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DOI | 10.1016/j.yrtph.2015.12.020 |
Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone | |
Poet, T. S.1; Schlosser, P. M.2; Rodriguez, C. E.3,4; Parod, R. J.5; Rodwell, D. E.6; Kirman, C. R.7 | |
发表日期 | 2016-04-01 |
ISSN | 0273-2300 |
卷号 | 76页码:102-112 |
英文摘要 | The developmental effects of NMP are well studied in Sprague Dawley rats following oral, inhalation, and dermal routes of exposure. Short-term and chronic occupational exposure limit (OEL) values were derived using an updated physiologically based pharmacokinetic (PBPK) model for NMP, along with benchmark dose modeling. Two suitable developmental endpoints were evaluated for human health risk assessment: (1) for acute exposures, the increased incidence of skeletal malformations, an effect noted only at oral doses that were toxic to the dam and fetus; and (2) for repeated exposures to NMP, changes in fetal/pup body weight. Where possible, data from multiple studies were pooled to increase the predictive power of the dose response data sets. For the purposes of internal dose estimation, the window of susceptibility was estimated for each endpoint, and was used in the dose response modeling. A point of departure value of 390 mg/L (in terms of peak NMP in blood) was calculated for skeletal malformations based on pooled data from oral and inhalation studies. Acceptable dose response model fits were not obtained using the pooled data for fetal/pup body weight changes. These data sets were also assessed individually, from which the geometric mean value obtained from the inhalation studies (470 mg*hr/L), was used to derive the chronic OEL. A PBPK model for NMP in humans was used to calculate human equivalent concentrations corresponding to the internal dose point of departure values. Application of a net uncertainty factor of 20-21, which incorporates data-derived extrapolation factors, to the point of departure values yields short-term and chronic occupational exposure limit values of 86 and 24 ppm, respectively. (C) 2016 The Authors. Published by Elsevier Inc. |
英文关键词 | Occupational exposure limit;Benchmark dose;PBPK modeling;Developmental toxicity;Window of susceptibility |
语种 | 英语 |
WOS记录号 | WOS:000375514200013 |
来源期刊 | REGULATORY TOXICOLOGY AND PHARMACOLOGY
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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/60259 |
作者单位 | 1.Summit Toxicol, Richland, WA USA; 2.US EPA, Res Triangle Pk, NC 27711 USA; 3.US EPA, Washington, DC 20460 USA; 4.Coca Cola Co, Atlanta, GA USA; 5.BASF Corp, Wyandotte, MI USA; 6.Rodwell & Associates, Houston, TX USA; 7.Summit Toxicol, Orange Village, OH USA |
推荐引用方式 GB/T 7714 | Poet, T. S.,Schlosser, P. M.,Rodriguez, C. E.,et al. Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone[J]. 美国环保署,2016,76:102-112. |
APA | Poet, T. S.,Schlosser, P. M.,Rodriguez, C. E.,Parod, R. J.,Rodwell, D. E.,&Kirman, C. R..(2016).Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone.REGULATORY TOXICOLOGY AND PHARMACOLOGY,76,102-112. |
MLA | Poet, T. S.,et al."Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone".REGULATORY TOXICOLOGY AND PHARMACOLOGY 76(2016):102-112. |
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