PMID- 36760168 OWN - NLM STAT- MEDLINE DCOM- 20231218 LR - 20231218 IS - 1520-5851 (Electronic) IS - 0013-936X (Linking) VI - 57 IP - 46 DP - 2023 Nov 21 TI - Associations of Urinary Phthalate Metabolites with Thyroid Function and the Mediated Role of Cytokines: A Panel Study of Healthy Children. PG - 17808-17817 LID - 10.1021/acs.est.2c07656 [doi] AB - Evidence on joint association of a phthalate mixture with thyroid function among children and its underlying mechanism is largely unknown. We aimed to explore the associations of 10 urinary phthalate metabolites (mPAEs), either as individuals or as a mixture, with thyroid function indicators [free thyroxine, free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH)] in 144 children aged 4-12 years with up to 3 repeated visits across 3 seasons. Significant and positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) with TSH, as well as monobenzyl phthalate (MBzP) with FT3 in dose-response manners. The relationship between MEHP and TSH remained robust in multiple-phthalate models. Bayesian kernel machine regression (BKMR) models revealed overall linear associations of the 10 mPAE mixture with higher TSH and FT3 levels, and MEHP and MBzP were major contributors. Meanwhile, MEHP, MiBP, and MnBP were linked to the elevation of multiple cytokines including CCL 27, CCL3, CXCL1, and IL-16. Among them, IL-16 mediated the relationships of MEHP and MiBP with TSH, and the mediated proportions were 24.16% and 24.27%, respectively. Our findings suggested that mPAEs dominated by MEHP were dose-responsively associated with elevated TSH among healthy children and mediated by IL-16. FAU - Yang, Huihua AU - Yang H AD - Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Zheng, Yuming AU - Zheng Y AD - The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China. FAU - Lai, Xuefeng AU - Lai X AD - Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Zhao, Lei AU - Zhao L AD - Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Liu, Linlin AU - Liu L AD - Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Liu, Miao AU - Liu M AD - Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Guo, Wenting AU - Guo W AD - Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Yang, Liangle AU - Yang L AUID- ORCID: 0000-0001-9751-1904 AD - Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Fang, Qin AU - Fang Q AD - Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Zhu, Kejing AU - Zhu K AD - Zhuhai Center for Disease Control and Prevention, Zhuhai 519000, China. FAU - Dai, Wencan AU - Dai W AD - Zhuhai Center for Disease Control and Prevention, Zhuhai 519000, China. FAU - Mei, Wenhua AU - Mei W AD - Zhuhai Center for Disease Control and Prevention, Zhuhai 519000, China. FAU - Zhu, Rui AU - Zhu R AD - Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Zhang, Xiaomin AU - Zhang X AUID- ORCID: 0000-0002-1919-3629 AD - Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. LA - eng PT - Journal Article DEP - 20230209 PL - United States TA - Environ Sci Technol JT - Environmental science & technology JID - 0213155 RN - 6O7F7IX66E (phthalic acid) RN - 0 (Environmental Pollutants) RN - FU2EWB60RT (mono-(2-ethylhexyl)phthalate) RN - 0 (Interleukin-16) RN - 0 (mono-isobutyl phthalate) RN - ZI46LWZ45G (monobutyl phthalate) RN - 0 (Phthalic Acids) RN - 9002-71-5 (Thyrotropin) SB - IM EIN - Environ Sci Technol. 2023 Oct 3;57(39):14769. PMID: 37733917 MH - Child MH - Humans MH - Environmental Exposure MH - *Environmental Pollutants MH - Thyroid Gland/metabolism MH - Bayes Theorem MH - Interleukin-16 MH - *Phthalic Acids/metabolism MH - Thyrotropin OTO - NOTNLM OT - BKMR OT - cytokines OT - mediation effects OT - phthalates OT - thyroid function EDAT- 2023/02/11 06:00 MHDA- 2023/12/18 06:42 CRDT- 2023/02/10 02:02 PHST- 2023/12/18 06:42 [medline] PHST- 2023/02/11 06:00 [pubmed] PHST- 2023/02/10 02:02 [entrez] AID - 10.1021/acs.est.2c07656 [doi] PST - ppublish SO - Environ Sci Technol. 2023 Nov 21;57(46):17808-17817. doi: 10.1021/acs.est.2c07656. Epub 2023 Feb 9.