The Impact of Pesticides - Academy Publish

Based on these available published human data along with data of May et al. (1992)on plasma concentration-time course of carbaryl in volunteers, Bouchard et al.(2008) developed a carbaryl-specific toxicokinetic model (Figure 5). This modelrelates the absorbed dose of carbaryl, the evolution of its body burden and that of itsmetabolites to the cumulative urinary amounts of biomarkers excreted over giventime periods. Specific input compartments were introduced in the model to simulateabsorption through the skin (slow release into the blood stream) and the GI tract;inhalation exposure was considered kinetically similar to a constant intravenous (iv)exposure, and was thus modeled by direct inputs to the blood compartment. Themodel is also comprised of a blood compartment to represent total carbaryl burdenin blood and tissues in dynamical equilibrium with blood; separate metabolitecompartments to describe independently the body burden of the relevant carbarylmetabolites, namely 1-naphthol, 4-(hydroxyl)-1-naphtyl-N-methylcarbamate andnon-monitored carbaryl metabolites; specific excretion compartments to representcumulative amounts of each urinary carbaryl metabolite, that is one compartmentfor the sum of free and conjugated 1-naphtol, one for 4-(hydroxyl)-1-naphtyl-Nmethylcarbamateand another to describe excretion of non-monitored or nonobservedmetabolites in urine. Unlike OP models, as observed time courses ofmetabolites in urine decreased linearly, no storage compartment was added in thismodel (Bouchard et al., 2008).To determine a BRV for 1-naphthol in 24-h urine collections in order to preventcholinergic effects in workers exposed to carbaryl, the available repeated-exposureNOEL dose of 0.06 mg/kg/day (0.3 µmol/kg/day) was used (Wills et al., 1968) andcorresponding daily absorbed NOEL dose was estimated. The latter then served tosimulate a typical 8-h dermal exposure in workers to a total absorbed dosecorresponding to this daily absorbed NOEL dose. Corresponding 1-naphtholexcretion in 24-h collections following the onset of exposure was proposed as aBRV and was established at 32 nmol/kg bw/day (Bouchard et al., 2008).The proposed BRV was subsequently applied to occupational exposure situations,and total amounts of 1-naphthol excreted in the 24-h urine of greenhouse workersexposed to carbaryl reported in two studies (Samuel et al., 2002; Bouchard et al.,2008) was compared to the suggested reference value. Bouchard et al. (2008)quantified total amounts of 1-naphthol in 24-h urine collections following the onsetof a carbaryl application or the beginning of work in treated area. Similarly, Samuelet al. (2002) determined 24-h urinary amounts of 1-naphthol in individuals whohandled plants or flowers treated with carbaryl. In both studies, all workers exceptone exhibited 1-naphthol values below the proposed BRV (Table 3).Overall, comparison of the different proposed BRVs for specific urinary biomarkersof chlorpyrifos, malathion, parathion and carbaryl showed that values are similar inall cases as presented in Table 2. Likewise, values for non-specific metabolites, suchas APs, are also in the same range although toxicokinetic models are specific to eachinsecticide. Nonetheless, to suitably assess occupational exposure, BRVs forspecific metabolites should be preferred to those of non-specific biomarkers,although the latter may provide valuable information on overall OP exposure.Phthalimide-like fungicidesFungicides constitute a large class of chemical substances frequently used inagriculture and horticulture, especially captan (N-(trichloromethylthio)-4-AcademyPublish.org - The Impact of Pesticides115