Roberts Georgia K, Waidyanatha Suramya, Kissling Grace E, Fletcher Brenda L, Silinski Melanie A R, Fennell Timothy R, Cunny Helen C, Robinson Veronica Godfrey, Blystone Chad R
Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
RTI International, Research Triangle Park, NC, USA.
Toxicol Rep. 2016 Sep 11;3:774-783. doi: 10.1016/j.toxrep.2016.09.004. eCollection 2016.
Butyl paraben (BPB) is an antimicrobial used in a variety of consumer products. Due to widespread human exposure and reported estrogenic activity, the National Toxicology Program quantified internal exposure during critical periods of development. Time-mated female Hsd:Sprague Dawley SD rats were administered 0, 1500, 5000 or 15,000 ppm BPB NIH-07 feed, , from gestation day (GD) 6 to postnatal day (PND) 28. Dam plasma, amniotic fluid and fetuses were collected on GD18 and pup and dam plasma were collected on PNDs 4, 10, 14, 21 and 28 and analyzed for free (unconjugated) and total (unconjugated and conjugated) BPB using liquid chromatography-tandem mass spectrometry. Free BPB was below the limit of quantitation in fetuses (LOQ 1.91 ng BPB/g fetus) and amniotic fluid (LOQ 0.17 ng BPB/mL amniotic fluid) at 1500 ppm. Analyte levels in amniotic fluid were less than 1% of maternal plasma, suggesting limited placental transfer. Total BPB in PND4 pup plasma was less than 5% of dam plasma in all exposure groups, suggesting low lactational transfer. However, at nearly all time points and exposure groups, there were higher levels of free BPB in pup versus dam plasma, suggesting limited conjugation in pups. Pup conjugation of BPB was age-dependent, not reaching the percent-conjugation in dams (>99%) until PNDs 21 to 28. These data illustrate low placental and lactational transfer of dietary BPB and that poor conjugation in pups during early lactation results in higher exposure to free BPB in pups compared to dams.
对羟基苯甲酸丁酯(BPB)是一种用于多种消费品的抗菌剂。由于人类广泛接触且有报道称其具有雌激素活性,美国国家毒理学计划对发育关键期的体内暴露量进行了量化。将时间匹配的雌性Hsd:Sprague Dawley SD大鼠从妊娠第6天(GD)至出生后第28天(PND)给予含0、1500、5000或15000 ppm BPB的NIH-07饲料。在GD18收集母鼠血浆、羊水和胎儿样本,在PND4、10、14、21和28收集幼崽和母鼠血浆,并使用液相色谱-串联质谱法分析游离(未结合)和总(未结合和结合)BPB。在1500 ppm时,胎儿(定量下限为1.91 ng BPB/g胎儿)和羊水(定量下限为0.17 ng BPB/mL羊水)中的游离BPB低于定量下限。羊水中的分析物水平低于母体血浆的1%,表明胎盘转运有限。在所有暴露组中,PND4幼崽血浆中的总BPB低于母鼠血浆的5%,表明乳汁转运较低。然而,在几乎所有时间点和暴露组中,幼崽血浆中的游离BPB水平均高于母鼠血浆,表明幼崽中的结合作用有限。幼崽对BPB的结合作用具有年龄依赖性,直到PND21至28才达到母鼠中的结合百分比(>99%)。这些数据表明,饮食中的BPB经胎盘和乳汁的转运较低,且幼崽在哺乳早期结合能力较差,导致其与母鼠相比暴露于更高水平的游离BPB。