PMID- 37897874
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20231127
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Linking)
VI  - 181
DP  - 2023 Nov
TI  - Exposure to organophosphate flame retardants and plasticizers is positively 
      associated with wheeze and FeNO and eosinophil levels among school-aged children: 
      The Hokkaido study.
PG  - 108278
LID - S0160-4120(23)00551-2 [pii]
LID - 10.1016/j.envint.2023.108278 [doi]
AB  - Exposure to organophosphate flame retardants and plasticizers (PFRs) increases 
      the risk of asthma and allergies. However, little is known about its association 
      with type 2 inflammation (T2) biomarkers used in the management of allergies. The 
      study investigated associations among urinary PFR metabolite concentrations, 
      allergic symptoms, and T2 biomarkers. The data and samples were collected between 
      2017 and 2020, including school children (n = 427) aged 9-12 years living in 
      Sapporo City, Japan, among the participants of "The Hokkaido Study on Environment 
      and Children's Health." Thirteen urinary PFR metabolites were measured by 
      LC-MS/MS. Allergic symptoms were assessed using the International Study of Asthma 
      and Allergies in Childhood questionnaire. For T2 biomarkers, the peripheral blood 
      eosinophil counts, fraction of exhaled nitric oxide level (FeNO), and serum total 
      immunoglobulin E level were measured. Multiple logistic regression analysis, 
      quantile-based g-computation (qg-computation), and Bayesian kernel machine 
      regression (BKMR) were used to examine the associations between the health 
      outcomes of the individual PFRs and the PFR mixtures. The highest concentration 
      of PFR was Sigmatris(1-chloro-isopropyl) phosphates (SigmaTCIPP) (Median:1.20 nmol/L). 
      Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) was significantly associated with 
      a high odds ratio (OR, 95%CI:1.36, 1.07-1.72) for wheeze. TDCIPP (OR, 95%CI:1.19, 
      1.02-1.38), Sigmatriphenyl phosphate (SigmaTPHP) (OR, 95%CI:1.81, 1.40-2.37), and 
      Sigmatris(2-butoxyethyl) phosphate (SigmaTBOEP) (OR, 95%:1.40, 1.13-1.74) were 
      significantly associated with increased odds of FeNO (>/=35 ppb). SigmaTPHP (OR, 
      95%CI:1.44, 1.15-1.83) was significantly associated with high eosinophil counts 
      (>/=300/muL). For the PFR mixtures, a one-quartile increase in all PFRs (OR, 
      95%CI:1.48, 1.18-1.86) was significantly associated with high FeNO (>/=35 ppb) in 
      the qg-computation model. The PFR mixture was positively associated with high 
      FeNO (>/=35 ppb) and eosinophil counts (>/=300/muL) in the BKMR models. These results 
      may suggest that exposure to PFRs increases the probability of asthma, allergies, 
      and T2 inflammation.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Zeng, Yi
AU  - Zeng Y
AD  - Graduate School of Health Sciences, Hokkaido University, 060-0812 Sapporo, Japan.
FAU - Goudarzi, Houman
AU  - Goudarzi H
AD  - Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, 
      060-8638 Sapporo, Japan.
FAU - Ait Bamai, Yu
AU  - Ait Bamai Y
AD  - Center for Environmental and Health Sciences, Hokkaido University, 060-0812 
      Sapporo, Japan; Toxicological Center, University of Antwerp, Universiteitsplein 
      1, 2610 Wilrijk, Belgium.
FAU - Ketema, Rahel Mesfin
AU  - Ketema RM
AD  - Center for Environmental and Health Sciences, Hokkaido University, 060-0812 
      Sapporo, Japan; Faculty of Health Sciences, Hokkaido University, 060-0812 
      Sapporo, Japan.
FAU - Roggeman, Maarten
AU  - Roggeman M
AD  - Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, 
      Belgium.
FAU - den Ouden, Fatima
AU  - den Ouden F
AD  - Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, 
      Belgium.
FAU - Gys, Celine
AU  - Gys C
AD  - Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, 
      Belgium.
FAU - Miyashita, Chihiro
AU  - Miyashita C
AD  - Center for Environmental and Health Sciences, Hokkaido University, 060-0812 
      Sapporo, Japan.
FAU - Ito, Sachiko
AU  - Ito S
AD  - Center for Environmental and Health Sciences, Hokkaido University, 060-0812 
      Sapporo, Japan.
FAU - Konno, Satoshi
AU  - Konno S
AD  - Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, 
      060-8638 Sapporo, Japan.
FAU - Covaci, Adrian
AU  - Covaci A
AD  - Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, 
      Belgium.
FAU - Kishi, Reiko
AU  - Kishi R
AD  - Center for Environmental and Health Sciences, Hokkaido University, 060-0812 
      Sapporo, Japan.
FAU - Ikeda-Araki, Atsuko
AU  - Ikeda-Araki A
AD  - Center for Environmental and Health Sciences, Hokkaido University, 060-0812 
      Sapporo, Japan; Faculty of Health Sciences, Hokkaido University, 060-0812 
      Sapporo, Japan. Electronic address: AAraki@cehs.hokudai.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20231020
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (tris(1,3-dichloroisopropyl) phosphate)
RN  - 0 (Flame Retardants)
RN  - 0 (Plasticizers)
RN  - 0 (Organophosphates)
RN  - 0 (Phosphates)
RN  - 0 (Biomarkers)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Humans
MH  - Child
MH  - *Flame Retardants/analysis
MH  - Plasticizers/adverse effects
MH  - Eosinophils/chemistry/metabolism
MH  - Chromatography, Liquid
MH  - Bayes Theorem
MH  - Tandem Mass Spectrometry
MH  - Organophosphates/urine
MH  - Phosphates
MH  - *Hypersensitivity
MH  - *Asthma/epidemiology
MH  - Inflammation
MH  - Respiratory Sounds/etiology
MH  - Biomarkers/urine
MH  - Nitric Oxide
OTO - NOTNLM
OT  - BKMR
OT  - FeNO
OT  - PFRs
OT  - Peripheral blood eosinophils
OT  - Qg-computation
OT  - Serum total IgE
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/10/29 06:46
MHDA- 2023/11/27 12:44
CRDT- 2023/10/28 18:03
PHST- 2023/06/26 00:00 [received]
PHST- 2023/10/14 00:00 [revised]
PHST- 2023/10/18 00:00 [accepted]
PHST- 2023/11/27 12:44 [medline]
PHST- 2023/10/29 06:46 [pubmed]
PHST- 2023/10/28 18:03 [entrez]
AID - S0160-4120(23)00551-2 [pii]
AID - 10.1016/j.envint.2023.108278 [doi]
PST - ppublish
SO  - Environ Int. 2023 Nov;181:108278. doi: 10.1016/j.envint.2023.108278. Epub 2023 
      Oct 20.