zero order absorption

Toxicokinetics

PHCL 4760/5760

Homework Assignment #7

One-Compartment Zero-Order Absorption Homework

DUE: Tuesday, October 2, 2018 at start of class

1. An 84 kg University of Toledo groundskeeper who is spraying a 100 mg/L solution of the

insecticide dieldrin (MW = 381; logP = 4.56) on some trees exposes 100 cm2 of his skin to the

solution over a 4 hr period. Dieldrin has a half-life of about 6 months, a volume of distribution of

about 40 L/kg, and a dermal permeability of about 3 x 10-6 cm/sec.

(a) Estimate the absorption rate during the exposure period assuming the blood concentration is

much lower than the skin concentration (i.e., take the blood level to be zero in the skin

absorption equation).

(b) Estimate how it takes after exposure begins for the groundskeeper’s plasma dieldrin levels to

reach 1 ng/L.

(c) Estimate the maximum plasma dieldrin concentration in ng/L that will occur in this

groundskeeper due to this exposure.

(d) Estimate how long it will take after exposure ends for the groundskeeper’s plasma dieldrin

levels to drop back down to 1 ng/L.

2. In the example problems performed in class, parameters were estimated from rat plasma toluene

levels measured during and after a 4 hr exposure to 100 ppm toluene. These measurements were

made without any other contaminating gases in the rat’s environment. The same researchers

made identical measurements in rats during a 4 hr exposure to 100 ppm toluene in an

environment that also contained 100 ppm m-xylene and 100 ppm ethylbenzene. The plasma

toluene levels under these conditions were as follows:

Time, t

(hr)

Concentration

(mg/L)

0.00 0.000

0.25 0.250

0.50 0.465

1.00 0.809

2.00 1.253

3.00 1.496

4.00 1.630

4.08 1.565

4.50 1.176

5.00 0.783

5.50 0.531

6.00 0.361

Assuming the toluene uptake rate is the same as used in the in-class example (1.4 mg/hr),

perform the following analyses.

(a) Using the post-exposure data (t ≥ 4hr), estimate k, t1/2, V, and CL for toluene under these

gas mixture conditions.

(b) Using the data collected during the exposure period (t ≤ 4 hr), estimate the same

parameters. Assume Css equals the concentration at 4 hr.

(c) Determine the AUC under these conditions, and calculate V and CL by the AUC method.

(d) Compare these results to those determined in the class examples for the toluene-only

exposure. What parameters are the same and what parameters are significantly different for

the mixture versus only toluene?

Graduate Students Only (PHCL 5760):

3. List as many possible mechanisms as you can think of that could be partly responsible for the

changes observed in Problem #2. Explain how each of your listed mechanisms could contribute

to the observed changes.