Accomplishments
2006-2007 CROET Highlights
What has CROET done for Oregon?
• Brought federal dollars into the Oregon economy
CROET receives base operations funding from the Oregon Workers’ Compensation System that, year after year, CROET scientists have successfully leveraged to win federal and other research dollars. For every dollar invested by the State’s Workers’ Benefit Fund, CROET”s world-class scientists have brought an averaged $2.40 of federal and private grant funding into the Oregon economy (see chart below). Federal dollars for research in Oregon have a significant positive impact on the state’s economy. Expenditures for goods and services, as well as the salaries of scientific and support personnel, produce a multiplier effect on the purchase of goods and services and creation of businesses that support the needs of Oregon’s research institutions. Moreover, research coming out of CROET has a greater than average impact on the state’s economy from the new technologies and jobs that spin off from productive research, as exemplified later in this report. In a study conducted by Oregon State University, multiplier effects on the economy from the infusion of federal grant funds were estimated to range from 2 up to 10 dollars per federal dollar received.
• Conducted workplace studies and applications research
CROET conducts workplace surveys so that prevention and research needs can be identified, and applications research to bring the benefits of science to the workplace floor. It also reaches out to provide education and information to the Oregon workforce and beyond.
Oregon Fatality Assessment and Control Evaluation (OR-FACE) Program
Dr. Gary Rischitelli leads the Oregon Fatality Assessment and Control Evaluation (OR-FACE) program that tracks, investigates, and reports on occupational fatalities in Oregon. In 2006, OR-FACE recorded 79 occupational fatalities in 67 incidents. In 2007, OR-FACE recorded 69 fatalities in 67 incidents. OR-FACE investigates incidents in specific national and local target areas of concern and, between 2006-2007, produced 9 investigation reports with safety recommendations. During 2006-2007, falls became a leading area of concern, and OR-FACE published a hazard alert on falls from elevated work areas, ladders, and suspension from a height. In 2007, OR-FACE published its third annual report summarizing data from 2005 and included an abstract of each incident. The report charted frequencies by age, gender, race/ethnicity, time, month, county, industry, occupation, and event. Principal areas of concern were highlighted in relation to transportation, falls, and contact with objects or equipment. Through its research, OR-FACE has identified several priority areas of concern within specific sectors of the Oregon workforce, including transportation (motor vehicles, trucking), logging, and young workers. Young workers aged 16-24 are involved in 15% of all Oregon fatalities, a finding that inspired establishment of the Oregon Young Worker Health and Safety Coalition, co-sponsored by OR-FACE and the University of Oregon’s Labor Education & Research Center (LERC). The Coalition’s activities include developing occupational safety and health curricula for teens, disseminating educational materials for teachers, conducting teacher education workshops, outreach to employers, and public information campaigns. OR-FACE investigation reports and other publications are available on the program’s website (www.ohsu.edu/croet/face). Investigation reports from Oregon and other FACE states are also available through the National Institute for Occupational Safety and Health (www.cdc.gov/niosh/face), which funds the program.Health Promotion Intervention Model Being Developed for Truck Drivers
Safety and Health Promotion for Truck Drivers (SHIFT), a program developed and headed by Dr. Ryan Olson, is a 6-month safety and health promotion program designed for commercial truck drivers. Commercial truck drivers account for 15% of occupational fatalities, 8% of musculoskeletal injuries, and have a 10-12 year shortened life span. Long and unusual work hours, prolonged sitting, limited food choices, and demanding work put drivers at risk for serious illness and injury - most notably heart disease and back injuries. Drivers who joined the SHIFT program completed training and worked toward goals, including weight loss, diet and safe driving. Drivers competed in teams to achieve the largest improvements in health and safety measures, and were rewarded for both participation and high achievement. To help drivers accomplish their health and safety goals, the program included computer-based training, self-management activities and individualized health coaching. This evidence-based health promotion intervention was funded by a National Occupational Research Agenda (NORA) priority grant from the Northwest Center for Occupational Health & Safety. Please visit www.ohsushift.com to learn more.Self-Assessment and Self-Management Program Helps Truckers Avoid Musculoskeletal Injury
Behavioral self-monitoring (BSM) methods, where individuals repeatedly observe, evaluate, and record aspects of their own behavior, can produce valuable assessment data about injury hazards and near misses. Dr. Ryan Olson has developed and studied BSM assessment with less-than-truckload (LTL) truck drivers. LTL work involves hauling partially loaded trailers, making multiple daily stops, and performing frequent and demanding material handling work in a variety of customer environments. To address this difficulty, Dr. Olson’s research team employed two data collection methods: (1) intensive video monitoring, in which direct observation of work habits and environments were achieved through the use of a customized camera system installed in a working trailer and (2) behavioral self-monitoring, in which individuals repeatedly observed, evaluated, and recorded aspects of their own behavior and environmental conditions. Dr. Olson found that each instance of manual material handling increases the potential for severe (hazardous) body postures by 7%, whereas obtaining customer forklift assistance and preventing manual materials handling by palletizing transported materials decreased this potential by 12% and 20%, respectively. Comparisons between experimenter video observations and driver self-observations showed that drivers are quite accurate at self-assessing hazards that are environmental, frequent, and easy to discriminate, but less so at assessing potentially harmful body postures and rare work-related events or environments. These findings suggest areas in which positive interventions can reduce risk for injury, including organizational management of ground stops (e.g. facilitating the use of forklifts), re-engineering handles and steps that lead into trailers, and having workers self-assess the prevalence of certain work exposures. The results of this project are an important step forward in understanding and preventing musculoskeletal injuries among isolated workers and in advancing our knowledge about the reliability of ergonomic self-assessments.Study on Vigilance Performance Enhances Error & Threat Detection
Human performance on visual screening tasks is increasingly important to public and workplace safety. These tasks require human operators to detect rare but potentially dangerous signals or threats on some type of visual display. Examples include: aviation security workers searching for unusual passenger behaviors and prohibited items in luggage; radiologists screening for tumors or other abnormalities in sophisticated body images, and manufacturing workers searching for potentially dangerous and costly deviations in high-tech production processes. Dr. Olson collaborated with Lindsey Hogan and Matthew Bell of Santa Clara University (Santa Clara, California) to develop a simulated baggage-screening task that uses x-ray images provided by the Transportation Security Administration to investigate factors that enhance vigilant search behaviors. It is known that observers in visual search tasks miss threats at increasing rates as threats become less frequent (i.e. anomalous objects such as weapons in luggage are relatively rare). The research team tested a “Vigilance Reinforcement Hypothesis” (VRH), which proposes that signal detection reinforces search behaviors, and predicts more intense searching and better signal detection when signals are abundant. Dr. Olson has completed two laboratory studies that are supportive of this prediction, and has applied to the National Science Foundation (NSF) for funding to support continued work on learning phenomena that could be used to enhance signal detection, such as reinforcing variability in visual search patterns, and using planted signals as an intervention method to sustain vigilant search behaviors.Computer-based Training Effective for Immigrant Orchard Workers
W. Kent Anger, PhD, CROET Senior Scientist and Associate Director, has been developing and testing the effectiveness of a computer-based training system that is competent across cultures and is now available commercially. It is designed to be effective with the full range of occupational populations, from uneducated (no schooling) immigrant agricultural workers to office workers with graduate educations. Dr. Anger’s lab is shared with staff scientist Dr. Diane Rohlman, whose independent research focuses on neurotoxic effects in young workers and children of workers exposed to pesticides at work. Latinos dominate the agricultural workforce in Oregon and throughout the US. Many have limited years of education in countries with different systems of education than in the US. Drs. Anger and Rohlman have been investigating whether computer-based instruction (CBI) is suitable for this work group, which generally has an average of 5-6 years of education, though some have not been to school at all. Ladder safety was studied in a Latino orchard workforce that reported little computer experience and reported an average 5.6 years of formal education. The orchard workers rated the training highly and their knowledge of ladder safety improved substantially as measured by standardized tests. More importantly, there was a significant increase in safe work practices immediately after training, at 40 days after training and at 60 days, indicating that the learning was durable over time. This demonstrates that an agricultural workforce can learn job safety from CBI, translate the knowledge to work practice changes, and maintain those changes over time. Dr. Anger published this work in the International Journal of Training and Development.OHSU and Drs. Anger and Rohlman have a significant financial interest in Northwest Education Training and Assessment, LLC, a company that may have a commercial interest in the results of this research and technology. This potential conflict was reviewed, and a management plan, approved by the OHSU Conflict of Interest in Research Committee, was implemented.
• Continues to be a trusted information resource for Oregon workers
CROET has been proactively engaged in providing timely occupational health and safety information to employees, employers, health and safety professionals, doctors and nurses.
Toxicology Information Center (TIC)
Directed by Dr. Fred Berman, the TIC provides free scientifically accurate information for those with questions or concerns about chemical, biological, physical or other agents encountered in the workplace and elsewhere. In 2006-2007, Dr. Berman handled hundreds of consultation requests from occupational safety and health professionals, business owners, government agencies, physicians and nurses, the media, and the general working public. Inquiries covered a variety of issues, as shown on the chart. Chemical agents of concern included solvents, heavy metals, insecticides, fungicides, and herbicides. Physicians often called seeking information on a variety of potentially occupation-related health complaints.Calls in regard to indoor mold were common as were calls related to acute and chronic medical problems that were attributed to exposure to chemical agents. Each request took from less than an hour up to several days to respond to fully. The TIC is open from 7:30 a.m. to 4:00 p.m., Monday through Friday. Walk-in visitors have access to a variety of resources, including computers, databases, government reports, textbooks, and journals that are devoted to toxicology-related issues.
CROETweb.com
CROETweb.com is an occupational safety and health resource directory that contains links to over 1200 occupational safety and health resources focusing on day-to-day workplace issues. CROETweb serves thousands of users who regularly bookmark this resource, those who subscribe to the monthly electronic newsletter, and those searching by search engine (e.g. Google) for occupational health and safety topics on the web. It is widely recognized and respected by industrial health and other safety professionals as well as the general public. CROETweb was accessed an average 12,000-16,000 times per month for a total of 166,134 ‘hits’ in 2007. This monthly average hit rate has increased yearly since the inception of CROETweb.• CROETweb added 11 new home page topics, for a total of 83 in 2006
Hospitality – Hotel, Restaurant and Kitchen; Landscaping; Logging & Forestry; Acids & Bases; Chromium; Avian Flu; Occupational Asthma; Occupational Reproductive Hazards; Materials for Safety Talks; OSH Professional Development; and Safety, Language and Culture.
• An additional 13 topics were significantly revamped in 2007
Acids and Bases; Asbestos; EMF and Cell Phones; Beryllium; Ergonomics; Office Ergonomics; MSDS Resources; Avian Flu; Healthcare; Solvents; Pesticides; Respirators; Transportation)
• Annual page hits – 2006: 162,838
2007: 166,134
• More than 1,250 links are posted on CROETweb.com, including Oregon-specific information from
OR-OSHA.
Chemical Risk Information Service (CRIS)
OSHA regulations require employers to maintain Material Safety Data Sheets (MSDS) for hazardous chemicals used in their workplace. This often proves to be a difficult record-keeping task, and it can be burdensome to ensure that employees have quick access to health and safety information in the workplace when they need it. Since 1998, CROET’s Chemical Risk Information Service, directed by Dr. Gregory Higgins, has helped a growing number of local and international industries manage and distribute chemical safety information through its Internet-based MSDS management system. CROET’s working relationship with the Oregon Poison Center also ensures that employees covered by the program have ready access to medical information in the event of exposure. During 2006-2007, the Chemical Risk Information Service added five new clients, and now provides MSDS management services to 40 municipal, construction, and service companies, most of which are Oregon-based. Also during this period, this program began working with SafetyCal, a chemical labeling company located in Eugene, to begin developing a service to link CROET’s MSDS program with their labeling service so that clients can have a one-stop location to meet OSHA right-to-know regulations. Enhancements were made to the website and database during this period. CROET continues to provide expert MSDS management services at a reasonable cost, which is attractive to both small and large organizations.Health and Safety Training Symposia
CROET provides two health and safety symposia per year, one sponsored jointly with Portland State University. Topics are determined based on solicited and unsolicited feedback from the Oregon occupational health and safety professional community. The target audience includes health and safety professionals, occupational nurses and physicians, loss control specialists and human resource representatives, although the targeted group varies based on the symposium topic. The purpose of the symposia is to provide timely, up-to-date presentations, forums and discussions on workplace safety and health issues. CROET presented the following symposia in 2006-2007:Substance Use and Safety in the Workplace
November 2, 2007, Portland State University, Portland, Oregon
Safety at Work in Informal and Non-Traditional Settings: Protecting Vulnerable Workers
June 8, 2007 at the NECA/IBEW Electrical Training Center, Portland, Oregon
Workplace Violence Prevention
December 8, 2006 at the Native American Center at Portland State University, Portland, Oregon
Safety and Health for the Limited English Speaking Workforce: Challenges & Successes
June 9, 2006 at the Ambridge Event Center, Portland, Oregon
Regional Health and Safety Conferences
OR-OSHA sponsors the majority of health and safety conferences that CROET attends; these conferences are an important means by which CROET reaches out to working Oregonians. Workers and businesses learn about CROET and what it has to offer, and CROET personnel learn about the needs and concerns of workers and the industries that employ them. Moreover, CROET scientists are often asked to give health and safety presentations in addition to providing conference exhibits. Overall, conferences represent a tremendous networking opportunity for CROET outreach personnel. The following are safety and health conferences attended by CROET during 2006-2007:2006
• Oregon Governor’s Fire Service Summit
• NIOSH/NORA Town Hall Meeting
• Agriculture, Forestry and Fishing
• Bob Bryant Memorial Cascade Occupational Safety & Health Conference
• Oregon Workers’ Compensation Educational Conference
• HealthCare Ergonomics Conference
• Central Oregon Occupational Safety & Health Conference
• Southern Oregon Occupational Safety & Health Conference
• Northwest Occupational Health Conference
• NexCon 2006 - Next Generation Construction Summit: Defining the New Critical Path
• Western Pulp & Paper Workers Safety & Health Conference
2007
• Oregon Governor’s Occupational Safety & Health Conference
• Blue Mountain Occupational Safety & Health Conference
• Central Oregon Occupational Safety & Health Conference
• Southern Oregon Occupational Safety & Health Conference
• Northwest Occupational Health Conference
“Research to the Public” Exhibit
Jackie Shannon, Ph.D. developed and implemented a “Research to the Public” exhibit as part of the Oregon Museum of Science and Industry’s Body Worlds. This interactive exhibit (Nutrition Worlds) provided participants with an opportunity to obtain tailored feedback on their diet, including measurements of height, weight, waist circumference and percent body fat, measurements of blood glucose, HDL, LDL and total cholesterol levels. Participants also had the opportunity to become “research subjects”, where de-identified data on diet, body composition, cholesterol measures, and salivary samples for DNA extraction and genotyping were obtained. Over 3000 individuals participated in this project and provided data as part of this “Research to the Public” project. Nutrition Worlds is now being converted into an off the shelf exhibit with the capacity to be used at large health fairs throughout the year. This type of outreach benefits workers and the general public by increasing awareness of factors that contribute to healthy lifestyles and a healthy workforce.• Helped build biotech in Oregon
CROET scientists Stephen Lloyd PhD & Amanda McCullough PhD are interested in DNA mutations and the mechanisms cells use to repair DNA damage induced by environmental stresses, including sunlight. Through basic research into the biomolecular mechanisms of ultraviolet (UV) radiation-induced DNA mutation and repair, they have devised and are now developing a novel strategy for preventing UV-induced skin cancer. Since mammals have only one system for repairing sunlight-induced DNA damage, their strategy is to supply skin cells with a second DNA repair system, which can be applied topically as a lotion to the skin. This involves the use of lipid coatings and protein tags that effectively allows the targeting of the DNA repair system to the cell nucleus, where it can be effective, thereby providing an extra level of protection against UV-induced DNA mutation. The technology has been shown in laboratory experiments to almost completely repair UV-induced DNA damage within 2 hours of application. Drs. McCullough and Lloyd have formed a company, Restoration Genetics, Inc., to develop and commercialize this technology as a therapy for prevention of skin cancer. This technology is explained in more detail in CROET Newsletter Vol. 14, #1, which can be downloaded at: http://www.ohsu.edu/croet/about/pubs.cfm
• Became global ambassadors for CROET, OHSU and Oregon workers
The Global Health Center (GHC)
The newly formed Global Health Center (GHC), housed in the CROET Toxicology Information Center, facilitates OHSU collaboration with the global health community to promote quality and equity in health care at home and abroad. Through the GHC, CROET and OHSU are working with domestic and international communities to develop programs for students, faculty, staff and partners that will promote global health awareness, research, education and advocacy. Dr. Peter Spencer, CROET Director and Senior Scientist, serves as Interim Director of the Global Health Center. Dr. Spencer has long studied the causes and solutions to neglected human diseases in developing countries, and hopes to spawn a new generation of medical and research professionals certified in global health. Built on the principle that there can be an effective two-way exchange on matters such as cultural competency, health education, research opportunities and clinical practice, the long-range goal of the GHC is to maintain a compact, efficient operation on the campus and invest in building healthcare capacity in global communities. In 2007, planning began for transdisciplinary global health courses involving faculty, students and staff. This includes a health and hygiene community exchange program, championed by CROET’s Valerie Palmer, that brings Portland’s refugees from Africa together with students and faculty from OHSU schools of Dentistry, Nursing and Medicine, and other OHSU-based programs of the OSU College of Pharmacy.• Conducted laboratory research aimed at preventing or mitigating the adverse
effects of workplace injuries and exposures
Injury and Recovery of the Nervous System and Muscles
CROET scientists conduct basic research that examines the causes of injury to nerves and muscles in order to identify protective, preventative, and recovery methodologies for such injuries.
New Discoveries on Nervous System Effects of Environmental Pollutants, Statin Drugs, and Pesticides
Biomarkers allow us to determine when chemical exposures reach a toxic level and identify the need for medical intervention. Pamela Lein, PhD has discovered that polychlorinated biphenyls (PCBs), a class of developmental neurotoxicants and environmental pollutant, interfere with neuronal connections in the developing brain by disrupting normal patterns of nerve growth and plasticity (the ability of neurons to change in response to environmental stimulus). This is the first identification of a specific neurodevelopmental event that is altered by exposure to PCBs. Dr. Lein also discovered that exposure to PCBs during development actually alters the susceptibility of the adult brain to damage caused by lack of oxygen that occurs during a stroke. In a related discovery, Dr. Lein found a novel mechanism by which statins, the commonly prescribed lipid-lowering drugs, decrease neuroinflammation – this effect may explain clinical reports and experimental studies identifying a potential therapeutic effect of statins in diverse neuroinflammatory conditions such as migraine headaches, arthritis and asthma. Dr. Lein also discovered that chlorpyrifos, an organophosphate (OP) pesticide still commonly used in the U.S. and throughout the world, interferes with axonal outgrowth in developing neurons via a unique mechanism that involves interference with the morphogenic activity but not the enzymatic activity of acetylcholinesterase (the enzyme responsible for degrading the neurotransmitter, acetylcholine) – this has important ramifications regarding the use of acetylcholinesterase activity as a biomarker of exposure to toxic levels of OPs.Nerve Support Protein Plays Unique Role in Neuromuscular Development
By understanding basic mechanisms of neuromuscular development and maintenance, we will learn how to repair muscle and nerve connections damaged in workplace accidents. The wiring of the nervous system during development is coordinated by molecular signals exchanged between neurons, glial cells (support cells which ensheath neurons), and target cells that receive innervation. Bruce L. Patton, Ph.D. is studying signals that coordinate these cellular interactions. His interest is focused on the extracellular proteins that mediate direct contact between neurons, glia, and skeletal muscle fibers. The principal component of the extracellular protein matrix that covers a type of glial cell called the Schwann cell and skeletal muscle fibers is a glycoprotein called laminin. The Patton laboratory discovered four novel types of laminin; two are specifically associated with muscle fibers, and are concentrated at sites of synaptic contact, and the other two comprise the primary scaffold of the Schwann cell basal lamina. Patton’s lab has used a combination of genetic mutational studies in mice and cell and biochemical studies to show that each laminin subtype plays a unique and primary role during neuromuscular development as well as a continuing role in maintaining the mature tissue. For example: laminin-11 localizes nerve terminal differentiation at embryonic synaptic sites in muscle; laminin-9 organizes the active zones (transmitter release sites) in mature motor nerve terminals; laminins-2 and -8 regulate Schwann cell responses to axonal cues during nerve myelination — they act cooperatively to match the number and type of Schwann cells to the number and type of axons; and laminin-2 stabilizes the muscle membrane during contractions. Current research in the Patton lab is directed at determining precise activities (e.g. differentiation, proliferation, signaling, motility support), and the cellular receptors and pathways that mediate the laminins’ effects.Chronic Disease and Working Safety
Chronic disease takes a significant toll on our workforce just as it does in the broader community. CROET research seeks to discover causes of chronic diseases that are produced or exacerbated by workplace factors and identifies processes or procedures that can prevent or ameliorate those diseases and improve workplace safety.
Fruit Flies Enhance Our Understanding of Human Neurodegenerative Diseases
Doris Kretzschmar, PhD is interested in identifying genes and cellular mechanisms that underlie progressive degeneration of the nervous system, such as occurs in Alzheimer’s disease. She has used specialized mutant and transgenic Drosophila melanogaster (fruit fly) lines to analyze, at the functional and molecular level, a protein called Swiss-Cheese/Neuropathy Target Esterase, which is involved in organophosphate pesticide-induced neuronal degeneration. Dr. Kretzschmar discovered that dysregulation of another cellular protein, known as protein kinase A, when it occurs in the absence of a functional Swiss-Cheese/Neuropathy Target Esterase, leads to neurodegeneration. This finding promises to be of functional significance to our understanding of several important human neurodegenerative diseases. Dr. Kretzschmar is also using her fruit fly model to analyze the physiological and pathological functions of amyloid precursor proteins, which are key factors in the pathology of Alzheimer’s disease.Discoveries of Circadian Clock Function Leads to Enhanced Understanding of Sleep-Wake Cycles
Chuck Allen, PhD is interested in the brain’s circadian clock, which controls our sleep-wake cycles. Disruption of the circadian clock, such as occurs in workers who work odd shifts, plays an important role in increasing our risk for occupational accidents and chronic diseases. Most organisms, from plants to primates, display circadian rhythms, which are daily oscillations of physiological processes. The master circadian clock driving these circadian rhythms in mammals is located in a nerve group within the brain called the suprachiasmatic nucleus (SCN). Each SCN neuron expresses a molecular clock, which must be synchronized to other SCN neurons by neurotransmitter chemicals. Special classes of retinal cells that measure light intensity maintain the time-dependent coupling between the circadian clock and daily light-dark cycles. The long-term goal of Dr. Allen’s research is to identify the signaling mechanisms within the SCN and retina that generate and entrain circadian rhythms. In 2006-7, Dr. Allen discovered a variety of cellular mechanisms that control how light-induced signals are processed and passed to areas of the brain that are involved in circadian clock function. A goal of this research is to increase our understanding of circadian clock function so that effective strategies for mitigating the adverse and potentially dangerous effects of shift work and odd work situations can be developed.Organic Solvents Illuminate our Understanding of Neurological Disorders
Neurotoxic disorders of occupational, therapeutic, or other origin, in which the causative agent is identified, usually present as self-limiting neurodegenerative diseases that impact motor, sensory and other nerve functions. Similarly, some chemical agents, acting alone or aided by a susceptible genetic background, also seem to play a role in the cause of progressive neurodegenerative diseases (e.g., sporadic amyotrophic lateral sclerosis (ALS) and Parkinson’s disease). However, the molecular cascade over the long latent period from the beginning of natural disease development to clinical expression is unsolved and a key subject of investigation. Dr. Peter Spencer, Dr. Mohammad Sabri and Dr. Desire Tshala-Katumbay use organic solvents as tools to probe and model, over much shorter time scales, the human neurodegenerative diseases that take such a long time to develop. This requires exploration of the molecular mechanisms underlying the neurotoxic properties of these chemicals, which in turn is helpful in newly identifying hazardous substances in the workplace. New methods to identify and characterize the hazardous properties of chemicals require validation before they can be used to protect public health. One powerful method uses microarrays to capture changes in gene expression of tissues that have been exposed to chemicals and drugs. Microarray technology allows scientists to track the expression of thousands of genes at once. Dr. Spencer and his colleagues joined with six other leading laboratories to determine whether similar results could be obtained when experiments were replicated as closely as possible. The common over-the-counter analgesic acetaminophen was used as the test article because it is well established to produce liver toxicity. The study revealed similarities and some unexplained differences in data generated from different laboratories, but overall new information was captured on the molecular mechanisms of the drug’s liver toxicity. The study confirmed the value of microarrays in detecting, characterizing and understanding chemical toxicity. With validation of the method established, these scientists can now utilize microarrays to understand the pathological changes that occur following short- and long-term exposure to organic solvents.Computational Modeling of Genetic Variation Aids Our Understanding of Occupational Disease
Dr. Harvey Mohrenweiser is interested in reducing morbidity and mortality in individuals with elevated genetic susceptibility to common exposure-related diseases. Obesity, non-traditional work schedules and age are common exposures associated with increased risk of disease, injury and impaired performance. Such exposures have major negative consequences for health care and Worker Compensation costs for Oregon workers and the cost of doing business for Oregon businesses. Genetic variation has a clear role in modifying the susceptibility of individuals to these exposures; however, the problem of identifying the molecular basis for aberrant disease susceptibility is very complex, especially if the deviation from average disease susceptibility and contribution of multiple genes/variants and exposures are all small. Continued development of new experimental designs and approaches to data analysis will be required to address these complex problems, and they must be conquered if the potential for individualization of health care and medicine is to become a reality. Major progress has been made in identifying “disease causing” genes by studying susceptible families. Through computational and biochemical methods, Dr. Mohrenweiser has predicted that approximately 50% of all gene sequence alterations that have been identified in human genetic variation studies also alter protein function and potentially modify an individual’s risk of disease. This begins to explain the role of family history in predicting disease risk. DNA sequence variation with potential to impact gene expression is commonly observed in studies of DNA repair genes and genes with important roles in the response of cells to environmental agents. Dr. Mohrenweiser successfully employed statistical approaches to identify genetic variants that contribute to variation in the capacity of cells to repair damaged DNA. Genetic variation in DNA repair genes with key roles in repair of DNA damage caused by exposure to sunlight was found to explain about 20% of the variation among individuals at risk for melanoma. This is a very early step in efforts to identify people at elevated risk for this disease, as well as other diseases.Integrity of DNA (DNA damage, genetic alterations and disease)
Human health and risk for disease ultimately depend on the integrity of our DNA, the genetic material that provides the body’s blueprint for manufacturing proteins that carry out the function of cells and organs. Aberrant forms of DNA can produce inherited diseases, and changes in DNA during life are believed to trigger cancer and many other chronic diseases. Such changes can result from exposure to certain chemicals found in the workplace and others in the diet and medications. Two broad types of DNA changes are recognized: DNA damage and DNA silencing.
Genotoxicants Disrupt Neurodevelopment and Induce Neurodegenerative Disease Processes
Glen Kisby, PhD is interested in the role of DNA damage and DNA repair in neurodevelopment and neurodegenerative diseases, and in the influence of environmental factors (e.g., occupation, stress, diet) on brain tissue DNA repair. Synucleinopathies and tauopathies, neurological diseases that result from the pathological accumulation of alpha-synuclein and tau proteins, are important neuropathological hallmarks of neurodegenerative diseases, including Alzheimer’s disease and the prototypical neurodegenerative disorder, Western Pacific amyotrophic lateral sclerosis/Parkinson-dementia complex (ALS/PDC). The cycad plant has been shown to be a strong causal factor for ALS/PDC. Dr. Kisby has shown that the cycad plant genotoxicant, MAM, disrupts cellular processes that regulate tau and synuclein through a DNA damage mechanism. Further investigation of the relationship between MAM-induced DNA damage and tau protein metabolism during early brain development could provide important clues about how cycads contribute to the neurodegeneration in PDC and related neurological disorders (e.g., Alzheimer’s and Parkinson’s disease). Dr. Kisby has also shown that MAM, as well as the chemotherapeutic agent nitrogen mustard, disrupts early brain development through a DNA damage-mediated mechanism. These findings suggest that the specific combination of DNA lesion and DNA repair capacity within a neuron are key factors that determine whether the immature brain is vulnerable to a particular genotoxicant. Such factors are expected to be particularly important for understanding how environmental genotoxicants or chemotherapeutic agents induce their long-term effects on the developing brain. An understanding of these processes will enable us to avoid workplace/environmental exposures that increase our risk for neurological disease as well as allow us to develop new treatments for such diseases. Following this line of thought, Dr. Kisby has shown that the brain of aging animals on a caloric-restricted diet is more efficient at repairing DNA damage than animals on an unrestricted diet. This finding indicates that dietary changes can have a positive effect on the DNA repair capacity of the brain, particularly among the aging population.Pesticides May Induce Oxidative Stress and DNA Damage in Agricultural Workers
Multiple studies have reported associations between exposure to agricultural chemicals and various health outcomes including cancer, Parkinson’s disease and other neurological diseases. Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to these adverse health effects. In recent in vivo and in vitro studies, Dr. Kisby has found evidence that organophosphate pesticides induce oxidative stress and DNA damage in agricultural workers. The method of detecting such changes, called biomarkers, increases our understanding of the link between pesticides and a number of health outcomes (e.g., neurological disorders and cancer). This work has been accepted for publication in the journal Toxicology and Applied Pharmacology.Mechanisms Behind Insulin Secretion Diseases Being Uncovered
ATP-sensitive potassium (KATP) channels are gated by the intracellular nucleotides ATP and ADP, the major energy molecules within cells. As such, they couple cell metabolism to membrane excitability and regulate a variety of physiological processes including insulin secretion, vasodilatation, neurotransmitter release, and cell defenses against cardiac and brain ischemia. Malfunction of KATP channels due to genetic mutations has been shown to cause congenital hyperinsulinism, diabetes, and delayed cardiomyopathy. The primary research focus of Show-Ling Shyng, PhD is to understand the role of KATP channels in health and disease, in particular with regard to the regulation of insulin and glucose homeostasis. Dr. Shyng has discovered new mechanisms by which mutations affect ion channel function to cause insulin secretion diseases. Her ultimate goal is to develop therapeutic strategies to combat diseases caused by KATP channel dysfunction resulting from genetic mutations or environmental/occupational exposures.Dietary Factors Alter Susceptibility to Cancer
Jackie Shannon, Ph.D., uses epidemiologic methods to investigate the role of bioactive food components and metabolic dysregulation in the early stages of cancer development. She is interested in: 1) the role of dietary compounds, including omega-3 fatty acids and sulforaphane (an anticancer, antidiabetic and antimicrobial compound found in cruciferous vegetables) in the early development and prevention of prostate and breast cancer; 2) genetic susceptibility and dietary interactions in breast and prostate cancer prevention; and 3) metabolic dysregulation (including obesity and lipid metabolism) in cancer prevention. Dr. Shannon published her most recent findings on the relationship between omega-3 fatty acids and breast cancer risk. She is building upon her work by obtaining funding to begin one of OHSU’s first chemoprevention trials for women newly diagnosed with ductal carcinoma in situ. Her long-term goal is to enhance the overall health of the workforce through the discovery of factors that reduce the incidence of cancer in our population.New Gene Silencing System Facilitates Cancer Research
Gene silencing occurs when a gene that should be expressed in a cell turns off unexpectedly. It is a common component of cancer. Aberrant gene silencing plays a causal role in cancer because it leads to inactivation of tumor suppressor genes. The endpoints of silencing are fairly well defined: promoter region DNA methylation and repressive histone modifications. Mitchell Turker, PhD has devised a system to trigger and study gene silencing in mammalian cells. The new system will be useful to determine how workplace and environmental exposures could initiate gene silencing and also to identify diets or drugs that could be designed to prevent gene silencing from occurring.Mutation Discovery May Lead to New Skin Cancer Prevention Strategies
Dr. Mitchell Turker has identified a combination of cellular exposures that lead to an unusual mutation induced by exposure to ultraviolet radiation (UV). Although rare in most cancers, this mutation (termed the tandem mutation) is found commonly in skin cancers and is due to sun exposure. A combination of UVB, which is the damaging form of ultraviolet light found in sunlight, and oxidative stress was shown to effectively induce the tandem mutation. This observation is aimed at developing strategies to prevent skin cancers, such as those that occur among outdoor workers. Dr. Turker is continuing a long-term project to identify the types of mutations induced by exposure to ionizing radiation. Ionizing radiation is found at low levels in our environment and is used commonly in diagnostic x-rays and in cancer treatment. Knowledge of the types of mutations induced by this form of radiation will be helpful to determine whether a person has been exposed, the consequences of exposure, and to estimate the level of exposure.New Research Discovers Mechanisms Underlying How Tumor Cells Resist Chemotherapy
Occupational and environmental exposure to chemicals such as butadiene (a major building block in the synthetic rubber and plastics industries) and acrolein (a major contaminant in gasoline and diesel vapors and cigarette smoke) represent a significant health hazard and are classified as human cancer-causing agents. Results from the laboratory group of Stephen Lloyd, PhD demonstrate the mechanisms by which exposure to these chemicals causes modifications in DNA that lead to mutations and transformation of normal cells into cancer cells. These studies were extended to show that these chemicals undergo complex secondary chemical reactions in which the two strands of DNA can be crosslinked to one another, a form of DNA damage that usually leads to cell death. Crosslinking DNA is one of the major mechanisms by which chemotherapeutic agents kill cancer cells. Even though these chemicals can crosslink the DNA strands, further work by the Lloyd group has shown that cells have special enzymes that can copy DNA even if it is crosslinked. This finding has implications for chemotherapeutic treatment of cancers, providing the first evidence for how cells (especially tumor cells) might resist killing by crosslinking agents.Skin Cancer Prevention Therapeutic Shown to Enhance Repair of Sunlight-Induced DNA Damage in Human Skin
Even though the Pacific Northwest is generally associated with only modest sun exposure, the state ranks in the top 5 nationally for sunlight-induced skin cancers. This is a significant hazard for working Oregonians. Although the reasons underlying the high incidence of skin cancer in Oregonians are complex, it is well established that sun exposure is the primary cause of non-melanoma skin cancers. It is important to take steps to prevent or at least significantly reduce the onset of this disease. Toward this goal, the research laboratories of Drs. Amanda McCullough and Stephen Lloyd have combined research interests and expertise to develop a potential prevention therapy for these skin cancers. Together, they have patented DNA repair enzymes that when delivered to human skin cells, rapidly repair sunlight-induced DNA damage. Their investigations have recently shown that when human skin is grown in the laboratory, repair of sunlight damage rapidly occurs when the DNA repair lotion is applied. These studies are aimed at obtaining FDA safety approval for initial human clinical trials.Chronic Low-dose Formaldehyde Exposure Results in DNA Damage Processed by the Homologous Recombination Pathway in Yeast
Formaldehyde exposure occurs both in occupational settings and household environments. Formaldehyde is a respiratory irritant associated with asthma and “sick building syndrome”, and exposure is associated with the occurrence of nasopharyngeal cancers and DNA damage. In order to identify and characterize the biochemical mechanisms for repair of formaldehyde-induced DNA damage, the McCullough lab is utilizing a yeast model system that allows the entire genome to be screened for genes that confer formaldehyde sensitivity. These studies have identified specific biochemical pathways that protect cells from the cytotoxic effects of acute and chronic formaldehyde exposures, results that will impact the assessment of exposure limits considered safe for humans.2004-2005 CROET Highlights
Surveillance, Applications and Outreach
CROET conducts workplace surveillance so that prevention and research needs can be identified, and applications research to bring the benefits of science to the workplace floor. It also reaches out to provide education and information to the Oregon workforce and beyond.
Oregon Fatality Assessment and Control Evaluation (OR-FACE) Program
Dr. Gary Rischitelli leads the Oregon Fatality Assessment and Control Evaluation (OR-FACE) program that tracks, investigates, and reports on occupational fatalities in Oregon. Each incident is investigated, entered in a database, and codes are added for industry, occupation, and event. During 2004 and 2005, OR-FACE recorded 62 and 67 fatalities, respectively. OR-FACE investigates incidents in specific national and local target areas of concern, and each year produces about 12 investigation reports with safety recommendations. During 2004-05, OR-FACE also published two hazard alerts — one on electrocution from high-voltage power lines during highway work and another on the unexpected finding that parked vehicles are a common cause of fatal injury. In 2005, OR-FACE published its first annual report, summarizing data from the program’s first full year of operation in 2003. The report charted frequencies by age, gender, race/ethnicity, day, time, month, county, industry, occupation, and event and included an abstract of each incident. Principal areas of concern were highlighted in relation to logging, mobile machinery, and transportation. In the 2004 annual report, an additional area of concern was observed in an elevated fatality rate among workers aged 65 and over, including a high incidence of falls and suicide. OR-FACE investigation reports and other publications are available on the program’s website (www.ohsu.edu/croet/face). Investigation reports from Oregon and other FACE states are also available in the electronic library maintained by the National Institute for Occupational Safety and Health (www.cdc.gov/niosh/face), which funds the program.Computer-based Training Effective for Shop Floor Workers (food services)
In collaboration with an urban hospital in Portland, Dr. Kent Anger provided interactive computer-based safety training to workers in a food services department that supplies food to hospital patients, visitors, and staff. The food services workers evaluated the training very positively. Based on tests given before and after the training, knowledge improved significantly. Generalization of the knowledge to the workplace was confirmed by increased accuracy in answering on-the-job questions that required application of knowledge to the work setting. Observations were also made of work practices and workplace conditions before and after the training. Problematic kitchen conditions, such as puddles, decreased after-training and after-adjustment for increasing production/workload. Work practice improvement was seen in three-fourths of the workers. These findings demonstrate that the benefits of computer-based safety instruction extend to blue collar workers who do not usually receive computer-based training, which is only rarely studied. It is even more rare for research to study and report changes in reaction (did they like the training?), knowledge, and behavior or work practice change, which adds confidence to the findings. This and other studies demonstrate, in an experimentally rigorous way, that computer-based training can be used with workers on the shop floor, not just in offices where it is most typically used. This work was published in the Journal of Safety Research.Evidence of Increased Pesticide Metabolic By-Products in Agricultural Areas
Dr. William Lambert and others at CROET have been investigating the possibility that children of migrant farm workers are at increased risk of exposure to organophosphate (OP) pesticides due to “carry-home” transport processes and residential location. Although this at-risk status is generally recognized, few available reports describe the extent of this exposure among agricultural communities. It is very difficult to measure the very low levels of pesticide exposures, so Dr. Lambert and others at CROET quantified the metabolic products of organophosphate pesticides in samples of urine from 176 children, 2-6 years of age. The children were from three Oregon communities hosting differing agricultural industries: pears, cherries, and fruit berries. Up to three spot samples of urine were collected from children at the beginning, mid-point, and end of their parents’ work seasons. The median levels of dimethylthiophosphate (DMTP), the most commonly detected metabolite of OP pesticides, was 2.5 to 4 times higher in urine samples from children in the agricultural communities when compared to a reference group of children who lived in an urban community and whose parents did not work in agriculture. After controlling for confounders, the median level of DMTP in children in the pear community was 1.92 times higher than the level in children of the berry community and 1.75 times higher than the level in children of the cherry community. DMTP levels increased across the work season only within the berry community. Levels decreased in the cherry community and remained constant in the pear community. This variation across time in pesticide levels within the children who were followed demonstrates the need for multiple urine samples to accurately characterize longer term and/or cumulative exposure. This variability could be attributed to the types and amounts of organophosphate pesticides used, the timing of applications and degradation of residues in the environment, work operations and hygiene practices, the proximity of housing to orchards and fields, or the movement of these working families.Improved Training for Beginning Flight Students
Flight students have the highest risk of landing accidents when flying solo during their first 30 hours of training. Since training innovations may help prevent these potentially fatal crashes, Dr. Ryan Olson investigated the potential benefits of one type of interactive training for new flight students. Personal Computer-Based Aviation Training Devices (PCATDs) are increasingly sophisticated and affordable, but are currently approved only for limited instrument training with experienced students. Dr. Olson hypothesized that PCATDs could be used strategically to prevent landing crashes among novice pilots. In 2005, Dr. Olson published evidence in the Journal of Aviation/Aerospace Education and Research that experimental PCATD training during the first 30 flight hours may improve multiple performance measures. Since no measurable harm was found, early PCATD training should be tested more aggressively as a risk-management intervention.CROET Outreach Expansion Continues
CROETweb.com is the Center’s occupational safety and health resource directory that provides information 24 hours a day, seven days a week.• CROETweb topics expanded from 46 different English topics in 2004 to 72 topics
• Spanish-language topic pages expanded from 37 in 2004 to 60 topic pages
• More than 1,250 links are posted on the CROETweb page
more than 19,000 downloads in 2004-2005.
Symposia
• When Employees’ Personal Lives Interact with Occupational Safety and Health • The Multidimensional Causes of Accidents and Injuries
Exhibits
• Central OR-OSHA; Southern OR-OSHA; Cascade Western Pulp & Paper (OR-OSHA)• Northwest Occupational Health Conferences
• Governor’s Occupational Safety and Health (GOSH) Conference
• NexCon Construction Summit
• Oregon Governor’s Fire Service Summit
• Healthcare Ergonomics
• Oregon Worker Compensation Educational Conference
Collaboration/Advisory
CROET Advisory Committee
Injury and Recovery of the nervous System and Muscles
CROET scientists conduct basic research that examines the causes of injury to nerves and muscles in order to identify protective, preventive, and recovery methodologies for such injuries.
Organophosphate but not Pyrethroid Pesticides Associated with Airway Muscle Spasm
Important Mechanisms of Neuronal Protein Transport Revealed
Dominant Schwann Cell Role in Nerve Function and Recovery from Injury
2003 CROET Highlights
Workplace fatality surveillance in Oregon produces hazard alerts, interactive website
CROET and the Oregon Departments of Human Services and Consumer & Business Services received a cooperative agreement from the National Institute of Occupational Safety and Health (NIOSH) to identify, investigate, and develop prevention strategies for traumatic occupational fatalities in Oregon. Oregon joins 13 other U.S. states in the NIOSH-sponsored Fatality Assessment & Control Evaluation (FACE) program. In the first year of the program (2003), Dr. Gary Rischitelli (Principal Investigator) and Dr. Joan Rothlein have conducted in-depth investigations of over 30 occupational fatalities in Oregon and developed industry-specific recommendations for prevention. For example, one hazard alert focused on electrocutions in Oregon companies using the same equipment (truck-mounted guard rail installer). These hazard alerts and other reports are available at http://www.ohsu.edu/croet/face. This interactive website provides current information on demographic factors in Oregon fatalities.
Computer-based training effective in people with limited formal education
CROET’s cTRAIN computer-based training, developed by Dr. Kent Anger, continued to grow in 2003. Content programs on safety in food service and drywall finishing have increased worker knowledge and safe work practices. In addition, the content programs have been well received by workers in those industries. The food services research has been accepted for publication in the Journal of Safety Research. Begun in November, a collaboration between CROET and Medford’s Bear Creek Corporation demonstrated that cTRAIN computer-based training can be used to provide critical safety training (ladder safety) to the entire agricultural workforce of orchard workers, including some who had no formal education. Work began on a new grant to use cTRAIN in Oregon vineyards.
(http://www.ohsu.edu/croet/faculty/anger/)
CROET website adds second home page to improve access
CROET’s website was divided into two separate, but complementary, websites in July. One site (http://www.ohsu.edu/croet/) contains information about CROET faculty and staff projects, while the other is devoted exclusively to CROET’s popular and well-regarded occupational safety and health resource directory (http://www.croetweb.com). This change provides easier access to both the resource directory and to CROET research capabilities, outreach, and education. CROET’s occupational safety and health resource directory, organized into 46 topic areas, contains links to over 1,000 resources and serves as a major source of safety and health information for working Oregonians and their families. All resources are now stored in a database resulting in new functionality. For example, the website can be sorted for Oregon-specific or Spanish-language materials, and a new search tool allows for specialized searches. Another added functionality of the website is the ability to accept online registrations for CROET’s annual health and safety symposia. This resulted in increased efficiency and decreased expenditures for paper and mailing. All of CROET’s newsletters dating back to 1999 have been made available online, also reducing mailing costs.
Toxicogenomics, a cutting-edge technology, begins at CROET
Toxicogenomics is a new technology that promises to revolutionize understanding of chemical risk, disease mechanisms, and even treatment options. The heart of the technology is the microarray, a glass plate containing up to 20,000 “spots” of genetic material obtained from an animal such as the mouse. These spots can be used to interrogate molecules derived from animals that have been exposed to test chemicals. The resulting pattern of microarray response indicates which cellular networks are affected. In 2003, Dr. Peter Spencer and colleagues completed development and initiated research operations of this new laboratory. OHSU and CROET thus became part of NIH National Institutes of Environmental Health Sciences (NIEHS) Toxicogenomics Research Consortium; this consortium includes the Massachusetts Institute of Technology, Fred Hutchinson Cancer Research Center, University of Washington, Duke University, and University of North Carolina. CROET is using the microarray technology to assess the neurotoxicity of organic solvents, including those used as cleaners and degreasers. (http://www.ohsu.edu/croet/research/centers/toxicogenomics/)
New mechanism of organophosphate pesticide damage reveals very low-concentration effects
Nervous system damage follows high-concentration exposures to organophosphate (OP) pesticides such as chlorpyrifos. A metabolite of the pesticide reduces the activity of the enzyme acetylcholinesterase (AChE) which normally acts as a brake on repeated, uncontrolled firing of nerve cells. AChE reduction is therefore widely used as a biomarker or internal measure of exposure to OP pesticides. However, recent animal studies suggest that pesticide concentrations that do not inhibit the AChE may still cause damage to the nervous system in very young or still-developing animals. Learning, memory, and motor behavior are implicated. Assessing risk to children has been complicated by the fact that the mechanisms by which organophosphate pesticides disrupt the developing nervous system are not understood. CROET’s Dr. Pamela Lein recently found that chlorpyrifos blocks the effect of AChE in growing nerve cell (axon) processes, and at levels below those required to reduce AchE activity. Since disruption of axon growth has been associated with functional deficits, these findings reveal a mechanism that explains how exposure to very low levels of OP pesticides could cause behavioral problems in children. Since many of the same mechanisms that regulate axon growth in the developing nervous system also influence axon regrowth following injury, Dr. Lein’s work raises the possibility that exposure to low levels of pesticides may also interfere with nerve regeneration in adults following work-related injuries. Further, these data raise questions of the sensitivity of AChE activity for monitoring damage following exposure to OP pesticides. (http://www.ohsu.edu/croet/faculty/lein/)
One more piece of the sleep-wake jigsaw puzzle
A significant number of Oregonians work nontraditional hours. They are staying awake and working while a part of the brain called the suprachiasmatic nucleus (SCN) is telling them it is time to sleep. Nerve cells in the SCN contain a “molecular clock” that keeps 24-hour time. Through the work of Dr. Charles Allen, CROET is studying how these nerve cells translate the molecular clock information into an output signal that regulates activities such as sleep and wakefulness. Before now, it was believed that “rhythmic” neurons—that cycle on and off during the day and night—controlled our circadian rhythm and thus caused us to sleep and wake. However, in 2003, Dr. Allen discovered a group of SCN neurons that are important for driving behavioral and hormonal rhythms, but that are not rhythmic — they do not cycle on and off over time. These findings suggest that the molecular clock that controls sleep and wakefulness is an interaction between rhythmic and non-rhythmic neurons. These observations add another piece of information to complete the puzzle of how the brain generates timing information. A better understanding of the brain timing mechanism will help develop more effective strategies for workers to handle the health and performance challenges arising from rotating or night work schedules. (http://www.ohsu.edu/croet/faculty/allenc/)
Nerve repair: Protein promotes nerve development
Nerves regenerate imperfectly following injury in adults. Nerve formation requires growth of the nerve fiber process (axon), multiplication of attendant Schwann cells to match the length and number of axons, and the formation by Schwann cells of an axon ensheathment that is called myelin. These steps occur on a precise schedule during development and are recapitulated during nerve regeneration after injury. The molecular mechanisms that control the developmental schedule are still largely unknown. Genetic defects in children with a congenital neuropathy have provided a clue. There is a protein missing in these children, called laminin, which normally covers the surface of Schwann cells in the nerve. Working with laboratory mice, Dr. Bruce Patton’s research group found that Schwann cells actually make multiple versions or types of laminin. Mice engineered to lack two versions of the laminin protein were completely unable to produce myelin and unable to walk. They tested the feasibility of genetic therapy for these myelin defects by re-engineering the mice to make large amounts of a third version of laminin, which is normally present at very low levels in nerves. The additional protein stimulated myelin formation and enabled the mice to walk. (To see a movie of these mice, visit http://www.ohsu.edu/croet/research/highlights/nerverepair.html.) By increasing the output of this protein in children with neuropathy, or in injured patients, nerve development and regeneration might be improved. Perhaps more importantly, future studies aimed at discovering how the laminins promote myelin formation by Schwann cells may allow the development of drugs that act like laminins, to promote myelination without genetic engineering. (http://www.ohsu.edu/croet/faculty/patton/)Reducing ultraviolet light exposure to prevent skin cancers
Exposure to solar radiation is the single most significant risk factor associated with the development of skin cancer. More than half of all new cancers are skin cancers, with the total number of new cases exceeding 1 million annually. Occupational exposure to deleterious amounts of natural ultraviolet (UV) sunlight (for example, enough to cause a sunburn) occurs in the farming, maritime, and construction industries, and all of these workers are classified as high-risk groups for skin cancer. This type of skin cancer is named “non-melanoma,” and it is the most common type of skin cancer. Fortunately, it is usually not malignant or life-threatening. In an effort to prevent or at least delay the onset of non-melanoma skin cancers, research in the laboratories of Dr. Amanda McCullough and Dr. Stephen Lloyd has focused on novel ways to enhance the capacity of skin cells to repair DNA damage caused by sunlight overexposure. If skin can rapidly repair damage from sun overexposure, most skin cancer will not develop. Their research has shown, in a test system consisting of human cells, that the application of a specific type of enzyme repairs the damage caused by UV light by as much as 10 times faster than the skin’s natural repair enzymes. They have been issued a patent for enzymes that have the potential to reduce or prevent non-melanoma skin cancers and suppression of the body’s immune system, another danger that follows UV overexposure. This technology will allow the development of new DNA repair enzymes that can be introduced into human epidermal (skin) cells through a skin lotion, to rapidly initiate the repair of damage to DNA caused by exposure to UV light. This new DNA repair system is expected to reduce the frequency and rate of onset of non-melanoma skin cancer and prevent or greatly alleviate UV-induced suppression of the immune system. (http://www.ohsu.edu/croet/faculty/mccullough/)
Motor proteins and muscle strength
In order to grow and maintain nerve processes, special molecules called motor proteins transport molecules from the nerve cell bodies, where they are made, out into the axon and dendritic processes, where they do their work. The neuronal transport system is particularly important for motor nerve cells that control muscles, because their axons reach all the way from the the spinal cord out into the arms and legs, where they supply muscles. Loss of motor nerve cells results in profound muscle weakness, as seen in poliomyelitis and Lou Gehrig's disease. Two CROET groups are studying the role of motor proteins in nerve cells. The Banker lab is developing imaging methods to visualize the movement of motor proteins and nutrients in living cells. They have found that some motor proteins are “smart”— they take their cargoes only to a specific location in the cell — unlike their “dumb” colleagues that can’t distinguish between axons and dendrites. Smart motors may be important for ensuring that key cellular molecules always go to the right destination. (http://www.ohsu.edu/croet/faculty/banker/).A second team, led by Dr. Mohammad Sabri, has been investigating how certain solvents used in industry may lead to adverse effects on the nervous system. They discovered that solvent-derived chemicals react with motor and other proteins, causing them to accumulate in swellings that disrupt function and cause muscle weakness. (http://www.ohsu.edu/croet/faculty/sabri/ and http://www.ohsu.edu/croet/faculty/spencer/)
New health effects of pesticides—oxidative stress studied
Most studies involving pesticide exposures compare reported exposure to health effects, such as evidence of damage to the brain and nervous system. However, the amount and frequency of “exposure” is based on statements by the exposed individuals. Dr. Glen Kisby is studying the biological mechanisms of pesticide exposure to health effects. With former CROET faculty member Dr. Linda McCauley, Dr. Kisby is studying potent organophosphate pesticides (OPs) such as those used in Oregon. OP pesticides have been found to produce oxidative stress. Oxidative stress occurs when oxygen free radicals (oxygen molecules) combine with other molecules in a way that damages those molecules or prevents them from performing their normal function. Dr. Kisby and Dr. McCauley compared pesticide applicators with farmworkers who do not apply pesticides and with people who do not work on farms (controls). The levels of oxidative stress as measured in urine (DNA damage), blood (oxidized lipids), and white blood cells (activity of a DNA repair protein) were much higher in farmworkers and pesticide applicators than in controls. Additional research is under way to confirm and expand these findings in the laboratory and in the field in Oregon. (http://www.ohsu.edu/croet/faculty/kisby/)
2002 CROETHighlights
Nanotechnology: Guidance Proteins Control Growth of Neurons
Drs. Gary Banker and Bruce Patton are exploring the application of nanotechnology—the technology used in the semiconductor industry to make computer chips—to study how growing nerve fibers interact with physical and chemical features in their environment. The goal is to produce interactions between living nerve cells and silicon chips bearing microelectronic circuits, leading to the development of neural prosthetic devices that could restore function of damaged nerves or damaged brain tissue. One of the key challenges in this work is to adapt nanofabrication methods to allow patterning of proteins, including the proteins that guide growing axons, without destroying their biological activity. In 2002, these investigators developed a novel two-step approach that allows formation of accurate patterns while preserving protein function. They have gone on to show that, by preparing patterns combining two different guidance proteins, the growth of axons and dendrites can be controlled independently. This project, which involves collaborations with scientists at Cornell University, is part of one of ten Science and Technology Centers in the country funded by the National Science Foundation to encourage technology transfer and innovative approaches to interdisciplinary activities. (http://www.ohsu.edu/croet/faculty/banker/index.html) (http://www.ohsu.edu/croet/faculty/patton/)
cTRAIN: Ergonomics Training for Drywall Finishers and Food Service Workers
CROET’s program to develop effective individual training methods for occupational safety and health continued to grow in 2002. Our computer-based training program, cTRAIN, was developed by Dr. Kent Anger, CROET Associate Director, and Dr. Diane Rohlman in collaboration with Mr. John Kirkpatrick of the Painters District Council. Research continued on the basic principles underlying training, an area almost devoid of research in working adults, demonstrating again the superiority of interactive training(quizzing during training with immediate feedback on answer accuracy). Quiz frequency appeared to be important for some material, with accuracy on the post-test declining in a program with up to 17 screens of information prior to a quiz, but not in programs with more frequent quizzes. Interestingly, open-book quizzes during training produced slightly better recall than closed-book quizzes, when evaluated later by a closed-book test. New programs for drywall finishing (ergonomic and other issues), lab safety, and food handling were developed and began field testing. The food services safety and health content program increased knowledge of fire safety and hazards such as those leading to slips and falls. (http://www.ohsu.edu/croet/faculty/anger/)
Superfund Grant: Findings and Impacts
Now in its third year, CROET’s federally funded Superfund Basic Research Center (SBRC) conducts research important to the health of Oregon workers and their environment. Scientists at CROET, Oregon State University, and Battelle Pacific Northwest are working together on a broad range of biomedical and environmental engineering projects. CROET scientists Dr. Mohamed Sabri and Dr. Peter Spencer are studying chemicals that damage the nervous system. Their work has uncovered a potent nerve axon toxin, 1,2-diacetylbenzene (DAB), which is found as a minor component in a number of organic solvent mixtures, including gasoline. 1,2-DAB reacts with proteins to form a blue pigment that can be found in urine, where it may provide a marker of exposure to this and chemically related solvent chemicals with neurotoxic potential. Dr. Jennifer Field, an SBRC scientist based at Oregon State University, is studying ways to enhance microbial transformation (degradation) of trichloroethylene (TCE), a common toxic contaminant at Superfund sites. Natural degradation of TCE in groundwater can be quite inefficient and slow, and toxic metabolic products including vinyl chloride can accumulate if degradation does not proceed to completion. Dr. Field and her colleagues are developing a technology that can speed degradation rates and help prevent accumulation of toxic metabolites. With further refinement, this technology may one day produce an inexpensive, non-toxic chemical additive mixture that will dramatically speed up the rate of groundwater decontamination in comparison to currently existing remediation strategies. (http://www.ohsu.edu/croet/sbrc/)
Toxicology Information Center: TIC Focus Expands
CROET’S Toxicology Information Center (TIC) is a special purpose library with holdings relevant to CROET’s mission and with access to the world’s electronic resources on the Internet. The TIC, under the directorship of Fred Berman, DVM, PhD, responds to inquiries from professionals and the lay public regarding chemicals encountered inthe workplace, home, or other environments. Examples from the more than 250 phone and Internet queries received last year include: health risks from carbon monoxide, chlorine, freon, trichloroethylene (TCE), benzene, diesel and aviation fuel, and childhood lead exposure. The TIC has also been fielding an increasing number of questions about the broad area of occupational health, beyond its initial scope of toxicology. Just as CROET’s research, education, and website have expanded over the years to broad areas of occupational safety and health, the TIC now responds to all occupational health inquiries. The resources of the TIC, including computers, are available to the public Monday through Friday from 8 a.m. until 5 p.m. For more information or to join the CROET mailing list, visit our website or contact CROET by phone at 503-494-4273. (http://www.ohsu.edu/croet/outreach/tic.html)
CROETweb Evolves: Site Redesign, Electronic Newsletter, Movies, Larger Focus Group
CROETweb is a major source of occupational safety and health information for all Oregonians, as well as a repository of information about the Center’s many activities. Designed as a directory, the resource area of CROETweb contains links to hundreds of resources for health and safety professionals. Pages are dedicated to all major Oregon industries and occupations, as well as to a variety of safety and health topics that are updated on a regular basis. CROETweb was redesigned in 2002 to improve the navigation and usability of the website. A monthly email newsletter was begun to provide information about “what’s new” on the CROET website, as well as upcoming events. Subscriptions to the newsletter are received daily. Six short movies were created that feature CROET scientists describing their research and how it benefits Oregon. They are available at CROET’s home page. Several Oregon safety and health professionals were recruited as new members to CROET’s Web Focus Group, which provides feedback about the website and makes content recommendations for the occupation and industry pages. Activity on CROETweb continued to increase. Hits on the site grew to over 190,000 in 2002 (up nearly 80 percent from 2001) with more than 50,000 visitors (up 72 percent from 2001). Oregon safety and health specialists tell
us they visit CROETweb frequently. (http://www.croetweb.com)
Education: Responding Across the Full Spectrum of Educational Needs
CROET’s education program has a broad scope. The focus of our training programs ranges from occupational safety and health professionals to graduate students and postdoctoral trainees (funded by grants), and from college students in our summer student program to high school students visiting for one or more days in a CROET laboratory. In 2002, we held seminars targeted at the occupational safety and health community: (1) Developing More Effective Training, and (2) Office Workers, the latter as part of our collaboration with Portland State University’s Occupational Health Psychology Program. CROET also staffed Brain Awareness Week at OMSI, providing neurobehavioral testing for many attendees, from children to post-retirement adults. CROET continued to participate actively in Oregon’s Saturday Academy program, including mentoring young women as part of the Advocates for Women in Science, Engineering and Mathematics (see award for Dr. Mohammed Sabri in Selected 2002 Accomplishments). (http://www.ohsu.edu/croet/outreach/)
Chemical Risk Information Service: Expanded Services to Oregon Business
CROET’s fee-based Chemical Risk Information Service is a 24/7 toxicological risk information program designed to help business and industrial clients comply with the OSHA Hazard Communication Standard. Directed by Greg Higgins, PhD, the program expanded services during 2002 by adding LaserJet printer products to the family of Hewlett Packard (HP) products already drawing on CROET’s unique service. Worldwide access is now provided for customers needing MSDSs for HP inkjet and LaserJet printer cartridges and inks. The chemical risk program also began upgrading database management capabilities this year by converting website operations to Microsoft SQL Server. This change is expected to streamline operations, improve customer response time, and provide the infrastructure necessary for continued growth. (http://www.ohsu.edu/croet-cris)
CROET 2001 Highlights
Toxicology Information Center: Responding to Oregonians’ Questions
CROET’S Toxicology Information Center (TIC) is a special purpose library with holdings relevant to the mission of CROET, its scientists and staff, and with access to the world’s electronic resources on the Internet. The TIC’s printed collection is centered on current publications in industrial, occupational, environmental, and epidemiological research, as well as a core group of basic science journals selected by CROET faculty and staff. Among the TIC resources are special collections of information about occupational and environmental issues assembled from a wide variety of scientific literature, governmental reports, and Internet resources (reviewed). Under the directorship of Fred Berman, DVM, PhD, the TIC is a valuable public information resource, as demonstrated by an ever-increasing number of inquiries from people concerned about the risks of exposure to chemicals encountered in the workplace or home environment. Most inquiries come via telephone, but an increasing number of interested parties are contacting the TIC by email through the CROET website. The TIC is now offering a monthly Internet Sleuthing Workshop. This hands-on Internet information course is available in the TIC the second Friday of each month from 1-3 p.m. The resources of the TIC, including the use of several computers, are available to the public Monday through Friday from 8 a.m. until 5 p.m. (http://www.croetweb.com)
CROETweb: Visitors and Hits Continue to Grow
CROETweb, the Center’s website, serves as a major source of occupational safety and health information for all working Oregonians. Designed as a resource directory, the website contains links to hundreds of resources for health and safety professionals. The website has pages dedicated to all major Oregon industries and occupations as well as a variety of safety and health topics. Oregon safety and health specialists visit CROETweb frequently. The most popular occupational safety and health pages in 2001 were semiconductors, restaurant and kitchen safety, artists, back injuries and prevention, and cell phones/EMF safety. New topics/web pages were added in 2001: bioterrorism, ergonomics, evaluating health-related websites, and shiftwork. In September, 2001, Holly Sherburne, MS, joined CROET as the new full-time Web Manager. Ms. Sherburne has a background in toxicology outreach and education, as well as extensive website design and coding experience. In 2001, the home page was revised, reducing loading time by two-thirds, and the update schedule was accelerated. Increasingly, websites from Oregon and around the world link to CROETweb. The number of “visitors” to the website increased to more than12,000, and hits exceeded 100,000 (up over 15 percent from 2000). (http://www.ohsu.edu/croet or http://www.croetweb.com)
Chemical Risk Information Service: Helping Oregon Business
CROET’s Chemical Risk Information Service is a 24/7 toxicological and risk information program designed to help business and industrial clients comply with the OSHA Hazard Communication standard. Directed by Greg Higgins, PhD, with Sundii Moser Gillespie, RN, BA, CSPI, as Program Manager, this program provides client employees and consumers a centralized source for round-the-clock access to Material Safety Data Sheets(MSDSs). Our Worker Right-to-Know Program helps employers give their employees access to MSDSs for the hazardous chemicals
present in their workplace. We provide toll-free phone access to the program, and MSDSs are available via fax and through our website. Clients also have immediate access to advice from licensed health care professionals via the Oregon Poison Center. Our Product Stewardship program provides a toll-free number for clients to place on their product labels or packing information as a resource for customers who have safety questions concerning the product. This program offers a convenient way for companies to provide their customers with global access to
product safety information and product MSDSs. Our client list of Oregon businesses served by the Chemical Risk Information Service continues to grow, and during 2001 we added eight new clients from the construction and high-tech industries. (http://www.ohsu.edu/croet-cris/)
Superfund Grant: Supports Worker Safety and Health
CROET’s federally funded Superfund Basic Research Center continued its studies of toxic environmental chemicals important to working Oregonians. Scientists at CROET are investigating the neurotoxic effects of aromatic solvents, studying how chlorinated solvents can interact with DNA to cause mutations, and examining how exposure to trace levels of toxic chemicals can affect the early development and maturation of the brain. Collaborating scientists at Battelle are performing cutting-edge computational chemistry studies to characterize the interaction of aromatic solvents with nerve cells and studying how toxic chemicals are absorbed by the body and to what extent they reach particularly vulnerable organs such as the brain. Consortium partners at Oregon State University are pursuing a parallel line of research that investigates how chlorinated solvents behave once they enter the environment and contaminate groundwater. The work conducted by our Superfund Center will lead to a greater understanding of how toxic environmental chemicals can impact nearby residents and workers and will also develop improved cleanup methods. The CROET-led Superfund Center is directed by Peter Spencer, PhD, FRCPath and Greg Higgins, PhD. (http://www.ohsu.edu/croet/sbrc/home_page.html)
Responding to State Requests: Hepatitis C and Public Safety Workers
Last year, CROET researchers prepared a literature review for the Oregon Legislature regarding the risks associated with Hepatitis B and C in police, fire, Emergency Medical Services, and correctional personnel. Because we found important gaps in the scientific literature regarding the prevalence of hepatitis among police, fire, and correctional officers, the Legislature asked CROET researchers to conduct a study to estimate the prevalence of, and risk factors for, Hepatitis C among public safety workers in Oregon. Testing was conducted in Spring, 2001, in Salem, Portland, Corvallis, Keizer, Independence, Monmouth, Dallas, Albany, McMinnville, and Newberg. Of the 719 public safety workers who volunteered to have their blood tested, 710 (98.8 percent) were negative and seven (1.0 percent) were positive. Thus, seroprevalence rates in Oregon are below that reported in the general population and lower than, or similar to, those published for other public safety officer populations. These data suggest that the occupational contribution to risk for hepatitis is small and that, in the absence of data demonstrating a significant association with occupational risk factors, non-occupational risk factors probably predominate. Nonetheless, employers and employees should continue to seek to reduce opportunities for exposure to blood and body fluids through the implementation of exposure control methods.(http://www.ohsu.edu/croet/faculty/rischitelli/index.html)
Collaborative Training Information Repository: A Practical Demonstration
CROET’s Dr. Mitchell Altschuler worked closely with Portland’s Painters District Council and their associated contractors to design a secure web-based database containing records of member training, medical evaluations, and respirator fit testing. The database, named the Collaborative Training Information Repository (cTIR), can be updated by the District Council and accessed by signatory contractors to confirm and document employee training. Updates trigger automatic recalculation of items such as current-year training hours, important for proper
calculation of pay rates. Prior to the cTIR, contractors telephoned the District Council data specialist who reviewed records for the worker and mailed documentation to the contractor, adding personnel costs to the District Council and delays for the contractor. The cTIR Internet system allows the contractor to verify training records 24/7,and it eliminates the need for redundant training that was often repeated when records could not be obtained and time was of the essence. Both the District Council and construction contractors have praised the system. The design elements of this demonstration program are available and can be modified for any occupational specific issue. A generic demonstration is available on CROETweb for review, in 2002. (http://www.ohsu.edu/croet/faculty/anger/index.html)
Partnerships in Surveillance and Prevention: New Workers’ Compensation Data
CROET scientists are engaged in a collaborative project with the Oregon Department of Health and Human Services and workers’compensation insurers in the state, which will demonstrate the value of working with insurers to recognize injury trends and opportunities for prevention strategies. Currently, Oregon data on work-related injuries and illnesses are only reported for those injuries/illnesses that are serious enough to cause more than three days of work loss (defined as “time-loss” injuries). Private and public workers’ compensation (WC) insurers, however, maintain databases of all injuries, both time-loss and those in which employees return to work within three days (defined as “medical-only” cases). This project is testing the feasibility of merging WC claims data from multiple insurers into a common database that will provide information on differences in the disabling “time-loss” and “medical-only” claims among different insurers according to type of injury/illness, age and gender of claimants, type of industry and occupation. Comparisons will be made in the profile of occupational injury and illness available in state WC databases and the profile available in data from insurers. This project will demonstrate the utility of complete insurer databases in monitoring clusters of illness and injury, trends and patterns of claims, and identifying new intervention opportunities as they emerge. (http://www.ohsu.edu/croet/faculty/mccauley/index.html)
cTRAIN: Computerized Training Program Expands
CROET’s interactive training program to develop effective individual training methods for occupational safety and health continued to grow in 2001 with initiation of two new federal grants to CROET and an OR OSHA grant to the Painters and Drywall Finishers. cTRAIN was developed by CROET Associate Director Dr. Kent Anger in collaboration with Mr. John Kirkpatrick of the Painters District Council. In 2001, the basic principles underlying cTRAIN were examined to determine how frequently quizzes and feedback are needed for maximum recall and learner acceptance. A collaboration with Monrovia, a wholesale plant nursery in Dayton, Oregon, led to the development of new system training instructions (“how to use” cTRAIN) presented in Spanish that were effective for Latino migrant workers with limited education. Collaborations to create new content in cTRAIN were also developed with the Oregon Association of Nurserymen, a labor and industry consortium involving drywall finishers, and OHSU offices responsible for food handling and lab safety. (http://www.ohsu.edu/croet/faculty/anger/index.html)
What Muscles Tell Their Nerves: New Signal for Proper Synapse Function Found
Recovery from traumatic injury requires accurate, functional reconnection of nerves with their targets. Nerves do form synapses on appropriate targets during embryonic development, and these synapses contain microdomains called active zones, where the chemical neurotransmitter is secreted. At the neuromuscular junction, the large synapse between motor neuron and muscle fiber, multiple active zones are positioned very precisely across the synapse from the folds in the postsynaptic surface of the muscle cell. This arrangement has been preserved over several hundred million years of vertebrate evolution, showing the importance of carefully controlling the site of neurosecretion. Mice were genetically engineered to lack a muscle protein, causing their motor nerves to locate active zones randomly in the nerve terminal. The discovery that this protein is a key factor in guiding nerves to reconnect with the proper muscle area will guide efforts to improve recovery from neuromuscular injury. (http://www.ohsu.edu/croet/faculty/patton/index.html)
Risk Assessment for Multnomah County Divers: Addressing Local Concerns
On December 1, 2000, the Portland Harbor was listed as an EPA Superfund site because Willamette River sediments are contaminated with metals, pesticides, polychlorinated biphenyls, and petroleum products. Several months later, CROET researcher Joan Rothlein, PhD, was asked by the Multnomah County Sheriff’s Office to assist with an evaluation of potential occupational exposures to contaminants in the Portland Harbor among members of the department who dive and patrol in the Portland Harbor as part of their search and rescue activities. With the cooperation of Oregon Department of Environmental Quality(DEQ), EPA, and ATSDR, Dr. Rothlein and other CROET scientists are addressing the health and safety concerns of members of the Sheriff’s Office by: (1) Identifying microbial and chemical hazards in the water and sediment in the Portland Harbor and other dive locations from federal reports; (2) Evaluating personal protective equipment options; (3) Calculating possible human health risk using reported contaminant levels and information on the location and duration of each dive extracted from individual dive logs. (http://www.ohsu.edu/croet/faculty/rothlein/index.html)
