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人体单次口服萘、芴、菲和芘后的毒代动力学分析。

Toxicokinetic analyses of naphthalene, fluorene, phenanthrene, and pyrene in humans after single oral administration.

机构信息

Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.

Department of Health, Environment & Safety, Eulji University, Sungnam, Gyeonggi, Republic of Korea.

出版信息

Sci Total Environ. 2023 Apr 20;870:161899. doi: 10.1016/j.scitotenv.2023.161899. Epub 2023 Jan 27.

DOI:10.1016/j.scitotenv.2023.161899
PMID:36716884
Abstract

Polycyclic aromatic hydrocarbons (PAHs) are generated by incomplete combustion of organic matter. They have health effects in multiple organs and can cause lung, skin, and bladder cancers in humans. Although data regarding their toxicity is available, information on the absorption, distribution, metabolism, and excretion of PAHs in humans is very limited. In the present study, deuterium-labeled naphthalene (Nap), fluorene (Flu), phenanthrene (Phe), and pyrene (Pyr) were orally administered as a single dose (0.02-0.04 mg/kg) to eight healthy adults. Both serum and urine samples were monitored for 72 h after the exposure. Parent compounds and PAH metabolites (monohydroxy-PAHs; OH-PAHs) were measured by headspace-solid phase microextraction coupled with gas chromatography-mass spectrometry and high-performance liquid chromatography-tandem mass spectrometry, respectively. Based on the time-concentration profiles in serum and urine, non-compartmental analysis was performed, and two-compartment models were constructed and validated for each PAH. Subsequently, all of the parent compounds were rapidly absorbed (T: 0.25 to 1.50 h) after oral administration and excreted in urine with a biological half-life (T) of 1.01 to 2.99 h. The fractional urinary excretion (F) of OH-PAHs ranged from 0.07 % to 11.3 %; their T values ranged from 3.4 to 11.0 h. The two-compartment models successfully described the toxicokinetic characteristics of each PAH and its metabolites. F and the two-compartment models could be useful tools for exposure simulation or dose-reconstruction of PAHs. The results of this study will provide useful information for interpreting biomonitoring data of PAHs.

摘要

多环芳烃(PAHs)是有机物质不完全燃烧产生的。它们对多个器官都有健康影响,可导致人类患肺癌、皮肤癌和膀胱癌。虽然已有关于其毒性的数据,但关于 PAHs 在人体内的吸收、分布、代谢和排泄的信息非常有限。在本研究中,将氘标记的萘(Nap)、芴(Flu)、菲(Phe)和芘(Pyr)作为单一剂量(0.02-0.04mg/kg)口服给予 8 名健康成年人。在暴露后 72 小时内监测血清和尿液样本。通过顶空固相微萃取与气相色谱-质谱联用和高效液相色谱-串联质谱分别测定母体化合物和 PAH 代谢物(单羟基-PAH;OH-PAHs)。基于血清和尿液中的时浓度曲线,进行非房室分析,并为每种 PAH 构建和验证两房室模型。随后,所有母体化合物在口服后迅速被吸收(T:0.25 至 1.50 小时),并以 1.01 至 2.99 小时的生物半衰期(T)在尿液中排泄。OH-PAHs 的尿中排泄分数(F)范围为 0.07%至 11.3%;其 T 值范围为 3.4 至 11.0 小时。两房室模型成功描述了每种 PAH 及其代谢物的毒代动力学特征。F 和两房室模型可作为 PAHs 暴露模拟或剂量重建的有用工具。本研究的结果将为解释 PAHs 的生物监测数据提供有用信息。

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