bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethical Issues Related to Animal Welfare Considerations in the Toxicology Laboratory
Authors: Phalen Robert F.
Published: December 2009

Toxicologists are required to maintain high ethical standards in their studies in order to comply with regulations and to meet the expectations of colleagues and the public. Ethical standards are continually evolving, due to regulatory actions, recommendations of professional organizations and public perceptions. Toxicologists, as do the large majority of all adults, subscribe to the principles of ‘animal welfare’ as opposed to the principles of ‘animal rights’ which opposes all human use of animals. Animal welfare in the toxicology laboratory is based on veterinary standards, accreditation standards, professional society standards, and on principles, such as the ‘3 Rs’: ‘Reduction’ (minimizing the number of animals used); ‘Refinement’ of procedures in order to minimize pain and distress; and ‘Replacement’ of animals by nonsentient models. Toxicologists strive to eliminate animal pain and distress, to use humane end points, to use humane methods for euthanasia and to provide for the health and safety of animal subjects. Toxicologists should also consider their responsibility to educate the public about what they do and why.

It is clear that the Animal Rights Movement, with the help of new and expanding, federal, state, and local laws, is rapidly making much animal research cost ineffective as well as extremely wasteful of the research scientist's time

(Guyton, 1988)
Chemical Terrorism
Authors: Ballantyne Bryan
Published: December 2009

Terrorism has a very long history. Terrorism has been defined terrorism as deliberately and violently targeting civilians for political purposes. One of the objectives of terrorism may be to generate a disproportionate response and thereby alienate the population against the state. The range of weaponry potentially available to terrorists is wide and variable: weapons used may include guns or explosive devices, radioactive/nuclear sources, biological organisms and toxins (bioterrorism) or xenobiotic chemicals (chemical terrorism). Chemicals that might be used include irritant and/or disorienting materials, nauseating materials, psychogenic materials and severely toxic and lethal agents. The only major chemical terrorist action to date was the two instances of use in Japan of sarin, an organophosphorus ester G‐agents, where there was large‐scale mass casualties. While many other compounds could be used in chemical terrorism (eg cyanide, arsine), the only other mass casualty situation to date involving terrorism was the death of many innocent citizens in an anti‐hostage situation in Moscow; this appears to have caused by the authorities' response, rather than the action of the terrorists.
Evaluating the Long‐term Health Consequences ofUnitedStates Combat Deployments: Toxicology and the Law
Authors: Brown Mark , Hyams Kenneth
Published: December 2009

With each war, the US Department of Veterans Affairs (VA) has been called on by veterans and their families, the US public, government leaders and the media to quickly provide information on the health consequences of combat deployment. VA must rapidly address difficult‐to‐answer health questions each time troops are deployed. Are veterans experiencing more health problems than expected? Have deployment‐related environmental hazards led to health problems among returning veterans? Are troops experiencing greater rates of cancers or mortality? How has deployment affected the veteran's family and reproductive health? Long‐term epidemiological studies provide the most accurate information about morbidity and mortality, but since they take years to complete, VA has had to resort to faster approaches to address veterans' health needs, including: voluntary clinical examination registries, specialized combat‐related clinical care programmes, and most recently, electronic ‘combat veteran rosters’ based on VA's comprehensive computerized health records. Another limitation of long‐term studies is that they generally fail to link specific deployment‐related environmental hazards to unique health outcomes because of the lack of useful environmental exposure data and troop location information during chaotic wartime deployments. Developing equitable healthcare and assistance policies for combat veterans related to environmental hazards therefore cannot be totally reliant on good science, and frequently cannot be based on research studies of the exposed veterans themselves. Consequently, VA has often developed governmental healthcare and disability‐assistance policies based on thorough reviews of all relevant scientific literature related to groups with well‐characterized exposures, whether military or civilian, by an independent scientific group such as the US National Academies of Sciences Institute of Medicine (IOM).
Biological Toxins in Warfare and Terrorism
Authors: Evans R. Gregory
Published: December 2009

Toxins are harmful biological agents produced by bacteria, plants and animals. They differ from chemical agents in that they are naturally occurring, are nonvolatile and, except for mycotoxins, are not dermally active. Toxins can be much more toxic than chemical agents. They are also not persistent in the environment and are not transmittable from person to person. Toxins that are stable in the environment, highly toxic and easy to produce are candidates for use as biological weapons. Some toxins, such as mycotoxins andricin, require much larger quantities than toxins such asbotulinumto be effective in an open‐air aerosol exposure; however, they can be effectively used in an indoor release. In this chapter, we will discuss the four toxins that are considered most likely to be used as biological weapons either by state entities or terrorist organizations. The list includes one highly lethal toxin, botulinum, two fairly lethal toxins, ricin and mycotoxins, and one that is considered primarily an incapacitating agent, staphylococcal enterotoxin B. Botulinum is a Center for Disease Control and Prevention (CDC) Category A agent, while the other toxins are CDC Category B agents.
Toxicology and Disasters
Authors: Illing H. Paul A.
Published: December 2009

Although disasters may take many forms, they include the toxic consequences of large‐scale exposure to chemicals due to nature, major accident or deliberate terrorism. This chapter first examines some of the definitions associated with major accident hazards. It then classifies and examines major incidents involving toxic chemicals, including those resulting from nature, those resulting from human activity and those resulting from the interaction between nature and human activity. Included under human activity are disasters arising from escapes from industrial plant, from fire, from food and drink and from environmental pollution. Finally disaster prevention and mitigation is examined, with particular reference to the toxicological inputs into land use and emergency planning.
Toxicology of Pesticides
Authors: Dewhurst Ian C. , Marrs Timothy C.
Published: December 2009

Pesticides are a group of substances with heterogeneous toxicity, whose desired activity is the killing of unwanted living organisms. The main groups are insecticides, fungicides, herbicides and rodenticides. Many, but not all, pesticides have mammalian toxicity that is related to their toxicity to the target organism. To be weighed against their mammalian toxicity are the facts that insects and fungi are important sources of agricultural loss and give rise to much damage to buildings, where construction is often of wood. Furthermore, many insects carry diseases such as malaria and sleeping sickness, which in the absence of control measures may render land uninhabitable or agriculturally unusable. The key to a successful pesticide is selective toxicity and some of the more modern pesticides have actions that are target‐organism specific. In recent years, there has been some concern as to the possibility of deleterious effects from multiple pesticides exposure, either as residues in food or at the workplace. Another recent development is the use of microbial pest control agents: these are plant‐protection products that have a micro‐organism, that is, a bacterium, fungus, virus, protozoan, microscopic nematode or microsporidium, as the active material.
Dermal Toxicology of Cosmetics and Body‐Care Products
Authors: Basketter David , Lea Linda
Published: December 2009

There is a tendency in both regulatory thinking and in public perception towards the view that cosmetics are in some way different from other products. The reality of course is that they are formed from a combination of chemical ingredients, raw materials which, in fact, can be found in a very wide range of products. Consequently, the toxicology considerations which apply to other products also apply to cosmetics and body‐care products. Application of appropriate toxicological review of product ingredients and of the final formulation is key to meeting the requirement that such products do not cause harm to the consumer. Failure to undertake such a review to an adequate standard gives rise to a risk of adverse reactions. In this chapter, we set out some general thoughts on how a review of product safety generally should be approached for these types of product. Wherever possible, emphasis has been placed on the minimization and/or elimination of the need for in vivo testing.
Organic Solvents
Authors: Leira Håkon L. , Fonnum Frode , Syversen Tore
Published: December 2009

This chapter describes the exposure, absorption, metabolism and toxic effects, particularly effects to the nervous system, of organic solvents. Since both occupational and domestic exposure is usually to mixtures of individual solvents rather than to single compounds, the metabolic interaction of solvents is addressed, as well as toxic effects of mixtures. Organic solvents have many clinical effects in common, but some solvents have individual effects, for example, the polyneuropathy induced byn‐hexane, leukaemia induced by benzene and ventricular fibrillation induced by chlorinated solvents. Such effects, as well as particular metabolic profiles are described in individual sections on aliphatic solvents (chlorinated and nonchlorinated), alicyclic and aromatic solvents, alcohols and glycol ethers. Future challenges include exposure assessment, particularly with regard to occupational exposure. Furthermore, the mechanisms underlying the effects of organic solvents on the central nervous system are still not clear. Further work is also needed regarding carcinogenic properties, the role of genetic polymorphisms and possible immunotoxicological effects.
Toxicology of Substances that Affect Performance and Behaviour
Authors: Thompson John P.
Published: December 2009

The use of drugs to enhance performance has become a matter of increasing concern in recent years. However, with the advent of a greater range of pharmacologically active substances, and the possibility of psychological or financial reward, the temptation to use drugs in the pursuit of enhanced sporting performance or body image has increased.

Regulation of drugs in sport seeks to prevent the use of banned substances and techniques whilst allowing the legitimate use of therapeutic interventions for genuine medical conditions. The use of performance enhancing drugs may be accompanied by serious, even life threatening side effects.

Performance enhancing drugs may be used at the time of competition, or as a ‘training aid’ outside the competitive season, for example to increase muscle bulk. Their effect may be to increase strength or to allow a greater power output, for example by increasing oxygen delivery to tissues. Abused drugs include androgenic anabolic steroids, creatine, beta‐2 agonists, beta blockers, peptide hormones and diuretics. Techniques to improve oxygen delivery include the use of high altitude training, autologous blood transfusions and the use of erythropoietin.

Successful detection of abused drugs is fundamental for regulatory programs to be successful. Such programs should include random out of season testing, rigorous sample handling protocols and reliable analytical techniques. The advent of synthetic hormones with structures similar or identical to endogenous hormones presents significant regulatory challenges. Determination of the use of proscribed substances may involve setting threshold concentrations or defining acceptable ratios of different hormones. As more sophisticated techniques of abuse develop it may become necessary for regulatory programs to use increasingly invasive sampling techniques, to determine hormone profiles for individual athletes and even to undertake challenge tests which seek to differentiate endogenous from exogenous hormone production.
Poisons of Plant Origin
Authors: van der Merwe Deon
Published: December 2009

Almost all of us are in frequent contact with plants that share the places where we live and work as cultivated house and garden plants, weeds and other vegetation. We also routinely ingest plants as food, food contaminants or herbal medicines. Since many plant species produce potentially toxic compounds, it is not surprising that plant poisoning is a frequently encountered, and in some instances, serious health hazard. Wide variation in the toxic dose of plant material, due to differences in toxic‐compound potency and concentrations in plant tissues, makes the outcome of exposures to toxic plants highly variable. Most exposures do not lead to poisoning, but under certain conditions severe disease or death can occur. It is a significant challenge for healthcare workers to differentiate between exposures that require immediate and aggressive treatment from those that are benign. Although a vast number of plant species are potentially toxic, plant poisoning can be classified into groups based on toxic compounds shared between plant species and common toxicity syndromes. Using this approach, some of the most common and important plant poisonings are discussed in terms of the plants that are typically involved, the toxic agents and their mechanisms of action, risk factors, toxicity syndrome descriptions and suggested management strategies.
Botulism
Authors: Lonati Davide , Rossetto Ornella , Fenicia Lucia , Locatelli Carlo
Published: December 2009

Botulism is a paralytic illness caused by botulinum neurotoxins (BoNTs) produced by three clostridium species (Clostridium botulinum, Clostridium butyricumandClostridium baratii). Seven immunological BoNTs, (A–G) have been recognized. Human botulism has been mainly caused by type‐A, B, E and rarely by F neurotoxins. BoNT is a simple dichain polypeptide that consists of a 100 kDa ‘heavy’ chain joined by a single disulfide bond to a 50 kDa ‘light’ chain. The toxin's light chain is a Zn2+‐containing endopeptidase that blocks acetylcholine‐containing vesicles from fusing with the terminal membrane of the peripheral cholinergic terminals, resulting in flaccid muscle paralysis and alteration of autonomic functions. Three common and naturally occurring botulism types have been identified: foodborne, wound and intestinal botulism (including infant and adult forms). Two other forms are man‐made: inhalation botulism could result from aerosolization of BoNTs from laboratory accidents or deliberate dissemination, whereas iatrogenic botulism is related to incorrect usage of injected BoNTs for cosmetic or therapeutic purposes. The clinical syndrome is characterized by symmetrical cranial nerve palsies followed by a descending, symmetrical, flaccid paralysis that may progress to respiratory compromise and death. The diagnosis is essentially clinical and can be confirmed by the detection of BoNTs in human or in food samples; in the infant and intestinal forms, BoNTs‐producing Clostridia can be isolated from stools. Current management is based on supportive treatment (including respiratory support in severe cases) and antitoxin administration that, if early practised, may prevent or limit the extent of the paralysis, but will not reverse it.
Occupation, Toxic Exposures and Health Effects
Authors: Lewinsohn Hilton C.
Published: December 2009

This chapter reviews the subject of occupation, toxic exposures and human health. A brief historic update of occupational illness is mentioned. Further, the chapter reviews processes involving chemicals and their uses, with summaries of some forms of occupational diseases found. Current knowledge of toxicological exposure is dealt with briefly and discusses attempts to develop means of improving the safety of the work environment in which they occur. It is pointed out that the occupational physicians must be aware of toxic effects of materials in the workplace. The prevention of hazards and management of occupational illnesses will rely on collaboration between managers, industrial hygienists and medical officers, all intimately involved. Routes of exposure, target organs affected and control of those hazards are discussed in this chapter. Medical evaluation of health in industry is revised and an outline presented for the establishment of a medical surveillance programme.
Laboratory Recognition of Potential Xenobiotic Respiratory Sensitizers
Authors: Ward Marsha D.W. , Pucheu‐Haston Cherie
Published: December 2009

The immune system functions to establish and maintain homeostasis to protect the body from infectious agents and certain tumours. However, the interaction between the immune system and some xenobiotics can perturb this homeostasis, resulting in adverse health events, including the development of hypersensitivity reactions in genetically predisposed individuals. The dramatic increase in protein‐induced respiratory hypersensitivity in the USA and other industrialized nations over the last few decades is presumably the result of changes in environment, lifestyle and/or medical practices. This chapter provides an overview of selected laboratory methods used in the identification and health‐risk assessment of potential respiratory sensitizers. We describe animal models of hypersensitivity that have been used to elucidate disease pathogenesis and hazard identification. Methods for animal exposure, sample collection and end‐point assessment are also discussed. In addition toin vivomodels, the development ofin vitroscreening techniques and the utility of technologies such as protein and gene expression microarrays, PCR and multiplexing systems in hazard screening are also described. The models and methods discussed in this chapter have been used in our laboratory and others, not only to determine the risks associated with bioaerosol exposure, but also to elucidate disease mechanism and potential intervention targets.
National and International Aspects on Bioterrorism and Biosecurity
Authors: Bossi Philippe
Published: December 2009

Bioterrorism is defined as the intentional use or threatened use of micro‐organisms or toxins derived from living organisms to cause death or diseases in humans, animals or plants on which we depend. More than 150 pathogens have been reported to be potential agents for bioterrorism. The last deliberate release of anthrax in the United States in October 2001 had a worldwide impact. The need for bioterrorism preparedness and planning for response at multiple levels has been recognized in many countries, which set up new administrative and operational structures in order to deal with the new kind of threat. On the wider international level, a concerted global‐health security action to strengthen the public‐health response to the threat of international biological, chemical and radionuclear terrorism has been initiated. Governments and international entities with responsibilities related to maintenance of peace, security, safety and health protection reviewed urgently their political, economic, diplomatic, military and legal means to face up to such attacks and embarked upon major efforts to increase their preparedness.
Cellular Tight Junctions as Mediators of Adverse Effects
Authors: Sambuy Yula
Published: December 2009

Tight junctions are highly complicated and finely regulated structures that provide for the barrier and exchange functions of epithelia and endothelia at the interface between the internal organs and the external environment, and are therefore frequently exposed to noxious stimuli. Recent evidence points to epithelial and endothelial barrier dysfunction, resulting from changes in structure of the tight junctions, as an important early toxic event, preceding more severe damage to the cells. Increased tight junction permeability has also been implicated in the pathogenesis of several multifactorial diseases, frequently involving an exaggerated inflammatory response. Some examples of tight junction alterations occurring after exposure to toxic stimuli, including ethanol, heavy metals and oxidative stress, will be discussed in more detail. In addition, the implications of barrier dysfunction in pathological conditions including hereditary disorders of tight junction proteins, cancers, microbial infections, inflammatory bowel disease, multiple sclerosis and coeliac disease will be presented.
Chemokines as Mediators of Toxicant‐Induced Inflammation and Fibrosis
Authors: Huaux François , Lo Re Sandra , Lison Dominique
Published: December 2009

There is compelling evidence that chemokines are implicated in the development of tissue inflammation and fibrosis induced by xenobiotics. This chapter reviews recent experimental observations which further delineate how chemokines and their receptors participate in the development of these adverse reactions. Studies tracking chemokines and chemokine receptors show their marked expression in murine lung or liver tissue after exposure to very diverse toxicants inducing inflammation and fibrosis, such as certain inorganic particles (silica), antibiotics (bleomycin) and industrial solvents (carbon tetrachloride, CCl4). Chemokines control leukocyte trafficking in response to these toxic agents. This is supported by evidence that antibody or genetic blockade of the CCL2/CCR2, CXCL1–2/CXCR1–2 as well as CCL11/CCR3 chemokine/receptor pairs reduce toxicant‐induced inflammation or fibrosis by limiting the pathological migration of macrophages, neutrophils or eosinophils, respectively. However, the control of chemokine expression is not always associated with the impairment of leukocyte infiltration, and animal models of lung and liver toxicity have highlighted unexpected functions for chemokines including the orchestration of cellular differentiation and angiogenesis as well as fibrocyte tissue accumulation. Although these recent experimental studies do not yet provide a completely clear insight into the exact role of chemokines in the pathogenesis of these diseases in humans, the recognition that chemokines and their receptors are able to determine the persistence of inflammatory cell infiltrates and fibroproliferative repair in response to toxicants has opened a new area of research. Future studies will be directed at the potential implications of novel chemokine‐based therapies for the unsolved inflammatory and fibrotic responses associated with toxic agent exposure.
Ethical Issues in Toxic Chemical Hazard Evaluation, Risk Assessment and Precautionary Communications
Authors: Viau Claude
Published: December 2009

Questions that are central to the examination of ethical issues in the risk‐assessment process are: Who needs to be protected, against what and how? These questions attract attention to the value‐laden judgement of the risk‐assessment process itself. This is the background upon which potential ethical pitfalls associated with the professional act of risk assessment are examined. Scientific risk assessments should contribute to improving public health rather than to serving pure ideology of interest groups. Toxicological risk assessment is the art of translating basic toxicological and epidemiological information into recommendations for risk‐management decisions. The framing of the risk questions shapes the risk assessment itself and is therefore subjected to the biases and values of those who launch the risk‐management process. Ill‐defined risk questions will result in ill‐assessed risks. Risk questions are, in essence, complex, and attempts to simplify them may severely distort the real questions that need to be addressed. Beyond biomedical aspects, risks to health include social components that are intrinsically part of the risk and should be given appropriate consideration. The controversial precautionary principle can be used as a sound evolutionary approach to risk decision‐making provided it is approached in a consistent, transparent manner.
Food Allergy and Intolerance
Authors: Løvik Martinus
Published: December 2009

Food allergy is caused by immunologically mediated over‐reactivity against food components, and may be IgE mediated or non‐IgE mediated. The most serious form and the one of concern for regulatory authorities, is IgE‐mediated food allergy. Food intolerances often have unknown mechanisms. However, lactose intolerance and fructose intolerance are caused by known enzyme deficiencies, and gluten intolerance is caused by an autoimmune reaction elicited by gluten protein. IgE‐mediated food allergy often occurs together with skin allergy and respiratory allergy. The diagnosis of food allergy rests on three pillars: the case history, the demonstration of a specific IgE against the food in serum or by skin‐prick testing, and food challenge. Testing alone will grossly overestimate the presence of a clinically manifest food allergy. The diagnosis of food allergy is often difficult and resource‐demanding. Food allergy is most common in small children, but may be underestimated in young adults. There are geographical variations with regard to prevalence and which foods represent the most common allergens. Epidemiological data on food allergy are often uncertain. No validated animal models of food allergy exist. Prediction of allergenicity of a new protein depends on the overall weight of evidence derived from several sources, including comparison to known allergens in allergen databases.
Drugs of Addiction in the Domestic, Occupational and Sports Environment
Authors: Adatsi Felix K.
Published: December 2009

A pattern and frequency of the inappropriate use of certain drugs eventually culminates in their classification as drugs of abuse or addiction. The classes of drugs of addiction include stimulants, central nervous system (CNS) depressants and sedatives, opiates, hallucinogens and inhalants. Amphetamines, methamphetamines, MDMA and cocaine are some of the drugs well recognized for their stimulating effects. Alcohol continues to be the main drug of abuse among CNS depressant drugs, and several licit drugs among the benzodiazepines, barbiturates and sedative hypnotics, obtained by overprescription are also found among the CNS drugs of abuse. Among the opiates, traditional drugs, such as morphine and heroin, are still popular among drug users. However, the ease of acquisition due to trafficking and overprescription of hydrocodone, oxycodone, methadone and propoxyphene has given popularity to these drugs among the opiates. Of all drugs considered, marijuana is probably a close second to alcohol in frequency and popularity among drug abusers. Inhalants are popular amongst youths, but are also abused by adults and homosexuals for their potential to enhance sexual enjoyment. The use of these drugs varies from location to location. While use of some of the drugs cuts across both occupational and socioeconomic groups, others are used predominantly within certain occupational groups. The driving force behind any future classification of a drug as a drug of addiction will be determined, not so much by its intended use, but by the drug user. Additionally, the availability of a drug and its regulation, or absence of regulation, will likely contribute to its abuse potential. The longer it takes for the recognition of the abuse potential of a drug, the greater the probability that the drug will acquire a classification as an abused drug. What follows the identification and classification of a drug as being a drug of addiction is a swath of adverse effects due to abuse, and which cut across the social, economic and political profile of society at a staggering cost, measurable eventually in terms of the level and extent of human suffering.
Glutathione and Glutathione‐S‐Transferase in Detoxification Mechanisms
Authors: Li Xianchun
Published: December 2009

Glutathione (GSH) and glutathione‐S‐transferases (GSTs) are two primary lines of defence against both acute and chronic toxicities of electrophiles and reactive oxygen/nitrogen species. GSH confers cellular protection by directly or enzymatically reducing free radicals and reactive species (RS), and conjugating endogenous and exogenous electrophiles. GSTs are a superfamily of Phase 2 detoxification enzymes that detoxify both RS and toxic xenobiotics, primarily by catalysing GSH‐dependent conjugation and redox reactions. Both GSH content and GST enzyme activities are under tight homeostatic control. Under normal conditions, neither GST enzyme activities nor GSH levels operate at their maximum capacity. Upon exposure to mild oxidative and electrophilic stress, they are concomitantly induced to achieve efficient protection. This chapter provides an updated understanding about GSH synthesis, the utilization of GSH for detoxification against RS, drugs and toxic xenobiotics, and its recycling from glutathione disulfide (GSSG) and GSH conjugates. This chapter also reviews the united classification/nomenclature system, structure, catalytic mechanism and functions of GST enzymes. Another focus of this chapter is the well‐characterized antioxidant response element (ARE)/nuclear factor‐erythroid‐2‐related factor 2 (Nrf2)‐Kelch‐like ECH associating protein 1 (Keap1) signalling pathway that regulates the basal and induced expression of GST and GSH homeostasis genes in mammals.
Xenobiotic‐Induced Inflammation: Pathogenesis and Mediators
Authors: Clements Peter J. M.
Published: December 2009

Inflammation is an extremely complex and fascinating adaptive process by which fluid, electrolytes, plasma proteins and leukocytes accumulate in the extravascular spaces, in response to a variety of noxious stimuli. These inducers of inflammation include trauma, infectious agents, neoplastic cells and xenobiotics. Such stimuli are sensed by various cellular mechanisms via complex pathways of intracellular signalling resulting in the release of inflammatory mediators. These mediators comprise a large number of molecules ranging from nitric oxide to small amines, peptides, proteins, lysosomal enzymes and lipid derivatives, which act on target effector cells such as leukocytes, endothelial cells and fibroblasts to change their phenotype and orchestrate the inflammatory process. The function of inflammation is to dilute, contain and remove the inducing stimuli in preparation for healing and regeneration. However, inflammation can persist, resulting in tissue damage and possibly functional compromise. Xenobiotics can induce inflammation by a variety of different mechanisms, many of which result in cell injury, degeneration and/or necrosis, either directly or indirectly, by parent or metabolite. This cytotoxicity may be related to pharmacology or to the generation of toxic intermediates in the affected cells. Xenobiotics may also activate inflammatory/immune cells to release inflammatory mediators in nonspecific ways, or by stimulating a specific immune response. The pattern of morphologic and functional changes induced by these mechanisms differs according to the target cell population affected and persistence of inducing stimuli. The pathogenesis of inflammation at the tissue, cellular and molecular levels is reviewed: these mechanisms also apply to inflammation induced by xenobiotics. It is important to note that superantigen‐mediated cytokine release, or immune‐mediated mechanisms of inflammation may be poorly predicted by preclinical toxicity studies. A detailed knowledge of the pathogenesis and molecular mechanisms involved in inflammation can facilitate the design ofin vitroorin vivostudies to predict or investigate these responses when associated with xenobiotic administration.
Space Toxicology: Toxicological Risk Management of Human Health during Space Exploration
Authors: Khan‐Mayberry Noreen N. , James John T.
Published: December 2009

Since the beginning of manned spaceflight, NASA has considered the overall health of astronaut crew members as vital for individual performance and wellbeing, as well as overall mission success. This was the impetus for the birth of space toxicology. Humans interacting with chemical constituents in enclosed or closed‐loop environments are intrinsic to spaceflight; therefore these chemical exposures must be controlled and maintained at a level that is not detrimental to crew health. Despite engineering efforts, hundreds of chemicals will potentially be encountered in the closed‐loop environment during spaceflight. Some chemicals that must be considered are those produced biologically by the crew members, as well as those originating from vehicular components, payload experiments and use of utility compounds. This chapter will ‘voyage’ to various facets of the discipline of space toxicology and its history, the unique astronaut population and spaceflight‐induced physiological changes, air revitalization and water recovery, risk assessment and management, sources of chemical toxins and NASA's vision for future exploration.
Long‐term Adverse Health Consequences from Exposure to Products Generated from Major Disaster Sites
Authors: Mauer Matthew P.
Published: December 2009

Major disasters have been a constant reality since ancient times, repeatedly causing disruption, illness and death. This review presents epidemiological evidence regarding long‐term health effects from a selection of major disasters, which represent some of the more thoroughly studied events in history. The World Trade Center disaster, Bhopal and Seveso chemical releases, Chernobyl nuclear accident and Mount St. Helens and Soufriere Hills volcanic eruptions are discussed in some detail. While this review provides an overview of potential long‐term health outcomes from several types of disasters, it also illustrates the gaps in knowledge that exist for some of these events. There exists a relative lack of research on long‐term health effects for many types of disasters. By illuminating these issues, this review may help to emphasize the importance of focussing efforts and available resources on the study of long‐term health effects related to future disasters.
Empirical Methods and Default Approaches in Consideration of Exposure Duration in Dose–Response Relationships
Authors: Woodall George M. , Gift Jeffrey S. , Foureman Gary L.
Published: December 2009

This contribution is concerned with exploring the relationship of the duration or time and concentration components of exposure. Under many exposure scenarios, especially those characterized as acute (i.e. brief duration to high concentrations), both components are critical in eliciting the toxic response. Historical guidance on the inter‐relationship of these components has been based in large part on mathematical models and theory (e.g. the ‘Haber’C × t  =  krelationship and toxic load or TL phenomenon) and limited to lethality as the toxic response. This report features a suite of methods and approaches accommodating empirical data that characterize both lethal and nonlethal responses. Case studies are used to demonstrate the flexibility of these methods with regard to the type and amount of available data, as well as providing examples and insight into other aspects, including how variability arises, its consequences and how it may be addressed.
Toxicological Considerations in Relation to the Regulatory Safety Evaluation of Medical Devices
Authors: Kammula Raju
Published: December 2009

Medical devices and their component materials are potential sources of toxins that may produce undesirable local and/or systemic toxic responses when used clinically. The evaluation of toxic responses of medical devices using various toxicological test methods is also called biocompatibility evaluation of medical devices. The evaluation of toxicity (biocompatibility) of medical devices has been a complex task, because the devices are made of a diverse range of materials and have various intended uses, with body contact ranging from transient skin contact to permanent implantation. The safety and effectiveness of medical devices marketed in the United States (USA) is regulated by the Center for Devices and Radiological Health (CDRH) of the US Food and Drug Administration (FDA). The medical devices marketed in the European Union (EU) are required to comply with EU Medical Devices Directive 93/42/EEC, which specifies requirements for safety assessment. There are several national and international standards that address the toxicological evaluation of medical devices. In recent years the FDA—in particular the CDRH—uses and accepts toxicological data generated using the national and international biocompatibility standards to evaluate the safety of medical devices. The EU and Japan (MHLW) also use and accept toxicological data generated using international standards. This chapter is an introduction to a relatively new and rather complicated field in toxicology—the toxicological testing of medical devices. It discusses the toxicological considerations for establishing the safety of medical devices to meet the requirements of regulatory agencies. The guidelines for testing of medical devices are discussed and a general description of the various test procedures given. Developments in the field of biocompatibility regarding international harmonization are also addressed.
Photoallergy
Authors: Dubakienė Rūta
Published: December 2009

Photosensitive skin reactions occur when human skin abnormally reacts to ultraviolet radiation or visible light. The forms of photosensitivity are phototoxity and photoallergy. Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent in the human population. Several hundred substances, chemicals or drugs may invoke phototoxic or photoallergic reactions. In order to avoid photosensitive reactions it is essential to determine the photosensitizing properties of such substances before drugs are introduced in therapy or products made available on the market. This chapter reviews the mechanisms of photosensitization, explains the most important differences between phototoxic and photoallergic reactions, summarizes the most common photosensitzers and presents the clinical features and diagnostic procedures of phototoxic and photoallergic reactions.
Effects of nutritional supplements on aggression, rule‐breaking, and psychopathology among young adult prisoners
Authors: Zaalberg Ap , Nijman Henk , Bulten Erik , Stroosma Luwe , van der Staak Cees
Published: December 2009

Objective: In an earlier study, improvement of dietary status with food supplements led to a reduction in antisocial behavior among prisoners. Based on these earlier findings, a study of the effects of food supplements on aggression, rule‐breaking, and psychopathology was conducted among young Dutch prisoners. Methods: Two hundred and twenty‐one young adult prisoners (mean age=21.0, range 18–25 years) received nutritional supplements containing vitamins, minerals, and essential fatty acids or placebos, over a period of 1–3 months. Results: As in the earlier (British) study, reported incidents were significantly reduced (P=.017, one‐tailed) in the active condition (n=115), as compared with placebo (n=106). Other assessments, however, revealed no significant reductions in aggressiveness or psychiatric symptoms. Conclusion: As the incidents reported concerned aggressive and rule‐breaking behavior as observed by the prison staff, the results are considered to be promising. However, as no significant improvements were found in a number of other (self‐reported) outcome measures, the results should be interpreted with caution. Aggr. Behav. 36:117–126, 2010. © 2009 Wiley‐Liss, Inc.
Brookite Formation in TiO2Ag Nanocomposites and Visible‐Light‐Induced Templated Growth of Ag Nanostructures in TiO2
Authors: Es‐Souni Mohammed , Es‐Souni Martha , Habouti Salah , Pfeiffer Nicole , Lahmar Abdelilah , Dietze Matthias , Solterbeck Claus‐Henning
Published: December 2009

TiO2Ag‐nanocomposites exhibit various desirable properties that make them suitable for a variety of applications, for example in photocatalysis and as bactericidal coatings. In this work, a new method for processing TiO2Ag nanocomposites is presented. The nanocomposite films are fabricated from one precursor solution with high silver loading of up to 50%. The resulting films exhibit a microstructure consisting of TiO2AgxO nanocomposites with a largely XRD‐amorphous TiO2 matrix containing brookite nanocrystals. This specific microstructure absorbs in the visible range so that photoreduction of Ag ions can be accomplished by using visible light. The thin films can be patterned using simple shadow masks. The illuminated areas show a high density of self‐organized nanoparticles (SNPs) and nanorods (SNRs), which are templated by the TiO2 porous network. The particle size can be tuned by varying the irradiation time. Most of the SNPs and SNRs form faceted crystals, which are mostly a combination of {111} and {110}. The application of these films as substrates for surface‐enhanced Raman scattering is shown. Enhancement factors as high as 4.6 × 106 could be obtained using rhodamine 6G dye molecules. More applications should involve photocatalytic water purification using visible light.
Measuring enthalpy of fast exothermal reaction with micro‐reactor‐based capillary calorimeter
Authors: Wang K. , Lu Y. C. , Shao H. W. , Luo G. S.
Published: December 2009

This work presents a new micro‐reactor‐based capillary calorimeter for the enthalpy measurement of fast exothermal reactions. The new calorimeter was operated in the continuous way and the reaction enthalpy can be easily measured with the online temperatures from detached sensor chips. A standard reaction system and an industrial reaction system were selected to test this new calorimeter with homogeneous and heterogeneous reaction processes. The measurement was taken place at nearly adiabatic situations and the reaction enthalpy was calculated from the rising of temperature. High accuracy and good repeatability were obtained from this new calorimeter with relative experimental errors less than 3.5% and 2.4%, respectively. The temperature response was quick in this new calorimeter too, which was benefit to the low cost of reactive component. The fast and accurate measurement was contributed to the nice mixing performance and strict plug flowing in the calorimeter. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Experimental study of the hydraulic operation of an annular centrifugal contactor with various mixing vane geometries
Authors: Wardle Kent E. , Allen Todd R. , Anderson Mark H. , Swaney Ross E.
Published: December 2009

The annular centrifugal contactor is a combination mixer/centrifuge that has been developed for solvent extraction processes for recycling used nuclear reactor fuel. The experimental observations presented were part of a simulation‐focused research effort aimed at providing a more complete understanding of the fluid flow within these contactors to enable further advancements in design and operation of future units and greater confidence for use of such contactors in a variety of other solvent extraction applications. Laser doppler velocimetry (LDV), particle image velocimetry (PIV), pressure measurements, and high‐speed video imaging for a range of flow rates and rotor speeds were performed to characterize the flow of water in the annular mixing region of the contactor using three different mixing vane geometries. It was found that the geometry of the mixing vanes has a significant impact on the annular liquid height and general flow in the contactor mixing zone. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Population balance model for nucleation, growth, aggregation, and breakage of hydrate particles in turbulent flow
Authors: Balakin Boris V. , Hoffmann Alex C. , Kosinski Pawel
Published: December 2009

This article describes a computational model for the size evolution of hydrate particles in a pipeline‐pump system with turbulent flow. The model is based on the population balance principle, and the simulation results were validated with data from an experimental study of a flow loop containing hydrate particles reported in the literature. It is found that the particle size is significantly influenced by aggregation and breakage, related to shear in the flow, and that these effects are comparable to those of growth and nucleation, related to diffusional processes. Two different approaches for hydrate growth and nucleation, one of continuous nucleation during the process and one of only an initial nucleation‐pulse, were used. This was done to compare the aggregation and breakage parameters which come out when fitting the models output to experiment. These two approaches are found to give rise to similar aggregation/breakage parameters, lending credence to the pbm‐based modeling. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Socially biased learning among adult cottontop tamarins (Saguinus oedipus)
Authors: Dillis Christopher , Humle Tatyana , Snowdon Charles T.
Published: December 2009

We presented adult cottontop tamarins (Saguinus oedipus) with a novel foraging task that had been used previously to examine socially biased learning of juvenile observers [Humle & Snowdon, Animal Behaviour 75:267–277, 2008]. The task could be solved in one of two ways, and thus allowed for an analysis of behavioral matching between an observer and a skilled demonstrator (trained to use one of the two methods exclusively). Because the demonstrator was an adult in both this study and the juvenile study, the influence of the observer's age could be isolated and examined, as well as the behavior of demonstrators toward observers of different ages. Our main goals were to (1) compare adults and juveniles acquiring the same task to identify how the age of the observer affects socially biased learning and (2) examine the relationship between socially biased learning and behavioral matching in adults. Although adults spent less time observing the trained demonstrators than did juveniles, the adults were more proficient at solving the task. Furthermore, even though observers did not overtly match the behavior of the demonstrator, observation remained an important factor in the success of these individuals. The findings suggested that adult observers could extract information needed to solve a novel foraging task without explicitly matching the behavior of the demonstrator. Adult observers begged much less than juveniles and demonstrators did not respond to begging from adult. Skill acquisition and the process of socially biased learning are, therefore, age‐dependent and are influenced by the behavioral interactions between observer and demonstrator. To what extent this holds true for other primates or animal species still needs to be more fully investigated and considered when designing experiments and interpreting results. Am. J. Primatol. 72:287–295, 2010. © 2009 Wiley‐Liss, Inc.