The International Life Sciences Institute (ILSI), a nonprofit, public foundation, was established in 1978 to advance the sciences of nutrition, toxicology, and food safety. ILSI promotes the resolution of health and safety issues in these areas by sponsoring research, conferences, publications, and educational programs. Through ILSI's programs, scientists from government, academia, and industry unite their efforts to resolve issues of critical importance to the public. As part of its commitment to understanding and resolving health and safety issues, ILSI is pleased to sponsor this series of monographs that consolidates new scientific knowledge, defines research needs, and provides a background for the effective application of scientific advances in toxicology and food safety. Alex Malaspina President International Life Sciences Institute Contents Series Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . xiii . . . . . . . . . . . . . Part I. Integrative Approach to Assessing Human Health Risk: Two Contemporary Problems Chapter 1. Integrating Diverse Data Sets to Assess the Risks of Airborne Pollutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 R.o. McClellan, R.G. Cuddihy, w.e. Griffith, and J. L. Mauderly Chapter 2. Risk Assessment for Radon Inhalation Based on Animal Exposure Data and Human Epidemiology . . . . . . . 23 . F. Steinhausler Part II. Types of Evidence: General Strengths and Weaknesses Section 1. Epidemiological Chapter 3. Inhalation Hazards: The Interpretation of Epidemiologic Evidence. . . . . . . . . . . . . . . . . . . . 39 . . . . . . . J.e. Bailar Chapter 4. Problems in Interpreting Epidemiological Data 49 P.N. Lee Section 2. Animal Chapter 5. Rodent Carcinogenicity Studies: Their Value and Limitations. . . . . . . . . . . . . . . . . . . . . . . . . . 61 . . . . . . . . . .

The Third International \ orkshop on "The in Vitro Effects of Mineral Dusts" was held on October 1 - 4, 1984 in Schluchsee, Black Forest, Federal Republic of Germany. In six sessions, 93 participants from 14 countries (USA 32, France 17, United Kingdom 12, FRG 11, Canada 9, Belgium 3, Hungary 1, Italy 2, India 1, Nether lands 1, Norway 1, Poland 1, Portugal 1, Turkey 1) treated and discussed the following subjects: - Significance of the physico-chemical properties of inhalable mineral dusts (mine dusts, asbestos, Man-Made Mineral Fibres - MMMF). - Cellular effects of inhalable mineral dusts with special regard to target ce 11 s. - Immune response and immune toxicity. - Carcinogenicity and interrelated genotoxic and non-genotoxic effects. - Effect of cell metabolism in combination with inflammation and fibrogenesis. - Significance and credibility of in vitro test systems. For the pathogenesis of biological effects and diseases caused by inhalable mineral dusts a number of factors may be significant such as: - Type of dust - Dose of dust - Size and shape of dust particles, and especially - Surface properties of dust particles, which inter alia determine the - sorption properties, e.g. for environmental substances."

The Dutch experience has influenced the debate on euthanasia and death with dignity around the globe, especially with regard to whether physician-assisted suicide and euthanasia should be legitimized or legalized. A review of the literature reveals complex and often contradictory views about the Dutch experience. Some claim that the Netherlands offers a model for the world to follow; others believe that the Netherlands represents danger, rather than promise, and that the Dutch experience is the definitive answer regarding why we should not make active euthanasia and physician-assisted suicide part of our lives. Given these contradictory views, it has become clear that fieldwork is essential to developing a more informed opinion. Having investigated the Dutch experience for a number of years, and after thoroughly reading the vast literature published in English, I went to the Netherlands for one month in the summer of 1999 to get a feel for the local situation. I felt that this would provide the basis on which I could better interpret the findings of the available literature. I visited the major centers of medical ethics, as well as some research hospitals, and spoke with leading figures in the euthanasia policy and practice. The time spent was extremely beneficial and enriching. I followed in the footsteps of Carlos Gomez, who 1 published a book following one month of extensive research in the Netherlands.

This volume, written by a range of international experts, covers a wide range of topics involving organic fluorine compounds. Each chapter is preceded by a summary and includes extensive illustrations and references. The chapters cover atmospheric chemistry, application of 19F NMR, partition, degradation and transformation, naturally occurring organic fluorine compounds, toxicology of perfluoroalkanes and phosphorofluoridates, and application of aromatic compounds to the elucidation of the mechanism of cytochrome P450.

All industrial countries have developed regulatory systems to assess and manage the risk of chemical substances to the working and natural environment. The pressure to harmonize these often specialized regulatory systems is increasingly strong at the international level. Such harmonization not only entails the assessment of particular chemicals, but also the way assessment procedures and their boundary with risk management is organized. As these initiatives intensify, they increasingly raise important questions of how to integrate national differences in the international regulatory arena. How will national consultation procedures relate to international decision-making on chemical risks? How will differences in national risk assessment procedures be accommodated? How will the international regulatory system be integrated with different national styles of regulation and government? Presenting the experiences and insights of both people from within the worlds of risk assessment and management and from the field of Science Studies, this book forms a state-of-the-art in the discussion on the Politics of Chemical Risk. By offering scenarios, or sketches of a regulatory future, it points to the choices that can be made and the opportunities to be explored. As such, it offers an agenda for environmental and occupational scientists, policy-makers and students of science and technology alike.

In 2000 OpdenKamp Registration & Notification organized a two-day symposium in The Hague, The Netherlands, on The Practical Applicability of Toxicokinetic Models in the Risk Assessment of Chemicals'. Several speakers from Europe and the United States were invited to present the different aspects. A vast range of areas was discussed in relation to toxicological modeling and risk assessment, such as occupational toxicology and biomonitoring, exposure to organic solvents and crop protection products, dose-response relations in carcinogenicity, regulatory toxicology, estimation of dermal penetration, uptake and disposition of organic chemicals in fish, the possibilities of in vitro methods in hazard and risk assessment, and the extrapolation between animal and human species. Based on their presentations, the speakers prepared comprehensive papers for this symposium book, reflecting the state of the art of modeling and toxicological risk assessment at the beginning of the third millennium.

The soil-transmitted nematode parasites, or geohelminths, are - called because they have a direct life cycle, which involves no intermediate hosts or vectors, and are transmitted by faecal contamination of soil, foodstuffs and water supplies. They all inhabit the intestine in their adult stages but most species also have tissue-migratoryjuvenile stages, so the disease manifestations they cause can therefore be both local and systemic. The geohelminths together present an enormous infection burden on humanity. Those which cause the most disease in humans are divided into three main groupings, Ascaris lumbricoides (the large roundworm), Trichuris trichiura (whipworm), and the blood-feeding hookworms (Ancylostoma duodenale and Necator americanus ), and this book concentrates on these. These intestinal parasites are highly prevalent worldwide, A. lumbricoides is estimated to infect 1471 million (over a quarter ofthe world's population), hookworms 1277 million, and T. trichiura 1049 million. The highly pathogenic Strongyloides species might also be classified as geohelminths, but they are not dealt with here because the understanding of their epidemiology, immunology and genetics has not advanced as rapidly as for the others. This is primarily because of the often covert nature of the infections, with consequent difficulties for analysis. If there is ever a second edition of this book, then there will hopefully be much to say about this infection.

Over the last few decades new data on the distribution, pathogenicity, diagnosis, treatment and control of trematode infections and diseases in man and animals, including zoonotic trematodiasis, have emerged from various geographical regions. These new data are compiled in this book together with existing information to fulfil the present need. Seven major trematode-induced disease groups, namely, schistosomiasis, paragonimiasis, fascioliasis and fasciolopsiasis, dicrocoeliasis and eurytremiasis, clonorchiasis and opisthorchiasis, paramphistomiasis, and diseases due to intestinal trematode infections are dealt with in this book. These diseases still rank as a major cause of morbidity and mortality - both in man and in livestock - mainly in the tropics, and contribute to the socio-economic problems. Many of these diseases are also zoonoses, some major and others potential. The intended readership of this treatise include postgraduate students of medical and veterinary parasitology, research workers as well as medical practitioners, veterinarians, tropical diseases specialists, veterinary public health specialists and teachers concerned with trematode infections and trematodiasis of man and animals.

This book presents the latest research in quantifying complex mixtures in the environment and analyzing their potential impact on human health. Many of the manuscripts reported in these proceedings represent the most up-to-date measurements of population exposures in Central and Eastern Europe. These studies are of value to health and environmental professionals around the world as they develop strategies for assessing exposures, remediating contaminated environments, and improving public health.

The automobile is one of the inventions that has made a decisive contribution to human mobility, and consequently it has become an inseparable part of modern human society. However, it is through this widespread use that its negative impacts on the environment have become so highly visible. Achievements in improving the ecological characteristics of the automobile are highly impressive: a modern car emits only a fraction of the amounts of noise and exhaust pollutants produced by its predecessors 30 years ago. The contributions to this book were written by experts, most of whom have been actively involved in the development of modern automobiles and their combustion engines for more than 30 years. They have participated in all phases of the ecological development of the automobile and summarize their experience and know-how in this book .

Heavy metals can be emitted into environment by both natural and anthropogenic sources, mainly mining and industrial activity. Human exposure occurs through all environmental media. Infants are more susceptible to the adverse effects of exposure. Increasing attention is now being paid to the mental development of children exposed to heavy metals. The purpose of this book is to evaluate the existing knowledge on intellectual impairment in children exposed to heavy metals in their living environment and to identify the research needs in order to obtain a clearer picture of the situation in countries and regions at risk, in which the economy is closely related to metallurgy and heavy metals emission, and to recommend a strategy for human protection. In greater detail the main objectives could be formulated as follows: to review the principal sources of single, and complex mixtures of, heavy metal pollutants in the environment; to identify suitable methodology for chemical analyses in the environment and in humans; to evaluate the existing methods for measuring mental impairment, including their reliability and validity; to recommend a standard testing protocol to be used in future research; to assess the future role of environmental heavy metal pollution in countries and regions at risk and its effects on children's neurological development; to recommend a prevention strategy for protecting children's health and development.

At the present time there are renewed global efforts to control the major tropical infections and to stem the tide of malnutrition, the two serious, often intertwined, problems that contribute to much of the morbidity and mortality in under privileged populations. Many international organizations have joined hands with national governments and with the private sector to search for new approaches to problems that beset much of the developing world, including countries in the tropical region. This volume continues the tradition of the previous publication in the Series. A variety of fare is offered to readers: explanations of the activities and achievements of the UNDP/World Bank/WHO Special Programme for Re search and Training in Tropical Diseases; and studies of infant mortality, schistosomiasis, trypanosomiasis, helminths, lactase deficiency, oral rehydration therapy, functional consequences of iron deficiency, and fertility control. Au thoritative state-of-the-art reviews provide a critical analysis of recent data. I hope the Series will continue to prove useful to all those working in the tropics and to those in the industrialized countries whose awareness of physical health problems of the Third World is relatively limited. R. K. Chandra St. John's, Newfoundland VlI Contents Chapter 1. The Special Programme for Research and Training in Tropical Diseases . . . . . . . . . . . . . . . . . . . DAVID S. ROWE 1. Origins, Objectives, and Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. The Modus Operandi of the Programme. . . . . . . . . . . . . . . . . . . . . . 3 2. 1. Scientific Working Groups. . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. 2. Research Strengthening Group. . . . . . . . . . . . . . . . . . . . . . . . . 7 2. 3. The Scientific and Technical Advisory Committee. . . . . . . . . 7 2. 4. Joint Coordinating Board. . . . . . . . . . . . . . . . . . . . . . . . . . . . ."

PREFACE xv Il Y a une ou deux decennies les ingenieurs ont crn ou voulu faire croire que l'automatisation des systemes de production et de contrOle permettrait de s'affranchir entierement de ce maillon faillible que constitue l'Homme.On a meme vu une reunion scientifique se reunir sur Ie theme "L'homme element limitatif de l'utilisation des systemes d'armes." Dne telle attitude montre avant tout que 1'0n n'a pas su integrer l'utilisateur dans la conception du systeme considere. Elle consacre la faillite d'un concept. On est revenu a une notion plus realiste de la situation. En effet, meme dans les systemes dits "entierement automatises" on trouve toujours un ou plusieurs hommes, indispensables pour surveiller Ie deroulement du processus, intervenir lorsque se produit une defaillance, voire reprendre en main l'ensemble des operations lorsque survient un incident. Le developpement des automatismes modifie evidemment la tache de 1'0perateur. L'homme contribue moins directement a la production elle-meme, en ce sens qu'on n'exige plus de lui un effort physique. On lui confie, dans des conditions de travail encore inhabituelles et auxquelles il n'est pas specialement prepare, des systemes dont les couts sont tres eleves et qui risquent d'etre deteriores s'il commet la moindre faute. Sans compter les risques qu'il est alors susceptible de faire courir a ses concitoyens. Le bon sens reprenant le dessus, on s'interesse maintenant a la place de l'Homme confronte a ces situations qu'il rencontre de plus en plus frequemment dans l'industrie.

Transport and mobility are essential parts of the current organization of society. Complex activities are interwoven in such a way that problems occurring from the actual process of constant movement cannot be separated, as they are so tightly interconnected.

This book examines the health effects of transport and mobility by addressing the major issues related to the subject and analyzing their consequences. Thus not only are air pollution, noise, and sedentarism and its related endocrine problems discussed, but topics such as jet-lag, accidents and violent displacement are also addressed. The strength of this book over others in the field lies in its multidisciplinary approach to the issues by a number of experts in different scientific fields who are documenting the health effects of transport and mobility. Moreover, it enhances the understanding of the issues by integrating information from different geographical regions.

Audience: Presented in a comprehensive manner, this book is useful as both grassroots, background information and state-of-the art knowledge to a wide range of readers, including experts and non-experts alike, professionals in both environmental and health sciences, decision-makers, research scientists, journalists, and post-graduate students.

Awareness that many aspects of public health are influenced by climate is growing dramatically. Results presented at the Wengen conference make clear that the science and art of integrating climate knowledge into the control of climate sensitive diseases on a year to year time frame, as well as careful assessments of the potential impacts of climate change on health outcomes over longer time frames, is advancing rapidly. This book provides a snapshot of these emerging themes.

In Risk Analysis of Complex and Uncertain Systems acknowledged risk authority Tony Cox shows all risk practitioners how Quantitative Risk Assessment (QRA) can be used to improve risk management decisions and policies. It develops and illustrates QRA methods for complex and uncertain biological, engineering, and social systems - systems that have behaviors that are just too complex to be modeled accurately in detail with high confidence - and shows how they can be applied to applications including assessing and managing risks from chemical carcinogens, antibiotic resistance, mad cow disease, terrorist attacks, and accidental or deliberate failures in telecommunications network infrastructure. This book was written for a broad range of practitioners, including decision risk analysts, operations researchers and management scientists, quantitative policy analysts, economists, health and safety risk assessors, engineers, and modelers.

Nanotechnology is rapidly invading many aspects of modern society - from science, research and engineering to industrial and commercial applications and, inevitably, to man and his environment. One of the biggest challenges, therefore, is managing environmental, health and safety risks of nanomaterials. Yet, the information necessary to assess their long term effects is scarce. Systematic research into what potentially makes engineered nanomaterials hazardous, how this translates into risk, and how these can be managed will be vital and involves interdisciplinary collaboration.

The first International Symposium on Nanotechnology and Occupational Health, in 2004, brought together hygienists, manufacturers, toxicologists, materials scientists, regulators and researchers. It pointed the way to what needs to be done. The second International Symposium, 2005, Minneapolis, Minnesota, demonstrated the power and potential where there is a will: with nearly three times as many attendants, and with contributions from academics, industry, policymakers, non-government organizations and even lawyers, this second symposium established that, while there is international concern over how to ensure safe nanotech-workplaces, there is also progress being made in developing the required knowledge.

This volume, a reprint from a special issue of the Journal of Nanoparticle Research, mainly draws from work presented at the 2005 symposium, diverse but united by the need for a holistic view of nanotechnology and risk.

Aimed at students taking a course on visual perception, this textbook considers what it means for a man, a monkey and a computer to perceive the world. After an introduction and a discussion of methods, the book deals with how the environment produces a physical effect, how the resulting "image" is processed by the brain or by computer algorithms in order to produce a perception of "something out there." It also discusses color, form, motion, distance, and also the sensing of three dimensionality, before dealing with visual perception and its role in awareness and consciousness. The book concludes with discussions of perceptual development, blindness, and visual disorders. Visual perception is by its very nature an interdisciplinary subject that requires a basic understanding of a range of topics from diverse fields, and this is a very readable guide to all students whether they come from a neuroscience, psychology, cognitive science, robotics, or philosophy background.

Environmental Chemistry is a relatively young science. Interest in this subject, however, is growing very rapidly and, although no agreement has been reached as yet about the exact content and limits of this interdisciplinary discipline, there appears to be increasing interest in seeing environmental topics which are based on chemistry embodied in this subject. One of the first objectives of Environ mental Chemistry must be the study of the environment and of natural chemical processes which occur in the environment. A major purpose of this series on Environmental Chemistry, therefore, is to present a reasonably uniform view of various aspects of the chemistry of the environment and chemical reactions occurring in the environment. The industrial activities of man have given a new dimension to Environ mental Chemistry. We have now synthesized and described over five million chemical compounds and chemical industry produces about hundred and fifty million tons of synthetic chemicals annually. We ship billions of tons of oil per year and through mining operations and other geophysical modifications, large quantities of inorganic and organic materials are released from their natural deposits. Cities and metropolitan areas of up to 15 million inhabitants produce large quantities of waste in relatively small and confined areas. Much of the chemical products and waste products of modern society are released into the environment either during production, storage, transport, use or ultimate disposal. These released materials participate in natural cycles and reactions and frequently lead to interference and disturbance of natural systems."

With parasitic diseases increasing worldwide it s vitally important that radiologists in particular stay up to date with developments. In this brilliantly useful volume, the authors cover the imaging findings for parasitic diseases that can affect the human body using modern imaging equipments. Every chapter consists of a short description of causative agent, epidemiology, clinical manifestations, laboratory tests, and imaging findings with illustrative examples of parasitic diseases."

This book reviews recent trends and developments in the study of the impact that the environment has on human reproduction. It thoroughly examines these issues, using the most modern techniques and methods available, to analyze the manner in which both male and female fertility can be affected and assessed. Coverage examines such diverse factors as toxic environmental contaminants, air pollution, and exposure to medical drugs.

This book grew out of an effort to salvage a potentially useful idea for greatly simplifying traditional quantitative risk assessments of the human health consequences of using antibiotics in food animals. In 2001, the United States FDA's Center for Veterinary Medicine (CVM) (FDA-CVM, 2001) published a risk assessment model for potential adverse human health consequences of using a certain class of antibiotics, fluoroquinolones, to treat flocks of chickens with fatal respiratory disease caused by infectious bacteria. CVM's concern was that fluoroquinolones are also used in human medicine, raising the possibility that fluoroquinolone-resistant strains of bacteria selected by use of fluoroquinolones in chickens might infect humans and then prove resistant to treatment with human medicines in the same class of antibiotics, such as ciprofloxacin. As a foundation for its risk assessment model, CVM proposed a dramatically simple approach that skipped many of the steps in traditional risk assessment. The basic idea was to assume that human health risks were directly proportional to some suitably defined exposure metric. In symbols: Risk = K x Exposure, where "Exposure" would be defined in terms of a metric such as total production of chicken contaminated with fluoroquinolone-resistant bacteria that might cause human illnesses, and "Risk" would describe the expected number of cases per year of human illness due to fluoroquinolone-resistant bacterial infections caused by chicken and treated with fluoroquinolones."

The International Section on Machine and System Safety was founded in 1975 to deal with questions on occupational risks in this ?eld at the inter- tional level. It is a member of the Special Commission on Prevention of the International Social Security Association (ISSA). The Special Commission is a body within ISSA that focuses on work-related risks. It has 11 inter- tional Sections as members. ISSA was founded in 1927 with its headquarters in Geneva. It is working worldwide in over 150 countries with nearly 370 member institutions from all ?elds of social security. TheSection on Machine and System Safety, when it was founded, had its focus on machine safety, particularly on the ma- facturing of safe machinery, on assisting developing countries to be able to buy safe used machinery, and on delivering clear operating instructions. Our members and partners are: * institutions for safety and health at work; * insurance companies dealing with work-related risks; * research institutions; and * various enterprises, e.g. manufacturers, importers and users of machines and systems/installations. We thus bring together the experiences of our members and partners. The role of the operators soon grew in importance, and their capability for ha- ling machinery became an important factor for the safety and success of enterprises. The growing importance and complexity of handling different man-machine-environment situations created new challenges and led to - larging the Section's tasks to machine and system safety.

This is an essential portable handbook on bioterrorism and disaster medicine. Its practical and comprehensive text features chapters pertinent to bioterrorism, infectious disease, microbiology, virology, public health, epidemiology, and disaster medicine. It will serve as a practical guide for situation-specific disasters; recognize what injuries or illnesses to expect; provide proactive guidelines to define specific diseases; and give a guide of appropriate personnel protective equipment during these large-scale emergencies. It is an essential companion to those either interested or currently working in any of the aforementioned fields.

The quality of food is such a live issue at the moment that this title is an essential tool for researchers in a variety of disciplines. It provides a review of the key features of trace elements in soils, plants and the food web on which human beings survive. The authors' intention is to summarize up-to-date interdisciplinary data for the concise presentation of our understanding of trace-element transfer in the chain from soil to man.