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DOI | 10.1002/jat.3269 |
Development and application of a human PBPK model for bromodichloromethane to investigate the impacts of multi-route exposure | |
Kenyon, Elaina M.; Eklund, Christopher; Leavens, Teresa; Pegram, Rex A. | |
发表日期 | 2016-09-01 |
ISSN | 0260-437X |
卷号 | 36期号:9页码:1095-1111 |
英文摘要 | As a result of its presence in water as a volatile disinfection byproduct, bromodichloromethane (BDCM), which is mutagenic, poses a potential health risk from exposure via oral, dermal and inhalation routes. We developed a refined human physiologically based pharmacokinetic (PBPK) model for BDCM (including new chemical-specific human parameters) to evaluate the impact of BDCM exposure during showering and bathing on important measures of internal dose compared with oral exposure. The refined model adequately predicted data from the published literature for oral, dermal and bathing/showering exposures. A liter equivalency approach (L-eq) was used to estimate BDCM concentration in a liter of water consumed by the oral route that would be required to produce the same internal dose of BDCM resulting from a 20-min bath or a 10-min shower in water containing 10 mu gl(-1) BDCM. The oral liter equivalent concentrations for the bathing scenario were 605, 803 and 5 mu gl(-1) BDCM for maximum venous blood concentration (Cmax), the area under the curve (AUCv) and the amount metabolized in the liver per hour (MBDCM), respectively. For a 10-min showering exposure, the oral L-eq concentrations were 282, 312 and 2.1 mu gl(-1) for Cmax, AUC and MBDCM, respectively. These results demonstrate large contributions of dermal and inhalation exposure routes to the internal dose of parent chemical reaching the systemic circulation, which could be transformed to mutagenic metabolites in extrahepatic target tissues. Thus, consideration of the contribution of multiple routes of exposure when evaluating risks from water-borne BDCM is needed, and this refined human model will facilitate improved assessment of internal doses from real-world exposures. Published 2015. This article has been contributed to by US Government employees and their work is in the public domain in the USA. A refined human physiologically based pharmacokinetic (PBPK) model for bromodichloromethane (BDCM) (including new chemical-specific human parameters) was developed to evaluate the impact of BDCM exposure during showering and bathing on important measures of internal dose compared with oral exposure. Analyses demonstrated large contributions of dermal and inhalation exposure routes to an internal dose of the parent chemical reaching the systemic circulation. Thus, consideration of the contribution of multiple routes of exposure when evaluating risks from water-borne BDCM is highly desirable. |
英文关键词 | bromodichloromethane;multi-route exposure;PBPK model |
语种 | 英语 |
WOS记录号 | WOS:000379954000003 |
来源期刊 | JOURNAL OF APPLIED TOXICOLOGY
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来源机构 | 美国环保署 |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/62348 |
作者单位 | US EPA, Integrated Syst Toxicol Div, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA |
推荐引用方式 GB/T 7714 | Kenyon, Elaina M.,Eklund, Christopher,Leavens, Teresa,et al. Development and application of a human PBPK model for bromodichloromethane to investigate the impacts of multi-route exposure[J]. 美国环保署,2016,36(9):1095-1111. |
APA | Kenyon, Elaina M.,Eklund, Christopher,Leavens, Teresa,&Pegram, Rex A..(2016).Development and application of a human PBPK model for bromodichloromethane to investigate the impacts of multi-route exposure.JOURNAL OF APPLIED TOXICOLOGY,36(9),1095-1111. |
MLA | Kenyon, Elaina M.,et al."Development and application of a human PBPK model for bromodichloromethane to investigate the impacts of multi-route exposure".JOURNAL OF APPLIED TOXICOLOGY 36.9(2016):1095-1111. |
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