平成13年度内分泌攪乱化学物質のヒトへの健康影響調査研究報告書

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6 A 1, A ng ml (n=1276) ng ml n ng ml(n=30) ng ml(n=30) 5 A ng ml

7 A 1930 Dodds DES , , A 30 A, EDC ELISA

8 1,276 A ng ml A ng ml ng ml ng ml A ng ml A ng ml A A GC MS HPLC EDC ELISA DES DES A

9 A 1999 GC MS ELISA ELISA 1,000 A

10 ( ) ELISA

11 , ELISA HPLC ELISA ng/ml 2.51 ng/ml 0 n= ng/ml ng/ml 0.14ng/ml n=305 p ng/ml ng/ml ng/ml n= ng/ml ng/ml ng/ml n=50 p Hypospadia, Cardiac malformation 2, Ear malf. NT

12 ng/ml /4 1/ ( ) A A in vitro

13

14 Sumiyoshi Y, Hirahara F, Sakamoto S: Studies on the frequency of congenital malformations in Japan and Asian countries. Congenital Anomalies, 40: S76-S86, Chaki O, Gorai I, Yoshikata H,.Kikuchi R, Hirahara F: The heterogeneity in bone mineral density and biochemical markers of bone turnover in response to hormone replacement. Osteoporosis Int, 11(2): , Chaki O, Yoshikata H, Kikuchi R, Nakayama M, Uchiyama Y, Hirahara F, Gorai I: The predictive value of biochemical markers of bone turnover for bone mineral density in postmenopausal Japanese women. Journal of Bone and Mineral Research, 15: , Yoshida H,Sakakibara H, Ohkouchi C, Hirose M, Uemura T, Tage M, Hirahara F: Gene expression of cyclic nucleotide phosphodiesterase (PDE) subtypes in rat hypothalamus and their effect on GnRH secretion from GnRH neuron. Acta Obst Gyneac Jpn, 52: S490, DepinH, Uemura T, Funabashi T, Kondoh Y, Hirahara F, Mitsushima D: Changes in the number of GnRh and GAD67 immunoreactive cells in the peri-ovlt region of the hypothalamus in old-aged female rats. Acta Obst Gyneac Jpn, 52: S490, He D, Mitsushima D, Uemura T, Hirahara F, Funabashi T, Shinohara K, Kimura F: Effects of naloxone on the serum luteinizing hormone level and the number of Fos-positive gonadotropin-releasing hormone neurons in immature female rats. Brain Research, 858: , Arpino C, Brescianini S, Robert E, Castilla EE, Cocchi G, Cornel MC, Vigan C, Lancaster PAL, Merlob P, Sumiyoshi Y, Zampino G, Renzi C, Rosano A, Mastroiacovo P: Teratogenic effects of antiepileptic drugs: use of an international database on malformations and drug exposure (MADRE). Epilepsia, 41(11): , Inayama Y, Shoji A, Odagiri S, Hirahara F, Ito T, Kawano N, Nakatani Y: Ditection of pulmonary metastasis of low-grade endometrial stromal sarcoma 25 years after hysterectomy. Pathol Res Pract, 196: , Ohyama M, Itani Y, Yamanaka M, Imaizumi K, Nishi T, Ijiri R, Tanaka Y: Umbilical cord ulcer : a serious in utero complication of intestinal atresia. Placenta, 21: ,

15 Still GnRH antagonist (GnRHant) GnRH receptor mrna, Lh subunit mrna 52 S GABAA GnRH GnRH GT1-7 NMDA MED : /08/13 GnRH GT IUD Quality of life (QOL) Fetus as a patient

16 Kanagawa Birth Defects Monitoring Program: KAMP KAMP , , , , BPA BPA : ng/ml ng/ml : ng/ml ng/ml : ng/ml ng/ml : ng/ml ng/ml BPA BPA

17 BPA Kanagawa Birth Defects Monitoring Program; KAMP KAMP , , A ELISA , , , % ,000

18 KAMP KAMP KAMP KAMP 1990 PCB,DDT KAMP A 3), 4) 30 BPA ng/ml ng/ml ng/ml ng/ml ng/ml, ng/ml BPA BPA BPA

19 BPA BPA BPA ( ) 1, ng/ml ( ,868.0 ng/ml ) 1, ng/ml ( 1, ,672.3 ng/ml ) :3, ,368.6 ng/ml, 2, ,101.0 ng/ml ( ) 1) 11 p ) 12 p ) vom Saal FS: Bisphenol A alters development in mice at human exposure levels , ) A , ) 13 21, 2002

20 1 KAMP KAMP ,077 2, g 2,242g 3, g g

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23 A 1 2

24 A

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26 1. / 2. cm kg cm kg

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29 PMB=proportion of male births [ 2000] (1) (2) (1) (2) [Mocarelli et al., 2000] [ 1998] [Sakamoto M, et al., 2001] [Dickinson H and Parker L, 1994] Mizuno [2000] 1970

30 proportion of male babies=pmb PMB PMB PMB 95% 95% PMB 13 PMB PMB 16 PMB PMB PMB 99% [2000]

31 PMB PMB 95% [Imaizumi and Murata 1981, Bigger et al., 1999] 1) PMB 1 PMB ) PMB 1 PMB 95% PMB 2 95% % 3

32 95% 3) PMB 3 PMB 4 PMB PMB PMB 99% ) PMB % PMB 5) PMB 95% PMB 5 21 PMB 5% PMB 95% PMB 5% PMB [ 2000]

33 PMB PMB PMB PMB % PMB % PMB Imaizumi murata[1981] 99% PMB [Williams FLR et al. 1992] [2000] (1) (2) (3) (3) 95% PMB 2 3

34 3 1 2 PMB 2 PMB 3 PMB 70 [ 1999] PMB 3 PMB PMB 1970 [Sakamoto M, et al., 2001] [Yoshimura T, et al., 2001]

35 Mizuno[2000] Mizuno 6 (1) / (2) (3) 1970 Imaizumi Murata[1981] PMB Mizuno [ 1989] Mizuno[2000]

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37 1) 70: ; )Mocarelli P, Gerthoux PM, Ferrari E, Patterson Jr DG, Kieszak SM, Brambilla P, Vincoli N, Signorini S, Tramacere P, Carreri V, Sampson EJ, Turner WE, Needham LL. Paternal concentrations of dioxin and sex ratio of offspring. Lancet 355: ; ) 63, p )Sakamoto M, Nakano A, Akagi H. Declining Minamata male birth ratio associated with increased male fetal death due to heavy methylmercury pollution. Environ Res 87:92-98; )Dickinson H and Parker L. Do alcohol and lead change the sex ratio? J theor Biol 169: ; )Mizuno R. The male/female ratio of fetal deaths and births in Japan. Lancet 356; : )Imaizumi Y and Murata M. The changing sex ratio in Japan. Jpn J Hunan Genet 26; 71-81: )Bigger RJ, Wohlfahrt J, Westergaard T, Melbye M. Sex ratios, family size, and birth order. Am J Epidemiol 150; : ) Secular trends of sex ratios at birth in Japan., 47:945-55; )Williams FLR, Lawson AB, Lloyd OL. Low sex ratio of births in areas at risk from air pollution from incinerators, as shown by geographical analysis and 3-dimensional mapping. Int J Epidemiol 21; : ) p.266, )Yoshimura T, Kaneko S, Hayabuchi H. Sex ratio in offspring of those affected by dioxin and dioxin-like compounds: the Yusho, Seveso, and Yucheng incidents. Occup Environ Med 58; : ) 36; 13-18: 1989.

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