{"title":"The Influence of Temperature on Toxicity","authors":"C. Gordon, P. Rowsey","doi":"10.1002/9780470744307.GAT032","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT032","url":null,"abstract":"Our 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. \u0000 \u0000 \u0000Keywords: \u0000 \u0000thermoregulation; \u0000autonomic; \u0000behavioural; \u0000radiotelemetry; \u0000thermal stress; \u0000organophosphate insecticides; \u0000fever","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123487666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxicities Associated with Parenteral Nutrition","authors":"J. Aschner, Heather M. Furlong","doi":"10.1002/9780470744307.GAT053","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT053","url":null,"abstract":"Parenteral nutrition is a life-sustaining therapy for patients with structural or functional intestinal diseases who are unable to tolerate sufficient enteral intake or absorb sufficient calories to support energy requirements. Despite its unquestionable value under these circumstances, prolonged dependence on parenteral nutrition is fraught with potentially life-threatening complications related to the presence of unintended chemical and microbial contaminants of parenteral nutrition solutions, and insufficient knowledge of the optimal dosing of various parenteral nutrition additives thought to be essential to human nutrition. Infants and children with congenital or acquired gastrointestinal tract diseases who are dependent on parenteral nutrition to supply essential nutrients and calories for growth and development are particularly vulnerable. This chapter will review the potential toxicities associated with both unintended contaminants in parenteral nutrition, including microbes, phthalates, bisphenol-A, particulates, lipid peroxidation products and aluminium, as well as intentional supplementation with potentially toxic substances, including trace metals, amino-acid mixtures and lipid emulsions, when provided in excessive amounts or suboptimal ratios, or when normal metabolism or excretion are altered by an underlying medical condition. Practical applications and areas in need of further laboratory and human research are highlighted. \u0000 \u0000 \u0000Keywords: \u0000 \u0000parenteral nutrition; \u0000microbial contamination; \u0000precipitates; \u0000phthalates; \u0000bisphenol-A; \u0000aluminium; \u0000essential trace-metal toxicity; \u0000amino acids; \u0000lipid emulsions; \u0000neonate; \u0000infant","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127867951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Poisons of Animal Origin","authors":"G. Wedin, D. Keyler, E. Bilden","doi":"10.1002/9780470744307.GAT148","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT148","url":null,"abstract":"A great number of species in the animal kingdom possess means by which they subdue prey or defend against predators. Human encounters with these species may result in bites or stings that produce local injury or systemic toxicity ranging from local pain and varying degrees of tissue injury to systemic illness, organ failure and even death. Most of these animals deliver a dose of venom when they bite or sting, but some produce or accumulate toxin in their flesh that may produce illness if ingested. Venoms are generally complex mixtures of proteins and enzymes, but few are very well understood. Antivenoms have been produced to treat exposures to some species, but treatment generally consists of supportive measures and treatment of symptoms. This chapter presents an overview of some of more common animal species found throughout the world, the toxic syndromes they produce and current therapeutic strategies. \u0000 \u0000 \u0000Keywords: \u0000 \u0000ants; \u0000antivenom; \u0000beaded lizard; \u0000stinging fish; \u0000gila monster; \u0000Hymenoptera; \u0000jellyfish; \u0000scorpion; \u0000shellfish; \u0000snake; \u0000spider; \u0000stingray; \u0000venom","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131263425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxicological Considerations for Pharmaceutical Products","authors":"L. Reid","doi":"10.1002/9780470744307.GAT115","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT115","url":null,"abstract":"This chapter is designed to highlight some of the general toxicologic concepts, for example species selection, duration and dosing, which should be taken into consideration when designing a nonclinical investigatory programme intended to support development of pharmaceutical agents. The extent and types of studies needed as well as their timing relevant to the stage of clinical development are discussed. For questions regarding nonclinical development programmes for specific products, regional regulatory agencies should be consulted. \u0000 \u0000 \u0000Keywords: \u0000 \u0000nonclinical; \u0000pharmaceutical; \u0000medicinal; \u0000drug; \u0000regulatory toxicology; \u0000ICH","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131614423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Metabolomic Perspective of Small Molecule Toxicity","authors":"A. Patterson, J. Idle","doi":"10.1002/9780470744307.GAT016","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT016","url":null,"abstract":"Recent advances in small molecule profiling, including ultraperformance liquid chromatography and time-of-flight mass spectrometry, have given unprecedented views of the metabolic response to toxic stimuli. Metabolomics, the process of measuring the concentration changes in metabolites of biofluids such as urine, serum, sweat or saliva or that of intact cells, tissues or single-celled organisms, is the missing piece of the omics puzzle (genomics, transcriptomics, proteomics) necessary for providing a holistic view (DNA, RNA, protein and metabolites) of the biological response to a toxicant. Furthermore, metabolomics is an essential addition to any toxicity biomarker-screening programme, as evidenced by its strong foothold in both pharmaceutical and academic settings. Here we discuss metabolomic science with respect to its past and future contributions to the field of toxicology and describe blueprints necessary for conducting a well-designed and robust metabolomics experiment from sample collection to data acquisition and analysis. Metabolomics holds great promise as a tool for advancing the field of toxicology by uncovering novel biomarkers of toxic responses and by significantly improving xenobiotic metabolite identification. \u0000 \u0000 \u0000Keywords: \u0000 \u0000metabolomics; \u0000metabonomics; \u0000metabolism; \u0000metabolic profiling; \u0000metabolite identification; \u0000xenobiotic; \u0000ultraperformance liquid chromatography; \u0000time-of-flight mass spectrometry; \u0000NMR; \u0000UPLC-ESI-QTOFMS","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121868054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic Toxicology Testing and its Relevance to Human Risk and Safety Evaluation","authors":"E. Lorge","doi":"10.1002/9780470744307.GAT076","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT076","url":null,"abstract":"Genotoxicity 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. \u0000 \u0000 \u0000Keywords: \u0000 \u0000genotoxicity; \u0000genetic toxicology; \u0000mutagenesis; \u0000mutagen; \u0000risk assessment; \u0000toxicology","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134223962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxicology of the Endocrine System","authors":"R. Kapp, J. Thomas","doi":"10.1002/9780470744307.GAT072","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT072","url":null,"abstract":"The 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. \u0000 \u0000 \u0000Keywords: \u0000 \u0000endocrine toxicology; \u0000hormones; \u0000biochemical regulation; \u0000endocrine disruptors; \u0000endocrine modulation; \u0000endocrine receptors; \u0000endocrine target organs","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122001670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxicology of the Placenta","authors":"Ramesh C. Gupta","doi":"10.1002/9780470744307.GAT088","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT088","url":null,"abstract":"Placental 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. \u0000 \u0000 \u0000Keywords: \u0000 \u0000placental toxicity; \u0000foetal toxicity; \u0000abused drugs; \u0000metals; \u0000mycotoxins; \u0000alcohol; \u0000smoke; \u0000pesticides; \u0000environmental contaminants","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126155101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk Assessment of Chemicals","authors":"L. Stuchal, S. Roberts","doi":"10.1002/9780470744307.GAT118","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT118","url":null,"abstract":"Risk assessment of chemicals is a process that results in a quantitative and/or qualitative estimate of risk posed by chemical exposure. It includes identification of the hazard, a dose-response assessment, exposure assessment and risk characterization. The process of risk assessment continually evolves as science refines estimates of exposure and toxicity. There are two main types of risk assessment, human health and ecological, which have evolved separately to a large extent. Human health risk assessment is concerned with the protection of individuals. It considers hazard and risk to sensitive subpopulations, such as children and the elderly. Ecological risk assessment is concerned with protecting the environment and considers multiple species. Because the entity of concern is the ecosystem, the focus is on protection of populations rather than individuals. Both types of risk assessments typically utilize models to estimate the dose of chemical received and the likelihood that toxicity will occur in a particular exposure scenario. These models incorporate assumptions about exposure and toxicity, and must address both variability and uncertainty associated with risk estimates. Risk assessment is an important tool in managing potential public health and environmental impacts resulting from the use of chemicals. \u0000 \u0000 \u0000Keywords: \u0000 \u0000risk assessment; \u0000hazard assessment; \u0000toxicity; \u0000uncertainty factors; \u0000dose-response relationship; \u0000deterministic risk; \u0000probabilistic risk; \u0000exposure; \u0000threshold dose; \u0000benchmark dose; \u0000ecological risk assessment","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127271685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chemical and Biological Occupational Hazards in the Toxicology Laboratory","authors":"B. Ballantyne","doi":"10.1002/9780470744307.GAT051","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT051","url":null,"abstract":"In addition to the chemical, physical, flammability, thermal, electrical and radiation hazards common to laboratories in general, toxicology laboratories have specific occupational hazards that require their recognition, appreciation and development of management practices for protective and precautionary measures. These include exposure to test chemicals of poorly understood toxicology and to control chemicals of high biological potency. Additionally there may be exposure to allergenic materials such as latex or animal allergens, and to transmissible animal diseases. This chapter reviews the routes and natures of hazardous exposures in the toxicology laboratory, specific allergenic and infective problem areas, and necessary protective and precautionary measures. \u0000 \u0000 \u0000Keywords: \u0000 \u0000animal allergens; \u0000latex; \u0000sensitization; \u0000zoonoses; \u0000protection; \u0000precautionary measures; \u0000atopy; \u0000respiratory function tests; \u0000skin-prick tests; \u0000solvents; \u0000carcinogens; \u0000laboratory safety","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121280450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
