评估人类通过大鼠毒代动力学实验和文献数据外推接触噻虫嗪的风险。
Evaluation of the risk of human exposure to thiamethoxam by extrapolation from a toxicokinetic experiment in rats and literature data.
机构信息
Ministry of Education Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, PR China.
Ministry of Education Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, PR China.
出版信息
Environ Int. 2023 Mar;173:107823. doi: 10.1016/j.envint.2023.107823. Epub 2023 Feb 13.
Previous studies suggest that exposure to thiamethoxam (TMX) may cause adverse effects to human. However, the distribution of TMX in various organs of human body and the associated risk are little-known. This study aimed to explore the distribution of TMX in human organs by extrapolation from a toxicokinetic experiment in rats and to assess the associated risk based on literature data. The rat exposure experiment was performed using 6-week female SD rats. Five groups of rats were oral-exposed to 1 mg/kg TMX (water as solvent) and executed at 1 h, 2 h, 4 h, 8 h and 24 h after treatment, respectively. The concentrations of TMX and its metabolites in rat liver, kidney, blood, brain, muscle, uterus and urine were measured in different time points using LC-MS. Data on concentrations of TMX in food, human urine and blood as well as human cell-based in vitro toxicity of TMX were collected from the literature. After oral exposure, TMX and its metabolite clothianidin (CLO) were detected in all organs of the rats. The steady-state tissue-plasma partition coefficients of TMX for liver, kidney, brain, uterus and muscle were 0.96, 1.53, 0.47, 0.60 and 1.10, respectively. Based on literature analysis, the concentration of TMX in human urine and blood for general population were 0.06-0.5 ng/mL and 0.04-0.6 ng/mL, respectively. For some people, the concentration of TMX in human urine reached 222 ng/mL. By extraplation from rat experiment, the estimated concentrations of TMX in human liver, kidney, brain, uterus and muscle for general population were 0.038-0.58, 0.061-0.92, 0.019-0.28, 0.024-0.36 and 0.044-0.66 ng/g, respectively, well below the relevant concentrations for cytotoxic endpoints (HQs ≤ 0.012); however, for some people they could be up to 253.44, 403.92, 124.08, 158.40 and 290.40 ng/g, respectively, with very high developmental toxicity (HQ = 5.4). Therefore, the risk for highly exposed people should not be neglected.
先前的研究表明，噻虫嗪（TMX）暴露可能对人体产生不良影响。然而，TMX 在人体各器官中的分布及其相关风险尚不清楚。本研究旨在通过大鼠毒代动力学实验外推，探讨 TMX 在人体器官中的分布，并基于文献数据评估其相关风险。该大鼠暴露实验采用 6 周龄雌性 SD 大鼠进行。将 5 组大鼠经口暴露于 1mg/kg TMX（水为溶剂），分别于给药后 1h、2h、4h、8h 和 24h 处死。采用 LC-MS 法测定不同时间点大鼠肝、肾、血、脑、肌肉、子宫和尿中 TMX 及其代谢物的浓度。从文献中收集了 TMX 在食物、人尿和血液中的浓度以及 TMX 基于细胞的体外人毒性数据。经口暴露后，TMX 及其代谢物噻虫胺（CLO）在大鼠所有器官中均有检出。TMX 在大鼠肝、肾、脑、子宫和肌肉中的稳态组织-血浆分配系数分别为 0.96、1.53、0.47、0.60 和 1.10。基于文献分析，一般人群的人尿和血液中 TMX 浓度分别为 0.06-0.5ng/mL 和 0.04-0.6ng/mL。对于一些人，人尿中 TMX 浓度达到 222ng/mL。根据大鼠实验外推，一般人群的人肝、肾、脑、子宫和肌肉中 TMX 的估计浓度分别为 0.038-0.58、0.061-0.92、0.019-0.28、0.024-0.36 和 0.044-0.66ng/g，均低于细胞毒性终点（HQs≤0.012）的相关浓度；然而，对于一些人，其浓度分别高达 253.44、403.92、124.08、158.40 和 290.40ng/g，具有很高的发育毒性（HQ=5.4）。因此，高度暴露人群的风险不容忽视。
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