Showing papers in "Critical Reviews in Toxicology in 1981"

Naturally occurring toxic alkaloids in foods.

Abstract: (1981). Naturally Occurring Toxic Alkaloids in Foods. CRC Critical Reviews in Toxicology: Vol. 9, No. 1, pp. 21-104.

In vitro studies on the mode of action of the phorbol esters, potent tumor promoters, part 2.

Abstract: (1981). In Vitro Studies on the Mode of Action of the Phorbol Esters, Potent Tumor Promoters, Part 2. CRC Critical Reviews in Toxicology: Vol. 8, No. 3, pp. 199-234.

Saturable metabolism and its relationship to toxicity

Abstract: Metabolism plays a central role in regulating the toxicity of a variety of chemicals. Relatively innocuous substances can be converted to highly toxic metabolites. Conversely, toxic substances can be biotransformed to less harmful metabolites or be excreted, thus limiting their duration of biological action. Virtually all metabolism and many excretory processes utilize specific binding proteins, i.e., enzymes and carrier proteins. These metabolic and carrier-mediated excretory clearance pathways are capacity-limited, becoming saturated at sufficiently high substrate concentrations. Saturable metabolic clearance processes lead to dose-dependent pharmacokinetics for many chemicals. When dose-dependent pharmacokinetics prevail, internally significant parameters, such as area under the curve for concentration of toxicant at active sites and the amount of metabolite formed during inhalation exposure, are not linearly related to externally significant parameters such as administered dose or inspired concentration. Dose-response curves should relate observed effects to some internally significant parameter. Toxic response should often be indexed to area under the curve relationships or total amount metabolized, instead of dose or inspired concentration. The former parameters are complexly related to the latter. The nature of the relationship depends on the kinetic constants for metabolic and excretory clearance. Pharmacokinetic analyses of dose-dependent clearance mechanisms provide an understanding of how one transforms externally significant parameters to internally significant parameters under various exposure conditions. Consideration of metabolic clearance at the organ level illuminates the importance of physiological factors, showing unequivocally that blood flow may be rate-limiting for metabolism under many exposure conditions. Recognition of the potential for this behavior is essential to the proper design and evaluation of certain toxicological experimentation. Development of comprehensive pharmacokinetic descriptions of the influence of saturable clearance on delivery of active chemical to target sites augurs well for improving both intraspecies and interspecies extrapolation of toxicity data. This is a critical area of contemporary toxicology. Dose selection for chronic studies could also be improved by knowledge of the dose-dependence of pharmacokinetic parameters in proposed test species. The field of toxicology reviewed here represents an interface between pharmacokinetic research and studies on basic mechanisms of toxic action. It entails utilization of quantitative concepts to better understand the physiological and biochemical controls which regulate the expression of the toxicity of various chemicals. Much work remains to be accomplished in this exciting area of toxicological research. Some of the predictions of the pharmacokinetic analyses are still tentative and require more definitive experimentation...

Natural carcinogenic products of plant origin.

Abstract: (1981). Natural Carcinogenic Products of Plant Origin. CRC Critical Reviews in Toxicology: Vol. 8, No. 3, pp. 235-277.

The regulation of epidermal hyperplastic growth.

Abstract: (1981). The Regulation of Epidermal Hyperplastic Growth. CRC Critical Reviews in Toxicology: Vol. 9, No. 2, pp. 151-200.

Phospholipids of the lung in normal, toxic, and diseased states.

Abstract: The highly pulmonary concentration of 1,2-dipalmitoyl-sn-glycerol-3-phosphorylcholine (dipalmitoyllecithin) and its implication as an important component of lung surfactant have promoted investigation of phospholipid metabolism in the lung. This review will set the contents including recent informations for better understanding of phospholipid metabolism of the lung in normal state (physiological significances of lung phospholipids, characteristics of phospholipids in lung tissue and alveolar washing, biosynthetic pathways of dipalmitoyllecithin, etc.) as well as in toxic states (pulmonary oxygen toxicity, etc.) and in diseased states (idiopathic respiratory distress syndrome, pulmonary alveolar proteinosis, etc.) Since our main concern has been to clarify the most important route for supplying dipalmitoyllecithin, this review will be focused upon the various biosynthetic pathways leading to the formation of different molecular species of lecithin and their potential significance in the normal, toxic, and diseased lungs.

An interpretative literature analysis evaluating the effects of power plant chlorination on freshwater organisms

Abstract: The extensive use and possible ecological effects of chlorine have prompted several reviews on chlorine toxicity to aquatic organisms. Although numerous data are available on the ecological effects of chlorine, an interpretative analysis and synthesis of the current data base is lacking. The first objective of this study was to collect, synthesize, and review chlorine data related to biofouling control in freshwater thermoelectric power plants. The second objective of this literature analysis was to identify deficiencies in available data in order to recommend future research which will enable better evaluation of ecological effects of power plant cooling water chlorination in freshwater systems.