Darnerud Per Ola, Bergman Åke
Department of Organismal Biology, Environmental Toxicology, Norbyvägen 18A, SE-752 36 Uppsala, Sweden.
Department of Environmental Science (ACES), Stockholm University, SE-106 92 Stockholm, Sweden; Department of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden; College of Environmental Science and Engineering, Tongji University, Shanghai, China.
Environ Int. 2022 May;163:107195. doi: 10.1016/j.envint.2022.107195. Epub 2022 Apr 18.
Even though the chlorinated paraffins (CPs) have been on the environmental pollution agenda throughout the last 50 years it is a class of chemicals that only now is discussed in terms of an emerging issue with extensive annual publication rates. Major reviews on CPs have been produced, but a deeper understanding of the chemical fate of CPs, including formation of metabolites in animals and humans, is still missing. Thus, the present review aims to critically compile our present knowledge on the disposition, i.e. Adsorption, Disposition, Metabolism, and Excretion (ADME) of CPs in biota and to identify research needs. We conclude that CPs could be effectively absorbed from the gastro-intestinal tract (GI) tract, and probably also from the lungs, and transported to various organs. A biphasic elimination is suggested, with a rapid initial phase followed by a terminal phase, the latter (e.g., fat tissues) covering half-lives of weeks and months. CPs are metabolized in the liver and excreted mainly via the bile and faeces, and the metabolic rate and type of metabolites are dependent on chlorine content and chain length. Results that strengthen CP metabolism are in vivo findings of phase II metabolites in bile, and CP degradation to carbon fragments in experimental animals. Still the metabolic transformations of CPs are poorly studied, and no metabolic scheme has yet been presented. Further, toxicokinetic mass balance calculations suggest that a large part of a given dose (not found as parent compound) is transformation products of CPs, and in vitro metabolism studies present numerous CP metabolites (e.g., chloroalkenes, chlorinated ketones, aldehydes, and carboxylic acids).
尽管在过去50年里，氯化石蜡一直是环境污染议程上的议题，但这一类化学品直到现在才作为一个新兴问题被广泛讨论，每年的发表率都很高。关于氯化石蜡已经有了一些主要综述，但对其化学归宿，包括在动物和人体内代谢产物的形成，仍缺乏更深入的了解。因此，本综述旨在批判性地汇总我们目前关于生物群中氯化石蜡处置（即吸收、分布、代谢和排泄，ADME）的知识，并确定研究需求。我们得出结论，氯化石蜡可从胃肠道有效吸收，可能也可从肺部吸收，并转运至各个器官。建议存在双相消除过程，初始阶段迅速，随后是终末阶段，后者（如脂肪组织）的半衰期长达数周和数月。氯化石蜡在肝脏中代谢，主要通过胆汁和粪便排泄，代谢率和代谢产物类型取决于氯含量和链长。支持氯化石蜡代谢的结果包括胆汁中II期代谢产物的体内研究结果，以及实验动物中氯化石蜡降解为碳碎片的结果。然而，氯化石蜡的代谢转化研究仍很薄弱，尚未提出代谢途径。此外，毒代动力学质量平衡计算表明，给定剂量的很大一部分（未发现为母体化合物）是氯化石蜡的转化产物，体外代谢研究也呈现出众多氯化石蜡代谢产物（如氯烯烃、氯化酮、醛和羧酸）。
