Biokinetic processes

For information on physicochemical properties, toxic potential and potency, environmental distribution and fate, and biokinetic processes... 

The Pb uptake module, where Pb uptake is indexed as pg Pb absorbed per day, is the interface between the exposure module and the biokinetic processing of absorbed Pb quantities to provide an output as PbB, in the form of a probabilistic expression. The daily amounts of absorbed Pb are calculated for each environmental medium through computations of Pb levels in the medium, amount of the medium ingested, and the bioavailability or fraction of daily Pb intake that is absorbed. Bioavailability can be the default selection diet and water Pb uptake of 50% soils and dusts, 30%. Alternatively, users can select bioavailabilities other than default if additional data exist for other percentage uptake rates. The specific topic of bioavailability of lead as a function of environmental medium containing Pb was described in the previous chapter. 

Numerous observations of non-linear relationships between PbB concentration and lead intake in humans provide further support for the existence of a saturable absorption mechanism or some other capacity limited process in the distribution of lead in humans (Pocock et al. 1983 Sherlock et al. 1984, 1986). However, in immature swine that received oral doses of lead in soil, lead dose-blood lead relationships were non-linear whereas, dose-tissue lead relationships for bone, kidney and liver were linear. The same pattern (nonlinearity for PbB and linearity for tissues) was observed in swine administered lead acetate intravenously (Casteel et al. 1997). These results suggest that the non-linearity in the lead dose-PbB relationship may derive from an effect of lead dose on some aspect of the biokinetics of lead other than absorption. Evidence from mechanistic studies for capacity-limited processes at the level of the intestinal epithelium is compelling, which would suggest that the intake-uptake relationship for lead is likely to be non-linear these studies are discussed in greater detail in Section 2.4.1. 

The biokinetic modeling of physiological, pharmacological, and toxicological processes. 

Before the details of a particular reactor are specified, the biochemical engineer must develop a process strategy that suits the biokinetic requirements of the particular organisms in use and that integrates the bioreactor into the entire process. Reactor costs, raw material costs, downstream processing requirements, and the need for auxiliary equipment will all influence the final process design. A complete discussion of this topic is beyond the scope of this chapter, but a few comments on reactor choice for particular bioprocesses is appropriate. 

Since a risk assessment for a particular chemical is related to the exposure scenario, toxicity data generated in in vitro systems need to be translated to a dose or a dosage regime for an intact organism. This process, referred to as QIVTVE , includes an interpretation of the chemical s biokinetic behavior. This enables the conversion of an in vitro-derived concentration-effect relationship to a dose-response relationship in vivo. The processes involved in this reverse dosimetry are described in Chap. 24. The development of physiologically based biokinetic (PBBK) models [19] is crucial in this process [13, 20]. 

Since many biokinetic and toxicodynamic processes are determined by the concentration of a chemical that is freely available, it is also necessary to quantify the processes of protein binding in the in vitro systems and indicate where these processes deviate from the ones in vivo [30],... 

Major run-off events are a feature of most intertidal areas associated with estuaries. The high flows may limit nutrient processing due to decreased water residence times however, if concentration increases with flow, nutrient processing may increase depending only on the biokinetics of the process. The concentration of nitrate in river water tends to increase with... 

The model equations employing biokinetics of Groot et al. and PV data of Gudernatsch et al. were solved using an iterative procedure in a computer program to optimize process parameters for minimum total cost. The hybrid PV + distillation process yields better utilization of the sugar in the feed because of decrease in inhibition. The results indicated that the raw material and membrane fixed cost contribute more than 80% of the direct production cost. Further, the direct production cost of EtOH cost for the hybrid process was found to be 12%-16% lower than the conventional process. 

Three main areas are associated with the flow of further work bioreactors, kinetics, and conversion. This pathway will also be followed in this book (Chapters 3-6). (Chapter 4 is a detailed look at the problems associated with the coupling of kinetic and transport phenomena in the formulation of an analysis of process kinetics.) The goal in each of the three main areas is the establishment of a mathematical model. In correspondence with the main objective of this book (see Sect. 1.2), the hallmark of this procedure lies in the careful formulation of the biokinetics. Basic research is primarily interested... 

Figure 2.22. Schematic representation of the basic experimental situation in bio-process/bioreactor analyses, where the interactions between physical transports (kj ) and biokinetic rates (kh) in the liquid phase are thought to be representative for the process rates in the solid phase of cell mass (kf,). At the same time, response lags of measuring electrodes (k ) have to be taken into account. G, gas phase L, liquid phase S, solid phase or substrate E, enzyme or electrode I, intermediary metabolites or products P, end product N, nucleus R, ribosomes M, mitochondria a, anabolism jS, catabolism Fq = gas flow rate n = agitators rotational speed.

No doubt additional effort is needed in the kinetic analysis of a process to optimize a laboratory-scale bioreactor using the criteria listed in Table 4.3. The results, however, should justify the effort. Figure 4.11 illustrates this problem showing that biokinetics seems to be dependent from the type of bioreactor. Productivity is plotted for a stirred tank with increasing rotational speed n and is compared with that in the cycle tube cyclone reactor (Ringpfeil, 1980). 

Figure 4.22. Batch process evaluation using the integrated form of biokinetics (see Equs. 4.36a-e) with the aid of a graphical trial and error method.

Sensors are fundamental components of all sensor networks, and their quality depends heavily on industry advances in signal conditioning and processing, microelectrome-chanical systems, and nanotechnology. Sensors are classified into three categories physiological, biokinetic, and ambient environmental sensors. 

Toxicokinetics describes the biokinetics of toxic substances. It includes the kinetic processes for toxic substances which govern the movement into, within, and from the bodies of human populations. The overall lead toxicoki-netic process includes (1) the uptake, i.e., absorption rate, of lead into the bloodstream from various body compartments such as the lung or G1 tract (2) movement within the bloodstream followed by transport internally to target tissues and their cellular components (3) retention within one or more tissues and finally (4) excretion from the body by various systemic pathways. Older literature made incorrect reference to lead toxicokinetics as lead metabolism, but the latter term is more correctly employed with toxic substances undergoing actual chemical transformation within such processes as addition or removal of chemical groups and oxidative or reductive changes. 

A central biokinetic parameter governing the operation of this compartmental model is the compartmental transfer time. These times cover Pb movement among the various compartments set forth in Figure 9.3. Times are based on plasma Pb. At steady state, the ratios of Pb masses in tissue compartments to plasma Pb masses are equivalent to the ratios of transfer times from tissues to plasma and ECF, and from plasma/ECF to tissues. Transfers are also assumed to be from the central to tissue compartments by a first-order kinetic process (White et al., 1998). 

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