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用于治疗新冠病毒感染的药物是否会导致人类健康风险?一项识别潜在风险的假设性研究。

Can pharmaceutical drugs used to treat Covid-19 infection leads to human health risk? A hypothetical study to identify potential risk.

机构信息

Department of Civil Engineering, Indian Institute of Technology Delhi, Hauz Khas, Delhi 110016, India.

出版信息

Sci Total Environ. 2021 Jul 15;778:146303. doi: 10.1016/j.scitotenv.2021.146303. Epub 2021 Mar 9.

Abstract

This is the first study to assess human health risks due to the exposure of 'repurposed' pharmaceutical drugs used to treat Covid-19 infection. The study used a six-step approach to determine health risk estimates. For this, consumption of pharmaceuticals under normal circumstances and in Covid-19 infection was compiled to calculate the predicted environmental concentrations (PECs) in river water and in fishes. Risk estimates of pharmaceutical drugs were evaluated for adults as they are most affected by Covid-19 pandemic. Acceptable daily intakes (ADIs) are estimated using the no-observed-adverse-effect-level (NOAEL) or no observable effect level (NOEL) values in rats. The estimated ADI values are then used to calculate predicted no-effect concentrations (PNECs) for three different exposure routes (i) through the accidental ingestion of contaminated surface water during recreational activities only, (ii) through fish consumption only, and (iii) through combined accidental ingestion of contaminated surface water during recreational activities and fish consumption. Higher risk values (hazard quotient, HQ: 337.68, maximum; 11.83, minimum) were obtained for the combined ingestion of contaminated water during recreational activities and fish consumption exposure under the assumptions used in this study indicating possible effects to human health. Amongst the pharmaceutical drugs, ritonavir emerged as main drug, and is expected to pose adverse effects on r human health through fish consumption. Mixture toxicity analysis showed major risk effects of exposure of pharmaceutical drugs (interaction-based hazard index, HI: from 295.42 (for lopinavir + ritonavir) to 1.20 for chloroquine + rapamycin) demonstrating possible risks due to the co-existence of pharmaceutical in water. The presence of background contaminants in contaminated water does not show any influence on the observed risk estimates as indicated by low HQ values (<1). Regular monitoring of pharmaceutical drugs in aquatic environment needs to be carried out to reduce the adverse effects of pharmaceutical drugs on human health.

摘要

这是第一项评估因暴露于用于治疗新冠病毒感染的“再利用”药物而导致人类健康风险的研究。该研究采用六步方法来确定健康风险估计值。为此,根据正常情况和新冠病毒感染期间的药物使用情况,计算了河水中和鱼类中的预测环境浓度(PEC)。由于成年人受新冠大流行影响最大,因此对其进行了药物风险评估。使用大鼠中的无观察到不良效应水平(NOAEL)或无观察到效应水平(NOEL)值来估算可接受日摄入量(ADI)。然后,使用估计的 ADI 值来计算三种不同暴露途径(i)仅在娱乐活动中意外摄入受污染地表水,(ii)仅通过食用鱼类,以及(iii)通过娱乐活动中意外摄入受污染地表水和食用鱼类的综合途径的预测无效应浓度(PNEC)。在本研究中使用的假设下,通过娱乐活动期间意外摄入受污染的地表水和鱼类摄入的联合暴露,获得了更高的风险值(危害商数,HQ:337.68,最大值;11.83,最小值),表明可能对人类健康产生影响。在药物中,利托那韦成为主要药物,预计通过食用鱼类对人类健康产生不良影响。混合毒性分析显示,药物暴露的主要风险效应(基于相互作用的危害指数,HI:从洛匹那韦+利托那韦的 295.42 到氯喹+雷帕霉素的 1.20)表明由于水中共存药物可能存在风险。受污染水中背景污染物的存在并没有像低 HQ 值(<1)所表明的那样对观察到的风险估计值产生任何影响。需要对水中药剂进行常规监测,以减少药剂对人类健康的不良影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d19/7942154/b0ef6359e5e6/ga1_lrg.jpg

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