Abstract

Carbon nanotubes (CNTs) are nanomaterials presenting an occupational inhalation risk during production or handling. The International Agency for Research on Cancer classified one CNT, Mitsui-7 (MWNT-7), as ‘possibly carcinogenic to humans’. In recognition of their similarities, a proposal has been submitted to the risk assessment committee of ECHA to classify all fibers with ‘Fibre Paradigm’ (FP)-compatible dimensions as carcinogenic. However, there is a lack of clarity surrounding the toxicity of fibers that do not fit the FP criteria. In this study, we compared the effects of the FP-compatible Mitsui-7, to those of NM-403, a CNT that is too short and thin to fit the paradigm. Female Sprague Dawley rats deficient for p53 (GMO) and wild type (WT) rats were exposed to the two CNTs (0.25 mg/rat/week) by intratracheal instillation. Animals (GMO and WT) were exposed weekly for four consecutive weeks and were sacrificed 3 days or 8 months after the last instillation. Exposure to both CNTs induced acute lung inflammation. However, persistent inflammation at 8 months was only observed in the lungs of rats exposed to NM-403. In addition to the persistent inflammation, NM-403 stimulated hyperplasic changes in rat lungs, and no adenomas or carcinomas were detected. The degree and extent of hyperplasia was significantly more pronounced in GMO rats. These results suggest that CNT not meeting the FP criteria can cause persistent inflammation and hyperplasia. Consequently, their health effects should be carefully assessed.

摘要

碳纳米管 (CNT) 是一种纳米材料，在生产或处理过程中存在职业吸入风险。国际癌症研究机构将一种碳纳米管 Mitsui-7 (MWNT-7) 列为“可能对人类致癌”。认识到它们的相似性，已向 ECHA 风险评估委员会提交了一份提案，将所有具有“纤维范式”(FP) 兼容尺寸的纤维归类为致癌物。然而，不符合 FP 标准的纤维的毒性尚不明确。在这项研究中，我们将兼容 FP 的 Mitsui-7 的效果与 NM-403 的效果进行了比较，NM-403 是一种太短太薄而不适合范例的 CNT。p53 (GMO) 缺陷的雌性 Sprague Dawley 大鼠和野生型 (WT) 大鼠通过气管内滴注暴露于两种 CNT（0.25 mg/大鼠/周）。动物（GMO 和 WT）连续 4 周每周暴露一次，并在最后一次滴注后 3 天或 8 个月处死。暴露于两种碳纳米管均会诱发急性肺部炎症。然而，仅在暴露于 NM-403 的大鼠肺部观察到 8 个月时的持续炎症。除了持续性炎症外，NM-403 还刺激大鼠肺部发生增生性变化，未检测到腺瘤或癌。增生的程度和范围在转基因大鼠中明显更为明显。这些结果表明，不符合 FP 标准的 CNT 会导致持续性炎症和增生。因此，应仔细评估它们对健康的影响。暴露于两种碳纳米管均会诱发急性肺部炎症。然而，仅在暴露于 NM-403 的大鼠肺部观察到 8 个月时的持续炎症。除了持续性炎症外，NM-403 还刺激大鼠肺部发生增生性变化，未检测到腺瘤或癌。增生的程度和范围在转基因大鼠中明显更为明显。这些结果表明，不符合 FP 标准的 CNT 会导致持续性炎症和增生。因此，应仔细评估它们对健康的影响。暴露于两种碳纳米管均会诱发急性肺部炎症。然而，仅在暴露于 NM-403 的大鼠肺部观察到 8 个月时的持续炎症。除了持续性炎症外，NM-403 还刺激大鼠肺部发生增生性变化，未检测到腺瘤或癌。增生的程度和范围在转基因大鼠中明显更为明显。这些结果表明，不符合 FP 标准的 CNT 会导致持续性炎症和增生。因此，应仔细评估它们对健康的影响。增生的程度和范围在转基因大鼠中明显更为明显。这些结果表明，不符合 FP 标准的 CNT 会导致持续性炎症和增生。因此，应仔细评估它们对健康的影响。增生的程度和范围在转基因大鼠中明显更为明显。这些结果表明，不符合 FP 标准的 CNT 会导致持续性炎症和增生。因此，应仔细评估它们对健康的影响。