Guruge Keerthi S, Noguchi Michiko, Yoshioka Koji, Yamazaki Eriko, Taniyasu Sachi, Yoshioka Miyako, Yamanaka Noriko, Ikezawa Mitsutaka, Tanimura Nobuhiko, Sato Masumi, Yamashita Nobuyoshi, Kawaguchi Hiroaki
National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
Joint Faculty of Veterinary Medicine, Kagoshima University, Korimoto, Kagoshima, Japan.
J Appl Toxicol. 2016 Jan;36(1):68-75. doi: 10.1002/jat.3145. Epub 2015 Apr 15.
In this study, we evaluated the efficacy of a novel minipig strain, the Microminipig (MMPig), as an animal model for studying the pharmacokinetics of a mixture of 10 perfluoroalkyl acids (PFAAs). After a single oral dose was given, we found that the blood depuration of PFAAs (blood t1/2), which we calculated using first-order elimination curves, ranged from 1.6 to 86.6 days. Among the five body compartments analyzed, the liver was the greatest site of accumulation of perfluorooctanesulfonate and longer chain perfluorinated carboxylates such as perfluorodecanoic acid, perfluoroundecanoic acid and perfluorododecanoic acid. We observed an increasing accumulation trend of perfluorinated carboxylates in the organs associated with the fluorinated carbon chain length. The perfluorononanoic acid burden was the highest among the treated compounds 21 days after a single exposure, as 29% of the given perfluorononanoic acid dose was accumulated in the tissues. The persistence of PFAAs in edible pig tissues even after 21 days post-exposure raises concerns about the safety of swine products. This was the first study to use MMPigs to elucidate the pharmacokinetics of a group of environmental pollutants. We found that MMPigs could be excellent experimental animals for toxicological studies due to their easy handling, cost efficacy for target compounds and ease of waste treatment.
在本研究中，我们评估了一种新型小型猪品系——微型小型猪（MMPig）作为研究10种全氟烷基酸（PFAA）混合物药代动力学的动物模型的有效性。给予单次口服剂量后，我们发现，使用一级消除曲线计算得出的PFAA血液净化时间（血液半衰期）为1.6至86.6天。在所分析的五个身体腔室中，肝脏是全氟辛烷磺酸和较长链全氟羧酸（如全氟癸酸、全氟十一烷酸和全氟十二烷酸）的最大蓄积部位。我们观察到，全氟羧酸在与氟化碳链长度相关的器官中的蓄积趋势增加。单次暴露21天后，全氟壬酸在受试化合物中的负荷最高，因为给予的全氟壬酸剂量的29%蓄积在组织中。即使在暴露21天后，PFAA在可食用猪组织中的持久性也引发了对猪肉产品安全性的担忧。这是首次使用MMPig阐明一组环境污染物药代动力学的研究。我们发现，MMPig因其易于处理、对目标化合物具有成本效益且易于废物处理，可能成为毒理学研究的优秀实验动物。
