Comparative pulmonary toxicological assessment of oil combustion particles following inhalation or instillation exposure
Comparative pulmonary toxicological assessment of oil combustion particles following inhalation or instillation exposure
复制标题
DOI：
10.1093/toxsci/kfj123
复制
发表时间：
2006-05-01
影响因子：
3.8
通讯作者：
Dreher, KL
中科院分区：
文献类型：
--
作者：
Costa, DL;Lehmann, JR;Dreher, KL
关于颗粒物（PM）的肺内滴注（IT）作为啮齿动物吸入暴露（IH）的替代物的有效性，一直存在争议。关注点集中在剂量、剂量率和材料在肺内的分布。将IH施用的渣油飞灰（ROFA）的急性毒性与IH等效剂量的单次IT推注的影响进行了比较。雄性Sprague道利大鼠（60日龄）仅经鼻暴露于类似于12 mg/m3的IH，持续6小时。用中子活化法测定了暴露后立即解剖的ROFA的叶间剂量分布。钒和镍被用作ROFA标记物。IT给予IH等效剂量（110 μ g）显示相似（< 15%）的小叶间分布，下叶剂量除外（IT > IH相似于25%）。在暴露后24、48和96 h进行气道高反应性（AHR）、支气管肺泡灌洗液（BALF）成分和组织病理学评价。IH组的AHR受治疗的影响最小（p > 0.05），但在IT后24和48 h均显著增加（相似于40%）。通过BALF蛋白、乳酸脱氢酶和中性粒细胞的变化测量，两组的炎症在所有时间点几乎相同。肺泡炎和支气管炎症/上皮细胞肥大在IT后24 h显著，但在IH后不明显。相反，肺泡出血，充血和气道渗出液在IH后48小时明显，但IT组不明显。因此，IT-ROFA在96小时内的肺叶分布和损伤生物标志物方面模仿IH，而形态学改变和AHR似乎更依赖于给药方法。
Controversy persists regarding the validity of intratracheal instillation (IT) of particulate matter (PM) as a surrogate for inhalation exposure (IH) in rodents. Concerns center on dose, dose-rate, and distribution of material within the lung. Acute toxicity of a residual oil fly ash (ROFA) administered by IH was compared to those effects of a single IT bolus at an IH-equivalent dose. Male Sprague Dawley rats (60 days old) were exposed by nose-only IH to similar to 12 mg/m(3) for 6 h. Inter-lobar dose distribution of ROFA, dissected immediately post exposure, was assayed by neutron activation. Vanadium and nickel were used as ROFA markers. IT administration of the IH-equivalent dose (110 mu g) showed similar (< 15%) interlobular distribution, with the exception of the inferior lobe dose (IT > IH similar to 25%). Evaluation of airway hyperreactivity (AHR), bronchoalveolar lavage fluid (BALF) constituents, and histopathology was conducted at 24, 48, and 96 h post exposure. AHR in the IH group was minimally (p > 0.05) affected by treatment, but was significantly increased (similar to 40%) at both 24 and 48 h post IT. Inflammation in both groups, as measured by alterations in BALF protein, lactate dehydrogenase and neutrophils, was virtually identical at all time points. Alveolitis and bronchial inflammation/epithelial hypertrophy were prominent 24 h following IT, but not apparent after IH. Conversely, alveolar hemorrhage, congestion, and airway exudate were pronounced at 48 h post-IH but not remarkable in the IT group. Thus, IT-ROFA mimicked IH in terms of lobar distribution and injury biomarkers over 96 h, while morphological alterations and AHR appeared to be more dependent on the method of administration.