Table 3.
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 |
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 |
BBt+Δt = BBt + Δt(famDImat,t − kelim × 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 |
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 |
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 |
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,t+Δt = BBINF,t + Δt(faiDIINF,t − kelim,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. |