The Basis for Tolerance

Gawronski, S.W., L.C. Haderlie, and J.C. Stark (1987). Metribuzin metabolism as the basis for tolerance in barley (Hordeum vulgare L.). 

After acceptable design tolerances have been agreed to by all parties, then these become the basis for system design and unit acceptance criteria. 

These SPI tables can also be used as the basis for establishing standards for molded products between the designer, molder, and customer. Users will find that two separate sets of values are represented. Commercial values represent common production tolerances that can be achieved at the most economical level. Fine values represent closer tolerances that can be held, but at a greater cost. The selection of one or the other will depend on the application under consideration and the economics involved. 

There are two criteria to use as the basis for evaluation. The design life of the shelf is determined by deciding what the product will tolerate in deflection and still be useful. This is combined with the cost effectiveness value the product must meet. For example, we can say that if it costs A" the life must be A months, if it costs Y it must last B months, and if it costs Z, it must last C months. This can be presented as a table or it can be graphed as the criteria range that it must meet. 

In their studies of the flavoprotein inhibitor, DPI, Bennett and colleagues [91, 120] found that DPI inhibited GTN-induced accumulation of cGMP to the same extent in aortae from naive and from GTN-tolerant animals. They argued that, if inactivation of flavoproteins is a major cause of tolerance, then there should be less scope for further, DPI-induced inactivation in tolerant animals, compared with naive ones. Their conclusion, accordingly, was that, while flavoproteins may participate in biotransformation of organic nitrates and associated vasodilation, their alteration cannot be the basis for nitrate tolerance. 

For many substances the body s own mechanisms for de-toxification and repair mean that low doses of some chemicals can be tolerated without experiencing any adverse effects. However, once a certain threshold has been exceeded then the degree of adverse effect is related to the dose. The highest dose at which no adverse effects are observed in the most susceptible animal species is identified as the No Observed Adverse Effect Level (NOAEL). The NOAEL is used as the basis for setting human safety standards for food additive Acceptable Daily Intakes (ADIs)4... 

The construction of carbocydic compounds by ring-annulation procedures frequently plays a prominent role in total synthesis. The tolerance of various functional groups in the zinc reagents employed in copper-catalyzed asymmetric 1,4-additions forms the basis for three novel catalytic enantioselective annulation methods discussed here. 

The basis for contrast agents derived from nutrional products was Intralipid, which had been prepared from phospholipids obtained from soy bean oil and egg yolk [86]. Intralipid was chemically modified by iodination into Intraiodol, which contained 50 mgl mbThe particles formed in the emulsion were mostly taken up by the hepatocytes and to a lesser extent by the RES [87,88]. Intraiodol was better tolerated than EOE-13 or its precursor, AG 60.99. The addition of cholesterol to Intraiodol resulted in NRI 757 with an iodine concentration of 42 mg mL b Further modifications by replacing the iodinated triglycerides of Intraiodol by ethiodized poppy seed oil and reducing the cholesterol content to... 

The most frequently used POD for threshold effects (Section 4.2) is the NOAEL (Section 4.2.4). This NOAEL is generally obtained from studies in experimental animals. If reliable human data are available to derive the NOAEL, this value is preferable to the NOAEL from experimental animals. Where a NOAEL cannot be derived, a LOAEL, if available, can be used. An alternative POD to the NOAEL/LOAEL is the benchmark dose (BMD) (Section 4.2.5). The tolerable intake can also, in some cases, form the basis as the POD. In this chapter, the POD will be denoted as a derived no-effect level (DNEL) in order to provide a general term for the various types of PODs that can form the basis for the risk characterization. 

When epidemiological studies form the basis for the risk assessment of a single chemical or even complex mixtures, such as various combustion emissions, it may be stated that in those cases the effects of combined action of chemicals have been incorporated. Examples can, for instance, be found in the updated WHO Air Quality guidelines (WHO 2000). Thus, the guideline value for, e.g., ozone was derived from epidemiological studies of persons exposed to ozone as part of the total mixture of chemicals in polluted ambient air. In addition, the risk estimate for exposure to polycyclic aromatic hydrocarbons was derived from studies on coke-oven workers heavily exposed to benzo[fl]pyrene as a component of a mixture of PAH and possibly many other chemicals at the workplace. Therefore, in some instances the derivation of a tolerable intake for a single compound can be based on studies where the compound was part of a complex chemical mixture. 

Proximate Analysis. This includes (he determination of total moisture, volatile matter, and ash and the calculation of fixed carbon for coals and cokes. The term Proximate" should not be confused with Ihe word approximate." since all Proximate Analysis tests are performed according lo rigid specifications and tolerances. Proximate Analysis results may be used lo establish the rank of coals to show the ratio of combuslible lo incombustible constituents, lo provide the basis for buying and selling coal, and to evaluate for beneliciation, or other purposes. 

The kinetics of the excretion of various silver compounds are well characterized in animals and limited human data exist for inhalation and oral exposure. Further study into (1) the underlying basis for observed species differences (2) quantitation of the elimination of dermally absorbed silver compounds and (3) the basis for observed interpersonal differences in tolerance would aid in identification of human subpopulations with varying susceptibilities to the toxic effects of silver. 

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