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DOI10.1093/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
ISSN1096-6080
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
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
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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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