W. Kent Anger

Studying Health Outcomes in Farmworker Populations Exposed to Pesticides

A major goal of studying farmworkers is to better understand how their work environment, including exposure to pesticides, affects their health. Although a number of health conditions have been associated with pesticide exposure, clear linkages have yet to be made between exposure and health effects except in cases of acute pesticide exposure. In this article, we review the most common health end points that have been studied and describe the epidemiologic challenges encountered in studying these health effects of pesticides among farmworkers, including the difficulties in accessing the population and challenges associated with obtaining health end point data. The assessment of neurobehavioral health effects serves as one of the most common and best examples of an approach used to study health outcomes in farmworkers and other populations exposed to pesticides. We review the current limitations in neurobehavioral assessment and strategies to improve these analytical methods. Emerging techniques to improve our assessment of health effects associated with pesticide exposure are reviewed. These techniques, which in most cases have not been applied to farmworker populations, hold promise in our ability to study and understand the relationship between pesticide exposure and a variety of health effects in this population.

Correlating neurobehavioral performance with biomarkers of organophosphorous pesticide exposure.

There is compelling evidence that adverse neurobehavioral effects are associated with occupational organophosphorous pesticide (OP) exposure in humans. Behavioral studies of pesticide applicators, greenhouse workers, agricultural workers and farm residents exposed repeatedly over months or years to low levels of OPs reveal a relatively consistent pattern of neurobehavioral deficits. However, only two studies have demonstrated a link between neurobehavioral performance and current biomarkers of OP exposure including blood cholinesterase (ChE) activity and urinary levels of OP metabolites. A variety of reasons may explain why so few studies have reported such correlations, including differing individual and group exposure histories, differing methodologies for assessing behavior and exposure, and lack of a reliable index of exposure. Alternatively, these data may suggest that current biomarkers (ChE, urine metabolites) are neither predictive nor diagnostic of the neurobehavioral effects of chronic OP pesticide exposures. This review focuses on the evidence that neurobehavioral performance deficits are associated with occupational OP pesticide exposure and concludes that research needs to return to the basics and rigorously test the relationships between neurobehavioral performance and both current (ChE and urine metabolites) and novel (e.g., inflammation and oxidative stress) biomarkers using human and animal models. The results of such studies are critically important because OP pesticides are widely and extensively used throughout the world, including situations where exposure controls and personal protective equipment are not routinely used.

Neurobehavioural tests and systems to assess neurotoxic exposures in the workplace and community.

T he nervous system has, since the earliest recorded history of workplace hazards, been a sensitive target organ for chemical exposures. Technological advances as well as disasters such as the mercury exposures during the 1950s in Minimata and the 1970s in Iraq led to reduced workplace exposures during the mid 1900s and a consequent shift from the detection of obvious debility (for example, tremors, paralysis) detectable with even gross clinical methods, w5 to the detection of subtle subclinical effects. Hänninen and colleagues were the first to tackle this issue by studying carbon disulfide exposures in the viscose rayon industry. Hänninen, a clinical psychologist at Finland’s Institute of Occupational Health, employed the tools of her discipline, and experimental psychologists brought in the tools employed in the laboratory. A new field, human behavioural neurotoxicology, began to emerge.

Test-Retest Reliability of Psychological and Neurobehavioral Tests Self-Administered by Computer:

A series of 12 psychological and 7 neurobehavioral performance tests were administered twice to a nonclinical normative sample with 1 week between administrations. The tests were presented in a self-administered computerized format. One week test-retest reliabilities were comparable to conventional administration formats. The results suggest that individual test reliability is not affected when tests are administered as part of an extensive multi-measure battery. Computer administered test reliability coefficients also were compared to a Mixed Format (computer-conventional) administration with mixed format reliabilities generally similar to the reliabilities of published conventional tests but also generally lower than same format testing. Compared to psychological test reliability, neurobehavioral test reliability appeared more vulnerable to decreases with mixed format testing. These conclusions should not be generalized to all computer implemented tests as the qualities of the test implementation will affect the outcome.

Effectiveness of Total Worker Health Interventions

Total Worker Health (TWH) was introduced and the term was trademarked in 2011 by the National Institute for Occupational Safety and Health (NIOSH) to formally signal the expansion of traditional occupational safety and health (OSH) to include wellness and well-being. We searched PubMed, PsycINFO, and other databases using keywords TWH, health promotion, health protection, and variants for articles meeting the criteria of (a) employing both occupational safety and/or health (OSH, or health protection) and wellness and/or well-being (health promotion, or HP) in the same intervention study, and (b) reporting both OSH and HP outcomes. Only 17 published studies met these criteria. All but 1 of the 17 TWH interventions improved risk factors for injuries and/or chronic illnesses, and 4 improved 10 or more risk factors. Several TWH interventions reported sustained improvements for over a year, although only 1 is readily available for dissemination. These results suggest that TWH interventions that address both injuries and chronic diseases can improve workforce health effectively and more rapidly than the alternative of separately employing more narrowly focused programs to change the same outcomes in serial fashion. These 17 articles provide useful examples of how TWH interventions can be structured. The promise of simultaneous improvements in safety, health, and well-being leads to the call to pursue TWH research to identify and disseminate best practices.

Biomarkers of Chlorpyrifos Exposure and Effect in Egyptian Cotton Field Workers

Background Chlorpyrifos (CPF), a widely used organophosphorus pesticide (OP), is metabolized to CPF-oxon, a potent cholinesterase (ChE) inhibitor, and trichloro-2-pyridinol (TCPy). Urinary TCPy is often used as a biomarker for CPF exposure, whereas blood ChE activity is considered an indicator of CPF toxicity. However, whether these biomarkers are dose related has not been studied extensively in populations with repeated daily OP exposures. Objective We sought to determine the relationship between blood ChE and urinary TCPy during repeated occupational exposures to CPF. Methods Daily urine samples and weekly blood samples were collected from pesticide workers (n = 38) in Menoufia Governorate, Egypt, before, during, and after 9–17 consecutive days of CPF application to cotton fields. We compared blood butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) activities with the respective urinary TCPy concentrations in each worker. Results Average TCPy levels during the middle of a 1- to 2-week CPF application period were significantly higher in pesticide applicators (6,437 μg/g creatinine) than in technicians (184 μg/g) and engineers (157 μg/g), both of whom are involved in supervising the application process. We observed a statistically significant inverse correlation between urinary TCPy and blood BuChE and AChE activities. The no-effect level (or inflection point) of the exposure–effect relationships has an average urinary TCPy level of 114 μg/g creatinine for BuChE and 3,161 μg/g creatinine for AChE. Conclusions Our findings demonstrate a dose–effect relationship between urinary TCPy and both plasma BuChE and red blood cell AChE in humans exposed occupationally to CPF. These findings will contribute to future risk assessment efforts for CPF exposure.

Neurobehavioral effects of exposure to trichloroethylene through a municipal water supply.

We studied a population-based sample of 143 residents of a community in which the municipal water supply had been contaminated with trichloroethylene (TCE) and related chemicals from several adjacent hazardous waste sites between 1981 and 1986. A hydraulic simulation model was used in conjunction with a geographic information system (GIS) to estimate residential water supply exposures to TCE; 80% of the participants had potential TCE exposure exceeding the maximum contaminant level (5 ppb). The Neurobehavioral Core Test Battery (NCTB), tests of visual contrast sensitivity, and the profile of mood states (POMS) were administered approximately 6 years following peak concentrations of TCE in municipal drinking water. Multivariate analysis of variance adjusted for potential confounders was used to compare mean test scores of residents classified by estimated TCE exposure ( 5-10, >10-15, >15 ppb). TCE exposure >15 ppb was associated with poorer performance on the digit symbol, contrast sensitivity C test, and contrast sensitivity D test and higher mean scores for confusion, depression, and tension. We found evidence of a strong interaction between exposure to TCE and alcohol consumption; the associations for the NCTB and POMS among persons in the high-exposure group who also consumed alcohol were stronger and were statistically significant for the Benton, digit symbol, digit span, and simple reaction time tests, as well as for confusion, depression, and tension. This study adds to the evidence that long-term exposure to low concentrations of TCE is associated with neurobehavioral deficits and demonstrates the usefulness of GIS-based modeling in exposure assessment.

Discriminating mild parkinsonism: methods for epidemiological research.

Methods for the efficient and accurate detection of parkinsonism are essential for epidemiological studies. We sought to determine whether parkinsonism could be detected by a neurologist from a videotaped assessment and whether neurobehavioral methods (motor, cognitive, and sensory) discriminated between patients with Parkinsons disease (PD) and controls. Fifteen patients with mild PD (Hoehn and Yahr I‐III) were compared to 15 age‐, sex‐, and education‐matched controls. Each participant underwent a videotaped neurological examination (based on the Unified Parkinsons Disease Rating Scale, UPDRS), administered by a trained technician, and reviewed by a neurologist, as well as a series of neurobehavioral tests. The neurologist identified PD patients with 86% sensitivity and 100% specificity. Among the neurobehavioral tests, finger tapping, combined with one or more among olfaction, visual contrast sensitivity, or Paired Associates Learning, correctly classified 90%, or more, of subjects. Individual psychological tests did not discriminate reliably between groups. We conclude that videotaped assessments of parkinsonism or objective tests of motor and sensory function can accurately detect patients with PD. Both approaches have potential for identifying PD cases, but the latter may be more efficient for screening. Mov. Disord. 16:33–40, 2001.

Development of the Behavioral Assessment and Research System (BARS) to detect and characterize neurotoxicity in humans

The Behavioral Assessment and Research System (BARS) is a computer-based testing system designed to assess neurobehavioral function in humans. It was developed to provide a series or battery of neurobehavioral tests optimized for the detection of neurotoxicity in non-mainstream human populations, specifically people with limited education or literacy. Key to meeting this goal were simply-stated instructions divided into an elemental series of steps, a 9BUTTON response unit to replace the computer keyboard for responding, and spoken instructions. Modifications all underwent serial testing in target populations to successively hone the changes to be more effective. A similar process was followed when developing adjustable parameters, test reliability assessments, and when implementing these tests with populations from different cultural groups and children. The principles and experiences that guided the development of BARS should inform the development of future testing systems to ensure that the new tests can be used with non-mainstream populations, which may be increasingly subject to neurotoxic exposures.

Chlorpyrifos exposures in Egyptian cotton field workers

Neurobehavioral deficits have been reported in Egyptian pesticide application teams using organophosphorus (OP) pesticides, but whether these effects are related to OP pesticide exposures has yet to be established. In preparation for a comprehensive study of the relationship between OP pesticide dose and neurobehavioral deficits, we assessed exposure within this population. We conducted occupational surveys and workplace observations, and collected air, dermal patch and biological samples from applicators, technicians and engineers involved in chlorpyrifos applications during cotton production to test the hypotheses that: (1) dermal exposure was an important contributor to internal dose and varied across body regions; and (2) substantial differences would be seen across the three job categories. Applicators were substantially younger and had shorter exposure histories than did technicians and engineers. Applicators and technicians were observed to have relatively high levels of skin or clothing contact with pesticide-treated foliage as they walked through the fields. Both dermal patch loadings of chlorpyrifos and measurements of a chlorpyrifos-specific metabolite (TCPy) in urine confirmed substantial exposure to and skin absorption of chlorpyrifos that varied according to job category; and dermal patch loading was significantly higher on the thighs than on the forearms. These findings support our hypotheses and support the need for research to examine neurobehavioral performance and exposures in this population. More importantly, the exposures reported here are sufficiently high to recommend urgent changes in work practices amongst these workers.