An Internet Database for the Classification and Dissemination of Information About Hazardous

INTERNET DATABASE 1

An Internet Database for the Classification and Dissemination of Information about Hazardous Chemicals and Occupational Diseases

J. A. Brown, MD, MPH Consultant, Specialized Information Services, National Library of Medicine Consultant, Energy Employees Occupational Illness Compensation Program, U.S. Department of Labor Correspondence to J. A. Brown, 5426 Orca Place NE, Tacoma, WA. E-mail: [email protected]

ABSTRACT

Background

The amount of information about hazardous agents in the workplace exceeds the capacity of human memory. There is a need to accurately represent or map this scientific knowledge for digital storage and retrieval.

Methods

A relational database of hazardous chemicals and occupational diseases was constructed by first collecting and sifting through the large volume of information. The information was indexed with a controlled vocabulary and documented with references to the scientific literature.

Results

The evolving database is available on the website of the National Library of Medicine. It enables users to browse categories and query by pick lists. Users can drill down to find specific information that may be useful for intervention and prevention.

Conclusions

The large amount of information needed to support decisions concerning occupational exposures and diseases can be distilled, classified, and summarized in a relational database and disseminated by means of the World Wide Web to assist in the prevention of work-related diseases. INTERNET DATABASE 2

INTRODUCTION

Knowledge mapping that links occupational exposures to acute and chronic diseases can be useful for public health. Knowledge mapping begins with the big picture, and all of the information is kept in perspective. The need for knowledge mapping is great because there is so much information about occupational exposures and diseases; it is easy to get lost in the details. Thousands of new pages are published daily in journal articles, book chapters, and Internet websites. The problem today is how to extract the specific information needed and how to make it accessible to people who can intervene and prevent disease. [Berner and Moss, 2005]

One of the first attempts to map the knowledge domain of occupational hazards for the purpose of disease prevention was made by Rutstein et al. in 1983 and later updated by Mullan and Murthy in 1991. The authors introduced the concept of occupational sentinel health events or SHE(O)s. The 1991 update included 64 occupational diseases linked to causal agents and associated industries, processes or occupations. "This list may serve as a framework for occupational health surveillance at the state and local level. It may also be used as a guide for practicing physicians caring for patients when there is a question of occupational illness." [Mullan and Murthy, 1991]

The effectiveness of public health interventions is dependent upon the collection, analysis, and dissemination of information. [Macgruder et al., 2005] Modern computer systems can help to make public health decisions more timely and information-driven. [Friede et al., 1995] The computer's strength in data storage and computational speed complement the human strength of general knowledge, creativity, and perspective on the usefulness of the information. To be useful, the large amount of information available must be organized into a format that is easy to query and understand. Otherwise, the quantity of information can be overwhelming and lead to decisions that are wrong or suboptimal. This organizing process involves extracting the critical information from the huge volume of available data. [Parsaye and Chignell, 1993] The preliminary work done in sifting through the information and classifying it for digital processing enables users "to focus on the key problems while ignoring a vast sea of irrelevancy." [O'Carroll et al., 2003]

The author of the current paper has developed a decision-support relational database called "Haz-Map" to map the knowledge domain of occupational exposures and diseases. One definition of information is "data placed in context." [O'Carroll et al., 2003] The goal of the Haz-Map project is to place each piece of information in the context of the whole database in the same way that each organ is understood in the context of INTERNET DATABASE 3 the whole body. Expressed in another way, "Exposure assessment and health evaluation need to be seen as two pieces of a whole; information about exposure is required to fully evaluate the health endpoints, and information about health effects is required to design an appropriate exposure assessment study." [Seixas, 1996]

The original idea for Haz-Map was, "Why can't we have a relational database of toxic chemicals and occupational diseases to store and query information similar to ones used by companies to manage data about employees, products, and customers? Instead of querying for all employees with the first name "David" AND living in the city of "Fresno," the query will be for all chemicals tagged as potential causes of "Toxic pneumonitis" AND linked to the Industrial Process "Welding."

MATERIALS AND METHODS

The first step in the project was to collect and distill the facts needed to prevent occupational diseases. Distilling refers to the process of sifting through the information for inclusion or exclusion. Only the most useful information is included. [Parsaye and Chignell, 1993] Next, the information was classified using a controlled vocabulary of names for agents, adverse effects, industrial processes, non-occupational activities, diseases, signs & symptoms, hazardous job tasks, jobs, and industries. The ability to formulate questions with controlled search terms is one of the building blocks of evidence-based practice. [Saranto and Tallberg, 2003; Bakken, 2001] Finally, information about each object was summarized. Summaries document the source of information with references to the scientific literature.

Using the Microsoft® Access relational database, all of the information was placed into the fields of eight tables. The information included chemical, biological, and radiation hazards. Excluded from the database were hazards caused by noise, cold, heat, repetitive motion, and other physical hazards. Field values available in Microsoft Access include text, memo, number, yes/no, and hyperlink.

The first content added was information on about 700 chemicals from the NIOSH Pocket Guide to Chemical Hazards [National Institute for Occupational Safety and Health (NIOSH), 1997]. Using the yes/no fields in the Agents table, each chemical was flagged for the presence or absence of adverse effects as shown in Table 1. Next, using selected references from the scientific literature, the author added to the database any other chemical or biological agents linked to occupational asthma, toxic pneumonitis, chronic bronchitis, lung cancer, neuropathy, Parkinson's syndrome, methemoglobinemia, aplastic anemia, hemolytic anemia, contact dermatitis, chloracne, liver injury, kidney injury, and INTERNET DATABASE 4

simple or chemical asphyxiation. All agents causing interstitial fibrosis (pneumoconioses and hypersensitivity pneumonitis) were tagged with "fibrosis." All agents caustic to the skin or listed in the Chemical Hazards Response Information System (CHRIS) database [United States Coast Guard, 2001] as causing burns (first, second, or third degree) were tagged with "skin burns." All chemicals in the category "Solvents" were tagged with "CNS Solvent Syndrome." Also tagged on the basis of categories were "Organophosphate," 'Organochlorine," and "Carbamate" pesticides. An "Uncoupler" is a chemical like pentachlorophenol that can cause a hypermetabolic state by poisoning cellular respiration (uncoupling oxidative phosphorylation).

Table 1. Controlled Vocabulary for Adverse Effects.

Category *Adverse Effect Lung Toxin Asthma, Pneumonitis, Chronic Bronchitis, Fibrosis, and Cancer Neurotoxin Neuropathy, Parkinson's Syndrome, and CNS Solvent Syndrome Hematotoxin Methemoglobinemia, Aplastic Anemia, and Hemolytic Anemia Dermatotoxin Contact Dermatitis, Chloracne, and Skin Burns Carcinogen Known, Probable, or Possible Other Tissue Hepatotoxin, Nephrotoxin, and Reproductive Toxin Toxin Other Poison Organophosphate, Carbamate, Organochlorine, Uncoupler, Chemical Asphyxiant, and Simple Asphyxiant

*When looking at a chemical profile, the Adverse Effects for that chemical are displayed. The Adverse Effects are also used to query the database.

Following the lead of the American Governmental Conference of Industrial Hygienists (ACGIH) [2005], chemicals that can cause methemoglobinemia were divided into primary and secondary. Similarly, chemicals that can cause hepatic injury were divided into primary and secondary. A primary agent is one that has been reported to cause methemoglobinemia or hepatitis in the work environment. A nephrotoxin is defined as a chemical that is potentially toxic to the kidneys in the occupational setting.

In addition to adverse effects, the Agents table also has fields to show pertinent information about properties, thresholds, and exposure INTERNET DATABASE 5 limits. A premium is placed on information that helps the user to distinguish between significant and harmless exposures. The information should help to answer the question, "Given that the worker received a dose, what is the probability of harm?"

The relationships of the tables in the database are shown in Figure 1. When available, standard classification systems were used: Standard Occupational Classification (SOC) system for jobs [2000], the North American Industry Classification System (NAICS) for industries [2002], and the International Classification of Diseases (ICD-9) for diseases [2006].

The two levels of information in Haz-Map are chemicals (the industrial hygiene perspective) and diseases (the epidemiological perspective). Each industrial process is linked to all agents associated with that process. Each hazardous job task is linked to all diseases associated with that job task. Each hazardous job task is also linked with all jobs and industries associated with that job task.

Signs & Symptoms Industries

Occupational Hazardous Diseases Job Tasks Occupations

Industrial Processes *Toxic Chemicals Home Activities

*This is also referred to as the Agents table. Most records are toxic chemicals, but there are also biological agents in this table, e.g., natural latex rubber.

Figure 1. Two Levels of Information in Haz-Map: Diseases and Agents. INTERNET DATABASE 6

Notice that a bi-directional arrow indicates a many-to-many relationship between two tables. This enables users to find all chemicals linked to each disease and all diseases linked to each chemical. Similarly, they can see all findings (signs & symptoms) of a disease or all diseases with the finding.

Agents in the database were linked to industrial processes and non- occupational activities. Linkage indicates the potential for exposure to the agent. As mentioned earlier, each agent in the database was flagged for adverse effects including asthma, pneumonitis, neuropathy, anemia, hepatotoxicity, and skin sensitization. At the chemical level, the concern is the potential toxic effects of the agents.

At the disease level, the concern is work-related diseases based on case reports or epidemiologic studies. Occupational diseases in the database were linked to findings (signs and symptoms of the disease) and hazardous job tasks. Hazardous job tasks increase workers risk for significant exposure and subsequent disease. Linkage between job tasks and jobs or industries indicates an increased likelihood for workers in those jobs or industries to engage in the hazardous job tasks. In this database, chronic occupational diseases are linked to both jobs and industries, while acute diseases and infectious diseases are linked only to jobs. Cancers were not linked to jobs, industries, or findings. (Studies linking cancer with jobs and industries are historical. It is difficult to apply these links to current jobs and industries. There is such a wide range of findings depending on the stage of the cancer. Also, occupational cancers have such a long latency that diagnosis of a case is not likely to affect prevention.)

Diseases are also linked to agents (chemical or biological). Linkage between an agent and a disease indicates that sufficient exposure to the agent is associated with an increased risk of developing the disease. For chronic diseases, linkage between an agent and a disease means that a causal relationship has been determined based on human case reports or epidemiological studies. Carcinogens are linked only if they have been designated as known human carcinogens by the International Agency for Research on Cancer (IARC) [2007]. In some cases, IARC does not list the target organs, but Haz-Map follows the interpretation published in Schottenfeld and Fraumeni's Cancer Epidemiology and Prevention. [Siemiatycki, 2006]. Acute diseases, for the most part, are also linked to chemicals based on reports of cases in humans.

There are three exceptions to the rule that an agent-disease link indicates human evidence as the basis for the link. The first exception is the disease "Solvents, acute toxic effect." This disease is linked to all agents in the Major Category, "Solvents" in the Haz-Map database. Not all organic solvents have been reported to cause this disease, but it is assumed that all agents in the Solvents category have the potential to cross the blood-brain barrier and cause the solvent syndrome. The third exception is the disease "Encephalopathy, INTERNET DATABASE 7 acute toxic." This disease is linked to all chemicals flagged as "Other CNS Neurotoxin." Similarly, the fourth exception is the disease "Pneumonitis, toxic," which is linked to all chemicals flagged as causing this adverse effect. (Toxic pneumonitis is both a disease and an adverse effect.) Toxic pneumonitis is defined as noncardiogenic pulmonary edema induced by acute exposure to metal fumes or toxic gases and vapors after a spill or confined space accident. The "major irritant inhalants" are ammonia, bromine, chlorine, chlorine dioxide, diborane, ethylene oxide, formaldehyde, hydrogen chloride, hydrogen fluoride, methyl isocyanate, nitrogen dioxide, ozone, phosgene, and sulfur dioxide. [LaDou, 2007] While human cases have been documented for the major irritant inhalants, there are many chemicals with similar corrosive effects on tissues that have the potential to cause toxic pneumonitis if inhaled. For most of these chemicals, toxic pneumonitis has never been reported in humans. The agent- disease link is not established from human cases but is deduced from animal or other evidence.

Information from textbooks, journal articles, and electronic databases was classified and summarized to create the database. A bibliography including online resources is regularly updated at http://hazmap.nlm.nih.gov/hazref.html. [National Library of Medicine (NLM), 2007a] This page also shows the reference labels that are used throughout Haz-Map to reference source material, e.g., ATSDR Case Studies. [Agency for Toxic Substances and Disease Registry (ATSDR), 2007] Several databases were used heavily in the early development of Haz-Map including Hazardous Substances Data Bank (HSDB) [NLM, 2007b] ACGIH Documentation of the TLVs and BEIs (ACGIH, 2007), ATSDR ToxProfiles (ATSDR, 2006), Documentation for Immediately Dangerous to Life or Health Concentrations (IDLH) [NIOSH, 1995], and NIOSHTIC [NIOSH, 2007]. The early development of the content also relied on textbooks of occupational medicine. [LaDou, 2007; Rom, 2007; Rosenstock, 2004; Sullivan and Krieger, 2001; Zenz et al., 1994] The Mullan and Murthy paper [1991] was used for the initial list of occupational diseases. Other major sources were Harber et al. [1996], Hendrick et al. [2002], Stellman [1998], Marks and DeLeo [1997], Kanerva et al. [2000], Kanerva et al. [2004] Lewis [2002], O'Neil et al. [2006], Mason et al. [2005], Reigart and Roberts [1999], and Fosberg and Mansdorf [2003]. The list of Malo and Chan-Yeung [2006] was used for the agents causing occupational asthma. Frazier and Hage [1998] was the main source for reproductive hazards. Industrial processes were based on Burgess [1995]. Infectious disease reference books include Heymann [2004], Guerrant et al. [2006], Gorbach et al. [2004], and Mandell et al. [2005]. Ionizing radiation as a cause of cancer is based on Boice [2006], and other occupational cancer is based on Siemiatycki [2006]. Other databases that have been used extensively in recent years include ChemIDplus [NLM, 2007c], Occupational Health Guidelines for Chemical Hazards [NIOSH, 1995], International Chemical Safety Cards [IPCS, 2007], CAMEO [EPA, 2001], CHEMINFO [CCOHS, 2007], EXTOXNET [Extension Toxicology Network, 1995], and the North American Emergency Response Guidebook [U.S. Department of Transportation, 2004]. INTERNET DATABASE 8

RESULTS

The database currently contains 1534 chemical and biological agents, 212 diseases, 122 signs and symptoms, 276 jobs, 104 job tasks, 51 industrial processes, 621 industries, and 26 non-occupational activities. Current statistics show 239 chemicals associated with toxic pneumonitis, 387 agents with skin sensitization, 258 agents with occupational asthma, and 129 agents with reproductive toxicity.

For the 1534 chemical and biological agents, information includes uses, adverse effects, associated industrial processes, and threshold values useful for exposure assessment. For the 224 occupational diseases, information includes associated symptoms, high-risk job tasks, jobs, and industries. The database contains a total of 1109 hyperlinks to PubMed at the National Library of Medicine and other scientific websites. Two hundred and fifty Medical Subject Heading (MeSH) terms allow instant PubMed searches for articles related to the disease or finding identified by the term.

In comparison to the original SHE(O) conditions compiled by Mullan and Murthy, the twenty caused by infections were expanded into 105 occupational infections with 18 of these in the category of "Travel Infections." Eight SHE(O) diseases were not added to the database, Silotuberculosis, Tetanus, Talcosis, Agranulocytopenia, Cerebellar Ataxia, Carpal Tunnel Syndrome, Mononeuritis, and Noise-Induced Hearing Loss. Acute/chronic renal failure was not included as a disease, but "nephrotoxin" is one of the adverse effects for agents. The 13 occupational cancers in the SHE(O) list were expanded to 19 cancers, Bladder Cancer, Bone Cancer, *Brain Cancer, *Colorectal Cancer, *Esophagus Cancer, Liver Cancer, *Kidney Cancer, Laryngeal Cancer, Leukemia, Lung Cancer, Melanoma, Pleural Mesothelioma, Peritoneal Mesothelioma, Nasal Sinus Cancer, *Nasopharynx Cancer, *Pancreatic Cancer, Skin Cancer, *Stomach Cancer, and *Thyroid Cancer. The current list combines all leukemias, and cancer of the scrotum is listed as a type of skin cancer. Additional cancers not included in the SHE(O) list are underlined. The asterisk (*) means that no agents were causally linked to the cancer in the Haz-Map database.

Additional diseases not in the SHE(O) list are, Chronic Obstructive Pulmonary Disease (includes Chronic Bronchitis), Irritant-Induced Asthma, Irritant-Induced Vocal Cord Dysfunction, Oil Acne, Chloracne, Contact Urticaria, Benign Pneumoconioses, Other Pneumoconioses, Hard Metal Disease, Chronic Sinusitis, Simple Asphyxiation, Chemical Asphyxiation, Inhalation Fever, and poisoning by Manganese, Cadmium, Chromium, Mercury, Lead, Arsenic, Fumigants, Pentachlorophenol, Hydrofluoric Acid, Organochlorines, and Carbamates/Organophosphates. To the SHE(O) list of four specific forms of Hypersensitivity Pneumonitis were added 24 more specific types. INTERNET DATABASE 9

Job tasks are important components to consider when evaluating the health risks of specific occupations. [Burkhart et al., 1993; McDonald et al., 2004] In the Haz-Map database, hazardous job tasks link diseases with occupations and industries. An example of a job task is "Work in microwave popcorn plant that uses diacetyl for flavoring." This job task is linked to the disease, "Bronchiolitis Obliterans." Clicking the hyperlink for this disease will take the user to the NIOSH ALERT page entitled, "Preventing Lung Disease in Workers Who Use or Make Flavorings." [NIOSH, 2004] This job task is linked to the following SOC jobs: Food Batchmakers; Food Cooking Machine Operators and Tenders; Laborers and Freight, Stock, and Material Movers, Hand; and Mixing and Blending Machine Setters, Operators and Tenders. This job task is also linked to the following NAICS industry: Other Snack Food Manufacturing.

The content of Haz-Map is continuously revised, updated, and expanded. At this time, it is published only by the National Library of Medicine at http://hazmap.nlm.nih.gov/. [2007d] The user-interface provides a text search function as well as a way to search each table by names or synonyms. Pick lists and drop-down lists are available, and the user can query the database for all agents that match an adverse effect AND an industrial process. Also, the user can query the database for all diseases that match a job AND a finding. Each chemical record displays chemical properties and adverse effects. Chemical properties include occupational exposure limits, vapor pressures, odor thresholds, half-life, lethal concentrations, flammability, etc. Definitions of chemical properties and adverse effects are available through hyperlinks to the glossary. The Home page has links to a Help page, a Glossary, and References.

Statistics compiled on the server computer at the Specialized Information Services Division of the National Library of Medicine show that the Haz-Map website received 4,165 visitors and 19,988 hits in March 2003 and 64,140 visitors and 522,503 hits in March 2007. For March 2007, the total number of hits (basically, the number of mouse clicks made to navigate the web site) on the Haz-Map web were approximately 7% of the total hits for all of the TOXNET databases that include ChemIDplus, HSDB, and 10 other databases.

During the past two years, the Agent-Disease links from Haz-Map have been incorporated into the Department of Labor’s Site Exposure Matrices (SEM) database, currently being used for the Energy Employees Occupational Illness Compensation Program (EEOICP). "The mission of the Energy Employees Occupational Illness Compensation Program is to deliver benefits to eligible employees and former employees of the Department of Energy, its contractors and subcontractors or to certain survivors of such individuals, as provided in the Energy Employees Occupational Illness Compensation Program Act." [DOL, 2007a] The latest statistics show that 158,001 claims have been received. Payments have been made for 37,774 claims, and the total compensation that has been paid so far is $3,319,637,545. [DOL, 2007b] INTERNET DATABASE 10

EEOICP is providing financial and technical support for the author to continue developing the content of Haz-Map consistent with the way it has been developed in the past. New agents and their health effects are being added to the database based on chemicals that have been used at Department of Energy sites where claimants worked. As pointed out by O'Carroll et al., "Decision support systems can provide preliminary analysis that allows scarce human resources to focus on the key problems while ignoring a vast sea of irrelevancy." [2003]

DISCUSSION

Mapping geography is an ancient discipline that came to fruition after the age of discovery in the 15th century. [Encyclopaedia Britannica Online. 2007] Mapping knowledge domains is a relatively new art and science that began with the age of information in the 19th century. [Fisher et al. 2002] Similarities in both types of mapping are that: 1.) information must first be collected, sifted, and classified; 2.) concentric design makes it necessary to draw the big picture first and to add the details as more information becomes available; 3.) the scale of the map limits the amount of information that can be included. For example, not every dirt road and trail is included in most road maps, but only the major thoroughfares. From this, it should be clear that by design Haz-Map does not include every disease that has ever been reported in the workplace. Its purpose is to sift through the voluminous and scattered information as it currently stands, to summarize the established occupational diseases, both current and historical, and to show their associated causal agents. It is up to future mapmakers to build a better map and to fill in the details as more complete knowledge is gained.

A few words should be said about the intended audience of Haz- Map. Haz-Map was originally designed by a health and safety professional for health and safety professionals. With the opportunity to publish the database on the website of the National Library of Medicine came a new audience—workers and the general public seeking the facts about work- related health effects. In this age of information, it is clear that all information is becoming available, not just to an elite group, but to all people. Haz-Map is just one of the resources available to help professionals and non-professionals to make decisions regarding occupational exposures and diseases. Alongside other resources such as PubMed searches and new editions of occupational medicine textbooks, the value of Haz-Map will depend on how well it is updated and maintained in the coming years.

"Surveillance in occupational health is defined as the systematic collection and analysis of information concerning hazards, disease, or injury for the purpose of prevention of occupational disease or injury." It involves "the INTERNET DATABASE 11 collection of information after an action and the use of that information in a feedback loop to change the circumstances that lead to the effect of interest." [Halperin, 1996] Mullan and Murthy described their list of SHE(O)s as a "framework for occupational health surveillance." [Mullan and Murthy, 1993] In a similar way, the Haz-Map database plays a role in surveillance. "Health hazard surveillance is the ongoing collection, analysis, evaluation and dissemination of information aimed at improving the health, work ability, and well being of workers." [Kauppinen and Toikkanen, 1999] Effective occupational health surveillance can benefit the sentinel cases, their coworkers, other workers in the industry, and people in other settings who were exposed to the agent. [Azaroff et al., 2002]

One of the roles of surveillance in occupational health is to provide information to motivate intervention. [Halperin, 1996] Case definitions include information about signs and symptoms, diagnostic tests, and nonoccupational causes. Lists of case definitions, like those disseminated by the Haz-Map database, can foster improved recognition and prevention. [Matte et al., 1989]

Like the SHE(O) list, Haz-Map differs from conventional surveillance systems in that the information is collected from secondary sources in the medical literature rather than from the actual health events. The SHE(O) system has been tied to direct intervention in the SENSOR program. [Matte et al., 1989] There is no conventional surveillance linked to the Haz-Map database. However, the new computer technologies have opened doors for public health surveillance that were not available when the SHE(O) list was first published in 1983 and updated in 1991. Physicians and scientists, now armed with personal computers, can distill information from online databases and summarize that information to improve surveillance. Personal computers also help authors to manipulate large amounts of data with easy-to-use relational databases and other software applications used for sorting, classifying, updating, and disseminating immediately to the people who need to know. Continuously updated lists of occupational diseases and their case definitions can now be disseminated directly to health and safety professionals and to workers seeking information on the Internet about occupational exposures and diseases. Compared to the past, there is now much more information. Fortunately, there are also much better tools for processing and communicating that information to those who can intervene and prevent diseases in the workplace.

ACKNOWLEDGMENTS

The author wishes to thank the following for their assistance: Scott Barnhart, Matt Keifer, Carl Brodkin, Noah Seixas (University of Washington), Jeff Burgess (University of Arizona), Tim Gilmore (Group Health Cooperative), Patricia A. Stewart (National Cancer Institute), and Moira Chan-Yeung INTERNET DATABASE 12

(University of British Columbia). The author has been receiving financial assistance from the U.S. National Library of Medicine since 2000 and from the Department of Labor since 2006.

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