Multiple Site Responses

As discussed earlier, when the human body is exposed to toxic chemicals, multiple responses are induced. These responses are summarized in Table 4.9. 

It goes without saying that not all xenobiotics elicit all the responses listed in Table 4.9. Many toxins, however, do elicit multiple responses. Complicating the picture is the fact that not all bodily responses are primary ones, that is, direct reactions to the absorbed toxin. Secondary reactions can and do occur. Examples of these are a metabolite (and not parent compound) that is an actual toxin, OS inhibiting the action of a free radical inhibitor, and immunosuppression impacting metabolism. 

Even though a chemical is known to hit multiple organs, it does not always impact them all. 

MET metabolized by the body RB receptor binding END endocrine disrupting OS oxidative stress producing IM immune system suppressants. Xs denote elicited responses s denote no known response. 

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Abbyad P, Shi XH, Childs W, McAnaney TB, Cohen BE, Boxer SG (2007) Measurement of solvation responses at multiple sites in a globular protein. J Phys Chem B 111(28) 8269-8276... 

A metal cluster can be considered as a polynuclear compound which contains at least one metal-metal bond. A better definition of cluster catalysis is a reaction in which at least one site of the cluster molecule is mechanistically necessary. Theoretically, homogeneous clusters should be capable of multiple-site catalysis. Many heterogeneous catalytic reactions require multiple-site catalysis and for these reasons discrete molecular metal clusters are often proposed as models of metal surfaces in the processes of chemisorption and catalysis. The use of carbonyl clusters as catalysts for hydrogenation reactions has been the subject of a number of papers, an important question actually being whether the cluster itself is the species responsible for the hydrogenation. Often the cluster is recovered from the catalytic reaction, or is the only species spectroscopically observed under catalytic conditions. These data have been taken as evidence for cluster catalysis. 

Chapter 12, Section 2). It is generally accepted that the site responsible for the oxidation of dihydrogen and the reduction of protons is the nickel-containing assembly, possibly exploiting its capacity to shuttle between the multiple oxidation states Ni(III)/Ni(II)/Ni(I)/Ni(0). 

O Malley KL, Anhalt MJ, Martin BM, Kelsoe JR, Winfield SL, et al. 1987. Isolation and characterization of the human tyrosine hydroxylase gene identification of 5 alternative splice sites responsible for multiple mRNAs. Biochemistry 26 6910-6914. 

Trichotillomania, listed in the DSM-IV under Impulse Control Disorders Not Elsewhere Classified ( 252), is characterized by impulses to pull out one s hair, often involving multiple sites (scalp, eyebrows, and eyelashes commonly pubic, axillary, chest, and rectal areas less commonly) ( 253). Some clinicians have proposed that this condition is a variant of OCD, based on similarities in phenomenology, family history, and response to treatment. Originally thought to occur more frequently in females, it has become evident that it may affect males just as often. Many victims of this disorder have histories beginning in childhood and refractoriness to all attempted remedies. Co-morbidity of trichotillomania with mood, anxiety, substance abuse, and eating disorders is also common (254). Others have noted that trichotillomania may also coexist with mental retardation and psychotic disorders (see Appendix Q). 

Figure 1 This circular design suggests the possibility of dynamic interactions among the several well-established or suspected dietary factors that may influence drug response in humans. Arrows from each factor in the outer circle are wavy to indicate that effects of each dietary factor on drug response may occur at multiple sites and through different processes. The inner circle suggests that effects of dietary factors may be modified by many other environmental, as well as by genetic, factors.

The molecular basis for the evolution of distinct kdr mutations in different insects and arachnids remains unclear. Assuming that the pyrethroid binding site(s) (and/or the pyrethroid response domain) is composed of multiple amino acid residues, there are two ways by which different mutations can be selected in different insects and arachnids. First, the random mutation hypothesis mutation in any pyrethroid binding site/response domain affects pyrethroid toxicity without impacting normal sodium channel functional properties. Thus, selection of different mutations in different insects and arachnids is purely random. Second, the nonrandom mutation hypothesis mutation in any pyrethroid binding site/response domain affects pyrethroid toxicity, but some mutations also drastically alter normal sodium channel functional properties in one species, but not in another, presumably because of different sodium channel backbone sequences. That is, there may be severe fimess costs for some mutations, if placed out of their native protein context. 

The process safety professional will have primary interest in the data that indicates process safety system performance. This audience includes both process safety professionals at a given site as well as those who have multiple-site or corporate responsibilities. Process safety professionals often document and report selected metrics, but much of the raw data is generated by others, such as operations and maintenance personnel. It is important for the process safety professional to reach agreement with those generating the data on how that data is transmitted to him or her. Issues to resolve in developing a data exchange plan include, but are not limited to ... 

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