Positive association between concentration of phthalate metabolites in urine and microparticles in adolescents and young adults

Environ Int. 2016 Jul-Aug:92-93:157-64. doi: 10.1016/j.envint.2016.04.006. Epub 2016 Apr 20.


Di-(2-ethylhexyl) phthalate (DEHP) has been used worldwide in various products for many years. In vitro studies have shown that exposure to DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) induces endothelial cell apoptosis. Moreover, exposure to DEHP had been linked to cardiovascular risk factors and cardiovascular diseases in epidemiological studies. Circulating microparticles have been known to be indicators of vascular injury. However, whether DEHP or its metabolites are independently associated with microparticles in humans remains unknown. From 2006 to 2008, we recruited 793 subjects (12-30years) from a population-based sample to participate in this cardiovascular disease prevention examination. Each participant was subjected to interviews and biological sample collection to determine the relationship between concentrations of DEHP metabolites MEHP, mono(ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethly-5-oxoheyl) phthalate in urine and concentrations of endothelial microparticles (CD62E and CD31+/CD42a-), platelet microparticles (CD62P and CD31+/CD42a+), and CD14 in serum. Multiple linear regression analysis revealed that an ln-unit increase in MEHP concentration in urine was positively associated with an increase in serum microparticle counts/μL of 0.132 (±0.016) in CD31+/CD42a- (endothelial apoptosis marker), 0.117 (±0.023) in CD31+/CD42a+ (platelet apoptosis marker), and 0.026 (±0.007) in CD14 (monocyte, macrophage, and neutrophil activation marker). There was no association between DEHP metabolite concentration and CD62E or CD62P. In conclusion, a higher MEHP concentration in urine was associated with an increase in endothelial and platelet microparticles in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to DEHP and atherosclerosis.

Keywords: CD14; CD31; CD42a; DEHP (di-(2-ethylhexyl) phthalate); MEHP (mono(2-ethylhexyl) phthalate); Microparticles.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / urine
  • Diethylhexyl Phthalate / chemistry
  • Diethylhexyl Phthalate / metabolism*
  • E-Selectin
  • Environmental Pollutants / chemistry
  • Environmental Pollutants / metabolism
  • Environmental Pollutants / urine
  • Female
  • Humans
  • Male
  • Particle Size
  • Particulate Matter / chemistry*
  • Phthalic Acids / chemistry
  • Phthalic Acids / metabolism*
  • Phthalic Acids / urine
  • Risk Factors
  • Young Adult


  • Biomarkers
  • E-Selectin
  • Environmental Pollutants
  • Particulate Matter
  • Phthalic Acids
  • SELE protein, human
  • phthalic acid
  • Diethylhexyl Phthalate