Microsoft Word 塑化劑DEHP參考資料(醫療衛生人員版)PC.doc

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2 錄 3 4 DEHP 6 DEHP 6 DEHP DEHP 9 DEHP 10 DEHP 12 DEHP 12 DEHP 每 (TDI)(NOAEL) 13 TFDA Q&A ( ~ ) 20 DEHP 27 2

3 DEHP 汙 DEHP 產歷產龐內產 DEHP 眾 DEHP 污眾 DEHP 晚 () DEHP DEHP ( 眾 DEHP 夠 24 徵 DEHP 眾 3

4 DEHP DEHP 氯烯 (PVC) 產 DEHP DEHP 每 DEHP 每 DEHP 1 mg DEHP 產 PVC DEHP 狀 DEHP DEHP DEHP 睪巢狀睪 DEHP 內 DEHP 睪內 DEHP 睪 DEHP 內份 DEHP DEHP PPAR αperoxisome Proliferators Activated Receptor DEHP DEHP DEHP 2B DEHP 4

5 DEHP DEHP NOAEL 5 mg/kg/day DEHP NOAEL 500 mg/kg/day () DEHP LOAEL 40 mg/kg/day DEHP 每每 (Tolerable Daily Intake, TDI) NOAEL (2005 ) DEHP 0.05 mg/kg/day NOAEL 內內 5

6 DEHP DEHPBis (2-ethylhexyl) phthalate 苯 (2-) 酯苯酯 Phthalates esters, PAEs DEHP 產氯烯 (Polyvinyl chloride, PVC) 產 C 6 H 4 (C 8 H 17 COO) 2 溫 DEHP PVC 產 DEHP DEHP 97 DEHP PVC ATSDR2002 苯 DEHP 佔 2006 PVC 產 DEHP PVC 產 () PVC 氧氨酯剎 DEHP PVC 產產 DEHP 另苯 cellulose acetate phthalate, CAP 苯 DEHP 每 DEHP 戶 DEHP 奶奶產 DEHP 6

7 DEHP 每 mg DEHP 錄 PVC 產 DEHP DEHP (Tolerable Intake, TI)DEHP TI DEHP DEHP 每 (Tolerable Daily Intake, TDI) 狀 DEHP TDI DEHP PVC DEHP 频 (FDA ) DEHP 產 DEHP DEHP 產 DEHP PVC 餵餵產 DEHP 餵狀 DEHP 7

8 () DEHP DEHP () 產內苯產說 ) DEHP PVC () DEHP PVC 苯酯 Tri-octyl trimellitate, TOTM 酰酯 (Acetyl-tri-n-butyl citrate, ATBC 酰 Buturyl-tri-n-hexyl citrate, BTHC 苯酯 Dioctyl terephthalate, DOTP. DEHP PVC DEHP DEHP 產 DEHP PVC ECMO 减 DEHP DEHP PVC ( 烯烯 - ethylene-vinyl acetate 矽烯 ) 說 DEHP PVC 份 8

9 ()DEHP DEHP (Lethal dose 50%, LD 50) 25 / (25000 mg/kg) DEHP LD / ( mg/kg) DEHP 產 mono-2-ethylhexyl phthalate (MEHP) DEHP ()DEHP 3 DEHP 氧 no-observedadverse-effect-levels, NOAEL 28.9 mg/kg/day ()lowest-observed-adverse-effect-level, LOAEL mg/kg/day 產 LOAEL 292 mg/kg/day 餵 DEHP 104 NOAEL DEHP 500 mg/kg 28.9 mg/kg/day 36.1 mg/kg/day LOAEL mg/kg/day () () DEHP 內 DEHP 睪 Leydig cell 睪酮睪睪 DEHP 氧 DEHP 睪內值 1. DEHP DNA 9

10 2. DEHP (anal-genital distance, AGD) 3. DEHP 4. 苯酯 5. 內苯酯產 (Consumer Products Safety Commission, CPSC) 苯酯 3 - DEHP - 睪巢狀睪 - 每每每 0.1, 0.024, mg DEHP - 每每每 0.037, mg DEHP - (13 49 歲 ) 每每每 mg DEHP DEHP () DEHP MEHP 2-2-ethylhexanol DEHP MEHP 2- 內 DEHP MEHPMEHP 內 ( 酯酶酶胰酶 ) 胰 DEHP 苯 (12-14%) MEHP DEHP ㄧDEHP DEHP 產 MEHP 10

11 DEHP MEHP DEHP (0.64 mg/kg) DEHP 4-8 () 內 DEHP 產 MEHP(6.4 to 12.7%) I1.9 to 2.1% IV1.8 to 3.7% V25.6 to 33.8% VI19.7 to 24.0% VII4.0 to 5.3% IX25.9 to 33.0% <1% MEHP VIIIX <2 hr - 苷 (conjugation) 苷佔 65~99%() () DEHP 每每 10 mg DEHP 內 15 25% of DEHP 66 mg DEHP 31% of DEHP DEHP 8-16 MEHP IX X DEHP 5 IV X 10 DEHP 值 DEHP3 mg/kg 16% 4 內 11~28% 24 內 20~31% 47 內 47 MEHP 7.3% IX 24.7%VI 14.9% 值 DEHP 內胰酶酯酶 DEHP DEHP DEHP 氧 DEHP DEHP 奶 DEHP (bioavailability) 值 50% 歲內 75100% 75% 100% 5% 100% 11

12 DEHP DEHP α 氧 PPAR α Peroxisome Proliferators Activated Receptor 氧另 DEHP PPAR α DEHP 產 MEHP MEHP antiandrogentic 氧睪 PPAR α DEHP 3 DEHP IARC DEHP 2B 咖啡醃黃份酚蔻份氧鈦 : oxazepam, phenazopyridine hydrochloride, phenoxybenzamine, phenobarbital, phenytoin, propylthiouracil, methylthiouracil, metronidazole, griseofulvin, medroxyprogesterone acetate, 黃黃 DEHP DEHP 產錄 DEHP NOAEL LOAEL DEHP DEHP NOAEL 5 mg/kg/da DEHP NOAEL 500 mg/kg/da DEHP LOAEL 40 mg/kg/da 12

13 DEHP 每 (TDI)(NOAEL) 每 (Tolerable Daily Intake, TDI) no-observed-adverse-effect-levels, NOAEL NOAEL 另 NOAEL 值 TDI safety/uncertainty factors (SF/UF)(1).(2). (3) TDI (mg/kg/day) = (NOAEL LOAEL*) (mg/kg/day) Uncertainty Factor TDI TDI 內 NOAEL 5 mg/kg/day 100 每 (TDI) 0.05 mg/kg/day 50 µ g/kg/day () DEHP 2 DEHP (NOAEL) 60 mg/kg/day 100 值 0.6 mg/kg/day DEHP LOAEL 250 mg/kg/day 300 值 0.8 mg/kg/day () DEHP DEHP 值 2004 DEHP NOAEL 4.8 mg/kg/day 值 mg/kg/day 0-3 值 0.02 mg/kg/day3-12 值 mg/kg/day() 2010 DEHP 值 mg/kg/day( ) 13

14 *: LOAEL lowest-observed-adverse-effect-level TFDA 污產查 TFDA DEHP 汙 DEHP TDINOAEL : DEHP 產 DEHP 狀產 2,000 ppm 2 mg 狀產 1,000 ppm 1mg 狀產 600 ppm 0.6 mg 狀產 ppm 5-17 mg 22 8 DEHP 污每 2 每 1 18 DEHP 800 ppm 每 DEHP mg mg/kg/day TDI NOAEL 內 (TFDA) DEHP 絕份 50 ppm 內絕份眾 DEHP (TDI) (NOAEL) 內 ; (TDI) 內眾說 ; 污說 TDI 份 NOAEL 內 ; 步內 NOAEL 內眾眾 ( ) 查 (Biomarker) 14

15 眾步 Q&A 每眾 DEHP TDINOAEL 眾污產汙每產眾產幫狀哪查睪狀 15

16 夠步睪胰咖啡醃黃份酚份氧鈦產產值查查產 16

17 產產查產污產產查徵產查查錄查查查查徵徵哪查查睪歲徵徵沉歲徵徵巢 17

18 內查內另值值內份內你絕說每脫奶步挪戶另內產 18

19 佈產產眾內吳ㄧ內 6 ㄧ內 7 ㄧ內 3 ㄧ內 3 吳 mlwu@vghtpe.gov.tw hcong@vghtpe.gov.tw DEHP 汙您您您眾 DEHP 您您您歷 - 您稅 - 脫眾 19

20 您您您您您您您盼您您 PVC 產每 DEHP DEHP DEHP Health Canada 每 DEHP µg/kg/day 640 a,b,c Pollack a,b,c Faouzi a,b,c c Dine e Mettang1996 產 6-90 f Jacobson1977 Doull1999 Plonait1993 Health Canada d Mazur1989 Loff ug/ d / Kambia f 63 Jaeger and Rubin b 2.5 (ECMO) f Sjoberg1985b Butch e Barry f Health Canada f Pearson1993 a: 70 每 b: area under curve, AUC c: 每 4 DHEP d: PVC DEHP e: DEHP f: DEHP 20

21 . PVC 產每 DEHP DEHP DEHP Health Canada (4 kg) 每 DEHP µg/kg/day n Midazolam24 ml n Fentanyl29 ml n Propofol1%,10 ml, 24h 7 a 33 a 1640 a 30 a %, , 33 a c b a Loff2000 Loff2000 Loff2002 Plonait1993 Sjoberg1985a Sjoberg1985b 20 ml a Loff ml 232 a 20 ml a - 14,000 d Schneider µg/kg/ 10 0 PVC Karle1997 3,490 e µg/kg/ 10 氧氧 130 f Health Canada f Health Canada 2002 Latini 1999 內 2830 FDA2002 ( ) a: 內 DEHP b: area under curve, AUC d: DEHP d: e: f: DEHP 21

22 . DEHP TI/dose ratio* TI/dose ratio* ( ) DEHP (mg/kg/day) DEHP (mg/kg/day) PVC EVA! 鐮狀狀 * DEHP 值 0.6 mg/kg/day 值 0.04 mg/kg/day EVA: ethylene-vinyl acetate 烯烯 22

23 . DEHP 產 NOAEL LOAEL 值 NOAEL LOAEL mg/kg/day mg/kg/day David 2000a 氧 David 2000a 睪 Poon 1997 (vacuolation) 5.8 David 2000a Moore 1997 份睪 5.8 David 2000a David 2000a 292 David 1999 睪 Berger 1885 胰 12,500 胰 David 睪 Wolfe Gray 產 Tyl Lamb

24 . DEHP NOAEL LOAEL ( 睪 ) 2 () 餵 (NOAEL, mg/kg/day) (LOAEL, mg/kg/day) Rhodes Agarwal Parmar SiddiquiSrivastava Saxena Oishi GrayGangolli NTP Poon () Rhodes Pugh Kurata DEHP 2 5 mg/kg/day 40 mg/kg/day * 500 mg/kg/day mg >400 mg >5000 mg mg >800 mg >10000 mg mg >1200 mg >15000 mg mg >1600 mg >20000 mg mg >2000 mg >25000 mg mg >2400 mg >30000 mg 值 NOAEL mg/kg/day LOAEL mg/kg/day NOAEL mg/kg/day * 24

25 . DEHP 3 (µg/kg/day) NOAEL (mg/kg/day) RfD3; (LOAEL) 1000 EPA 1991; Carpenter 1953 TDI; Health Canada 1994; Wolkowski-Tyl 1984 MRL(); ATSDR 2002; Lamb MRL() ; ATSDR 2002; David 2000a; 2002 TDI; WHO 2003 TDI; EU CSTEE 1998; Poon 1997; Arcadi 1998 TDI; ( ECB/EU (RAR-DEHP) 2004; Wolfe 2003,) TDI; ( ECB/EU (RAR-DEHP) 2004; Wolfe 2003 ) TDI; ECB/EU (RAR-DEHP) 2004; Wolfe 2003 TDI; BfR and EFSA 2005; Wolfe & Layton 2003 ADI;; CPSC Carlson 2010; Dostal 1987a,b ADI;; CPSC Carlson 2010; David 2000a; Moore 1996 ADI;; CPSC (LOAEL) 1000 Carlson 2010; Bibra 1990; ECB 2008 ADI;; Carlson 2010; Poon 1997 CPSC 2010 ADI;; (LOAEL) 1000 Carlson 2010; David 2000a CPSC 2010 ADI;; CPSC (LOAEL) 1000 Carlson 2010; Gray 2009 RfD (, Reference Dose), TDI ( 每, Tolerable Daily Intake), MRL ( 值, Maximal Residue Level), ADI ( 每, Acceptable Daily Intake) CPSC 產 DEHP 2,3 (mg/kg/day) (1349 歲 )

26 . DEHP 污每 (TDI) 2,3 (2005 ) 0.05 mg/kg/day (2010 ) * mg/kg/day (2010 ) * 0.1 mg/kg/day mg 0.58 mg 1 mg mg 1.16 mg 2 mg mg 1.74 mg 3 mg mg 2.32 mg 4 mg mg 2.90 mg 5 mg mg 3.48 mg 6 mg * 產 26

27 27

28 DEHP (Silva et al.; Koch et al., 2006) 3 1. Scientific Committee on Emerging and Newly-Identified Health Risks (SCENIHR), Opinion on the safety of medical devices containing DEHP plasticized PVC or other plasticizers on neonates and other groups possibly at risk. European Commission ( 2.Centre for Devices and Radiological Health, Safety assessment of di(2-ethylhexyl)phthalate (DEHP) released from PVC medical devices. Food and Drug Administration, USA ( 3.Toxicity review of is di (2-ethylhexyl) phthalate (DEHP). The US Consumer Product Safety Commission s (CPSC s) Health Sciences staff assessment of the potential toxicity associated with DEHP, April 1,

b. 在大鼠和小鼠長期飼養的研究, 發現 DINP 對肝臟和其他器官具有毒性, 可增加肝細胞腺瘤的發生率, 但這些影響只發生在囓齒目動物身上, 並不適用於人類 Q3. 起雲劑為何

b. 在大鼠和小鼠長期飼養的研究, 發現 DINP 對肝臟和其他器官具有毒性, 可增加肝細胞腺瘤的發生率, 但這些影響只發生在囓齒目動物身上, 並不適用於人類 Q3. 起雲劑為何環境荷爾蒙 Q & A 以下文章內容載自行政院衛生署食品藥物管理局 [ 起雲劑遭塑化劑汙染專區 ] 之 Q & A: http://www.fda.gov.tw/content.aspx?site_content_sn=2481 1. 塑化劑相關問題 Q1. 什麼是起雲劑? 起雲劑是一種合法的