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CSL file.

PROGRAM

POP toxicokinetic model

Coded by Marc-Andre Verner

Units

Time: hours

Volumes: L

Quantities: ug

INITIAL ! Start of initial section

! Individual information

! These can be imported for individuals from

! Excel spreadsheets using the script

! Verner_2012_script.m
! Dyad ID

CONSTANT ID                     = 2005         ! ID number

! Maternal variables

CONSTANT AGE_delivery                 =  ! Age of mother at
                                 25.634  delivery (years)

CONSTANT PREPREGNANCY_BW         = 61.0  ! Pre-pregnancy body
                                         weight (kg)

CONSTANT WEIGHT_GAIN_PREGNANCY   = 12.5  ! Weight gain during
                                         pregnancy (kg)

CONSTANT POSTPARTUM_WEIGHT_1     = 63.0  ! Postpartum weight at
                                         first weighing (kg)

CONSTANT POSTPARTUM_WEIGHT_2     = 62.0  ! Postpartum weight at
                                         second weighing (kg)

CONSTANT                              =  ! Age of mother at
AGE_POSTPARTUM_WEIGHT_1          26.134  first postpartum
                                         weighing (years)

CONSTANT                              =  ! Age of mother at
AGE_POSTPARTUM_WEIGHT_2          26.634  second postpartum
                                         weighing (years)

! Child variables

CONSTANT SEX                        = 1  ! Child sex (0: female,
                                         1: male)

CONSTANT GESTATIONAI AGE         = 0.76  ! Gestational age at
                                         birth (years)

CONSTANT BIRTHWEIGHT              = 3.3  ! Child birth weight
                                         (kg)

CONSTANT CHILD_WEIGHT_1          = 7.75  ! Child weight at 1st
                                         measurement

CONSTANT CHILD_WEIGHT_2          = 12.6  ! Child weight at 2nd
                                         measurement

CONSTANT CHILD_WEIGHT_3          = 18.2  ! Child weight at 3rd
                                         measurement

CONSTANT AGE_CHILD_WEIGHT_1     = 0.521  ! Child age at first
                                         weight measurement
                                         (years)

CONSTANT AGE_CHILD_WEIGHT_2     = 1.333  ! Child age at second
                                         weight measurement
                                         (years)

CONSTANT AGE_CHILD_WEIGHT_3     = 4.246  ! Child age at third
                                         weight measurement
                                         (years)

! Breast-feeding variables

CONSTANT                          = 0.5  ! Duration of exclusive
DURATION_EXCL_Breastfeedi ng             breastfeeding (years)

CONSTANT                          = 0.5  ! Total duration
DURATION_TOTAL_Breastfeeding             breastfeeding (years)

CONSTANT FRACTION_BF_1m           = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 1)

CONSTANT FRACTION_BF_2m           = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 2)

CONSTANT FRACTION_BF_3m           = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 3)

CONSTANT FRACTION_BF_4m           = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 4)

CONSTANT FRACTION_BF_5m           = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 5)

CONSTANT FRACTION_BF_6m           = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 6)

CONSTANT FRACTION_BF_7m           = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 7)

CONSTANT FRACTION_BF_8m           = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 8)

CONSTANT FRACTION_BF_9m           = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 9)

CONSTANT FRACTION_BF_10m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 10)

CONSTANT FRACTION_BF_11m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 11)

CONSTANT FRACTION_BF_12m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 12)

CONSTANT FRACTION_BF_13m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 13)

CONSTANT FRACTION_BF_14m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 14)

CONSTANT FRACTION_BF_15m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 15)

CONSTANT FRACTION_BF_16m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 16)

CONSTANT FRACTION_BF_17m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 17)

CONSTANT FRACTION_BF_18m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 18)

CONSTANT FRACTION_BF_19m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 19)

CONSTANT FRACTION_BF_20m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 20)

CONSTANT FRACTION_BF_21m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 21)

CONSTANT FRACTION_BF_22m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 22)

CONSTANT FRACTION_BF_23m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 23)

CONSTANT FRACTION_BF_24m          = 0.5  ! Fraction of food
                                         intake attributable to
                                         breast milk (month 24)

! Dosing variable

CONSTANT DOSE                    = 0.01  ! Daily oral dose
                                         (ug/kg)

CONSTANT COMPOUND                   = 5  ! 1:PCB52, 2:PCB105,
                                         3:PCB118, 4:PCB138,
                                         5:PCB153,

                                         ! 6:PCB170, 7:PCB180,
                                         8:PCB187, 9:DDE,
                                         10:DDT, 11:HCB

! Sample variables

CONSTANT MOTHER_AGE_SAMPLE         = 23  ! Age of mother at
                                         blood/cord/milk sample
                                         (years)

CONSTANT POP_LEVEL                = 116  ! Mother fat pop level
                                         (ug/kg lipid)

END ! End of initial section


DYNAMIC ! Start of dynamic sections
! Length of simulations

TSTOPage = AGE_delivery + 5    ! Length of simulation /
                               mother's age (yrs)

TSTOP = 24. * 365. * TSTOPage  ! Length of simulation (hrs)

POINTS = 300                   ! Number of points in plot

schedule stopthesim.at. TSTOP  ! Schedule end of simulation

discrete stopthesim            ! When simulation reaches
                               stopthesim event

termt(.true.)                  !...terminate simulation

end                            ! End of discrete event

! Simulation parameters

ALGORITHM IALG = 2       ! Use Gear algorithm

MAXTERVAL MAXT = 24      ! Maximum interval for integrations

MINTERVAL MINT = 1.0     ! Minimal interval for integrations

CINTERVAL CINT = 24      ! Communication interval

DERIVATIVE               ! Start of DERIVATIVE SECTION


! Age at conception

AGE_CONCEPTION = AGE_DELIVERY-GESTATIONAL_AGE ! Mother's age at conception (years)

! Basal body weight

! (not taking pregnancy weight changes into account)

! Curves are based on 50th percentile charts and adjusted for individual measurements
! Mother

table tab1e_bw_mother     1,10/0.0, 0.5, 1.0, 2.0, 5.0, 10.0,
                          13.0, 16.0, 20.0, 100.0, 3.4, 7.2, 9.5,
                          12.1, & 18.0, 33.0, 46.0, 54.0, 58.0, 58.0/

Diff_profi1e              = (1-Switch_conception) * (AGE *
                          (PREPREGNANCY_BW-tab1e_bw_mother(Age_
                          conception))/Age_conception) & + Switch_
                          Conception * (PREPREGNANCY_BW-tab1e_
                          bw_mother(Age_conception))

BW                        = Diff_profi1e + tab1e_bw_mother(Age)

! Child

table tab1e_bw_males,     1,10/0.0, 0.5, 1.0, 2.0, 5.0, 10.0, 13.0,
                          16.0, 20.0, 100.0, 3.5, 7.8, 10.3, 12.7,
                          & 18.0, 32.0, 46.0, 61.0, 71.0, 71.0/

table tab1e_bw_femnales,  1,10/0.0, 0.5, 1.0, 2.0, 5.0, 10.0, 13.0,
                          16.0, 20.0, 100.0, 3.4, 7.2, 9.5, 12.1, &
                          18.0, 33.0, 46.0, 54.0, 58.0, 58.0/

NORM_BW_CHILD             = sex * tab1e_bw_ma1es(Age_chi1d)+(1-sex)
                          * tab1e_bw_fema1es(Age_chi1d)

Diff_norm_birth           = BIRTHWEIGHT-(sex * 3.5 + (1-sex) * 3.4)

Diff_norm_WEIGHTl         = CHILD_WEIGHT_1-(sex * tab1e_bw_ma1es
                          (AGE_CHILD_WEIGHT_1)+(1-sex) * tab1e_
                          bw_fema1es(AGE_CHILD_WEIGHT_1))

Diff_norm_WEIGHT2         = CHILD_WEIGHT_2-(sex * tab1e_bw_ma1es
                          (AGE_CHILD_WEIGHT_2)+(1-sex) *
                          tab1e_bw_fema1es(AGE_CHILD_WEIGHT_2))

Diff_norm_WEIGHT3         =CHILD_WEIGHT_3-(sex * table_bw_males
                          (AGE_CHILD_WEIGHT_3)+(1-sex) * table_
                          bw_females(AGE_CHILD_WEIGHT_3))

Diff_profile_child =      (SWITCH_DELIVERY-SWITCH_AGE_CHILD_WEIGHT1)
                          * (Diff_norm_birth+AGE_child *
                          (Diff_norm_WEIGHT1-Diff_norm_birth)/AGE
                          _CHILD_WEIGHT_1) &

                          +(SWITCH_AGE_CHILD_WEIGHT1-SWITCH_AGE_
                          CHILD_WEIGHT2)* (Diff_norm_WEIGHT1+(Age_
                          child-AGE_CHILD_WEIGHT_1) &

                          * (Diff_norm_WEIGHT2-Diff_norm_WEIGHT1)/
                          (AGE_CHILD_WEIGHT_2-AGE_CHILD_WEIGHT_1)) &

                          +(SWITCH_AGE_CHILD_WEIGHT2-SWITCH_AGE_CHILD
                          _WEIGHT3) * (Diff_norm_WEIGHT2+(Age_child-
                          AGE_CHILD_WEIGHT_2) &

                          * (Diff_norm_WEIGHT3-Diff_norm_WEIGHT2)/
                          (AGE_CHILD_WEIGHT_3-AGE_CHILD_WEIGHT_2)) &

                          +SWITCH_AGE_CHILD_WEIGHT3 * Diff_norm_WEIGHT3

BW_child                  =Diff_profile_child+NORM_BW_CHILD

! Fetus

table                    1,7/0.0, 0.217, 0.353, 0.463, 0.551,
table_fetal_weight,      0.639, 0.768, 0.0, 0.0, 0.26, 0.69,
                         1.25, 2.02, 3.28/

NORM_BIRTHWEIGHT_FOR_GA  = table_fetal_weight(GESTATIONAL_AGE)

RATIO_BIRTHWEIGHT_NORM   = BIRTHWEIGHT/NORM_BIRTHWEIGHT_FOR_GA

FETAL_WEIGHT             = (SWITCH_CONCEPTION-SWITCH_DELIVERY)
                         * RATIO_BIRTHWEIGHT_NORM *
                         table_fetal_weight(FETAL_AGE)


! BODY FAT

! Based on data from

! Fomon et al. 1982

! and ICRP 2002
! Mother

table bodyfat_mother,    1,17/0.0, 0.08, 0.17, 0.25, 0.33, 0.5, 1, 2, 4,
                         6, 8, 10, 12, 16, 29, 39, 69, 0.15, 0.16, 0.21
                         & 0.24, 0.25, 0.17, 0.16, 0.17, 0.19, 0.23,
                         0.26, 0.29, 0.31, 0.41/

FAT_GAIN_PREGNANCY       = 0.75 * (WEIGHT_GAIN_PREGNANCY
                         - Birthweight-5.8)

SLOP E_GAIN_PREGNANCY    = (SWITCH_CONCEPTION-SWITCH_

                         DELIVERY)*(FAT_GAIN_PREGNANCY*
                         (AGE-AGE_CONCEPTION)/GESTATIONAL_AGE)

FAT_POSTPARTUM_WEIGHT_1  = POSTPARTUM_WEIGHT_1-PREPREGNANCY
                         _BW

FAT_POSTPARTUM_WEIGHT_2  = POSTPARTUM_WEIGHT_2-PREPREGNANCY
                         _BW

SLOPE_LOSS_POSTPARTUM    = (SWITCH_DELIVERY-SWITCH_
                         POSTPARTUM_WEIGHT_1) &

                         * (FAT_GAIN_PREGNANCY-(FAT_
                         GAIN_PREGNANCY-FAT_POSTPARTUM_
                         WEIGHT_1) &

                         * (AGE-AGE_DELIVERY)/(AGE_POSTPARTUM
                         _WEIGHT_1-AGE_DELIVERY)) &

                         +(SWITCH_POSTPARTUM_WEIGHT_1-
                         SWITCH_POSTPARTUM_WEIGHT_2) &

                         * (FAT_POSTPARTUM_WEIGHT_1-(FAT_POSTPARTUM_
                         WEIGHT_1-FAT_POSTPARTUM_WEIGHT_2) &

                         * (AGE-AGE_POSTPARTUM_WEIGHT_1)/
                         (AGE_POSTPARTUM_WEIGHT_2-AGE_
                         POSTPARTUM_WEIGHT_1)) &

                         +SWITCH_POSTPARTUM_WEIGHT
                         _2 * FAT_POSTPARTUM_WEIGHT_2

VOL_FAT_MOTHER           = (BW*bodyfat_mother(age))+SLOPE_
                         GAIN_PREGNANCY+SLOPE_
                         LOSS_POSTPARTUM

table bodyfat_female,    1,17/0.0, 0.08, 0.17, 0.25, 0.33, 0.5, 1,
                         2, 4, 6, 8, 10, 12, 16, 29, 39, 69, 0.15,
                         0.16, 0.21, & 0.24, 0.25, 0.26, 0.24,
                         0.20, 0.17, 0.16, 0.17, 0.19, 0.23, 0.26,
                         0.29, 0.31, 0.41/

table bodyfat_male,      1,17/0.0, 0.08, 0.17, 0.25, 0.33, 0.5, 1,
                         2, 4, 6, 8, 10, 12, 16, 21, 36,
                         69, 0.14, 0.15, 0.19, & 0.23, 0.25, 0.25,
                         0.23, 0.20, 0.16, 0.14, 0.13, 0.14, 0.17, 0.16,
                         0.17, 0.20, 0.33/

VOL_FAT_CHILD            = (SWITCH_CONCEPTION-SWITCH_DELIVERY)*
                         FETAL_WEIGHT*(sex*0.14+(1-sex)*0.15)&

                         +SWITCH_DELIVERY*(BW_child*(sex*bodyfat_
                         male(age_child) + (1-sex)*bodyfat_female
                         (age_child))) & +0.001


! Breast-feeding

! Data from Salmenpera 1985

! and Kent 1999
! Volume of milk
ingested (L/H)

VOLUME_MILK_          = (BW_child * (-0.0024 * Age_child + 0.0063))
excl_0_12m
feeding (l/h)
(Salmenpera et
al. 1985)

VOLUME_MILK_12_24m_   = ((-0.2049 * AGE_child)+0.4508)/24
(l/h)(Kent 1999)

FRACTION_BF           = (SWITCH_DELIVERY-SWITCH_CHILD_1m) *
breast-feeding        FRACTION_BF_1m &

                      + (SWITCH_CHILD_1m-SWITCH_CHILD_2m) *
                      FRACTION_B F_2 m &

                      +(SWITCH_CHILD_2m-SWITCH_CHILD_3m) *
                      FRACTION_BF_3m &

                      +(SWITCH_CHILD_3m-SWITCH_CHILD_4m) *
                      FRACTION_BF_4m &

                      +(SWITCH_CHILD_4m-SWITCH_CHILD_5m) *
                      FRACTION_BF_5m &

                      +(SWITCH_CHILD_5m-SWITCH_CHILD_6m) *
                      FRACTION_BF_6m &

                      + (SWITCH_CHILD_6m-SWITCH_CHILD_7m) *
                      FRACTION_B F_7m &

                      + (SWITCH_CHILD_7m-SWITCH_CHILD_8m) *
                      FRACTION_B F_8m &

                      + (SWITCH_CHILD_8m-SWITCH_CHILD_9m) *
                      FRACTION_B F_9m &

                      +(SWITCH_CHILD_9m-SWITCH_CHILD_10m) *
                      FRACTION_BF_10m &

                      + (SWITCH_CHILD_10m-SWITCH_CHILD_11m) *
                      FRACTION_B F_11m &

                      +(SWITCH_CHILD_11m-SWITCH_CHILD_12m) *
                      FRACTION_BF_12m &

                      +(SWITCH_CHILD_12m-SWITCH_CHILD_13m) *
                      FRACTION_BF_13m &

                      + (SWITCH_CHILD_13m-SWITCH_CHILD_14m) *
                      FRACTION_B F_14m &

                      +(SWITCH_CHILD_14m-SWITCH_CHILD_15m) *
                      FRACTION_BF_15m &

                      +(SWITCH_CHILD_15m-SWITCH_CHILD_16m) *
                      FRACTION_BF_16m &

                      + (SWITCH_CHILD_16m-SWITCH_CHILD_17m) *
                      FRACTION_B F_17m &

                      + (SWITCH_CHILD_17m-SWITCH_CHILD_18m) *
                      FRACTION_B F_18m &

                      + (SWITCH_CHILD_18m-SWITCH_CHILD_19m) *
                      FRACTION_B F_19m &

                      + (SWITCH_CHILD_19m-SWITCH_CHILD_20m) *
                      FRACTION_B F_20m &

                      + (SWITCH_CHILD_20m-SWITCH_CHILD_21m) *
                      FRACTION_B F_21m &

                      +(SWITCH_CHILD_21m-SWITCH_CHILD_22m) *
                      FRACTION_BF_22m &

                      + (SWITCH_CHILD_22m-SWITCH_CHILD_23m) *
                      FRACTION_B F_23m &

                      +(SWITCH_CHILD_23m-SWITCH_CHILD_24m) *
                      FRACTION_BF_24m

VOLUME_MILK           = (SWITCH_DELIVERY-SWITCH_END_EXCLUSIVE_
                      BREASTFEEDING) * &
                      ((1-SWITCH_CHILD_12m) * VOLUME_MILK_excl_0_12m
                      &

                      +(SWITCH_CHILD_12m-SWITCH_CHILD_24m) *
                      VOLUME_MILK_12_24m ) &

                      +(SWITCH_END_EXCLUSIVE_BREASTFEEDING-SWITCH_
                      END_TOTAL_BREASTFEEDING) * &

                      FRACTION_B F * (((1-SWITCH_CHILD_12m) *
                      VOLUME_
                      MILK_excl_0_12m &

                      +(SWITCH_CHILD_12m-SWITCH_CHILD_24m) *
                      VOLUME_MILK_12_24m))

! Fraction of
lipids in
breast milk
(taken from
Verner et al.
2009)

FRACTION_LIPIDS       = (SWITCH_DELIVERY-SWITCH_END_
_MILK                 TOTAL_BREASTFEEDING)*&
                      (0.0034*LOG (max (0.00001,
                      AGE-Age_delivery))+0.0414)

! Volume of milk
ingested (L/H)

VOLUME_MILK_          ! Milk
excl_0_12m            consumption
                      during exclusive
                      breast-

VOLUME_MILK_12_24m _  ! Milk
(l/h)(Kent 1999       consumption from
                      12 up to 24
                      months

FRACTION_BF           ! Fraction of
breast-feeding        food intake
                      attributable to

VOLUME_MILK           ! Switch
                      exclusive
                      breast-feeding
                      (I/O)

                      ! Volume
                      exclusive bf 0-12
                      months (l/h)

                      ! Volume 12-24
                      months (l/h)

                      ! Switch partial
                      breast-feeding
                      (I/O)

                      ! Fraction
                      exclusive bf 0-12
                      months (l/h)

                      ! Fraction bf
                      12-24 months
                      (l/h)

! Elimination

initial

CONSTANT           = 22776  !  PCB-52         ** Ritter et
HALF_LIFE_PCB52                Half-life      al. 2011
                               (hours)

CONSTANT HAL       = 45552  !  PCB-105        ** Ritter et
F_LIFE_PCB105                  Half-life      al. 2011
                               (hours)

CONSTANT HAL       = 81468  !  PCB-118        ** Ritter et
F_LIFE_PCB118                  Half-life      al. 2011
                               (hours)

CONSTANT           = 94608  !  PCB-138        ** Ritter et
HALF_LIFE_PCB138               Half-life      al. 2011
                               (hours)

CONSTANT          = 126144  !  PCB-153        ** Ritter et
HALF_LIFE_PCB153               Half-life      al. 2011
                               (hours)

CONSTANT HAL      = 135780  !  PCB-170        ** Ritter et
F_LIFE_PCB170                  Half-life      al. 2011
                               (hours)

CONSTANT HAL      = 100740  !  PCB-180        ** Ritter et
F_LIFE_PCB180                  Half-life      al. 2011
                               (hours)

CONSTANT           = 91980  !  PCB-187        ** Ritter et
HALF_LIFE_PCB187               Half-life      al. 2011
                               (hours)

CONSTANT          = 113880  !  DDE Half-life  ** Wolfe et
HALF_LIFE_DDE                  (hours)        al. 2000

CONSTANT           = 43800  !  DDT Half-life  ** Smith et
HALF_LIFE_DDT                  (hours)        al. 1999

CONSTANT           = 52560  !  HCB Half-life  ** To-Figueras
HALF_LIFE_HCB                  (hours)        et al. 1997

end

if(compound.eq. 1) then
HALF_LIFE = HALF_LIFE_PCB52
else if(compound.eq. 2) then
HALF_LIFE = HALF_LIFE_PCB105
else if(compound.eq. 3) then
HALF_LIFE = HALF_LIFE_PCB118
else if(compound.eq. 4) then
HALF_LIFE = HALF_LIFE_PCB138
else if(compound.eq. 5) then
HALF_LIFE = HALF_LIFE_PCB153
else if(compound.eq. 6) then
HALF_LIFE = HALF_LIFE_PCB170
else if(compound.eq. 7) then
HALF_LIFE = HALF_LIFE_PCB180
else if(compound.eq. 8) then
HALF_LIFE = HALF_LIFE_PCB187
else if(compound.eq. 9) then
HALF_LIFE = HALF_LIFE_DDE
else if(compound.eq. 10) then
HALF_LIFE = HALF_LIFE_DDT
else if(compound.eq. 11) then
HALF_LIFE = HALF_LIFE_HCB
end if
! Rates of transfer

RATE_MILK_LIPIDS_INTAKE  = SWITCH_BREASTFEEDING * VOLUME_MILK *
                         FRACTION_LIPIDS_MILK

BREASTMILK_TRANSFER      = C_MOTHER * RATE_MILK_LIPIDS_INTAKE

RAO                      = BW * DOSE/24

ELIMINATION              = A_MOTHER * log(2)/HALF_LIFE

ELIMINATION_child        = SWITCH_DELIVERY * (A_CHILD *
                         1og(2)/HALF_LIFE)

MOTHER_FETUS_TRANSFER    = (SWITCH_CONCEPTION-SWITCH_DELIVERY) *
                         (C_MOTHER)

FETUS_MOTHER_TRANSFER    = (switch_conception-switch_delivery) *
                         (c_child)

! Rates of transfer

RATE_MILK_LIPIDS_INTAKE  ! Rate of milk
                         lipid intake (l
                         lipids/h)

BREASTMILK_TRANSFER      ! Rate of POP
                         intake in
                         children
                         (ug/h)

RAO                      ! Rate of POP
                         intake in
                         mothers (ug/h)

ELIMINATION              ! Elimination
                         rate in
                         mothers

ELIMINATION_child        ! Elimination
                         rate in
                         children

MOTHER_FETUS_TRANSFER    ! Placental
                         diffusion from
                         mother to
                         fetus

FETUS_MOTHER_TRANSFER    ! Placental
                         diffusion from
                         fetus to
                         mother

! Age

RAGE = 1/24./365.                       ! Rate of
                                        increase in
                                        mother's age
                                        (years/h)

AGE = INTEG(RAGE, 0.)                   ! Age of mother
                                        (years)

AGE_child = SWITCH_DELIVERY*(AG         ! Age of child
E-AGE_delivery)                         (years)

FETAI_AGE =                             ! Age of fetus
SWITCH_CONCEPTION*(AGE-AGE_CONCEPTION)  (years)

! SWTICHES
initial
SWITCH_CHILD_1m                     = 0
SWITCH_CHILD_2m                     = 0
SWITCH_CHILD_3m                     = 0
SWITCH_CHILD_4m                     = 0
SWITCH_CHILD_5m                     = 0
SWITCH_CHILD_6m                     = 0
SWITCH_CHILD_7m                     = 0
SWITCH_CHILD_8m                     = 0
SWITCH_CHILD_9m                     = 0
SWITCH_CHILD_10m                    = 0
SWITCH_CHILD_11m                    = 0
SWITCH_CHILD_12m                    = 0
SWITCH_CHILD_13m                    = 0
SWITCH_CHILD_14m                    = 0
SWITCH_CHILD_15m                    = 0
SWITCH_CHILD_16m                    = 0
SWITCH_CHILD_17m                    = 0
SWITCH_CHILD_18m                    = 0
SWITCH_CHILD_19m                    = 0
SWITCH_CHILD_20m                    = 0
SWITCH_CHILD_21m                    = 0
SWITCH_CHILD_22m                    = 0
SWITCH_CHILD_23m                    = 0
SWITCH_CHILD_24m                    = 0
SWITCH_MOTHER_20y                   = 0
SWITCH_CONCEPTION                   = 0
SWITCH_DELIVERY                     = 0
SWITCH_POSTPARTUM_WEIGHT_1          = 0
SWITCH_POSTPARTUM_WEIGHT_2          = 0
SWITCH_BREASTFEEDING                = 1
SWITCH_END_EXCLUSIVE_BREASTFEEDING  = 0
SWITCH_END_TOTAL_BREASTFEEDING      = 0
SWITCH_AGE_CHILD_WEIGHT1            = 0
SWITCH_AGE_CHILD_WEIGHT2            = 0
SWITCH_AGE_CHILD_WEIGHT3            = 0
C_MOTHER_3RULE                      = 0
end

schedule child1m.xn. (0.0833-AGE_child)
discrete child1m
  SWITCH_CHILD_1m = 1
End
schedule child2m.xn. (0.167-AGE_child)
discrete child2m
  SWITCH_CHILD_2m = 1
End
schedule child3m.xn. (0.250-AGE_child)
discrete child3m
  SWITCH_CHILD_3m = 1
End
schedule child4m.xn. (0.333-AGE_child)
discrete child4m
  SWITCH_CHILD_4m = 1
End
schedule child5m.xn. (0.417-AGE_child)
discrete child5m
  SWITCH_CHILD_5m = 1
End
schedule child6m.xn. (0.500-AGE_child)
discrete child6m
  SWITCH_CHILD_6m = 1
End
schedule child7m.xn. (0.583-AGE_child)
discrete child7m
  SWITCH_CHILD_7m = 1
End
schedule child8m.xn. (0.667-AGE_child)
discrete child8m
  SWITCH_CHILD_8m = 1
End
schedule child9m.xn. (0.750-AGE_child)
discrete child9m
  SWITCH_CHILD_2m = 1
End
schedule child10m.xn. (0.833-AGE_child)
discrete child10m
  SWITCH_CHILD_10m = 1
End
schedule child11m.xn. (0.917-AGE_child)
discrete child11m
  SWITCH_CHILD_11m = 1
End
schedule child12m.xn. (1.000-AGE_child)
discrete child12m
  SWITCH_CHILD_12m = 1
End
schedule child13m.xn. (1.0833-AGE_child)
discrete child13m
  SWITCH_CHILD_13m = 1
End
schedule child14m.xn. (1.167-AGE_child)
discrete child14m
  SWITCH_CHILD_14m = 1
End
schedule child15m.xn. (1.250-AGE_child)
discrete child15m
  SWITCH_CHILD_15m = 1
End
schedule child16m.xn. (1.333-AGE_child)
discrete child16m
  SWITCH_CHILD_16m = 1
End
schedule child17m.xn. (1.417-AGE_child)
discrete child17m
  SWITCH_CHILD_17m = 1
End
schedule child18m.xn. (1.500-AGE_child)
discrete child18m
  SWITCH_CHILD_18m = 1
End
schedule child19m.xn. (1.583-AGE_child)
discrete child19m
  SWITCH_CHILD_19m = 1
End
schedule child20m.xn. (1.667-AGE_child)
discrete child20m
  SWITCH_CHILD_20m = 1
End
schedule child21m.xn. (1.750-AGE_child)
discrete child21m
  SWITCH_CHILD_21m = 1
End
schedule child22m.xn. (1.833-AGE_child)
discrete child22m
  SWITCH_CHILD_22m = 1
End
schedule child23m.xn. (1.917-AGE_child)
discrete child23m
  SWITCH_CHILD_23m = 1
End
schedule child24m.xn. (2.000-AGE_child)
discrete child24m
  SWITCH_CHILD_24m = 1
End
schedule mother20y.xn. (20-AGE)
discrete mother20y
  SWITCH_MOTHER_20y = 1
End
schedule conception.xn. (AGE_CONCEPTION-AGE)
discrete conception
  SWITCH_CONCEPTION = 1
End
schedule mothersample.xn. (MOTHER_AGE_SAMPLE-AGE)
discrete mothersample
  C_MOTHER_3RULE = C_MOTHER
End
schedule delivery.xn. (AGE_delivery-AGE)
discrete delivery
  SWITCH_DELIVERY = 1
End
schedule agepostpartumweight1.xn. (AGE_POSTPARTUM_WEIGHT_1-AGE)
discrete agepostpartumweight1
  SWITCH_POSTPARTUM_WEIGHT_1 = 1
End
schedule agepostpartumweight2.xn. (AGE_POSTPARTUM_WEIGHT_2-AGE)
discrete agepostpartumweight2
  SWITCH_POSTPARTUM_WEIGHT_2 = 1
End
if(DURATION_TOTAL_Breastfeeding.eq. 0) then
  SWITCH_BREASTFEEDING = 0
endif
schedule endexclbf.xn. (DURATION_EXCL_Breastfeeding-AGE_child)
discrete endexclbf
  SWITCH_END_EXCLUSIVE_BREASTFEEDING = 1
End
schedule endtotalbf.xn. (DURATION_TOTAL_Breastfeeding-AGE_child)
discrete endtotalbf
  SWITCH_END_TOTAL_BREASTFEEDING = 1
End
schedule agechildweight1.xn. (AGE_CHILD_WEIGHT_1-AGE_child)
discrete agechildweight1
  SWITCH_AGE_CHILD_WEIGHT1 = 1
End
schedule agechildweight2.xn. (AGE_CHILD_WEIGHT_2-AGE_child)
discrete agechildweight2
  SWITCH_AGE_CHILD_WEIGHT2 = 1
End
schedule agechildweight3.xn. (AGE_CHILD_WEIGHT_3-AGE_child)
discrete agechildweight3
  SWITCH_AGE_CHILD_WEIGHT3 = 1
End
! Mass balance differential equations
RA_MOTHER  =                                            ! Rate of
           RAO-ELIMINATION-MOTHER_FETUS_TRANSFER+FETUS  amount in
                                                        maternal
                                                        compartment
                                                        (ug/h)

           _MOTHER_TRANSFER- & BREASTMILK_TRANSFER

A_MOTHER   = INTEG(RA_MOTHER, 0.0)                      ! Amount in
                                                        maternal
                                                        compartment
                                                        (ug)

C_MOTHER   = A_MOTHER/(VOL_FAT_MOTHER)                  !
                                                        Concentration
                                                        in maternal
                                                        lipids (ug/kg
                                                        or ng/g)

RA_CHILD   = MOTHER_FETUS_TRANSFER-FETUS_MOTHER_        ! Rate of
                                                        amount of POPs
                                                        in child
                                                        compartment
                                                        (ug/h)

           TRANSFER- &
           ELIMINATION_child+BREASTMILK_TRANSFER

A_CHILD    = INTEG(RA_CHILD, 0.0)                       ! Amount in
                                                        child
                                                        compartment
                                                        (ug)

C_CHILD    = A_CHILD/(VOL_FAT_CHILD)                    !
                                                        Concentration
                                                        in child
                                                        lipids (ug/kg
                                                        or ng/g)



! Maximum blood concentration in child

initial

MAX_C_CHILD = 0

TMAX_C_CHILD = 0

end

if(C_CHILD>MAX_C_CHILD.AND. AGE_child

>0.AND. AGE_child <3.75)then

MAX_C_CHILD=C_CHILD

TMAX_C_CHILD=AGE_child

Endif
! Area under the curve

AUC_CHILD   =INTEG(C_CHILD, 0.0)
AUC_MOTHER  =INTEG(C_MOTHER, 0.0)

! Save monthly concentrations

initial

C1M   = 0
C2M   = 0
C3M   = 0
C4M   = 0
C5M   = 0
C6M   = 0
C7M   = 0
C8M   = 0
C9M   = 0
C10M  = 0
C11M  = 0
C12M  = 0
C13M  = 0
C14M  = 0
C15M  = 0
C16M  = 0
C17M  = 0
C18M  = 0
C19M  = 0
C20M  = 0
C21M  = 0
C22M  = 0
C23M  = 0
C24M  = 0
C25M  = 0
C26M  = 0
C27M  = 0
C28M  = 0
C29M  = 0
C30M  = 0
C31M  = 0
C32M  = 0
C33M  = 0
C34M  = 0
C35M  = 0
C36M  = 0
C37M  = 0
C38M  = 0
C39M  = 0
C40M  = 0
C41M  = 0
C42M  = 0
C43M  = 0
C44M  = 0
C45M  = 0
end
schedule c1mrecord.xn. (0.083-AGE_Child)
discrete c1mrecord
C1M = C_CHILD
end
schedule c2mrecord.xn. (0.167-AGE_Child)
discrete c2mrecord
C2M = C_CHILD
end
schedule c3mrecord.xn. (0.250-AGE_Child)
discrete c3mrecord
C3M = C_CHILD
end
schedule c4mrecord.xn. (0.333-AGE_Child)
discrete c4mrecord
C4M = C_CHILD
end
schedule c5mrecord.xn. (0.417-AGE_Child)
discrete c5mrecord
C5M = C_CHILD
end
schedule c6mrecord.xn. (0.500-AGE_Child)
discrete c6mrecord
C6M = C_CHILD
end
schedule c7mrecord.xn. (0.583-AGE_Child)
discrete c7mrecord
C7M = C_CHILD
end
schedule c8mrecord.xn. (0.667-AGE_Child)
discrete c8mrecord
C8M = C_CHILD
end
schedule c9mrecord.xn. (0.750-AGE_Child)
discrete c9mrecord
C9M = C_CHILD
end
schedule c10mrecord.xn. (0.833-AGE_Child)
discrete c10mrecord
C10M = C_CHILD
end
schedule c11mrecord.xn. (0.917-AGE_Child)
discrete c11mrecord
C11M = C_CHILD
end
schedule c12mrecord.xn. (1.0-AGE_Child)
discrete c12mrecord
C12M = C_CHILD
end
schedule c13mrecord.xn. (1.083-AGE_Child)
discrete c13mrecord
C13M = C_CHILD
end
schedule c14mrecord.xn. (1.167-AGE_Child)
discrete c14mrecord
C14M = C_CHILD
end
schedule c15mrecord.xn. (1.250-AGE_Child)
discrete c15mrecord
C15M = C_CHILD
end
schedule c16mrecord.xn. (1.333-AGE_Child)
discrete c16mrecord
C16M = C_CHILD
end
schedule c17mrecord.xn. (1.417-AGE_Child)
discrete c17mrecord
C17M = C_CHILD
end
schedule c18mrecord.xn. (1.500-AGE_Child)
discrete c18mrecord
C18M = C_CHILD
end
schedule c19mrecord.xn. (1.583-AGE_Child)
discrete c19mrecord
C19M = C_CHILD
end
schedule c20mrecord.xn. (1.667-AGE_Child)
discrete c20mrecord
C20M = C_CHILD
end
schedule c21mrecord.xn. (1.750-AGE_Child)
discrete c21mrecord
C21M = C_CHILD
end
schedule c22mrecord.xn. (1.833-AGE_Child)
discrete c22mrecord
C22M = C_CHILD
end
schedule c23mrecord.xn. (1.917-AGE_Child)
discrete c23mrecord
C23M = C_CHILD
end
schedule c24mrecord.xn. (2.0-AGE_Child)
discrete c24mrecord
C24M = C_CHILD
end
schedule c25mrecord.xn. (2.083-AGE_Child)
discrete c25mrecord
C25M = C_CHILD
end
schedule c26mrecord.xn. (2.167-AGE_Child)
discrete c26mrecord
C26M = C_CHILD
end
schedule c27mrecord.xn. (2.250-AGE_Child)
discrete c27mrecord
C27M = C_CHILD
end
schedule c28mrecord.xn. (2.333-AGE_Child)
discrete c28mrecord
C28M = C_CHILD
end
schedule c29mrecord.xn. (2.417-AGE_Child)
discrete c29mrecord
C29M = C_CHILD
end
schedule c30mrecord.xn. (2.500-AGE_Child)
discrete c30mrecord
C30M = C_CHILD
end
schedule c31mrecord.xn. (2.583-AGE_Child)
discrete c31mrecord
C31M = C_CHILD
end
schedule c32mrecord.xn. (2.667-AGE_Child)
discrete c32mrecord
C32M = C_CHILD
end
schedule c33mrecord.xn. (2.750-AGE_Child)
discrete c33mrecord
C33M = C_CHILD
end
schedule c34mrecord.xn. (2.833-AGE_Child)
discrete c34mrecord
C34M = C_CHILD
end
schedule c35mrecord.xn. (2.917-AGE_Child)
discrete c35mrecord
C35M = C_CHILD
end
schedule c36mrecord.xn. (3.0-AGE_Child)
discrete c36mrecord
C36M = C_CHILD
end
schedule c37mrecord.xn. (3.083-AGE_Child)
discrete c37mrecord
C37M = C_CHILD
end
schedule c38mrecord.xn. (3.167-AGE_Child)
discrete c38mrecord
C38M = C_CHILD
end
schedule c39mrecord.xn. (3.250-AGE_Child)
discrete c39mrecord
C39M = C_CHILD
end
schedule c40mrecord.xn. (3.333-AGE_Child)
discrete c40mrecord
C40M = C_CHILD
end
schedule c41mrecord.xn. (3.417-AGE_Child)
discrete c41mrecord
C41M = C_CHILD
end
schedule c42mrecord.xn. (3.500-AGE_Child)
discrete c42mrecord
C42M = C_CHILD
end
schedule c43mrecord.xn. (3.583-AGE_Child)
discrete c43mrecord
C43M = C_CHILD
end
schedule c44mrecord.xn. (3.667-AGE_Child)
discrete c44mrecord
C44M = C_CHILD
end
schedule c45mrecord.xn. (3.750-AGE_Child)
discrete c45mrecord
C45M = C_CHILD
end
END ! DERIVATIVE
END ! DYNAMIC
END ! PROGRAM
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Publication:Environmental Health Perspectives
Article Type:Table
Date:Jan 1, 2013
Words:3861
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