Discovery Sciences, RTI International, 3040 E Cornwallis Road, Research Triangle Park, NC, 27709, USA.
UNC Nutrition Research Institute, The University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA.
Part Fibre Toxicol. 2022 Jan 5;19(1):3. doi: 10.1186/s12989-021-00444-9.
Nanoparticles (NPs) are increasingly incorporated in everyday products. To investigate the effects of early life exposure to orally ingested TiO NP, male and female Sprague-Dawley rat pups received four consecutive daily doses of 10 mg/kg body weight TiO NP (diameter: 21 ± 5 nm) or vehicle control (water) by gavage at three different pre-weaning ages: postnatal day (PND) 2-5, PND 7-10, or PND 17-20. Cardiac assessment and basic neurobehavioral tests (locomotor activity, rotarod, and acoustic startle) were conducted on PND 20. Pups were sacrificed at PND 21. Select tissues were collected, weighed, processed for neurotransmitter and metabolomics analyses.
Heart rate was found to be significantly decreased in female pups when dosed between PND 7-10 and PND 17-20. Females dosed between PND 2-5 showed decrease acoustic startle response and when dosed between PND 7-10 showed decreased performance in the rotarod test and increased locomotor activity. Male pups dosed between PND 17-20 showed decreased locomotor activity. The concentrations of neurotransmitters and related metabolites in brain tissue and the metabolomic profile of plasma were impacted by TiO NP administration for all dose groups. Metabolomic pathways perturbed by TiO NP administration included pathways involved in amino acid and lipid metabolism.
Oral administration of TiO NP to rat pups impacted basic cardiac and neurobehavioral performance, neurotransmitters and related metabolites concentrations in brain tissue, and the biochemical profiles of plasma. The findings suggested that female pups were more likely to experience adverse outcome following early life exposure to oral TiO NP than male pups. Collectively the data from this exploratory study suggest oral administration of TiO NP cause adverse biological effects in an age- and sex-related manner, emphasizing the need to understand the short- and long-term effects of early life exposure to TiO NP.
纳米颗粒（NPs）越来越多地被应用于日常产品中。为了研究早期经口摄入 TiO NP 对雄性和雌性 Sprague-Dawley 幼鼠的影响，雄性和雌性幼鼠在三个不同的断奶前阶段（出生后第 2-5 天、第 7-10 天或第 17-20 天）每天通过灌胃接受 4 次连续剂量的 10mg/kg 体重 TiO NP（直径：21±5nm）或载体对照（水）。在出生后第 20 天进行心脏评估和基本神经行为测试（运动活动、转棒和听觉惊跳）。幼鼠在出生后第 21 天被处死。选择组织进行神经递质和代谢组学分析。
当在 PND 7-10 和 PND 17-20 之间给药时，雌性幼鼠的心率显著降低。在 PND 2-5 之间给药的雌性幼鼠表现出听觉惊跳反应减少，在 PND 7-10 之间给药的雌性幼鼠表现出转棒试验性能下降和运动活动增加。在 PND 17-20 之间给药的雄性幼鼠表现出运动活动减少。所有剂量组的脑组织中神经递质和相关代谢物的浓度以及血浆的代谢组学特征都受到 TiO NP 给药的影响。TiO NP 给药干扰的代谢途径包括涉及氨基酸和脂质代谢的途径。
向幼鼠口服 TiO NP 会影响基本的心脏和神经行为表现、脑组织中神经递质和相关代谢物的浓度以及血浆的生化特征。研究结果表明，与雄性幼鼠相比，雌性幼鼠在早期经口暴露于 TiO NP 后更有可能出现不良后果。总的来说，这项探索性研究的数据表明，口服 TiO NP 以年龄和性别相关的方式引起不良的生物学效应，强调需要了解早期接触 TiO NP 的短期和长期影响。
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