Reference no: EM132459044

Question 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.

Question 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):

Question 3. List as many possible mechanisms as you can think of that could be partly responsible for the changes observed Explain how each of your listed mechanisms could contribute to the observed changes.