Toxicological mechanisms

In the 1960s and 1970s, the organophosphate and carbamate compounds replaced the chlorinated hydrocarbons as the most prominently used insecticides. These two families of insecticides share a common toxicological mechanism, the inhibition of cholinesterase enzymes in the nervous systems of... 

More sophisticated probabilistic models are used by EPA to comply with the aggregate and cumulative risk provisions of the FQPA. These models consider rolling windows of exposure, toxicological equivalence factors for pesticides that have common toxicological mechanisms, and include methods to incorporate exposure from drinking water and residential pesticide use into the pesticide exposure estimates. 

A number of toxicological mechanisms have been proposed for hydrogen sulfide At extremely high concentrations it may exert a direct paralyzing effect on respiratory centers hydrogen sulfide is also known to inhibit cytochrome c oxidase, resulting in altered oxidative metabolism it can also disrupt critical disulfide bonds in essential cellular proteins. ... 

Ward, P. (2008) Importance of drug transporters in phar macokinetics and drug safety. Toxicology Mechanisms and Methods, 18, 1-10. 

Nielsen FH, Shuler TR, McLeod TG, et al. 1984. Nickel influences iron metabolism through physiologic, pharmacologic and toxicologic mechanisms in the rat. J Nutr 114 1280-1288. 

McLachlan. J A. R.M. Prali. and C.L. Marker Developmental Toxicology Mechanisms and Risk. Cold Spring Harbor Laboratory. Cold Spring Harbor, New York, NY. 1987. 

The molecular mechanisms underlying the detrimental effects caused by aluminum have yet to be fully understood [31]. The toxicological mechanisms of aluminum in plants or in animals probably involve alterations in many enzyme activities. There is a large number of proteins which requires nucleoside phosphates as substrates or is regulated by nucleoside phosphates, therefore aluminum can potentially interfere with the normal functions of these proteins [18]. Thus, it is important to understand some reactions that involve aluminum and nucleotides. In this review we are going to focus on the alterations caused by this metal in some enzymes that hydrolyze or transfer phosphate groups of nucleotides, like NTPases, NTPDases, and kinases. 

Hazle JD, Narayana PA, Dunsford HA (1991) In vivo NMR, biochemical, and histologic evaluation of alcohol-induced fatty liver in rat and a comparison with CC14 hepatotoxic-ity. Magnetic Resonance in Medicine 19 124-135 Hockings PD, Busza AL, Byrne J et al. (2003a) Validation of MRI measurement of cardiac output in the dog The effects of dobutamine and minoxidil. Toxicology Mechanisms Methods 13 39-43... 

Halstead, B.W 2002. The microbial biogenesis of aquatic biotoxins. Toxicology Mechanisms and Methods 12(2) 135-153. 

As outlined in the toxicity section above the toxicological mechanism of action of nerve agents is based on the chemical reactivity of the nucleophilic leaving group. Therefore, metabolism in terms of degradation by hydrolysis and binding to proteins determines bioavailability and elimination processes thus regulating toxicity. 

The concepts and the scientific data that support the use of UFs in human health risk assessment have progressed considerably during the past 50 years. The increase in knowledge of both interspecies and intraspecies susceptibility and variability, the toxicologic mechanisms of action, and the availability and evaluation of databases support the use of data-derived UFs. 

In addition to his large output of scientific papers. Dr. Stewart, was coauthor with D. Dunlop of Clinical Chemistry in Practical Medicine (E. S. Livingstone Ltd., New York, 1st ed., 1931 6th ed., 1962) with A. Stolman he was coeditor of Toxicology Mechanisms and Analytical Methods (Academic Press, New York, Vol. 1, 1960 Vol. 2, 1961). He was a member of the Editorial Board of Clinica Chimica Acta from the time of the foundation of that journal. He became Editor-in-Chief in 1960 and held this appointment until just before his death. 

Modem inhalation anesthetics are fluoiinated to reduce flammabihty. Initially, these inhaled agents were believed to be biochemically inert. Over the past 30 years, however, research findings have demonstrated that not only are inhaled anesthetics metabolized in vivo [27], but their metabolites are also responsible for both acute and chronic toxicities [28,29]. Therefore, the use of some anesthetics has been discontinued, including methoxyflurane because of its nephrotoxicity and other anesthetics are more selectively used, e.g. halothane due to a rare incidence of liver toxicity. Studies have also provided the impetus to develop new agents - isoflurane and desflurane - with properties that lower their toxic potential. The result has been improved safety, but there is room for further improvement as our insight into toxicological mechanisms expands. 

The pharmacologic and toxicologic mechanisms of the calcium channel blockers are complex. They include interference with electrical conduction through the atrioventricular node, decreased myocardial contractility, and direct vasodilation. Calcium channel blockers also interfere with pancreatic release of insulin. 

Cyanamide is not expected to release cyanide as part of its mechanism of toxicity. The principal toxicological mechanism of cyanamide is inhibition of aldehyde dehydrogenase. Cyanamide can produce acetaldehyde syndrome with concurrent exposure to alcohol, resulting in symptoms that include vomiting, parasympathetic hyperactivity, difficulty in breathing, and confusion. 

Molecular biology has progressed to the point where many of the toxicological mechanisms are now understood on a molecular level. This chapter surveys these mechanisms. The reader is directed to texts on the subject for a comprehensive treatment of the areaJ1,2 ... 

Savolainen H. Toxicological mechanisms in acute and chronic nervous system degeneration. Acta Neurol Scand Suppl 1982 92 23-35. 

In this chapter we introduce various techniques for fabricating miniature cell culture devices and cell-based biosensors, provide examples of human and animal cells immobilized on the chip devices, and explain different approaches to pattern multiple types of cells on one device. The application of nano and micro techniques in precise control over the cellular microenvironment is discussed. Selective cell-based biosensors are described later in the chapter. Finally, we conclude that these novel cell culture systems, coupled with predictions from in silico mathematical modeling, can potentially improve predictions of human clinical responses and enable better understanding of toxicological mechanisms. 

We expect that these novel cell culture systems, coupled with predictions from in silico and mathematical modeling, will provide new insights into the toxicity of environmental and pharmaceutical chemicals, expand our understanding of toxicological mechanisms, and improve prediction of human clinical responses. 

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