Key Laboratory of Food Safety Risk Assessment of Ministry of Health, China National Center for Food Safety Risk Assessment, Beijing 100021, China.
Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, Zhoushan Municipal Center for Disease Control and Prevention, Zhejiang 316021, China.
Toxicol In Vitro. 2022 Oct;84:105430. doi: 10.1016/j.tiv.2022.105430. Epub 2022 Jul 25.
Diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) are the two most widely used plasticizers (PAEs) that may act as endocrine disruptors and cause developmental toxicity.
We measured intrauterine exposure to DEHP and DBP which are the two most widely used phthalates (PAEs) in the cord blood of 50 postpartum women using ultra-HPLC-tandem mass spectrometry and solid-phase extraction. The embryotoxicity of DEHP and DBP was evaluated using the human embryonic stem cell test (hEST). Based on the intrauterine exposure concentration of DEHP and DBP in pregnant women and the reference point of toxic effects in hEST, we used the reference point index (RPI) method to assess the cumulative risk of DBP and DEHP.
The mean concentrations of DEHP and DBP were 99.9 μg/L and 24.7 μg/L, respectively. DEHP and DBP were weakly embryotoxic, and the benchmark dose lower confidence intervals were 29.99 and 0.99 μg/mL, respectively, as determined using hEST. Both DEHP and DBP inhibited embryonic development via PPAR/PTEN/Akt signal pathway.
The findings suggest that the cumulative risk in pregnant women with a high level of exposure should receive more attention in the future.
邻苯二甲酸二乙酯（DEHP）和邻苯二甲酸二丁酯（DBP）是两种最广泛使用的增塑剂（PAEs），可能作为内分泌干扰物并导致发育毒性。
我们使用超高效液相色谱-串联质谱法和固相萃取法测量了 50 名产后妇女脐带血中 DEHP 和 DBP 这两种最广泛使用的邻苯二甲酸酯（PAEs）的宫内暴露水平。DEHP 和 DBP 的胚胎毒性通过人胚胎干细胞测试（hEST）进行评估。根据孕妇体内 DEHP 和 DBP 的宫内暴露浓度和 hEST 中毒性作用的参考点，我们使用参考点指数（RPI）方法评估 DBP 和 DEHP 的累积风险。
DEHP 和 DBP 的平均浓度分别为 99.9μg/L 和 24.7μg/L。DEHP 和 DBP 具有较弱的胚胎毒性，hEST 测定的基准剂量下限置信区间分别为 29.99μg/mL 和 0.99μg/mL。DEHP 和 DBP 均通过 PPAR/PTEN/Akt 信号通路抑制胚胎发育。
这些发现表明，未来应更加关注高暴露水平孕妇的累积风险。
