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儿童和青少年内分泌干扰物邻苯二甲酸酯的风险评估及激素变化

Risk assessment of endocrine disrupting phthalates and hormonal alterations in children and adolescents.

机构信息

a Division of Toxicology , College of Pharmacy, Sungkyunkwan University , Suwon , Gyeonggi-do , South Korea.

b College of Natural Science , Changwon National University , Changwon , Gyeongnam , Korea.

出版信息

J Toxicol Environ Health A. 2018;81(21):1150-1164. doi: 10.1080/15287394.2018.1543231. Epub 2018 Nov 12.

DOI:10.1080/15287394.2018.1543231
PMID:30415604
Abstract

Risk assessment and hormone evaluation were carried out for di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), endocrine disrupting chemicals (EDCs), in 302 Korean children (n = 223) and adolescents (n = 79) (< age 19). Urinary and serum concentrations of DEHP, MEHP (mono(2-ethylhexyl) phthalate), DBP, MBP (monobutyl phthalate), and PA (phthalic acid, a common final metabolite of phthalates) were detected in children and adolescents. Daily exposure levels were estimated to be 16.45 ± 36.50 μg/kg b.w./day for DEHP, which is one-third of the tolerable daily intake (TDI) value (50 μg/kg b.w./day), but 14 out of 302 participants had a hazard index (HI = intake/TDI) value >1. The mean daily exposure level of DBP was 1.23 ± 1.45 μg/kg b.w./day, which is one-eighth of the TDI value (10 μg/kg b.w./day), but 1 out of 302 participants had a HI value > 1. Positive correlations were observed between serum DBP or MEHP, and serum estradiol (E2) and/or luteinizing hormone (LH) in prepubescent children. In addition, serum MBP levels were found to be negatively correlated with serum triiodothyronine (T3) or thyroxine (T4) in male participants, and serum DEHP levels with serum thyroid stimulating hormone (TSH) in female adolescents. Low-density lipoprotein (LDL) levels were positively correlated with serum PA levels in children and adolescents. DEHP, DBP or its metabolites may be associated with altered hormone levels in children and adolescents. Data suggest that exposure levels of DEHP and DBP in Korean children need to be reduced to levels below TDI to protect them from EDC-mediated toxicities. Abbreviations: DBP: dibutyl phthalate; DEHP: di(2-ethylhexyl) phthalate; E2: estradiol; EDC: endocrine disrupting chemical; EFSA: European Food Safety Authority; FSH: follicle stimulating hormone; HDL: high density lipoprotein; HI: hazard index; LDL: low density lipoprotein; LH: luteinizing hormone; MEHP: mono(2-ethylhexyl) phthalate; MBP: monobutyl phthalate; PA: phthalic acid; PPAR: peroxisome proliferator-activated receptor gamma; PVC: polyvinyl chloride; T3: triiodothyronine; T4: thyroxine; TDI: tolerable daily intake; TG: triglyceride; TSH: thyroid stimulating hormone; UPLC/MS/MS: Ultra Performance Liquid Chromatography/Tandem Mass Spectrometry; WWF: World Wildlife Fund.

摘要

对 302 名韩国儿童(n=223)和青少年(n=79)(<19 岁)进行了邻苯二甲酸二(2-乙基己基)酯(DEHP)和邻苯二甲酸二丁酯(DBP)等内分泌干扰化学物质(EDCs)的风险评估和激素评估。检测了儿童和青少年尿液和血清中 DEHP、MEHP(单(2-乙基己基)邻苯二甲酸)、DBP、MBP(单丁基邻苯二甲酸)和 PA(邻苯二甲酸,邻苯二甲酸酯的常见终末代谢物)的浓度。DEHP 的日暴露水平估计为 16.45±36.50μg/kg bw/天,这是可耐受日摄入量(TDI)值(50μg/kg bw/天)的三分之一,但 302 名参与者中有 14 人的危害指数(HI=摄入量/TDI)值>1。DBP 的平均日暴露水平为 1.23±1.45μg/kg bw/天,这是 TDI 值(10μg/kg bw/天)的八分之一,但 302 名参与者中有 1 人的 HI 值>1。在青春期前儿童中,血清 DBP 或 MEHP 与血清雌二醇(E2)和/或黄体生成素(LH)呈正相关。此外,在男性参与者中,血清 MBP 水平与血清三碘甲状腺原氨酸(T3)或甲状腺素(T4)呈负相关,而在女性青少年中,血清 DEHP 水平与血清促甲状腺激素(TSH)呈负相关。儿童和青少年的低密度脂蛋白(LDL)水平与血清 PA 水平呈正相关。DEHP、DBP 或其代谢物可能与儿童和青少年激素水平的改变有关。数据表明,需要将韩国儿童的 DEHP 和 DBP 暴露水平降低到 TDI 以下,以保护他们免受 EDC 介导的毒性。缩写词:DBP:邻苯二甲酸二丁酯;DEHP:邻苯二甲酸二(2-乙基己基)酯;E2:雌二醇;EDC:内分泌干扰化学物质;EFSA:欧洲食品安全局;FSH:卵泡刺激素;HDL:高密度脂蛋白;HI:危害指数;LDL:低密度脂蛋白;LH:黄体生成素;MEHP:单(2-乙基己基)邻苯二甲酸;MBP:单丁基邻苯二甲酸;PA:邻苯二甲酸;PPAR:过氧化物酶体增殖物激活受体γ;PVC:聚氯乙烯;T3:三碘甲状腺原氨酸;T4:甲状腺素;TDI:可耐受日摄入量;TG:甘油三酯;TSH:促甲状腺激素;UPLC/MS/MS:超高效液相色谱/串联质谱法;WWF:世界自然基金会。

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