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Title: Pharmacokinetic concepts in assessing intake of pentachlorophenol by rats after exposure through drinking water.

Authors: Reigner, B G; Gungon, R A; Bois, F Y; Zeise, L; Tozer, T N

Published In J Pharm Sci, (1992 Nov)

Abstract: 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 After a 4-day washout, a PCP dose of 2.5 mg/kg was given intravenously, and blood was withdrawn at selected times for 2 days.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.

PubMed ID: 1447716 Exiting the NIEHS site

MeSH Terms: Administration, Oral; Animals; Infusions, Intravenous; Male; Models, Biological; Pentachlorophenol/administration & dosage; Pentachlorophenol/blood; Pentachlorophenol/pharmacokinetics*; Pentachlorophenol/toxicity; Rats; Rats, Sprague-Dawley; Water Supply*

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