PMID- 33882432
OWN - NLM
STAT- MEDLINE
DCOM- 20210702
LR  - 20230214
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Print)
IS  - 0160-4120 (Linking)
VI  - 154
DP  - 2021 Sep
TI  - Individual and joint effects of phthalate metabolites on biomarkers of oxidative 
      stress among pregnant women in Puerto Rico.
PG  - 106565
LID - S0160-4120(21)00190-2 [pii]
LID - 10.1016/j.envint.2021.106565 [doi]
AB  - Exposures to phthalate compounds have been linked to adverse birth outcomes, 
      potentially through oxidative stress mechanisms. We explored associations between 
      mixtures of biomarkers of phthalate and phthalate replacement metabolites and 
      oxidative stress using lipid peroxidation biomarker 8-iso-prostaglandin-F2alpha 
      (8-iso-PGF2alpha). As 8-iso-PGF2alpha can be generated via both chemical (nonenzymatic) 
      and enzymatic lipid peroxidation pathways, we calculated the ratio of 
      8-iso-PGF2alpha/prostaglandin F2alpha in an attempt to distinguish the potential 
      contributions of the two pathways. Urinary biomarker measurements were taken from 
      775 pregnant women in the Puerto Rico Testsite for Exploring Contamination 
      Threats (PROTECT) longitudinal birth cohort at up to three time points during 
      gestation (16-20, 20-24, and 24-28 weeks gestation). Adaptive elastic net with 
      pairwise linear interaction terms (adENET-I) was used to determine individual 
      phthalate metabolites and phthalate interactions that were predictive of lipid 
      oxidative stress biomarkers, and to subsequently create environmental risk scores 
      (ERS) to represent weighted sums of phthalate exposure for each individual at 
      each study visit. Repeated ERS were then used in linear mixed effects models to 
      test for associations between biomarkers of phthalate mixtures and biomarkers of 
      oxidative stress. We also used Bayesian kernel machine regression (BKMR) to 
      explore nonlinearity and interactions between phthalate metabolites within the 
      mixture. An increase from the first to fourth quartile of phthalate ERS derived 
      from adENET-I was associated with a 96.7% increase (95% CI: 74.0, 122) in the 
      hypothesized chemical fraction of 8-iso-PGF2alpha and a 268% increase (95% CI: 139, 
      465) in the hypothesized enzymatic fraction of 8-iso-PGF2alpha. BKMR analyses also 
      suggested strong linear associations between the phthalate mixture and biomarkers 
      of lipid oxidative stress. Various phthalates displayed nonlinear relationships 
      with both chemical and enzymatic fractions of 8-iso-PGF2alpha, and we observed some 
      evidence of interactions between metabolites in the mixture. In conclusion, 
      exposure to phthalate mixtures was strongly associated with linear increases in 
      biomarkers of lipid oxidative stress, and differences observed between 
      hypothesized chemical and enzymatic lipid peroxidation outcomes highlight the 
      need to critically assess pathways of 8-iso-PGF2alpha generation in relation to 
      environmental exposures.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Cathey, Amber L
AU  - Cathey AL
AD  - Department of Environmental Health Sciences, University of Michigan School of 
      Public Health, Ann Arbor, MI, USA.
FAU - Eaton, Jarrod L
AU  - Eaton JL
AD  - Department of Environmental Health Sciences, University of Michigan School of 
      Public Health, Ann Arbor, MI, USA.
FAU - Ashrap, Pahriya
AU  - Ashrap P
AD  - Department of Environmental Health Sciences, University of Michigan School of 
      Public Health, Ann Arbor, MI, USA.
FAU - Watkins, Deborah J
AU  - Watkins DJ
AD  - Department of Environmental Health Sciences, University of Michigan School of 
      Public Health, Ann Arbor, MI, USA.
FAU - Rosario, Zaira Y
AU  - Rosario ZY
AD  - Graduate School of Public Health, Medical Sciences Campus, University of Puerto 
      Rico, San Juan, PR, USA.
FAU - Velez Vega, Carmen
AU  - Velez Vega C
AD  - Graduate School of Public Health, Medical Sciences Campus, University of Puerto 
      Rico, San Juan, PR, USA.
FAU - Alshawabkeh, Akram N
AU  - Alshawabkeh AN
AD  - College of Engineering, Northeastern University, Boston, MA, USA.
FAU - Cordero, Jose F
AU  - Cordero JF
AD  - College of Public Health, University of Georgia, Athens, GA, USA.
FAU - Mukherjee, Bhramar
AU  - Mukherjee B
AD  - Department of Biostatistics, University of Michigan School of Public Health, Ann 
      Arbor, MI, USA.
FAU - Meeker, John D
AU  - Meeker JD
AD  - Department of Environmental Health Sciences, University of Michigan School of 
      Public Health, Ann Arbor, MI, USA. Electronic address: meekerj@umich.edu.
LA  - eng
GR  - P42 ES017198/ES/NIEHS NIH HHS/United States
GR  - R01 ES031591/ES/NIEHS NIH HHS/United States
GR  - P30 ES017885/ES/NIEHS NIH HHS/United States
GR  - UH3 OD023251/OD/NIH HHS/United States
GR  - R01 ES032203/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210423
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (Biomarkers)
RN  - 0 (Phthalic Acids)
RN  - 6O7F7IX66E (phthalic acid)
SB  - IM
MH  - Bayes Theorem
MH  - Biomarkers/metabolism
MH  - Female
MH  - Humans
MH  - Oxidative Stress
MH  - *Phthalic Acids/toxicity
MH  - Pregnancy
MH  - *Pregnant Women
MH  - Puerto Rico
PMC - PMC9923976
MID - NIHMS1870736
OTO - NOTNLM
OT  - Birth cohort
OT  - Mixtures analysis
OT  - Oxidative stress
OT  - Phthalate
EDAT- 2021/04/22 06:00
MHDA- 2021/07/03 06:00
PMCR- 2023/02/13
CRDT- 2021/04/21 20:15
PHST- 2021/02/03 00:00 [received]
PHST- 2021/03/15 00:00 [revised]
PHST- 2021/04/06 00:00 [accepted]
PHST- 2021/04/22 06:00 [pubmed]
PHST- 2021/07/03 06:00 [medline]
PHST- 2021/04/21 20:15 [entrez]
PHST- 2023/02/13 00:00 [pmc-release]
AID - S0160-4120(21)00190-2 [pii]
AID - 10.1016/j.envint.2021.106565 [doi]
PST - ppublish
SO  - Environ Int. 2021 Sep;154:106565. doi: 10.1016/j.envint.2021.106565. Epub 2021 
      Apr 23.