Search Results

Toxicology is a difficult scientific field that attempts to determine whether chemicals are harmful. There are many different ways that a chemical can cause harm, all influenced by the dosage and the route of exposure. This chapter gives a basic explanation for the public of how the toxicity, and therefore safety, of active ingredients is determined. Government regulation of repellent products provides considerable safety because groups of toxicologists give careful consideration to the amount of exposure and the potential for harm. Labels on products that limit the number of applications or restrict who can use a product are based on careful science.

The organisms that make Natural Products have been producing tens of thousands of different chemicals, totalling billions of tonnes every year, for billions of years. Hence, organisms have evolved to survive, indeed thrive, in the presence of these chemicals. The mechanisms evolved by organisms to cope with their chemical load are likely to be the same mechanisms used by organisms, including humans, to cope with new chemicals introduced into use by humans. This chapter shows how the subjects of toxicology and ecotoxicology can usefully be informed by the knowledge of NPs.

This chapter provides an overview of the book and a summary of each subsequent chapter. It highlights the volume's two major goals: to examine the range of methodological decisions and interpretive judgments that permeate policy‐relevant scientific research and to explore ways of making these choices more responsive to a range of public values (in addition to those of deep pockets, which have abundant resources to spend on research). It also introduces readers to the book's central case study, hormesis, which involves seemingly beneficial effects produced by low doses of substances that are normally toxic. Chapters 2 and 3 perform two preliminary tasks: (1) They clarify the major categories of value judgments that contribute to differing evaluations of the generalizability and regulatory implications of hormesis; and (2) they argue that societal values should not be completely excluded from influencing any of these categories of judgments. Chapters 4 through 6 develop the book's three primary lessons, corresponding to the three “bodies” that Sheila Jasanoff emphasizes as central to obtaining trustworthy public‐policy guidance from scientific experts. These lessons concern how to safeguard the body of scientific knowledge from interest groups, how to ascertain the best advisory bodies for guiding policy makers and directing the course of future research, and how to provide the bodies of experts themselves with an ethics of expertise. Chapter 7 argues that the lessons drawn in chapters 2 through 6 are applicable not only to the hormesis case but also to other areas of policy‐relevant research, such as endocrine disruption and multiple chemical sensitivity (MCS).

This chapter examines the history of hormesis research as an important case study of the ways in which methodological and interpretive judgments enter scientific practice. It organizes these choices into four major categories. First, judgments pervade the choice of research projects and the design of studies. One of the important questions in this regard is what kinds of studies to prioritize, given the limited funding available to examine the low‐dose effects of toxicants. Second, crucial decisions are involved in developing scientific language. The hormesis case study (as well as the multiple chemical sensitivity and endocrine disruption cases examined in Chapter 7) provides vivid examples of how the choice of scientific terms and categories can subtly influence policy discussions. Third, judgments play a crucial role in the interpretation and evaluation of studies. This third category of methodological choices is especially important to understand in the hormesis case, because it is largely responsible for the disagreements between proponents and opponents of claims about the generalizability and regulatory implications of hormesis. Fourth, there are important decisions to make about how to apply research results in the context of formulating public policy. For example, efforts to apply hormesis to regulatory policy must come to grips with difficult questions about how to balance potentially beneficial and harmful effects of toxic chemicals.

This final chapter reviews the book's major claims and considers important directions for future scholarship. The analyses in the preceding chapters suggest at least three promising avenues for future work: (1) further philosophical studies of the roles that various sorts of values should play in scientific research; (2) new scientific investigations of the biological effects of toxicants at low doses; and (3) ongoing social‐scientific research on how to incorporate a representative range of societal values in science. Regarding the role of values in science, leading philosophers of science disagree both about the extent to which scientific theory choice is underdetermined by epistemic values and about the conditions under which nonepistemic values should be employed in resolving this underdetermination. Related questions include whether the conceptual distinction between epistemic and nonepistemic values holds up to critical scrutiny and whether it is possible to draw a convincing distinction between practical decisions about how to act and epistemic judgments about what to believe. Regarding new scientific investigations, it is probably more important in the near future for scientific research to focus on hazards like endocrine disruption and toxic‐chemical mixtures than on hormesis, especially because sensitive populations like children are probably already exposed to mixtures of toxicants at levels above the hormetic dose range. Nevertheless, hormesis research may still be valuable in some fields, such as pharmaceutical development. Finally, with respect to social‐science research, it would be helpful to develop new strategies for addressing conflicts of interest, new research on the sorts of deliberative mechanisms that are effective in particular contexts, and further studies on how to effectively disseminate scientific information to its recipients.

Chapter 1 provides a map of key environmental health research and regulatory institutions, including the National Institute of Environmental Health Sciences (NIEHS), the National Toxicology Program (NTP), and the Environmental Protection Agency (EPA). It also considers the goals and perspectives of the chemical industry and of environmental health and justice activists.Focusing, then, on the contentious politics of the environmental health arena, it explores how the practices of environmental health scientists have been shaped by the forces and struggles in the field in which they operate

Several types of chemical information are needed including information on inherent chemical characteristics, chemical production and use, chemical release and exposure, and alternatives to hazardous chemicals. The Environmental Protection Agency and other government agencies and private services have developed many tools, models and estimation techniques for generating the needed data. New advances in computational toxicology can now provide “automated high-throughput” estimates of various chemical characteristics without the slow and costly chemical testing of the past. There are also significant efforts to improve chemical information transfer within supply chains and increase chemical information disclosure to the public.

Chemical safety is the general term for managing the hazards and risk associated with particular chemicals, both to protect workers and residents in the community. Hazards associated with chemicals may include poisoning, irritation, chemical burns, foul odour, allergies, explosion, fire and combustion products, release of heat or induction of cold. A particular problem with chemical safety occurs when workers enter confined spaces, places that are enclosed such air does not circulate freely and gases or vapours can collect at high concentrations and cause poisoning. Toxicology is the science that studies how chemicals are handled in the body and how they affect the body in causing injury or illness.

This chapter describes the adoption of the concept of environment by environmental activists in the United States between the 1950s and the 1980s. It argues that the modern environmental movement’s roots lie as much in consumerism as they do in nature protection or conservation. In the postwar United States, economic growth, technological advances, and social changes confronted consumers with numerous products whose origins and characteristics were obscure and unfamiliar, including plastics, pharmaceuticals, and pesticide-treated fruits and vegetables. At the same time, new techniques of chemical analysis and toxicological testing were revealing that the harmful side-effects of many products were not confined to those who directly purchased or consumed them. Drawing on the evolutionary theory of the day, physicians, scientists, writers, and activists such as Rachel Carson, Wilhelm Hueper, and Murray Bookchin argued that humanity might not be able to adapt quickly enough to the changes it was making to its own environment—a threat that they argued demanded radical technological, social, and legal responses. The chapter concludes by describing the rise of the environmental justice movement, which challenged the universalism of earlier environmentalists by calling attention to the unequal distribution of environmental risks.

The decision that a new chemical entity (NCE) is a serious candidate for development entails a financial commitment that is the most important one that a pharmaceutical or biotech company can make. The next most important set of decisions is concerned with making sure that development is aimed at a rational and focused set of objectives. Ending up "somewhere else" usually means failure. The two most important activities to ensure ending up in the right place are • preparing the Target Product Profile (TPP); • managing the disparity between results and expectations: the gap analysis. Since just about every development plan has a TPP, there would seem to be nothing new to say, so why devote most of a chapter to this subject? The answer is that the ways in which TPPs are prepared and the formats in which they appear vary enormously. Few seem to be the result of an exhaustive process and, as with most planning and preparatory activities, the process is just as important as the outcome. The objective is to provide a concise, structured basis for designing a development plan that (if successfully implemented) will lead to an uncomplicated approval process and to the desired labeling and data sheets in all markets. The TPP is a summary of requirements for an optimal but realistic profile of the product. • It precisely defines the expectations for the compound, with an explanation for these expectations, so that if they are not fulfilled, a rational analysis of the continuing viability of the compound can be carried out. • It is well-researched and detailed, including competitor and commercial information, and anticipates the environment at the planned date of launch. • Although written when there is little information about the drug in question, it is based on a solid foundation of objective data and not on outlandish or wishful thinking. • It is a relatively fixed document and should only be amended when changes are based on factors that could not have been foreseen when the TPP was originally drafted, such as the introduction of a new class of drugs for the same indication or a change in the standard of care.

Chapter 2 examines how scientists have used the ongoing conflicts, challenges, values, and narratives embedded in the contentious politics of environmental health to articulate the persistent challenges facing their field. It defines the concept of a “consensus critique”—an effort to bring stakeholders together around a set of shared concerns that transcend their substantive political, economic, and/or social differences. In this case, the consensus critique points to technical challenges and procedural limitations extant in toxicology testing, the environmental health risk assessment and regulation that diverse stakeholders tend to agree are problematic, even as they disagree vehemently about substantive and political matters, such as specific regulations.

This chapter examines the role of the University of Chicago Toxicity Laboratory in the development of toxicology and in scientific efforts to support defence during World War II. The Toxicity Laboratory was one of the first institutions devoted entirely to toxicological research. Some research topics pursued there provide important links in such areas as the joint toxicity and resistance to antimalarial drugs. E. M. K. Geiling directed several programs on behalf of the war through the Toxicity Laboratory. In addition to studying antimalarial drug therapies, scientists at the Toxicity Laboratory devoted considerable effort to the analysis of nitrogen mustards. In general, Geiling and the growing group of scientists at the Tox Lab carried out a broad range of studies with implications for pharmacology and for toxicology as a distinct discipline.

This chapter highlights lessons learned from a hundred years of risk assessment from pesticides. As the scale of agriculture developed to industrial proportions, farmers increasingly relied on chemical inputs, specifically insecticides, to control crop damage as a result of insect infestations. The methods developed by E. M. K. Geiling and FDA scientists revealed the value of toxicology in characterizing risks of chemicals in the marketplace. Meanwhile, the book Silent Spring highlighted the tragic irony of legislation and pesticide use. While organophosphates posed a significant risk to humans and wildlife, most remained in the market until the EPA completed its comprehensive review in 2006. To this day, organophosphates are still among the most widely used pesticides in the world, with tragic consequences for farm workers, children, and wildlife populations.

This chapter describes the basic principles of toxicology and their application to occupational and environmental health. Topics covered include pathways that toxic substances may take from sources in the environment to molecular targets in the cells of the body where toxic effects occur. These pathways include routes of exposure, absorption into the body, distribution to organs and tissues, metabolism, storage, and excretion. The various types of toxicological endpoints are discussed, along with the concepts of dose-response relationships, threshold doses, and the basis of interindividual differences and interspecies differences in response to exposure to toxic substances. The diversity of cellular and molecular mechanisms of toxicity, including enzyme induction and inhibition, oxidative stress, mutagenesis, carcinogenesis, and teratogenesis, are discussed and the chapter concludes with examples of practical applications in clinical evaluation and in toxicity testing.