = 20.425
   BWSW=1
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:365;
        ATRAIN(ii)  = DOSES0;
      end
      ATRAIN(1)

      start @nocallback

      aucpod = AUCPLTRI

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
   dm = [dm; ix aucpod DOSES0*1000.]
   check = 0;
   DOSES0 = STARTDOSE;
end

% ATRAIN is in mg/kg
% convert to ug/kg

% Output final doses
"    Parent         Dose (mg/kg)"
[dm(:,1) dm(:,3)]

PoDoralturf.m

%Other Turf Activities (Children 1 to < 2, and Adults)
%Daily exposure time is assumed to be 1.5 hours/day
%All exposures were set to be continuous for 21 days
%For oral exposures 4 replenishments per hour, and 6 replenishments per day.
%Calculate POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing

% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];

CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above
STARTDOSE = 2.42   ;
check = 0;
toltgt = 0.002;

% use scientific notation, so the small quantities are not displayed at zeros
format shorte

ATRAIN   = zeros(1,17521);
TT       = zeros(1,17521);


BWS0 = [11.0 69.0]; %kg
AGES0 = [1.077 20.425]; % Ages corresponding to BW requested

TSTOP = 21*24.;

for bwi = 1:size(AGES0,2)  %run for each of the BWs in BWS0

% Set the DW exposure schedule
for ix = 1:21;
    TT((ix-1)*6+1) = 10.+(ix-1)*24.;
    TT((ix-1)*6+2) = 10.25+(ix-1)*24.;
    TT((ix-1)*6+3) = 10.5+(ix-1)*24.;
    TT((ix-1)*6+4) = 10.75+(ix-1)*24.;
    TT((ix-1)*6+5) = 11.+(ix-1)*24.;
    TT((ix-1)*6+6) = 11.25+(ix-1)*24.;
    ATRAIN((ix-1)*6+1) = 1./6.;
    ATRAIN((ix-1)*6+2) = 1./6.;
    ATRAIN((ix-1)*6+3) = 1./6.;
    ATRAIN((ix-1)*6+4) = 1./6.;
    ATRAIN((ix-1)*6+5) = 1./6.;
    ATRAIN((ix-1)*6+6) = 1./6.;
end

   growth
   human
   BW=BWS0(bwi);
   AGE0 = AGES0(bwi)
   BWSW=1;
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:6*21;
         ATRAIN(ii)  = DOSES0/6.; %divide by number of events
      end

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.;

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
   dm = [dm; BWS0(bwi) aucpod DOSES0*1000.]
   check = 0;
   DOSES0 = STARTDOSE;
end

dmm=[];

for iz=1:size(AGES0,2)
 dmm = [dmm; BWS0(iz) dm(iz,3)];
end

% ATRAIN is in mg/kg
% convert to ug/kg

% Output final doses
"    BW           Dose (ug/kg)"
dmm

PoDinh.m

%Residential
%Handler (Adult only)
%Contact time with turf assumed to be 1.0 hours.
%All residential exposures were set to be continuous for 21 days.  
%Breathing Rate: adults - 0.64 m3/hr 


% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];

CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above
STARTDOSE = 1.;
check = 0;
toltgt = .001;
% use scientific notation, so the small quantities are not displayed at zeros
format shorte


% set exposure for 1 hour per day for 21 days
for ii = 1:21;
  TTIN(2*(ii-1)+1) = (ii-1.)*24.;
  INATRAIN(2*(ii-1)+1)  = 1.;
  TTIN(2*(ii-1)+2) = (ii-1.)*24.+1.;
  INATRAIN(2*(ii-1)+2)  = 0.;
end

TSTOP = 21*24.;

   growth
   human
   BW = 69.0; %kg
   AGE0 = 20.425; % Ages corresponding to BW requested
   QPC0 =0.64; %m3/hr
   QPC = QPC0 * 1000./(BW^0.75) %converted to L/hr/bw^0.75
   BWSW=1; % use lifestage code
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:365;
         if(INATRAIN(ii)>0);
            INATRAIN(ii)  = DOSES0;
         end
      end
      INATRAIN(1);

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
% INATRAIN is in mg/m3 (same as ug/L)

   dm = [BW aucpod DOSES0];

% Output final concentration
"    BW             Air (mg/m3)"
[dm(:,1) dm(:,3)]

PoDinhocc.m

%Occupational
%	The worker was assumed to be a female adult between the ages of 13 to 49, and had a body weight of 69 kg
%	The worker is exposed via inhalation for 8 hours/day, 5 days/week, for a total of 21 days
%	Breathing rates: mixer/loader = 1 m3/hr, applicator = 0.5 m3/hr, and PHED combo = 7.3 m3/hr.  


% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];

CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above

STARTDOSE = 1.;
check = 0;
toltgt = .001;

% use scientific notation, so the small quantities are not displayed at zeros
format shorte
INATRAIN   = zeros(1,17521);
TTIN       = zeros(1,17521);

QPC0x = [1 0.5 7.3]; %Breathing rates: mixer/loader ??? 1 m3/hr, applicator ??? 0.5 m3/hr, and PHED combo ??? 7.3 m3/hr.  

for ixx= 1:3 % run for all 3 breathing rates
% set exposure for 8 hour per day for 21 days (exposure 5 days out of 7)
for ii = 1:21;
if(mod(ii,7)==1)  % no dosing on the first day of the week
  TTIN(2*(ii-1)+1) = (ii-1.)*24.;
  INATRAIN(2*(ii-1)+1)  = 0;
  TTIN(2*(ii-1)+2) = (ii-1.)*24.+8.;
  INATRAIN(2*(ii-1)+2)  = 0.;
elseif(mod(ii,7)==2)  % no dosing on the second day of the week
  TTIN(2*(ii-1)+1) = (ii-1.)*24.;
  INATRAIN(2*(ii-1)+1)  = 0;
  TTIN(2*(ii-1)+2) = (ii-1.)*24.+8.;
  INATRAIN(2*(ii-1)+2)  = 0.;
else
  TTIN(2*(ii-1)+1) = (ii-1.)*24.;
  INATRAIN(2*(ii-1)+1)  = 1.;
  TTIN(2*(ii-1)+2) = (ii-1.)*24.+8.;
  INATRAIN(2*(ii-1)+2)  = 0.;
end
end

TSTOP = 21*24.; % End at 21 days

   growth
   human
   BW = 69.0; %kg
   AGE0 = 20.425; % Ages corresponding to BW requested
   QPC0 =QPC0x(ixx); %m3/hr
   QPC = QPC0 * 1000./(BW^0.75); %converted to L/hr/bw^0.75
   BWSW=1; % use lifestage code
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:21*2;
         if(INATRAIN(ii)>0);
            INATRAIN(ii)  = DOSES0;
         end
      end
      INATRAIN(1);

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.;

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
% INATRAIN is in mg/m3 (same as ug/L)
   plot(_t,_ci,_t,_cvtottri)
   dm = [dm; BW aucpod DOSES0];
   check = 0;
   DOSES0 = STARTDOSE;

end
% Output final concentration
"    BW             Air (mg/m3)"
[dm(:,1) dm(:,3)]

PoDinhturf.m

%Other Turf Activities (Children 1 to < 2, and Adults)
%Daily exposure time is assumed to be 1.5 hours/day
%All exposures were set to be continuous for 21 days

% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];

CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above

STARTDOSE = 1.;
check = 0;
toltgt = .001;

% use scientific notation, so the small quantities are not displayed at zeros
format shorte
INATRAIN   = zeros(1,17521);
TTIN       = zeros(1,17521);

BWS0 = [11.0 69.0]; %kg
AGES0 = [1.077 20.425]; % Ages corresponding to BW requested
QPC0x = [0.33 0.64]; %Breathing rates: children 0.33 m3/hr, adults = 0.64 m3/hr   


for ix= 1:2 % run for both ages

% set exposure for 1.5 hours per day for 21 days
for ii = 1:21;
  TTIN(2*(ii-1)+1) = (ii-1.)*24.;
  INATRAIN(2*(ii-1)+1)  = 1.;
  TTIN(2*(ii-1)+2) = (ii-1.)*24.+1.5;
  INATRAIN(2*(ii-1)+2)  = 0.;
end

  TSTOP = 21.*24.; % End at 21 days

   growth
   human
   BW=BWS0(ix);
   AGE0 = AGES0(ix)
   QPC0 = QPC0x(ix); %m3/hr
   QPC = QPC0 * 1000./(BW^0.75); %converted to L/hr/bw^0.75

   BWSW=1; % use lifestage code
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:21*2;
         if(INATRAIN(ii)>0);
            INATRAIN(ii)  = DOSES0;
         end
      end

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.;

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
% INATRAIN is in mg/m3 (same as ug/L)
   plot(_t,_ci,_t,_cvtottri)
   dm = [dm; BW aucpod DOSES0];
   check = 0;
   DOSES0 = STARTDOSE;

end
% Output final concentration
"    BW             Air (mg/m3)"
[dm(:,1) dm(:,3)]

PoDinhbys.m

%Residential Bystander - Inhalation assessment (Steady State) 
%Young Children (1 - 2 years old) and Females (13 - 49 years old)
%Exposure time is assumed to be 24 hours 
%Breathing rates: Children = 0.33 m3/hr, adults = 0.64 m3/hr 


% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];

CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above

STARTDOSE = 1.;
check = 0;
toltgt = .001;

% use scientific notation, so the small quantities are not displayed at zeros
format shorte
INATRAIN   = zeros(1,17521);
TTIN       = zeros(1,17521);

BWS0 = [11.0 69.0]; %kg
AGES0 = [1.077 20.425]; % Ages corresponding to BW requested
QPC0x = [0.33 0.64]; %Breathing rates: children 0.33 m3/hr, adults = 0.64 m3/hr   


for ix= 1:2 % run for both ages

% turn on exposure, constant for 24 hours/day
  TTIN(1) = 0.;
  INATRAIN(1)  = 1.;

  TSTOP = 21.*24.; % End at 21 days

   growth
   human
   BW=BWS0(ix);
   AGE0 = AGES0(ix)
   QPC0 = 0.64; %m3/hr
   QPC = QPC0 * 1000./(BW^0.75); %converted to L/hr/bw^0.75

   BWSW=1; % use lifestage code
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      INATRAIN(1)  = DOSES0;

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.;

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
% INATRAIN is in mg/m3 (same as ug/L)
   plot(_t,_ci,_t,_cvtottri)
   dm = [dm; BW aucpod DOSES0];
   check = 0;
   DOSES0 = STARTDOSE;

end
% Output final concentration
"    BW             Air (mg/m3)"
[dm(:,1) dm(:,3)]

PoDinhbysacute.m

%Residential Bystander - Inhalation assessment (Acute) 
%Acute: Females (13 - 49 years old)
%Exposure time is assumed to be 24 hours 
%Breathing rates: Children = 0.33 m3/hr, adults = 0.64 m3/hr 


% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];

CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above

STARTDOSE = 1.;
check = 0;
toltgt = .001;

% use scientific notation, so the small quantities are not displayed at zeros
format shorte
INATRAIN   = zeros(1,17521);
TTIN       = zeros(1,17521);


for ix= 1:3 % run for all 3 parent compounds

% turn on exposure, constant for 24 hours/day
  TTIN(1) = 0.;
  INATRAIN(1)  = 1.;

  TSTOP = 1.*24.; % End at 21 days

   growth
   human
   BW = 69.0; %kg
   AGE0 = 20.425; % Ages corresponding to BW requested
   QPC0 = 0.64; %m3/hr
   QPC = QPC0 * 1000./(BW^0.75); %converted to L/hr/bw^0.75
	 if(ix==2)
  	VMAXCATRA_ISO = 0.;	 %For propazine, set metabolism to DIA = 0
   elseif(ix==3)
		VMAXCATRA_ETHYL = 0.;	 %For simazine , set metabolism to DEA = 0
   end

   BWSW=1; % use lifestage code
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      INATRAIN(1)  = DOSES0;

      start @nocallback

      aucpod = AUCPLTRI;

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
% INATRAIN is in mg/m3 (same as ug/L)
   plot(_t,_ci,_t,_cvatra)
   dm = [dm; BW aucpod DOSES0];
   check = 0;
   DOSES0 = STARTDOSE;

end
% Output final concentration
"    BW             Air (mg/m3)"
[dm(:,1) dm(:,3)]

PoDdermgolf.m

%Golfer (Adult, Children 6 to 11, Youth 11 to 16)
%Residential dermal exposures, the fraction of skin in contact with triazines was set to 50%.  
%Daily exposure time is assumed to be 4 hours/day
%All golfer exposures were set to be continuous for 21 days

% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];


CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above
STARTDOSE = 2.42   ;
check = 0;
toltgt = .002;
% use scientific notation, so the small quantities are not displayed at zeros
format shorte

DATRAIN   = zeros(1,17521);
TTD       = zeros(1,17521);
EXPDERM = 1;

BWS0 = [32.0 57.0 69.0]; %kg
AGES0 = [9.99 15.41 20.425]; % Ages corresponding to BW requested

for ii = 1:21;
  TTD(2*(ii-1)+1) = (ii-1.)*24.;
  DATRAIN(2*(ii-1)+1)  = 1.;
  TTD(2*(ii-1)+2) = (ii-1.)*24.+4.;
  DATRAIN(2*(ii-1)+2)  = 0.;
end

TSTOP = 21*24.;
tic


for bwi = 1:size(AGES0,2)  %run for each of the BWs in BWS0
   growth
   human
   BW=BWS0(bwi);
   AGE0 = AGES0(bwi)
   BWSW=1;
   DERMRATE = 0.06/24.; % 6 percent abborbed in 24 hours

   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:365;
         if(DATRAIN(ii)>0);
            DATRAIN(ii)  = DOSES0;
         end
      end

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.;

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
   dm = [dm; BWS0(bwi) aucpod DOSES0];
plot(_t,_cvtottri)
   check = 0;
   DOSES0 = STARTDOSE;
end

% Output final doses
"    BW             Dose (ug/kg/day)"
[dm(:,1) dm(:,3)]

PoDdermmow.m

%Mowing (Adults and Children 11 to 16)
%Residential dermal exposures, the fraction of skin in contact with triazines was set to 50%.  
%Daily exposure time is assumed to be 1.0 hours/day
%All exposures were set to be continuous for 21 days

% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];


CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above
STARTDOSE = 2.42   ;
check = 0;
toltgt = 0.002;
% use scientific notation, so the small quantities are not displayed at zeros
format shorte

DATRAIN   = zeros(1,17521);


BWS0 = [57.0 69.0]; %kg
AGES0 = [15.41 20.425]; % Ages corresponding to BW requested

for ii = 1:21;
  TTD(2*(ii-1)+1) = (ii-1.)*24.;
  DATRAIN(2*(ii-1)+1)  = 1.;
  TTD(2*(ii-1)+2) = (ii-1.)*24.+1.;
  DATRAIN(2*(ii-1)+2)  = 0.;
end

TSTOP = 21*24.;
tic


for bwi = 1:size(AGES0,2)  %run for each of the BWs in BWS0
   growth
   human
   BW=BWS0(bwi);
   AGE0 = AGES0(bwi)
   BWSW=1;
   DERMRATE = 0.06/24.; % 6 percent abborbed in 24 hours

   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:365;
         if(DATRAIN(ii)>0);
            DATRAIN(ii)  = DOSES0;
         end
      end

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.;

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
   dm = [dm; BWS0(bwi) aucpod DOSES0];
   check = 0;
   DOSES0 = STARTDOSE;
end

% Output final doses
"    BW             Dose (ug/kg/day)"
[dm(:,1) dm(:,3)]

PoDdermturf.m

%Other Turf Activities (Children 1 to < 2, and Adults)
%Residential dermal exposures, the fraction of skin in contact with triazines was set to 50%.  
%Daily exposure time is assumed to be 1.5 hours/day
%All exposures were set to be continuous for 21 days

% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];


CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above
STARTDOSE = 2.42   ;
check = 0;
toltgt = 0.002;
% use scientific notation, so the small quantities are not displayed at zeros
format shorte

DATRAIN   = zeros(1,17521);

BWS0 = [11.0 69.0]; %kg
AGES0 = [1.077 20.425]; % Ages corresponding to BW requested

for ii = 1:21;
  TTD(2*(ii-1)+1) = (ii-1.)*24.;
  DATRAIN(2*(ii-1)+1)  = 1.;
  TTD(2*(ii-1)+2) = (ii-1.)*24.+1.5;
  DATRAIN(2*(ii-1)+2)  = 0.;
end

TSTOP = 21*24.;
tic


for bwi = 1:size(AGES0,2)  %run for each of the BWs in BWS0
   growth
   human
   BW=BWS0(bwi);
   AGE0 = AGES0(bwi)
   BWSW=1;
   DERMRATE = 0.06/24.; % 6 percent abborbed in 24 hours

   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:365;
         if(DATRAIN(ii)>0);
            DATRAIN(ii)  = DOSES0;
         end
      end

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.;

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
   dm = [dm; BWS0(bwi) aucpod DOSES0];
   check = 0;
   DOSES0 = STARTDOSE;
end

% Output final doses
"    BW             Dose (ug/kg/day)"
[dm(:,1) dm(:,3)]

PoDdermocc.m

%Occupational
%	The worker was assumed to be a female adult between the ages of 13 to 49, and had a body weight of 69 kg
%	The worker is exposed to either via skin for 8 hours/day, 5 days/week, for a total of 21 days


% POD in rat at daily dose of 2.42 mg/kg/day
% 1 year of dosing
% rat POD output: % ddd= 2.6234e+000 ---> average plasma TCT

% Run human model to match rat POD

prepare @clear @all
output @clear
dosereset

WEDITG	=	0	;
WESITG	=	0	;
CJVITG	=	0	;

dm=[];

CINT = 0.1 ; %Model runs in 0.1 hour or 6 minute increments

target = 6.2975e+001; %average TCT AUC of last 4 days in from rat POD above

STARTDOSE = 1.;
check = 0;
toltgt = .001;

% use scientific notation, so the small quantities are not displayed at zeros
format shorte
DATRAIN   = zeros(1,17521);
TTID       = zeros(1,17521);


% set exposure for 8 hour per day for 21 days (exposure 5 days out of 7)
for ii = 1:21;
if(mod(ii,7)==1)  % no dosing on the first day of the week
  TTD(2*(ii-1)+1) = (ii-1.)*24.;
  DATRAIN(2*(ii-1)+1)  = 0;
  TTD(2*(ii-1)+2) = (ii-1.)*24.+8.;
  DATRAIN(2*(ii-1)+2)  = 0.;
elseif(mod(ii,7)==2)  % no dosing on the second day of the week
  TTD(2*(ii-1)+1) = (ii-1.)*24.;
  DATRAIN(2*(ii-1)+1)  = 0;
  TTD(2*(ii-1)+2) = (ii-1.)*24.+8.;
  DATRAIN(2*(ii-1)+2)  = 0.;
else
  TTD(2*(ii-1)+1) = (ii-1.)*24.;
  DATRAIN(2*(ii-1)+1)  = 1.;
  TTD(2*(ii-1)+2) = (ii-1.)*24.+8.;
  DATRAIN(2*(ii-1)+2)  = 0.;
end
end

TSTOP = 21*24.; % End at 21 days

   growth
   human
   BW = 69.0; %kg
   AGE0 = 20.425; % Ages corresponding to BW requested
   BWSW=1; % use lifestage code
   DOSES0 = STARTDOSE;
   while (check==0)  %run until check is met
      for ii = 1:21*2;
         if(DATRAIN(ii)>0);
            DATRAIN(ii)  = DOSES0;
         end
      end
      DATRAIN(1);

      start @nocallback

      aucpod = (_aucpltri(5041)-_aucpltri(4081))/4.;

      if(abs((aucpod-target)/target)<toltgt)
         check = 1;
      else
         DOSES0 = DOSES0 * (target/aucpod);
      end
   end
% DATRAIN is in ug/kg
   plot(_t,_ci,_t,_cvtottri)
   dm = [dm; BW aucpod DOSES0];

% Output final concentration
"    BW             Dose (ug/kg/day)"
[dm(:,1) dm(:,3)]
        
