bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicology of Pesticides
Authors: Dewhurst Ian C. , Marrs Timothy C. 
Published: December 2009

AbstractPesticides 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

AbstractThere 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

AbstractThis 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

AbstractThe 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

AbstractAlmost 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

AbstractBotulism 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

AbstractThis 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

AbstractThe 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

AbstractBioterrorism 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

AbstractTight 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

AbstractThere 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

Abstract
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

AbstractFood 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

AbstractA 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

AbstractGlutathione (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.