Toxicokinetics lead absorption

The toxicokinetics of lead in children appears to be similar to that in adults, with the exception of the higher absorption of ingested lead in children. Most of the lead body burden in both children and adults is in bone a slightly large fraction of the body burden in adults resides in bone (Barry 1975). The difference may reflect the larger amount of trabecular bone and bone turnover during growth trabecular bone has a shorter retention halftime for lead than does cortical bone (See Section 2.3.3 for details). 

Toxicokinetic risk factors are those that can lead to increased Cmax (maximum concentration) and/or AUC (area under the curve of the concentration vs. time plot) of a given drug in a patient s liver. The drug in question can be the parent drug, its toxic metabolite, or a combination. The liver s increased exposure to drugs can be caused by increased drug absorption (e.g., for an orally administered medication) and/or decreased drug clearance. Some of the major causes of toxicokinetic risk factors are summarized next. 

Absorption, Distribution, Metabolism, Excretion. Examination of Section 2.6 clearly indicates that oral administration of NDMA has been the preferred route for studying its absorption, distribution, metabolism and excretion. This is not surprising since oral administration is easier to monitor when compared to other routes. The oral route seems to be the most pertinent to study since humans are most likely to be exposed to nitrosamines orally. Toxicokinetic data with regard to dermal and inhalation exposure of NDMA are clearly lacking. Furthermore, dermal and inhalation exposures may lead to different metabolic pathways and patterns of distribution and excretion, which could account for differences in the degree of toxicity exhibited by different routes of exposure. The metabolism of NDMA in isolated microsomal preparations seems to be well understood, but studies with cultured human cells could provide additional useful information. However, exploration of the denitrosation mechanism as an alternative to a-hydroxylation requires more attention. Determination of the urinary excretion of NDMA in control human volunteers and in individuals known to consume foods with high contents of nitrosamines could provide information concerning absorption and excretion of the xenobiotic. 

The toxicokinetics of lead— that is, its absorption, distribution, metabolism, and excretion— and its relevance to common biomaikers of exposure are schematically represented in Figure 3-1. 

Chapter 7 presents the levels of lead intakes in various subsets of affected human populations. The term intake as employed in the book describes amounts of media-specific Pb inhaled or ingested per unit time, typically daily, that enter the chief receiving body compartments the gastrointestinal (GI) and respiratory tracts. Chapter 8 describes the biokinetics of Pb, specifically the toxicokinetics of Pb in human populations and the toxicokinetic basis of lead exposure biomarkers. It deals with the absorption (uptake) rate of Pb, subsequent distribution of the element into the body post-uptake, the rate of retention over the short and long term, and the rate of short- or long-term excretion of the substance. 

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. 

Part 2 and its chapters presented the topic of human lead exposure in global and categorical terms, addressing the technical areas of lead intakes, uptakes (absorption), toxicokinetics, integration of toxicokinetics into in vivo disposition in a manner allowing quantitative assessments of lead exposure, etc. In contrast to these broadly descriptive aspects of human Pb exposme, the applied health discipline of quantitative risk assessment requires prescriptive approaches for site-specific, case-specific, and environmental scenario-specific lead exposure characterizations. Data from such specific exposure characterizations are combined with available data for lead dose—response relationships to arrive at some quantitative risk characterization indexed as some endpoint for human health risk. 

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