Dose-response relationships toxicokinetic biomarkers

Second, lead s kinetic behavior in vivo provides the means by which one can identify and exploit biomarkers of toxic lead exposures as well as determine the dose portion of critical dose—toxic response relationships for lead poisoning. Measurement of lead in whole blood and its relatively reliable use in determining both systemic lead exposure and the extent of toxic injury (dose—response relationships) is mainly feasible because we understand how Pb s toxicokinetic behavior in blood relates to the temporal and toxicological... 

PbP is a relatively rapid reflection of Pb uptake and distribution toxicokinetics in human populations (NAS/NRC, 1993 U.S. EPA, 2006) and is the in vivo medium by which Pb is excreted to urine through glomerular filtration in humans. This behavior in terms of rapid exchange of Pb with target tissues and PbP makes the latter a more temporally sensitive biomarker for toxicokinetics and toxicodynamics. Little has evolved in the more current toxicological literature on Pb to quantify dose—response relationships using PbP as the dose metric beyond attempts at elucidating the exposure marker trio of PbB, PbP, and Pb in bone. 

A critical question in fetal Pb toxicokinetics is how one best measures dose—response relationships among various exposure biomarkers as well as relationships governing dose—toxic response relationships. It is now accepted that bone Pb is a better biomarker in constmcting dose—toxic response relationships for a variety of toxic effects than are indicators such as PbB. This was demonstrated in Chapter 13 describing cardiovascular effects of Pb. 

An adequate characterization of the dose/exposure portion of reported dose—responses for lead requires discussion of the merits and limits of those exposure biomarkers which have traditionally been used and others which are relatively new and gaining favor. These two broad groups of exposure assessment instruments are further stratified in terms of temporal and toxicokinetic relationships for lead s associated toxic responses and in terms of accessibility and acceptability for routine use in the research and medical communities. 

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