Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1289/EHP1743 |
A Novel Method for the Development of Environmental Public Health Indicators and Benchmark Dose Estimation Using a Health-Based End Point for Chlorpyrifos | |
Zurlinden, Todd J.1; Reisfeld, Brad1,2 | |
2018-04-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES
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ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2018 |
卷号 | 126期号:4 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | BACKGROUND: Organophosphorus (OP) compounds are the most widely used group of insecticides in the world. Risk assessments for these chemicals have focused primarily on 10% inhibition of acetylcholinesterase in the brain as the critical metric of effect. Aside from cholinergic effects resulting from acute exposure, many studies suggest a linkage between cognitive deficits and long-term OP exposure. OBJECTIVE: In this proof-of-concept study, we focused on one of the most widely used OP insecticides in the world, chlorpyrifos (CPF), and utilized an existing physiologically based phammcokinetic (PBPK) model and a novel phammcodynamic (PD) dose response model to develop a point of departure benchmark dose estimate for cognitive deficits following long-term, low-dose exposure to this chemical in rodents. METHODS: Utilizing a validated PBPK/PD model for CPF, we generated a database of predicted biomarkers of exposure and internal dose metrics in both rat and human. Using simulated peak brain CPF concentrations, we developed a dose response model to predict CPF-induced spatial memory deficits and correlated these changes to relevant biomarkers of exposure to derive a benchmark dose specific to 'neurobehavioral changes. We extended these cognitive deficit predictions to humans and simulated corresponding exposures using a model parameterized for humans. RESULTS: Results from this study indicate that the human-equivalent benchmark dose (BMD) based on a 15% cognitive deficit as an end point is lower than that using the present threshold for 10% brain AChE inhibition. This predicted human-equivalent subchronic BMD threshold compares to occupational exposure levels determined from biomarkers of exposure and corresponds to similar exposure conditions where deficits in cognition are observed. CONCLUSIONS: Quantitative PD models based on neurobehavioral testing in animals offer an important addition to the methodologies used for establishing useful environmental public health indicators and BMDs, and predictions from such models could help inform the human health risk assessment for chlorpyrifos. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000431396900001 |
WOS关键词 | ORGANOPHOSPHATE PESTICIDES ; REPEATED EXPOSURES ; REPEATED ACQUISITION ; SUSTAINED ATTENTION ; AXONAL-TRANSPORT ; CHRONIC DIETARY ; WATER MAZE ; RATS ; MEMORY ; OXON |
WOS类目 | Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology |
WOS研究方向 | Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/22455 |
专题 | 资源环境科学 |
作者单位 | 1.Colorado State Univ, Dept Chem & Biol Engn, 1370 Campus Delivery, Ft Collins, CO 80523 USA; 2.Colorado State Univ, Sch Biomed Engn, Ft Collins, CO 80523 USA |
推荐引用方式 GB/T 7714 | Zurlinden, Todd J.,Reisfeld, Brad. A Novel Method for the Development of Environmental Public Health Indicators and Benchmark Dose Estimation Using a Health-Based End Point for Chlorpyrifos[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2018,126(4). |
APA | Zurlinden, Todd J.,&Reisfeld, Brad.(2018).A Novel Method for the Development of Environmental Public Health Indicators and Benchmark Dose Estimation Using a Health-Based End Point for Chlorpyrifos.ENVIRONMENTAL HEALTH PERSPECTIVES,126(4). |
MLA | Zurlinden, Todd J.,et al."A Novel Method for the Development of Environmental Public Health Indicators and Benchmark Dose Estimation Using a Health-Based End Point for Chlorpyrifos".ENVIRONMENTAL HEALTH PERSPECTIVES 126.4(2018). |
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