Chlorpyrifos determining exposure

Assessments of risks associated with the use of chlorpyrifos insecticide products for workers have been made. The assessments are based on the results of field studies conducted in citrus groves, a Christmas tree farm, cauliflower and tomato fields, and greenhouses that utilized both passive dosimetry and biomonitoring techniques to determine exposure. The biomonitoring results likely provide the best estimate of absorbed dose of chlorpyrifos, and these have been compared to the acute and chronic no observed effect levels (NOELs) for chlorpyrifos. Standard margin-of-exposure (MOE) calculations using the geometric mean of the data are performed however, probability (Student s f-test) and distributional (Monte Carlo simulation) analyses are deemed to provide more realistic evaluations of exposure and risk to the exposed population. 

In order to determine the dermal exposure of volunteers to chlorpyrifos, the penetration of chlorpyrifos through the outer whole-body dosimeter (coveralls) to the inner body dosimeter (t-shirt and briefs) was measured. The penetration factor was calculated for each volunteer in the study from the experimental data by dividing the amount of chlorpyrifos on the t-shirt and brief sample by the amount of chlorpyrifos on the torso section of the coveralls. This method of calculation assumes that the surface area of the torso section of the coveralls is nearly the same as the surface area of the t-shirt and briefs worn directly under the torso section of the coveralls. A mean penetration factor for each worker type was calculated by averaging all the worker volunteer... 

A total of 10,000 iterations or calculations of dose were performed as part of this simulation, and Figure 4 shows the resulting distribution of average daily doses of chlorpyrifos as determined by the Monte Carlo simulation. Common practice in exposure and risk assessment is to characterize the 50th percentile as a "typical" exposure and the 95th percentile as the "reasonable maximum" exposure.4 The distributional analysis for these calculated doses... 

Honeycutt, R.C., Day, Jr., E.W., Shurdut, B.A., and Vaccaro, J.R., Use of simultaneous biological monitoring and dermal dosimetry techniques to determine the exposure of chlorpyrifos to applicators and re-entry workers, in Worker Exposure to Agrochemicals Methods for Monitoring and Assessment, Honeycutt, R.C. and Day, E.W., Jr., Eds., Lewis Publishers, Boca Raton, FL, 2000, chap. 2. 

This study was conducted to evaluate and compare ADD determined using whole-body dosimetry with results of two situational exposure studies conducted following use of a flea fogger under natural conditions. Chlorpy-rifos was selected due to its general availability as a fogger for indoor flea control. Chlorpyrifos is poorly absorbed by the dermal route and readily cleared from the body in urine (Nolan et al., 1984). Trichloropyridinol was measured in 24-hr urine specimens of the volunteers and was converted to chlorpyrifos equivalents as a measure of absorbed dose. The study provided an opportunity to determine the relationship between intensive, high-contact dosimetry studies and the amounts of chlorpyrifos absorbed by two sets of adults who re-entered fogger-treated homes. 

The UK Pesticide Safety Directorate (PSD) has decided to use the TEF approach for assessment of combined risk from exposure to mixtures of acetyl cholinesterase inhibitors (organophosphate (OP) compounds and carbamates) (PSD 1999). Despite clear differences in the action of carbamates and OP compounds, the index compounds selected for all acetyl cholinesterase inhibitors were either aldicarb (carbamate) or chlorpyrifos (OP). The POD for determining relative potency was predetermined as the dose level that produced 20% inhibition of red blood cell cholinesterase in a 90-day dietary study in rats. 

Recently, Olson et al. (2000) and Benschop et al. (1998) have provided reports of animal studies of effects of repeated low-level exposure to nerve CWA. In rats, Olson et al. determined the LOAEL and NOEL of subacute dosages of sarin, administered, i.m. They found that the dose of sarin (GB) needed to produce a low but measurable blood ChE inhibition was 0.75 p-g/kg once a day for 4 days. Thus, the exposure in Olson s study would be described as subclinical. GB was paired with a variety of other chemicals to include chlorpyrifos, DEET (A,A-diethyl-m-toluamide), carbaryl, and PB. No neurobehavioral or neuropathologic effects could be attributable to dosing with GB alone or in any combination with the other chemicals. Rats were also evaluated using a functional observational battery (EOB) and a Eigure 8 Activity Monitor with no significant behavioral effects reported. Benschop et al. (1998) reported on the toxicokinetics of low-level inhalation exposure to soman in... 

Model refinement and validation for both the chltnpyrifos and the diazinon PBPK/PD models wa.s accomplished by conducting a scries of in vivo pharmacokinetic and pharmacodynamic studies in the rat and by evaluating the capability of the model to accurately simulate in vivo data published in the literature. The experimental details are fully described in Timchalk et ai (2002b) and Poet et at. (2004). In brief, these studies involved an acute oral exposure to chlorpyrifos or diazinon and the blood time course of the parent compounds and metabolites was determined, as well as the time course for the cholinesterase inhibition in several tissues. Representative results and model simulations are presented in Fig. 12 and 13 for the pharmacokinetic and pharmacodynamic response in rats following comparable oral doses (50 and 100 mg/kg) of chlorpyrifos and diazinon, respectively, The overall response was fairly comparable for these two insecticides, and the models reasonably simulated both dosimetry and the dose-dependent cholinesterase inhibition. These results arc very consistent with a fairly rapid oral absorption for both insecticides and subsequent metabolism and distribution of the active oxon metabolites. Figure 14 illustrates the capability of the diazinon PBPK/PD model to simulate rodent dosimetry data from the open literature and the capability of the model to accommodate alternative exposure routes (Poet et ai, 2004). In these examples, the time course of diazinon in plasma and cholinesterase inhibition in tissues (i.e.. blood,... 

---