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DOI | 10.1093/toxsci/kft333 |
Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages | |
Schroeter, Jeffry D.1; Campbell, Jerry2; Kimbell, Julia S.3; Conolly, Rory B.4; Clewell, Harvey J.2; Andersen, Melvin E.2 | |
发表日期 | 2014-04-01 |
ISSN | 1096-6080 |
卷号 | 138期号:2页码:412-424 |
英文摘要 | Formaldehyde is a nasal carcinogen in rodents at high doses and is an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde have relied on internal dose estimates in the upper respiratory tract. Dosimetry calculations are complicated by the presence of endogenous formaldehyde concentrations in the respiratory mucosa. Anatomically accurate computational fluid dynamics (CFD) models of the rat, monkey, and human nasal passages were used to simulate uptake of inhaled formaldehyde. An epithelial structure was implemented in the nasal CFD models to estimate formaldehyde absorption from air:tissue partitioning, species-specific metabolism, first-order clearance, DNA binding, and endogenous formaldehyde production. At an exposure concentration of 1 ppm, predicted formaldehyde nasal uptake was 99.4, 86.5, and 85.3% in the rat, monkey, and human, respectively. Endogenous formaldehyde in nasal tissues did not significantly affect wall mass flux or nasal uptake predictions at exposure concentrations > 500 ppb; however, reduced nasal uptake was predicted at lower exposure concentrations. At an exposure concentration of 1 ppb, predicted nasal uptake was 17.5 and 42.8% in the rat and monkey; net desorption of formaldehyde was predicted in the human model. The nonlinear behavior of formaldehyde nasal absorption will affect the dose-response analysis and subsequent risk estimates at low exposure concentrations. Updated surface area partitioning of nonsquamous epithelium and average flux values in regions where DNA-protein cross-links and cell proliferation rates were measured in rats and monkeys are reported for use in formaldehyde risk models of carcinogenesis. |
英文关键词 | formaldehyde;endogenous;nasal;computational fluid dynamics;pharmacokinetics |
语种 | 英语 |
WOS记录号 | WOS:000333293500016 |
来源期刊 | TOXICOLOGICAL SCIENCES
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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/60218 |
作者单位 | 1.Appl Res Associates Inc, Raleigh, NC 27615 USA; 2.Hamner Inst Hlth Sci, Res Triangle Pk, NC 27709 USA; 3.Univ N Carolina, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC 27599 USA; 4.US EPA, Integrated Syst Toxicol Div, NHEERL, ORD, Res Triangle Pk, NC 27711 USA |
推荐引用方式 GB/T 7714 | Schroeter, Jeffry D.,Campbell, Jerry,Kimbell, Julia S.,et al. Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages[J]. 美国环保署,2014,138(2):412-424. |
APA | Schroeter, Jeffry D.,Campbell, Jerry,Kimbell, Julia S.,Conolly, Rory B.,Clewell, Harvey J.,&Andersen, Melvin E..(2014).Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages.TOXICOLOGICAL SCIENCES,138(2),412-424. |
MLA | Schroeter, Jeffry D.,et al."Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages".TOXICOLOGICAL SCIENCES 138.2(2014):412-424. |
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