臺灣博碩士論文加值系統

壬基酚是一種工業化學物質，被廣泛使用在我們日常生活用品中。它是一種內分泌干擾物質，與雌激素類似，具有雌激素作用，一旦進入人體會干擾體內原本正常荷爾蒙的功能，包含可能改變青春期發育。本研究為一橫斷式研究，目的在了解台灣青春期學生體內壬基酚的濃度之地域性差異與青春期學生第二性徵之關係。
本研究對象來自台灣北、中、南、東部10~14歲415名青春期學生，分析其體內壬基酚濃度，並利用問卷來探討飲食習慣、第二性徵發育情形。尿液檢體、飲料樣本分別經固相萃取淨化、液液萃取後，以高效液相層析儀進行分析。
本研究中學生第二性徵發育情形，男學生出現比例最高為:青春痘(49.0%)、其次為體毛發育 (41.0%);女學生部分: 乳房發育 (71.7%)、青春痘 (59.5%)、體毛 (54.6%)、平均初經年齡11.4±1.0歲。
本研究同時探討不同年代之北部地區青春期學童第二性徵發育情形，結果發現， 2008年青春期男童在同年齡層第二性徵發生機率較2012年學童早。女生部分，在10~12.99歲時2012年青春期女學童出現乳房發育、體毛和月經的比例高於2008年青春期女學童，2012年青春期女學童初經年齡也低於2008年。除了乳房發育、體毛和出現月經外，其他性徵在2012年出現的比例普遍低於2008年的青春期女學童。
此外，北、中、南、東各地區青春期學生尿中壬基酚平均濃度分別為4.97±4.27μg/g creatinine、3.50±2.94μg/g creatinine、3.37±2.49μg/g creatinine、3.34±2.72μg/g creatinine，北部地區明顯高於其他地區。
經回歸模式校正年齡、BMI、睡眠時間、運動、地區後，結果顯示壬基酚暴露是女生初經年齡降低的顯著影響因子，顯示在NP濃度較高的族群，其初經年齡會提早0.20歲。年齡對女生長青春痘、體毛、臀部變大、出現月經有顯著影響 (OR=2.28；2.09；1.46；6.54)；BMI對女學生長體毛、脂肪變多、臀部變大、出現月經有顯著影響 (OR=1.10；1.22；1.10；1.23)；睡眠時間沒有顯著影響第二性徵發育。區域別方面，南區、東區比北區女學生容易長青痘 (OR=5.41;2.63)，中區、南區較北區女學生乳房發育比例高 (OR=6.11;3.77)，在控制其他變項後，中部女學童初經年齡比北部地區女學童平均多0.29歲 (β=0.29)。本研究建立台灣地區青春期學生體內壬基酚暴露情形，發現青春期學童體暴露到壬基酚情形相當普遍，所以值得進一步研究並持續追蹤長期暴露對第二性徵發育的影響。

4-Nonylphenol (NP) is industrial chemical substance used widely in our daily products. It is also an endocrine disruptor. The structure of nonylphenol is similar to estrogen. Once inside the human body, it disrupts the original function of hormone, including changes in puberty growth. This study aims to determine regional differences of nonylphenol for Taiwanese pubertal students and to clarify its correlation with development of secondary sexual characteristics.
Four hundreds and twenty-three adolescent students (aged from 10 to 14) were recruited from northern, central, southern, and eastern Taiwan. Their demographic data were collected using qustionnaires, their urine samples were also collected to analyze the NP concentration in their bodies. Urine and beverage samples were purified and assessed using high-performance liquid chromatography coupled with fluorescent detection.
The highest occurrence of secondary sexual characteristic for boys was having pimples (49.0%), followed by pubic hair development (41.0%). The highest occurrence of secondary sexual characteristic for girls was breast development (71.7%), followed by having pimples (59.5%), and pubic hair (54.6%). The average age of menarche occurred at 11.4±1.0years.
This research also studied the secondary sexual characteristics of adolescent schoolchildren of different ages in northern regions. The result showed that there were significant differences in the secondary sexual characteristics of the male students of 2008 and that of 2012. Adolescent boys in the 2008 study had a higher occurrence rate of secondary sexual characteristics than their 2012 counterparts. As for female students, the rate of appearance of pubic hair and menstrual during 10 to 12.99 of age is higher in the 2012 adolescent female students. Compared to their 2008 counterparts, their age of menarche also appeared to be lower. Except for the growth of pubic hair and occurrence of menstrual, other rate of sexual characteristics of the 2012 students were generally lower than those of 2008.
In addition, the mean concentration of urinary NP of the students were 4.97±4.27, 3.50±2.94, 3.37±2.49, and 3.34±2.72μg/g creatinine, from northern, central, southern, eastern, respectively.
According to regression models, after adjusting for age, BMI, sleeping, exercise habits and region, the results showed that exposure to nonylphenol was a risk for the advancement of menarche of age for girls. The menarcheal age decrease as the NP concentration increase. The above-median group had a 0.20 year earlier age of menarche.
Regression analysis showed a significant association between age and pubic hair development in girls. BMI is significantly associated with the occurrence pimple, pubic hair, widening of hips, and menstruation in girls (OR=1.10；1.22；1.10；1.23). Sleeping hour is not associated with secondary sexual characteristics. The odds ratio of breast development for central and southern girls (OR=6.11;3.77) are higher than northern counterparts.
Since NP exposure is quite common among Taiwanese, a large longitudinal study is warranted to examine the relationship between NP exposure and secondary sexual development for adolescent students .

摘要 I
Abstract III
表目錄 IX
圖目錄 XI
第一章 前言 1
第一節 研究緣起 1
第二節 研究目的 5
第二章 文獻探討 6
第一節 環境荷爾蒙介紹 6
第二節 壬基酚類特性 7
2-2-1壬基酚介紹 7
2-2-2壬基酚之物理、化學特性 8
2-2-3壬基酚模仿雌激素效應 8
第三節 壬基酚的用途與用量 9
2-3-1用途 9
2-3-2使用量 10
第四節 水環境流佈 11
2-4-1 地表水和沉積物 11
2-4-2地下水 13
2-4-3飲用水 14
2-4-4汙水處理廠 14
第五節 壬基酚的其他可能來源 15
2-5-1空氣 15
2-5-2土壤 16
2-5-3食物 17
第六節 壬基酚對生物體產生的影響 18
2-6-1水中生物 18
2-6-2囓齒動物 20
2-6-3人類 21
第七節 壬基酚在人體的分布代謝 22
第八節 人類青春期及第二性徵發育 22
2-8-1青春期定義 22
2-8-2第二性徵發育情形 25
2-8-3影響第二性徵發育之環境因素 26
第九節 環境荷爾蒙對青春期的影響 27
2-9-1壬基酚對動物青春期的影響 27
2-9-2壬基酚類對人類青春期的影響 28
第十節 台灣及其他各國的相關規定 29
2-10-1國內管制現況 29
2-10-2各國研究與管制情形 30
第三章 材料與方法 31
第一節 材料 31
3-1-1試藥 31
3-1-2器材 32
3-1-3儀器 32
第二節 方法 33
3-2-1研究對象 33
3-2-2尿液樣本收集 34
3-2-3飲料樣本收集 35
3-2-4壬基酚儲備溶液之配製 35
3-2-5檢量線之配製 35
3-2-6試劑配製 36
3-2-7尿液樣本前處理 36
3-2-8飲料樣本前處理 37
3-2-9儀器分析條件 38
3-2-10尿液中肌酸酐測定 38
3-2-11分析方法之驗證 39
3-2-12每日經由飲食之壬基酚攝取量估算方法 40
3-2-13健康風險評估 41
3-2-14統計分析 41
第四章 結果 43
第一節 分析方法之驗證 43
第二節 學生基本資料描述 43
第三節 學生性徵發育情形 46
4-3-1 男學生 46
4-3-2 女學生 47
第四節 學生第二性徵發育與年齡、身高、體重、BMI之相關性 48
4-4-1 男學生 48
4-4-2 女學生 48
第五節 每日攝取食物份量及每日壬基酚攝取量估計值 49
4-5-1包裝飲品NP濃度 49
4-5-2每日攝取食物份量及每日壬基酚攝取量估計值 50
4-5-3健康風險評估 52
第六節 學生尿液中之壬基酚濃度 54
第七節 影響尿液中壬基酚濃度之因素 54
第八節 影響青春期學生第二性徵發育因子之邏輯斯迴歸分析 55
4-8-1男學生部分 55
4-8-2女學生部分 56
第九節 不同年代青春期學童生長發育、第二性徵的差異分析 57
第五章 討論 62
第一節 國中小學生發育情形 62
5-1-1基本人口學資料 62
5-1-2第二性徵方面 63
第二節 受試者壬基酚濃度分布情形 65
5-2-1各國比較 65
5-2-2台灣地區不同族群壬基酚濃度比較 65
第三節 食物中壬基酚攝取量比較 67
第四節 第二性徵與壬基酚濃度關係 70
第五節 研究限制 72
第六章 結論 73
參考文獻 76
附錄 137

表目錄

Table 2.1. Nonylphenol (NP) levels in surface water and sediment samples. 90
Table 2.2 NP levels in air. 91
Table 4.1 The Method of Analyzing NP and recovery 92
Table 4.2 Physical development of study participants 93
Table 4.3 Physical development of study participants by region 94
Table 4.4 Demographic and exposure characteristics for adolescent students 95
Table 4.5 Occurrence of pubertal boys with secondary sexual characteristics by age group. 97
Table 4.6 Occurrence of pubertal boys with secondary sexual characteristics by region. 98
Table 4.7 Occurrence of pubertal girls with secondary sexual characteristics by age group. 99
Table 4.8 Occurrence of pubertal girls with secondary sexual characteristics by region. 100
Table 4.9 The correlations of secondary sexual characteristics,physical development and NP concentration in boys. 101
Table 4.10 The correlations of secondary sexual characteristics,physical development and NP concentration in girls. 102
Table 4.11 NP concentration for different beverage packaging materials 103
Table 4.12 NP concentration in different beverages and packing material 104
Table 4.13 The estimated consumption food stuffs by region and gender 105
Table 4.14 Estimated daily NP intake for pubertal students by region 106
Table 4.15 Concentrations of NP in Taiwan foodstuff samples 107
Table 4.16 Distributions of daily intake per body weight of pubertal students for region . 108
Table 4.17 Uncertainty analysis for daily intake of NP from different foods for Northern region 109
Table 4.18 Uncertainty analysis for daily intake of NP from different foods for Central region 110
Table 4.19 Uncertainty analysis for daily intake of NP from different foods for Southern region 111
Table 4.20 Uncertainty analysis for daily intake of NP from different foods for Eastern region 112
Table 4.21 Distributions of urinary nonylphenol 113
Table 4.22 Comparison of the urinary NP cocentrations across different studies. 114
Table 4.23 Comparison of urinary NP concentrations by demographic characteristics 115
Table 4.23 Comparison of urinary NP concentrations by demographic characteristics 116

Table 4.24 Multiple logistic regression model evaluating the association between NP concentrations and secondary sexual characteristics for pubertal boys. 118
Table 4.25 Regression models analyzing the association between NP concentrations and secondary sexual characteristics for pubertal girls. 119
Table 4.26 Physical development of study participants in north 120
Table 4.27 Occurrence of pubertal boys with secondary sexual characteristics by age group in north 121
Table 4.28 Occurrence of pubertal girls with secondary sexual characteristics by age group in north 122
Table 4.29 The estimated consumption food stuffs by region and gender in norh 123
Table 4.30 Estimated daily NP intake for pubertal students by north 124
Table 4.31 Distributions of urinary nonylphenol in north 125
Table 4.32 Regression models evaluating the association between NP concentrations and secondary sexual characteristics for pubertal boys in north. 126
Table 4.33 Regression models evaluating the association between NP concentrations and secondary sexual characteristics for pubertal girls in north. 127

圖目錄
Figure 1 Uses and distributions of nonylphenol 128
Figure 2 Standards for genital ratings. 129
Figure 3 Standards for pubic hair ratings in boys 130
Figure 4 Standards for breast ratings in girls 131
Figure 5 Standards for pubic hair ratings in girls 132
Figure 6 NP calibration curve 133
Figure 7 Occurrence of secondary sexual characteristics for adolescent boys 134
Figure 8 Occurrence of secondary sexual characteristics for adolescent girls 135
Figure 9 Disribution of total NP dietary intake for northern region through uncertainty analysis 136
Figure 10 Disribution of total NP dietary intake for central region through uncertainty analysis 136
Figure 11 Disribution of total NP dietary intake for southern region through uncertainty analysis 137
Figure 12 Disribution of total NP dietary intake for east region through uncertainty analysis 137

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