Human compartment

This chapter considers the recently developed tools and the latest versions of the old tools. Some of the tools comprise not only the environmental compartments used on environmental risk assessment but also the human compartment necessary for human health risk assessment. For this reason, when summarizing the models, as described in the second part of this chapter, several characteristics of human compartment are discussed as well. However, a detailed description of human compartment together with a wide range of tools developed for exposure and human risk assessment is presented in the next chapter. 

Table 27.8 (continued) Proposed Toxaphene Criteria for Protection of Natural Resources and Human Compartment Allowable Concentration... 

Over the last six decades, however, increased use of antimicrobial drugs, not only in human medicine, but in other areas, such as veterinary medicine, agriculture, and fish farming, has had an enormous impact on the microbial society. Nearly everywhere, the numbers of susceptible strains have reduced and resistant strains or variants have increased in numbers. It has been repeatedly reported that the susceptibility profile of bacteria in any human compartment, such as the skin, intestine, and respiratory tract, is very different from what it was in the pre-antibiotic era, and even 15 years ago. The same trend is reported from hospitals and homes. Multidrug resistance, that is resistance to several antimicrobial drugs, is commonly found in bacteria that cause infections as well as in commensal organisms. 

Consumption of the product reduces the mortahty rate of the human compartment (HH) according to mHH/(l + alPF). The larger the IPF (IPF is the rate of flow of mass through the industrial process [no mass is resident] flow) the lower the human mortality rate. Flere, a is a constant meant to reflect the effectiveness or efficiency of the industrial process in reducing the human mortality rate. For details, please refer to [3]. In this model, the solid arrows represent transfers of mass solely because of biological or geological drivers, with no interference fixim humans. The dashed arrows represent a transfer of mass from the RP to the IRP that occurs as a by-product of human activities as before, including consumption (HH IRP) and production... 

For most situations and conditions in daily life, the human can be represented adequately by a simple model that is helpful for understanding human thermal regulation. The model has two thermal compartments (Fig 5.1). The... 

Physiologically based toxicokinetic models are nowadays used increasingly for toxicological risk assessment. These models are based on human physiology, and thus take into consideration the actual toxicokinetic processes more accurately than the one- or two-compartment models. In these models, all of the relevant information regarding absorption, distribution, biotransformarion, and elimination of a compound is utilized. The principles of physiologically based pharmaco/ toxicokinetic models are depicted in Fig. 5.41a and h. The... 

The processes of electron transport and oxidative phosphorylation are membrane-associated. Bacteria are the simplest life form, and bacterial cells typically consist of a single cellular compartment surrounded by a plasma membrane and a more rigid cell wall. In such a system, the conversion of energy from NADH and [FADHg] to the energy of ATP via electron transport and oxidative phosphorylation is carried out at (and across) the plasma membrane. In eukaryotic cells, electron transport and oxidative phosphorylation are localized in mitochondria, which are also the sites of TCA cycle activity and (as we shall see in Chapter 24) fatty acid oxidation. Mammalian cells contain from 800 to 2500 mitochondria other types of cells may have as few as one or two or as many as half a million mitochondria. Human erythrocytes, whose purpose is simply to transport oxygen to tissues, contain no mitochondria at all. The typical mitochondrion is about 0.5 0.3 microns in diameter and from 0.5 micron to several microns long its overall shape is sensitive to metabolic conditions in the cell. 

The quantification of kinins in human tissues or body fluids has been limited due to the inherent difficulties in accurately measuring the concentration of ephemeral peptides. Today HPLC-based and RIA/capture-ELA measurements are established to determine kinins in human plasma, liquor or mine. Serine protease inhibitors need to be added to prevent rapid degradation of the kinins in vitro during sample preparation. Kinins and their degradation products have been studied in various biological milieus such as plasma/ serum, urine, joint fluids, kidney, lung and skeletal muscle [2]. Under normal conditions, the concentration of kinins in these compartments is extremely low for... 

PCBs have been implicated in the decline of certain populations of fish-eating birds, for example, in the Great Lakes of North America. Although their use is now banned in most countries and very little is released into the environment as a consequence of human activity, considerable quantities remain in sinks (e.g., contaminated sediments and landfill sites), from which they are slowly redistributed to other compartments of the environment. There continues to be evidence that PCB residues are still having environmental effects, for example, on birds and fish. 

Water makes up about 60% of the lean body mass of the human body and is distributed in two large compartments. 

Lynch DR, Guttmann RP (2002) Excitotoxicity perspectives based on N-methyl-D-aspartate receptor subtypes. J Pharmacol Exp Ther 300(3) 717-723 Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (1995) Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity. Ann Neurol 37(3) 373-380 Mamdouh Z, Chen X, Kerini LM, Maxfield FR, Muller WA (2003) Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesis. Nature 421(6924) 748-753... 

The overall results and individual PBPK models for trichloroethylene are discussed in this section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. Several PBPK models have been developed for inhaled trichloroethylene. In an early model by Fernandez et al. (1977), the human body was divided into three major compartments or tissue groups the vessel-rich group (VRG), muscle group (MG), and adipose tissue (fat) group (FG). The distribution of trichloroethylene in these... 

PBPK models have also been used to explain the rate of excretion of inhaled trichloroethylene and its major metabolites (Bogen 1988 Fisher et al. 1989, 1990, 1991 Ikeda et al. 1972 Ramsey and Anderson 1984 Sato et al. 1977). One model was based on the results of trichloroethylene inhalation studies using volunteers who inhaled 100 ppm trichloroethylene for 4 horns (Sato et al. 1977). The model used first-order kinetics to describe the major metabolic pathways for trichloroethylene in vessel-rich tissues (brain, liver, kidney), low perfused muscle tissue, and poorly perfused fat tissue and assumed that the compartments were at equilibrium. A value of 104 L/hour for whole-body metabolic clearance of trichloroethylene was predicted. Another PBPK model was developed to fit human metabolism data to urinary metabolites measured in chronically exposed workers (Bogen 1988). This model assumed that pulmonary uptake is continuous, so that the alveolar concentration is in equilibrium with that in the blood and all tissue compartments, and was an expansion of a model developed to predict the behavior of styrene (another volatile organic compound) in four tissue groups (Ramsey and Andersen 1984). 

Using high performance liquid chromatography plus GC-MS and a compart-mental model, the absorption of p-carotene was estimated as 22% (17.8% as intact P Carotene and 4.2% as retinoids) after ingestion of a single high dose of p-carotene-d8 (40 mg) in oil by one adult subject. This value was close to the 9 to 17% values obtained in earlier human lymph cannulation studies using radioisotopes. ... 

Thus the question arises as to what forms of haem proteins and transition metals are available in vivo that are capable of mediating the formation of damaging initiating or propagating species, since the majority of the iron and haem proteins in the human body are protected in vivo from exerting pro-oxidant activities by their compart-mentalization within their functional locations in the haem and non-haem iron-containing proteins and enzymes. 

Table 3-5. Reference Values of Parameters for the Compartment Model to Represent Time-dependent Particle Transport from the Human Respiratory...

Durbin and Schmidt (1985) proposed a model for tissue distribution and excretion of absorbed americium in humans. A unique feature of this model is that transfers from plasma to tissues are assumed to be instantaneous therefore, a central plasma (and blood) compartment is not included in the model (see Figure 3-10). Tissue compartments included in the model are slow and fast turnover bone compartments, representing cortical and trabecular bone, respectively liver and slow and fast turnover for other soft tissue compartments. Excretion pathways include urine and feces. Urinary excretion is represented as a sum of the contributions from bone, liver, and other soft tissues. Fecal americium is assumed to be excreted from the liver. 

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