Phthalate-induced oxidative stress and association with asthma-related airway inflammation in adolescents.
In Belgium, around 8.5% of the children have asthmatic symptoms. Increased asthma risk in children has been reported in relation to exposure to phthalate plasticizers but the underlying mechanisms are largely unknown.



The aim of this study was to identify if oxidative stress, assessed by excision of 8-hydroxydeoxyguanosine (8-OHdG) from damaged DNA, is an intermediate marker for the association between phthalate exposure and doctor-diagnosed asthma.



In 418 14-15-year-old youngsters, recruited as a representative sample of residents of Flanders (Belgium), personal exposure to phthalates was assessed by measuring phthalate metabolites in urine: mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP) and mono-ethyl phthalate (MEP). Analysis of 8-OHdG in urine was used as a sensitive biomarker of oxidative stress at the level of DNA. The presence of doctor-diagnosed asthma was elicited by a self-administered questionnaire. Associations were assessed using multiple linear and logistic regression models. Mediation was tested using Baron and Kenny's regression approach.



A significant increased risk of a youngster being diagnosed with asthma was found for both urinary MnBP (metabolite of dibutyl phthalate (DBP)) and the sum of the three di(2-ethylhexyl) phthalate metabolites (ΣDEHP=MEHP+MEHHP+MEOHP), with respective odds ratio of 1.84 [95% CI: 1.02, 3.32] for MnBP and 1.94 [95% CI: 1.07, 3.51] for ΣDEHP. In addition, we observed significant associations between all urinary phthalate metabolites and increased urinary levels of 8-OHdG. The associations were stronger in girls than in boys. We did not found evidence that 8-OHdG was associated with doctor-diagnosed asthma.



The results of our study are in line with other findings from epidemiological surveys and raise further concern about DEHP and DBP as risk factors for asthma, however, the underlying mechanisms are not yet well understood.
Flemish Institute for Technological Research (VITO), Mol, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium. Electronic address: frankencarmen@gmail.com.
Carmen
C
Franken
Flemish Institute for Technological Research (VITO), Mol, Belgium.
Nathalie
N
Lambrechts
Flemish Institute for Technological Research (VITO), Mol, Belgium.
Eva
E
Govarts
Flemish Institute for Technological Research (VITO), Mol, Belgium.
Gudrun
G
Koppen
Provincial Institute for Hygiene, Antwerp, Belgium.
Elly
E
Den Hond
Flemish Institute for Technological Research (VITO), Mol, Belgium.
Daniëlla
D
Ooms
Flemish Institute for Technological Research (VITO), Mol, Belgium.
Stefan
S
Voorspoels
Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt, Belgium.
Liesbeth
L
Bruckers
Political and Social Sciences, University of Antwerp, Antwerp, Belgium.
Ilse
I
Loots
Provincial Institute for Hygiene, Antwerp, Belgium.
Vera
V
Nelen
Department of Public Health, Ghent University, Ghent, Belgium; Department of Food Safety and Food Quality, Ghent University, Ghent, Belgium.
Isabelle
I
Sioen
Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium; Department of Public Health & Primary Care, Leuven University, Leuven, Belgium.
Tim S
TS
Nawrot
Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel, Brussels, Belgium.
Willy
W
Baeyens
Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel, Brussels, Belgium; Department of Radiotherapy and Nuclear Medicine, Ghent University, Ghent, Belgium.
Nicolas
N
Van Larebeke
Flemish Institute for Technological Research (VITO), Mol, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Greet
G
Schoeters
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D001249:Asthma / Q000453:epidemiology* / Q000652:urine; D001530:Belgium / Q000453:epidemiology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D016017:Odds Ratio; D018384:Oxidative Stress; D010795:Phthalic Acids / Q000652:urine*
D004785:Environmental Pollutants; D010795:Phthalic Acids; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
8-hydroxydeoxyguanosine; Doctor-diagnosed asthma; Human biomonitoring; Oxidative stress; Phthalate