Toxicological information series, I

FUNDAMENTAL

AND

APPLIED

14,439-443

TOXICOLOGY

TOXICOLOGICAL

(I

990)

INFORMATION

Toxicological

SERIES, I

Information

GEORGE J. COSMIDES Toxicology

It$ormation

Program,

Received

National

December

Library

of Medicine,

27, 1988: accepted

October

Bethesda,

Maryland

20894

30, 1989

Toxicological Information. COSMIDES, G. J. (1990). Fundam. Appl. Toxicol. 14, 439-443. Thispaper presents a brief history of the evolution of toxicological information in the United States since I966 when concern over the hazards ofthe ubiquitous chemicals in the environment was translated into recommendations for action by The Panel on the Handling of Toxicological Information of the President’s Science Advisory Committee. It describes some of the data bases that were developed as a result of these recommendations and introduces a series of papers that discuss toxicology information resources, their content, and their accessibility. The series is a project of the Information Handling Committee of the Society of Toxicology. Papers II-V of this series will be published in subsequent issues of Fundamental and Applied Toxicology. 0

1990

Society

of Toxicology.

In 1987, at the behest of the President of the Society of Toxicology, the Information Handling Committee developed a proposal which outlined the objectives of a series of articles on toxicology and related information resources to be published in Fundamental and Applied Toxicology. With the concurrence of the Board of Publications and the Editor, it was agreed that this special series of articles focus on toxicological information and be published as a committee project in accordance with the objective “that the journals of the Society play a more active role in the education arena” (Editoiial Note, 1988). This series of papers provides reviews on information resources that deal with: 1. the framework of toxicology information; 2. community “right-to-know” on potentially toxic substances; 3. responding to chemical emergencies; and

4. forensic toxicology. 439

The need for a toxicology information “system” was recognized in a U.S. Public Health Service report entitled “Toxicology: A Status Report” dated October 7, 1964 (Brodie et al., 1964). This report resulted in the publication of the lead article in the June 18, 1965 issue of Science which outlined some problems in toxicology and offered recommendations on how these problems should be approached (Brodie et al., 1965). Among the recommendations made in this article entitled “Toxicology and the Biomedical Sciences,” were a number dealing with information processing and communication. The information explosion in the arena of chemical-biological interactions had raised the problem of how to compile and store data in a form readily applicable to toxicology and pharmacology. One of the most crucial needs of the time was a computer-based system for the storage and retrieval of information on the biological effects of chemicals. A system was required which would provide quickly, on request, an annotated bibliography of 0272-0590/90$3.00 Copyright All

rights

0

1990

of reproduction

by the

Society in any

ofToxicology. form

reserved.

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published information in response to a specific question formulated by an inquirer. There was a need for more complete indexing of papers dealing with chemical-biological interactions; the needs for automatic abstracting, logical question programs, citation indexing, and association indexing were noted. The construction of a glossary of terms suitable for use with automated equipment was viewed as a requirement which would be difficult to fulfill. Indeed, a unified common language was needed because the various disciplines had different glossaries of terms and classifications of knowledge, and without a common language, the questions asked would retrieve the wrong answers. This perception of the need for a specialized toxicology information “system” evolved in an era when the number and variety of chemicals that affect the public increased at an alarming rate and created public health problems of major proportions. This era continues, and we are still confronted with a profusion of chemicals in the form of industrial and municipal wastes, air and water pollutants, herbicides, pesticides, cosmetics, and food additives, as well as drugs and a myriad of other industrial chemicals to which all segments of our population are exposed either deliberately or inadvertently in the course of daily living. Of particular importance are the effects of these ubiquitous chemicals to which people are exposed at low concentrations over prolonged periods, because in these cases the toxic effects develop slowly, are subtle, and are difficult to discern (The White House, 1966). Dictionaries still define toxicology as the study of poisons, their actions, their detection, and the treatment of the conditions produced by them; it is commonly perceived as an acute phenomenon. Social organizations exist to handle problems created by acute toxic or lethal doses of chemicals because there are sporadic and accidental emergencies of this type. Since it is a matter of dosage, most chemicals are toxic to some degree in some manner. The toxic effects which appear after long-term,

low-level exposure are equally significant and potentially just as disastrous. The human body has remarkable tolerance for the exogenous chemicals to which it is exposed in the environment and the workplace, but it is possible that under the onslaught of the increased numbers, varieties, and concentrations of chemical substances this protective tolerance may no longer be adequate to ensure good health over a 70-year-plus life span. The phenomenon of long-term, low-level exposure to chemicals has spawned related new concepts and a vocabulary which includes terms like carcinogenesis, teratogenesis, and mutagenesis. These terms have now become household words. For some of the associated hazards, such as from the carcinogens found in automobile exhaust fumes or cigarette smoke, we are unlikely to find more compelling evidence of their deleterious effects. Not only are these long-term “toxic” effects important to the individual whose health may have been damaged, they may be of grave importance to the future well-being of the human race. It still remains for industrial and governmental bodies to utilize in the public interest all the information now available, and for the scientific community to continue experimentation on the basic mechanisms of such long-term “toxic” effects and to find ways of preventing or attenuating their hazard (Brodie et al., 1965). THE TOXICOLOGICAL INFORMATION SYSTEM In order to examine the ramifications of chemical hazards to those who live in industrialized societies, President Lyndon B. Johnson requested the advice of The Panel on the Handling of Toxicological Information of The President’s Science Advisory Committee (PSAC). The PSAC Report on the Handling of Toxicological Information, which made a number of important recommendations, was released by the President in June 1966 (The White House, 1966). Because of the wide-

TOXICOLOGICAL

spread interest in problems associated with the handling of toxicological information, the President directed that it be published and made generally available. Among the recommendations of the PSAC report, preeminent was the recommendation “that there be established, by the Department of Health, Education, and Welfare, a computer-based facility to cope with the flood of toxicological information and to make it quickly available to people with a legitimate need for it.” In 1967, the Toxicology Information Program (TIP) of the National Library of Medicine was founded as a direct outgrowth of this recommendation. In 1987, the TIP celebrated its 20th anniversary. It has set the pace by using the latest technology to impose a coherent structure on the growing and widely disbursed literature and activities of toxicology. The Program has initiated a number of “firsts” widely hailed by the toxicology community as being of critical importance in answering important research, clinical, and emergency needs. Indeed, as its 20th anniversary approached, the Society of Toxicology issued a special commendation to the Program for two decades of sustained high quality services to toxicology. The Society cited the Program’s “vital chemical and toxicological services, used in the development of knowledge for the improvement of public health and safety and the protection of the environment.” A similar honor was bestowed upon the TIP by the American Academy of Clinical Toxicology “for superior informational services in the area of clinical toxicology.” Among TIP’s ground breaking innovations was the creation of TOXLINE in 1972. It was the first online retrieval service dedicated to the toxicology literature. CHEMLINE, a companion file, became the first online chemical dictionary to link nomenclature, structural information, and CAS Registry Numbers to the location of information in other files containing references and data. In 1978, the Toxicology Data Bank (TDB) became the first online factual data bank focusing upon the toxic and other attributes of

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potentially hazardous chemicals. The extensive peer review process developed for TDB was unique in the building of data banks. TDB was eventually subsumed by the larger and more comprehensive Hazardous Substances Data Bank (HSDB) in 1985 as one of the data banks accessible on the new TOXNET system developed by the TIP. HSDB has retained the peer review process. It has not taken long for HSDB to prove its worth as an invaluable information adjunct for emergency response personnel in the handling of chemical spills and other accidents. In 1986, the Chemical Carcinogenesis Research Information System (CCRIS) of the National Cancer Institute and in 1987 the Registry of Toxic Effects of Chemical Substances (RTECS) of the National Institute for Occupational Safety and Health (NIOSH) joined the TOXNET family of data banks. During 1988, a number of new data bases were considered’ for addition to the TOXNET system. Some of these were made publicly available in 1989 (National Library of Medicine, 1988). Toxicological information is all information which describes the effects of chemicals on living organisms or their component subsystems; including reports on exposure, and thus, the clinically and biochemically demonstrable effects, as well as the procedures for preventing or alleviating the untoward effects of such exposure. A small fraction of the millions of known chemicals have beneficial or therapeutic effects. A larger fraction has little or no effect that has been ascertained, and a small fraction is known to have distinct, observable, and deleterious effects on living organisms. Understanding how chemical substances act on biological systems is the province of toxicology/pharmacology; however, such understanding does involve all the branches of the chemical and biological sciences. Therefore, the source of this information is quite diffuse. Much of this information, especially if noticeable effects are found, is published in the open literature. A large accumulation of data on toxic effects, or the

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lack thereof, is often confined to the files of chemical and pharmaceutical manufacturers or in the files of regulatory agencies because of the alleged “proprietary” nature of the information found in these files. This represents a substantial body of information which does not get published. In addition, there are research programs of a classified nature within the Government which also generate toxicological information that does not find its way into the public literature. The clinician or the investigator rarely knows where an inquiry should be addressed when seeking information residing in these files. This problem still needs to be addressed because toxicological information should not be viewed as proprietary and should be easily accessible in the interest of a safe environment and the public health (The White House, 1966). THE

NEED

FOR TOXICOLOGICAL INFORMATION

Those synthesizing and testing new chemicals, those manufacturing and marketing chemicals, those regulating the use of these chemicals, and those using chemicals have a continuing need for information on the effects of chemical substances on biological systems and on the environment. The information needs of the different groups, as well as of the individuals within each group, vary widely with respect to urgency, information format, timeliness, manner of delivery, and comprehensiveness. In the words of the PSAC report, no group should be barred from access to the total accumulation of toxicological information. In varying degree each demands that the toxicological information “system”: (a) alert the user to new problems or important new understanding, (b) permit browsing in the accumulated literature, and (c) facilitate systematic searching of the accumulated literature with respect to a specific research or clinical problem. Toxicological information is generated in every part of the globe, is published in many

languages, and finds its way into the basic bibliographic network through a multiplicity of channels. The system for accomplishing this dissemination is vast, complex, and varies considerably in its sophistication. The basic difficulty with the information transfer network was its inability to assure completeness of coverage because information was distributed to thousands of journals and only a small fraction of the total is gathered in journals devoted to pharmacology or toxicology per se. At the same time, the network did not provide selectivity of coverage for the individual user. As the volume of information increased and as the sources of this information proliferated, this problem became greatly magnified. The current online data bases in toxicology bring some relief to this problem. However, each information service still tends to guard its own existence and none meets all the information needs of the scientific community. Each existing service has developed as a separate entity, unconcerned and often incompatible with the other services. Many sources of toxicological information still remained untapped. The existing information systems should be extended, supplemented, and coordinated (The White House, 1966). The U.S. Public Health Service Report (Brodie et al., 1964) recognized the following as a crucial need as early as 1964: “A comprehensive and exhaustive system for storage and retrieval of valid information on the interaction between chemical substances and biological systems. The existence of this system would, perhaps, allow the creation of those new broad scientific conceptualizations which will speed the progress of toxicology and pharmacology by quantum jumps.” This toxicology information system now exists; we need to improve it and we need to use it. The series of papers that will follow this introduction to toxicological information describe important information resources, their content, and their accessibility. ACKNOWLEDGMENTS The author thanks Norbert P. Page and the other members of the Information Handling Committee, Soci-

TOXICOLOGICAL ety of Toxicology, for their support. Our appreciation is also expressed to the authors of this series of articles on toxicology information resources.

REFERENCES BRODIE,B.B.,COSMIDES,G.J.,KETY,S.S.,ANDRALL, D. P. (1964). Toxicology: A Status Report (U.S. Public Health Service Report, October 7, 1964). Office of the Assistant Secretary for Health, DHHS, Washington, DC. BRODIE,B.B.,COSMIDES,G.J.,ANDRALL,D.P.(~~~~). Toxicology and the biomedical sciences: New pro-

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grams recommended for increasing research and training in toxicology and pharmacology. Science 148 (3677),

1547-1554.

Editorial Note (1988). Contemporary issues in toxicology. Toxicol. Appl. Pharmacol. 95349-362. National Library of Medicine ( 1988). Programs and Services: Fiscal Year 1988. Specialized Information Services. p. 35. Office of Inquiries and Publications Management. National Library of Medicine. Bethesda, MD. The White House (1966). A Report qfthe President’s Science Advisory Committee: Handling of Toxicological In&mnation. Superintendent of Documents, U.S. Government Printing Office, Washington, DC.