The Impact of Pesticides - Academy Publish

ut it is a minor metabolite of folpet and only a very small fraction reaches bloodunchanged following an oral or dermal exposure.APPLICATION TO A CHILDREN POPULATIONThe toxicokinetic modeling approach previously described for occupational exposureto pesticides is also applicable to an environmental exposure of the general population.However, the approach requires some specific considerations. Contrary tooccupational exposure, the exact route, source and onset of an environmental exposureto pesticides, leading to a given set of population biomonitoring data, are generallyunknown. This is because there may be an exposure to multiple unidentifiedpesticides, that may or not share the same mechanism of action, and this may occur atvarying moments of the day and for different combinations of exposure routes (e.g.oral, inhalation, dermal). To account for these uncertainties, assumptions need to bemade in order to perform a health-based interpretation of biomonitoring data. This wasrecently done by Valcke and Bouchard (2009) with regard to OP exposure in achildren population for which urinary concentrations of AP metabolites measured infirst morning voids were available (Valcke et al., 2006).First, as the specific pesticides to which the children under study were exposed wereunknown, these authors assumed that all the methylphosphate (MP) metabolitesoriginated from an exposure to malathion only, whereas all the ethylphosphate (EP)metabolites stemmed from an exposure to CPF. These two assumptions were madebased on the following elements (Valcke and Bouchard, 2009): CPF and malathion were among the OPs to which the studiedpopulation was most likely exposed at the time of sampling; the availability of appropriate chemical-specific toxicokinetic modelsfor those OPs; the accessibility of human NOELs for these two pesticides (thusprecluding the need for uncertain animal-to-human extrapolation), thatare based on the inhibition of RBC-AChE activity, which is moresensitive to OP inhibition than the nervous system AChE, responsiblefor the toxic effect of OPs; the rather small NOEL values for malathion and CPF as compared tothose of other OPs, providing greater safety given that at least part ofthe measured metabolites likely result from the biotransformation ofother less toxic OPs.Valcke and Bouchard (2009) then used the toxicokinetic models for malathion(Bouchard et al., 2003) and CPF (Bouchard et al., 2005) to generate “NOELbiomarkerequivalents” (NBEs) corresponding to amounts of MP/EP metabolites in anovernight urine collection, expressed in nmol/kg bw. Hence, these authors simulatedthe time course of the targeted urinary metabolites for various dermal or oral exposurescenarios to the relevant NOELs. They also compensated for the uncertaintyassociated with the elapsed time between the onset of the exposure and the morningcollection of the urinary samples in the investigated children. Indeed, simulationsperformed with the models had previously shown that the lowest, thus mostconservative, excretion values of AP urinary metabolites were obtained considering adermal exposure scenario. On the other hand, urinary OP metabolites in children aregenerally attributed to dietary exposure (Fenske et al., 2002; Curl et al., 2003; Lu etal., 2005; Valcke et al., 2006; Lu et al., 2008). Thus, to obtain a range of conservativeNBEs that would encompass all the possible exposure regimens in children, threeAcademyPublish.org - The Impact of Pesticides119