title: Urinary t,t-muconic acid as a proxy-biomarker of car exhaust and neurobehavioral performance in 15-year olds.
abstract: BACKGROUND
  Traffic-related air pollution has been shown to induce neurotoxicity in rodents. Several recent epidemiological studies reported negative associations between residential outdoor air pollution and neurobehavioral performance. We investigated in a population of non-smoker adolescents the associations between the urinary concentration of trans, trans-muconic acid (t,t-MA-U), a metabolite of benzene and used as proxy-biomarker of traffic exposure, and two neurobehavioral domains, i.e. sustained attention and short-term memory.
  
  
  METHODS
  In the framework of an environmental health surveillance study in Flanders (Belgium), we examined between 2008 and 2014 grade nine high school students (n=895). We used reaction time, number of omission errors, and number of commission errors in the Continuous Performance Test to evaluate sustained attention, and for the evaluation of short-term memory we used maximum digit span forward and backward of the Digit Span Test. We measured blood lead (PbB) to assess the independent effect of t,t-MA-U on neurobehavioral outcomes.
  
  
  RESULTS
  This neurobehavioral examination study showed that a ten-fold increase in t,t-MA-U was associated with a 0.14 SD lower sustained attention (95% Confidence Interval: -0.26 to -0.019; p=0.02) and a 0.17 SD diminished short-term memory (95% CI: -0.31 to -0.030; p=0.02). For the same increment in t,t-MA-U, the Continuous Performance Test showed a 12.2ms higher mean reaction time (95% CI: 4.86-19.5; p=0.001) and 0.51 more numbers of errors of omission (95% CI: 0.057-0.97; p=0.028), while no significant association was found with errors of commission. For the Digit Span Tests, the maximum digit span forward was associated with a 0.20 lower number of digits (95% CI: -0.38 to -0.026; p=0.025) and maximum digit span backward with -0.15 digits (95% CI: -0.32 to 0.022; p=0.088). These associations were independent of PbB, parental education and other important covariates including gender, age, passive smoking, ethnicity, urinary creatinine, time of the day, and examination day of the week. For PbB, an independent association was only found with mean reaction time of the Continuous Performance Test (19.1ms, 95% CI: 2.43-35.8; p=0.025).
  
  
  CONCLUSIONS
  In adolescents, a ten-fold increase in the concentration of t,t-MA-U, used as a proxy-biomarker for traffic-related exposure, was associated with a significant deficit in sustained attention and short-term memory. The public health implications of this finding cannot be overlooked as the effect-size for these neurobehavioral domains was about 40% of the effect-size of parental education.
authors: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Michal
authors: M
authors: Kicinski
authors: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Nelly D
authors: ND
authors: Saenen
authors: Department of Neurology, Sint Dimphna Hospital, Geel, Belgium.
authors: Mineke K
authors: MK
authors: Viaene
authors: Department of Health, Provincial Institute for Hygiene, Antwerp, Belgium.
authors: Elly
authors: E
authors: Den Hond
authors: Flemish Institute for Technological Research, Environmental Risk and Health, Mol, Belgium.
authors: Greet
authors: G
authors: Schoeters
authors: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Michelle
authors: M
authors: Plusquin
authors: Department of Health, Provincial Institute for Hygiene, Antwerp, Belgium.
authors: Vera
authors: V
authors: Nelen
authors: Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium.
authors: Liesbeth
authors: L
authors: Bruckers
authors: Department of Public Health, Ghent University, Ghent, Belgium.
authors: Isabelle
authors: I
authors: Sioen
authors: Department of Sociology, University of Antwerp, Antwerp, Belgium.
authors: Ilse
authors: I
authors: Loots
authors: Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors: Willy
authors: W
authors: Baeyens
authors: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium; Louvain Centre for Toxicology and Applied Pharmacology, Université catholique de Louvain, Brussels, Belgium.
authors: Harry A
authors: HA
authors: Roels
authors: Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium; Department of Public Health and Primary Care, Environment & Health Unit, Leuven University, Leuven, Belgium. Electronic address: tim.nawrot@uhasselt.be.
authors: Tim S
authors: TS
authors: Nawrot
mesh_terms: D000293:Adolescent; D001288:Attention / Q000187:drug effects*; D001554:Benzene / Q000378:metabolism; D004784:Environmental Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D011594:Psychometrics; D013011:Sorbic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: D001335:Vehicle Emissions; C005939:muconic acid; D001554:Benzene; D013011:Sorbic Acid
keywords: Adolescents; Blood lead; Car exhaust; Neurobehavioral performance; Traffic-related air pollution; Trans, trans-muconic acid