Phosphate Flame Retardants and Plasticizers and Their Association with Reproductive and Steroid Hormone Levels among Peripubertal-Aged Children: The Hokkaido Birth Cohort Study.

Mar 10, 2025

Experts: Atsuko Ikeda,Takeshi Yamaguchi,Yu Ait Bamai,Maarten Roggeman,Yoshinori Ikenaka,Yi Zeng,Ayaka Yasuda,Rahel Mesfin Ketema,Megasari Marsela,Celine Gys,Fatima den Ouden,Sachiko Itoh,Akie Nakamura,Takeya Kitta,Masafumi Kon,Atsushi Manabe,Adrian Covaci,Reiko Kishi

This cross-sectional study investigated associations between exposure to organophosphate flame retardants and plasticizers (PFRs) and reproductive and steroid hormones in peripubertal children from the Hokkaido Birth Cohort (429 children aged 9-12 years; between September 2017 and March 2020). Thirteen urinary PFR metabolites and 14 plasma steroid hormones were investigated using LC-MS/MS and four reproductive hormones were investigated using immunoassays. Linear regression for single PFR, quantile g-computation, and Bayesian machine kernel regression (BKMR) models for the PFR mixtures were used to examine the association between hormones and PFRs. Among boys, significant positive associations were observed between estradiol and ΣTCIPP and ΣTBOEP, and inverse associations were identified between insulin-like factor-3 (INSL3) and ΣTCIPP, and between luteinizing hormone (LH) and ΣEHDPHP. The PFR mixture was associated with the trends of increasing estradiol and androstenedione, and decreasing cortisol, cortisone, LH, inhibin B, and INSL3. Among girls, androstenedione and ΣTCIPP, testosterone and ΣEHDPHP, (androstenedione + testosterone)/DHEA-S and ΣTCIPP, and ΣEHDPHP and ΣTPHP were significantly correlated. The PFR mixture showed trends of increasing testosterone, androstenedione, and inhibin B, and decreasing cortisol, cortisone, and INSL3. Individual PFRs and PFR mixtures altered steroids and reproductive hormones in peripubertal children.

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ABOUT THE EXPERTS

Atsuko Ikeda,Takeshi Yamaguchi,Yu Ait Bamai,Maarten Roggeman,Yoshinori Ikenaka,Yi Zeng,Ayaka Yasuda,Rahel Mesfin Ketema,Megasari Marsela,Celine Gys,Fatima den Ouden,Sachiko Itoh,Akie Nakamura,Takeya Kitta,Masafumi Kon,Atsushi Manabe,Adrian Covaci,Reiko Kishi

Atsuko Ikeda

Faculty of Health Sciences, Hokkaido University, Kita 12, Nishi 5, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Center for Environmental and Health Sciences, Hokkaido University, Kita 12, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Takeshi Yamaguchi

Center for Environmental and Health Sciences, Hokkaido University, Kita 12, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Faculty of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.

Yu Ait Bamai

Center for Environmental and Health Sciences, Hokkaido University, Kita 12, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Toxicological Center, University of Antwerp, Building S- Room S.551, Universiteitsplein 1, Wilrijk 2610, Belgium.

Maarten Roggeman

Toxicological Center, University of Antwerp, Building S- Room S.551, Universiteitsplein 1, Wilrijk 2610, Belgium.

Yoshinori Ikenaka

One Health Research Center, Kita Hokkaido University, Kita 20, Nishi 10, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.

Yi Zeng

Faculty of Health Sciences, Hokkaido University, Kita 12, Nishi 5, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Center for Environmental and Health Sciences, Hokkaido University, Kita 12, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Creative Research Institution, Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo, Hokkaido 060-0021, Japan.

Ayaka Yasuda

Faculty of Health Sciences, Hokkaido University, Kita 12, Nishi 5, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Graduate School of Pharmacy, Hokkaido University of Health Sciences, 1757 Kanazawa, Tobetsu, Hokkaido 061-0293, Japan.

Rahel Mesfin Ketema

Faculty of Health Sciences, Hokkaido University, Kita 12, Nishi 5, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Center for Environmental and Health Sciences, Hokkaido University, Kita 12, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Megasari Marsela

Faculty of Health Sciences, Hokkaido University, Kita 12, Nishi 5, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Celine Gys

Toxicological Center, University of Antwerp, Building S- Room S.551, Universiteitsplein 1, Wilrijk 2610, Belgium.

Fatima den Ouden

Toxicological Center, University of Antwerp, Building S- Room S.551, Universiteitsplein 1, Wilrijk 2610, Belgium.

Sachiko Itoh

Center for Environmental and Health Sciences, Hokkaido University, Kita 12, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.

Akie Nakamura

Department of Molecular Endocrinology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo 157-8535, Japan.

Takeya Kitta

Asahikawa Medical University, 1-1-1 Midorigaokahigashi 2 Jo, Asahikawa, Hokkaido 078-8510, Japan.

Masafumi Kon

Faculty of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.

Atsushi Manabe

Faculty of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.

Adrian Covaci

Toxicological Center, University of Antwerp, Building S- Room S.551, Universiteitsplein 1, Wilrijk 2610, Belgium.

Reiko Kishi

Center for Environmental and Health Sciences, Hokkaido University, Kita 12, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.