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The Impact of Pesticides - Academy Publish

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absorbed NOEL dose was estimated. Simulated urinary amounts <strong>of</strong> thesemetabolites in 24-h collections considering an 8-h dermal exposure to a totalabsorbed dose equivalent to the daily absorbed NOEL dose were proposed as BRVs.With these considerations, BRV values <strong>of</strong> 26 and 45 nmol/kg bw were obtained,respectively, for 3,5,6-TCP and APs in 24-h urine collections (Bouchard et al.,2005).<strong>The</strong> BRVs were applied to practical situations, and hence were used to assess theimportance <strong>of</strong> exposure and potential effects in the groups <strong>of</strong> workers assessed bySamuel et al. (2002) and Fenske and Elkner (1990). In both studies, total amounts <strong>of</strong>3,5,6-TCP in 24-h urine collections were quantified in greenhouse workersfollowing the onset <strong>of</strong> an application <strong>of</strong> CPF or manipulation <strong>of</strong> treated plants(Samuel et al., 2002), or in workers exposed to CPF following structural controltreatment <strong>of</strong> houses (Fenske and Elkner, 1990). As displayed in Table 3, the workers<strong>of</strong> these studies presented 3,5,6-TCP values in 24-h urine collections lower than theproposed BRV.ParathionParathion (O,O-diethyl O-p-nitrophenyl phosphorothioate, CAS 56-38-2) is a potentnon-systemic insecticide and acaricide with some fumigant action. Like other OPinsecticides, it exerts its neurotoxic action by inhibiting nervous system AChEactivity, both in insects and humans (Sidell, 1994; Maroni et al., 2000a; Gosselin etal., 2004). Although there are now application restrictions due to its high toxicity,the use <strong>of</strong> parathion is still a concern in many countries (Denga et al., 1995;Akgur et al., 1999).<strong>The</strong> ACGIH ® and the GCIHH ® (German Commission for the Investigation <strong>of</strong>Health Hazards <strong>of</strong> Chemical Compounds in the Work Area) proposed a 30%inhibition <strong>of</strong> RBC-AChE activity compared to the individual’s baseline as abiological reference value. A more specific biological reference value based onurinary concentration <strong>of</strong> p-nitrophenol (p-NP) parathion metabolite in a spot urinesample has also been proposed, given that it is detectable in urine far before anyinhibition <strong>of</strong> enzymatic activity occurs (Arterberry et al., 1961; Richter et al., 1992).<strong>The</strong> ACGIH BEI ® value was set to 0.5 mg <strong>of</strong> p-NP/g <strong>of</strong> creatinine (0.34 mmol p-NP/mol creatinine) while the GCIHH BAT ® value was established at 0.5 mg <strong>of</strong> p-NP/L <strong>of</strong> urine. However, parathion is eliminated through the kidneys by glomerularfiltration or active secretion (Michalke, 1984; Jokanovic, 2001), such that its urinaryconcentration decreases with increasing urinary flow rate (Boeniger et al., 1993) andis thus subject to significant variations with time. A more reliable sampling strategythan spot urine samples is to quantify total amounts <strong>of</strong> metabolites excreted in urineover given time periods (Woollen, 1993; Ross et al., 2001). In this perspective,Gosselin et al. (2004) developed a toxicokinetic model to absorbed doses <strong>of</strong>parathion to urinary biomarker measurements and to propose, using modelpredictions, BRVs for parathion metabolites, p-NP and APs, in the form <strong>of</strong>cumulative amounts <strong>of</strong> urinary metabolites following the onset <strong>of</strong> an occupationalexposure (Figure 4B).Again, the model is based on knowledge on biotransformation pathways <strong>of</strong>parathion. After systemic absorption, it is either rapidly hydrolyzed to p-NP andDETP or oxidized to paraoxon in the liver mainly, or stored in lipids. Paraoxonrepresents 20% <strong>of</strong> the biotransformation while the hydrolysis constitutes 80% <strong>of</strong> thebiotransformed parathion (Poore and Neal, 1972; Hayes, 1982; Jokanovic, 2001).<strong>Academy</strong><strong>Publish</strong>.org - <strong>The</strong> <strong>Impact</strong> <strong>of</strong> <strong>Pesticides</strong>113

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