Toxicant metabolism

The special topics discussed are (i) the biological aspects of heterocyclic compounds, i.e. their biosynthesis, toxicity, metabolism, role in biochemical pathways, and their uses as pharmaceuticals, agrochemicals and veterinary products (ii) the use of heterocyclic compounds in polymers, dyestuffs and pigments, photographic chemicals, semiconductors and additives of various kinds and (iii) the use of heterocyclic compounds as intermediates in the synthesis of non-heterocyclic compounds. 

Effects of Metaboiism on Toxicity. Metabolism plays an important role in the toxicity of trichloroethylene because many of its metabolites are themselves toxic. Many differences among species in their responses to trichloroethylene exposure may be attributed to differences in the rates at which they metabolize the parent compound (Dekant et al. 1986b Prout et al. 1985). 

Ahlborg UG, TM Thunberg (1980) Chlorinated phenols occurrence, toxicity, metabolism, and environmental impact. CRC CritRev Toxicol 1 1-35. 

Chengelis CP, Neal RA. 1980. Studies of carbonyl sulfide toxicity Metabolism by carbonic anhydrase. Toxicol Appl Pharmacol 55 198-202. 

Clark, D.G., and M.H.Litchfield. 1969. The toxicity, metabolism, and pharmacologic properties of propylene glycol 1,2-dinitrate. Toxicol. Appl. Pharmacol. 15 175-184. 

The final class of pharmacotherapy drugs alters the metabolism of certain target drugs, thereby causing a build up of toxic metabolic products that make a person feel extremely ill. The best known of these metabolism-modifiers is Antabuse (disulfiram), a drug primarily used to discourage people from drinking alcohol. 

The rat will usually be the species of choice for the standard oncogenicity study because there is greater confidence in its predictivity for human carcinogenicity than the mouse or hamster. The species chosen, however, should be the most appropriate based on considerations such as pharmacology, repeated-dose toxicity, metabolism and toxicokinetics. 

Acetazolamide, others Inhibition of the enzyme prevents dehydration of H2CO3 and hydration of CO2 Reduces reabsorption of HC03 in the kidney, causing self-limited diuresis hyperchloremic metabolic acidosis reduces body pH, reduces intraocular pressure Glaucoma, mountain sickness, edema with alkalosis Oral and topical preparations available duration of action 8-12 h Toxicity Metabolic acidosis, renal stones, hyperammonemia in cirrhotics... 

Some chemicals that strongly bind to biological receptors (ligands) can produce toxicity directly. However, most toxic chemicals are not intrinsically reactive and must be metabolized to reactive intermediates that often covalently bind to macromolecules (DNA, proteins, etc.), and, if present at a sufficient level, lead to toxicity. Metabolism generally serves to make lipophilic compounds more hydrophilic in order to facilitate excretion through the liver and into the bile for excretion into the feces or through the kidneys and into the urine. This process generally... 

Although mechanisms of toxicity for specific chemicals or classes of chemicals may not be published as such, not infrequently there exists throughout the scientific literature sufficient toxicity, metabolism, and other biochemical studies on an existing chemical or of chemicals in its class. The bits of information contained in these studies are much like pieces of a puzzle, that when carefully analyzed and correctly placed together form a clearer and more complete picture that may reveal the mechanism of toxicity. 

Timbrell JA, Facchini V, Harland SJ, et al. Hydralazine-induced lupus is there a toxic metabolic pathway Eur J Clin Pharmacol 1984 27 555. 

It is interesting to note that a number of researchers have attempted, more or less successfully, to construct reliable mathematical models which combine structural elements and experimental data to predict the toxicities of new substances not yet experimentally tested for humans and other species.110152 Furthermore pharmacology, toxicity, metabolism and enzyme-inhibiting effects of fluorine-containing aromatic systems (e.g., anilines, ben-zothiadiazines, butyrophenones, corticoids, phenothiazines, steroids, uracils) have been discussed in depth in the literature.153-156... 

Surh, Y.J. and Lee, S.S. Capsaicin, a double-edged sword toxicity, metabolism, and chemopreventive potential, Life Sci. 1995, 56, 1845-1855. 

Ahlborg, U. G. Thurnberg, T. M. (1980). Chlorinated phenols occurrence, toxicity, metabolism, and environmental impact. Critical Reviews in Toxicology, 7, 1-35. Allard, A-S., Remberger, M. Neilson, A. H. (1987). Bacterial O-methylation of halogen substituted phenols. Applied and Environmental Microbiology, 53, 839—45. 

Aflatoxin B, is regarded as hepatocarcinogen and genotoxic (2,9). Exhaustive reviews on toxicity, metabolism, and epidemiological studies are provided by IARC and more recently by several authors (2,4). 

One week after starting to take metformin 850 mg in divided dose a 74-year-old man became confused and disoriented and had speech abnormalities and bilateral horizontal gaze-evoked nystagmus. Electroencephalography suggested a toxic-metabolic... 

Lactic acidosis is a severe and potentially fatal form of mitochondrial toxicity. Metabolic stress or vitamin deficiencies (riboflavin, carnitine) might provoke it. There is suggestive evidence of clinical benefit with riboflavin therapy (846). 

Is an ingredient, inpurity, degradation product, metabolite, or radioactive isotope of a substance described by paragraph (1) of this definition, or some other substance related to a substance described by that paragraph, which is used in the study to assist in characterizing the toxicity, metabolism, or other characteristics of a substance described by that paragraph. 

Wada O, Manabe S, Iwai H, et al. 1982. [Recent progress in the study of analytical methods, toxicity, metabolism and health effects of organotin compounds.] Sangyo Igaku 24 24-54. (Japanese)... 

A major physiological function of the kidney is to remove toxic metabolic wastes and excess fluids from the blood stream. This function may be impaired through chronic degeneration or as a result of injury. Hemodialysis is the most commonly prescribed means of blood purification for end-stage renal disease. The worldwide dialysis patient population approached 1 million at the end of the 20th century. 

Calcium and magnesium are very abundant in soils, and soils deficient in Ca are rare, calcium status is maintained when lime is added to correct acidity. Plant cells contain relatively large concentrations of Ca, but most of it is bound in the cell-wall as the pectate (about 60%) or sequestered in different organelles (Clarkson, 1984). Ca affects the permeability of the cytoplasmic membrane and its deficiency leads to malformation of the growing parts of the plant. Hewitt and Smith (1975) have discussed the early experiments on the morphological effects of Ca deficiency. Calcium is often found in combination with organic acids, for example oxalic acid, a soluble, toxic metabolic by-product is converted to insoluble calcium oxalate. 

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