bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunotoxicology
Authors: Luebke Robert W. , Beamer Celine A. , Bowman Christal , DeWitt Jamie , Gowdy Kymberly , Johnson Victor J. , Shepherd David M. , Germolec Dori M. 
Published: December 2009

AbstractThe immune system is a complex set of cellular and soluble mediators that protects the body against infectious agents and neoplasias. Innate immune responses do not require antigen recognition or clonal expansion and thus provide a rapid defence response against pathogenic organisms. The adaptive immune response is more complex, requiring recognition of foreign antigens via cell‐surface receptors, production of growth factors, proliferation of antigen‐specific lymphocytes and activation of effector mechanisms that are ultimately directed against infectious agents or cancerous cells. While immune responses are usually beneficial, hypersensitivity reactions and autoimmune diseases are examples of inappropriate responses that may occur in genetically susceptible individuals following exposure to an environmental trigger. Immunotoxicology is the subdiscipline of toxicology that focusses on the unintended effects of chemical exposure on the immune system. There is extensive evidence to suggest that following exposure to particular chemicals unintended immunosuppression, unintended immunostimulation, hypersensitivity or autoimmunity may occur. Chemical‐induced modulation of the immune system may result in adverse outcomes such as increased incidences of infectious or neoplastic diseases, allergy/asthma or autoimmune diseases. This chapter presents an overview of immune responses and how these responses may be affected by xenobiotics.
Genetic Toxicology Testing and its Relevance to Human Risk and Safety Evaluation
Authors: Lorge Elisabeth 
Published: December 2009

AbstractGenotoxicity is a major concern in toxicity evaluation as it may cause carcinogenicity and/or genetic diseases. Therefore genotoxicity has become a part of the toxicity regulatory assessment. Over 30 years of practice in genotoxicity, various tests and tools have been developed, validated and refined. The protocols of the most currently used tests were improved and the experimental conditions were monitored more satisfactorily. In this chapter, the main genotoxicity tests required by the current International Conference on Harmonisation (ICH) battery are reviewed, as well as the most commonly used experimental systems added to the battery for follow‐up testing, with their advantages and limits. The evaluation of genotoxicity results is also extensively considered. In this exercise, it is shown how the knowledge accumulated in the last years can be used to improve results evaluation with special references to the assessment and level of cytotoxicity, metabolic activation, aneuploidy, non‐DNA reacting mutagens, thresholds and risk assessment.
Carcinogenesis and Carcinogens that are also Genotoxic
Authors: McGregor Douglas 
Published: December 2009

AbstractThe definition of a carcinogen in an experimental context is an agent which increases the incidence of any neoplasm irrespective of whether it is lethal, potentially lethal or benign. As genetic factors are fundamental in carcinogenesis these are briefly reviewed. A description of some of the problems associated with carcinogenicity experiments and the interpretation of their results is presented. Particular emphasis is given to so‐called genotoxic carcinogens. ‘So‐called’ because there are unresolved difficulties in defining the weight and strength of evidence required for concluding that genotoxicity is indeed the mode of carcinogenic action (MOA), rather than simply concluding that the MOA is unknown. A genotoxic MOA that is based on reactivity with DNA may lead currently to the unverifiable and therefore counter‐scientific default assumption that there is no dose without an effect on cancer incidence. Carcinogenicity test design, including the use of the maximum tolerated dose, is briefly discussed. This is followed by consideration of issues and challenges presented in the interpretation of results by the basic pathology, the grouping of tumours for statistical analysis, the use and abuse of historical control data, interpretation of high‐dose effects, the use of transgenic animals and the identification of noncarcinogens. Finally, division of the roles of risk assessors and risk managers is outlined.
Structure–Activity Relationships for Carcinogenic Potential
Authors: Venkatapathy Raghuraman , Wang Nina Ching Y. , Martin Todd M. , Harten Paul F. , Young Douglas 
Published: December 2009

AbstractTwo important disadvantages of long‐term animal bioassays are that testing involves substantial amounts of time and money, and that high doses are usually used in the testing process. These disadvantages can be circumvented using (quantitative) structure‐activity relationships ((Q)SARs). In the field of computational toxicology, (Q)SARs are predictive models that provide a quantitative measure of the relationship between the chemical structure and a measure of a given health‐related end point. Such relationships can be expressed in terms of continuous dose‐response data (e.g. carcinogenic potency) based on some type of regression analysis for quantitative end points, or a dichotomous classification (e.g. yes/no‐type answers for carcinogenicity, etc.) based on discriminant analysis or other pattern recognition techniques for qualitative end points. There are a limited number of (Q)SAR models to predict the carcinogenicity of various chemicals, a majority of which relate the carcinogenic potency to measures of carcinogenicity such as mutagenicity, lethal dose (LD50) or the maximum tolerated dose (MTD). Other (Q)SAR models relate the carcinogenicity of a chemical to its structure, either in terms of its chemical fragments (groups of one or more atoms that make up the chemical structure) or in terms of its physical and chemical properties. In addition, a variety of commercial and noncommercial software that contain modules to predict the carcinogenicity of chemicals are also available.
Short‐term Tests for the Determination of Genotoxic and Carcinogenic Potential of Xenobiotics
Authors: Dhawan Alok 
Published: December 2009

AbstractThe advent of industrial revolution has seen a significant increase in the number of chemicals being released into the environment and it becomes imperative to check their toxic potential. Exposure to such compounds produces chemical changes in DNA, which are generally repaired by the DNA‐repair enzymes. Hence, adequate tests have to be conducted for risk assessment and hazard prediction of these chemicals. Earlier, only long‐term animal bioassays, involving lifetime studies on animals, were used to classify substances as mutagens/carcinogens. These tests were cumbersome, time‐consuming, resource‐intensive and expensive. Therefore, rapid, sensitive and less resource intensive short‐term tests were developed for testing of new chemical entities. A ‘battery’ of three to four of these short‐term tests has now been proposed by a number of regulatory agencies for classification of the compounds as mutagenic or carcinogenic. Although several short‐term tests are available, molecular biology andin silicomethods are now being developed to predict the genotoxicity and carcinogenicity of chemicals at an early stage for interventional strategies to be implemented in time.
Reproductive Toxicology
Authors: Makori Norbert , Oneda Satoru , McElhatton Patricia R. , Ratcliffe Jennifer M. , Sullivan Frank 
Published: December 2009

AbstractThis article introduces some of the newer approaches for biopharmaceuticals reproductive toxicity testing, and includes the classical small molecules testing paradigms. The scientific basis for concern about exposure to agents that cause reproductive toxicity is discussed in various contexts, including aspects of adult male or female sexual function and fertility, embryology and teratology, and the F1 offspring and lactation in the context of interfere with the production or development of normal offspring which could be reared to sexual maturity, capable in turn of reproducing the species. Reproductive toxicology is divided into two major classes: (i) adverse effects on reproductive ability or capacity in adult males and females, i.e. effects on sexual behavior and fertility and (ii) adverse effects on maintenance of pregnancy (embryo‐fetal loss) and developmental outcome of the offspring, i.e. developmental toxicity. The former is assessed in both males and females as exposure of a toxicant applies to both, while the latter is assessed in only female and their concepti/offsprings as exposure only occurs during pregnancy where the male is used only for mating purposes and is not exposed to the reproductive toxicant.
Drug Toxicity in Neonates, Infants and Young Children
Authors: Choonara Imti 
Published: December 2009

AbstractNeonates, infants and young children may experience the same drug toxicity as adults. They may also experience specific drug toxicity that adults do not experience. This may be associated with toxicity related to growth and development, for example the adverse effect of corticosteroids on growth or development of the brain following exposure in the early period of neonatal life. Alternatively they may develop a specific toxicity in relation to a condition that does not occur in adults, for example Reye's syndrome following exposure to salicylates during the presence of a viral infection. The altered drug metabolism within paediatric patients is an additional risk factor for drug toxicity. This is most marked in the neonatal period and is illustrated by the impaired metabolism of chloramphenicol which results in cardiovascular collapse. Similarly, the altered metabolism of antiepileptic drugs such as sodium valproate in children less than two years of age predisposes this particular age group to hepatotoxicity. Other specific examples of drug toxicity in paediatric patients are given in this chapter and these include examples of percutaneous and excipient toxicity.
Air Pollution
Authors: Maynard Robert L. 
Published: December 2009

AbstractAir pollution science has undergone a renaissance in the last two decades. Common air pollutants are now known to have effects on health at low concentrations such as occur in many developed countries. Epidemiological studies have led to this new appreciation, toxicological studies have tended to lag behind. Particles have attracted much attention and current attention is focused on particles of very small diameter. Both short term variation in concentrations of, and long term exposure to particles have been shown to have effects on range of health end‐points including premature death, hospital admissions and symptoms. That such low concentrations, indeed there is no discernable threshold, should have effects has been difficult to explain toxicologically. Recent work, however, has shown that effects on the cardiovascular system, perhaps due to metallic species included in or on particles may explain the effects. Work on gases has lagged a little behind that on particles but work on the oxidative properties of ozone and nitrogen dioxide and the finding that concentrations of ozone are increasing, in part due to climate change, is now leading to increased interest in these pollutants. Air pollution science is developing rapidly and is receiving further stimulus from new work in the nano‐toxicology area. That further advances will be made in the coming decade is certain.
Indoor Air Quality
Authors: Jørgensen Rikke B. , Hanssen Sten O. , Bakke Jan V. , Jensen Ellen K. 
Published: December 2009

AbstractIndoor air quality depends on a number of factors, including the outdoor air quality, ventilation, the amount of fresh air provided indoors, and the amount of air pollution derived from numerous indoor sources. Indoor environments are usually characterized by exposure to a complex mixture of different agents at very low exposures, mostly far below any known threshold level of biological effect. However, since people spend more than 90% of their time indoors, these low concentrations may have an impact on health and wellbeing. Those with asthma, allergies and other hypersensitivities are particularly vulnerable to inferior indoor environments. Dampness in buildings and combustion processes are probably the major pollution sources. The most important effects on public health are probably allergic respiratory sensitization, aggravation of allergic diseases, increased susceptability to respiratory infection and worsening of chronic obstructive lung diseases. The pollutants in the indoor air are gases and particles. The most typical inorganic gases are CO, NO2, CO2and O3. Important organic gases are volatile organic compounds (VOCs) including formaldehyde, phthalates and flame retardants. Combustion processes (tobacco smoke, heating, cooking, frying, grilling) are the main indoor sources of smaller nonbiological particles. Biological particles originate typically from pet allergens, house dust mites, pollen and micro‐organisms.
Multiple Chemical Sensitivity: Toxicological Questions and Mechanisms
Authors: Pall Martin L. 
Published: December 2009

AbstractCases of multiple chemical sensitivity (MCS) are initiated by exposure to organic solvents and three classes of pesticides. Each of these can act indirectly to increase NMDA activity and the toxic effects of members of each of these classes can be lowered by using NMDA antagonists. Other chemicals, mercury, H2S and CO exposure may also initiate cases of MCS and have toxic responses mediated through increased NMDA activity. Thus each of these types of chemicals appears to act as a toxicant through increased NMDA activity. Six additional types of evidence suggest roles for elevated NMDA activity in MCS, suggesting that this response is involved, not only in MCS case initiation, but also in response to low‐level chemicals in those who are already sensitive. The inference that chemicals act as toxicants in MCS is confirmed by three genetic studies showing that five genes that encode enzymes that metabolize these chemicals act to determine MCS susceptibility.The chronic nature of MCS is thought to be produced by a local biochemical vicious cycle mechanism, the NO/ONOO−cycle, which is initiated by nitric oxide acting through its oxidant product peroxynitrite, which are both produced in MCS in response to excessive NMDA activity. Cycle elements, including NMDA activity, intracellular calcium, nitric oxide and peroxynitrite are thought to interact with other mechanisms, including neural sensitization in the brain and neurogenic inflammation in peripheral tissues to produce the high‐level chemical sensitivity that is the hallmark of MCS. This complex model of MCS is supported by the following types of observations: MCS correlates in the chronic phase of illness, extensive animal model studies implicating almost all NO/ONOO−cycle elements, clinical trial data in the related illnesses chronic fatigue syndrome and fibromyalgia, and a variety of objectively measurable responses to low‐level chemical exposure in MCS patients, responses that should be further studied as possible specific biomarker tests for MCS. While plausible mechanisms are proposed for the generation of both shared and specific symptoms and signs in MCS, there are little data on whether these mechanisms are actually involved in generating these symptoms and signs in MCS. Previous claims that MCS is produced by some sort of psychogenic mechanism have multiple flaws and are inconsistent with the various types of evidence discussed above. Several areas of research are discussed in which the author argues that research will be richly rewarded.
Assessing Impacts of Environmental Contaminants on Wildlife
Authors: Sullivan Joseph P. , Hill Elwood F. 
Published: December 2009

AbstractThe impact of a toxic xenobiotic, natural or anthropogenic, on wildlife is difficult to evaluate because factors that influence exposure and risk vary widely among natural systems. Then, when considering the confounding influences of chemical interactions and the presence of natural toxics and toxins, widely diverse studies are needed to assess impacts of contamination on wildlife. In brief, wildlife toxicology has been described as the integration of three principal strategies: (i) laboratory screening to predict which chemicals may be acutely toxic or cause more subtle effects, such as reproductive impairment, behavioural aberrations or developmental changes; (ii) controlled studies where subjects are confined to a simulated natural environment and (iii) studies of natural populations. This chapter presents an overview of wildlife toxicology and contaminant risk assessment as traditionally evaluated, but also includes discussion of recent concepts of immunotoxicology, endocrine disruption and the presence of pharmaceuticals in nature. The focus is on anthropogenic chemicals and avian wildlife with comparisons to other taxa as appropriate. Birds have served as primary models because they have diverse behaviours and habitat associations and can be effectively studied in captivity and nature.
Soil and Fresh Water
Authors: Flaten Trond Peder , Steinnes Eiliv 
Published: December 2009

AbstractIn nature, soil and water systems are intimately inter‐related through a complex web of interactions. In this chapter, the nature and properties of soils are reviewed with emphasis on chemical composition and the binding, cycling and transformation of chemical substances in soil. The main focus is on metals, but organic compounds are also discussed. Water is discussed mainly as an exposure route from soil to humans. Various aspects of pollution of soil and water systems are discussed, including industry and mining, long‐range atmospheric transport, pesticides and fertilizers and waste disposal sites. The possible health effects of soil and water acidification are treated, with emphasis on cadmium, lead, mercury and aluminium. Finally, some health aspects of drinking water are discussed, with emphasis on instances where toxic substances at least partly have their origin in soils, and where drinking water constitutes an important exposure pathway from soils to humans. This includes arsenic, with a focus on West Bengal, fluoride, water hardness, nitrate and chlorination by‐products.
Biological Criteria for Water Quality in Relation to Human Health
Authors: Howd Robert A. 
Published: December 2009

Abstract
Development of regulatory criteria for contaminants in drinking water has been formalized with widely accepted risk assessment conventions and guidelines in North America and Europe. Acceptable levels for chemicals which are considered noncarcinogenic are estimated using an uncertainty‐factor approach, while for carcinogens a quantitative extrapolation is performed, based on cancer incidence in humans or animals. These methods incorporate a precautionary approach in order to minimize the risk of any adverse effects from exposure to drinking water, considering variability in both exposure and sensitivity to potential toxic effects. The wide variety of toxic agents and end points provide more than ample opportunities for controversies and disagreements, as well as further research. However, the current regulatory system is responsible for delivering consistently high‐quality water, which has resulted in a tremendous improvement in public health.
Interactions between Occupational and Environmental Factors in Toxicology, Hazard Evaluation and Risk Assessment
Authors: Gomes James , Meek B. 
Published: December 2009

AbstractOccupational and environmental exposures to toxicants rarely occur in isolation or singly and the potential for multiple exposures occurring with different degrees of overlap and multiple numbers of toxicants is high. Interactions occur when multiple chemicals are present in biological systems at the same time. The nature and the intensity of the interactions vary greatly from individual to individual and are dependent upon a number of factors. Primarily, the interaction response is dependent both upon the chemicals in question and the individual that is exposed. Chemical‐associated factors include mechanisms or modes of action of the chemicals, timing of exposure and dose of exposure. Individual‐associated factors include personal characteristics, lifestyle factors, physiological factors and genetic factors. An integrated systems‐biology approach is necessary to evaluate the exposure, the interaction and the biological response. Newer technologies (omics) could play a significant role in assessing the risk of interaction from exposure to multiple toxins.
Susceptibility of Children to Environmental Xenobiotics
Authors: Woolf Alan D. , Sandel Megan 
Published: December 2009

AbstractThe growth of interest in paediatric environmental health reflects a widespread recognition that the impact of the environment on children's health is of major importance for this and succeeding generations. Children have a greater vulnerability to the adverse health effects of many environmental toxicants and xenobiotics than do adults, by virtue of their smaller size, increased weight‐adjusted intake of toxicants, developmental differences in body systems and functions, overall physiological and toxicodynamic differences, and differences in the environments they inhabit, the air they breathe, the foods they eat and the behaviours they display every day. The overall impact of such adverse effects of the environment, manifested by subsequent poorer health and the need for costly healthcare services, is amplified by the longer lifespans of children and is associated with intergenerational transmission of harmful effects, to the detriment of mankind. Conversely there is also great potential for averting such harmful effects by improving the quality of the environment and sparing children the consequences of such exposures.
Occupational Toxicology
Authors: Jin Chuanfang , Werntz Charles M. , Ducatman Alan M. 
Published: December 2009

Abstract
Occupational diseases are both over‐ and underdiagnosed. Both problems are important, but underdiagnosis in populations dwarfs the intermittent problem of occasional overdiagnosis in individuals. A Venn‐diagram approach to occupational disease includes: (i) a correct clinical diagnosis (specific ICD code or else a clear description of the clinical presentation), (ii) an understanding of the patient's exposure history (toxic exposures, including some sense of ‘dose’) and (iii) an understanding of the actual human toxicology/epidemiology of the exposure(s) in question (evidence‐based exposure‐outcome assessment). Incomplete understanding of the clinical presentation or failure to understand the exposure explains the large background of missed diagnoses. Fanciful attributions of exposure‐outcome relationships explain intermittent overdiagnoses. Following an overview of the occupational history, and laboratory testing, this chapter surveys the literature covering a broad range of toxic exposure‐outcome information.