Environmental Pollution ( IF 7.6 ) Pub Date : 2020-04-19 , DOI: 10.1016/j.envpol.2020.114595 Ting Zhu , Xiao-Bo Zheng , Xiao Yan , Bin Tang , Jing Zheng , Xiao-Jun Luo , Chun-You Zhu , Yun-Jiang Yu , Bi-Xian Mai
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Phosphorus flame retardants (PFRs) have been widely detected in environmental media and human samples. Understanding the distribution and biotransformation of PFRs is important for toxicological research of PFRs in humans. C57BL/6 mice were administered with 300 mg/kg body weight/day of tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) for 35 consecutive days. The liver, kidney, muscle, feces, urine and hair samples were collected to investigate the distribution of TDCIPP and its diester, bis (1,3-dichloro-2-propyl) phosphate (BDCIPP), as well as other potential metabolites of TDCIPP. Concentrations of TDCIPP in muscle (535.7 ± 192.2 ng/g wet weight) were significantly higher than those in liver (186.9 ± 55.0 ng/g wet weight) and kidney (43.5 ± 12.0 ng/g wet weight) (p < 0.05), while concentrations of BDCIPP were higher in kidney (2189.2 ± 420.7 ng/g wet weight) and liver (1337.1 ± 249.6 ng/g wet weight) than other tissues. The distribution of TDCIPP and BDCIPP in mice is tissue-specific, TDCIPP tends to accumulate in muscle, while BDCIPP tends to enrich in kidney and liver. BDCIPP was prone to be eliminated by urine, which may result in the high levels of BDCIPP in urine. Urine and feces had significantly higher concentrations of BDCIPP than TDCIPP (p < 0.05), which demonstrated that BDCIPP is an important metabolite of TDCIPP. Hair could serve as a suitable and reliable biomarker for TDCIPP and also metabolites of TDCIPP. Multifarious metabolites of TDCIPP were identified in various matrices of mice, especially urine. Seven novel metabolites of TDCIPP were identified for the first time. TDCIPP metabolic pathways involved oxidative dealkylation, oxidative dehalogenation, reoxidation, dehalogenation with dehydrogenation. The metabolites identified in the present study could serve as candidate biomarkers for future human biomonitoring studies.
中文翻译:
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磷酸三(1,3-二氯-2-丙基)酯在小鼠体内的分布和生物转化
磷阻燃剂(PFR)已在环境介质和人体样品中被广泛检测到。了解PFR的分布和生物转化对于人类PFR的毒理学研究非常重要。连续35天给C57BL / 6小鼠服用300 mg / kg体重/天的磷酸三(1,3-二氯-2-丙基)酯(TDCIPP)。收集肝脏,肾脏,肌肉,粪便,尿液和头发的样本,以研究TDCIPP及其二酯,双(1,3-二氯-2-丙基)磷酸酯(BDCIPP)以及TDCIPP的其他潜在代谢产物的分布。肌肉中TDCIPP的浓度(535.7±192.2 ng / g湿重)明显高于肝脏(186.9±55.0 ng / g湿重)和肾脏(43.5±12.0 ng / g湿重)(p <0.05),而肾脏(2189.2±420.7 ng / g湿重)和肝脏(1337.1±249.6 ng / g湿重)中BDCIPP的浓度高于其他组织。TDCIPP和BDCIPP在小鼠中的分布是组织特异性的,TDCIPP倾向于在肌肉中积累,而BDCIPP倾向于在肾脏和肝脏中富集。BDCIPP容易被尿液清除,这可能导致尿液中BDCIPP含量高。尿液和粪便中BDCIPP的浓度明显高于TDCIPP(p <0.05),表明BDCIPP是TDCIPP的重要代谢产物。头发可以作为TDCIPP以及TDCIPP代谢产物的合适且可靠的生物标记。在小鼠的各种基质中,尤其是尿液中,都发现了TDCIPP的多种代谢产物。首次鉴定了TDCIPP的7种新型代谢物。TDCIPP代谢途径涉及氧化脱烷基,氧化脱卤,再氧化,脱卤脱氢。本研究中鉴定出的代谢物可作为未来人类生物监测研究的候选生物标志物。