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The paper summarizes an open panel discussion and breakout session by scientists and lay participants that focused on new approaches to identifying exposure to pesticides in humans during the New Paths: Health and Safety in Western Agriculture conference, November 11-13, 2008. Featured were reports on the available results from the Washington State Cholinesterase Monitoring Program, a statewide program for handlers of class I and II organophosphate (OP) and carbamate pesticides, identification of adducts to inhibited cholinesterase by use of protein digestion and mass spectrometry and antibody-based methods, including enzyme-linked immunosorbent assay (ELISA) for pyrethroids. One presenter proposed that the Environmental Protection Agency (EPA) should establish that pesticide registrants develop and provide diagnostic and/or biomonitoring tools to assess human exposure to their chemicals in the process of and as a requirement for pesticide registration. Finally, a follow-up breakout session focused on the new methods presented in the panel and discussion of the speaker's proposal for EPA. Breakout discussants pointed out the benefits of such a proposal but also pointed to some of its weaknesses. Several scientists suggested that a requirement that public release of analytical methods and identity of metabolites and methods for synthesizing metabolites would provide more flexibility to the academy in conducting studies of potential human exposure.

The most economical blood test for the monitoring of workers who are exposed to organophosphate pesticides is serum cholinesterase; however, serum cholinesterase can be affected by conditions other than pesticide exposure. The results of studies in Europe indicate a 4% prevalence of congenital serum cholinesterase deficiency. Prevalence rates in the United States have not been reported. In this study, 127 workers who were part of an employee health program were evaluated. Workers who had decreased serum cholinesterase levels on baseline testing before pesticide exposure were evaluated for a congenital deficit in serum cholinesterase. Five (3.9%) individuals had baseline measurements below the laboratory normal reference value: 4 (3.1 %) were heterozygote for the deficiency, and the remaining individual did not return to test for the genetic deficiency. No one was found to have the homozygote deficiency. The prevalence of congenital deficiency in serum cholinesterase in a midwestern population was 3.1-3.9%. We found it useful to incorporate the knowledge of who has a congenital deficiency into our employee health program, the purpose of which is to monitor workers who spray organophosphates.

A scientific panel assembled by the U.S. Environmental Protection Agency (EPA) determined that variability in cholinesterase (ChE) activities in the agency's pesticide/animal study database likely was due to a lack of accepted guidelines for ChE methodology. A series of trials was held in which participating laboratories measured ChE activity in blood and brain samples from untreated and pesticide-treated rats using a colorimetric assay method. The degree of inhibition of ChE activity in plasma and brain samples compared to controls was consistent among most of the laboratories. The ChE activity in erythrocyte samples differed more between laboratories due to a high blank, low erythrocyte AChE activity and hemoglobin absorption at the wavelength of the assay. Strategies are suggested for minimizing the variability of ChE activity in hemoglobin-rich samples.

The US Environmental Protection Agency now requires ocular toxicity testing to support the registration of organophosphorus pesticides. As a first step toward guideline development for the conduct of these studies, preliminary protocols for ocular toxicity testing in the non-rodent and rodent are being proposed by the Office of Pesticide Programs. Proposed protocol parameters include determination of animal health status, measurement of plasma, erythrocyte and retinal cholinesterase activities, ocular assessment by routine ophthalmological examination, slit lamp biomicroscopy, fundic observations, tonometry, electroretinography and determination of objective refractivity, pupillary response and tracking. Gross and detailed histopathological examinations of ocular system components would also be conducted. Associated questions and concerns with regard to ocular toxicity testing are presented. The Agency plans to hold a workshop in the near future to discuss issues related to protocol refinement and guideline development.

This article is a review of blood cholinesterase activity in a cohort of urban pesticide applicators ranging from 1680 to over 3800 workers. During the period 1981-1991, 208, 788 blood samples were taken for measurement of cholinesterase activity with an average of 6 samples per year from each worker. A total of 150 workers or 0.44% of the cohort was removed from exposure to cholinesterase-inhibiting insecticides because of decreased cholinesterase activity. No worker required treatment for signs of cholinesterase inhibition.

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. A framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.

Five occupants of an office developed symptoms compatible with organophosphate intoxication after application of chlorpyrifos, a moderately toxic pesticide. Recovery of erythrocyte cholinesterase levels occurred during the subsequent three months but followed an exponential distribution rather than the constant rate of recovery most investigators have assumed. This pattern suggests redistribution of the active organophosphate after absorption to a second body compartment with subsequent slow release of the still active substance into the bloodstream.

Frequencies of the CHE1*A allele were estimated on the basis of a sample of 999 Caucasians (1.5%) and 1,015 Negroids (0.84%) from Curitiba, Brazil. The frequency found in the Negroid subsample allows an estimate of 50 +/- 15% of Caucasoid admixture and an average gene flow in the white-black direction of the order of 5.6% per generation.

Following reports of ten cases of possible organophosphate pesticide poisoning in florists exposed to pesticide residues on cut flowers, we conducted a prospective random-sample survey to determine residual pesticide levels on flowers imported into the United States via Miami, Florida. A sample of all flowers imported into Miami on three days in January 1977 showed that 18 (17.7 per cent) of 105 lots contained pesticide residue levels greater than 5 ppm, and that three lots had levels greater than 400 ppm. Azodrin (monocrotophos) was the most important contaminant with levels of 7.7--4,750 ppm detected in nine lots. We examined 20 quarantine workers in Miami and 12 commercial florists exposed to contaminated flowers. Occasional nonspecific symptoms compatible with possible organophosphate exposure were noted, but we found no abnormalities in plasma or red blood cell cholinesterase levels. This study documents a previously unrecognized potential source of occupational pesticide exposure and suggests that safety standards should be set for residue levels on cut flowers.