Xenobiotics definition

Phosphatases are numerous and important enzymes (see also Chapt. 2). They are classified as phosphoric monoester hydrolases (phosphatases, EC 3.1.3), phosphoric diester hydrolases (phosphodiesterases, EC 3.1.4), triphosphoric monoester hydrolases (EC 3.1.5), diphosphoric monoester hydrolases (pyrophosphatases, EC 3.1.7), and phosphoric triester hydrolases (EC 3.1.8) [21] [63]. Most of these enzymes have a narrow substrate specificity restricted to endogenous compounds. However, some of these enzymes are active toward xenobiotic organophosphorus compounds, e.g., alkaline phosphatase (EC 3.1.3.1), acid phosphatase (EC 3.1.3.2), aryldialkylphosphatase (para-oxonase (PON1), EC 3.1.8.1) and diisopropyl-fluorophosphatase (tabunase, somanase, EC 3.1.8.2) [64 - 70]. However, such a classification is far from definitive and will evolve with further biochemical findings. Thus, a good correlation has been found in human blood samples between somanase and sarinase activities on the one hand, and paraoxonase (PON1) type Q isozyme concentrations on the other [71]. 

The definition of a poison, or toxicant, also involves a qualitative biological aspect because a compound, toxic to one species or genetic strain, may be relatively harmless to another. For example, carbon tetrachloride, a potent hepatotoxicant in many species, is relatively harmless to the chicken. Certain strains of rabbit can eat Belladonna with impunity while others cannot. Compounds may be toxic under some circumstances but not others or, perhaps, toxic in combination with another compound but nontoxic alone. The methylenedioxyphenyl insecticide synergists, such as piperonyl butoxide, are of low toxicity to both insects and mammals when administered alone but are, by virtue of their ability to inhibit xenobiotic-metabolizing enzymes, capable of causing dramatic increases in the toxicity of other compounds. 

The success of the project to describe the human genome along with progress in the definition of polymorphisms in human xenobiotic-metabolizing enzymes and other proteins will certainly lead to the ability to define populations and individuals at increased risk from a particular chemical insult. This ability will be extended and put on a more mechanistic basis by advances in the new disciplines of proteomics and metabonomics. 

Since a large number of xenobiotics are metabolized to free radicals, an overall view of this area is not obvious. By definition, free radical metabolites must exist free of the enzyme, and, therefore, enzyme-xenobiotic transition states with free radical character such as are thought to exist in the cytochrome P-450 substrate complex are excluded. It follows that if the rate of formation of the free radical is fast enough, it can be detected with electron spin resonance, and will have the same ESR spectrum as the free radical made by purely chemical means. 

Sawicki, R.M., Definition, detection and documentation of insecticide resistance, in Combating resistance to xenobiotics Biological and chemical approaches, Chichester, England Ellis Horwood, 1987, p. 105. 

For the purposes of this chapter, reproductive toxicity will refer to any manifestations of xenobiotic exposure, including endocrine disruption (see discussion below), reflecting adverse effects on any of the physiological processes and associated behaviors and/or anatomical structures involved in animal reproduction or development (Figure 36.1). This is a fairly broad definition which encompasses developmental toxicity, as well as any toxic... 

Xenobiotics Xenobiotics are defined as exogenously administered or endogenously produced foreign substances that impair and ultimately damage the ecology and homoeostasis of cellular systems. This definition also includes medicinal preparations, (s. p. 52)... 

Data shown in Table 3 indicate a definite increase of chlorine content in the products of interaction between HAs and chlorophenoxy compounds, thus suggesting the occurred incorporation of xenobiotic chlorinated units into the humic polymer. 

For all these reasons, PBPK models are and will continue to be increasingly used in toxicology. This is especially true in risk assessment studies since better definition of the internal tissue dose, may contribute to reduce the uncertainty associated with extrapolation to human beings of responses observed in animal toxicity studies in which animals usually receive high doses of xenobiotics by routes often different from the one(s) anticipated in human exposures. 

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