Accomplishments
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
Chronic Disease and Working Safely
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.
Model of Metabolic Syndrome in Obesity
The growing epidemic of human obesity is estimated to affect more than 60 million adult Americans, with secondary consequences including, but not limited to, decreased job performance, increased medical costs, decreased life span, non-alcohol-induced fatty liver disease, increased cardiovascular disease, and an increased incidence of stroke and type 2 diabetes. A majority of the obese population (more than 45 million Americans) has a combination of at least four of these diseases, collectively known as the Metabolic Syndrome. The underlying cause of thesediseases is believed to be a combination of genetic susceptibility and chemical stressors, including exposure to pro-oxidant chemicals. Recently, Dr. Stephen Lloyd and his group have created genetically modified mice that are unable to repair certain types of oxidative DNA damage, and discovered that these mice develop symptoms consistent with all the defining hallmarks of the Metabolic Syndrome: severe obesity, disruptions in blood lipids, insulin resistance, and hyperleptinemia. Oxidative damage is believed to underlie some occupational disorders as well as diseases affecting broad segments of our population. The outcome of these investigations will be to provide a working model of the Metabolic Syndrome with which to design and test effective human therapies. By reducing the incidence or severity of disease associated with obesity, a healthier and more productive workforce can be realized.Neurodegeneration: Drosophila, a Model Test System
Mechanisms Underlying Chronic Health Effects of Organic Solvents are Illuminated
Organic solvents are valuable chemicals with a multitude of uses in a variety of industry sectors. While many are considered safe, a few solvents have the potential to cause neurological disease. Identifying the bad actors, and the reasons for their neurotoxicity, continues to be an important area of investigation in the laboratories of Dr. Peter Spencer and Dr. Mohammad Sabri. Previously reported studies revealed that both straight chain (aliphatic) and ring-structure (aromatic) solvents have neurotoxic potential if their metabolites possess chemical side chains with a particular (gamma-diketone) structure. Advanced methods of protein and gene analysis (toxicogenomics, see below), in combination with mass spectrometry, are being applied to understand why these chemicals are problematic and how they attack the nervous system. Drs. Spencer and Sabri demonstrated that the neurotoxicity of these solvents is directly related to a variety of specific chemical and physical characteristics of proteins, such that proteins in the nervous system are differentially susceptible to damage from the solvent metabolites. They also found that the loss of neuroproteins is accompanied by changes in gene expression that precede the onset of pathological changes in nerve fibers that underlie the appearance of neurological disease. This is hoped to lead to an understanding of how to predict which organic solvents have the potential to cause neurotoxicity and which are safe to use in the workplace.Publication in Nature Methods Sets Standards for the Practice of Toxicogenomics, a Leading-edge Research Method to Assess Impacts of Stressors on Gene Expression and Its Relationship with Health and Disease
Toxicogenomics is a powerful method to analyze the response of biological systems to changes induced by chemicals, drugs, trauma, and other agents that cause disease and injury. Tens of thousands of genes are simultaneously interrogated to determine whether and how gene expression has been changed from the normal state. The resulting mass of data is interpreted with software that reveals alterations in molecular networks that correlate with abnormal function or a disease state. The reproducibility of this new technique was examined by a CROET investigative team, part of a prestigious Toxicogenomics Research Consortium (TRC) funded by the National Institutes of Environmental Health Sciences (NIEHS). CROET at OHSU carried out experiments conjointly with TRC members at NIEHS, MIT, Fred Hutchinson Cancer Research Center, University of Washington, Duke University and University of North Carolina. The collaborative research effort revealed critical elements, including the quality and stability of the microarray platform, the precision of the experimental procedures, anchoring gene expression data to established biological landmarks, and the power of innovative biostatistical methods to extract information from the mountain of data that results from toxicogenomics experiments. In sum, these studies show the challenges as well as the strengths of toxicogenomics as a tool to probe and increase understanding of health and disease.(Bammler, et al., Nature Methods, 2005; 2: 351-356).
Reducing the Risk of Prostate Cancer
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.
Persistence of DNA Damage After a Single Exposure to Ionizing Radiation
DNA damage represents one of the earliest steps in the development of cancer because such damage can lead to mutations in genes that function to prevent cancer. Mutation is defined as changes in DNA structure that alter the ability of a gene to make a protein. Because proteins constitute the basic functional machinery of cells, the resultant change in the amount or activity of a protein (after DNA mutation) can fundamentally alter cellular behavior. Ionizing radiation, such as the common X-ray or ultraviolet radiation from sunlight, causes two types of DNA damage: (1) breaks in the DNA strand and (2) damage to nucleotides, the building blocks of DNA. Cells have a variety of mechanisms to repair DNA damage and hence avoid the induction of a harmful mutation. Dr. Mitchell Turker’s laboratory is asking whether DNA damage caused by exposure to ionizing radiation persists in tissues or whether the damage is fixed by DNA repair mechanisms. Some mouse tissues are exposed to ionizing radiation while others are shielded from exposure. DNA damage is assessed in tissues of the irradiated mice by examining chromosome structure (chromosomes contain the DNA strands) long after treatment. The results demonstrated that specific types of chromosome abnormalities caused by ionizing radiation persist for two years and at levels that were essentially the same as those observed one to four weeks after exposure. Although the ionizing radiation dosages used for this experiment were far higher than those employed in diagnostic procedures, these results support the concept that such procedures should be limited only to those necessary for medical evaluations. While we have learned a great deal about acute exposures, the effects of long-term exposure to low doses of ionizing radiation is still an open question.Mutations Increase with Age in Mouse Tissues
The greatest risk factor for cancer is age, and cancer is more common in older than in younger persons. This is believed to reflect basic changes in cell structure and function as people get older, but the exact nature of these changes remains to be determined. One type of cellular change that is important in cancer is gene mutation, which occurs when the DNA sequence is altered and expression of genes required to prevent cancer is lost. Dr. Turker examined the frequency of mutations most commonly found in cancer cells of two cell types from mice ranging in age from 6 months to 36 months (laboratory mice rarely live past 40 months of age). The cell types examined were those found in connective tissue and kidney epithelial cells. Most tumors that increase with age arise from epithelial cells. The results of Dr. Turker’s experiments demonstrated a steady increase in the frequency of mutations for the kidney cells as a function of age, which was higher at all ages in the female mice. Interestingly, female mice do not live as long as male mice in the strain that was used for this study. For the connective tissue cells, an age-related increase in mutations was only observed for female mice and only in the oldest females. These results demonstrate that mutations with relevance for cancer increase with age mostly in epithelial cell types and suggest that this cell-type-specific increase plays an important role in cancers that arise in older individuals.Business Spinoffs
The federal government, the State of Oregon, and OHSU encourage the translation of research findings into immediate real-world benefits to society. Often that is in the form of commercial products that generate income for OHSU, part of which returns directly to the laboratory where the idea for the product was generated. This is a natural outgrowth of CROET’s legislative mandate since many of its research activities are aimed at solving workplace probems, either through prevention or treatment. Two corporate spinoffs and one for-fee service operating within CROET have achieved significant milestones in 2004-2005. They are described below.
Restoration Genetics, Inc .
The occurrence of skin cancer is rapidly increasing, affecting more than 1 million people in the United States annually. Sunlight exposure produces DNA damage or lesions, and they in turn can produce cancer. Human cells have only one mechanism to repair these DNA lesions, whereas lower organisms possess multiple pathways for protection against the adverse effects of sunlight exposure. In order to implement proactive strategies to prevent skin cancer, Dr. Amanda McCullough and Dr. Stephen Lloyd have discovered, characterized and patented multiple DNA-repair enzymes that possess activities that can initiate a second DNA-repair pathway in human cells. Cell-based studies have demonstrated that repair of sunlight- induced DNA damage can be improved 100 fold over that of non-treated cells. Based on these patented technologies, Drs. McCullough and Lloyd co-founded a start-up biotechnology research and development company, Restoration Genetics, Inc., in August 2004. In 2005, the McCullough and Lloyd laboratories were awarded a Springboard Grant from OHSU to facilitate start-up operations for the company. Additionally, a BioScience Innovation Fund Grant from OHSU was awarded to provide funds to demonstrate the feasibility of incorporating these enzymes in an active form in skin-specific vesicles that, upon topical application to skin, will enhance repair of sunlight-induced DNA damage. What this promises is a post- sunburn application that can reverse the damage done to the DNA in the skin. These technologies have the potential to repair the most harmful damage caused by sunlight exposure. By restoring the cellular DNA to its original state, mutations that could lead to cancer are prevented and theNorthwest Education Training and Assessment, LLC (NwETA)
Computer-based training is efficient but developed largely by and for well-educated segments of the working population. In 1999-2001, Dr. Kent Anger and Dr. Diane Rohlman developed cTRAIN, a computer-based training software aimed at training populations that had limited or no experience with computers. In 2005, the cTRAIN software was licensed by OHSU to Northwest Education Training and Assessment (www.nweta.com), an OHSU spin-off company formed by Dr. Anger, Dr. Rohlman and other colleagues. The goal of the company is to commercialize cTRAIN and use the proceeds from sales to evolve the software in order to maintain and enhance its utility and competitiveness with other training software. The software presents training created in Dr. Anger’s laboratory, but it also has an editing tool in which new content topics can be created. The cTRAIN computer-based training program received seed funding from an OR-OSHA grant to the Painter’s District Council. Through this grant, Dr. Anger and Mr. Kirkpatrick developed training content on respiratory protection that is still in use at the Painter’s District Council Training Center today. Federal grants further supported the development of content on slip-and-fall safety in food service operations, ladder safety in agriculture, ergonomic issues in dry wall finishing, hazard communication, Worker Protection Standard for agricultural workers, and a variety of training content programs for vineyards. This led to a small business grant to NwETA from the National Institute of Environmental Health Sciences and a cooperative agreement from the National Institute for Occupational Safety and Health (NIOSH) to develop training content programs for vineyards in collaboration with Leda Garside, RN, BSD, of Tuality Healthcare ¡Salud! Services. NwETA’s goal is to bring the efficiencies and advantages of computer-based training to every working person, including those in the workforce with limited or no education.Chemical Risk Information Service
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 computer-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 2004-2005, the Chemical Risk Information Service provided MSDS management services to more than 35 municipal, construction, and service companies, most of which are Oregon-based. CROET is currently focused on upgrading the database system and improving client websites for MSDS management. All database files and websites were relocated from CROET’s local server to OHSU’s main server bank, which improved the security and reliability of the service. We also began development of improved search codes for clients to retrieve MSDSs, so that they can begin to search not only by product name, but also by key location parameters at their facilities. This change allows clients to use CROET’s system as an inventory control mechanism, as well as a source for MSDSs. CROET continues to provide expert MSDS management service at a reasonable cost which is attractive to both small and large organizations.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)


