title: The impact of ambient air pollution on the human blood metabolome.
abstract: Biological perturbations caused by air pollution might be reflected in the compounds present in blood originating from air pollutants and endogenous metabolites influenced by air pollution (defined here as part of the blood metabolome). We aimed to assess the perturbation of the blood metabolome in response to short term exposure to air pollution.
  
  
  
  We exposed 31 healthy volunteers to ambient air pollution for 5h. We measured exposure to particulate matter, particle number concentrations, absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and particulate matter oxidative potential. We collected blood from the participants 2h before and 2 and 18h after exposure. We employed untargeted metabolite profiling to monitor 3873 metabolic features in 493 blood samples from these volunteers. We assessed lung function using spirometry and six acute phase proteins in peripheral blood. We assessed the association of the metabolic features with the measured air pollutants and with health markers that we previously observed to be associated with air pollution in this study.
  
  
  
  We observed 89 robust associations between air pollutants and metabolic features two hours after exposure and 118 robust associations 18h after exposure. Some of the metabolic features that were associated with air pollutants were also associated with acute health effects, especially changes in forced expiratory volume in 1s. We successfully identified tyrosine, guanosine, and hypoxanthine among the associated features. Bioinformatics approach Mummichog predicted enriched pathway activity in eight pathways, among which tyrosine metabolism.
  
  
  
  This study demonstrates for the first time the application of untargeted metabolite profiling to assess the impact of air pollution on the blood metabolome.
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, The Netherlands. Electronic address: J.J.Vlaanderen@uu.nl.
authors.forename: J J
authors.initials: JJ
authors.lastname: Vlaanderen
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: N A
authors.initials: NA
authors.lastname: Janssen
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Hoek
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Keski-Rahkonen
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: D K
authors.initials: DK
authors.lastname: Barupal
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, The Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: F R
authors.initials: FR
authors.lastname: Cassee
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Gosens
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Strak
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Steenhof
authors.affiliation: US National Cancer Institute, Bethesda, MD, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Lan
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Brunekreef
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Scalbert
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, The Netherlands.
authors.forename: R C H
authors.initials: RCH
authors.lastname: Vermeulen
mesh_terms: D000293:Adolescent; D000393:Air Pollutants / Q000633:toxicity*; D001769:Blood / Q000378:metabolism*; D004781:Environmental Exposure; D004784:Environmental Monitoring; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D009426:Netherlands; D013997:Time Factors; D055815:Young Adult
chemical_list: D000393:Air Pollutants
keywords: Air pollution; Blood; Cardio-respiratory health effects; Metabolite profiling; Particulate matter components