bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicology and Biological Monitoring of Metals
Authors: Nordberg Monica , Nordberg Gunnar F. 
Published: December 2009

AbstractThere are 67 elements classified as metals and the present chapter presents a review of the toxicology and evidence for useful biological monitoring of 29 of these elements and their various chemical compounds. Introductory sections of the chapter deals with general aspects of metal toxicology. Emphasis is given to the fundamental importance of speciation of metals. The chemical species is defined as the specific form of an element defined as to isotopic composition, electronic or oxidation state and /or complex or molecular structure. Consideration of specific chemical species is of fundamental importance in toxicology and biological monitoring. Advances in chemical analytical methods has made it possible in recent years to use biological monitoring i.e., repeated measurements of metallic compounds in tissues or biological fluids in order to evaluate occupational or environmental exposures and health risks. For all the elements dealt with in this chapter the importance of chemical species is considered when reviewing the uptake, metabolism and excretion; toxic effects and dose‐response relationships; carcinogenicity; genotoxicity as well as biological monitoring. The following metals and their compounds are covered in the present chapter: Aluminium, Antimony, Arsenic, Barium, Beryllium, Bismuth, Cadmium, Chromium, Cobalt, Copper, Gallium and Semiconductor compounds, Germanium, Indium, Iron, Lead, Manganese, Mercury, Molybdenum, Nickel, Palladium, Platinum, Selenium, Silver, Tellurium, Thallium, Tin, Titanium, Tungsten and Zinc.
Poisons of Animal Origin
Authors: Wedin Gregory P. , Keyler Daniel E. , Bilden Elisabeth F. 
Published: December 2009

AbstractA 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.
Ricin: Chemistry, Sources, Exposures, Toxicology and Medical Aspects
Authors: Lord J. Michael , Griffiths Gareth D. 
Published: December 2009

AbstractThe chapter covers the origins of ricin toxin, which is present in the seeds of the many cultivars of the castor oil plant. The structure and biogenesis of the dimeric (A and B chain toxin) ricin (RCA60) is described, compared with the related, but less toxic,Ricinusagglutinin (RCA120) and the toxic activity of ricin, theN‐glycosidase activity of the A chain, is explained. The intoxication process is further described and developed throughin vitroandin vivostudies, which then focus on several possible routes of exposure. These include inhalation, that route which has been the primary focus of military‐oriented research through oral and parenteral routes of intoxication; histopathology and symptomatology are described, using evidence from human cases of ricin poisoning, wherever possible. Information is then presented on the development of medical countermeasures against ricin poisoning, including pretreatment approaches (vaccines) and postexposure approaches, which include antitoxins. More novel and currently research‐based studies are considered, including inhibitors ofN‐glycosidase, substrate competitors or approaches to interfere with the binding of the ricin B chain to galactose moieties.
Biotechnology: Safety Assessment of Biotherapeutics and Agribiotechnology‐Derived Foods
Authors: Thomas John A. 
Published: December 2009

Abstract
The advent of recombinant DNA (rDNA) technologies has accelerated progress in developing large proteinaceous molecules with therapeutic properties. Such development has resulted in alternative sources for hormones (e.g. insulin, growth hormone), for immunomodulators, selected neurological disease therapies and for human monoclonal antibodies (Mab).
Not only have advances occurred in human therapies, but considerable progress has been made in designing genetically modified (GM) food crops(e.g. soy beans, corn, etc.) that require the use of less chemical herbicides, can be grown with high yields, and are often more nutritious.
These advances in rDNA have provided both medicine and agriculture with new avenues for therapeutic agents and food crops. Many of the safety evaluation protocols involving rDNA products necessitate a battery of pre‐clinical tests that include protein allergenicity and immunotoxicity, genotoxicity, and other specific assays.
Basic Toxicological Issues in Product‐Safety Evaluations
Authors: Hobson David W. 
Published: December 2009

AbstractProduct safety has become a keystone in the market success and longevity of many different types of products, such as pharmaceuticals, medical devices and a wide diversity of consumer products, including toys, health products, cosmetics, toys, food products and so on. Toxicologic testing for some types of products is required for registration by various international agencies, for example, pharmaceuticals, pesticides, medical devices and bulk chemicals. Other products, while not having strict registration testing requirements, should be evaluated for safety due to the potential for liability and loss of market share, as well as branding, should the product prove to have toxicologic issues while in routine consumer use. Toxicologists with appropriate training and experience, and the product‐safety programmes they develop can, therefore, can have a significant impact on the success and longevity of a wide variety of products, if they are involved throughout the product life cycle, from the design of the product, through development and manufacturing, then on into the marketplace in postmarket surveillance. Basic toxicological issues to be addressed in a complete product‐safety programme include the gathering of information to aid in product design, the development of specific toxicological tests and the design of toxicological‐testing programmes, as well as postmarket vigilance activities.
Oncology Biomarkers
Authors: Tainsky Michael A. 
Published: December 2009

AbstractBiomarkers hold tremendous promise for diagnostic devices and are useful for monitoring the effectiveness of clinical interventions. Biomarkers are also used to stratify oncology patients to the most appropriate treatment. Effective biomarkers for the early detection of cancer can provide a patient with a better outcome which will translate into more efficient delivery of healthcare. Early detection technologies applied to population‐based screening for cancer have resulted in reductions in disease‐associated mortalities from cancers that are otherwise deadly if allowed to progress to an advanced stage. These screening technologies have proven that early detection will decrease the morbidity and mortality from cancer. Biomarkers can provide prognostic information on disease, enabling interventions with the appropriate therapeutic agents as well as early decisions and corrections of cancer treatment. There is a plethora of novel genomic, proteomic and metabolomic technologies that can be used to discover and validate tumour biomarkers individually and, where necessary, in combinations. Although biomarkers have the potential to provide personalized diagnostic, prognostic and therapeutic information, the devices to implement them clinically must supply healthcare providers with simple algorithms for step‐by‐step approaches to their patients.
Developmental Immunotoxicology
Authors: Dietert Rodney R. 
Published: December 2009

AbstractDevelopmental immunotoxicology (DIT) is the study of the impact of chemicals, drugs, physical factors and other agents on the immune system of the nonadult (prenatal, neonatal and juvenile). To achieve complete maturation and full competence, the immune system undergoes a series of novel maturational events during critical windows of development. These events lack exact equivalents in the adult. Not surprisingly, disruption of these early‐life events can have profound and persistent adverse consequences impacting the health and wellbeing of the affected child or adult. Because the developing immune system has been shown to be more sensitive to environmentally induced disruption than is the fully matured immune system of an adult, determination or of immuntoxic risk for the non adult is a growing concern. A dysfunctional immune system appears to be linked to many of the most prevalent chronic diseases of children and adults. For this reason, improved DIT safety testing and resulting immunotoxicity‐associated risk reduction, could have a significant health benefit. This chapter describes: (i) the windows of vulnerability for the developing immune system, (ii) toxicants reported to disrupt immune development, (iii) the importance of gender in risk of developmental immunotoxicity, (iv) the nature of the adverse health outcomes resulting from developmental immunotoxicity and (v) approaches to developmental immunotoxicity safety testing.
Biological Correlates of Low‐Level Electromagnetic‐Field Exposure
Authors: Behari Jitendra 
Published: December 2009

AbstractBiological effects of electromagnetic‐field exposure have been a subject of continuing concern for a number of reasons. The effects have been broadly divided into two parts: thermal and nonthermal, though the demarcation between the two is not well defined. Recently, a large amount of experimental data has accumulated, indicating a variety of biological effects much below the accepted criteria for safe exposure. The biological effects, which may or may not involve health implications, are many. This includes the blood‐brain barrier, ornithidine decarboxylase, the role of Ca2+, melatonin, DNA strand breakage and free‐radical formation. Some of these parameters are often implicated in tumour promotion. Propagation of the signal through plasma membrane has raised questions regarding the modality of its amplification. While a number of mechanisms have been proposed (e.g. stochastic resonance, cooperativism, etc.), they may be active separately or in unison to bring about the desired amplification and control the cellular function. The formulation for setting the criteria for safety standards then needs further scrutiny, particularly for health risks from microwave exposure from wireless communication. The role of other exposure parameters, such as frequency, modulation, polarization and intermittence of exposure, may also be considered. This then suggests the necessity to have a re‐look at the concept of specific absorption rate (SAR) defining dosimetry and criteria for safety standards. The possibility of application of cross fields to restrict the formation of free radicals, and possibly cancer promotion, is also presented.
Susceptibility of Neonatal Rats to Xenobiotics
Authors: Hirata‐Koizumi Mutsuko , Hasegawa Ryuichi , Hirose Akihiko , Ema Makoto 
Published: December 2009

AbstractCurrent risk assessments of xenobiotics, especially industrial chemicals, are usually based on animal studies. Although many types of toxicity studies are conducted to cover different developmental stages, evaluation for the early postnatal period is not adequate. In this chapter, special attention is directed to the susceptibility of neonatal animals to chemical toxicity. We introduce comparative analysis of the toxic susceptibility of neonatal and young rats to 20 chemicals as examples, and discuss a range of uncertainty factors important in the risk assessment of susceptible groups such as neonates and infants. The results reveal higher susceptibility of neonates to 11 chemicals and lower susceptibility to six chemicals compared with young rats, and one exceptional case of highly specific toxicity in neonates. These phenomena show the importance of studying sensitivity to toxic insults in the early stages of life. It suggests that an uncertainty factor of 10‐fold for human variability can be considered appropriate for risk assessment, unless particular toxicity in neonates or infants has been demonstrated, or there is other relevant and credible information regarding the chemical.
Phototoxicology
Authors: Nash J. Frank 
Published: December 2009

AbstractPhototoxicology is the study of adverse events resulting from the interaction between light and a test material. Measurement of the target chromophore absorption profile is the first step in a phototoxicological assessment. Determination of acute photoirritation potential is achieved using thein vitro3T3 neutral red uptake phototoxicity assay. The photoirritation or photoallergenicity potential of a test material may be evaluated usingin vivoanimal testing. Human evaluations of photoirritation or photoallergy potential are available to confirm the absence of such effects. Long‐term photo co‐carcinogenicity testing has been evaluated using the SKH1 albino hairless mouse model. This is often preceded or replaced by photogenotoxicity testing; for example,in vitrophoto‐Ames, photoclastogenicity studies. For either photo co‐carcinogenicity or photogenotoxicity testing, the outcome interpretation is often uncertain due to the absence of known human positive controls and the predictive validity of such studies. In the USA and Europe, there are regulatory guidelines for photosafety testing of pharmaceutical/cosmetic test materials. The multivariate nature of phototoxicology requires careful attention to the experimental conditions and photobiological considerations, for example light source and dosimetry. Any potential photohazard identified usingin vitroorin vivomethods must be judged in the context of product use and light exposure.
Biomarkers of Exposure to Carcinogens
Authors: Scheepers Paul T.J. 
Published: December 2009

AbstractIn human exposure assessment a biomarker is a parent substance, metabolite or addition product (adduct) that can be measured in blood, urine, exhaled air or in other biological tissues. The biomarker provides information on the internal exposure to a chemical substance. Biomarkers can be used to evaluate exposure to carcinogenic substances in the workplace or in the general environment. If the parent compound is used as a biomarker, information on uptake from different sources and via different routes can be obtained. Use of a metabolite or adduct to DNA or proteins also provides information on bioavailability and metabolic activation. The half‐life of biomarkers determines the moment of sample collection relative to time of exposure. Some biomarkers are mechanism‐based and provide useful information on the formation of genotoxic intermediates. Most biomarkers reflect systemic bioavailability rather than a target dose, which sometimes limits the interpretation in terms of assessment of cancer risk. The method of sample collection, pretreatment, transportation, storage and a reproducible and sensitive method of analysis should be selected with care. Background values and biological limit values provide a framework for interpretation. The study protocol should comply with international standards in ethics of biomedical studies involving human subjects.
Cardiac Toxicity of Anthracyclines
Authors: Olson Richard D. , Cusack Barry J. 
Published: December 2009

AbstractCardiotoxicity of anthracyclines limits their therapeutic potential. In thein vitroacute model, anthracyclines produce cardiotoxicity in minutes or hours at concentrations near 100 μM, through a mechanism involving impairment of sarcoplasmic reticulum (SR) function and requiring the quinone moiety, most likely through a non‐free‐radical process. The chronic cardiotoxicity is more complex, but may also involve SR. Additional mechanisms in the chronic model of anthracycline cardiotoxicity may include impairment of triiodothyronine function, cardiac protein degradation, free‐radical generation, apoptosis, cardiac metabolite formation, impairment of iron metabolism and oestrogen‐dependent up‐regulation of nitric oxide synthase (NOS). Thus, prevention or attenuation of anthracycline cardiotoxicity may be achieved by favourably manipulating these mechanisms.
Significance of Biochemical Markers in Applied Toxicology
Authors: Gil Fernando , Hernández Antonio F. 
Published: December 2009

AbstractThe use of biological markers in the evaluation of disease risk has increased markedly in the last decades. The relationship between toxic levels of chemicals in the body and their toxic response is rather complex because it depends on several factors, including toxicokinetic and genetic aspects. Biomarkers allow the assessment of the potential interaction and impact of xenobiotics on living organisms. A biomarker was originally defined as the concentration of toxic agents, or their metabolites, in biological samples. However, the concept of biomarker has been further expanded, including those biological changes resulting from interaction between chemicals and their cellular or molecular targets, as well as genetically determined polymorphisms of enzymes involved in Phase I and II of metabolism, which are responsible for the differential susceptibility of individuals to chemical agents. This chapter discusses examples of biomarkers of exposure, effect and susceptibility and their usefulness in toxicology.
From Diet to Detox: Controversial Therapies in Autistic Spectrum Disorders
Authors: Fitzpatrick Michael J. 
Published: December 2009

Abstract
An increased public awareness of autism has resulted in a rising trend of diagnoses, creating the impression of an ‘epidemic’. Many parents of children newly diagnosed with autism have been impressed by plausible theories blaming vaccines and other environmental causes. Many have also been captivated by claims that ‘biomedical’ treatments—including special diets and supplements, ‘detox’ regimes and medications—can achieve dramatic results. The current fad for unorthodox biomedical interventions in autism includes an eclectic collection of therapies which have no coherent scientific rationale and for which evidence of either efficacy or safety is lacking.
High‐Performance Alkaline Polymer Electrolyte for Fuel Cell Applications
Authors: Pan Jing , Lu Shanfu , Li Yan , Huang Aibin , Zhuang Lin , Lu Juntao 
Published: December 2009

AbstractAlthough the proton exchange membrane fuel cell (PEMFC) has made great progress in recent decades, its commercialization has been hindered by a number of factors, among which is the total dependence on Pt‐based catalysts. Alkaline polymer electrolyte fuel cells (APEFCs) have been increasingly recognized as a solution to overcome the dependence on noble metal catalysts. In principle, APEFCs combine the advantages of and alkaline fuel cell (AFC) and a PEMFC: there is no need for noble metal catalysts and they are free of carbonate precipitates that would break the waterproofing in the AFC cathode. However, the performance of most alkaline polyelectrolytes can still not fulfill the requirement of fuel cell operations. In the present work, detailed information about the synthesis and physicochemical properties of the quaternary ammonia polysulfone (QAPS), a high‐performance alkaline polymer electrolyte that has been successfully applied in the authors' previous work to demonstrate an APEFC completely free from noble metal catalysts (S. Lu, J. Pan, A. Huang, L. Zhuang, J. Lu, Proc. Natl. Acad. Sci. USA 2008, 105, 20611), is reported. Monitored by NMR analysis, the synthetic process of QAPS is seen to be simple and efficient. The chemical and thermal stability, as well as the mechanical strength of the synthetic QAPS membrane, are outstanding in comparison to commercial anion‐exchange membranes. The ionic conductivity of QAPS at room temperature is measured to be on the order of 10−2 S cm−1. Such good mechanical and conducting performances can be attributed to the superior microstructure of the polyelectrolyte, which features interconnected ionic channels in tens of nanometers diameter, as revealed by HRTEM observations. The electrochemical behavior at the Pt/QAPS interface reveals the strong alkaline nature of this polyelectrolyte, and the preliminary fuel cell test verifies the feasibility of QAPS for fuel cell applications.
Near IR Sensitization of Organic Bulk Heterojunction Solar Cells: Towards Optimization of the Spectral Response of Organic Solar Cells
Authors: Koppe Markus , Egelhaaf Hans‐Joachim , Dennler Gilles , Scharber Markus C. , Brabec Christoph J. , Schilinsky Pavel , Hoth Claudia N. 
Published: December 2009

AbstractThe spectroscopic response of a poly(3‐hexylthiophene)/[6,6]‐phenyl‐C61‐butyric acid methyl ester (P3HT/PCBM)‐based bulk heterojunction solar cell is extended into the near infrared region (NIR) of the spectrum by adding the low bandgap polymer poly[2,6‐(4,4‐bis‐(2‐ethylhexyl)‐4H‐cyclopenta[2,1‐b;3,4‐b´]‐dithiophene)‐alt‐4,7‐(2,1,3‐benzothiadiazole)] [PCPDTBT] to the blend. The dominant mechanism behind the enhanced photosensitivity of the ternary blend is found to be a two‐step process: first, an ultrafast and efficient photoinduced charge transfer generates positive charges on P3HT and PCPDTBT and a negative charge on PCBM. In a second step, the positive charge on PCPDTBT is transferred to P3HT. Thus, P3HT serves two purposes. On the one hand it is involved in the generation of charge carriers by the photoinduced electron transfer to PCBM, and, on the other hand, it forms the charge transport matrix for the positive carriers transferred from PCPDTBT. Other mechanisms, such as energy transfer or photoinduced charge transfer directly between the two polymers, are found to be absent or negligible.
Impact of retention on trans‐column velocity biases in packed columns
Authors: Gritti Fabrice , Guiochon Georges 
Published: December 2009

AbstractThe heights equivalent to a theoretical plate of a weakly and strongly retained compounds were measured on two packed columns having different average mesopore sizes. The measurements were carried out in two different cases, with access to the mesopores by the sample molecules blocked (filled with n‐nonane) or not. The experimental results demonstrate that the eddy dispersion terms of both columns are significantly smaller for porous than for nonporous particles. Two simultaneous phenomena explain this observation. First, packed columns are radially heterogeneous which causes significant trans‐column velocity biases warping the bands. Second, radial dispersion contributes to mass transfer across the column, relaxing the radial concentration gradients that are caused by these velocity biases. The impact of these biases is minimized when the pores of the particles are not blocked; it decreases with increasing residence time and radial dispersion coefficient of the solutes. © 2009 American Institute of Chemical Engineers AIChE J, 2009