The Impact of Pesticides - Academy Publish

greenhouse workers exposed to malathion following a spraying episode or work in atreated area (Bouchard et al., 2003). As depicted in Table 3, urinary values of MCAand DCA in the workers under study ranged between 1.7 and 21% of the proposedBRV for MCA and 1.1 to 32% of the BRV for DCA. Similar results were obtainedwhen comparing biomonitoring results of Márquez et al. (2001) on measured totalamounts of MCA excreted over a 24-h period in three Spanish greenhouse workersfollowing application of malathion (31.7, 8.6, and 6.3 nmol/kg, considering a bodyweight of 70 kg) with the proposed BRVs (Table 3).ChlorpyrifosChlorpyrifos (O,O-diethyl-O-3,5,6-trichloro-2-pyridylphosphorothioate, CAS2921-88-2) is a non-systemic insecticide used to control a wide range of insectpests. Toxicity is induced by chlorpyrifos (CPF) bioactivation product, CPF-oxon,which is an AChE inhibitor (Namba et al., 1971; Huff et al., 1994; Sultatos, 1994).According to studies in animals and humans, CPF is nearly completely metabolizedto 3,5,6-trichloro-2-pyridinol (3,5,6-TCP) and AP metabolites, i.e. diethylthiophosphate (DETP) and diethyl phosphate (DEP), whatever the route-of-entry.These metabolites are then essentially excreted in urine (Bakke et al., 1976; Nolanet al., 1984; Griffin et al., 1999). Several studies in field workers assessed CPFexposure by measuring urinary 3,5,6-TCP as a specific biomarker, and DETP andDEP as non specific biomarkers (Jitsunari et al., 1989; Fenske and Elkner, 1990;Cocker et al., 2002).Considering this biotransformation data along with available kinetic time courses involunteers, Bouchard et al. (2005) developed a chlorpyrifos-specific toxicokineticmodel (Figure 4A). Similar to malathion model, this model describes thebiodisposition kinetics of CPF and its metabolites in humans with a minimumnumber of compartments and parameters. It allows predicting the time courses ofCPF and its metabolites under different exposure routes (oral, dermal and/orinhalation) and temporal scenarios (single or repeated intermittent or continuousexposures). The parameters were established using the data of Nolan et al. (1984)and Drevenkar et al. (1993) in individuals orally exposed to CPF. The modelincludes specific inputs to represent the amounts of CPF bioavailable at each site-ofentry(skin, gastro-intestinal tract, respiratory tract), a specific body compartment todescribe the CPF blood burden (i.e. arterial and venous blood including tissueblood), a storage compartment to represent CPF in lipids or reversibly bound totissue proteins, two metabolite compartments to represent distinctly the body burdenof 3,5,6-TCP and AP metabolites, and two urinary compartments to representseparately the cumulative urinary excretions of 3,5,6-TCP and AP metabolites.Furthermore, based on the study of Smith et al. (1967), the model considers thateach mole of CPF in the body is eventually broken down into one mole of 3,5,6-TCP and one mole of AP, and metabolite excretion occurs only through the renalroute. The model was validated using the data of Nolan et al. (1984) in dermallyexposed individuals (on the forearm), and the data of Brzak (2000) and Griffin et al.(1999) in orally exposed subjects.As was done for malathion, the model then served to estimate BRVs for 3,5,6-TCPand AP metabolites in urine. The available repeated-exposure NOEL dose of 0.1mg/kg/day of chlorpyrifos (20 µmol/day for a 70 kilogram individual), which didnot induce significant inhibition of RBC-AChE activities, was used (Coulston et al.,1972; McCollister et al., 1974; Mattsson et al., 2001), and the corresponding dailyAcademyPublish.org - The Impact of Pesticides112