國人幼童的鄰苯二甲酸酯類化合物（Phthalate）內在暴露和相關的荷爾蒙及發育健康效應

It’s been striking that phthalate as Hormonal disruptor has been increased during the past 30 years and the levels have been found particularly high in Taiwan environment. Children are at special risk because they are during fast growth and development with necessary fine tone of hormonal regulations. The specific aims and hypotheses of this study are focused on child and listed as the follows:1. Phthalate survey for children 2. Assessments of gender-related behavior changes associated with the exposure 3. Phthalate internal dose and steroid hormonal changes 4. Phthalate associated with motor and cognitive development in children. Design: We obtained biologic samples of umbilical cord blood, urin,breast milk from pregnant women urine, blood from the toddlers to 2-3 and 4-6 year old to analyze hormone and the exposed dose of phthalate monoesters(MEHP, 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP, 2cx-MMHP, MnBP, MiBP, MBzP, oxo-MiNP, OH-MiNP, cx-MiNP) by LC/MS/MS. Using two kind of statistical methods, parameter(t-test, the chi-square, linear regression ) and nonparameter analyze. Result: This research object is the preschool children altogether is 126, boy has 58, girl 68. The data of statistical analysis shows that the language meter intelligence quotient (adjusts child's sex, age and guardian's school record) are negatively correlated with 5OH-MEHP(β=-0.310), 5oxo-MEHP (β= -0.296) and 5cx-MEPP(β=-0.298), the PSAI score (adjusts child's sex, age and guardian's school record) is negatively correlated with 2cx-MMHP(β=-0.374, p< 0.05). The concertration ratio of MBzP and oxo-MiNP of 4-6 year old preschoolers’ urine with only 6% and 3% are lower than the limit of detection (LOD) value. The concertration ratio of MBzP, oxo-MiNP, OH-MiNP, cx-MiNP of 2-3 year old preschoolers’ urine, 13%, 20%, 3% and 3%, are lower than LOD value, The concertration ratio of MBzP, oxo-MiNP, OH-MiNP, cx-MiNP of pregnant women’s urine, 36%, 60%, 60% and 61%, are lower than the LOD value; The concertration ratio of MEHP, MnBP, MiBP of the umbilical cord blood are 100% detectable, the monoester might pass through placenta to fetal. Breast milk has above 90% are lower than LOD value, except MEHP, MnBP, MiBP. The phthalate monoesters of 2-3 year old and 4-6 year old preschoolers’ urine have higher concentration than that of the mothers. The different age of exposure have not certain correlation with hormone. TSH, T3, T4, leptin and LH could appear positive or negative correlation during the different age. TRAb, PRL and E2 have positively correlated with phthalate monoesters (p<0.05), and FT4, IGF1, IGFBP3, TBG, Adiponectin, FSH, TT, PG are negatively correlated. Correlation is the most significant between MiBP and hormone, then is MEHP and MnBP. This result is in accordance with the rodent data. According to the literature reported the compounds with short alkyl chain like MiBP have stronger toxicity. Phthalate monoesters showed negative correlation with IGFBP3 reached 7 items, then are 5 items with T3 and TT. Conclusion: 4-6 year old preschoolers and 2-3 year old toddler all are generally under the exposure of phthalate ester. Children’s thyroid function and steroid hormone could be influenced upon the phthalate esters exposure. IGFBP3 is the principle binding protein for IGF1 and IGF1 plays an important role on growth and the development, IGFBP3 and phthalate esters have significant correlation. These outcomes will help us to understand how does phthalate esters affect children and protect children from damage.