Phthalate exposure and its effects on onset of puberty

• Project/Area Number: 26670321
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hygiene and public health
• Research Institution: Hokkaido University
• Principal Investigator: Araki Atsuko 北海道大学, 環境健康科学研究教育センター, 准教授 (00619885)
• Co-Investigator(Kenkyū-buntansha): 三井 貴彦 山梨大学, 総合研究部, 准教授 (90421966) ; 池野 多美子 北海道大学, 環境健康科学研究教育センター, 客員研究員 (80569715) ; Goudarzi Houman (GOUDARZI Houman) 北海道大学, 医学研究科, 助教 (40713607) ; 伊藤 佐智子 北海道大学, 環境健康科学研究教育センター, 特任講師 (90580936) ; 宮下 ちひろ 北海道大学, 環境健康科学研究教育センター, 特任准教授 (70632389)
• Co-Investigator(Renkei-kenkyūsha): KISHI Reiko 北海道大学, 環境健康科学研究教育センター, 特別招へい教授 (80112449)
• Research Collaborator: AITBAMAI Yu 北海道大学, 環境健康科学研究教育センター, 特任助教 (90752907)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 環境 / 衛生 / フタル酸エステル / 第二次性徴 / 性ホルモン / 遺伝子 / 性腺機能

Outline of Final Research Achievements

Phthalates are ubiquitous environmental chemicals, which are widely used as plasticizes. Humans are exposed to phthalates since fetal life, and their endocrine disrupting properties has been concerned. However, prenatal exposure to phahalates and their effects on fetus onset of puberty in human are not well known. In this study, onset of puberty were examined among children registered to Sapporo cohort, the Hokkaido Study. Among those approached, 150 (45.6%) responded. Total effects of MEHP (primary metabolite of the most widely used phthalate, DEHP) levels in maternal blood was significantly positively associated with onset of puberty; natural log increase of MEHP (app. 2.67), onset of puberty delayed 7.17（95%CI：2.89-11.5）months among boys. Although progesterone and inhibin B were inversely associated with MEHP, none of hormones showed indirect effect of MEHP to onset of puberty. Girls did not show any association between MEHP, hormones, or onset of puberty.

Research Products

• [Journal Article] Prenatal di-2-ethylhexyl phthalate exposure and cord blood adipokine levels and birth size: The Hokkaido study on environment and children's health (2017)
  • Author(s): Minatoya M., Araki A., Miyashita C., Sasaki S., Goto Y., Nakajima T., Kishi R.
  • Journal Title: Sci Total Environ Volume: 579 Pages: 606-611
  • DOI: 10.1016/j.scitotenv.2016.11.051
  • NAID: 120006551571
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prenatal di(2-ethylhexyl) phthalate exposure and disruption of adrenal androgens and glucocorticoids levels in cord blood: The Hokkaido Study (2017)
  • Author(s): Araki A., Mitsui T., Goudarzi H., Nakajima T., Miyashita C., Itoh S., Sasaki S., Cho K., Moriya K., Shinohara N., Nonomura K., Kishi R.
  • Journal Title: Science of the Total Environment Volume: 581-582 Pages: 297-304
  • DOI: 10.1016/j.scitotenv.2016.12.124
  • NAID: 120006558980
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Relationship between the Second-to-Fourth Digit Ratio and Behavioral Sexual Dimorphism in School-Aged Children. (2016)
  • Author(s): Mitsui T, Araki A, Miyashita C, Ito S, Ikeno T, Sasaki S, Kitta T, Moriya K, Cho K, Morioka K, Kishi R, Shinohara N, Takeda M, Nonomura K.
  • Journal Title: PLoS One. Volume: 11(1) Issue: 1 Pages: e0146849-e0146849
  • DOI: 10.1371/journal.pone.0146849
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of adrenal androgens during the prenatal period on the second to fourth digit ratio in school-aged children (2016)
  • Author(s): Mitsui T., Araki A., Goudarzi H., Miyashita C., Ito S., Sasaki S., Kitta T., Moriya K., Cho K., Morioka K., Kishi R., Shinohara N., Takeda M., Nonomura K.
  • Journal Title: Steroids Volume: 113 Pages: 46-51
  • DOI: 10.1016/j.steroids.2016.06.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 【講座 子どもを取り巻く環境と健康】第13回 環境化学物質曝露による内分泌系への影響（2）性ホルモン (2016)
  • Author(s): 荒木敦子, 伊藤佐智子, 岸玲子
  • Journal Title: 公衆衛生 Volume: 80（3） Pages: 221-227
  • Acknowledgement Compliant
• [Journal Article] 環境化学物質の次世代影響に関する出生コホート研究：環境と子どもの健康に関する北海道スタディの成果と課題 (2016)
  • Author(s): 岸玲子, 宮下ちひろ, 荒木敦子
  • Journal Title: アンチ・エイジング医学 Volume: 12（2） Pages: 067-076
  • Acknowledgement Compliant
• [Journal Article] Associations of Perfluoroalkyl Substances (PFASs) with Lower Birth Weight: An Evaluation of Potential Confounding by Glomerular Filtration Rate Using a Physiologically Based Pharmacokinetic Model (PBPK). (2015)
  • Author(s): M. A. Verner, A. E. Loccisano, N. H. Morken, M. Yoon, H. Wu, R. McDougall, M. Maisonet, M. Marcus, R. Kishi, C. Miyashita, M. H. Chen, W. S. Hsieh, M. E. Andersen, H. J. Clewell, 3rd and M. P. Longnecker.
  • Journal Title: Environ Health Perspect Volume: 123 Issue: 12 Pages: 1317-1317
  • DOI: 10.1289/ehp.1408837
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effects of in utero exposure to polychlorinated biphenyls, methylmercury, and polyunsaturated fatty acids on birth size (2015)
  • Author(s): C. Miyashita, S. Sasaki, T. Ikeno, A. Araki, S. Ito, J. Kajiwara, T. Todaka, N. Hachiya, A. Yasutake, K. Murata, T. Nakajima and R. Kishi
  • Journal Title: Sci Total Environ Volume: 533 Pages: 256-265
  • DOI: 10.1016/j.scitotenv.2015.06.108
  • Peer Reviewed / Open Access
• [Journal Article] Effects of prenatal Leydig cell function on the ratio of the second to fourth digit lengths in school-aged children (2015)
  • Author(s): Mitsui T., Araki A., Imai A, Sato S., Miyashita C., Ito S., Sasaki S., Kitta T., Moriya K. Cho K., Morioka K., Kihsi R., Nonomura K
  • Journal Title: PLOS One Volume: 10(3) Issue: 3 Pages: e0120636-e0120636
  • DOI: 10.1371/journal.pone.0120636
  • NAID: 120005606031
  • Peer Reviewed / Open Access
• [Journal Article] The Association of Prenatal Exposure to Perfluorinated Chemicals with Maternal Fatty Acids during Pregnancy and the Birth Weight of their Offspring:The Hokkaido Study (2015)
  • Author(s): Reiko Kishi, Tamie Nakajima, Houman Goudarzi, Sachiko Kobayashi, Seiko Sasaki, Emiko Okada, Chihiro Miyashita, Sachiko Itoh, Atsuko Araki, Tamiko Ikeno, Yusuke Iwasaki, and Hiroyuki Nakazawa
  • Journal Title: Environmental Health Perspective Volume: 印刷中 Issue: 10 Pages: 1038-1045
  • DOI: 10.1289/ehp.1408834
  • Peer Reviewed / Open Access
• [Journal Article] Comparisons of urinary phthalate metabolites and daily phthalate intakes among Japanese families (2015)
  • Author(s): Yu Ait Bamai, Atsuko Araki, Toshio Kawai, Tazuru Tsuboi, Eiji Yoshioka, Ayako Kanazawa, Shi Cong, Reiko Kishi
  • Journal Title: International Journal of Hygiene and Environmental Health Volume: in press Issue: 5 Pages: 461-470
  • DOI: 10.1016/j.ijheh.2015.03.013
  • NAID: 120005820699
  • Peer Reviewed / Open Access
• [Journal Article] Prenatal maternal blood triglyceride and fatty acid levels in relation to exposure to di(2-ethylhexyl)phthalate: a cross-sectional study. (2015)
  • Author(s): Jia X, Harada Y, Tagawa M, Naito H, Hayashi Y, Yetti H, Kato M, Sasaki S, Araki A, Miyashita C, Ikeno T, Kishi R, Nakajima T.
  • Journal Title: Environ Health Prev Med. Volume: In press Issue: 3 Pages: 168-178
  • DOI: 10.1007/s12199-014-0440-4
  • NAID: 210000000370
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 【講座 子どもを取り巻く環境と健康】第10回 乳幼児のアレルギーと胎児期・小児期の可塑剤・難燃剤曝露 (2015)
  • Author(s): 荒木敦子, アイツバマイゆふ, 岸玲子
  • Journal Title: 公衆衛生 Volume: 79 Pages: 876-881
• [Journal Article] 環境化学物質がホルモン環境および身体的変化に与える影響について (2015)
  • Author(s): 三井貴彦, 武田正之, 篠原信雄, 野々村克也, 荒木敦子, 岸玲子
  • Journal Title: Endcrine Disrupter News Letter Volume: 18 Pages: 6-6
• [Journal Article] 胎児期の有機フッ素化合物曝露による児の健康への影響 (2015)
  • Author(s): 荒木敦子, 宮下ちひろ, 岸玲子
  • Journal Title: Endcrine Disrupter News Letter Volume: 18 Pages: 5-5
• [Journal Article] 【講座 子供を取り巻く環境と健康】第5回 短半減期化学物質の曝露実態 (2015)
  • Author(s): 荒木敦子, アイツバマイゆふ, 岸玲子
  • Journal Title: 公衆衛生 Volume: 79 Pages: 485-490
• [Journal Article] 【講座 子供を取り巻く環境と健康】第1回「奪われし未来」にしない (2015)
  • Author(s): 岸玲子
  • Journal Title: 公衆衛生 Volume: 79 Pages: 193-199
• [Journal Article] Prenatal maternal blood triglyceride and fatty acid levels in relation to exposure to di(2-ethylhexyl)phthalate: a cross-sectional study (2015)
  • Author(s): Jia X., Harada Y., Tagawa M., Naito H., Hayashi Y., Yetti H., Kato M., Sasaki S., Araki A., Miyashita C., Ikeno T., Kishi R., Nakajima T.
  • Journal Title: Environ Health Prev Med Volume: in press
  • NAID: 210000000370
  • Peer Reviewed / Open Access
• [Journal Article] Association between maternal exposure to di(2-ethylhexyl) phthalate and reproductive hormone levels in fetal blood: The Hokkaido Study on Environment and Children's Health (2014)
  • Author(s): Araki A., Mitsui T., Miyashita C., Nakajima T., Naito H., Ito S., Sasaki S., Cho K., Ikeno T., Nonomura K., Kishi R.
  • Journal Title: PLOS One Volume: 9(10) Issue: 10 Pages: e109039-e109039
  • DOI: 10.1371/journal.pone.0109039
  • NAID: 120005476155
  • Peer Reviewed / Open Access
• [Journal Article] 【公害・環境問題の変貌と新展開】 環境化学物質の次世代影響 出生コーホート研究による成果と今後の課題 (2014)
  • Author(s): 岸玲子
  • Journal Title: 公衆衛生 Volume: 78(8)
• [Presentation] The Hokkaido study on Children’s Environment and Health: Sapporo cohort and Hokkaido large-scale cohort (2017)
  • Author(s): Araki, A., Kishi, R.
  • Organizer: The 3rd International Symposium on Environmental Health Environmental health now, what are the big questions?
  • Place of Presentation: Seoul National University, Seoul, Korea
  • Year and Date: 2017-02-13
  • Int'l Joint Research / Invited
• [Presentation] Identification of Risks of Endocrine Disrupting Chemicals Based on Early Life Exposure Assessment: The Hokkaido Study (2016)
  • Author(s): Kishi, R.
  • Organizer: International Frontier Forums of Reproductive Medicine and 2016 International Symposium on Construction and Application of Birth Cohort
  • Place of Presentation: Nanjing Medical University, Nanjing, China
  • Year and Date: 2016-11-19
  • Int'l Joint Research / Invited
• [Presentation] Association between prenatal phthalates and BPA exposures and fatal adipokines and birth size: the Hokkaido Study on Environment and Children's Health (2016)
  • Author(s): Minatoya M., Araki A., Miyashita C., Yamamoto J., Onoda Y., Matsumura T., KIshi R.
  • Organizer: PPTOX V. Kitakyushu International Conference Center
  • Place of Presentation: Kitakyushu International Conference Center, Kitakyushu, Japan
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] Environmental endocrine-disrupting chemicals and their effects to children: 13 years progress of the Hokkaido Birth Cohort Study (2016)
  • Author(s): Kishi, R.
  • Organizer: PPTOX V.
  • Place of Presentation: Kitakyushu International Conference Center, Kitakyushu, Japan
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] Prenatal exposure to prganochlorine pesticides and steroid hormones profiles in fetal blood: The Hokkaido Study (2016)
  • Author(s): Araki A., Miyashita C., Mitui T., Goudarzi H., Itoh S., Mizutani F., Chisaki Y., Sasaki S., Moriya K., Cho K., Shinohara N., Nonomura K., Kishi R.
  • Organizer: PPTOX V.
  • Place of Presentation: Kitakyushu International Conference Center, Kitakyushu, Japan
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] Maternal exposure to endocrine disrupting chemicals (perfluoro-alkyls, phthalates and PCB/dioxins) and children’s reproductive hormone levels at birth; the Hokkaido Study on Environment and Children’s Health (2016)
  • Author(s): Kishi R., Araki A., Miyashita C., Itoh S., Goudarzi H.
  • Organizer: 25th EPICOH
  • Place of Presentation: Universidad Pompeu Fabra, Barcelona, Spain
  • Year and Date: 2016-09-05
  • Int'l Joint Research / Invited
• [Presentation] Maternal exposure to endocrine disrupting chemicals (perfluoro-alkyls, phthalates and PCB/dioxins) and children’s reproductive hormone levels at birth; the Hokkaido Study on Environment and Children’s Health (2016)
  • Author(s): Kishi R., Araki A., Miyashita C., Itoh S., Goudarzi H.
  • Organizer: EPICOH2016
  • Place of Presentation: Universidad Pompeu Fabra, Barcelona, Spain
  • Year and Date: 2016-09-04
  • Int'l Joint Research
• [Presentation] Prenatal exposure to organochlorine pesticides and reproductive hormones in fetal blood: The Hokkaido Study (2016)
  • Author(s): Araki A., Miyashita C., Itoh S., Mitsui T., Mizutani F., Chisaki Y., Sasaki S., Cho K., Nonomura K., Kishi R.
  • Organizer: ISEE2016: 28th Annual Conference International Society for Environmental Epidemiology
  • Place of Presentation: Auditorium Parco della Musica, Roma, Italy
  • Year and Date: 2016-09-01
  • Int'l Joint Research
• [Presentation] Prenatal Di(2-ethylhexyl)phthalate Exposure and Reprocuctive Hormone in Cord Blood - The Hokkaido Study (2016)
  • Author(s): Araki A., Kishi R.
  • Organizer: ISEE-ISES AC2016
  • Place of Presentation: Hokkaido University, Sapporo, Japan
  • Year and Date: 2016-06-26
  • Int'l Joint Research
• [Presentation] ヒト血清中フタル酸エステル代謝物の分析 (2016)
  • Author(s): 小野田優, 梅原美加, 西岡宗一郎, 水谷太, 佐藤修乃, 苣木洋一, 湊屋街子, 宮下ちひろ, 荒木敦子, 岸玲子
  • Organizer: 第25回環境化学討論会
  • Place of Presentation: 新潟コンベンションセンター(新潟県・新潟市）
  • Year and Date: 2016-06-08
• [Presentation] DEHP曝露による胎生期ステロイドホルモンプロファイルへの影響-北海道スタディ (2016)
  • Author(s): 荒木敦子, ホウマヌグウダルジ, 三井貴彦, 那須民江, 宮下ちひろ, 伊藤佐智子, 佐々木成子, 長和俊, 野々村克也, 岸玲子
  • Organizer: 第86回日本衛生学会学術総会
  • Place of Presentation: 旭川市文化会館（北海道・旭川市）
  • Year and Date: 2016-05-11
• [Presentation] Effects of prenatal exposure to perfluoroalkyl acids on risk of allergic diseases at 4 years old children: The Hokkaido Study (2015)
  • Author(s): H. Goudarzi, S. Kobayashi, C. Chen, A. Araki, C. Miyashita, S. Ito and R. Kishi
  • Organizer: 第67回北海道公衆衛生学会
  • Place of Presentation: 旭川医科大学 (北海道・旭川市)
  • Year and Date: 2015-11-21
• [Presentation] 胎児期の母と学童期の児の喫煙曝露とADHD-RSとの関連‐北海道スタディ‐ (2015)
  • Author(s): 西原進吉，池野多美子，小林澄貴，佐々木成子，岸玲子
  • Organizer: 第74回日本公衆衛生学会大会
  • Place of Presentation: 長崎ブリックホール (長崎県・長崎市)
  • Year and Date: 2015-11-04
• [Presentation] Prenatal BPA exposure and cord blood adipokines, birth weight and child growth: the Hokkaido Study of Environment and Children’s health (2015)
  • Author(s): M. Minatoya, S. Sasaki, A. Araki, C. Miyashita, J. Yamamoto, T. Matsumura and R. Kishi
  • Organizer: ISEE 2015
  • Place of Presentation: Reboucas Conference Center, San Paulo (Brazil)
  • Year and Date: 2015-08-30
  • Int'l Joint Research
• [Presentation] Allergic disease in relation to phthalates in house dust and urine (2015)
  • Author(s): A. Araki, Y. Ait Bamai and R. Kishi
  • Organizer: ISEE 2015
  • Place of Presentation: Reboucas Conference Center, San Paulo (Brazil)
  • Year and Date: 2015-08-30
  • Int'l Joint Research
• [Presentation] 胎児期ビスフェノールA曝露影響に関する臍帯血DNA網羅的メチル化解析-北海道スタディ (2015)
  • Author(s): 小林祥子, 三浦りゅう, 川口章夫, 宮下ちひろ, 三宅邦夫, 松村徹, 山本潤, 石塚真由美, 荒木敦子, 久保田健夫 , 岸玲子
  • Organizer: 第4回日本DOHaD研究学術集会
  • Place of Presentation: 昭和大学 (東京都・品川区)
  • Year and Date: 2015-08-01
• [Presentation] Twelve years of progress in the Hokkaido birth cohort study on environment and children's health: malformation, development and allergy (2014)
  • Author(s): Kishi R.
  • Organizer: International Symposium of Environmental Medicine Program
  • Place of Presentation: NTUH International Convention Center, Taipei (Taiwan)
  • Year and Date: 2014-10-16 – 2014-10-17
• [Presentation] Twelve Years of Progress in the Hokkaido Birth Cohort Study on Environment and Children's Health: Focused on Dioxins and PFCs (2014)
  • Author(s): Kishi R.
  • Organizer: Summit on Child Health and the Environment
  • Place of Presentation: Hong Kong Academy of Medicine Building, Aberdeen (Hong Kong)
  • Year and Date: 2014-10-11 – 2014-10-13
• [Presentation] Association between maternal exposure to di(2-ethylhexyl) phthalate and sex hormone levels in fetal blood (2014)
  • Author(s): Araki A., Mitsui T., Miyashita C., Nakajima T., Nakazawa H., Sasaki S., Ikeno T., Cho K., Itoh S., Nonomura K., Kishi R.
  • Organizer: 26th Annual International Society for Environmental Epidemiology Conference - From Local to Global: Advancing Science for Policy in Environmental Health
  • Place of Presentation: Husky Union Building, the University of Washington, Seattle (USA)
  • Year and Date: 2014-08-24 – 2014-08-28
• [Presentation] Effect of PFOS and PFOA exposure in utero on reproductive hormones levels at birth (2014)
  • Author(s): Itoh S., Araki A., Miyashita C., Nakazawa H., Mitsui T., Cho K., Sasaki S., Ikeno T., Nonomura K., Kishi R.
  • Organizer: 26th Annual International Society for Environmental Epidemiology Conference - From Local to Global: Advancing Science for Policy in Environmental Health
  • Place of Presentation: Husky Union Building, the University of Washington, Seattle (USA)
  • Year and Date: 2014-08-24 – 2014-08-28
• [Presentation] フタル酸エステル類の胎児期曝露による次世代影響に関する疫学研究 (2014)
  • Author(s): 荒木敦子, 岸玲子
  • Organizer: 第84回 日本衛生学会学術総会
  • Place of Presentation: 岡山コンベンションセンター （岡山県・岡山市）
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] DEHPへの胎児期曝露による児の性ホルモン濃度への影響 (2014)
  • Author(s): 荒木敦子, 三井貴彦, 宮下ちひろ, 那須民江, 伊藤佐智子, 佐々木成子, 長和俊, 池野多美子, 野々村克也, 岸玲子
  • Organizer: 第84回 日本衛生学会学術総会
  • Place of Presentation: 岡山コンベンションセンター （岡山県・岡山市）
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] PFOS. PFOAの胎児期曝露が与える児の出生時性ホルモン濃度への影響 (2014)
  • Author(s): 伊藤佐智子, 荒木敦子, 宮下ちひろ, 中澤裕之, 三井貴彦, 長和俊, 佐々木成子, 池野多美子, 野々村克也, 岸玲子
  • Organizer: 第84回 日本衛生学会学術総会
  • Place of Presentation: 岡山コンベンションセンター （岡山県・岡山市）
  • Year and Date: 2014-05-25 – 2014-05-27
• [Remarks] 北海道大学 環境健康科学研究教育センター 研究実績
  • URL: https://www.cehs.hokudai.ac.jp/research/yearly/
• [Remarks] 環境と健康ひろば
  • URL: https://www.cehs.hokudai.ac.jp/hiroba/
• [Remarks] 環境と子どもに関する研究・北海道スタディ
  • URL: https://www.cehs.hokudai.ac.jp/hokkaidostudy/
• [Remarks] 北海道大学 環境健康科学教育研究センター 研究業績
  • URL: http://www.cehs.hokudai.ac.jp/research/yearly/
• [Remarks] 環境と健康ひろば
  • URL: http://www.cehs.hokudai.ac.jp/hiroba/
• [Remarks] 環境と子どもに関する研究・北海道スタディ
  • URL: http://www.cehs.hokudai.ac.jp/hokkaidostudy/
• [Remarks] 環境と子どもに関する北海道研究・北海道スタディ
  • URL: http://www.cehs.hokudai.ac.jp/hokkaidostudy/