bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental Neurotoxicity
Authors: Makris Susan L. , Raffaele Kathleen C. 
Published: December 2009

AbstractThis chapter describes the essential elements of the developmental neurotoxicity (DNT) study, which is intended to screen for adverse effects of pre‐ and postnatal exposure on the development and function of the nervous system. The background and history of the guideline are discussed, illustrating the extensive research, collaborative international scientific efforts and interlaboratory studies that have contributed to its development, and thus demonstrating its validity, sensitivity, reliability and cross‐species comparability. The end points assessed in the guideline DNT study are addressed in detail; these include functional observations, developmental landmarks, auditory startle, motor activity, learning and memory (cognitive) testing and postmortem evaluations (brain weight, qualitative neuropathology and quantitative morphometry). End‐point‐specific issues, consideration of critical windows of development, special vulnerabilities of the developing nervous system and interpretation of the data are discussed. A review of the use of DNT study data in human‐health risk assessment demonstrates the value of the study.
Toxicology of the Placenta
Authors: Gupta Ramesh C. 
Published: December 2009

AbstractPlacental toxicology deals with the adverse effects of toxic substances on the placenta, the mother and the foetus. It is a fascinating subject which receives attention from biologists, toxicologists, teratologists, pharmacologists, physicians and regulatory agencies. Structural or functional damage to the placenta can lead to abortion, birth defects, stillbirth, premature birth and many other complications. Since the placenta is an entry organ to the foetus, and the ‘placental barrier’ is merely a false notion, the placenta remains vulnerable to the adverse effects of many toxicants. The placenta is a complex organ to study since it continually changes throughout gestation. This organ is further complicated by multiple pregnancies in many species, including humans. The placenta plays several roles in the development of the foetus by serving as the lung, gut, kidney and endocrine/exocrine gland. Additionally, it supplies vital nutrients and gases to the foetus. This chapter describes the placental toxicity of drugs of abuse, alcohol, tobacco products, metals, pesticides, environmental toxicants and mycotoxins.
Aquatic Toxicology: Concepts, Practice, New Directions
Authors: Wells Peter G. 
Published: December 2009

AbstractThis chapter presents a broad overview of the principles, practice and some of the new developments in aquatic toxicology. The field has matured rapidly over the past 30‐40 years. Many acute and chronic toxicity testing methods have been developed and standardized for application in environmental protection. Basic research has been conducted with many species across the aquatic phyla, with a wide range of contaminants. Critical linkages have been made to other aquatic disciplines ensuring that a comprehensive understanding of exposure, uptake, metabolism and discharge of chemicals, in many aquatic species under many conditions, is fully realized. New issues, such as the effects of pharmaceuticals, are being investigated with urgency. Aquatic toxicology is now supported in many countries by a wide range of research programmes, graduate programmes, training courses and publications, assuring its place in basic and applied toxicology.
Environmental Endocrine Toxicology
Authors: Bjerregaard Poul 
Published: December 2009

AbstractDisorders in sexual development have increased in frequency in certain geographical regions during the latter half of the 20th century. In humans, this is expressed as elevated prevalence of testicular cancer, cryptorchidism and hypospadias and decreased sperm counts, collectively termed the ‘Testicular Dysgenesis Syndrome’ (TDS). A fairly large number of chemicals in widespread use (i.e. alkylphenols, phthalates, bisphenol, PCBs, pesticides) have been shown to interfere with the synthesis and/or the function of sex hormones, and exposure to some of these chemicals (individually or in mixtures) compromises normal sexual development in animals in tests in the laboratory. The occurrence of TDS in humans seems to be associated with general life style factors, but although associations between TDS and exposure to certain chemicals (e.g. PCBs, phthalates, pesticides) have been demonstrated, firm causal relationships have not yet been established. In nature, effects caused by exposure to discharged hormones or chemicals with endocrine disrupting properties have been firmly documented among snails, fish, amphibians, reptiles, birds and mammals: The anti‐fouling biocide tributyltin masculinizes female snails, synthetic p‐pill estrogens and natural estrogens feminize male fish downstream discharges from sewage treatment plants, effluents from pulp and paper mills masculinize female fish and various chlorinated hydrocarbons have feminized higher vertebrates such as alligators and birds.
Occupational Toxicology and Occupational Hygiene within the
E
uropean
U
nion (
EU
) Chemicals Regulation
Authors: Fairhurst Steven , Ball Elanor 
Published: December 2009

Abstract

The purpose of this chapter is to discuss the interplay between the disciplines of toxicology and occupational (or industrial) hygiene in understanding and controlling the hazards and risks to health posed by chemicals, in an occupational setting. Ten years ago, the chapter ‘Industrial Toxicology and Hygiene’, produced for the second edition of
General and Applied Toxicology
, offered a perspective on the main approaches, roles and responsibilities that, in a regulatory context, had held for a considerable period of time within chemical legislation. This updated chapter is written from within the European Union (EU) at a time when it is embarking on a new era of chemicals legislation that promises to change things profoundly. On 1 June 2007 the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation came into force in the EU. This legislation changes the nature and balance of roles between industry and regulatory authorities—and modifies the conventional approaches to, and interplay between, toxicology and occupational hygiene—in regulating industrial and commercial chemicals within the EU. In its information requirements for registration purposes, REACH creates a tension between desires to improve the extent and quality of data available on chemicals, but also to minimize experimental animal testing. In relation to toxicology, this poses challenges to all concerned. REACH removes the distinction and associated data‐expectation requirements between ‘new’ and ‘existing’ substances within the EU. REACH also expands and reinforces the ‘customer care’ principle that suppliers of chemicals take responsibility for understanding the uses to which their chemicals are to be put and specifying the risk management measures that should be followed in such uses. This will be a big challenge to the occupational hygiene profession. And all of this also comes at a time when the EU is in the process of adopting the globally harmonized system (GHS) of classification and labelling (C&L) of chemicals, which will modify the EU C&L system that has operated for the previous several decades. So it is a time of change—and no one is quite sure how things will work out in the next 10 years. This chapter attempts to portray how these recent developments build on, or change, what has gone before, and discusses some of the key issues that are ahead for the toxicology and occupational‐hygiene fields, operating in this new regulatory context.
Forensic Toxicology
Authors: Vuori Erkki , Ojanperä Ilkka 
Published: December 2009

Abstract
Forensic toxicology is today much more than a part of investigating causes of death or identifying those driving under the influence of intoxicants. Society needs forensic toxicology services in a wider context in the name of safety and legal protection. The need is manifested in workplace testing, child welfare, drug‐facilitated crime investigations and doping control. The discipline also has responsibility for investigating acts of terrorism and environmental pollution. Forensic toxicological analysis typically consists of an initial analysis and, in positive cases, a confirmatory analysis with mass spectrometry. The samples analyzed depend on the question to be answered. If being under the influence is to be ascertained, a blood sample is obligatory. A positive urine laboratory result reveals use or exposure to a foreign substance. Alternative samples include hair, which opens a large window for detecting drug use, and oral fluid, which is easy to collect noninvasively and without embarrassment. The results of forensic toxicological investigations, compiled in databases for later research, can also be used to reveal changing trends in illicit drug abuse and to improve drug safety in general. Because of the legal contexts in forensic toxicological investigations, legislation concerning sampling and civil rights must be strictly followed, and the same also applies to the chain of custody regarding the handling of samples.
Essentials of Epidemiology for Toxicologists
Authors: Coggon David 
Published: December 2009

AbstractEpidemiology is concerned with the distribution and determinants of health in populations. The applications of epidemiology that are of most relevance to toxicology lie in the identification and characterization of toxic hazards, the assessment of risks from toxic exposures, and the evaluation of measures designed to control such risks. Most epidemiological studies focus on the occurrence of disease, but other health outcomes such as symptoms and disability may also be investigated.Incidence (the rate at which new cases of disease occur in a population) is the measure of disease frequency of most relevance to study of causation. Other measures such as mortality (the incidence of death from a disease) and prevalence (the proportion of a population who are cases at a point in time or during a specified period) may be used as a proxy for incidence, but results must then be interpreted with added care. Where disease rates vary importantly by sex and age, comparison between populations may be enhanced by use of sex‐ and age‐specific rates, or by standardizing rates for sex and age.Various statistics are used to summarize associations between ‘risk factors’ and health outcomes, each with its particular applications. Attributable risk is relevant when making decisions in risk management for individuals. Relative risk (RR) (or the closely related odds ratio) is most useful when considering whether associations are likely to be causal. Population attributable risk and attributable proportion are useful in risk management for populations. The attributable fraction in exposed (AFexp) is used when determining causal attribution for purposes of compensation.Major considerations in the design and interpretation of epidemiological studies are bias (a systematic tendency to underestimate or overestimate a parameter of interest), chance and confounding (which occurs when the risk factor of interest is associated with a ‘confounding’ factor that independently determines the risk of developing the health outcome under study). Assessment of the potential impact of chance is helped by statistical inference using either hypothesis‐testing (p‐values) or confidence intervals.Categories of epidemiological investigation include descriptive studies, ecological studies, cohort studies, case–control studies, cross‐sectional surveys and randomized and nonrandomized experiments. Each of these study methods has its particular applications, strengths and limitations.In addition to bias, chance and confounding, other considerations when interpreting and comparing epidemiological findings are the ways in which exposures and health outcomes have been classified, and the potential for biological modification of causal associations by ‘effect modifiers’. In addition, epidemiological results should always be viewed in the context of relevant biology, including what is known from toxicological studies in the laboratory.
Toxicogenomics in Risk Assessment
Authors: Makris Susan L. , Euling Susan Y. 
Published: December 2009

AbstractToxicogenomicsis defined as the application of genomic technologies to study the adverse effects of environmental and pharmaceutical chemicals on human health and the environment. It integrates toxicant‐specific alterations in gene, protein, and metabolite expression patterns with phenotypic responses of cells, tissues and organisms. These data, depending on the type of data and study design, have the potential for use in various stages of risk assessment; that is, hazard characterization, dose‐response assessment and exposure identification. As genomic technologies produce global molecular response data, they provide a new and unique source of information that can inform mode of action, intraspecies variability and susceptibility, interspecies variability and/or cross‐species extrapolation, and/or cumulative risk. Considerations and future challenges regarding the use of toxicogenomic data in risk assessment such as variability in response, experimental design, analysis of data, and training, are described, and regulatory agency guidance and efforts in this field are summarized.
Education of the Toxicologist
Authors: Snyder Robert , Richardson Jason R. 
Published: December 2009

Abstract
The aim of this chapter is to describe the training of toxicologists. It stresses the need for students to understand the development of toxicology as a distinct discipline despite its close ties to other disciplines such as pharmacology, pathology, and so on. It emphasizes the need for students to be broadly and firmly grounded in each of the basic medical sciences. The study of past discoveries and the early initiation of their own research efforts should lead students into the appreciation of hypothesis building and the application of scientific methods to challenge their hypotheses. It is essential that students learn to use the extensive toxicological literature, much of which is now available online. Students should be trained to write scientific papers and should be prepared to describe the results of their work in well‐organized discussions. Ultimately, the success of the student will be a measure of the scholarly interaction with the student's mentor. Toxicology training should permit the student to enter into a career in basic or applied research. Many students opt for postdoctoral fellowships to help them decide upon how best to build a career. It is recognized that some differences can be identified when comparing training programs, for example, in the USA, Great Britain and Germany. However, experience has shown that each has prepared students to meet the challenges faced by modern toxicologists.
Radiation Terrorism
Authors: McFee Robin Beverly 
Published: December 2009

Abstract
Among the categories of Weapons of Mass Destruction (WMD)—chemical, biological, radiological, nuclear and explosive, the two that revive images of horror on a par with ‘doomsday’ scenarios are the radiological and nuclear agents. While all five pose a serious risk to health, and have been used by nations, terrorists and insurgents throughout human history, most healthcare professionals are familiar with treating trauma and have a background—at least rudimentary—in treating pathogens and certain chemical toxicants, although the WMD versions of pathogens and chemicals are clearly more dangerous. But few healthcare professionals have had the experience of working with, let alone recognizing or treating, a radiation‐induced illness or injury. In the December World at Risk Report published by the Commission on Weapons of Mass Destruction Proliferation and Terrorism impanelled by the US Government, their conclusion in terms of the availability of radiological and nuclear materials, entities willing to use them and the increased opportunity to develop weapons—rudimentary or otherwise was as follows: ‘The sobering reality is the risks are growing faster than our multilayered defences. Our margin of safety is shrinking, not growing’. Mass exposures to a radiological or nuclear event will pose a unique and unprecedented challenge—at least in the last 50 years—a challenge that health‐care professionals remain undertrained for, and most facilities continue to be untested and underprepared. Yet emergency medical services, hospitals and medical professionals are looked upon as the critical response arm of preparedness. While a nuclear or radiological event may be considered a low likelihood—it is clearly a high consequence exigency. As such, our facilities and healthcare professionals need to update or develop plans, increase training and implement more skills‐based efforts. The analogy is simple—our communities are depending upon us to save them… yet we do so with little more than perhaps annual drills or table‐top exercises. Would we allow a colleague to intubate one of our loved ones based upon practising that skill only once a year? Why then, facing the complexities of diagnosing and managing a radiation event in our region, would we be satisfied with single annual exercises? In the aftermath of the Litvinenko murder with polonium‐210, the increasing likelihood of Iran and other nations acquiring some form of radiological weaponry, re‐emergence of nuclear energy as an alternative to fossil fuels and the resulting proliferation of radioactive waste—now is the time to address radiation preparedness. Towards that end, this chapter will discuss the global threats, key medical considerations, essential equipment and other important issues necessary to enhance preparedness.
Depleted Uranium: Toxicology and Health Consequences
Authors: Miller Alexandra C. 
Published: December 2009

AbstractDepleted uranium (DU) is a dense heavy metal and an alpha particle emitter used in military and industrial applications. Exposure can occur via wounding, ingestion or inhalation. Several recent studies have investigated the potential health effects of this unique heavy metal. Thesein vitroandin vivoinvestigations have not only demonstrated the neoplastic transforming ability, the mutagenicity and the genotoxicity of DU, but also the neurotoxicity of DU. Studies using neoplastically transformed human cells and the athymic nude mouse assay demonstrated the carcinogenic potential of DU. DU exposure has been shown to induce genomic instability in a human cell model and alpha‐particle radiation is responsible for some of the cellular damage induced by DU. Chronic long‐term internal exposure to embedded DU could be a carcinogenic risk and comparisons to other types of uranium exposure, i.e., occupational inhalation of natural uranium, are problematic. Chronic internal exposure studiesin vivohave demonstrated that DU is leukemogenic and neurotoxic. Epidemiological studies are inconclusive and the use of depleted uranium in armor‐penetrating munitions remains a source of controversy because of the numerous unanswered questions about its long‐term health effects.
Toxicology of Food Additives
Authors: Barlow Susan M. 
Published: December 2009

AbstractChemicals have been used to preserve food and to add colour and taste to food for centuries. Following the considerable increase in the use of food additives in processed foods from the mid‐twentieth century, safety assessment of food additives has been conducted on a formal basis at national and international levels. Currently, over 400 individual additives are listed by the international Codex Alimentarius for use in food traded around the world. Current approaches to the safety assessment of food additives generally require an extensive database of kinetic, metabolic and toxicity studies to be generated. Toxicity studies are usually conducted in laboratory animals and the types of study generally cover all the various life‐stages. Human studies are rarely available, but human data on absorption, metabolism and tolerance may be available. Studies are designed to show, not only any adverse effects, but also to identify doses below which no adverse effects occur (the no observed adverse‐effect level or NOAEL). Acceptable daily intakes (ADIs) for food additives are derived by examination of the outcomes of the toxicity studies, and usually are based on the overall NOAEL for the most sensitive effect in the most sensitive species. In order to ensure absence of toxic effects in the exposed human population, conservative ADIs are derived by application of safety or uncertainty factors to the overall NOAEL.
Safety Assessment of Foods Obtained from Crops Developed Using Biotechnology
Authors: Delaney Bryan 
Published: December 2009

AbstractThe current chapter discusses historical perspectives on the development and commercialization of genetically engineered (GE) crops developed using biotechnology, and the safety assessment of foods obtained from these crops. Most currently commercialized GE crops express transgenic proteins that confer agronomic traits, including insect resistance and herbicide tolerance that are intended to increase crop yield. Methods to assess the safety of transgenic proteins used in GE crops for potential allergenicity and toxicity are discussed. Additionally, the principles of substantial equivalence as applied to the safety assessment of foods obtained from GE crops are discussed. Numerous examples are presented to emphasize the comprehensive nature of the safety‐assessment process conducted for these products prior to commercialization to demonstrate that the transgenic proteins are safe and that the foods obtained from the currently marketed GE crops are as safe as those obtained from non‐GE crops.
Toxicology of Biocides
Authors: Ballantyne Bryan 
Published: December 2009

AbstractBiocides are generally defined as chemicals or biological agents that are capable of destroying, preventing or rendering harmless, pathogenic organisms. In terms of regulatory activity, the scope of biocides has expanded to the extent that they are regarded as nonagricultural biocides. Their use requires that they be registered and approved through national and international regulatory schemes. Biocides are extensively used in industry, domestically, agriculturally and with medical and veterinary applications. Thus, they find widespread use, particularly in pulp and paper manufacturing, in personal care products, preservatives and as sanitizers, disinfectants and sterilants. Because they are reactive with pathogenic organisms, biocides are potentially toxic and, through misuse, can result in adverse health effects. This review discusses the use patterns, chemistry, toxicology, human health effects and environmental aspects, of several representative biocides of a wide range of chemical structures and applications.