Inverse associations of bisphenol A and phthalate metabolites with serum bilirubin levels in Korean population

  • Yoonjeong Choi
  • Sun Ju Lee
  • Jooeun Jeon
  • Keum Ji Jung
  • Sun Ha JeeEmail author
Research Article


Bisphenol A (BPA) and phthalates are endocrine disruptors that can induce oxidative stress. Serum bilirubin has antioxidant properties and may serve as a biomarker of oxidative stress. The objective of this study was to explore the relationship of BPA and phthalates with serum bilirubin levels in a Korean population. Urinary concentrations of BPA and six phthalate [mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono-benzyl phthalate (MBzP)] were measured in 709 participants. Serum concentrations of BPA and three phthalate metabolites [MnBP, MiBP, and mono-(2-ethylhexyl) phthalate (MEHP)] were measured in 752 participants. After excluding missing variables, associations between above chemicals and serum bilirubin levels were analyzed using multivariate linear regression with age, sex, BMI, GGT, GOT, GPT, and alcohol intake adjustment. Participants were further stratified by sex. Among the urinary chemicals, BPA and four phthalate metabolites (MnBP, MEOHP, MEHHP and MECPP) were inversely associated with serum bilirubin levels (BPA: β = − 0.071, P < 0.0001; MnBP: β = − 0.055, P = 0.025; MEOHP: β = − 0.101, P < 0.0001; MEHHP: β = − 0.106, P < 0.0001; MECPP: β = − 0.052, P = 0.003). In a case of serum chemicals, only MiBP showed significantly positive association (β = 0.036, P = 0.016). After stratification by sex, the associations of urinary BPA remained both in male and female, of which urinary phthalates disappeared in female. The association of serum MiBP was disappeared after stratification. Urinary BPA and phthalate metabolites were inversely associated with serum bilirubin levels, whereas serum MiBP showed positive association with bilirubin. These results could provide clues for understanding the mechanisms of endocrine disruptor from oxidative stress to excretion from our body.


Bisphenol  Phthalate Endocrine disruptors Bilirubin Inverse association Linear models 



We are extremely grateful to the staff of the Korean Medical Institute (KMI, Seoul, Korea) health examination centers who recruited our participants.

Source of funding

This work was supported by a grant (18162MFDS121) from the Ministry of Food and Drug Safety, Republic of Korea.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants

The Institutional Review Board of Yonsei University approved this study protocol (No. 4–2017-1078).

Informed consent

This cross-sectional study involves human and signed written consent form was obtained from all participants from 2015 to 2016.

Supplementary material

11356_2019_5205_MOESM1_ESM.docx (1.2 mb)
ESM 1 (DOCX 1241 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Public Health, Graduate SchoolYonsei UniversitySeoulSouth Korea
  2. 2.Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public HealthYonsei UniversitySeoulSouth Korea

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