• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文会议>Annual conference of the International Society of Exposure Science >Introduction to kinetics as connector of external and internal dose: importance for risk assessment
【24h】

Introduction to kinetics as connector of external and internal dose: importance for risk assessment

机译：作为外部和内部剂量连接器的动力学简介：风险评估的重要性

获取原文
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

An introduction on the importance of insight in kinetics for the estimation of internal exposure will be given. Human risk assessment is generally based on external dose metrics. There is an increasing awareness that this process can be improved if exposure assessment focuses on internal rather than external exposure estimates. One of the main advantages hereof is that exposure from different sources can be combined, especially if exposure to a substance occurs via multiple routes, i.e., oral, inhalation and/or dermal exposure. At present, the most common way is to add up the doses taken up via the respective exposure routes, at best adjusted for the fraction absorbed per route of exposure. The internal exposure then is often expressed as internal dose per kg body weight. However, each route of exposure is characterized by kinetic processes that determine the fate of a substance in the body and thus the internal exposure. Four steps can be distinguished: absorption, distribution, metabolism and excretion. Insight in these processes is essential for an adequate estimation of the internal exposure, i.e., the internal exposure at the site (organs, tissues) where toxicity is expected. The first question then raised is what the appropriate internal dose metric will be. Some toxic effects are related to tissue concentration while for other effects tissue dose is the best descriptor. This understanding underlines the necessity of taking into account the exposure rate, i.e., the impact on the internal exposure of the exposure dose in combination with the exposure duration. A short exposure to a high dose will lead to a different internal exposure pattern (and thus a different outcome of toxicity) than exposure to the same dose spread over a longer period of time. The more so, since at high doses saturation of kinetic processes may occur. A second point is knowledge about whether the toxicity is caused by the parent compound one is exposed to or by one of its metabolites. For instance, if a metabolite is the toxic agent, oral exposure may lead to different toxicity than dermal exposure to the same dose since following oral exposure all substance first passes the liver (the main organ for metabolism) before being distributed throughout the body. Internal exposure estimates that can be related to toxic effects can reduce uncertainties involved in human risk assessment but an adequate insight in route-specific kinetics is a prerequisite.
机译：将介绍有关洞察力的动力学对于内部暴露估算的重要性。人类风险评估通常基于外部剂量指标。越来越多的人意识到，如果暴露评估着重于内部而不是外部暴露估计，则可以改善这一过程。本文的主要优点之一是可以组合来自不同来源的暴露，尤其是如果通过多种途径（即口服，吸入和/或皮肤暴露）发生某种物质的暴露，则尤其如此。目前，最常见的方法是将通过各自的暴露途径吸收的剂量加起来，最好根据每种暴露途径吸收的比例进行调整。然后，内部暴露通常表示为每千克体重的内部剂量。但是，每种暴露途径的特征在于动力学过程，这些过程决定了体内某种物质的命运，进而决定了内部暴露。可以区分四个步骤：吸收，分布，代谢和排泄。这些过程的洞察力对于充分估计内部暴露（即预期毒性的部位（器官，组织）的内部暴露）是至关重要的。然后提出的第一个问题是适当的内部剂量指标将是多少。一些毒性作用与组织浓度有关，而对于其他作用，组织剂量是最好的描述。这种理解强调了必须考虑暴露率，即，将暴露剂量对内部暴露的影响与暴露持续时间相结合。与长时间暴露于相同剂量的药物相比，短暂暴露于高剂量的药物会导致不同的内部暴露方式（从而导致不同的毒性结果）。更是如此，因为在高剂量下可能发生动力学过程的饱和。第二点是关于毒性是由母体化合物暴露于其代谢产物还是由其代谢产物之一引起的知识。例如，如果代谢产物是有毒的物质，则口服暴露与相同剂量的皮肤暴露相比，可能会导致毒性不同，因为口服暴露后，所有物质首先会通过肝脏（代谢的主要器官），然后才分布到全身。可能与毒性作用有关的内部暴露估计值可以减少人类风险评估中涉及的不确定性，但前提是必须对特定路线的动力学有足够的了解。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号