Pharmacokinetic concepts in assessing intake of pentachlorophenol by rats after exposure through drinking water.
The objective of this study was to predict concentrations of a toxicant in plasma after exposure to the toxicant through drinking water using basic pharmacokinetic principles. As an example, we studied pentachlorophenol (PCP), a widely used wood preservative of public health concern as an environmental pollutant. We added PCP to the drinking water (30 micrograms/mL) of five rats for 3 days. Blood was sampled, and water consumption was monitored every 12 h on the days 1 and 2 and every 3 h on day 3. After a 4-day washout, a PCP dose of 2.5 mg/kg was given intravenously, and blood was withdrawn at selected times for 2 days. PCP concentrations in plasma were measured by capillary gas chromatography. A one-compartment model with zero-order input and kinetic parameters (clearance, volume of distribution, and bioavailability) estimated after intravenous administration adequately predicted PCP concentrations in plasma during exposure to PCP. The average steady-state concentration (Css), which reflects the overall exposure, was predicted using the clearance (CL) concept [i.e., Css = (bioavailability.rate of intake)/CL] and compared with the observed value. The data for PCP demonstrate the potential utility of CL and other kinetic concepts in assessing exposure to a toxicant in drinking water, food, or air.
Reigner
B G
BG
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446.
Gungon
R A
RA
Bois
F Y
FY
Zeise
L
L
Tozer
T N
TN
D000284:Administration, Oral; D000818:Animals; D007262:Infusions, Intravenous; D008297:Male; D008954:Models, Biological; D010416:Pentachlorophenol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014881:Water Supply
D010416:Pentachlorophenol