The concept of zero and no-effect plays a major role in toxicology. Issues discussed in this chapter include the nature of the adverse responses produced at the level of the organism and population. Humans and animals evolved in an environment bathed in all sorts of chemicals. Some compounds were toxic and others beneficial and even essential, serving as nutrients and medicines. Even vitamins at low doses can be severely toxic at excessive doses. The historical transition of toxicology from (...) the science of poisons to today’s focus on safety is the source of semantic confusion over interpreting terms ranging from poisonous, hazardous, having zero effect, and nothing happens. How serious must an adverse effect be to be considered toxicologically significant? The chapter follows the development of Paracelsus’ dictum “Dose makes the poison.” Different approaches to quantitating a toxicologic response are presented, paying particular attention to the difference between a no effect dose, and one that produces a mild effect that defines the metrics we use for safe limits of exposure, versus a maximum tolerable dose. Detection of a biological effect no different than seen in control animals, or the normal population, should not be of concern. Chemical exposure does not equate to toxicity. (shrink)

This article examines the way in which public controversies affect regulatory science. It describes the controversy that unfolded in Europe around the use of the ninety-day rat-feeding tests for the risk assessment of genetically modified plants. This type of test had been criticized for almost two decades by toxicologists, nongovernmental organizations, and industry alike for its inability to capture the specific health effects of GM plants. But GM risk assessment experts showed great reluctance to move toward a more systematic use (...) of other tests, such as chronic two-year studies or toxicogenomic techniques, and made sure that official guidance continues to recommend the use of the ninety-day rat-feeding study. The article shows that these tactics of standardization are a defining feature of regulatory science, and a resource for toxicity experts to defend their authority and credibility against competing expertises that arise during controversies. (shrink)

Inmaculada de Melo-Martín and Kristen Intemann consider whether, from the perspective of the argument from inductive risk, ethical and political values might be logically, epistemically, pragmatically, or ethically necessary in the “core” of scientific reasoning. In each case, they argue that there are significant conceptual problems. In this comment, employing regulatory uses of high-throughput toxicology at the US Environmental Protection Agency as a case study, I respond to some of their claims about the notion of “pragmatic necessity.” I conclude (...) that, while an inductive risk framework has some significant limitations, it is still conceptually and rhetorically valuable. (shrink)

If scientists rely on assumptions rather than logic, empirical confirmation, and falsification, they are no longer doing science but ideology – which is, by definition, unethical. As a recent US National Academy of Sciences report put it, “bad science is always unethical.”1 This article discusses several ways in which toxicologists can fall into ideology – bad, therefore unethical, science. In part because of the increasing expense of pollution control, some toxicologists have been reexamining pollution dose-response curves that are non-monotonic, that (...) is, curves in which the direction of some response changes with increasing or decreasing dose.2 Ethanol is a classic example of a non-monotonic dose-response curve because moderate drinking is associated with lower risks of heart disease, whereas heavy drinking is associated with higher risks.3,4 If some low-dose pollutants exhibit adaptive or “beneficial effects,”5 this might suggest re-thinking pollution regulations which presuppose linear no-threshold (LNT) dose-response curves. (shrink)

This chapter is designed to direct the reader’s attention to those aspects of pharmacology, toxicology, and pathology that are crucial for professionals committed to serving the needs of animals and society. The essential topics mentioned herein from these disciplines merit focus of veterinary students during their time in college. Further, it is important to note that a deep understanding in preclinical and paraclinical subjects like anatomy, physiology, microbiology, and parasitology helps in fostering crucial competencies in pharmacology and pathology. The (...) aim of the chapter is not to provide exhaustive knowledge about these core topics but rather to pinpoint to important elements that are indispensable for veterinarians to excel in the practice of veterinary medicine. (shrink)

Environmental risk assessment is often affected by severe uncertainty. The frequently invoked precautionary principle helps to guide risk assessment and decision-making in the face of scientific uncertainty. In many contexts, however, uncertainties play a role not only in the application of scientific models but also in their development. Building on recent literature in the philosophy of science, this paper argues that precaution should be exercised at the stage when tools for risk assessment are developed as well as when they are (...) used to inform decision-making. The relevance and consequences of this claim are discussed in the context of the threshold of the toxicological concern approach in food toxicology. I conclude that the approach does not meet the standards of an epistemic version of the precautionary principle. (shrink)

This essay’s principal objective is to examine how, when confronted with a case of possible criminal poisoning, early nineteenth-century English toxicologists sought to generate and to represent their evidence in the courtroom. Its contention is that in both these activities toxicologists were inextricably engaged in a complex communicative exercise. On the one hand, they distanced themselves from the instabilities of language, styling themselves as testifiers to fact alone. But at the same time, they saw themselves as deeply implicated in the (...) difficulties of forging a coherent signifying system out of a disparate collection of signs that in themselves bore no intrinsic meaning. The analysis has three main components: first, to suggest why criminal poisoning featured so prominently in the burgeoning legal literature on evidence which provided the framework for expert testimony in English courts; next, to show that the scientific evidence offered by toxicologists in poisoning cases can be usefully understood as a form of language; and finally, to suggest that this recourse to signs informed the toxicologist’s encounter with another type of courtroom expert—the legal advocate—who was equally interested in manipulating signs in order to construct legally sanctioned proof.Author Keywords: Evidence; Expertise; Poisoning; Testimony; Toxicology. (shrink)

This paper considers the continued use of simpler model organisms in newer forms of toxicological research in order to inform philosophical understandings of the epistemic roles played by such organisms in the contemporary life sciences. We focus on the emerging domain of ‘precision toxicology’ and consider three uses of model organisms within it, namely as (1) models of toxic effects and other forms of environmental exposures; (2) indicator species; and (3) bioremediators. We analyze the epistemic implications of these uses, (...) arguing that they represent hybrid forms of modelling in comparison to traditional uses of model organisms, and identify similarities and differences between these emerging research practices and the model organism repertoire being adapted for use in this domain. Model organisms are simultaneously viewed as tools for intervention and representation within precision toxicology, in ways that differ from the model organism repertoire both in terms of the extent to which the models fit applied research goals and how they foster evolutionary and developmental understanding. Hence we argue that model organisms remain highly influential models in the life sciences but are being used in research more closely associated with the concept of ‘precision,’ and characterized by an ethos of intervention particularly in response to the environmental challenges associated to climate change and attention to the evolutionary and developmental grounding of health and disease. In closing, we reflect on the ways in which using the analytic framing associated with the repertoires approach facilitates the tracking of these developments in the contemporary life sciences. We also assess how they may affect the construction and significance of model systems over coming decades particularly in relation to precision-related research. (shrink)

In nineteenth-century British India, criminal legal proceedings had erected a functional hierarchy between the “unreliable” evidence of human testimonies and the “reliable” testimony of dead bodies, and colonial law endorsed the distant and sanitized laboratories of the Chemical Examiners as the latter’s most authoritative source. This article probes the idealized legal and epistemological distinction between sites of forensic work situated inside and outside laboratories in British India by examining colonial toxicological research through the lens of its working objects. Following the (...) archival trail of decomposing dead bodies and chemical preservatives, it examines the socially embedded technical, cultural, and material practices through which medico-legal specimens were prepared before authoritative scientific experts could extract toxicological evidence from them. It focuses especially on the critical role that the “medico-legal Domes,” a group of technicians recruited almost exclusively from one of the most marginalized and stigmatized caste groups in India, played in these processes. Juxtaposing the practical value of their service with the structural devaluation of their labor in colonial forensic research, it makes visible the strategic maneuvers that were required to secure the image of laboratory-based toxicology as a source of forensic certainty that seemingly stood above its ambient bureaucratic, social, and cultural contexts. (shrink)

Hybrid scientific fields consist of a collection of knowledge-producing and -utilising organisations, fulfilling a dual role of providing specific knowledge services as well as contributing to increased scientific understanding. In this article, the processes that govern scientific knowledge production in hybrid scientific fields are explored. While such sets of organisations are targeted in science policy as receivers of resources, as well as providers of services and other knowledge products, attention in science studies is all but lacking. Data from a study (...) on toxicology as a representative of public health sciences are used. The author will focus on the effects on scientific research and its organisational relations by discussing three social processes relevant to knowledge production, problem choice, resource distribution, and reputational control. (shrink)

This essay explores how the enhanced sensitivity of chemical tests sometimes produced unforeseen and puzzling problems in nineteenth-century toxicology. It focuses on the earliest uses of the Marsh test for arsenic and the controversy surrounding “normal arsenic”—that is, the existence of traces of arsenic in healthy human bodies. The essay follows the circulation of the Marsh test in French toxicology and its appearance in the academy, the laboratory, and the courtroom. The new chemical tests could detect very small (...) quantities of poison, but their high sensitivity also offered new opportunities for imaginative defense attorneys to undermine the credibility of expert witnesses. In this context, toxicologists had to dispel the uncertainty associated with the new method and come up with arguments to refute the many possible criticisms of their findings, among them the appeal to normal arsenic. Meanwhile, new descriptions of animal experiments, autopsies, and cases of poisoning produced a steady flow of empirical data, sometimes supporting but in many cases questioning previous conclusions about the reliability of the chemical tests. This challenging scenario provides many clues about the complex interaction between science and the law in the nineteenth century, particularly how expert authority, credibility, and trustworthiness were constructed, and frequently challenged, in the courtroom. (shrink)

One way to do socially relevant investigations of science is through conceptual analysis of scientific terms used in special-interest science (SIS). SIS is science having welfare-related consequences and funded by special interests, e.g., tobacco companies, in order to establish predetermined conclusions. For instance, because the chemical industry seeks deregulation of toxic emissions and avoiding costly cleanups, it funds SIS that supports the concept of "hormesis" (according to which low doses of toxins/carcinogens have beneficial effects). Analyzing the hormesis concept of its (...) main defender, chemical-industry-funded Edward Calabrese, the paper shows Calabrese and others fail to distinguish three different hormesis concepts, H, HG, and HD. H requires toxin-induced, short-term beneficial effects for only one biological endpoint, while HG requires toxin-induced, net-beneficial effects for all endpoints/responses/subjects/ages/conditions. HD requires using the risk-assessment/regulatory default rule that all low-dose toxic exposures are net-beneficial, thus allowable. Clarifying these concepts, the paper argues for five main claims. (1) Claims positing H are trivially true but irrelevant to regulations. (2) Claims positing HG are relevant to regulation but scientifically false. (3) Claims positing HD are relevant to regulation but ethically/scientifically questionable. (4) Although no hormesis concept (H, HG, or HD) has both scientific validity and regulatory relevance, Calabrese and others obscure this fact through repeated equivocation, begging the question, and data-tri mm ing. Consequently (5) their errors provide some undeserved rhetorical plausibility for deregulating low-dose toxins. (shrink)

This Book is the 4th and final volume of the series under the title, “Introduction to Basics of Pharmacology and Toxicology” – with a primary focus on clinical pharmacology and therapeutics aspects. The initial and major part of this volume provides an extensive description of the use of drugs in clinical practice – with a clear and accessible overview of all the key prescribing topics needed for clinicians and researchers involved in the pharmacology segment. Emphasizing the safe and effective (...) administration of drugs, this volume helps readers understand the principles of clinical pharmacology to prevent medication errors. This title is also intended for researchers involved in clinical trials and developing a protocol. It is highly significant for practitioners who must critically analyze the literature of published clinical trials and assess the benefits of each trial, as well as its implications for patient care and treatment. A chapter on clinical trial ethics has been included and presented in a well-organized and sequential manner. Problems related to drug use in paediatrics, geriatric, and perinatal pharmacology have also been introduced as separate chapters. Researchers are introduced to the regulatory framework and the critical guidelines they must follow to meet agency approval standards. Full of numerous examples and the latest drug regulation guidelines, makes this volume a must have resource for all early, mid-career and senior clinicians as well as researchers. This is a highly informative and carefully presented book, providing scientific insights for scholars with an interest in clinical pharmacology. (shrink)

The ability of powerful and well-funded interest groups to steer scientific research in directions that advance their goals has become a significant social concern. This ability is increasingly being recognized in the peer-reviewed literature and in the findings of deliberative expert consensus committees. For example, there is increasing recognition that efforts to address climate change have been stymied in part by a powerful network of conservative foundations, which fund think tanks and other organizations that constitute a “climate change counter movement”. (...) Sociologist Robert Brulle recently found that the total annual income for 91 powerful.. (shrink)

The Adverse Outcome Pathway (AOP) concept is a knowledge assembly and communication tool to facilitate the transparent translation of mechanistic information into outcomes meaningful to the regulatory assessment of chemicals. The AOP framework and associated knowledgebases (KBs) have received significant attention and use in the regulatory toxicology community. However, it is increasingly apparent that the potential stakeholder community for the AOP concept and AOP KBs is broader than scientists and regulators directly involved in chemical safety assessment. In this paper (...) we identify and describe those stakeholders who currently—or in the future—could benefit from the application of the AOP framework and knowledge to specific problems. We also summarize the challenges faced in implementing pathway-based approaches such as the AOP framework in biological sciences, and provide a series of recommendations to meet critical needs to ensure further progression of the framework as a useful, sustainable and dependable tool supporting assessments of both human health and the environment. Although the AOP concept has the potential to significantly impact the organization and interpretation of biological information in a variety of disciplines/applications, this promise can only be fully realized through the active engagement of, and input from multiple stakeholders, requiring multi-pronged substantive long-term planning and strategies. (shrink)

This article investigates the question of how forensic toxicologists established the credibility of chemical analytical methods in poisoning lawsuits in the nineteenth century. After encountering the problem of laypersons in court, forensic toxicologists attempted to find strategies to make their evidence compelling to an untrained audience. Three of these strategies are discussed here: redundancy, standard methods, and intuitive comprehensibility. Whereas redundancy was not very practical and legally prescribed standard methods were not very popular with most forensic toxicologists, intuitive comprehensibility proved (...) effective and popular. This strategy relied on employing methods which did not require chemical knowledge to be understandable. The methods aimed to generate a visual aid and to be obvious in their results. Two forms of this strategy are discussed here: the presentation of the actual material and explicit comparison. I argue that this shift towards presenting forensic toxicology expertise as evident represents an important step in the history of forensic expertise. (shrink)

This article analyses three chapters of an early medieval compendium of toxicology preserved in the manuscript Vendôme, Bibliothèque Municipale, 109 (11th century) and, with variants, in the Liber de Venenis of Sante Ardoini (Venetiis, 1492). These chapters were composed from extracts of late antique medical texts: one derives from the Medicina Plinii and provides readings different from the transmitted ones; another extract is from the ancient Latin translation of Dioscorides known as B, and contains hitherto unknown fragments of this (...) translation; finally, the compendium ends with an adapted version of the chapter on the herb ‘basilisca’ transmitted in the Herbarium of Pseudo-Apuleius, which presents new variants and an additional fragment on harvesting the plant, and provides information that makes possible a textual emendation of that work. (shrink)

In this article, I outline elements of a ‘philosophical toxicology’, as recently proposed by Jens Soentgen. At that, I understand philosophy as a contemplation of orientation in the world. As there is a growing sentiment that we live in a ‘toxic age’, a philosophical toxicology aims at fostering orientation in a world marked by chemical pollution. I suggest nine points where philosophical approaches can contribute to the clarification of questions posed by modern toxicity phenomena. I then focus on (...) one of them, namely the conceptual analysis of the terms poison and toxicity. I propose Wittgenstein’s family resemblance framework as a means to represent the growing diversity of toxicity phenomena. I describe the problem of arbitrariness connected to it and ask what gives the term toxicity its contour. I answer this by positing four focal points of meaning for the concepts of poison and toxicity, before ending with a phenomenological account of the poisoned body. (shrink)

Des mortalités anormales frappent les ruchers d’Europe et d’autres continents depuis un peu plus de vingt ans. Depuis le début des troubles, des suspicions pèsent sur des insecticides d’un genre nouveau, utilisés en traitement de semences. La législation prescrivant l’évaluation des risques environnementaux de toute substance insecticide dès avant sa mise sur le marché, des apiculteurs sont allés consulter les dossiers portant sur les molécules suspectées, ce qui les a amenés à s’impliquer dans la critique et l’élaboration des règles d’évaluation, (...) et à côtoyer le monde des experts en toxicologie de l’abeille.Beehives across Europe and other continents have been affected by abnormal mortality for the last twenty years. Since these problems first appeared, suspicion has fallen on a new type of insecticide, which is used to treat seeds. The legislation prescribes environmental risk assessments of any insecticide substance before it reaches the market, and beekeepers therefore decided to consult the files concerning the suspect molecules. As a result, they became involved in critically reviewing and developing assessment rules, and thus came to rub shoulders with experts in bee toxicology. (shrink)

Urine toxicology testing among birthing people in the United States remains a clinical practice often informed more by personal values and conscious and unconscious biases, than by medical evidence and ethical obligations. As empirical evidence addressing harms and benefits of toxicology testing in pregnancy grows, and national organizations are taking a moral stance around clinical practice, no published structure explicitly positions the evolving data within an ethical framework. We draw on a model of applied ethics to inform a (...) set of concrete recommendations about what clinicians ought to do with regards to the practice of urine toxicology testing of pregnant patients. These methods facilitate a relationship between empirical data regarding toxicology testing in pregnancy and ethical norms. Our findings serve as a practical guide for clinicians and policymakers seeking clinical guidance around urine toxicology testing in pregnancy as well as a model for future translation of theoretical approaches into clinical action. (shrink)

Toxicology, the science of poisons, is a multidisciplinary field whose teaching is divided up between medicine, pharmacy and chemistry. This article uses toxicology textbooks to study disciplinary and editorial issues. The first part shows, through a serial and comparative approach, how the publication of toxicology textbooks promoted and legitimated the institutionalisation of a discipline with porous borders. The second part presents the editorial history of the Manuel complet de médecine légale [Complete Textbook of Legal Medicine] (10 eds; (...) 1821-1880) by Briand & Chaudé and the disciplinary consequences of the insertion of a Traité élémentaire de chimie légale [Elementary Treatise on Legal Chemistry] written by pharmacist-chemists. (shrink)

It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one (...) empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics. (shrink)

In this paper we argue for a naturalistic solution to some of the methodological controversies in regulatory science, on the basis of two case studies: toxicology and health claim regulation. We analyze the debates related to the scientific evidence that is considered necessary for regulatory decision making in each of those two fields, with a particular attention to the interactions between scientific and regulatory aspects. This analysis allows us to identify two general stances in the debate: a) one that (...) argues for more permissive standards of evidence and for methodological pluralism, and b) an opposing one that not only defends strict evidence requirements but also stipulates the use of one particular scientific methodologies for data generation. We argue that the real-world outcomes produced by alternative regulatory options are a vital piece of information that allows for the empirical assessment of these two stances. In particular, this information on outcomes makes it possible to analyze which standards of evidence and scientific methods generate the most useful knowledge as input for regulatory decision making. Our conclusion is that instead of an a priori selection of methodologies and standards, such decisions ought to be based on empirical evidence related to real-world outcomes. (shrink)

This article tracks the transformation of beagle dogs from a common breed in mid-twentieth century American laboratories to the de jure standard in global toxicological research by the turn of the twenty-first. The breed was dispersed widely due to the expanding use of dogs in pharmacology in the 1950s and a worldwide crisis around pharmaceutical safety following the thalidomide scandal of the 1960s. Nevertheless, debates continued for decades over the beagle’s value as a model of carcinogenicity, even as the dogs (...) became legislated stand-ins for human beings in multiple countries. Situating beagles as a biocommodity, the article calls for more sustained attention to the “political economy” of laboratory organism breeding, use, and production. The story of American commercial breeder Marshall Farms offers insight into the role of for-profit companies in contemporary laboratory animal provision, as the article makes a case for the value of a global perspective on transnational corporations as key sites of scientific practice and collaboration. (shrink)

In this article we discuss two divergent accounts of non-human animals as analog models of human biomedical phenomena. Using a classical account of analogical reasoning, toxicologists and teratologists claim that if the model and subject modeled are substantially similar, then test results in non-human animals are likely applicable to humans . However, the same toxicologists report that different species often react very differently to the same chemical stimuli . The best way to understand their findings is to abandon the classical (...) view of analogical - i.e., linear - reasoning, and replace it with a version informed by chaos theory. We briefly outline the current understanding of chaos, and trace its implications for toxicology and teratology. (shrink)

The genetically manipulated organism crisis demonstrated that technological development based solely on the law of the marketplace and State protection against serious risks to health and safety is no longer a warrant of ethical acceptability. In the first part of our paper, we critique the implicitly individualist social-acceptance model for State regulation of technology and recommend an interdisciplinary approach for comprehensive analysis of the impacts and ethical acceptability of technologies. In the second part, we present a framework for the analysis (...) of impacts and acceptability, devised—with the goal of supporting the development of specific nanotechnological applications—by a team of researchers from various disciplines. At the conceptual level, this analytic framework is intended to make explicit those various operations required in preparing a judgement about the acceptability of technologies that have been implicit in the classical analysis of toxicological risk. On a practical level, we present a reflective tool that makes it possible to take into account all the dimensions involved and understand the reasons invoked in determining impacts, assessing them, and arriving at a judgement about acceptability. (shrink)

Claude Bernard, the father of scientific physiology, believed that if medicine was to become truly scientiifc, it would have to be based on rigorous and controlled animal experiments. Bernard instituted a paradigm which has shaped physiological practice for most of the twentieth century. ln this paper we examine how Bernards commitment to hypothetico-deductivism and determinism led to (a) his rejection of the theory of evolution; (b) his minima/ization of the role of clinical medicine and epidemiological studies; and (c) his conclusion (...) that experiments on nonhuman animals were, "entirely conclusive for the toxicology and hygiene of man". We examine some negative consequences of Bernardianism for twentieth century medicine, and argue that physio/ogy's continued adherence to Bernardianism has caused it to diverge from the other biological sciences which have become increasingly infused with evolutionary theory. (shrink)

Cancer—and scientific research on cancer—raises a variety of compelling philosophical questions. This entry will focus on four topics, which philosophers of science have begun to explore and debate. First, scientific classifications of cancer have as yet failed to yield a unified taxonomy. There is a diversity of classificatory schemes for cancer, and while some are hierarchical, others appear to be “cross-cutting,” or non-nested. This literature thus raises a variety of questions about the nature of the disease and disease classification. Second, (...) philosophers of science have historically taken the aim of science to be arriving at true theories. However, scientists studying cancer come from a variety of disciplines, with different scientific as well as practical aims. Perhaps it is not surprising, then, that historians and philosophers of science do not seem to agree on how best to characterize the aim and structure of cancer research; it is far from clear whether the appropriate characterization of the aim is arriving at true theories, or even whether the proper units of analysis are “theories”, or instead, “models”, “explanatory frameworks”, “research programs”, “paradigms”, or perhaps, “experimental traditions”. With the rise of “big data” science—such as the Cancer Genome Atlas Project (or TCGA)—and “systems” approaches to the study of disease, both philosophers and historians of science are rethinking how best to describe and explain these distinctive kinds of scientific inquiry. -/- Third, cancer is in part a byproduct of our developmental and life history, as well as our evolutionary history. Cancer progression can be compared to a reversion of development, or, to the evolution of multicellularity. Thus, cancer raises intriguing questions about how we conceive of “functions”, “development”, and the role of our evolutionary history and particularly, selective trade-offs, in vulnerability to disease. -/- Last but not least, cancer research provides a case study for consideration of the roles of values at the science-policy interface. Epidemiological and toxicological research on cancer’s causes informs toxics law and regulatory policy, which raises a variety of questions about the nature of evidence and inductive risk in such contexts. (shrink)

Per- and polyfluoroalkyl substances (PFAS) are a large class of chemicals, whose carbon-fluorine bonds allow a wide range of industrial applications but also make them highly persistent. Since there is evidence about only a few of them and their properties may vary, one of the pressing issues regarding PFAS is how to group them for different purposes. In this paper, I aim to show how a recent panel of experts about grouping PFAS was co-opted in a way that favor the (...) fluorine industry. The panel consisted of eleven experts, including authors renowned for views in conflict with fluorine industry regulatory approaches, answering questions through an online application. Its main results along with the experts’ answers were published in 2022 in the journal Regulatory Toxicology and Pharmacology. Through a detailed analysis of all the material published and in dialogue with the literature about industry-funded research, I will present how choices in the design of the panel (e.g., which kind of consensus the exercise could capture, the ways questions were framed or even changed), in textual analysis (e.g., criteria for assembling opinions) and in the communication of the findings (e.g., what gets included or excluded) were made in an industry friendly way affecting two specific grouping approaches. I conclude with some lessons about this kind of influence of industry funding. (shrink)

Today, human pluripotent stem cell technologies find widespread application across biomedical research, as models for early human development, as platforms for functional human genomics, as tools for the study of disease, drug screening and toxicology, and as a renewable source of cellular therapeutics for a range of intractable diseases. The foundations of this human pluripotent stem cell revolution rest on advances in a wide range of disciplines, including cancer biology, assisted reproduction, cell culture and organoid technology, somatic cell nuclear (...) transfer, primate embryology, single‐cell biology, and gene editing. This review surveys the slow emergence of the study of human pluripotency and the exponential growth of the field during the past several decades. (shrink)

In this case study from litigation, I examine the origin of Monsanto-sponsored articles published in toxicology journals and the lay media that were designed to create doubt in critical evaluations of the herbicide, glyphosate. The role of ghostwriting and the use of third-party academics in the corporate defense of glyhphosate reveal that this practice extends beyond the corruption of medical journals and persists in spite of efforts to enforce transparency in industry manipulation of the scientific literature.

In vitro experimental approaches are of central importance to contemporary molecular and cellular biology and toxicology. However, the scientific value or impact of in vitro results depends on their relevance in vivo. In vitro effect studies address inobservable in vivo phenomena through experiments on analogous in vitro phenomena. We present a theoretical basis developed to evaluate the in vivo relevance of in vitro effect studies. As a case study, the procedure for measuring specific gene transcription in isolated cell nuclei (...) (nuclear run-off method) is analyzed It is concluded that current evidence fails to justify in vivo interpretations of nuclear run-off experiments within the framework of theoretical models of transcription, implying that quantitative in vivo interpretations are unwarranted. Qualitative interpretations of nuclear run-off experiments may be justified by inferring the best explanation, especially when significant in vitro effects follow in vivo perturbations.Elements of a general theory are proposed. It is concluded that quantitative in vivo interpretations are warranted primarily in biochemical quantitation of biomolecules, while studies on biological function should be interpreted qualitatively in terms of causal explanations. Inferences to the best explanations are strengthened through additional evidence and the creation of experimental differences (effects). (shrink)

It is widely recognized that endocrine disrupting compounds, such as Bisphenol A, pose challenges for traditional paradigms in toxicology, insofar as these substances appear to have a wider range of low-dose effects than previously recognized. These compounds also pose challenges for ethics and policymaking. When a chemical does not have significant low-dose effects, regulators can allow it to be introduced into commerce or the environment, provided that procedures and rules are in place to keep exposures below an acceptable level. (...) This option allows society to maximize the benefits from the use of the chemical while minimizing risks to human health or the environment, and it represents a compromise between competing values. When it is not possible to establish acceptable exposure levels for chemicals that pose significant health or environmental risks, the most reasonable options for risk management may be to enact either partial or complete bans on their use. These options create greater moral conflict than other risk management strategies, leaving policymakers difficult choices between competing values. (shrink)

Risk assessment is an evidence-based analytical framework used to evaluate research findings related to environmental and public health decision-making. Different routines have been adopted for assessing the potential risks posed by substances and products to human health. In general, the traditional paradigm is a hazard-driven approach, based on a monocausal toxicological perspective. Questions have been raised about the applicability of the general chemical risk assessment approach in the specific case of nanomaterials. Most scientists and stakeholders assume that the current standard (...) methods are in principle suitable, but point out that experimental aspects and practical guidelines need specific adaptations. Beyond this laboratory level, risk assessment of nanomaterials also faces a number of substantive and procedural limitations, which are intrinsically attributed to the general orthodoxy of the risk assessment concept. Moreover, the developed formalism used to organize scientific knowledge is closely interlinked with the underlying governance design and the mode of interaction between the two spheres of ‘science’ and ‘decisions’. This contribution will provide a closer look at the evolution of different institutional settings for risk assessment in the context of decision-making. Improved risk governance frameworks with different narratives, process designs and procedural elements will be compared. The question of a general principle of enhanced organization of risk assessment will be discussed taking account of the barriers of substantive and procedural limitations in the special case of nanomaterials. (shrink)

How do different experimental control strategies shape the production of biological knowledge? This paper examines Emil du Bois-Reymond’s electrophysiological investigations and Claude Bernard’s toxicological research in 19th-century physiology. Rather than viewing these as opposing methodologies, I analyze their approaches to nerve-muscle communication as complementary responses to shared epistemic challenges. Using Schickore’s framework for experimental control (2025), I show through a detailed historical analysis that experimental control functioned constitutively rather than merely technically in both research programs. Both scientists engaged in extensive (...) second-order experimentation, systematically exploring their experimental setups to determine what factors needed controlling. Du Bois-Reymond’s non-polarizable electrodes made possible new ways of understanding biological electricity as quantifiable phenomena, while Bernard’s ligature preparation constituted a method for understanding physiological functions as systematically separable within integrated organisms. Control practices and theoretical commitments co-evolved such that what counted as legitimate operationalization of theoretical principles was shaped by experimental practice. This analysis shows how experimental methodology and biological knowledge co-develop, suggesting implications for understanding methodological tensions in contemporary biological research. (shrink)

This paper critically explores how ‘chemicals at the nanoscale’ are defined under the Australian Industrial Chemicals Introduction Scheme (AICIS) and compares it with the definitions established by the United States Environmental Protection Agency (US EPA) and European Commission (EC). Focusing on the properties of particle size and solubility, it explores how Australian regulators have translated the underlying nanoscience into their formal definitional framework. It then considers the regulatory implications that may arise from the application of Australia’s specific interpretation. This study (...) reveals significant differences in how particle size and solubility are applied within nanomaterial definitions. AICIS structures its definitional framework around these physical properties as regulatory proxies for material risk, relying heavily on archetypal behaviours and characteristics that may not apply universally across all substances. In contrast, American and European frameworks more explicitly recognize these criteria have limited predictive capability for risk assessment and have designed frameworks that allow regulators greater flexibility in identifying and assessing nanoscale chemicals. In application, AICIS’ more simplified approach creates a narrower regulatory scope that may poorly correspond with toxicological outcomes. This has direct implications for which substances are included or excluded from more stringent regulatory oversight. Future legal research should subsequently explore how AICIS’ definition is applied in practice, focusing on how regulators pursue enforcement actions for materials that challenge these regulatory parameters. (shrink)

Despite their growing usage in commercial and industrial applications, nanomaterials have yet to be been thoroughly researched as to their potential health, safety, and environmental risk to human life after incorporation into new product improvement, development, design, and manufacturing processes. Identifying the appropriate governance framework for effective risk assessment analysis of toxicological risk to human beings—specifically manufacturing employees and consumers—and other living organisms, resulting from the development and application of these nanotechnology-based products, has yet to be scientifically determined. With major (...) regulatory gaps in the public regulation framework at national and international levels of governance, a proposed private governance framework is needed to assist the existing public regulatory framework with the proliferation of products and manufacturing processes utilizing nanomaterials. There are three distinct (yet complimentary) approaches available to develop a private governance framework to complement existing national public regulatory frameworks: responsible innovation, risk management, and voluntary guidelines/industry standards. The case for supporting a hybrid governance framework, combining public and private governance mechanisms, for nanotechnology is reflective of the current public policy environment that has emerged to best address health, safety, and environmental risk assessment issues concerning nanotechnology and nanomaterials. (shrink)

Although quite a bit has been written by philosophers of chemistry about the ontology of nanomaterials, this paper proposes to address the question of epistemic access to nanomaterials from the perspective of the phenomenology of technology, since this approach can provide important insights into nanotechnology's ability to yield transparent epistemic access to nanomaterials. In fact, I will argue that nanotechnology lends itself to the same sort of phenomenological analysis as other technologies (such as nuclear reactors) in which direct epistemic access (...) to the product of the technology is not possible due to the nature and/or features of that product. I will argue that nanotechnologies provide only a 'mediated access' to nanomaterials that requires chemical engineers to infer what is happening at the nanoscale from the information provided by the mediating devices. However, the indirect and interpretive nature of this epistemic relation increases the probability of 'misreading' what is occurring at the nanoscale and of unintended consequences from the manipulation of nanomaterials. This analysis concludes that, from the standpoint of safety, there are serious reasons for concern regarding nanotechnology due to the toxicological and environmental effects that may result from such unintended consequences. These concerns also stem from the fact that this problem is insurmountable because the phenomenological limits of epistemic access is endemic to nanotechnology itself. (shrink)

In September 2012, Gilles-Eric Séralini and seven coauthors published an article in Food and Chemical Toxicology claiming that rats fed Roundup©-resistant genetically modified maize alone, genetically modified maize with Roundup©, or Roundup© for 2 years had a higher percentage of tumors and kidney and liver damage than normal controls. Shortly after this study was published, numerous scientists and several scientific organizations criticized the research as methodologically and ethically flawed. In January 2014, the journal retracted the article without the authors’ (...) consent on the grounds that the research was inconclusive. In June 2014, Environmental Sciences Europe published a slightly modified version of the retracted paper. The publication, retraction and subsequent republication of the Séralini study raise important scientific and ethical issues for journal editors. Decisions to retract an article should be made on the basis of well-established policies. Articles should be retracted only for serious errors that undermine the reliability of the data or results, or for serious ethical lapses, such as research misconduct or mistreatment of animal or human subjects. Inconclusiveness, by itself, is not a sufficient reason for retracting an article, though a flawed study design might be. Retracted articles that are submitted for republication should undergo scientific review to ensure that they meet appropriate standards. Republished articles should be linked to the original, retracted publication. Journals that are reviewing studies with significant scientific and social implications should take special care to ensure that peer review is rigorous and fair. (shrink)

Isogenic lines, understood here as lines approaching genome‐wide homozygosity while remaining fertile and stable across successive generations, have transformed genetics and toxicology in vertebrate models. In zebrafish (Danio rerio), however, more than four decades of gynogenesis, clonal line production and inbreeding have not yielded stable, broadly usable fully homozygous resources. We argue that, in practice, this reflects biological constraints rather than merely technical limitations. Historical, genomic and developmental evidence points to three major barriers: polygenic and environmentally sensitive sex determination, (...) strong dependence on maternal factors during early development, and a structurally dynamic genome shaped by duplication, copy‐number variation and substrain divergence. Together, these features make extreme homozygosity biologically fragile, with recurrent sex‐ratio bias, infertility and line collapse, and they support experimental strategies that treat genetic background as a variable to be reported, tested and exploited rather than idealized away. (shrink)