Drinking Water and Health, Volume 9 Selected Issues in Risk Assessment (1989) / Chapter Skim
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2 Pharmacokinetics and the Risk Assessment of Drinking Water Contaminants
2 Pharmacokinetics and the Risk Assessment of Drinking Water Contaminants
Pages 108-120
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From page 108... ...
Finally, it discusses the pharmacokinetics related to interactions of multiple chemicals found in drinking water. Some of the more uncertain aspects of risk assessment are related to the extrapolation of data from animals to humans, from one route of exposure to another, from high doses to low doses, and, for carcinogens, from one target organ to another.
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From page 109... ...
PHYSIOLOGICALLY BASED PHARMACOKINETICS A physiologically based pharmacokinetic model uses basic physiologic and biochemical data to describe the distribution and disposition of xenobiotic compounds in the body at any given time (NRC, 1987)
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From page 110... ...
1 DESIGN/' CONDUCT E) (TRAPt MOTION CRITICAL EXPERIMENTS TO HUMANS COMPARE TO KINETIC DATA l l FIGURE 2-1 Flowchart illustrating processes involved in physiologically based pharmacokinetics.
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From page 111... ...
In the past, the application of physiologically based pharmacokinetics was limited to a few investigators because of the complexity of the mathematics involved, the large numbers of parameters in the models, and the requirement for simultaneous solution of many differential equations. In recent years, advances in computer science and readily available software for personal computers have overcome most of the computational limitations.
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From page 112... ...
Sensitivity analyses of parameters involved will be important for the improved understanding of physiologically based pharmacokinetic modeling, the design of research to improve models, and the interpretation and application of the results.
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From page 113... ...
0.0345 0.233 0.140 70.0 Lung (a) 0.410 2.72 1.64 772.0 Percentage of body weight Liver 4.0 4.0 4.0 3.14 Rapidly perfused tissue 5.0 5.0 5.0 3.71 Slowly perfused tissue 78.0 75.0 75.0 62.1 Fat 4.0 7.0 7.0 23.1 Flows (liters/hour)
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From page 114... ...
is given in Appendix A; a more detailed discussion appears in the report just mentioned (NRC, 19861. PHARMACOKINETICS INVOLVING INTERACTIONS Physiologically based pharmacokinetic modeling of toxic interactions is a new field, and the only published studies are limited to binary mixtures (Andersen et al., 1987b; Clewell and Andersen, 19851.
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From page 115... ...
from experimental gas-uptake studies (circles and triangles) and from physiologically based pharmacokinetic models (smooth curves)
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From page 116... ...
waste disposal sites might be consuming groundwater containing one or more of the chemicals listed at near the average concentrations shown, the concentrations of contaminants in public drinking water supplies used by most Americans (see Table 4-1) are much lower than the averages listed in Table 2-2.
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From page 117... ...
Recent preliminary findings of the National Toxicology Program (Germolec et al., in press) suggested that a mixture of 25 groundwater contaminants, at concentrations close to the averages listed in Table 2-2, is associated with mild but definite immunosuppression in B6C3F1 mice.
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From page 118... ...
· Several physiologically based pharrnacokinetic models of complex chemical mixtures simulating contaminated drinking water should be devel oped and subjected to rigorous validation testing. · The physiologically based pharmacokinetics of pesticides and some other, relatively nonvolatile chemicals should be studied.
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From page 119... ...
1979. A review of the applications of physiologically based pharmacokinetic modeling.
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From page 120... ...
1987. Toxicological studies of chemical mixtures of environmental concern at the National Toxicology Program: Health effects of ground water contaminants.
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