Accumulation in the Organism

A metal ion must interact with a biological surface before being taken up and having an effect. Such interactions can be conveniently modeled with the Langmuir model. 

FIGURE 1.1 Trends in adsorption metrics as a function of coordination chemistry for alkali and alkali earth (class [a]) metals and the alga, Spirogyra sp. (top panel), and a series of class (a), intermediate, and class (b) metals and the bacterium, Saccharomyces cerevisiae (bottom panel). The units of K in the top panel are M from an algal suspension with 0.5 x 10 to 0.1 X10 M of dissolved metal. 

FIGU RE 1.2 Ovchinnikov s (1979) estimated stability constants for valinomycin complexes (in methanol solvent) with a series of class (a) metals and one class (b) metal (Ag ) were plotted against the AN(AIP) metric. The AN(AIP) metric combines the influences of ion size or inertia and atomic ionization potential (Newman et al. 1998). As is clear in this figure, valinomycin is very selective for K+ and bonding with the one class (b) metal ion is more stable than might have been expected from the class (a) metal ion pattern. 

FIGURE 1.4 The percentage of injected metal bound to gastropod hemolymph protein as related to the metal ion softness. 

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An especially cogent argument for the acetaldehyde theory is the fact that considerable amounts of pyruvic acid accumulate in the organism... 

The presence of lead and hexavalent chromium in these products is of chronic hazard concern and the EU has classified these pigments as harmful substances. Lead is soluble at stomach-acid concentrations and can accumulate in the organism. The results of a high lead intake include inactivation of enzymes and disturbances in the synthesis of haemoglobin. Hexavalent chromium compounds are considered to be carcinogenic. For these reasons the usage of lead chromate pigments has declined considerably in recent years. 

Bioaccumulative A chemical is bioaccumulative if, when ingested or absorbed by an organism, it is not completely cleared and so accumulates in the organism, leading to increased time-integrated exposure of cells and tissues. 

Thus, the frequency of exposure is also an important factor because the concentration to which the organism, and more particularly the target site, is exposed can remain relatively constant or increase. As illustrated above, this is because repeated exposure may lead to accumulation of the chemical, depending on its half-life (see chap. 3), such that intake exceeds elimination. Thus the chemical can accumulate in the organism because of saturation of metabolism or elimination or because its physicochemical properties determine that the chemical becomes sequestered in tissues such as fat. Another factor in toxicity from chronic exposure can be the ability to repair damage or replace macro molecules and the speed with which this is done. If damage is not repaired or macro molecules are not replaced before the next exposure, then accumulation of damage or effect can also occur. 

FIGURE 8.1 Scheme of formation of radiolysis products accumulated in the organic phase of the extraction system TBP- -paraffin-HN03 aqueous solution. (Drawn from data in Refs. (21, 22, 34, 43, 50).)... 

Mode of action Several mechanisms have been identified by which chloroquine kills the organism after accumulating in the organism. 

Self-monltorlng on the part of the patient makes it possible to identify the beginning of water accumulation in the organism (> 1 litre), a reduced lactulose effect (which is inadequate for intestinal detoxification) and/or a latent phase of hepatic encephalopathy. In such cases, immediate outpatient treatment is generally reliable and swift in its therapeutic success. 

Reports of adverse reactions to povidone primarily concern the formation of subcutaneous granulomas at the injection site of intramuscular injections formulated with povidone. Evidence also exists that povidone may accumulate in the organs of the body following intramuscular injection. ... 

Attention must be drawn to the possibility of accumulation in the organism after frequent administration. 

The herbicidal effect of paraquat is attributable to the formation of superoxide anion (02 ). Superoxide anion is very toxic compound and is formed by the reaction of oxygen with paraquat radical (paraquat ). Plants, algae, and cyanobacteria have ferredoxin-NADP reductase to form NADPH for the reduction of carbon dioxide (see below). The chemolithoautotrophs also have NAD(P) (NAD and NADP) reductase to form NAD(P)H for the reduction of carbon dioxide. Paraquat [mid-point redox potential at pH 7.0 (Emj 0) = -0.43 V] radical is produced when paraquat is reduced by the catalysis of ferredoxin-NAD(P) reductase or NAD(P) reductase, which catalyzes the reduction of many compounds with of around -0.4 V. Although the aerobic organisms (and even many anaerobic organisms) have superoxide dismutase (SOD) which detoxifies superoxide anion in cooperation with catalase [ascorbate peroxidase in the case of plants (Asada, 1999)], the anion accumulates in the organisms when it is over-produced beyond the capacity of SOD. 

Although the PhaC is the key enzyme of PHA biosynthesis, it is not directly linked to the central metabolism. The enzyme must be provided with hydroxyacyl-CoA thioesters as substrates and for this a link between the central metabolism and the PhaC must exist or must be established [42]. If this is not ensured, no PHAs will be synthesized and accumulated in the organisms although a PhaC is... 

Benzimidazole derivatives are not toxic to mammals. Their acute oral lOj is generally higher than 2500 mg/kg for rats. Below 400 mg/kg subchronic toxicity cannot be detected in 90 days. They are not hazardous to bees and are toxic only above 100 mg/kg to fish. The active substances do not accumulate in the organism. Rats and dogs excrete 99% of the benomyl administered orally in the urine and feces within 72 hours. 

On the basis of long experiences and an immense amount of investigative material, phenoxy herbicides have been judged to be medium acute toxic and nonpersistent, and it has been determined that they do not accumulate in the organism. They are relatively toxic to fish and to organisms that serve as food for fish, while their normal use does not involve hazards for wildlife (Rowe and Hymas, 1954 Erne, 1975). They are generally hazardous to bees, so that their use is not permitted on flowering weeds. 

Following extraction, the crude plant extracts are often subjected to one or more liquid-liquid phase partitioning steps. Ethyl acetate and water are most frequently utilized with the resveratrol oligomers readily accumulating in the organic phase [45,71,84,86,92,96,106]. In other cases, more elaborate partitioning schemes have been used such as... 

Vitamin E, like other lipids, is digested and absorbed only in the presence of bile. Bile functions as the lipid emulgent and makes absorption of lipids in the intestinal epithelium possible. Vitamin E can be absorbed 30 to 90% while its assimilability amounts to about 30%, the rest being excreted from the organism. In adults, the concentration of a-T in plasma should exceed 30 pmol/L (Biesalski, 1997). A diet rich in vitamin E allows its accumulation in the organism, for example, in the liver, pituitary gland, and adrenals, as well as in adipose and muscular tissues. Vitamin E... 

In mammals, birds, insects, and some plants, compounds of the kynurenic acid group are end products of tryptophan metabolism. They are either excreted with the urine (E 1) or are accumulated in the organism. 8-Hydroxyquinaldic acid methyl ester is a feeding deterrent and aseptic of certain water beetles (E 5.1). 

Cadmium is a highly cumulative toxin with a biological half-life exceeding 10 years in man. It accumulates in the organism with age, particularly in the liver and in the kidneys, which contain about 50% of the amount stored in the organism (Friberg et al. 1979). 

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