التفاصيل البيبلوغرافية
| العنوان: |
Embracing a Weight-of-Evidence Approach for Establishing NOAELs for Nanoparticle Inhalation Toxicity Studies. |
| المؤلفون: |
Warheit, David B., Reed, Kenneth L., DeLorme, Michael P. |
| المصدر: |
Toxicologic Pathology; 2/1/2013, Vol. 41 Issue 2, p387-394, 8p |
| مصطلحات موضوعية: |
TOXICOLOGY of poisonous gases, PHYSIOLOGICAL effects of nanoparticles, CARBON nanofibers, DRUG side effects, BRONCHOALVEOLAR lavage, CELL proliferation, ALKALINE phosphatase, LACTATE dehydrogenase, LABORATORY rats |
| الشركة/الكيان: |
ORGANISATION for Economic Co-operation & Development |
| مستخلص: |
The goal of this article is to evaluate a recently published subchronic inhalation study with carbon nanofibers in rats and discuss the importance of a weight-of-evidence (WOE) framework for determining no adverse effect levels (NOAELs). In this Organization for Economic Cooperation and Development (OECD) 413 guideline inhalation study with VGCF™-H carbon nanofibers (CNFs), rats were exposed to 0, 0.54, 2.5 or 25 mg/m3 CNF for 13 weeks. The standard toxicology experimental design was supplemented with bronchoalveolar lavage (BAL) and respiratory cell proliferation (CP) endpoints. BAL fluid (BALF) recovery of inflammatory cells and mediators (i.e., BALF– lactate dehydrogenase [LDH], microprotein [MTP], and alkaline phosphatase [ALKP] levels) were increased only at 25 mg/m3, 1 day after exposure. No differences versus control values in were measured at 0.54 or 2.5 mg/m3 exposure concentrations for any BAL fluid endpoints. Approximately 90% (2.5 and 25 mg/m3) of the BAL-recovered macrophages contained CNF. CP indices at 25 mg/m3 were increased in the airways, lung parenchyma, and subpleural regions, but no increases in CP versus controls were measured at 0.54 or 2.5 mg/m3. Based upon histopathology criteria, the NOAEL was set at 0.54 mg/m3, because at 2.5 mg/m3, “minimal cellular inflammation” of the airways/lung parenchyma was noted by the study pathologist; while the 25 mg/m3 exposure concentration produced slight inflammation and occasional interstitial thickening. In contrast, none of the more sensitive pulmonary biomarkers such as BAL fluid inflammation/cytotoxicity biomarkers or CP turnover results at 2.5 mg/m3 were different from air-exposed controls. Given the absence of convergence of the histopathological observations versus more quantitative measures at 2.5 mg/m3, it is recommended that more comprehensive guidance measures be implemented for setting adverse effect levels in (nano)particulate, subchronic inhalation studies including a WOE approach for establishing no adverse effect levels; and a suggestion that some findings should be viewed as normal physiological adaptations (e.g., normal macrophage phagocytic responses—minimal inflammation) to long-term particulate inhalation exposures. [ABSTRACT FROM PUBLISHER] |
|
Copyright of Toxicologic Pathology is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder