Use of biological markers and pharmacokinetics in human health risk assessment.
There are two reasons to connect discussions of biological markers and pharmacokinetics. First, both tend to open up the black box between exposure and effect. Doing this promises more complete scientific understanding than simple input-output analysis, the possibility of better mechanism-based projection of risk beyond the range of possible direct observations, and the possibility of greater sensitivity of analysis, in some cases going from the organism to the cell as the unit of analysis. Second, pharmacokinetic (or similar pharmacodynamic) analysis will often be essential for appropriate interpretation of biological marker information. One needs some sort of dynamic model of the generation and loss of the marker in relation to exposure in order to use a biological marker, either to form a better measure of dosage (either accumulated past dose, or biologically relevant dose), or to make an improved prediction of effect. (For example, the use of a blood cadmium level alone to predict kidney effects might be inferior to predictions based on aggregate past accumulation of cadmium in the kidney, based on the past history of cadmium blood levels x time). Several examples will be discussed of the use of biomarkers and pharmacokinetics in risk assessments for both carcinogenesis and other effects.
Hattis
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M.I.T. Center for Technology, Policy and Industrial Development, Cambridge 012139.
D015415:Biomarkers; D001724:Birth Weight / Q000187:drug effects; D002274:Carcinogens, Environmental / Q000493:pharmacokinetics*; D004781:Environmental Exposure; D005298:Fertility / Q000187:drug effects; D006305:Health Status Indicators; D006801:Humans; D007226:Infant Mortality; D007231:Infant, Newborn; D008297:Male; D009420:Nervous System / Q000187:drug effects; D010684:Philosophy
D015415:Biomarkers; D002274:Carcinogens, Environmental