Pathways of Toxicity

Once a chemical enters the body of an animal (based on the route of entry), the chemical is subjected to metabolism by a variety of mechanisms. The toxicity of many chemicals is dependent on the metabolic rate and pattern of the system. Many tissues are capable of metabolizing substances. However, the maximum activities have been found to occur in the liver, followed by the lung, the intestine, the skin, and the kidneys. The nature of the chemical interactions, biochemical interactions, and metabolic transformations help to determine the toxicity of the chemical. A number of authors have written reviews about the biotransformation of many substances.19,25 28 

TABLE 2-2 Enzymes in Organs/Tissues of Rat and Metabolic Activities 

TABLE 2-3 Subcellular Fractions and Metabolizing Enzymes Associated  

Name of Enzymes Cytosol Microsomes Mitochondria Residues  

5 nmol of conjugated styrene-oxide/mg microsomal protein/min. 

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Key words Complexity, Computational models, In vitro models, Pathways of toxicity, Pharmacodynamics, Pharmacokinetics, Prediction, Omics data integration, Quantitative extrapolation, Toxicity, Variability... 

As discussed in the introduction, there are an innumerable numbCT of environmental chemicals for which little or no toxicity information is available and for many others for which it is inadequate. HTS studies could be invaluable at three related areas. First, they could identify those chemicals with the greatest potential toxicity and hazard which would then be prioritized for further testing. Second, they may be able to identify pathways of toxicity. Third, they may be able to identify and quantify metabolic pathways. 

Figure 10. Physiological pathways of toxicants in the body Manahan, 1994). Toxicant Protoxicant...

The many factors that affect the pathways of toxic materials in ecosystems are not well known. Therefore, it is difficult to predict exactly how and when such materials may enter the foodchain and to quantify the magnitude of their harmful effects. Faced by the actual and potential threat to public health, the most reasonable policy is to prevent the potential entry of the toxic materials into ecosystems at the source. 

The AHR Regulates Pathways of Toxicity Involving Metabolism of the Ligand... 

Also in all types of solid and liquid food assessment of the levels of toxic heavy metals has become a significant task in food control for securing public health, as for the overwhelming part of the population, which is not specifically exposed by occupation or other reasons such as metal implants, food is the most important potential and actual ingestion pathway of toxic heavy metals. 

An important aspect of ecotoxicology involves the pathways of toxicants into ecosystems and is very much tied with environmental chemistry. Toxic substances are transferred among the five environmental spheres as shown in Figure 2.22. The greatest concern is with the transfer of toxic substances into the biosphere, which can occur from water, air, the geosphere, and the anthrosphere. An important phenomenon is bioaccumulation in which toxic substances accumulate in tissue. The... 

Reactive carbonyls are formed as a normal part of oxidative metabolism The production and accumulation are enhanced in diabetes, due to a combination of chronic hyperglycemia and oxidative stress where they play a significant role in the development and progression of diabetic complications Increased accumulation of toxic carbonyls is also believed to play a role in a number of other conditionsMost research has focused on the enzymatic detoxification pathways of toxic carbonyls However, less attention has been paid to the excretion of carbonyls in the urine. 

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