Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Department of Environmental Science and Engineering, College of Engineering, National Pingtung University of Science and Technology, Pingtung 912, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Ecotoxicol Environ Saf. 2024 Nov 15;287:117281. doi: 10.1016/j.ecoenv.2024.117281. Epub 2024 Nov 6.
Our previous studies have revealed a correlation between urinary phthalates (PAE) metabolites and parabens and PM exposure and susceptibility to attention-deficit/hyperactivity disorder (ADHD) in school-age children. Our goal was to examine the relationships between urinary organophosphate flame retardants (OPFRs) and their metabolites and the susceptibility to ADHD in the same cohort of children. We recruited 186 school children, including 132 with ADHD and 54 normal controls, living in southern Taiwan to investigate five OPFRs (1,3-dichloro-2-propyl phosphate (TDCPP), tri-n-butyl phosphate (TnBP), tris (2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPHP)) and five OPFR metabolites (bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-n-butyl phosphate (DNBP), bis(2-chloroethyl) hydrogen phosphate (BCEP), di-(2-butoxyethyl) phosphate (DBEP), and diphenyl phosphate (DPHP)) in urine. ADHD patients' behavioral symptoms and neuropsychological function were assessed using the Swanson, Nolan, and Pelham Version IV Scale (SNAP-IV) and the Conners' Continuous Performance Test 3rd Edition (Conners CPT3), respectively. BCEP was predominant among urinary OPFRs and the metabolites in both the ADHD and control groups. ADHD children had significantly higher levels of urinary BDCPP, BCEP, DBEP, DPHP, TCEP, TBEP, TNBP, TPHP, and ΣOPFR compared to the controls. After controlling for age, gender, body mass index, PM exposure scenarios, and urinary phthalate metabolites, parabens, bisphenol-A and creatinine, levels of urinary BDCPP, TDCPP, and TBEP in ADHD children showed significant and dose-dependent effects on core behavioral symptoms of inattention. DNBP levels were positively correlated with neuropsychological deficits (CPT detectability, omission, and commission), while urinary DPHP in ADHD children were negatively related to CPT detectability and commission. Hyperactivity and impulsivity were not correlated with urinary OPFRs and their metabolites in ADHD children. In conclusion, the ADHD symptom of inattention and CPT performance may be closely associated with certain urinary OPFRs and their metabolites, independent of urinary PAE metabolites, parabens, and bisphenol-A in school-age-ADHD children.
我们之前的研究表明，尿中邻苯二甲酸酯（PAE）代谢物和对羟基苯甲酸酯与 PM 暴露和儿童注意力缺陷/多动障碍（ADHD）易感性之间存在相关性。我们的目标是在同一批儿童中研究尿有机磷酸酯阻燃剂（OPFR）及其代谢物与 ADHD 易感性之间的关系。我们招募了 186 名学龄儿童，包括 132 名 ADHD 儿童和 54 名正常对照儿童，居住在台湾南部，以调查五种 OPFR（1,3-二氯-2-丙基磷酸酯（TDCPP）、三正丁基磷酸酯（TnBP）、三（2-氯乙基）磷酸酯（TCEP）、三（2-丁氧基乙基）磷酸酯（TBEP）和磷酸三苯酯（TPHP））和五种 OPFR 代谢物（双（1,3-二氯-2-丙基）磷酸酯（BDCPP）、二正丁基磷酸酯（DNBP）、双（2-氯乙基）磷酸氢酯（BCEP）、二（2-丁氧基乙基）磷酸酯（DBEP）和磷酸二苯酯（DPHP））在尿液中。使用 Swanson、Nolan 和 Pelham 第四版量表（SNAP-IV）和 Conners 连续执行测试第三版（Conners CPT3）分别评估 ADHD 患者的行为症状和神经心理学功能。BDCPP、BCEP、DBEP、DPHP、TCEP、TBEP、TNBP、TPHP 和ΣOPFR 是 ADHD 组和对照组尿液中主要的 OPFR 及其代谢物。与对照组相比，ADHD 儿童的尿 BDCPP、BCEP、DBEP、DPHP、TCEP、TBEP、TNBP、TPHP 和ΣOPFR 水平明显升高。在控制年龄、性别、体重指数、PM 暴露场景和尿邻苯二甲酸酯代谢物、对羟基苯甲酸酯、双酚 A 和肌酐后，ADHD 儿童尿中 BDCPP、TDCPP 和 TBEP 的水平与注意力不集中的核心行为症状呈显著的剂量依赖性关系。DNBP 水平与神经心理学缺陷（CPT 可检测性、遗漏和错误）呈正相关，而 ADHD 儿童的尿 DPHP 与 CPT 可检测性和错误呈负相关。多动和冲动与 ADHD 儿童的尿 OPFR 及其代谢物无关。总之，ADHD 的注意力不集中症状和 CPT 表现可能与某些尿 OPFR 及其代谢物密切相关，与学龄期 ADHD 儿童的尿 PAE 代谢物、对羟基苯甲酸酯和双酚 A 无关。
