Screening of ToxCast Chemicals Responsible for Human Adverse Outcomes with Exposure to Ambient Air.
Lin QiaoLirong GaoDi HuangYang LiuChi XuDa LiMinghui ZhengPublished in: Environmental science & technology (2022)
Air pollution poses a major threat to global public health. Although there have been a few investigations into the relationships between organic pollutants and adverse outcomes, the responsible components and molecular mechanisms may be ignored. In this study, a suspect screening method combining comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF MS) with the Toxicity Forecaster (ToxCast) database was applied to analyze complex hydrophobic compounds in ambient air and prospectively figure out toxicologically significant compounds. Seventy-six ToxCast compounds were screened, including seven pollutants receiving less attention and five chemicals never published in the air previously. Given the concentrations, bioactivities, as well as absorption, distribution, metabolism, and excretion properties in vivo, 29 contaminants were assigned high priority since they had active biological effects in the vascular, lung, liver, kidney, prostate, and bone tissues. Phenotypic linkages of key pollutants to potential mechanistic pathways were explored by systems toxicology. A total of 267 chemical-effect pathways involving 29 toxicants and 31 molecular targets were mapped in bipartite network, in which 12 key pathogenic pathways were clarified, which not only provided evidence supporting the previous hypothesis but also provided new insights into the molecular targets. The results would facilitate the development of pollutant priority control, population intervention, and clinical therapeutic strategies so as to substantially reduce human health hazards induced by urban air.
Keyphrases
- air pollution
- gas chromatography
- human health
- public health
- particulate matter
- risk assessment
- mass spectrometry
- tandem mass spectrometry
- prostate cancer
- endothelial cells
- randomized controlled trial
- heavy metals
- lung function
- climate change
- gene expression
- high resolution mass spectrometry
- gas chromatography mass spectrometry
- working memory
- drinking water
- oxidative stress
- emergency department
- bone mineral density
- systematic review
- chronic obstructive pulmonary disease
- postmenopausal women
- electronic health record