Use of benchmark dose models in risk assessment for occupational handlers of eight pesticides used in pome fruit production.

The benchmark dose has been frequently recommended for the creation of points of departure for regulatory dose limits, but many regulations, including pesticide risk assessment and registration in the United States, continues to rely on NOAEL methods as the OECD toxicological standard methods recommend. This study used data from studies in support of pesticide registration for eight different compounds to build dose-response models and calculate benchmark doses and confidence limits. The results were compared to the NOAEL of the same study. A probabilistic estimate of dose was compared with all points of departure to demonstrate differences in the protective ability of each different selected limit. While neither the BMD/BMDL nor the NOAEL was consistently more protective, the advantage of using the BMD in quantifying the uncertainty of the point of departure is highlighted, and the feasibility of using current OECD-guideline studies for derivation of a BMD is demonstrated in these cases.

Comparative Probabilistic Assessment of Occupational Pesticide Exposures Based on Regulatory Assessments.

Implementation of probabilistic analyses in exposure assessment can provide valuable insight into the risks of those at the extremes of population distributions, including more vulnerable or sensitive subgroups. Incorporation of these analyses into current regulatory methods for occupational pesticide exposure is enabled by the exposure data sets and associated data currently used in the risk assessment approach of the Environmental Protection Agency (EPA). Monte Carlo simulations were performed on exposure measurements from the Agricultural Handler Exposure Database and the Pesticide Handler Exposure Database along with data from the Exposure Factors Handbook and other sources to calculate exposure rates for three different neurotoxic compounds (azinphos methyl, acetamiprid, emamectin benzoate) across four pesticide-handling scenarios. Probabilistic estimates of doses were compared with the no observable effect levels used in the EPA occupational risk assessments. Some percentage of workers were predicted to exceed the level of concern for all three compounds: 54% for azinphos methyl, 5% for acetamiprid, and 20% for emamectin benzoate. This finding has implications for pesticide risk assessment and offers an alternative procedure that may be more protective of those at the extremes of exposure than the current approach.

Ozone-Related Respiratory Morbidity in a Low-Pollution Region.

OBJECTIVE: We evaluated the effects of ozone on respiratory-related hospital admissions in three counties in Washington State from 1990 to 2006. We further examined vulnerability to ozone by key demographic factors. METHOD: Using linked hospital admission and ambient monitoring data, we estimated the age-, sex-, and health insurance-stratified associations between ozone (0 to 3 days' lag) and respiratory-related hospital admissions in King, Spokane, and Clark County, Washington. RESULTS: The adjusted relative risk (RR) for a 10 ppb increase in ozone at 3 days' lag was 1.04 (95% confidence interval [CI]: 1.02, 1.07) for Clark County, 1.03 (95% CI: 1.01, 1.05) for Spokane County, and 1.02 (95% CI: 1.01, 1.03) for King County. There was consistent evidence of effect modification by age. CONCLUSION: Ozone at levels below federal standards contributes to respiratory morbidity among high-risk groups in Washington.

Longitudinal assessment of occupational exposures to the organophosphorous insecticides chlorpyrifos and profenofos in Egyptian cotton field workers.

Chlorpyrifos (CPF) and profenofos (PFF) are organophosphorus (OP) insecticides that are applied seasonally in Egypt to cotton fields. Urinary trichloro-2-pyridinol (TCPy), a specific CPF metabolite, and 4-bromo-2-chlorophenol (BCP), a specific PFF metabolite, are biomarkers of exposure, while inhibition of blood butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) activities are effect biomarkers that may be associated with neurotoxicity. Urinary TCPy and BCP and blood BChE and AChE activities were measured in 37 adult Egyptian Ministry of Agriculture workers during and after 9-17 consecutive days of CPF application followed by an application of PFF (9-11 days), and a second CPF application (5 days) in 2008. During the OP applications, urinary TCPy and BCP levels were significantly higher than baseline levels, remained elevated following the application periods, and were associated with an exposure related inhibition of blood BChE and AChE. Analysis of blood AChE levels before and after the PFF application period suggests that individual workers with peak BCP levels greater than 1000 µg/g creatinine exhibited further inhibition of blood AChE with PFF application, demonstrating that PFF exposure had a negative impact on AChE activity in this highly exposed worker population. While large interindividual differences in exposure were observed throughout this longitudinal study (peak urinary BCP and peak TCPy levels for individuals ranging from 13.4 to 8052 and 16.4 to 30,107 µg/g creatinine, respectively), these urinary biomarkers were highly correlated within workers (r=0.75, p<0.001). This suggests that the relative exposures to CPF and PFF were highly correlated for a given worker. The variable exposures between job classification and work site suggest that job title and work location should not be used as the sole basis for categorizing OP exposures when assessing neurobehavioral and other health outcomes in Egyptian cotton field workers. Together, these findings will be important in educating the Egyptian insecticide application workers in order to encourage the development and implementation of work practices and personal protective equipment to reduce their exposure to CPF and PFF.

Implications of global climate change for the assessment and management of human health risks of chemicals in the natural environment.

Global climate change (GCC) is likely to alter the degree of human exposure to pollutants and the response of human populations to these exposures, meaning that risks of pollutants could change in the future. The present study, therefore, explores how GCC might affect the different steps in the pathway from a chemical source in the environment through to impacts on human health and evaluates the implications for existing risk-assessment and management practices. In certain parts of the world, GCC is predicted to increase the level of exposure of many environmental pollutants due to direct and indirect effects on the use patterns and transport and fate of chemicals. Changes in human behavior will also affect how humans come into contact with contaminated air, water, and food. Dietary changes, psychosocial stress, and coexposure to stressors such as high temperatures are likely to increase the vulnerability of humans to chemicals. These changes are likely to have significant implications for current practices for chemical assessment. Assumptions used in current exposure-assessment models may no longer apply, and existing monitoring methods may not be robust enough to detect adverse episodic changes in exposures. Organizations responsible for the assessment and management of health risks of chemicals therefore need to be more proactive and consider the implications of GCC for their procedures and processes.

Development of a computer-based survey instrument for organophosphate and N-methyl-carbamate exposure assessment among agricultural pesticide handlers.

BACKGROUND: Assessment of occupational pesticide exposures based on self-reported information can be challenging, particularly with immigrant farm worker populations for whom specialized methods are needed to address language and cultural barriers and account for limited literacy. An audio computer-assisted self-interview (A-CASI) survey instrument was developed to collect information about organophosphate (OP) and N-methyl-carbamate (CB) exposures and other personal characteristics among male agricultural pesticide handlers for an ongoing cholinesterase biomonitoring study in Washington State. OBJECTIVES: To assess the feasibility of collecting data using the A-CASI instrument and evaluate reliability for a subset of survey items. METHODS: The survey consisted of 64 items administered in Spanish or English on a touch-screen tablet computer. Participants listened to digitally recorded questions on headphones and selected responses on the screen, most of which were displayed as images or icons to facilitate participation of low literacy respondents. From 2006-2008, a total of 195 participants completed the survey during the OP/CB application seasons on at least one occasion. Percent agreement and kappa coefficients were calculated to evaluate test-retest reliability for selected characteristics among 45 participants who completed the survey on two separate occasions within the same year. RESULTS: Almost all participants self-identified as Hispanic or Latino (98%), and 97% completed the survey in Spanish. Most participants completed the survey in a half-hour or less, with minimal assistance from on-site research staff. Analyses of test-retest reliability showed substantial agreement for most demographic, work history, and health characteristics and at least moderate agreement for most variables related to personal protective equipment use during pesticide applications. CONCLUSIONS: This A-CASI survey instrument is a novel method that has been used successfully to collect information about OP/CB exposures and other personal characteristics among Spanish-speaking agricultural pesticide handlers.

Children's inhalation exposure to methamidophos from sprayed potato fields in Washington State: exploring the use of probabilistic modeling of meteorological data in exposure assessment.

We examined the significance of meteorology and postspray volatilization of methamidophos (an organophosphorus insecticide) in assessing potential inhalation risk to children in an agricultural community. We combined fluxes from sources and dispersion modeling with a range of possible local meteorology to create output to study the variability in potential community exposure as a result of changing temperature, wind speeds and wind directions. This work is based on an aerial spray drift study where air sampling measurements of methamidophos were made before, during and after a spray event were used to examine acute inhalation risk for children living in an Eastern Washington State community in close proximity (between 15 and 200 m) to sprayed potato fields. We compared the measured average air concentrations of methamidophos in the community to a "no observed adverse effect level" for subchronic inhalation to characterize acute and subchronic inhalation risks. The baseline estimates of inhalation exposure were below Environment Protection Agency's (EPA) level of concern based on a target margin of exposure of 300. As meteorological conditions during and after spraying influence the amount of material moving into areas where children reside we used historical meteorological data to drive model simulations that predicted likely air residue concentrations under different wind and temperature conditions. We also added variability to the decay constant and initial emission fluxes to create a 2-D simulation of estimated air concentrations in the community near the fields. This work provides a methodological framework for the assessment of air concentrations of pesticides from agricultural sprays in the absence of extended measurements, although including variability from meteorological conditions. The deterministic as well as the probabilistic risk analyses in this study indicated that postspray volatilization in the specific spray situation analyzed (methamidophos applied on potato fields in Eastern Washington) did not pose acute or subchronic risks as defined by the EPA. However, this study did not consider any pathway of exposure other than inhalation (e.g. diet, dermal, etc.) and the risk assessment should be evaluated in that context.

The assessment of occupational exposure to diazinon in Nicaraguan plantation workers using saliva biomonitoring.

A cross-sectional study with repeated sample collection in multiple days was conducted to assess diazinon exposures. Saliva and limited blood samples were collected from 10 banana plantation workers involved with diazinon application and their children aged 2-12 years living in Chinandega, Nicaragua. Diazinon concentration-time profiles in saliva varied between two plantations, which reflects the differences of work practices in each plantation. Salivary concentrations of diazinon measured in Plantation 1 applicators continued to increase 2 days after self-reported diazinon application, suggesting an ongoing exposure among these workers. However, salivary diazinon concentrations measured in Plantation 2 applicators were peaked 12 h prior to the first application, and then decreased 36 h post the first application. Diazinon concentrations in saliva were significantly correlated with the time-matched plasma samples collected from the same workers, which is in agreement with the previous published data from animal models. Children's exposure to diazinon through take-home pathway does not exist, as evident by the majority of nondetected saliva samples, and this finding was confirmed by the results from the urine samples. Severe dehydration was observed in many plantation workers and their children, resulting in the loss of some saliva samples, which no doubt have impaired the overall quality of the study results. Regardless, this article has demonstrated that saliva can be used to assess exposures to diazinon in pesticide applicators and children.

Lessons learned for the assessment of children's pesticide exposure: critical sampling and analytical issues for future studies.

In this article we examine sampling strategies and analytical methods used in a series of recent studies of children's exposure to pesticides that may prove useful in the design and implementation of the National Children's Study. We focus primarily on the experiences of four of the National Institute of Environmental Health Sciences/U.S. Environmental Protection Agency/ Children's Centers and include University of Washington studies that predated these centers. These studies have measured maternal exposures, perinatal exposures, infant and toddler exposures, and exposure among young children through biologic monitoring, personal sampling, and environmental monitoring. Biologic monitoring appears to be the best available method for assessment of children's exposure to pesticides, with some limitations. It is likely that a combination of biomarkers, environmental measurements, and questionnaires will be needed after careful consideration of the specific hypotheses posed by investigators and the limitations of each exposure metric. The value of environmental measurements, such as surface and toy wipes and indoor air or house dust samples, deserves further investigation. Emphasis on personal rather than environmental sampling in conjunction with urine or blood sampling is likely to be most effective at classifying exposure. For infants and young children, ease of urine collection (possible for extended periods of time) may make these samples the best available approach to capturing exposure variability of nonpersistent pesticides; additional validation studies are needed. Saliva measurements of pesticides, if feasible, would overcome the limitations of urinary metabolite-based exposure analysis. Global positioning system technology appears promising in the delineation of children's time-location patterns.

Noninvasive method for the assessment of dermal uptake of pesticides using attenuated total reflectance infrared spectroscopy.

Dermal absorption of pesticides is a primary exposure route for agricultural workers, but is not well characterized. Current measurement techniques are either invasive, such as tape-stripping, or require extensive sample preparation or analysis time, such as urinary metabolite monitoring or wipe sampling followed by gas chromatography analysis. We present the application of a noninvasive, spectroscopic approach for the measurement of pesticide absorption into skin. Attenuated total reflectance infrared spectroscopy (ATR-IR) was used to monitor directly the absorption of two pesticides--captan and azinphos-methyl--in ten volunteers over 20 min under occlusive conditions. We found substantial variability in absorption across subjects. Our results were comparable to those measured by the more traditional method of wipe-sampling followed by extraction and gas chromatography analysis. Multivariate data analysis, in the form of multivariate curve resolution (MCR), is a novel addition to this type of experiment, yielding time-resolved information unachievable by standard methods. These data are potentially more informative than the monitoring of blood or urinary metabolites because they can be acquired in essentially real-time, allowing observations of pesticide absorption on a rapid timescale rather than over hours or days.

Pesticide take-home pathway among children of agricultural workers: study design, methods, and baseline findings.

Farmworkers are exposed to pesticides and may take home pesticide residues to their families. In this paper, self-reported pesticide exposure and home practices to reduce the amount of pesticide residues taken home were examined among 571 farmworkers. Urine samples from a subsample of farmworkers and children and dust samples from households and vehicles also assessed pesticide exposure. Overall, 96% of respondents reported exposure to pesticides at work. Many employers did not provide resources for hand washing. Farmworkers' protective practices to keep pesticide residues out of the home were at a low level. In a subset of respondents, pesticide levels above the limit of quantitation were seen in the urine of children and adults and in house and vehicle dust. The results support the take-home pathway of pesticide exposure. Ways must be found to reduce this pesticide exposure among children of farmworkers.

Time-location analysis for exposure assessment studies of children using a novel global positioning system instrument.

Global positioning system (GPS) technology is used widely for business and leisure activities and offers promise for human time-location studies to evaluate potential exposure to environmental contaminants. In this article we describe the development of a novel GPS instrument suitable for tracking the movements of young children. Eleven children in the Seattle area (2-8 years old) wore custom-designed data-logging GPS units integrated into clothing. Location data were transferred into geographic information systems software for map overlay, visualization, and tabular analysis. Data were grouped into five location categories (in vehicle, inside house, inside school, inside business, and outside) to determine time spent and percentage reception in each location. Additional experiments focused on spatial resolution, reception efficiency in typical environments, and sources of signal interference. Significant signal interference occurred only inside concrete/steel-frame buildings and inside a power substation. The GPS instruments provided adequate spatial resolution (typically about 2-3 m outdoors and 4-5 m indoors) to locate subjects within distinct microenvironments and distinguish a variety of human activities. Reception experiments showed that location could be tracked outside, proximal to buildings, and inside some buildings. Specific location information could identify movement in a single room inside a home, on a playground, or along a fence line. The instrument, worn in a vest or in bib overalls, was accepted by children and parents. Durability of the wiring was improved early in the study to correct breakage problems. The use of GPS technology offers a new level of accuracy for direct quantification of time-location activity patterns in exposure assessment studies.

Assessment of organophosphorous pesticide exposures in the diets of preschool children in Washington State.

Twenty-four hour duplicate diet sampling was employed to investigate dietary pesticide exposures of children aged 2 to 5 years. Duplicate diets were collected from seven children living in the Seattle metropolitan area and six children living in Chelan and Douglas counties in Central Washington. Diet samples were collected from each child in the summer and again in the fall, and total daily diets were divided into four food categories: fresh fruits and vegetables, beverages, processed foods, and dairy products. A total of 88 individual food category samples were collected and analyzed for 15 organophosphorous (OP) pesticides. Three of the 13 children had no detectable OP pesticides in either of their diet samples, and 14 of the 26 duplicate diets did not contain detectable levels of OP pesticides. Sixteen individual food category samples contained detectable levels of at least one OP pesticide and two of these samples contained detectable levels of two OP pesticides. Of the 15 targeted pesticides, 6 were detected: azinphosmethyl, chlorpyrifos, malathion, methidathion, methyl parathion, and phosmet. Azinphosmethyl was detected most frequently (10% of all samples), particularly in samples containing apples or apple juice. The fresh fruits and vegetable category had the most frequent pesticide determinations, followed by beverages. OP pesticides were not present at detectable levels in any of the dairy samples. Malathion was the only OP pesticide detected in processed food samples, appearing in 4 of the 26 samples (15%). No detections were above the legal tolerances for residues on produce, however the acute population-adjusted reference dose (aPAD) for chlorpyrifos exposure of 1.7 microg/kg/day was exceeded by one subject during one sampling event. This subject's cumulative daily dose of chlorpyrifos equivalents was estimated to be 2.5 microg/kg/day.