Chlorpyrifos exposure studies

Successive 24-hr urine specimens were provided by each volunteer. Collection in the dosimeter studies began 24 hr prior to the chlorpyrifos exposure (study day 0) and continued for 3 days based upon the 27-hr half-life of chlorpyrifos in humans (Nolan et al., 1984). Pre-exposure controls were obtained in all cases. Total urine volume was measured for each of the days, and 20- to 30-mL portions were stored frozen prior to analysis. The Sacramento collections were 48 hr and the Riverside collections were approximately 84 hr after re-entry. 

Table 1.4 Comparison of concurrent biomonitoring and passive dosimetry data s from chlorpyrifos exposure studies (USEPA, 2001)...

Table 3 Chlorpyrifos Mixer-Loader, Applicator Exposure Study Parameters...

Table 5 presents data on field spike recoveries. Recoveries of chlorpyrifos from "low" spiked substrates in the California studies ranged from 62.5 to 126%, and recoveries of chlorpyrifos from "high" spiked substrates ranged from 93.7 to 133%. In the Florida, Arizona, and Michigan studies, all recoveries ("low" and "high") ranged from 61 to 158%. The field recoveries cited above were found to be reasonable and within the range of field recoveries seen in many worker exposure studies. 

Table 5 Chlorpyrifos Field Spike Recoveries, Chlorpyrifos Worker Exposure Study...

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 team led by Whyatt used regression analysis to assess whether there was a difference in the association between chlorpyrifos exposure and birth outcome before and after the EPA s action in the summer of 2000 which had ended residential use of chlorpyrifos. Prior to 2001, chlorpyrifos clearly had an impact on birth outcome, but after the EPA action taken in June 2000, levels of exposure declined and there was no longer a statistically significant association between insecticide exposure and birth outcome (Whyatt et al., 2004, 2005). This study provides encouraging evidence linking an action driven by the FQPA to a significant reduction in prenatal and infant exposures and risk. 

Chlorpyrifos provides an example of the utility of human pharmacokinetic models to estimate daily dose from biomonitoring data for a rapidly cleared pesticide. The urinary metabolite trichloro-2-pyridinol (TCP) is used in the NHANES study to monitor population exposure to chlorpyrifos (CDC 2005). Several epidemiologic studies have linked chlorpyrifos exposure to adverse birth outcomes through associations between urinary and blood biomarkers and have demonstrated maternal exposure and physiologic measurements in the neonate (Berkowitz et al. 2003, 2004 Whyatt et al. 2004 Needham 2005). 

Recent findings of indoor exposure studies of chlorpyrifos indicate that young children are at high risk to this semivolatile pesticide [134]. Even after a single broadcast use of chlorpyrifos by certified applicators in apartment rooms, it continued to accumulate on children s toys and hard surfaces 2 weeks after spraying. The estimated chlorpyrifos exposure levels from indoor spraying for children were estimated to be approximately 21-119 times above the current recommended reference dose from all sources [123]. 

Table 1 Field Phase of Chlorpyrifos Worker Exposure and Re-entry Studies...

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... 

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. 

The previous chapter presented results from field studies in which exposures were measured for workers involved with the use of the insecticide chlorpyrifos in several use scenarios and for persons who might re-enter treated areas. In this chapter, the results from these studies are handled by several methods to demonstrate the advantages of using probability and distributional analyses, rather than single point values, for the characterization of risks to pesticides. 

Based on the data from controlled human studies, the NOEL for plasma cholinesterase inhibition for a single dose of chlorpyrifos is between 0.1 and 0.5 mg/kg bw/day, and the more conservative 0.1 mg/kg bw/day (100 pg/kg bw/day) is used in this assessment as the acute NOEL for chlorpyrifos. The repeated dose NOEL in humans is 0.03 mg/kg bw/day (30 pg/kg bw/day), based on plasma cholinesterase activity, and this is the basis for the establishment of the reference dose of 0.003 mg/kg bw/day (3 pg/kg bw/day) used by the EPA in assessing dietary risk to chlorpyrifos. For the work described here, both NOELs are used as bases for assessing risks to persons who have the potential for non-dietary exposure to chlorpyrifos. For exposures that are infrequent or of short duration, the 100 pg/kg bw/day NOEL is assumed to be the more appropriate value, and the lower 30 pg/kg bw/day will be used in those situations in which exposure may be considered to be more frequent. ... 

The results from the several studies that have been conducted to measure exposures associated with the use of chlorpyrifos are summarized in Tables 1 and 2. Table 1 summarizes results from mixer-loader and applicator studies reported by Honeycutt et al.1 Listed for each work description are the number of replicates, the arithmetic mean, and the geometric mean for the replicates from both the passive dosimetry measurements and the biomonitoring tech-... 

Table 2 summarizes the re-entry exposure data from studies with chlorpyrifos.1 There are fewer replicates for these workers which would seem to be justified by the lower variability in the data sets. There are practically no differences between the arithmetic and geometric means for these data sets. 

Doses of chlorpyrifos in human volunteers were also estimated using physical measurements. Air sampling was conducted in order to estimate the inhalation dose to each volunteer. Dislodgeable residues were also measured throughout the study to estimate the dermal contribution to total dose. Finally, hand rinses were conducted on each volunteer immediately following the 4-hr activity period to assess the potential contribution to total dose from hand exposure and to estimate an oral dose to a crawling child. 

In our study, volunteers wearing either WBDs or bathing suits performed a set of choreographed Jazzercize routines on chlorpyrifos-treated carpet. These exercises at a low work level were designed to represent a maximum daily surface contact and transfer of chemicals such as pesticides. Results were similar to exposures of two sets of adults who used insecticide foggers in their 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. 

In animal studies, repeated inhalation of chlorpyrifos at 287 Hg/m (near the theoretical maximum vapor concentration) for 13 weeks caused no treatment-related changes in urinalysis, hematology, clinical chemistry, terminal body and organ weights, or pathology. Induction of delayed polyneuropathy in animals occurs only at doses that exceed the LD50." Peripheral neurotoxic effects could occur in humans after massive exposures at almost lethal doses (from which the patient is saved by intensive medical intervention). The possibility that subtle neurobehavioral effects are associated with pesticide exposure cannot be ruled out. ... 

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