<4D F736F F F696E74202D20A5CDA952AABAC1F4A7CEB1FEA4E22DC0F4B9D2B2FCBAB8BB582D DAE61AC46BEC7ACECA4A4A4DF205BACDBAE65BCD2A6A15D>

Size: px

Start display at page:

Download "<4D6963726F736F667420506F776572506F696E74202D20A5CDA952AABAC1F4A7CEB1FEA4E22DC0F4B9D2B2FCBAB8BB582D32303135303831372DAE61AC46BEC7ACECA4A4A4DF205BACDBAE65BCD2A6A15D>"

颂欢邰
7 years ago
Views:

1 生命的隱形殺手 - 環境荷爾蒙李俊璋特聘教授兼中心主任成功大學工業衛生科暨環境醫學研究所成功大學環境微量毒物研究中心中華民國 104 年 08 月 17 日 1

2 化學致癌物癌症 Rachel Carson and Her Silent Spring (1962) - 殺蟲劑 (e.g., dichloro-diphenyl trichloroethane: DDT) 2

3 內分泌干擾物質生長發育危害 Theo Colborn and Her Our Stolen Future (1996) 戴奧辛及多氯聯苯 (Dioxins and PCBs) 內分泌干擾物質假說 (Endocrine disruptor hypothesis) 3

4 內分泌干擾物質生殖系統危害 The Estrogen Effect: How Chemical Pollution Is Threatening Our Survival (2000) 鄰苯二甲酸酯 (Phthalates) 雌激素效應 - 不孕症 4

5 如何創造健康的生活環境? Christopher Gavigan Healthy Child Healthy World: Creating a Cleaner, Greener, Safer Home 為孩子打造無毒的成長環境如何安心選購食材, 讓家人吃得健康聰明挑選家具建材, 室內空氣不含毒善用天然清潔用品, 環境不再愈清愈毒選擇無毒的美容護膚品, 身體才能真正的清潔如何讓寵物免受化學產品的毒害 5

6 生殖系統危害現象 Fig 年 61 篇研究所載每毫升精液平均精子數之分布趨勢 <Carlson E et al., 1992> Fig 年突尼西亞 1835 位男性每毫升精液平均精子數之分布趨勢 <Feki1 et al., 2009> 6

7 內分泌系統內分泌系統 (Endocrine) 是負責調控動物體內各種生理恆定, 及生長發育功能正常運作的系統, 由分泌荷爾蒙的無管腺體所組成荷爾蒙又稱為激素, 是一種化學傳導物質, 自腺體分泌出來後, 藉由體液或進入血液經由循環系統運送到標的器官而產生作用 7

8 中樞系統刺激荷爾蒙分泌腺體回饋機制血液系統荷爾蒙標的器官 8

9 Endocrine Disruptor Hypothesis (by Theo Colborn) 外因性干擾生物體內分泌作用之化學物質, 可模擬類似天然的荷爾蒙, 欺騙身體而造成體內對荷爾蒙的過度作用, 或可能直接刺激或抑制內分泌系統或誘導造成內分泌系統的失調這些物質即稱為內分泌干擾物質或環境荷爾蒙 9

10 環境荷爾蒙 (by Taisen Iguchi) 內分泌干擾物質 (Endocrine Disrupting Chemicals, EDCs ) 1997 NHK 電視節目井口泰泉教授環境荷爾蒙 (Environmental Hormones) 10

11 Examples of Known Endocrine Disrupting Chemicals (EDCs) 農藥 : 可氯丹 DDT 環境污染物 : 戴奧辛 / 呋喃工業產品 : 多氯聯苯壬基酚雙酚 A 多溴二苯醚有機錫 ( 三丁基錫三苯醋錫 ) 鄰苯二甲酸酯重金屬 ( 鉛汞 ) 有機溶劑 ( 丙酮丁酮 ) 藥物 : 二乙基烯雌酚 (DES) 口服避孕藥植物型雌性激素世界各國或組織已彙整國內已管制之 EDCs 達 104 種, 尚有數十種可疑者仍在測試中 11

苯二甲酸酯重金屬 ( 鉛汞 ) 有機溶劑 ( 丙酮丁酮 ) 藥物 : 二乙基烯雌酚 (DES) 口服避孕藥植物

12 持久性有機污染物 Persistent organic pollutants(pops) 所謂持久性有機污染物係指某些有機化合物在環境中之分解性低, 可持續留累積存於環境中, 且易經由食物鏈產生生物濃縮, 最終具有對人體健康及生態環境產生不良效應之危險性 12

13 已知之持久性有機污染物 Aldrin Chlordane DDT Dieldrin Endrin Heptachlor Hexachlorobenzene Mirex Toxaphehene Dioxins Furans PCBs α- 六氯環己烷 β- 六氯環己烷六溴聯苯醚和七溴聯苯醚四溴聯苯醚和五溴聯苯醚十氯酮六溴聯苯靈丹五氯苯全氟辛烷磺酸全氟辛烷磺酸鹽和全氟辛基磺酰氟 13

14 戴奧辛 / 呋喃內分泌干擾效應 : 國內研究結果 14

15 多氯戴奧辛 / 呋喃之毒性多氯戴奧辛 / 呋喃 (polychlorodibenzo-p-dioxins and dibenzofurans,pcdd/fs) 對人體健康與動植物生態的不良影響在文獻中已有明確之記載, 依據文獻所載其毒性包括 : 1. 皮膚毒性 : 如痤瘡出現色素沈積 2. 神經系統毒性 : 如週圍神經傳導緩慢 3. 肝毒性 : 如肝臟腫大肝功能異常 4. 致癌性 : 如軟組織惡性淋巴腫瘤 5. 生殖系統毒性 : 如中毒者第二代多為女性胎兒 6. 內分泌干擾毒性 : 如血糖異常胰島素阻抗 15

皮膚毒性 : 如痤瘡出現色素沈積 2. 神經系統毒性 : 如週圍神經傳導緩慢 3. 肝毒性 : 如肝臟腫大肝功能異常 4.

16 台灣地區 PCDD/Fs 之排放來源金屬二次冶鍊 6% 集塵灰處理設施 13% 水泥窯 1% 其他 10% 2% 事業廢棄物焚化 ( 含一般事業醫療有害 ) 14% 燒結爐 24% 煉鋼業電弧爐 30% 16

17 戴奧辛之暴露途徑戴奧辛存在空氣土壤與底泥, 可經由呼吸和食入進入人體以下則是人體暴露於戴奧辛的可能途徑 : 透過呼吸進入 : 燃燒行為 ( 森林大火 ) 機動車輛的排煙及焚化爐金屬冶煉業排放廢氣透過飲食進入 : 就人體而言, 大約有 95% 以上之暴露來自食物, 尤其是魚類肉類及乳製品等水源污染 : 戴奧辛在水中的溶解性極低, 大部分會被水中底泥所吸附, 所以在水中含量極為微量 17

放廢氣透過飲食進入 : 就人體而言, 大約有 95% 以上之暴露來自食物, 尤其是魚類肉類及乳製品等

18 戴奧辛 / 呋喃與飯前血糖之關係 - 一般民眾 Hsiu-Ling Chen et al., Science of the Total Environment,

19 戴奧辛 / 呋喃與飯前血糖之關係 - 高污染民眾 Jung-Wei Chang et al., Epidemiology,

20 戴奧辛 / 呋喃與胰島素阻抗之關係 - 高污染民眾 Jung-Wei Chang et al., Epidemiology,

21 戴奧辛 / 呋喃汞交互作用對胰島素阻抗之影響 - 高污染民眾 Jung-Wei Chang et al., Journal of hazardous materials,

22 戴奧辛 / 呋喃與心血管疾病之關係 - 高污染民眾 Jung-Wei Chang et al., Journal of hazardous materials,

23 鄰苯二甲酸酯對孕婦及胎兒內分泌干擾效應 : 國內研究結果 23

24 什麼是 Phthalates (PAEs)? PAEs 鄰苯二甲酸酯是鄰苯二甲酸 (Phthalate acid) 的酯化衍生物, 為常見的塑膠塑化劑所謂塑化劑是指在塑膠原料加工時, 添加塑化劑可以改變塑膠成形時的物理性質, 使其物理性質變為較為柔軟, 易於加工 ; 或是添加塑化劑後, 可使得塑膠成品具有柔軟易於彎曲摺疊的性質 - H 2 O + ROH Phthalic acid Phthalic anhydride General chemical structure of phthalate ester 24

25 PAEs 的用途塑膠塑化劑化妝品香水之定香劑塑膠製品化妝品香水或具香味商品建築材料電線電纜外皮 Ω 保鮮膜 Ω 汽車內裝 Ω 醫療器材如輸液管血袋 Ω 玩具 25 Ref.: Api, 2001; ATSDR, 1995, 2001, 2002; Kavlock et al.,2002, 2006.

26 鄰苯二甲酸酯類主要用途 PAEs 種類 DEHP DBP BBP DEP DMP DINP (Di-isononyl phthalate) 主要應用產品建材 ( 地板壁紙電線外層 ) 汽車產品 ( 座椅內裝 PVC 地墊 ) 衣服 ( 鞋雨衣 ) 食品包裝兒童產品 ( 玩具奶嘴 ) 醫療用品 ( 輸血袋導管氧氣罩注射針筒 ) 香水 PVC 吸管電容器殺蟲劑真空幫浦油主要用於乳膠接合劑 (latex adhesive) 纖維塑膠 (cellulose plastic) 染料的溶劑 PVC 的塑化劑體香劑美髮藥品指甲油香水印刷用油墨醫療用品 (PVC 假牙 ) 玩具浴簾大量使用於乙烯地板 (vinyl tile) 食物運送帶 (food conveyor belt) 地毯 (carpet tile) 人造皮革 (artificial leather) 防水布 (tarpaulin) 汽車飾件 (automotive trim) 密封條 (Weather stripping) 交通錐 (traffic cone) 黏著劑 (adhesives) 美髮藥品香水印刷用油墨香水化妝品保養品沐浴用品鬍後水體香劑美髮藥品等纖維素酯膜塑膠之可塑劑美髮藥品 PVC 遮板 PVC 襯墊 PVC 管線 PVC 壁紙 PVC 玩具 PVC 吸管 PVC 運輸帶紡織品手套 26

27 鄰苯二甲酸酯於化妝品中的檢出率及濃度 PAEs 化合物檢出任一 PAEs 檢出率 (%) 平均濃度 ( 檢出最大濃度 ) (mg/kg) 美國 (n=72) 產品體香劑, 香水, 髮膠, 美髮慕絲, 美髮噴霧, 手部及身體乳液, 指甲油 DEHP 4 11 (25) 香水 DBP (890) 指甲油, 美髮噴霧, 體香劑 BBP 6 14 (46) 香水, 美髮噴霧 DEP 71 4,700 (280,000) 香水, 體香劑, 髮膠, 美髮慕絲, 美髮噴霧, 手部及身體乳液 DMP 1 33 (33) 體香劑資料來源 :Houlihan et al.,

28 鄰苯二甲酸酯於化妝品中的檢出率及濃度 PAEs 化合物檢出任一 PAEs 檢出率 (%) 平均濃度 ( 檢出最大濃度 ) (ppm) 美國 (n=48) 產品身體乳液, 美髮噴霧, 體香劑, 香水, 潤膚乳液, 髮膠, 美髮慕絲, 沐浴露, 洗髮精, 護手霜, 指甲油 DEHP 0 ND (<10ppm) - DBP 21 10,733 (59,815) 美髮噴霧, 體香劑, 指甲油 BBP 4 75 (107) 美髮噴霧, 指甲油 DEP 58 2,993 (38,663) 香水, 身體乳液, 美髮噴霧, 體香劑, 潤膚乳液, 髮膠, 美髮慕絲, 沐浴露, 護手霜, 指甲油 DMP 6 5,199 (15,395) 指甲油資料來源 :Houlihan et al.,

29 鄰苯二甲酸酯於化妝品中的檢出率及濃度 2002 歐洲 (n=34) PAEs 化合物檢出率 (%) 平均濃度 ( 檢出最大濃度 ) (mg/kg) 產品檢出任一 PAEs 79 體香劑, 香水, 美髮慕絲, 髮膠, 美髮噴霧 DEHP (24) 體香劑, 香水, 美髮慕絲, 美髮噴霧 DBP (150) 體香劑, 香水, 美髮慕絲, 美髮噴霧 BBP (6.6) 美髮噴霧 DEP 68 2,200 (19,000) 體香劑, 香水, 美髮慕絲, 髮膠, 美髮噴霧 DMP (2.2) 香水 DNOP (1.6) 體香劑資料來源 :Joseph,

30 PAEs 的暴露途徑 Food 食物攝入 Personal care products 皮膚吸收皮膚吸收 Cosmetics Building products 呼吸攝入 30

31 PAEs 的暴露途徑 PAEs 與塑膠以非共價鍵結方式混合, 極易自塑膠中釋出國人外食人口多, 很多食物加工包裝盛裝和加熱過程都可能用到塑膠製品, 造成 DEHP 趁機溶出滲入食物食物處理工人戴手套雖可防範食物遭細菌汙染, 卻會釋出 DEHP, 食物以塑膠製品盛裝並加熱, 更會大量釋出過去針對超商便當的研究, 也發現超商便當經加熱會大量溶出 DEHP, 便當材質多為 PVC, 一個重量四百公克的便當加熱後,DEHP 濃度達每日建議攝取量的 63.1%-92.2% 國人又常以塑膠袋裝填滾燙熱食, 只要溫度超過六十度, 就會溶出塑化劑 31

32 PAEs 的代謝途徑 Primary DEHP MEHP Human Secondary 32 -Albro, et al., 1982; ATSDR, 1993, Schmid, et al., 1985c.

33 研究目的 Part I: 孕婦鄰苯二甲酸酯暴露會干擾體內甲狀腺荷爾蒙分泌嗎? Human Reproduction 22, (2007) 量測孕婦尿液中鄰苯二甲酸酯代謝物含量量測孕婦血液中甲狀腺荷爾蒙含量檢核二者之相關性 33

34 研究目的 Part II: 孕婦鄰苯二甲酸酯暴露會影響新生兒健康狀態嗎? - Environment International (2008). 量測孕婦羊水中鄰苯二甲酸酯代謝物含量量測新生兒健康指標檢核二者之相關性 34

35 材料與方法 Interview- 83 subjects -alpha fetal protein (AFP) -free β-hcg -maternal age > 35 yrs -undergo amniocentesis Informed consent Amniotic fluid Phthalate monoesters Urine sample Phthalate monoesters Creatinine Serum sample TSH,T 3, T 4, FT 4 Follow up-76 subjects Urine sample Phthalate monoesters Creatinine Serum sample TSH,T 3, T 4, FT 4 Questionnaire Age, BMI, gestation Food consumption Cosmetic usage Follow up-65 subjects Newborns health Anogenital distance Gestational age Urine sample Phthalate monoesters Serum &Cord blood TSH,T 3, T 4, FT 4 Phthalate monoesters Gestation week week week First trimester Second trimester Third trimester Birth N Sampling 35

36 量測指標甲狀腺荷爾蒙 Thyroid stimulating hormone (TSH) Thyroxin (T 4 ) Triiodotyronine (T 3 ) Free thyroxin (FT 4 ) 問卷 Age, BMI, gestation age, Smoking, Medical care etc. Food consumption Cosmetic usage Personal care product usage Building characteristics 新生兒體格檢查 Anogenital distance (AGD) Birth weight Birth height Gestational age Anogenital index (AGI) AGI-W= AGD/ birth weight. AGI-L= AGD/ birth length. Anogenital distance (AGD) -Salazar-Martinez et al.,

37 結果與討論 37

38 Table I-1 受檢孕婦基本資料 (n = 76). 特性平均值標準偏差 Age (years) Body mass index (BMI) Duration of gestation (weeks) Pregnancies and births Number of current pregnancy Number of current birth Smoking status (n/%) Active smoker 0/0 Passive smoker 14/18.4 Non-smoker 62/81.6 Alcohol drinker (n/%) 0/0 New decoration of living/ working place during previous 1 year (n/%) a Home Moving to new decorated house 7/9.2 Just decorated 4/5.3 Workplace Moving to new decorated workplace 2/2.6 Just decorated 6/7.9 Medical care during previous 3 months (n/%) Blood transfusion 3/3.9 Intravenous drip 3/3.9 Oxygen mask 1/ a Moving to new decorated house or workplace means moved into a new building. Just decorated means the place you live or work have decorated recently such as painting or changing the floor.

39 Table I-2 台灣孕婦尿液中 PAE 代謝物含量分布 (μg/g creatinine). > 2.5 < 10 < 6 > 6.5 > 4.5 < 4 < 3.5 > 13 39

40 Table I-3 台灣孕婦血清中甲狀腺荷爾蒙含量分布 Hormones a Percentile Min 5th 50th 95th Max Reference range T 3 (ng/dl) T 4 ( g/dl) Free T 4 (ng/dl) TSH ( IU/mL) a The analytic sensitivities of T 3, T 4, free T 4, and TSH were 19.5 ng/dl, 0.42 g/dl, ng/dl and lu/ml, respectively; the coefficient variations of T 3, T 4, free T 4, and TSH were 2.9%, 4.2%, 3.1%, and 3.0%, respectively. 40

41 Urinary MBP Log MBP (ppb) Log MBP-c y = x R 2 = y = x R 2 = FT4 Urinary MBP Log MBP (ppb) Log MBP-c y = x R 2 = y = x R 2 = T4 A B Figure I-1. 孕婦第二週產期尿液中 MBP-c 含量與 (A) free thyroxine (FT 4 ), (B) thyroxine (T 4 ) 之相關性 41

42 Table I-4. 以多變項複回歸檢定血清中 FT 4 and T 4 含量與尿液中 PAEs 代謝物含量之相關性結果 Variables FT 4 (pmole/l) T 4 (nmole/l) Estimate Prob> t Estimate Prob> t Intercept Age BMI Gestational age MBP < MEP MEHP MBzP MMP a One outlier was excluded because of hypothyroidism (n=75). Multiple regression: FT 4 :R 2 =0.24, T 4 :R 2 =

43 Table II-1 男性與女性新生兒體格檢查結果 (n = 65). Health status 男嬰 (n=33) 女嬰 (n=32) P-value 3 Birth weight (g) 3171 ( ) 3002 ( ) Birth length (cm) 49.6 ( ) 48.3 ( ) 0.023* Gestational age (weeks) 39.0 ( ) Ano-genital distance (AGD) (mm) 1 23 (10-36) > 38.4 ( ) 16 (7-23) 0.020* <0.001* AGI-W(mm/kg) ( ) 5.37 ( ) 0.001* AGI-L ( 10 3 ) ( ) 3.29 ( ) <0.001* 1 The AGD of two girls and boys, respectively, were not available. 2 AGI=ano-genital index; AGI-W= AGD/birth weight; AGI-L=AGD/ birth length. 3 *: p<

44 Table II-2 男嬰與女嬰羊水中 PAEs 代謝物含量分布 (ng/ml, n=64) 1. Female infants Min 10 th 50 th 90 th Max MBP MEHP ND MEP ND ND ND MBzP ND ND ND MMP ND ND ND ND 2.92 Male infants Min 10 th 50 th 90 th Max MBP MEHP ND MEP ND ND ND MBzP ND ND ND MMP ND ND ND ND ND 1 One amniotic fluid sample was failed during analysis. 2 ND=not detected, detection limit of MMP, MEP, MBP, MBzP and MEHP were as follow: 1.4, 1.0, 1.4, 1.4, 0.9 ng/ml 44

45 3.5 3 y = x R 2 = Urinary MBP Amniotic fluid MBP Figure II-1 孕婦尿液中 MBP 含量與羊水中 MBP 含量之相關性 (n=59). 45

46 Table II-3 以孕婦羊水中 MBP 及 MEHP 中位數分高低濃度組後女嬰健康指標之分布及比較 (n = 31). Health status in female infants Low 4 (n=15) MBP-AF 2 MEHP-AF 3 High 4 (n=16) P-value 1 Low 4 (n=15) High 4 (n=16) P-value 1 Birth weight (g) 2810± ± * 2918± ± Birth length (cm) 47.3± ± * 48.1± ± Gestational age (weeks) 38.1± ± ± ± AGD (mm) 17.6± ± * 17.0± ± AGI-W (mm/kg) 6.2± ± * 6.0± ± * AGI-L ( 10 3 ) 3.7± ± * 3.6± ± * 46 1 Wilcoxon Rank Sum Test, *: p < 0.05; 2 AGD data were lacking for one female newborn in each group. 3 AGD data were lacking for two female newborns in the high MEHP-AF group. 4 Median levels of amniotic fluid MBP in low and high group were 67 and 104 ng/ml, respectively; those of MEHP were 9.5 and 38.8 ng/ml, respectively.

47 Table II-4. 以孕婦羊水中 MBP 及 MEHP 中位數分高低濃度組後男嬰健康指標之分布及比較 (n = 313). Health status in male infants Low (n=16) MBP High (n=17) P-value Low (n=16) MEHP High (n=17) P-value Birth weight (g) 3146± ± ± ± Birth length (cm) 49.2± ± ± ± Gestational age (weeks) 39.1± ± ± ± AGD (mm) 21.2± ± ± ± AGI-W (mm/kg) 6.6± ± ± ± AGI-L ( 10 3 ) 4.3± ± ± ± One male infant of each group in MBP-AF and MEHP-AF, respectively, were lack of AGD.

48 羊水中 MBP 與女嬰生產時之 AGI 呈現顯著負相關 10 6 AGI-W (mm/kg) y = x R 2 = AGI-L ( 103) y = x R 2 = A Log amniotic fluid MBP (ng/ml) B Log amniotic fluid MBP (ng/ml) Figure II-2 (A) 羊水中 MBP 與女嬰生產時 AGI-W 之線性回歸 (n=29, R 2 =0.14, p=0.043); (B) 羊水中 MBP 與女嬰生產時 AGI-L 之線性回歸 (n=29, R 2 =0.16, p=0.032). 48

49 鄰苯二甲酸酯對兒童內分泌干擾效應 : 國內研究結果 49

50 The definition of puberty and precious puberty Puberty is a complex process involving the activation and maturation of the hypothalamic-pituitary-gonadal (HPG) axis. The timing of puberty in humans approximates 10 years in girls and years in boys. However, it may range from as young as 8to13yearsin girls and from 9 to 14 years in boys. (Grumbach and Styne, 1998) Premature sexual development in the human female is presently defined as the appearance of any physical change characteristic of puberty with onset before 8 years of age. (Sippel, 1994)

51 Prevalence of precocious puberty Precocious puberty has a prevalence of 1 in 5,000 children and exists in girls more than boys by a ratio of 10:1. ( Nebesio & Pescovitz, 2005; Partsch & Sippell, 2001 ) The prevalence of PP was 20 to 23 per in girls, whereas the prevalence was five-fold lower for boys (<5 per ) in Denmark. (Teilmann et al., 2005)

52 Follow-up problems of precocious puberty Though girls who experience premature puberty grow faster than their peers due to accelerated bone growth, they fail to reach the normal adult height. ( Carel, 2006 ; Partsch & Sippell) Early menarche has been linked to greater risk of breast cancer as an adult; therefore, precocious onset would seem to increase that risk. ( Wang, Needham, & Barr, 2005; Zuckerman, 2001 ) Studies indicate that girls who become sexually mature at earlier ages are more likely to engage in risk-taking behaviors such as smoking, using alcohol or drugs, and engaging in unprotected sex. (Committee on Adolescent Health Care, 2006; Flanigan, 2003; Zuckerman, 2001 )

53 What factors are suspected to trigger the earlier onset of sexual maturation? The ethnic, genetic, pediatric obesity, environmental toxins that disrupt endocrine function, psychosocial stress, and early exposure to an increasingly sexualized society explanations for the earlier onset of sexual maturation. ( Lemonick, 2000 )

54 The regulation pathway of sexual hormone in female Phthalates???

55 Objectives To investigate the association and possible mechanism between exposure to phthalates and female puberty. To investigate the relationships between urinary monoester metabolites and the PAE levels in house dust for precocious puberty and normal girls, To develop effective intervention strategies to decrease the phthalates exposure for children.

56 Fig 1 The framework of this study

57 Sampling strategy for dust- 5 samples Bed (or sofa) Floor Upper floor Picture from 林文察 Major activity area (Sleeping room) Sample 1 Sample 2 Minor activity area (Parents room, living room, playroom et al.) Sample 3 Sample 4 Sample 5

58 Dust collection Using aluminum-made collector & cellulose filter Covering with aluminum foil and then sealing by parafilm after collecting enough dust sample

59 Questionnaires for phthalates exposure evaluation Dietary patterns Category: Main food (rice noodles, etc.), Vegetable (cabbages water celery, etc.), Meat (pork, poultry, etc.), Fruits, Snack and Nutritional supplement. Household usual habits 250 c.c. Cleaning frequency, cleaning products, cooking habits et al. Time-activity pattern and medical history Personal care products Children s habit Body lotion, shampoo, shower cream, soap, hair spray, nail polish, perfume et al. Maternal habits Perfume, cosmetics, lipstick et al.

60 Analysis of phthalate metabolites Phthalate metabolites monomethyl phthalate (MMP) monoethyl phthalate (MEP) monobutyl phthalate (MBP) monobenzyl phthalate (MBzP) mono-2-ethylhexyl phthalate (MEHP) mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) 250 c.c. Analytical method Urine sample

61 Results and discussions Table 1 The demographic characteristics of girls with CPP and prepubescent control girls. Item Control Group ( n = 31) CPP Group( n = 73) p-value b Age (years) a 6.8 ( ) 8.1 ( ) <0.001 Age at diagnosis (years) a ( ) - Height (cm) a ( ) ( ) <0.001 Weight (kg) a 22.6 ( ) 29.0 ( ) <0.001 BMI (kg/m 2 ) a 16.0 ( ) 16.8 ( ) 250 c.c FATHER S EDUCATION LEVEL (n) High school 6 27 College Graduate school 4 12 MOTHER S EDUCATION LEVEL (n) High school 8 32 College Graduate school 2 3 FAMILY S MONTHLY INCOME (n) Less than 70,000 NT$ More than 70,000 NT$ Abbreviations: [CPP] girls with central precocious puberty, [Control] prepubescent control girls, [BMI] body mass index, [NT$] New Taiwan Dollar. a Values are median (range); b continuous variables were tested using Mann Whitney U-Tests, and categorical variables using Fisher s Exact Tests

62 Results and discussions Table 2 Unadjusted and adjusted-creatinine concentrations of urinary phthalate monoesters in girls with central precocious puberty (CPP) and prepubescent control girls. CREATININE UNADJUSTED (ng/ml) Control Group (n = 29) CPP Group (n = 71) p-value 250 c.c. NHANES MMP 4.53 ( ) 6.95 ( ) < LOD-1.90 MEP 7.87 ( ) 19.1 ( ) < MBP 40.2 ( ) 60.4 ( ) MBzP 2.45 ( ) 6.22 ( ) MEHP 5.10 ( ) 8.23 ( ) MEHHP e 27.6 ( ) 59.6 ( ) MEOHP e 25.0 ( ) 56.9 ( ) CREATININE-ADJUSTED (μg/g creatinine) MMP 6.34 ( ) 8.10 ( ) < LOD-2.32 MEP 11.3 ( ) 25.4 ( ) MBP 67.2 ( ) 94.6 ( ) MBzP 3.74 ( ) 9.00 ( ) MEHP 9.04 ( ) 10.8 ( ) MEHHP e 27.7 ( ) 57.4 ( ) MEOHP e 25.8 ( ) 52.0 ( )

63 Results and discussions Table 3 Average levels [range] of kisspeptin and clinical examinations results of girls with central precocious puberty (CPP) and prepubescent control girls in this study. CPP Group (n = 40) Control Group Thel+LHRH LHRH + Leup/Men (n = 11) Subgroup Subgroup Subgroup p-value a (n = 13) (n = 12) 250 c.c. (n = 15) Age (years) 7.4 [ ] 7.0 [ ] 8.9 [ ] 9.0 [ ] <0.001 Kisspeptin (pmol/l) 1.95 [ ] 1.97 [ ] 2.16 [ ] 2.29 [ ] Bone age (years) [ ] 10.3 [8.8-12] 10.7 [ ] <0.001 b Basal LH (miu/ml) < [< ] 0.99 [< ] 1.03 [< ] Basal FSH (miu/ml) 1.65 [ ] 2.96 [ ] 4.81 [ ] 2.66 [ ] Basal E 2 (miu/ml) < [<8-15.5] 10.5 [<8-19.0] 16.6 [<8-102] Peak LH (miu/ml) [ ] 21.2 [ ] 27.6 [ ] <0.001 b a Kruskal- Wallis Test: p-value for the difference between the four groups; b Kruskal- Wallis Test: p-value for the difference between the CPP subgroups.

64 Results and discussions Kisspeptin (pmol/l) c.c. 1.2 Control Thel+ LHRH- LHRH+ Leup/Men Different development group Figure 1. Box plot of kisspeptin distribution in different development groups. 1: Control Group (n = 11); 2: CCP subgroup Thel+ LHRH : premature thelarche and a negative LHRH test result (n = 13); 3: CCP subgroup LHRH+: positive LHRH test result (n = 12); 4: CCP subgroup Leup/Men: being treated with leuprorelin acetate or had experienced menarche (n = 15). Dotted line: the mean level of kisspeptin-54 in each group. (P trend among the four groups after adjusting for age = 0.005)

65 Results and discussions Y = X R 2 = , p= Y = X R 2 = , p< Kisspeptin54 (pmol/l) Kisspeptin54 (pmol/l) c.c ln MMP ( ng/ml) ln MBP ( ng/ml) Y = X R 2 = , p= Y = X R 2 = , p= Kisspeptin54 (pmol/l) Kisspeptin54 (pmol/l) ln MBzP ( ng/ml) ln MBP-Cr ( ug/g-cr)

66 探討鄰苯二甲酸酯類暴露與女童性早熟發生之相關性及環境控管介入研究 66

67 Results (Intervention strategies) 介入項目健康食品及藥物的使用化妝品及個人衛生用品的使用塑膠容器的使用微波食物的食用塑膠袋或保鮮膜包裝食物的食用建材的接觸及洗手習慣時間活動模式限制使用細項基於用藥倫理及個人健康考量, 本項只紀錄但不限制女童使用, 但若與健康無相關者, 則仍勸說暫停使用一個禮拜限制精油香水乳液指甲油的使用, 沐浴乳及洗髮乳則記錄使用量及使用頻率限制塑膠碗保鮮盒市售飲料 PVC 杯水的使用限制微波便當及微波剩菜 ( 覆蓋保鮮膜 ) 的使用限制塑膠袋或保鮮膜包裝食物的食用詳實紀錄接觸巧拼地板玩耍及吃東西前未洗手的時間或次數若有上述行為發生則詳實紀錄發生時間及使用量介入期程 : 一個星期

68 Intervention strategy Figure Intervention design and timing of sample collection in this study.

69 Results and discussions Table Subjects who follow intervention guideline resulted in declining the level of urinary phthalate metabolites in this study. Phthalate concentration (ng/ml) Phthalate concentration (ug/g-creatinine) Pre-I Post-I P # Pre-I Post-I P # MMP (n=18) <0.001* ( ) ( ) ( ) ( ) 0.003* MEP (n=15) * ( ) ( ) ( ) ( ) 0.001* MBP(n=16) <0.001* ( ) ( ) ( ) ( ) 0.013* MBzP (n=19) <0.001* ( ) ( ) ( ) ( ) <0.001* MEHP(n=19) <0.001* ( ) ( ) ( ) ( ) 0.011* MEOHP (n=19) <0.001* ( ) ( ) ( ) ( ) 0.01* MEHHP (n=18) <0.001* ( ) ( ) ( ) ( ) 0.005* MECCP (n=18) <0.001* ( ) ( ) ( ) ( ) 0.006* # : Wilcoxon Signed Ranks Test; : Pair T Test; * : P<0.05

70 Results and discussions

71 Results and discussions

72 要怎麼降低或避免塑化劑的暴露? 避免喝塑膠杯裝市售飲料的習慣, 儘量自己帶不銹鋼杯或馬克杯避免以塑膠袋塑膠容器盛裝熱食或微波加熱, 平常的生活中也減少使用塑膠袋養成吃東西前洗手的習慣, 避免因手接觸室內灰塵而食入塑化劑避免用保鮮膜包覆食物進行微波或蒸煮兒童應避免在 PVC 地板上吃東西玩耍, 也不要直接睡在 PVC 地板上在 PVC 地板上活動後, 要保有洗手的習慣, 並避免幼童將手放置口中室內環境應定期吸塵以維持乾淨, 電器不用時應拔除插頭以避免經常在高熱狀態下逸散塑化劑多使用含天然成分或不含塑化劑之香水化妝品及個人衛生用品避免長期吃單一種類的高脂食品, 例如 : 可以交替食用豬肉牛肉雞肉或以魚類替代, 都可以降低塑化劑的可能暴露多喝白開水, 多攝取新鮮蔬果, 少吃高脂食物, 並保持心情愉悅

73 Thanks for your attention! Comments! 73

中文提要苏州市区女中学生多囊卵巢综合征发病率调查及发病相关因素分析中文提要目的 : 了解苏州市区女中学生中多囊卵巢综合征 (polycystic ovarian syndrom,pcos)

中文提要苏州市区女中学生多囊卵巢综合征发病率调查及发病相关因素分析中文提要目的 : 了解苏州市区女中学生中多囊卵巢综合征 (polycystic ovarian syndrom,pcos) 硕士学位论文 (2006 届 ) 苏州市区女中学生多囊卵巢综合征发病率调查及发病相关因素分析 Investigating the Incidence of Polycystic Ovarian Syndrome Among Adolescent Schoolchildren in Soochow City and Studying the