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A postgraduate training program in toxicology has been established in Germany. Theoretical training in toxicology is offered on a modular basis to candidates aiming at certification as an "Expert in Toxicology, DGPT." The certificate is awarded by the German Society of Experimental and Clinical Pharmacology and Toxicology [Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (DGPT)]. The precondition for entering the training program is a university degree in medicine, chemistry, biochemistry, biology, or a related subject. To be eligible to take the final examination for Expert in Toxicology, DGPT candidates must have at least 5 years of full-time practical experience in toxicology. They must have gained comprehensive knowledge in at least 1 relevant field, broad knowledge in another 2 fields, and basic knowledge in all 15 relevant fields of toxicology. Candidates must submit at least three independent peer-reviewed papers or professional assessments in toxicology or pharmacology. The course program for providing theoretical training is a joint venture of the German toxicological institutions involved in education. More than a dozen courses, covering the spectrum of fields in toxicology, are held each year at toxicological institutes of universities and research centers throughout Germany specializing in the respective fields. The courses provide candidates with instruction from Germany's leading authorities at research facilities in various fields of toxicology. They provide the best possible education in the spectrum of toxicological subdisciplines.
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Regulatory Toxicology encompasses the collection, processing and evaluation of epidemiological as well as experimental toxicology data to permit toxicologically based decisions directed towards the protection of health against harmful effects of chemical substances. Furthermore, Regulatory Toxicology supports the development of standard protocols and new testing methods in order to continuously improve the scientific basis for decision-making processes. The objective of the Working Group 'Regulatory Toxicology' within the Section of Toxicology of the 'German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT)', is the transparent discussion and further development of the scientific principles of Regulatory Toxicology. Present methodologies for risk assessment should be evaluated with the objective of finding harmonised standards. This objective is being achieved through informal meetings, symposia and written communications on both a national and as far as feasible international level. Principal target audiences are, in particular, members of the scientific community who work in government agencies, universities, and industry, as well as contract organisations and consulting institutions. Being experts in this field, they are expected to carry forward the outcomes of harmonisation processes related to testing methods and risk assessment.
The importance of forensic toxicology has been increasing until now, because of the increasing numbers of toxic substances and poisoning incidents. In Japan, a special translational word "houi-chudoku-gaku" has been used for the forensic toxicology especially in the field of legal medicine. The Japanese word, however, does not seem appropriate for translation of forensic toxicology, because it covers medicine, pharmacy and police sciences interdisciplinary. In 1980, Emeritus Prof. Hidetoshi Yoshimura created an appropriate word "hochudoku-gaku" for translation of forensic toxicology. In 1982, Prof. Yoshimura and his friends established the Japanese Association of Forensic Toxicology, consisting of people from legal medicine, pharmacy and police institutes. This Association enabled lively discussions among different fields and greatly contributed to advances of forensic toxicology in Japan. We started studies of forensic toxicology using gas chromatography (GC)/mass spectrometry (MS) in 1979. Until now, we delt with solid-phase extraction (1987-1994), surface ionization GC (1989-1997), negative ion chemical ionization MS (1981-now), solid-phase microextraction (1994-now), cryogenic oven trapping GC (1997-now), surface ionization organic MS (1998-now) and high-performance liquid chromatography/tandem MS (1998-now). In this review, the author presents some details of solid-phase microextraction, negative ion chemical ionization MS, cryogenic oven trapping GC and surface ionization organic MS. Unprecedented poisoning terrorism by use of sarin took place in Matsumoto and Tokyo in 1994 and 1995, respectively. On July 25, 1998, a curry poisoning incident using arsenious acid occurred in Wakayama, resulting in the death of 4 people and injury of 63 people. Since then, more than 30 imitative poisoning cases have been reported by mass communication within 1 year. In spite of the above continuing poisoning cases, almost no effective measures have been taken by the administration of our country and local governments. Many serious problems concerning poisoning and drug abuse are accumulating in Japan. In this review, the problems are also made manifest, and some proposals are presented to solve the problems.
The unprecedented advances in molecular biology during the last two decades have resulted in a dramatic increase in knowledge about gene structure and function, an immense database of genetic sequence information, and an impressive set of efficient new technologies for monitoring genetic sequences, genetic variation, and global functional gene expression. These advances have led to a new sub-discipline of toxicology: "toxicogenomics". We define toxicogenomics as "the study of the relationship between the structure and activity of the genome (the cellular complement of genes) and the adverse biological effects of exogenous agents". This broad definition encompasses most of the variations in the current usage of this term, and in its broadest sense includes studies of the cellular products controlled by the genome (messenger RNAs, proteins, metabolites, etc.). The new "global" methods of measuring families of cellular molecules, such as RNA, proteins, and intermediary metabolites have been termed "-omic" technologies, based on their ability to characterize all, or most, members of a family of molecules in a single analysis. With these new tools, we can now obtain complete assessments of the functional activity of biochemical pathways, and of the structural genetic (sequence) differences among individuals and species, that were previously unattainable. These powerful new methods of high-throughput and multi-endpoint analysis include gene expression arrays that will soon permit the simultaneous measurement of the expression of all human genes on a single "chip". Likewise, there are powerful new methods for protein analysis (proteomics: the study of the complement of proteins in the cell) and for analysis of cellular small molecules (metabonomics: the study of the cellular metabolites formed and degraded under genetic control). This will likely be extended in the near future to other important classes of biomolecules such as lipids, carbohydrates, etc. These assays provide a general capability for global assessment of many classes of cellular molecules, providing new approaches to assessing functional cellular alterations. These new methods have already facilitated significant advances in our understanding of the molecular responses to cell and tissue damage, and of perturbations in functional cellular systems. As a result of this rapidly changing scientific environment, regulatory and industrial toxicology practice is poised to undergo dramatic change during the next decade. These advances present exciting opportunities for improved methods of identifying and evaluating potential human and environmental toxicants, and of monitoring the effects of exposures to these toxicants. These advances also present distinct challenges. For example, the significance of specific changes and the performance characteristics of new methods must be fully understood to avoid misinterpretation of data that could lead to inappropriate conclusions about the toxicity of a chemical or a mechanism of action. We discuss the likely impact of these advances on the fields of general and genetic toxicology, and risk assessment. We anticipate that these new technologies will (1) lead to new families of biomarkers that permit characterization and efficient monitoring of cellular perturbations, (2) provide an increased understanding of the influence of genetic variation on toxicological outcomes, and (3) allow definition of environmental causes of genetic alterations and their relationship to human disease. The broad application of these new approaches will likely erase the current distinctions among the fields of toxicology, pathology, genetic toxicology, and molecular genetics. Instead, a new integrated approach will likely emerge that involves a comprehensive understanding of genetic control of cellular functions, and of cellular responses to alterations in normal molecular structure and function.
By using information from printed and online database guides, 18 online bibliographic databases (BD), which cover literature on toxicology were selected from 5 hosts. A search for literature containing information on three selected chemicals was carried out with each of the databases, and the number of documents relevant to toxicology found in them was compared by computer-assisted analysis. Some databases yielded very little information pertinent to toxicology, while others provided a considerable amount. In addition, the databases contained numerous duplicates (references common to more than one database). Most of the relevant documents could be obtained using only 8 of the 18 BDs selected. These databases are: Biosis Previews (BIOSIS), Chemical Abstracts (CA), Chemical Safety Newsbase (CSNB), Excerpta Medica (EMBASE), National Institute for Occupational Safety and Health (NIOSH), Scisearch, Toxicology Information Online (TOXLINE) and the former Toxicology Literature (TOXLIT).
This paper presents a brief history of the evolution of toxicological information in the United States since 1966 when concern over the hazards of the 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.
This paper assesses historical reasons that may account for the marginalization of hormesis as a dose-response model in the biomedical sciences in general and toxicology in particular. The most significant and enduring explanatory factors are the early and close association of the concept of hormesis with the highly controversial medical practice of homeopathy and the difficulty in assessing hormesis with high-dose testing protocols which have dominated the discipline of toxicology, especially regulatory toxicology. The long-standing and intensely acrimonious conflict between homeopathy and "traditional" medicine (allopathy) lead to the exclusion of the hormesis concept from a vast array of medical- and public health-related activities including research, teaching, grant funding, publishing, professional societal meetings, and regulatory initiatives of governmental agencies and their advisory bodies. Recent publications indicate that the hormetic dose-response is far more common and fundamental than the dose-response models [threshold/linear no threshold (LNT)] used in toxicology and risk assessment, and by governmental regulatory agencies in the establishment of exposure standards for workers and the general public. Acceptance of the possibility of hormesis has the potential to profoundly affect the practice of toxicology and risk assessment, especially with respect to carcinogen assessment.
The International Union of Toxicology (IUTOX) was founded in 1980 in Brussels. The initiative was started by the Society of Toxicology (SOT), USA, and the European Society of Toxicology in 1975 (EST), and the foundation prepared by an Inter Society Liason Committee. Eight National Societies of Toxicology were founding members of IUTOX besides SOT and EST. It now comprises 43 national/regional Societies from all over the world, representing over 20,000 toxicologists. Information has always been a key element in toxicology. Information exchange in IUTOX has evolved from letters and phone calls to fax, e-mail and the use of the Internet. Initially, newsletters were created which were mailed and later displayed on the Web. The website has been developed as a major information tool with many useful links, thereby providing information for the scientific community, the media and the lay public.
Toxicology historically has been directed at studying the mechanisms of adverse effects of isolated compounds on living organisms at high levels of exposure, forming the basis for risk and safety assessment. One way to refocus and mobilize new research funds would be to better match the priorities in regulatory issues and direct the research within the field of toxicology more to low-dose toxicology and risk--benefit analysis. Low-dose toxicology can only be developed when taking into account mechanistic insight and will require risk-benefit analysis and a definition of interactions between compounds at realistic doses of exposure, especially in the case of dietary constituents. This is because the biological effects at low levels of exposure not only may be adverse but also can be beneficial depending on the target organ, the actual end point studied, the receptors activated, and/or the gene expression, protein, and metabolite patterns affected. Toxicologists have the tools and knowledge to study mechanisms of biological effects of chemicals on living organisms, and they should redirect their focus from looking only at adverse effects at high levels of exposure to characterizing the complex biological effects, both adverse and beneficial, at low levels of exposure. This may even result in the notion that beneficial effects can be the result of reaction pathways that are generally considered adverse and vice versa. Low-dose toxicology not only will provide a significant research challenge for the years ahead but also should contribute to better methods for low-dose risk assessment for complex mixtures of chemical compounds. This refocusing from high- to low-dose effects turns the field from a science focusing on adverse effects into a science studying the biological effects of chemical compounds on living organisms, taking into account the realization that the ultimate biological effect of a chemical may vary with its dose, the end point or target organ considered, and/or the combined exposure with other chemicals. By defining the effects of chemicals on living organisms at physiologically relevant exposure levels, toxicologists may contribute not only to better risk and safety assessment but also to preventive medicine, generating knowledge on possible adverse and also beneficial effects of chemicals. In addition, it will result in an approach for food safety assessment more in line with that for drug safety assessment taking the risk-benefit balance into consideration.