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Center for Health and the Environment

Epidemiology and Preventive Medicine

Biomarkers of Pesticide Exposures

Developing, Improving and Applying Cost-Effective and Accurate Human Blood Cholinesterase Determinations - Research B (Barry Wilson).

Blood cholinesterases are important enzymes for monitoring exposures to agricultural chemicals and nerve agents of warfare and terror. We showed that commonly used kits for measuring cholinesterases are not optimal for determining acetylcholinesterase (AChE) activity yielding results that are not reproducible between clinical laboratories. Such findings led to a revision of the California regulations requiring clinical laboratories to standardize their results. Laboratories were contacted and invited to participate in a split sample study of human blood AChE and non-specific cholinesterase (BChE) assays. Laboratories measured erythrocyte (RBC) AChE and/or plasma BchE activities from undiluted and 50% diluted blood according to their practices. Aliquots were sent to Wilson's laboratory at UC Davis for assay using an optimized semi-automated plate reader version of the method of Ellman. Nine of 25 laboratories participated; two did their own comparisons. Best correlations were obtained with BChE activity. Acceptable correlations were 0.88 or above for 4 of 5 laboratories for BChE and 0.9 or above for only 2 of 7 laboratories for AChE. A bovine AChE RBC ghost "standard" was devised, tested and validated. The overall poor correlation of inter-laboratory cholinesterase results indicates an urgent need to standardize clinical procedures. Work continues with the clinical laboratories, first with comparing RBC ghost values and then with samples of whole blood. Supported by UC Davis NIOSH Center for Agricultural Health and Safety CDC U07/CCU906162-06), NIEHS Center for Environmental Health Science (ES05707), CA Offices of Environmental Health Hazard Assessment (99-E0021) and Department of Pesticide Regulation (98-0321).

Best Management Practices for Pesticide Use and Food Safety Among California's Small Farmers with Particular Reference to Limited English Speaking & Cultural Minority Farmers (Education B) (Desmond Jolly).

The project aims to maximize the impact of educational interventions with respect to the adoption of 'best practices' in pesticide use as well as in the management of microbiological hazards in agricultural production, post-harvest and marketing. By implication, if these intervention methods are effective, we will reduce the incidence of injuries and illnesses associated with these risk factors.

Various communication tools and media will be utilized in channeling the information to growers. A longitudinal study utilizing random surveys each year for the next five years will track changes in levels of awareness, knowledge, motivation and adoption of acceptable 'best practices.' Surveys and focus groups will also be used to evaluate the role and importance of alternate channels of communication. We will test whether communication channels and tools vary in terms of their effectiveness across different socioeconomic and demographic groups. This will inform our knowledge base as to how to more effectively transmit information to affect the behavior of a multicultural farm population.

Development and Implementation of Pyrethroid and Paraquat Immunoassays for Human Exposure Monitoring (Pilot 2) (Bruce Hammock).

One goal of this project is to develop, validate and implement rapid immunochemical-based analytical methods to monitor human exposure to pesticides in farmworkers. Our focus pesticides are paraquat and pyrethroids. There are more than 20 pyrethroids frequently used in agriculture, most of them contain a phenoxybenzyl group in their structures. Although selective metabolite assays for each pyrethroid are important when exposures are known, a class specific assay to metabolite m-phenoxybenzoic acid (PBA) is very useful and efficient for epidemiology studies and human exposure monitoring. Thus, validation of an immunoassay for PBA in human urine is included in this project. Paraquat, a heavily used herbicide, is a toxicologically and epidemiologically important compound. A more sensitive and selective assay is needed for human exposure monitoring. Finally, we will explore a new detection system using novel fluorogenic enzyme substrates toward increasing sensitivity and sample throughput.

The project has three specific aims. First, validate class-specific and compound specific pyrethroid immunoassays for human urinary monitoring; optimize immunoassays for the pyrethroid metabolite m-phenoxybenzoic acid; and validate the optimized assays in human urine samples. Second, develop a compound-specific immunoassay for paraquat; design and synthesize haptens; generate antibodies and screen haptens; and optimize assays and validate them in human urine. Finally, develop and apply fluorogenic alkaline phosphatase (AP) assays for ELISA; design and synthesize novel alkaline phosphatase (AP) specific substrates; screen AP substrates with model enzymes; optimize and evaluate the selected AP substrates for application to enzyme immunoassays; and investigate fluorogenic AP substrate assisted immunoassays for human exposure monitoring to pyrethroids and paraquat.

Epidemiology of Agricultural Injury & Ergonomics

Safety Education and Agricultural Injury among Rural California High School Students (Research F) (Stephen McCurdy).

In spite of its status as one of the nation's most hazardous industries, agriculture is unique in utilizing significantly more child labor than other less hazardous industries. Approximately 1.3 million persons younger than 20 years of age live on U.S. farms according to the 1991 census, and more than 120,000 children aged 14 perform agricultural work. There are approximately 100 fatal and 32,000 nonfatal injuries (15,000 of which are work-related) annually among children on U.S. farms. Efforts to reduce the toll of agricultural injury have included engineering improvements, education, and enforcement of existing laws. Although significant resources are devoted to education, few data exist to document its impact.

This project is a longitudinal observational study of California Central Valley high school students enrolled in a state-approved agricultural curriculum to evaluate the impact of agricultural safety curriculum on reducing risk and instilling safety attitudes and behaviors. Approximately 600 students will be followed through their school years; approximately half will receive the safety component (taught in Agricultural Mechanics classes) in the state-approved agriculture curriculum. The remaining students, although enrolled in the state-approved agricultural program, will not receive the safety component of the curriculum. Subjects will be surveyed regarding demographic characteristics, health and health behaviors, agricultural safety-related attitudes and practices, and injury experience in the preceding year. The survey will be repeated in subsequent years for four cycles of data collection. The study will evaluate whether students receiving the safety component manifest a reduced injury rate and higher levels of safety-related attitudes and reported practices compared to their peers who have not received the safety component of the curriculum.

An Intensive, Regional Approach to Occupational Research Priorities for California Farm Workers (Pilot 1) (Rick Mines and David Lighthall).

The goal of the proposed pilot research is to conduct a set of regional, intensive case study investigations of occupational safety and health problems facing California hired farm workers. The empirical foundation for the regional case studies is two extensive health surveys of 1,435 current and former California farm workers conducted by the California Institute for Rural Studies (CIRS) in 1999. The California Agricultural Workers Survey (CAWHS) interviewed 968 current farm workers regarding a comprehensive range of occupational health issues as well as physical examinations and blood chemistry analyses. Interviews were conducted in seven communities representing the six agricultural regions of the state. The Binational Health Survey (BHS) posed a similar range of questions to 162 current farm workers and 305 former farm workers residing in villages in Mexico but did not include physical exams. Phase I of the project consists of a regional assessment of key occupational risk exposure and related trauma. The regional analysis will particularly focus on (1) correlations between crop/tasks and chronic trauma and (2) an evaluation of the effectiveness of Worker Protection Standards (WPS) in respect to training and minimizing pesticide exposure. This analysis will serve as the basis for causal hypotheses that will guide the intensive fieldwork of Phase II. The goal of Phase II is to systematically investigate the validity of these hypotheses in their regional contexts via semi-structured interviews with workers, employers, occupational health specialists, health providers, and others. Analytical objectives to be included in the final report include (1) process understanding regarding onset, treatment, duration, and length of tenure impacts for common chronic injuries in each region, (2) worker-, care provider-, or employer-based barriers to treatment for occupational trauma, (3) explanations for WPS inadequacies in respect to training and compliance, (4) suggestions for improving access to occupational safety training and health care, (5) identification of gaps in the regulatory safety net for hired farm workers in the state, and (6) specification of emergent research hypotheses that merit follow-up research by specialists at the Western Center for Agricultural Health and Safety and elsewhere.

Current Costs of Occupational Injuries in Agriculture (Research E) (J. Paul Leigh).

Costs have become critical statistics in the ongoing debate about medical care. Recently, some estimates have been made of medical care and productivity costs associated with job-related injuries across all industries. A recent preliminary study suggests the industry of agriculture contributes a disproportionately high cost to the total cost for all industries. But this preliminary study applies to 1992. We propose to estimate the current (2001-2003) costs using methods that improve on those of the preliminary study and conduct a sensitivity analysis that allows for alternative assumptions.

Fatal injuries will be estimated with data from the Bureau of Labor Statistics' (BLS's) Census of Fatal Occupational Injuries adjusted for underreporting of minorities. Non-fatal injuries will be estimated with data from the BLS's Annual Survey and the National Institute for Occupational Safety and Health’s Traumatic Injury Surveillance of Farms (TISF) . The human capital/cost-of-illness method will be used. Costs will be split into direct and indirect categories. Within the direct category, we will include medical care costs, as well as medical and insurance administration. Within the indirect category we will include lost wages, lost fringe benefits, lost home production, and hiring and training costs for firms. Medical costs will be estimated with information from the National Council on Compensation Insurance (NCCI) as well as the Workers' Compensation Insurance Rating Bureau (WCIRB) of California. Administration costs will be based upon estimated ratios of overhead to benefits paid from private and government insurers. Lost wages will be estimated with a present value function that allows for varying wages and varying survival probabilities by gender and age. Fringe benefits and home production will be estimated with published ratios of fringe benefits to wages within agriculture and published ratios of home production to wages for those who work outside the home. Hiring and training costs will be similarly accounted for. These estimates will apply to each year 2001, 2002 and 2003. We will also attempt a comparison of agriculture to the costs in all other industries for the same years.

Prevention of Musculoskeletal Disorders in Hand Harvest of Vegetable Crops (Prevention B) (John Miles).

This project relates directly to three high priority objectives in the Healthy People 2000 report: research on hazard surveillance, development of control approaches, and effective use of controls. In addition to meeting high priority objectives in Healthy People 2000 this proposed project also meets two specific priorities of the National Occupational Research Agenda. Specifically, work-related musculoskeletal disorders and special populations at risk (i.e., nearly all workers involved are immigrants from Mexico or other Central American countries. The project's four main goals are: to improve prevention of high risk musculoskeletal disorders due to hand harvesting of vegetables; to demonstrate the application of ergonomic engineering intervention in a field agricultural workplace; to increase the understanding of the risk factors for musculoskeletal disorders and ergonomic methods among owner/operators, workers, and the agricultural community in general; and to add to research knowledge about ergonomic engineering approaches to agricultural injury control. The project's specific aims include: 1) recruit cooperating partners from among vegetable producers; 2) develop detailed ergonomic descriptions (including instrumented biomechanical, metabolic, and postural data) of identified risk factors for MSDs involved in hand harvest of leafy vegetables; 3) assess the incidence of MSDs and related symptoms among workers performing hand harvest of leafy vegetables; 4) study a field-ready prototype of existing model leafy vegetable harvest machine; 5) conduct cooperative field trials of prototype with producers; 6) estimate the impact of the prototype interventions on the ergonomics of hand harvest work tasks; 7) estimate the impact of the prototype interventions on the health outcomes; 8) assess productivity impacts and perceived &ldquot;adoptability&rdquot; of interventions; 9) evaluate cooperative intervention trials and compare with pre-intervention analyses; 10) communicate project findings to vegetable and other agricultural industry groups, to workers, and to community interests; and 11) report project findings in appropriate research and professional publications.

Incident Disease and Injury Among a Cohort of California Farmers and Farm Operators (Research A) (Marc Schenker).

Increased morbidity and mortality from all causes has been well documented in many agricultural settings, but there have been relatively few studies of morbidity and mortality among California farmers and farmworkers. California is the largest agricultural state with production of $28+ billion in farm commodities annually produced on 81,000 farms by up to 1.5 million people. This project involves an ongoing series of health studies among a cohort of California farmers aimed at identifying the prevalence and risk factors for acute and chronic disease, and ultimately at the prevention of disease in this population. The major focus is on hazards predominantly occurring among California and other Western farmers. The follow-up component allows us to measure disease incidence and its risk factors and to determine changes in work practices as this cohort ages. This cohort is closely connected to the exposure assessment studies of the Center. We hypothesize that agricultural work increases the risk of acute and chronic injury and illness, and that these occupational diseases result in increased disability and mortality.

The cohort was initially contacted in 1993, consisting of a representative statewide sample of 1,947 California farm operators. In 1995-96, we selected a stratified sub-sample of farmers to further investigate respiratory disease and symptoms. In 1998 we located 1,652 of the participants for a questionnaire follow-up that addressed incident disease, and several new outcomes including musculo-skeletal symptoms and disease. In addition we obtained baseline health and work information on 802 spouses (81% response) and enumeration of 600 children <18 years of age living on the farms of the study subjects.

In years 1 and 2 we will identify a subset of up to 100 farmers with and without respiratory symptoms from the 1995 case-base sample and conduct an intensive investigation of respiratory function and structure, focusing on the effects of agricultural dust exposure. This will involve extensive pulmonary function testing and HRCT scanning to characterize pulmonary fibrosis and obstructive changes. In year 3 we will conduct a follow-up survey of disease and symptom incidence and prevalence among the full sample of California farmers whom we surveyed in 1993 and spouses identified in 1998. We will also request death certificates and analyze cause-specific mortality for those individuals in the cohort who have died. In year 4 we will conduct additional case-based analyses of the cohort to identify specific risk factors for disease in the population. We specifically expect to study causes of musculo-skeletal symptoms or disease, although the final case definition will depend on findings of the cohort follow-up conducted in year 3. The existence of this representative sample of California farmers and farm managers provides a powerful tool for hypothesis generation and testing, focusing on agricultural risk factors for disease in California farmers.

Epidemiology of Agricultural Safty

Extending Pesticide Related Health and Safety Programs to Underserved Ag Populations in the Western United States (Education A) (Patrick J. O'Connor-Marer).

This project involves research to determine the most effective outreach and educational methods to communicate agricultural risks to underserved agricultural populations working in the Western United States. As part of the project, investigators will research and test established and new methods of extending agricultural health and safety information to individuals in these communities. This project's unique approach involves three areas of significance: (1) developing and testing effective pesticide-related health and safety training methods and materials that can be extended to underserved populations through members of their communities—these methods and materials will be designed to address the cultural, language, and educational variabilities of underserved populations in agricultural communities; (2) devising and testing innovative and practical techniques to assist agricultural employers of underserved populations in providing effective pesticide safety training and hazard awareness programs; and (3) evaluating effectiveness of various methods for extending agricultural pesticide-related health and safety information, resources, and training to health care providers, social service organizations, and other leaders within underserved agricultural communities.

The purpose of these activities is to reduce pesticide-related illnesses and injuries within the underserved populations and to develop educational and outreach models that will form the framework for ongoing, community-based programs for transferring important agricultural health and safety information and hazard awareness training to immigrant and Native American farming families and communities in California, Arizona, Hawaii, and other Western states.

Other Epidemiology A Cross-sectional Study of Respiratory Function and Paraquat Exposure Among Agricultural Workers in Costa Rica (Marc Schenker and Kiyoung Lee).

This is a cross-sectional study of respiratory function and paraquat exposure among agricultural workers in Costa Rica. The study includes two components: (1) an exposure assessment component, and (2) an epidemiological study with interviewer administered questionnaires and pulmonary function testing, including single breath diffusion capacity and oxygen desaturation testing. Kiyoung Lee is in charge of exposure assessment. The specific aims of the exposure assessment are to measure current paraquat exposure by biological markers in a subset of current farm workers and to characterize current and cumulative paraquat exposure among farm workers, based on work histories and exposure assessment results. This study will evaluate possible independent association of cumulative long-term paraquat exposure with respiratory symptoms and pulmonary function in study subjects. In the past year data collection in Costa Rica was completed. Questionnaire and pulmonary function data were obtained on 340 agricultural workers in Costa Rica. In addition, an extensive exposure assessment component under the direction of Dr. Kiyoung Lee collected air and biologic samples to assess paraquat exposure in the cohort. Bioassays were completed at UC Davis under the direction of Dr. Bruce Hammock.

Biological Monitoring of Occupational Exposure to Paraquat in Costa Rica (Kiyoung Lee).

The aim of this project is to measure paraquat urine level among herbicide applicators and farm workers. The 24-hour urine samples were collected during application day and analyzed by ELISA method. This study will provide the exposure distribution and determinant factor of the occupational exposure for cross-sectional epidemiological study.

Development of Ultimate Passive Sampler without Face Velocity Influence on Sampling Rate (Kiyoung Lee).

The aims of this research are to identify mass transfer characteristics of passive samplers that depend on face velocity, develop a personal sampler configuration that has negligible face velocity effect on sampling rate, and evaluate its performance under various conditions. This research will provide passive sampler configurations that can provide accurate measurements under fluctuating environmental conditions. Passive sampler will be an irreplaceable sampling device for exposure assessment, as long as the face velocity effect during the sampling can be minimized.

Exposure Assessment of Wood Smoke in Developing Countries (Kiyoung Lee).

The aim of this research is to understand the exposure profile of wood smoke in developing countries. As a majority of the world's population is exposed to wood smoke, better understanding of exposure and its health effects are needed. We measured exposure profile in Costa Rica, and will measure the exposure in Pakistan. This information will be critical to understand the reproductive health effect of wood smoke.