Environmental Health Program, P.O. Box: 3354, Riyadh, 11211, Saudi Arabia.
Environmental Health Program, P.O. Box: 3354, Riyadh, 11211, Saudi Arabia.
Int J Hyg Environ Health. 2023 Mar;248:114112. doi: 10.1016/j.ijheh.2023.114112. Epub 2023 Jan 17.
Phthalates are widely used plasticizers in various consumer products and medical devices, with some reporting as having estrogenic and anti-androgenic endocrine-disrupting effects. Premature neonates may be exposed to high levels of specific phthalates during hospitalization in the neonatal intensive care unit (NICU) because of reliance on multiple medical procedures that pose a possible health risk. The present study utilized seven urinary phthalate metabolites of dibutyl phthalate isomers [(di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP)], butylbenzyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP) that had been previously measured in 33 preterm neonates sampled at hospital admission (N = 23) and daily during their NICU stay (N = 260). We aimed to perform: (1) cumulative risk assessment (CRA) using the volume and creatinine-adjusted models; (2) examine the temporal variability of CRA from repeated measures and (3) estimate the risk of cumulative exposure to phthalates based on their anti-androgenic and/or estrogenic properties. We multiplied the relative activity of individual phthalates exhibiting estrogenic or anti-androgenic effects by daily intake. For each preterm neonate, CRA was assessed based on the hazard index (HI) metric [the sum of hazard quotients] based on three reference doses for anti-androgenicity: the tolerable daily intake (TDI) from the European Food Safety Authority, the reference dose (RfD-AA) published in 2010 and newly revised published in 2020 (NRfD-AA). The metabolites of BBzP and DEHP were 2-23 fold higher in preterm neonates during their NICU stay. Median HIs increased in the order of HI > HI > HI. In the creatinine-based model, 87% (92%), 87% (96%), and 100% (100%) of preterm neonates at admission (during NICU stay) showed HI, HI and HI exceeding 1, respectively with DEHP the most prevalent. The temporal reproducibility of HI (based on three reference doses) during preterm neonate stay in the NICU was high, with intra-class correlation coefficients ranging between 0.77 and 0.97, suggesting persistent exposure to phthalates. The four phthalates that preterm neonates were exposed to in the NICU exhibited estrogenic binding and anti-androgenic effects with median values (creatinine-based) of 98.7 and 56.9 μg/kg body weight/day, respectively. This was especially true for DEHP. The results indicate that preterm neonates in this NICU setting are probably at high risk of cumulative phthalate exposure with anti-androgenic properties that may have long-term adverse reproductive and developmental effects.
邻苯二甲酸酯是各种消费品和医疗器械中广泛使用的增塑剂，有一些报告称具有雌激素和抗雄激素内分泌干扰作用。由于早产儿在新生儿重症监护病房（NICU）中需要依靠多种可能存在健康风险的医疗程序，因此可能会接触到高水平的特定邻苯二甲酸酯。本研究利用了先前在 33 名早产儿入院时（N=23）和 NICU 住院期间（N=260）每日测量的七种邻苯二甲酸酯二丁酯异构体（邻苯二甲酸二正丁酯（DnBP）和邻苯二甲酸二异丁酯（DiBP））、丁基苄基邻苯二甲酸酯（BBzP）和邻苯二甲酸二（2-乙基己基）酯（DEHP）的七种尿邻苯二甲酸酯代谢物。我们旨在进行以下操作：（1）使用体积和肌酐调整模型进行累积风险评估（CRA）；（2）从重复测量中检查 CRA 的时间变异性；（3）根据其抗雄激素和/或雌激素特性估计累积暴露于邻苯二甲酸酯的风险。我们将表现出雌激素或抗雄激素作用的个别邻苯二甲酸盐的相对活性乘以每日摄入量。对于每个早产儿，根据危害指数（HI）指标[危害商数的总和]来评估 CRA，该指标基于三种抗雄激素性参考剂量：欧洲食品安全局的可耐受每日摄入量（TDI）、2010 年发布的参考剂量（RfD-AA）和 2020 年新修订的 RfD-AA。BBzP 和 DEHP 的代谢物在早产儿 NICU 住院期间的浓度是其入院时的 2-23 倍。中位数 HI 按 HI>HI>HI 的顺序增加。在肌酐基础模型中，87%（92%）、87%（96%）和 100%（100%）的早产儿在入院时（在 NICU 住院期间）HI、HI 和 HI 均超过 1，其中 DEHP 最为普遍。早产儿在 NICU 住院期间 HI（基于三种参考剂量）的时间重现性很高，组内相关系数在 0.77 到 0.97 之间，表明持续暴露于邻苯二甲酸酯。早产儿在 NICU 中接触的四种邻苯二甲酸具有雌激素结合和抗雄激素作用，基于肌酐的中位数分别为 98.7 和 56.9μg/kg 体重/天。这在 DEHP 中尤其如此。结果表明，在这种 NICU 环境下，早产儿可能面临高累积邻苯二甲酸暴露风险，具有抗雄激素特性，可能对生殖和发育产生长期不良影响。
