Chlorpyrifos studies

Diazinon and Ronnel. The conclusion that neutral hydrolysis of sorbed chlorpyrifos is characterized by a first-order rate constant similar to the aqueous phase value is strengthened and made more general by the results for diazinon, 0,0-diethyl 0-(2-iso-propyl-4-methyl-6-pyrimidyl) phosphorothioate, and Ronnel, 0,0-dimethyl 0-(2,4,5-trichlorophenyl) phosphorothioate (10). The results for the pH independent hydrolysis at 35°C for these compounds in an EPA-26 sediment/water system (p=0.040) are summarized in Table IV. Because the aqueous (distilled) values of k for diazinon and Ronnel are similar in magnitude to the value for chlorpyrifos, and because these values were shown by the chlorpyrifos study to be slow compared to sorption/desorption kinetics, computer calculations of were not deemed necessary and were not made for these data. 

Esters of 2,4-D. Studies of the alkaline hydrolysis of the methyl and n-octyl esters of 2,4-D in sediment/water systems (24), though less detailed than the chlorpyrifos studies, show similar effects. Results from Investigations using EPA-13 at pH s near 10 for the methyl and octyl esters of 2,4-D are summarized in Figure 7. Under the conditons in these experiments, the fractions of the methyl and octyl esters which are sorbed to the sediment are 0.10 and 0.87, respectively. The aqueous hydrolysis half-lives of the methyl and octyl esters at pH=10 are 3.6 and 27 minutes, respectively. In the sediment/water system, the methyl ester, which is mainly in the dissolved phase, hydrolyzes at a rate similar to that expected for the sediment-free system at the same pH. The octyl ester, on the other hand, hydrolyses at a rate which is considerably retarded (and non-first-order) when compared to the expected aqueous phase rate. Though the data are less detailed and do not permit calculations similar to those conducted for chlorpyrifos, it is clear that the effect of sorption is to considerably slow the alkaline hydrolysis rate. 

Osterloh, J.D, Loth, M., and Pond, S.M. (1983) Toxicologic studies in a fatal overdose of 2,4-D, MCPP, and chlorpyrifos, Journal of Applied Toxicology, 7 125-129. 

The test material for this study was Lorsban 4E Insecticide in 2.5-gallon plastic jugs, as well as Lorsban 50W in 5-pound bags. The reference standards were chlorpyrifos (0,0-diethyl-0-[3,5,6-trichloro-2-pyridinyl] phosphorothio-ate), CAS No. 002921-88-2 and 3,5,6-TCP (3,5,6-tiichloro-2-pyridinyl). 

Table 2 represents a summary of the design of the chlorpyrifos re-entry studies. Five sites (three in California, one in Arizona, and one in Florida) were selected. The California orange harvesting and lemon tree pruning represented high crop re-entry activities, while the Florida tomato and... 

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

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

Table 4 presents the amounts of chlorpyrifos used to fortify the various substrates in this study. Chlorpyrifos "low" spike levels for coverall sections (arms, legs, and torso) as well as t-shirts and briefs, handwashes, and head patches ranged from 5.1 pg to 1198 pg. "High" spike levels of these substrates ranged form 1456 pg to 191,720 pg. Air tubes and Gelman filters were fortified with only "low" amounts of chlorpyrifos which ranged from 0.1 pg to 36 pg. 

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...

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 1 Summary of Estimated Absorbed Doses from Mixer-Loader and Applicator Studies with Chlorpyrifos...

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. 

Table 1 Liquid Turf Study Adult Inhalation Dose of Chlorpyrifos Based on Air Monitoring Data...

Table 3 Liquid Turf Study Adult Dermal (Hands) Dose of Chlorpyrifos Based on the Handwash Analysis...

Table 4 Liquid Turf Study Total Adult Chlorpyrifos...

The granular turf study was handled in a manner very similar to the liquid turf study discussed above. As might be expected, the estimated doses of chlorpyrifos for nine volunteers were considerably lower than the estimated doses in the liquid study. The volunteers chlorpyrifos doses ranged from 0.31 pg/kg to 0.44 pg/kg using physical measurements average 0.36 pg/kg. Utilizing analysis of urine, the average dose was estimated to be 1.3 pg/kg (Table 6). 

Table 5 Liquid Turf Study Estimated Doses of Chlorpyrifos Based on Biomonitoring and Physical Measurements...

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. 

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. 

In our studies, the WBDs accumulated an average of 13,757 pg chlorpyrifos (n = 13), which would represent an administered dose of about 200 pg/kg. If the dermal absorption rate of chlorpyrifos is 9.6%/24 hr in humans (Thongsinthusak, personal communication), then the ADD would be 200 pg/kg x 0.096 = 19 pg/kg. If clothing penetration is taken into account, the estimated (daily) ADD resulting from the intensive 20-min contact period was about 2 pg/kg. 

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. 

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