The Impact of Pesticides - Academy Publish

Paraoxon is then either metabolized by an A-esterase into p-NP and DEP, or it bindsto proteins such as AChE (less than 20%) (Hayes, 1982; Jokanovic, 2001). Themetabolites p-NP and APs, i.e. DETP and DEP, are eliminated in urine and faeces.The model and its parameter values is also based on available data on the kinetics ofparathion and its metabolites in volunteers (Hartwell et al., 1964; Hayes et al., 1964;Maibach et al., 1971; Feldmann and Maibach, 1974; Morgan et al., 1977). Themodel consists of specific inputs to describe amounts of parathion bioavailable atthe skin surface, GI tract or respiratory tract; a body compartment to represent tissueburdens of parathion and paraoxon that rapidly reach and maintain a fixed ratio withblood burden; a storage compartment to characterize storage tissue burdens ofparathion and paraoxon that are slowly returned to blood; specific metabolitecompartments for p-NP or AP metabolites (the sum of DETP and DEP) in blood andin tissues in dynamic equilibrium with blood; retention compartments which delaysexcretion of p-NP or APs in urine; urinary and faecal compartments to representseparately cumulative excretion of total p-NP or APs in urine and faeces,respectively.Simulations were then performed to propose BRVs for p-NP and APs in urine usingan 8-h dermal scenario to a total dose corresponding to an available repeatedexposureNOEL dose of 4.8 mg/day (i.e., 58 µg/day/kg bw). The NOEL wasdetermined from the volunteer studies of Edson et al., (1964) and Rider et al. (1969)based on the inhibition of plasma-ChE or RBC-AChE. BRVs for p-NP and APs of 6and 2 nmol/kg bw, respectively, were derived in 12-h urine collections and 24 and15 nmol/kg bw, respectively, in 24-h urine samples. These values are expressed ascumulative amounts in urine over given time periods following the onset of anexposure episode.The suggested BRV value for p-NP may be considered protective on the basis ofresults obtained by Hayes et al. (1964) in volunteers exposed to parathion andshowing no significant inhibition of RBC-AChE (0%) and plasma-ChE (6%)activities at p-NP value of 15.9 µmol in 24-h urine collections (i.e. 24 nmol/kg bwassuming a body weight of 70 kg). The current applicability of these proposedBRVs to practical biomonitoring situations is difficult due to limits of the usage ofparathion in the USA since 1991 and increased parathion handling andpostapplication restrictions (EPA, 1999a).CarbarylCarbaryl (1-naphthyl methylcarbamate, CAS 63-25-2) is a contact insecticide of thecarbamate family, which inhibits ChE activity in humans. Most studies in exposedworkers measured ChE activity and the ACGIH recommends a RBC-AChE activityof 70% of the individual’s baseline as a BEI ® (ACGIH, 2011) while no biologicalreference value based on urinary biomarkers were proposed.The main urinary carbaryl metabolite in humans is 1-naphthol (over 85%) while 4-(hydroxy)-1-naphthyl N-,ethyl carbamate (free or glucurono-conjugate), 1-naphthylglucuronideand 1-naphthyl-sulfate are minor urinary metabolites (Knaak et al.,1965; Kozbelt, 1968; Chin et al., 1974; Feldmann and Maibach, 1974). 1-Naphtholis rapidly excreted in urine mostly within 24-h after absorption and mainly asglucurono- and sulfo-conjugates.AcademyPublish.org - The Impact of Pesticides114