Pharmacokinetics of 3, 5, 6-trichloro-2-pyridinol (TCPY), a chlorpyrifos metabolite, in rat saliva.
Smith-JN; Wang-J; Lin-Y; Timchalk-C
Toxicologist 2010 Mar; 114(1):397
Novel non-invasive techniques are being developed for biological monitoring (biomontitoring) of a variety of potential toxicants, including pesticides like chlorpyrifos (CPF); and saliva has been suggested as an ideal body fluid to biomonitor. In order to be acceptable, there is a need to understand salivary pharmacokinetics of CPF metabolites for extrapolation of saliva measurements to whole body exposures. In this context, in vivo pharmacokinetics of 3,5,6-trichloro-2-pyridinol (TCPy), a major metabolite of CPF, was quantitatively evaluated in rat saliva. Experimental results suggest that TCPy partitioning from plasma to saliva in rats is relatively constant over a range of varying physiological conditions. TCPy pharmacokinetics were very similar in blood and saliva (area under the curve (AUC) values were proportional and elimination rates ranged from 0.007 to 0.019 h-1) and saliva/blood TCPy concentration ratios were not affected by TCPy concentration in blood (p = 0.35) or saliva flow rate (p = 0.26). The TCPy concentration in saliva was highly correlated to the amount of unbound TCPy in plasma (r = 0.96), and the amount TCPy protein-binding in plasma was substantial (98.5%). The median saliva/blood concentration ratio (0.049) was integrated as a saliva/blood TCPy partitioning coefficient within an existing physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF. The model accurately predicted TCPy concentrations in saliva over a range of blood concentrations. These studies suggest that saliva TCPy concentration can be utilized to ascertain CPF exposure, and it is envisioned that the PBPK/PD can likewise be used to estimate CPF dosimetry based on the quantitation of TCPy in spot saliva samples obtained from biomonitoring studies.
Agricultural-chemicals; Airborne-particles; Biochemistry; Biohazards; Biological-effects; Biological-monitoring; Blood-analysis; Blood-sampling; Chemical-hypersensitivity; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Laboratory-animals; Laboratory-testing; Particle-aerodynamics; Particulates; Physiological-chemistry; Physiological-effects; Physiological-measurements; Physiological-response; Physiological-testing; Pulmonary-system; Quantitative-analysis; Salivary-glands; Statistical-analysis; Toxic-effects
Agriculture, Forestry and Fishing; Research Tools and Approaches: Exposure Assessment Methods
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah
Battelle Pacific Northwest Laboratories