Mast R W, Yu C P, Oberdörster G, McConnell E E, Utell M J
Everest Consulting Associates, 15 North Main Street, Cranbury, NJ 08512-3203, USA.
Inhal Toxicol. 2000 Dec;12(12):1141-72. doi: 10.1080/08958370050198511.
The purpose of this article is to review previous chronic inhalation studies in rats with refractory ceramic fiber (RCF), the mathematical modeling efforts to describe the deposition, clearance, and retention of RCF fiber in the rat and human, and the concept of "overload," and to assess the possibility that the maximum tolerated dose (MTD) was exceeded. Lastly, based on recent biopersistence and pulmonary clearance studies of several investigators with a particulate-free RCF, we examine the potential impact on the chronic RCF rat bioassay of coexposure to both RCF particulate and RCF fibers. The review concludes, inter alia, that RCF particulate coexposure probably had a major impact on the observed chronic adverse effects, that the MTD was probably exceeded at the highest exposure concentration of 30 mg/m(3) in the rat bioassay, and that inclusion of the highest dose in the risk assessment process may overstate human health risk if a linear rather than nonlinear model is used.
本文的目的是回顾先前对大鼠进行的难熔陶瓷纤维（RCF）慢性吸入研究、描述RCF纤维在大鼠和人体中的沉积、清除和滞留情况的数学建模工作以及“过载”概念，并评估是否超过了最大耐受剂量（MTD）。最后，基于几位研究人员近期对无颗粒RCF的生物持久性和肺部清除研究，我们考察了同时接触RCF颗粒和RCF纤维对慢性RCF大鼠生物测定的潜在影响。该综述尤其得出以下结论：同时接触RCF颗粒可能对观察到的慢性不良反应产生重大影响；在大鼠生物测定中，最高暴露浓度30 mg/m³时可能超过了MTD；如果使用线性而非非线性模型，在风险评估过程中纳入最高剂量可能会高估人类健康风险。
