Dose-rate effects of ethylene oxide exposure on developmental toxicity.
Dose-rate effects of ethylene oxide exposure on developmental toxicity.
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环氧乙烷暴露对发育毒性的剂量率影响。
DOI：
10.1093/toxsci/50.2.259
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
L. Ryan
中科院分区：
文献类型：
--
作者：
E. Weller;N. Long;A. Smith;P. Williams;S. Ravi;Janusz Gill;R. Henessey;W. Skornik;J. Brain;C. Kimmel;G. Kimmel;Lewis B Holmes;L. Ryan
在风险评估中，在未经测试的暴露持续时间内评估健康影响涉及假设浓度（C）和暴露持续时间（T）的等效倍数具有相同的影响。这种方法的局限性（归因于F。Haber，Zur Geschichte des Gaskrieges [On the history of gas warfare]，in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923]，1924，Springer，柏林，pp. 76-92），已经注意到在几项研究中。本文提出的研究旨在专门研究剂量率（C x T）效应，它形成了一个理想的案例研究，以实现统计模型，并检查风险评估中的统计问题。妊娠雌性C57 BL/6 J小鼠在妊娠第7天通过吸入暴露于环氧乙烷（EtO）1.5、3或6 h，暴露量为2100或2700 ppm-h的C x T倍数。选择EtO是因为其半衰期短、记录的发育毒性以及与职业环境中发生的暴露相关。用暴露于空气中相似时间的动物进行并行实验。使用为评估剂量率效应而开发的模型进行的统计分析显示，对胎仔死亡和吸收、畸形、冠臀长度和胎仔体重有显著影响。发现在妊娠第7天暴露于短时间、高暴露量EtO的动物比暴露于相同C x T倍数但暴露时间较长、较低的动物有更多的不良反应。风险评估的含义是，应用哈伯定律可能会导致在较短的暴露时间内低估风险，在较长的暴露时间内高估风险。需要进一步的毒理学和统计学研究来了解剂量率效应的机制，以及如何将机制信息纳入风险评估决策过程。
In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-h. EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process.
原肠胚形成过程中急性胚胎损伤导致角膜豆状核发育不全（彼得斯异常）。
影响因子：
1.2
作者：
Cook,CS;Sulik,KK
通讯作者：
Sulik,KK
设计发育毒性研究以评估剂量和持续时间的联合效应。
DOI：
10.1111/j.1539-6924.1994.tb00076.x
发表时间：
1994
期刊：
Risk analysis : an official publication of the Society for Risk Analysis
影响因子：
--
作者：
Scharfstein,DO;Williams,PL
通讯作者：
Williams,PL