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首頁> 美國衛(wèi)生研究院文獻>ISRN Toxicology >Safety Evaluation of Engineered Nanomaterials for Health Risk Assessment: An Experimental Tiered Testing Approach Using Pristine and Functionalized Carbon Nanotubes
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Safety Evaluation of Engineered Nanomaterials for Health Risk Assessment: An Experimental Tiered Testing Approach Using Pristine and Functionalized Carbon Nanotubes

機譯：用于健康風(fēng)險評估的工程納米材料的安全性評估：使用原始和功能化碳納米管的實驗性分層測試方法

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Increasing application of engineered nanomaterials within occupational, environmental, and consumer settings has raised the levels of public concern regarding possible adverse effects on human health. We applied a tiered testing strategy including (i) a first in vitro stage to investigate general toxicity endpoints, followed by (ii) a focused in vivo experiment. Cytotoxicity of laboratory-made functionalized multiwalled carbon nanotubes (CNTs) (i.e., MW-COOH and MW-NH2), compared to pristine MWCNTs, carbon black, and silica, has been assessed in human A549 pneumocytes by MTT assay and calcein/propidium iodide (PI) staining. Purity and physicochemical properties of the test nanomaterials were also determined. Subsequently, pulmonary toxic effects were assessed in rats, 16 days after MWCNTs i.t. administration (1 mg/kg b.w.), investigating lung histopathology and monitoring several markers of lung toxicity, inflammation, and fibrosis. In vitro data: calcein/PI test indicated no cell viability loss after all CNTs treatment; MTT assay showed false positive cytotoxic response, occurring not dose dependently at exceedingly low CNT concentrations (1 μg/mL). In vivo results demonstrated a general pulmonary toxicity coupled with inflammatory response, without overt signs of fibrosis and granuloma formation, irrespective of nanotube functionalization. This multitiered approach contributed to clarifying the CNT toxicity mechanisms improving the overall understanding of the possible adverse outcomes resulting from CNT exposure.
機譯：在職業(yè)，環(huán)境和消費者環(huán)境中工程納米材料的越來越多的應(yīng)用提高了公眾對可能對人體健康產(chǎn)生不利影響的關(guān)注程度。我們應(yīng)用了分層測試策略，包括（i）在體外的第一個階段研究一般的毒性終點，然后（ii）進行有針對性的體內(nèi)實驗。與原始MWCNT，炭黑和二氧化硅相比，實驗室制造的功能化多壁碳納米管（CNT）（即MW-COOH和MW-NH2）的細胞毒性已通過MTT分析和鈣黃綠素/碘化丙啶在人A549肺細胞中進行了評估（PI）染色。還確定了測試納米材料的純度和理化性質(zhì)。隨后，在MWCNTs腹腔注射16天后評估了大鼠的肺毒性作用。給藥（1微克/千克體重），研究肺組織病理學(xué)并監(jiān)測肺毒性，炎癥和纖維化的幾種標志物。體外數(shù)據(jù)：鈣黃綠素/ PI測試表明，所有CNT處理后細胞活力均沒有損失； MTT檢測顯示假陽性細胞毒性反應(yīng)，在極低的CNT濃度（1μg/ mL）下不依賴劑量。體內(nèi)結(jié)果表明，無論納米管功能如何，一般的肺毒性和炎癥反應(yīng)均無明顯的纖維化和肉芽腫形成跡象。這種多層次的方法有助于闡明CNT的毒性機制，從而提高了對CNT暴露可能產(chǎn)生的不良后果的總體了解。

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