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. Author manuscript; available in PMC: 2015 Aug 1.
Published in final edited form as: Crit Rev Toxicol. 2014 Aug;44(7):600–617. doi: 10.3109/10408444.2014.926306

Table 3.

Model parameters used in model simulations 1 for HCB in rats

Model
parameter
(units)
Variable Parameter
value
Comments
HCB dose
administered to
dam (mg/kg bw-
day)
DImat(t);
DImat,t
1 Assumption
Time step (days) Δt 0.5 Assumption
To minimize uncertainty introduced by using an
algebraic equation to solve a differential equation, Δt
should be much smaller than t1/2.
Fraction of
ingested HCB
absorbed by the
rat dam
(dimensionless)
fam 0.8 Koss and Koransky (1975)
HCB half-life in
rats (days)
t1/2 80 Yesair et al. (1986)
First order
elimination rate
constant for
HCB (day−1)
kelim 0.0087 kelim=ln(2)t21
If an offspring-specific t1/2 value is available, separate
kelim values may be calculated for the dam and the pup
(i.e. kelim and kelim,INF).
For this example, t1/2 of HCB in the offspring is
unknown, and only one kelim value was calculated
using a t1/2 reported for HCB in adult female rats.
Also for this example, kelim was used to describe
maternal HCB elimination during 3 weeks of gestation
but was replaced with kelac (defined below) for
elimination during 3 weeks of lactation.
Dam HCB body
burden (mg/kg)
BB(t);
BBt+Δt;
BBt
calculated BBtt = BBt + Δt(famDImat,tkelim × BBt)
Iterated over time for 3 weeks of gestation and 3 weeks
of lactation. BBt+Δt is body burden at the current time
step, and BBt is body burden at the previous time step.
BBt is assumed to be 0 at the first time step.
Fraction of HCB
stored in
maternal
adipose tissue
(dimensionless)
ff 0.9 Assumption
Fraction of
dam’s weight
that is fat (kg
fat/kg bw)
ffm 0.09 Fisher et al. (1990)
HCB
concentration in
milk fat (mg/kg
milk fat)
Cmilk fat,t calculated Cmilkfat,t=BBt×ffffm
Iterated over time for 3 weeks of lactation
Litter size
(number of
pups)
LS 10 Assumption
Pup ingestion
rate, week 1 (kg
milk/day)
CRmilk,t 0.0030 Calculated from experimentally determined milk
production values of 29.7, 54.3, and 59.1 g/rat/day
measured on lactation days 2, 7, and 14, respectively,
divided by 10 to get per pup ingestion rates (Knight,
Docherty, and Peaker, 1984)
Pup ingestion
rate, week 2 (kg
milk/day)
0.0054
Pup ingestion
rate, week 3 (kg
milk/day)
0.0059
Fraction of fat in
milk
(dimensionless)
fmbm 0.15 Welch and Findlay (1981)
Dam weight
during lactation
(kg)
BWmat 0.273 Knight et al. (1984)
Elimination rate
of HCB in dam
during lactation
(days−1)
kelac calculated kelac=kelim+CRmilk,t×ff×fmbm×LSffm×BWmat
Iterated over time for 3 weeks of lactation
Pup body
weight, week 1
(kg)
BWINF,t 0.0066 Knight et al. (1984) presented litter weights at different
time points in a figure. This figure was digitized using
the GetData Graph Digitizer (2008), and the values
were divided by 10 pups per litter to get average pup
body weights on lactation days 2, 7, and 14.
Pup body
weight, week 2
(kg)
0.014
Pup body
weight, week 3
(kg)
0.028
Offspring
lactational HCB
dose (mg/kg bw-
day)
DIINF,t calculated DIINF,t=(Cmilkfat,t×fmbm)×CRmilk,tBWINF,t
Iterated over time for 3 weeks of lactation
Fraction of
ingested HCB
absorbed by the
rat pup
(dimensionless)
fai 0.8 Assumption
Offspring HCB
body burden
(mg/kg)
BBINF,t+δt;
BBINF,t
calculated BBINF,tt = BBINF,t + Δt(faiDIINF,tkelim,INF × BBINF,t)
Iterated over time for 3 weeks of lactation. Iterations
may be extended to include time after lactation, with
appropriate adjustments to DIINF,t. DIINF,t = 0 after
lactation unless exposure to offspring continues via an
alternate (i.e. non-lactational) source.