Routes of Exposure, Dose, and Metabolism of Metals
2007 (English)In: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, 39-64 p.Chapter in book (Other academic)
The chapter first describes the main sources of exposure through air, food, and water but also points to unusual sources such as medical implants. Special attention is given to the processes of lung deposition and clearance of inhaled gases, vapors, and particulates, including ultrafine particles. In contrast to the extensive studies in the lung, absorption of metal in the gastrointestinal tract is less well understood. A diagrammatic example is given of the summation of all the absorption processes as they contribute to the total body burden. Since the publication of the first edition, new information has become available on the mechanisms of transport and distribution of metals in the body. In particular, it has been shown that several metals can cross cell membranes by specific carriers and ion channels intended for endogenous substrates. One well-documented example is the chromate oxyanion that is structurally similar to the sulfate anion and thereby gains entrance into the cell by the sulfate carrier. The fecal excretion of several metals occurs as the end result of extensive enterohepatic recirculation. In the case of certain organometallic species, the gut microflora may play a critical role converting the metal to the inorganic form, which is excreted in the feces. The renal accumulation and excretion of metals has also received considerable attention. The renal accumulation of cadmium in the form of its complex with the small molecular weight protein, metallothionein, still remains one of the best-documented mechanisms. Toxicokinetic models continue to be useful in providing a quantitative description of the overall body turnover of metals. They can be useful in establishing dose-response relationships where, for example, the range of half-times of elimination of a metal can contribute to the overall variance in the dose-response relationship. In addition to the observationally based models, pharmacokinetic models can be developed based a priori on physiological and mechanistic considerations. The chapter concludes with a consideration of indicator media that best reflect the dose to the critical organ.
Place, publisher, year, edition, pages
San Diego: Elsevier, 2007, 3. 39-64 p.
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:umu:diva-76456DOI: 10.1016/B978-012369413-3/50058-6ISI: 000311285300005ISBN: 978-0-12-369413-3OAI: oai:DiVA.org:umu-76456DiVA: diva2:636774