Toxicity dose descriptors from animal inhalation studies of 13 nanomaterials and their bulk and ionic counterparts and variation with primary particle characteristics

This study collects toxicity data from animal inhalation studies of some nanomaterials and their bulk and ionic counterparts. To allow potential grouping and interpretations, we retrieved the primary physicochemical and exposure data to the extent possible for each of the materials. Reviewed materials are compounds (mainly elements, oxides and salts) of carbon (carbon black, carbon nanotubes, and graphene), silver, cerium, cobalt, copper, iron, nickel, silicium (amorphous silica and quartz), titanium (titanium dioxide), and zinc (chemical symbols: Ag, C, Ce, Co, Cu, Fe, Ni, Si, Ti, TiO₂, and Zn). Collected endpoints are: a) pulmonary inflammation, measured as neutrophils in bronchoalveolar lavage (BAL) fluid at 0-24 hours after last exposure; and b) genotoxicity/carcinogenicity. We present the dose descriptors no-observed-adverse-effect concentrations (NOAECs) and lowest-observed-adverse-effect concentrations (LOAECs) for 88 nanomaterial investigations in data-library and graph formats. We also calculate ‘the value where 25% of exposed animals develop tumors’ (T25) for carcinogenicity studies. We describe how the data may be used for hazard assessment of the materials using carbon black as an example. The collected data also enable hazard comparison between different materials. An important observation for poorly soluble particles is that the NOAEC for neutrophil numbers in general lies around 1 to 2 mg/m³. We further discuss why some materials’ dose descriptors deviate from this level, likely reflecting the effects of the ionic form and effects of the fiber-shape. Finally, we discuss that long-term studies, in general, provide the lowest dose descriptors, and dose descriptors are positively correlated with particle size for near-spherical materials.

本研究收集了部分纳米材料及其块体形态与离子形态对应物的动物吸入毒性实验数据。为便于后续分组与科学解读，我们尽可能全面地检索了每种材料的核心理化性质与暴露相关数据。本次综述纳入的材料包括碳（炭黑、碳纳米管、石墨烯）、银、铈、钴、铜、铁、镍、硅（无定形二氧化硅与石英）、钛（二氧化钛）及锌的化合物（主要为单质、氧化物与盐类），其化学符号依次为：Ag、C、Ce、Co、Cu、Fe、Ni、Si、Ti、TiO₂及Zn。本次采集的观测终点包括：a) 肺部炎症：以末次暴露后0-24小时支气管肺泡灌洗液（bronchoalveolar lavage, BAL）中的中性粒细胞数量作为衡量指标；b) 遗传毒性与致癌性。我们以数据库与图表形式，针对88项纳米材料相关研究，整理并呈现了未观察到有害作用浓度（no-observed-adverse-effect concentrations, NOAEC）与最低观察到有害作用浓度（lowest-observed-adverse-effect concentrations, LOAEC）这两类剂量描述值。同时，我们还针对致癌性实验计算了「暴露动物中25%出现肿瘤时的剂量阈值（T25）」。我们以炭黑为例，阐述了该数据集可用于开展材料的危害评估。此外，本数据集还支持不同材料间的危害对比分析。针对难溶性颗粒，一项重要观测结果为：对应中性粒细胞计数的未观察到有害作用浓度普遍处于1~2 mg/m³区间。我们进一步讨论了部分材料的剂量描述值偏离该基准水平的原因，这大概率与离子形态效应及纤维形状效应相关。最后，我们指出：长期暴露实验通常可得到更低的剂量描述值，且对于近球形颗粒，剂量描述值与粒径呈正相关。