Diamond G L, Goodrum P E, Felter S P, Ruoff W L
Syracuse Research Corporation, North Syracuse, NY 13212-2510, USA.
Drug Chem Toxicol. 1998 May;21(2):223-51. doi: 10.3109/01480549809011649.
Estimating gastrointestinal absorption remains a significant challenge in the risk assessment of metals. This presentation reviews our current understanding of the gastrointestinal absorption of lead (Pb) to illustrate physiological mechanisms involved in metal absorption, new approaches that are being applied to the problem of estimating metal absorption in humans, and issues related to integrating this information into risk assessment. Absorption of metals can be highly variable in human populations because it is influenced by a variety of factors that include the chemical form of the metal, environmental matrix in which the ingested metal is contained, gastrointestinal tract contents, diet, nutritional status, age, and, in some cases, genotype. Thus, in risk assessment models, gastrointestinal absorption is best described as a variable whose distribution is determined in part by the above multiple influences. Although we cannot expect to evaluate empirically each of the above factors in human populations, we can expect to achieve a sufficiently detailed understanding of absorption mechanisms to develop conceptual and, eventually, quantitative models of absorption that account for some aspects of individual variability. A conceptual model is presented of the physiological processes involved in the transfer of ingested metals from the lumen of the gastrointestinal tract to the blood circulation. Components of the model include delivery to the site(s) of absorption; distribution among intracellular and extracellular ligands and transcellular and paracellular pathways of transfer across the gastrointestinal tract epithelium. The gastrointestinal absorption of Pb is discussed in the context of this model.
在金属风险评估中，估算胃肠道吸收仍然是一项重大挑战。本报告回顾了我们目前对铅（Pb）胃肠道吸收的理解，以阐明金属吸收所涉及的生理机制、用于估算人体金属吸收问题的新方法，以及将这些信息整合到风险评估中所涉及的问题。人群中金属的吸收可能存在很大差异，因为它受到多种因素的影响，包括金属的化学形态、摄入金属所处的环境基质、胃肠道内容物、饮食、营养状况、年龄，以及在某些情况下的基因型。因此，在风险评估模型中，胃肠道吸收最好被描述为一个变量，其分布部分由上述多种影响因素决定。虽然我们无法期望在人群中对上述每个因素进行实证评估，但我们可以期望对吸收机制有足够详细的了解，从而开发出能够解释个体变异性某些方面的概念性模型，并最终开发出定量模型。本文提出了一个概念模型，阐述了摄入的金属从胃肠道腔转移到血液循环所涉及的生理过程。该模型的组成部分包括输送到吸收部位；在细胞内和细胞外配体之间的分布，以及穿过胃肠道上皮细胞的跨细胞和细胞旁途径的转移。本文将在该模型的背景下讨论铅的胃肠道吸收。
