bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Temperature on Toxicity
Authors: Gordon Christopher J. , Rowsey Pamela J. 
Published: December 2009

AbstractOur understanding of the effects of temperature on toxic response has seen resurgence in the past several decades, with the development of better methods to study the integration of autonomic and behavioural thermoregulatory responses in rodents and other species. Radiotelemetry provides researchers with the best tool to study the thermoregulatory responses in undisturbed rodents exposed chronically or acutely to toxic chemicals. The thermoregulatory response to acute exposure to many toxic chemicals involves a regulated hypothermic response, characterized by an increase in autonomic thermoeffectors to increase heat loss and a behavioural preference for cooler temperatures. This thermoeffector response is quickly manifested by a marked drop in the core temperature in rodents. However, in humans and other large mammals, the hypothermic response is meagre due to their large thermal inertia. A combination of exposure to cool temperatures and a moderate hypothermic response has been found to benefit survival with a variety of toxic agents. Thus, the integrated thermoregulatory response of rodents to lower their core temperature seems to be an adaptive response. On the other hand, fever or hyperthermia is often seen in humans and other large mammals exposed to various toxicants. A fever is also seen in rodents provided that core temperature is monitored without disturbing the animal (e.g. telemetry). The universal effects of temperature on chemical toxicity calls for researchers to have a better understanding of the thermoregulatory effects of environmental toxicants.
Development of Tolerance to the Toxicity of Xenobiotics
Authors: Fonnum Frode 
Published: December 2009

AbstractThe development of tolerance to xenobiotics usually involves the inactivation of receptors or the induction of enzymes that bind or inactivate the xenobiotics. This review showns, as the main example, anticholinesterase, the effect of which is modified in several different ways. Tolerance depends on the internalization or inactivation of the muscarinic receptor or the nicotinic receptor. Also mentioned is the interaction of the adenosine receptor with the cholinergic system. Further, the importance of carboxylesterases, butyrylcholinesterase and phosphoric hydrolases in tolerance is discussed. An interesting topic included is the survival of acetylcholinesterase knock‐out animals. Finally the mechanism of tolerance to morphine in the locus coerulus is discussed as an example.
Pathological Techniques in Toxicology
Authors: Greaves Peter 
Published: December 2009

AbstractHistopathological evaluation remains an important part of the assessment of the adverse effects of xenobiotics on the whole organism. In addition to conventional special staining techniques and electron microscopy, new techniques involving immunocytochemistry, molecular biology and novel visualization procedures have provided additional objective techniques that have enabled better functional and morphological characterization of induced alterations in organs of the body. This chapter covers both conventional and new methods involved in the microscopical assessment of tissue changes induced by xenobiotics.
Clinical Chemistry in Toxicity Testing: Scope and Methods
Authors: Gosselin Sylvie , Ramaiah Lila , Earl Lesley 
Published: December 2009

AbstractNoncellular blood compartment (plasma or serum) and urine biochemical components are important indicators of overall animal health and can be used in conjunction with other parameters to investigate the toxicity of drugs and chemicals. This chapter describes the measurement and interpretation of clinical chemistry tests employed in toxicology studies in commonly used laboratory species. The introductory sections delineate methods for sample collection and data generation, and provide a general approach for data interpretation and reporting, with emphasis on distinguishing pre‐analytical/analytical variations from test material‐related changes. The following sections are organized by organ system, describing core clinical chemistry tests used in routine toxicology studies. These include protein, lipid and carbohydrate metabolisms, liver and kidney functions and electrolyte balance. Nonroutine tests evaluating cardiac and skeletal muscle, bone, blood vessels, the endocrine system, the nervous system are also presented. Because few clinical chemistry parameters are specific indicators of single organ toxicity, each section emphasizes the integrated interpretation of biochemistry changes with other study endpoints such as clinical signs, food consumption and bodyweight, haematology, electrocardiography, blood pressure and histopathology. Patterns of change are presented in the context of identifying organ toxicity.
Imaging Techniques in Neurotoxicology Research and Development
Authors: Hantson Philippe , Duprez Thierry 
Published: December 2009

AbstractThe impact of neuroimaging techniques in the work up of intoxicated patients is nowadays increasing regarding both macroscopic anatomical damage (CT and MR) and ultrastructural damage (DWI), but also regarding metabolic (MR spectroscopy) and functional impairment (fMRI). Perfusional status of diseased areas may also be investigated by magnetic resonance imaging (MRI) using exogenous or even endogenous tracers, and the density of membrane receptors can be investigated using isotopic techniques (positron emission tomography (PET), single photon emission computed tomography (SPECT)). There is growing evidence for elective sensitivity of defined brain areas like basal ganglia towards toxic exposure and for relative specificity of topographical brain damage for some substances, but with significant overlapping between toxins. Uncertain relationships between severity of brain abnormalities on CT or MR images at an acute phase and functional clinical outcome renders mandatory the investigation of better early prognostic parameters which could mainly involve DWI and1H‐MRS data in clinical routine, and fMRI data, perfusion parameters, and receptors density in the investigational field.
Nanotoxicology—The Toxicology of Nanomaterials
Authors: Gellein Kristin , Syversen Tore 
Published: December 2009

AbstractNanotoxicology is a new and fast‐growing discipline that deals with the interaction between engineered nanostructures and biological systems. Because of their size, these materials have unusual physicochemical properties that make them different from bulk materials of the same chemical composition. However, the same properties that make these materials very attractive in a range of technological applications, also raise concern about adverse effects in biological systems. Today, a limited amount of data is available on possible effects on man and the environment. Nanomaterials (NMs) are currently available in a wide variety of compositions, and traditional approaches of toxicity testing are often not directly applicable. Studies so far, bothin vivoandin vitro,indicate that these materials have the potential to cause adverse effects. As both the production volume and application range of NMs expands rapidly there is an urgent need to develop adequate toxicity testing and evaluation of these products.
Antidotal Studies
Authors: Bateman D. Nicholas , Marrs Timothy C. 
Published: December 2009

AbstractAntidotes for poisons may act in a variety of ways and, in some cases, two (or more) antidotes using different antidotal approaches, are used together. Antidote development depends on an extensive knowledge of the action of the poison, which the antidote is expected to counteract. Poisons and their antidotes may be studiedin vitro,in experimental animals or in humans. The design of experimental studies in animals and experimental and observational ones in humans presents major challenges. In the case of animal studies, the aim is to simulate realistic treatment scenarios.
Ophthalmic Toxicology
Authors: Ballantyne Bryan 
Published: December 2009

AbstractOphthalmic toxicology is a specialist area that deals with potentially adverse effects on the eye from chemicals and their metabolites, reaching the eye by local contact and from the systemic circulation, and also covers the effects that may be produced systemically by chemicals that have been absorbed into the circulation following topical contact with the eye. This chapter reviews, with illustrative examples, all these aspects of ophthalmic toxicology, with particular reference to causation, mechanisms of production of lesions, relevantin vivoandin vitrolaboratory testing procedures, the significance and clinical relevance of the observed effects. Site‐specific lesions and functional disturbances in the eye that are discussed in detail are those to the cornea, iris, ciliary body, aqueous humour production, the lens, retina, optic nerve and extraocular muscles. Systemic effects following topical contamination of the eye are discussed particularly for chemicals and drugs, and discussed in terms of the sites of absorption.
Cutaneous Toxicology
Authors: Hermansky Steven J. 
Published: December 2009

AbstractThe skin is the largest organ of the body. It serves many functions one of which is protection from the outside world, including chemical and microbiological insults. Skin ailments represent one of the most common complaints of patients in medical settings and account for significant loss of productivity in the workplace. Cutaneous toxicity from chemical exposures is responsible for many of these complaints. Skin reactions to chemicals often appear similar, but have many biological causes, including chemical irritation and sensitization (allergies). A primary goal of the cutaneous toxicologist is to predict the potential irritant and/or sensitization potential of chemicals. This chapter summarizes the varied effects that chemicals may have on the skin, including acute and chronic conditions. The chapter also describes the multiple methods to predict potential cutaneous chemical hazards that may be produced in the workplace or via consumer exposure to topical drugs and cosmetics. Important human, animal andin vitromethods to predict a chemical hazard are described.
Hepatotoxicity
Authors: Hinton Richard H. , Grasso Paul , Marrs Timothy C. 
Published: December 2009

AbstractThe liver has many physiological roles and is a key organ in detoxication. Furthermore, the liver is affected by a very large number of xenobiotics. The liver also has an immense capacity for self‐repair, so that the many abnormalities of structure or function in the liver reverse rapidly on cessation of xenobiotic exposure. Nevertheless the liver's defences can be overwhelmed. Acute liver failure can be caused by many compounds e.g. paracetamol (acetaminophen), while repeated liver damage, for example from ethanol, may lead to cirrhosis. While primary liver cancer is rare in Western Europe and North America, it is common in other parts of the world such as sub‐Saharan Africa, alcohol and aflatoxins being amongst the aetiological factors. Non‐dose‐dependent adverse effects on the liver are common with many classes of drug and may be sufficiently severe to require cessation of treatment. In the regulatory context it is important to recognize the difference between adaptive and toxic effects.
Toxicology of the Exocrine Pancreas
Authors: Foster John R. 
Published: December 2009

AbstractThe exocrine pancreas is not a common target organ for toxic drugs and chemicals. It is however the fifth most common human cancer in the western world, and acute and chronic pancreatitis, through various identifiable and unidentified causes, is a common disease in both the developed and developing countries of the world. Both inflammatory disease and cancer of the pancreas is correlated to lifestyle with poor diet and habits, such as moderate to high alcohol intake and smoking, having positive correlations to developing the disease. The chapter describes the functional anatomy of the organ together with its biochemistry that determines toxicity, in particular the role of oxidant damage in the development of cell and tissue damage is thought to be important. The consequences of toxic damage to the acinar cells are severe and primarily result from the auto‐activation and hence autodigestion of the tissue by the digestive enzymes normally contained within the exocrine cells, a cascade of apoptosis/necrosis and fibrosis with the ultimate collapse of the organ, subsequent shock, multi‐organ collapse and death. The organ has complex molecular mechanisms to prevent premature activation of the digestive enzymes and also has defence mechanisms present to neutralise any premature enzyme activation but these can be rendered ineffectual by factors such as alcohol abuse and a poor diet.Chemical exposure, through both occupational and consumer product usage, has been associated with the development of both pancreatic neoplastic and non‐neoplastic disease but the relationship between exposure and disease has never developed further than a simple association and it is likely that the development of pancreatic disease is a multi‐faceted combination of inter‐related events, none of which in isolation can induce disease. The pancreas has its own array of phase 1 and 2 metabolic enzyme systems and the role of pancreatic drug and chemical activation and detoxification in inducing toxicity is discussed together with the possible secondary effects of hepatic drug/chemical activation and detoxification.Finally the role of animal models of pancreatic disease is discussed in terms of their contribution to understanding the aetiology of the human conditions and the possible use of therapeutic intervention in treating the disease.
Cartilage and Bone as Target Tissues for Toxic Materials
Authors: Lansdown Alan B.G. 
Published: December 2009

AbstractBone and cartilage are important in providing functional rigidity to the body, but have central function in modulating mineral metabolism in the body. Both tissues are subject to toxic and genetically determined influences on mucopolysaccharide (ground substance) synthesis, hormonal changes and defects in mineral homeostasis. In prenatal development, skeletal development is sensitive to abnormalities in the intrauterine environment and in the availability ofS‐amino acids, trace metals and vitamin balances. Animal models have provided beneficial information on mechanisms of teratogenesis involving cartilage and bone, notably on the action of salicylates and hypervitaminosis, both of which involve impairment in mucopolysaccharide synthesis, ossification and osteoclast activity. Toxic changes in adult skeletal tissues are largely associated with functional impairment of bone as a source of minerals—calcium, phosphate, zinc, and so on, and the property of calcium hydroxyapatite to bind xenobiotic cations including lead and cadmium with no trace metal nutrient value. Toxic changes range from osteoporosis, and impairment in bone strength and functional capacity. Radioactive bone‐seeking metals including90Sr are a potential cause of bone tumours. Much remains to be understood concerning the interaction between the calcium‐binding capacity of hydroxyapatite and the putative nutritional importance of silicon and strontium. Further studies are needed to investigate the cytotoxic action of lead and cadmium in bone and cartilage and to understand the implication of chronic exposure to low levels of these and toxic metals on bone structure and function.
Toxicology of the Endocrine System
Authors: Kapp Robert W. , Thomas John A. 
Published: December 2009

AbstractThe endocrine system plays a critical role in regulating virtually every aspect of the body's functions and systems, including behaviour, nutritional processes, reproduction, growth and development, gastrointestinal tract, cardiovascular system and homeostasis. It includes various endocrine glands, for example, hypothalamus, pituitary, adrenals, gonads, thyroid and pancreas, that secrete specific hormones (or messengers) as well as specific receptors in target organs throughout the body, which are activated or deactivated by a series of biochemical reactions upon contact with the proper hormone, which ultimately modifies the target organ's activity. This is a complex and interactive system and malfunctions may have serious consequences. Disorders can arise internally from overactive or underactive hormone production, or they can arise from external exposures. Both can have life‐threatening effects on survival. It has been shown that many drugs and chemicals and some environmental chemicals can perturb the chemical balance of the endocrine system. Some chemicals may directly affect the normal function of the endocrine system by inhibiting specific enzymes, while others produce indirect effects that result in a pharmacological interaction between the hormone and the chemical which modulates the effect of the hormone. There are many variations on these mechanisms and effects and these are detailed in this chapter.
Cytogenetics
Authors: Anderson Diana , Baumgartner Adolf , Cemeli Eduardo 
Published: December 2009

AbstractVarious types of cytogenetic change can be detected in chromosomes, including structural chromosome aberrations, aneuploidy or sister chromatid exchanges. Chromosome aberration assays are used to detect chromosome damage (clastogenesis) in somatic and germinal cells by direct observation during metaphase analysis, or by indirect observation of micronuclei. Aberrations are mostly lethal to the cell during the cell cycle following their induction; they also indicate a potential to induce more subtle and transmissible chromosomal damage which survives cell division, producing heritable cytogenetic changes. Cytogenetic damage is usually accompanied by gene mutation. Structural and numerical abnormalities in somatic cells are involved in the aetiology of neoplasia, while in germ cells they can lead to perinatal mortality, dominant lethality or congenital malformations in the offspring. Over 80% of all structural aberrations in humans occurde novoand are of paternal origin. This chapter addresses the different cytogenetic changes and assays which measure gross chromosomal damage in human somatic and germ cellsin vitroandin vivo, as well as regulatory requirements for measuring them. Also to be considered are the growing importance of modern molecular cytogenetics, the Human Genome project and the awakening awareness of epigenetics as a biological concern.
Nongenotoxic or Epigenetic Carcinogenesis
Authors: Powell Christopher J. , Berry Sir Colin 
Published: December 2009

AbstractCarcinogens are considered nongenotoxic where they cannot be shown to interact directly with DNA in a number of short‐term screening assays, but which are capable of producing tumours in laboratory rodents in bioassays. Epigenetic events, either acting alone or in concert with genetically determined events, may produce tumours. A key feature is that dose‐threshold effects may be identifiable. In both the rat and the mouse, the liver is the most common site of nongenotoxic carcinogenesis. A special sort of hepatic carcinogenesis is that produced in rodents by peroxisome proliferators; this is of questionable significance for humans. Other important sites of non‐genotoxic carcinogenesis include endocrine glands notably the thyroid, bladder and, in the rat, the forestomach. Carcinoid tumours are tumours of the diffuse neuroendocrine cell populations, found particularly in the gastrointestinal tract. Their incidence is increased with certain drugs, notably the histamine H2 antagonists. Haemangiosarcoma, which may occur at a variety of sites, clearly arises by a number of mechanisms, some of which may be genotoxic. Mesothelioma, most often of the pleura, as a human response to asbestos, may be considered a form of non‐genotoxic carcinogenesis.
Epigenetic Mechanisms and their Toxicological Significance
Authors: Watson Rebecca E. 
Published: December 2009

AbstractEpigenetic mechanisms are processes that exert control over gene expression without altering the DNA sequence. These mechanisms essentially work as genetic switches, turning gene expression levels on and off in response to various stimuli. Currently, DNA methylation and histone modifications (particularly histone acetylation and methylation) are the best characterized and most commonly recognized epigenetic mechanisms, although in recent years attention has turned to additional epigenetic processes such as microRNAs. Together, these mechanisms form the epigenome, a dynamic, reversible construct necessary for differentiation, tissue‐specific functions, development and neurological function in eutherian mammals. However, aberrant epigenetic function may lead to untoward effects and can be a contributing factor to a variety of diseases including cancer and developmental/neurological disorders. This chapter summarizes major epigenetic mechanisms and their relevance to toxicologists, including their role in normal biological functions vs. disease‐associated processes, as well as how nutrition and xenobiotic stimuli influence the epigenome. An enhanced understanding of factors that affect the epigenome can assist in both predicting undesirable toxic outcomes and in designing therapeutic strategies.
Developmental Toxicology
Authors: DeSesso John M. , Willhite Calvin C. 
Published: December 2009

AbstractThe full range of development that is subject to injury—be it a consequence of maternal disease, nutritional excess or deficiency, xenobiotic or radiation exposure or as a result of infectious agents ‐ begins with the primordial germ cells of the individual's parents, proceeds through gametogenesis and concludes at the end of a person's natural life. The present chapter is focused upon understanding adverse reproductive outcome as a result of embryonic exposure to selected environmental chemicals and therapeutic drugs. The chapter begins with examples from ancient history and contemporary motion pictures, from the scientific literature and from the popular press. The text explains some of the fundamental steps taken and the genes involved in establishment of the vertebrate body plan. Examples are provided to illustrate how failure of proper gene expression and coordination at precise embryonic stages is responsible for the pathogenesis of specific congenital malformations. Consolidated presentations of experimental teratology and developmental toxicity studies are provided, along with the steps required to interpret the results of those studies in the context of human health risk assessment. The chapter contrasts the risks associated with misdirected speculation, irrational public fear and chemical rumors compared to the real public health consequences associated with maternal disease (e.g., alcoholism, diabetes, obesity) and nutritional deficiency (e.g., vitamin A, folates). The chapter concludes with the fundamental role of inappropriate embryonic gene expression in carcinogenesis. Increased understanding of genomic regulatory circuits in embryos has contributed to increased understanding of normal cell regeneration and turnover and how disturbances in those circuits lead to neoplasia and other degenerative diseases in children and adults.