Renal clearance of perfluorooctane sulfonate and perfluorooctanoate in humans and their species-specific excretion
Renal clearance of perfluorooctane sulfonate and perfluorooctanoate in humans and their species-specific excretion
复制标题
DOI：
10.1016/j.envres.2004.12.003
复制
发表时间：
2005-10-01
影响因子：
8.3
通讯作者：
Koizumi, A
中科院分区：
文献类型：
--
作者：
Harada, K;Inoue, K;Koizumi, A
全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA）在环境中被检测到，更具体地说，在野生动物和人类中也被检测到。然而，全氟化学品在人体内的毒代动力学方面尚不清楚。在这项研究中，我们测量了在京都居住超过10年的受试者中PFOA和PFOS的浓度。有月经的女性血清中的全氟辛酸和全氟辛烷磺酸浓度高于无月经的女性（P < 0.01），但在配偶中，这并不随年龄而变化;女性的浓度在≥ 60岁时达到男性的水平。然后，我们确定了年轻（20-40岁，每种性别N = 5）和老年（>= 60岁，每种性别N = 5）男女受试者的PFOA和PFOS肾脏清除率。所有年轻的雌性都在交配，而所有年老的雌性都没有。肾脏清除率比人类肾小球滤过率小10（-5）倍，表明人类肾脏中不存在主动排泄。假设采用一室模型，根据其血清半衰期，PFOA和PFOS的肾脏清除率约为总清除率的五分之一。在我们的人类受试者中未发现大鼠和日本猕猴中报告的肾清除率的性别差异。我们试图建立一个一室药代动力学模型，使用报告的半衰期在人体内。该模型简单，但可相当好地预测雄性和雌性动物的血清浓度。因此，我们建议，所有内部剂量的方法，使用药代动力学模型应采取，因为大的物种差异动力学存在的全氟辛酸和全氟辛烷磺酸。(c)2004年爱思唯尔公司All rights reserved.
Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are detected in the environment, as well as more specifically in wildlife and humans. However, the toxicokinetic aspects of perfluorochemicals in humans are unclear. In this study, we measured concentrations of PFOA and PFOS in subjects who had lived in Kyoto city for more than 10 years. The serum concentrations of PFOA and PFOS were higher in females who menstruated than those who did not menstruation (P < 0.01), but in mates this did not change by age; the levels in females reached those in males at an age of >= 60 years. We then determined the renal clearances of PFOA and PFOS in young (20-40 years old, N = 5 for each sex) and old (>= 60 years old, N = 5 for each sex) subjects of both sexes. All young females were menstruating, while all old females were not. The renal clearances were 10(-5)-fold smaller than the glomerular filtration rate in humans, suggesting the absence of active excretion in human kidneys. The renal clearances of PFOA and PFOS were approximately one-fifth of the total clearance based on their serum half-lives, assuming a one-compartment model. The sex differences in renal clearance that have been reported in rats and Japanese macaques were not found ill our human subjects. We tried to build a one-compartment pharmacokinetic model using the reported half-lives in human. The model was simple but could predict the serum concentrations in both males and females fairly well. We therefore suggest that all internal dose approach using a pharmacokinetic model should be taken because of the large species differences in kinetics that exist for PFOA and PFOS. (c) 2004 Elsevier Inc. All rights reserved.