Toxicity cell membrane-associated

The primary routes of entry for animal exposure to chromium compounds are inhalation, ingestion, and, for hexavalent compounds, skin penetration. This last route is more important in industrial exposures. Most hexavalent chromium compounds are readily absorbed, are more soluble than trivalent chromium in the pH range 5 to 7, and react with cell membranes. Although hexavalent compounds are more toxic than those of Cr(III), an overexposure to compounds of either oxidation state may lead to inflammation and irritation of the eyes, skin, and the mucous membranes associated with the respiratory and gastrointestinal tracts. Skin ulcers and perforations of nasal septa have been observed in some industrial workers after prolonged exposure to certain hexavalent chromium compounds (108—110), ie, to chromic acid mist or sodium and potassium dichromate. 

This reduction in self-aggregated AmB and the stability of the formulation suggested that LC-AmB could be a useful pharmaceutical formulation because it is generally accepted that the origin of toxicity toward mammalian cell membranes is free, self-associated AmB (2). 

Studies carried out with complete cells in vivo, cell membranes and other cell fractions point to the selective oxidation of phosphatidylserine (26) to a hydroperoxide (PS-OOH) on oxidative stress caused by toxic agents such as H2O2, t-BuOOH and cumyl hydroperoxide (27). Formation of PS-OOH is observed during apoptosis. These phenomena are important because of the cytotoxic effects of various peroxides used in commercial products coming into direct contact with the human body, as is the case of epidermal keratinocytes in contact with cosmetic formulations" ". The toxic effects of f-BuOOH are associated with vasoconstriction and damage to the vascular smooth muscles ". Global determination methods for primary lipid oxidation products are discussed in Section IV.B. 

The cell membranes are predominantly a lipid matrix or can be considered a lipid barrier with an average width of a membrane being approximately 75 A. The membrane is described as the fluid mosaic model (Figure 6.2) which consist of (1) a bilayer of phospholipids with hydrocarbons oriented inward (hydrophobic phase), (2) hydrophilic heads oriented outward (hydrophilic phase), and (3) associated intra- and extracellular proteins and transverse the membrane. The ratio of lipid to protein varies from 5 1 for the myelin membrane to 1 5 for the inner structure of the mitochondria. However, 100% of the myelin membrane surface is lipid bilayer, whereas the inner membrane of the mitochondria may have only 40% lipid bilayer surface. In this example the proportion of membrane surface that is lipid will clearly influence distribution of toxicants of varying lipophilicity. 

Toxicants and their associated effects also disturb the balance in the peroxic-antioxidant system which results in the accumulation of free radicals. These generate changes in the structure and function bf cell membranes (Telitchenko, 1974). As a result, the phospholipid bilayer of the membrane is destroyed, with fatal consequences (Sidorov, 1983). This phenomenon may be the cause of destruction of muscular tissue of fish. The reproductive system of fish is the part most susceptible to the influence of toxicants. Generative metabolism is the first to be affected by the adverse changes in the environment, which throws the entire reproductive cycle of a population into disorder. 

An important alcohol in toxicology studies is w-octanol, CH3(CH2)6CH2OH. This compound is applied to the measurement of the octanol-water partition coefficient, which is used to estimate how readily organic toxicants are transferred from water to lipids, a tendency usually associated with ability to cross cell membranes and cause toxic effects. As just one example, the octanol-water partition coefficient can be used to estimate the tendency of organic compounds to be taken up from water to the lipid gill tissue of fish. 

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