利用Tox21通路数据库评估石家庄市大气细颗粒物中多环芳烃激活毒性通路的风险

Risk assessment of fine particulate matter exposure using toxicity pathways of human lung cells

目的:采用Tox21毒性检测数据库中通路数据对2017年石家庄市供暖期大气细颗粒物(PM2.5)中多环芳烃(PAHs)的检测数据进行分析计算,评估PM2.5引起毒性通路激活的风险。方法:在石家庄市河北医科大学远离工业污染源设置1个采样点收集大气PM2.5,通过气相色谱-串联质谱法(GC-MS)检测美国环境保护署优先控制的16种PAHs的浓度。利用MPPD软件计算各PAHs单体在成人肺泡中的沉积量;检索Tox21毒性检测数据库中芳烃受体(Ah R)、核因子E2相关因子(Nrf2)、p53和核因子κB(NF-κB)各通路的剂量反应关系数据,计算各PAHs单体激活各通路的单位强度;结合PAHs在肺泡的沉积量和PAHs激活通路的强度,评估PM2.5激活各个通路的风险。结果:石家庄市供暖期PM2.5中PAHs检测结果显示,苯并[a]芘的日均浓度为9.13 ng/m3,日均浓度排名前3的苯并[b]荧蒽、荧蒽和芘的浓度分别为22.88、17.86及14.31 ng/m3。这16种PAHs以苯并[a]芘为参照的毒性当量浓度为17.74ng/m3。毒性通路激活风险预测结果提示激活强度最大的是NF-κB通路,其次是Ah R、Nrf2,p53被激活的可能性最弱,其中相对应的活性暴露比(AER)值分别为1.97、1.71、0.58和0.28。结论:石家庄市大气细颗粒物中PAHs的暴露,可能通过激活NF-κB和AhR信号通路增加致癌风险。

OBJECTIVE: To assess the toxicity pathway activation induced by PM2.5 using data fromTox21 10 K library based on the result of Ambient fine particulate matter-bound PAHs during heating period of2017 in Shijiazhuang. METHODS:Particle samples were collected in Hebei Medical University where it isaway from polluted industrial area. Concentrations of 16 US EPA priority PAHs were measured by GC-EI-MS.The deposition fractions of PM-bound PAHs in adult alveolar region of lung were determined by multiple-pathparticle dosimetry model. The potencies of PAHs in the Ah R,Nrf2,p53 and NF-κB pathways were calculatedusing data from the Tox21 10 K library. The assessment of risk from PM2.5 exposure was based on the alveolardeposition fraction combined with the potency of PAHs activated toxicity pathway. RESULTS: The averageconcentration of benzo[a]pyrene was 9.13 ng/m3. Daily concentrations of the top three chemicals in PM-boundPAHs were benzo[b]fluoranthene,fluoranthene and pyrene,and their average concentrations were 22.88、17.86 and 14.31 ng/m3 respectively. The benzo[a]pyrene equality concentration was 17.74 ng/m3. And the NF-κBpathway was most likely activated by PM-bound PAHs during the heating period and the second one was theAh R pathway which was followed by Nrf2. The p53 pathway was the least activated. The corresponding activity-to-exposure ratio values were 1.97,1.71,0.58 and 0.28. CONCLUSION:PM-bound PAHs in Shijiazhuangmight increase the risk of carcinogenesis via activation of the NF-κB and the Ah R pathways.