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Application of survival analysis methods to pulsed exposures: Exposure duration, latent mortality, recovery time, and the underlying theory of survival distribution models.

机译:生存分析方法在脉冲暴露中的应用:暴露时间,潜在死亡率,恢复时间和生存分布模型的基础理论。

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摘要

Ecotoxicologists adopted median lethal concentration (LC50) methods from mammalian toxicology. This conventional LC50 approach has shortcomings. Fixing the exposure duration and selecting the 50% mortality level result in loss of ecologically relevant information generated at all other times. It also ignores latent mortality that can manifest after exposure ends. As a result, it cannot adequately predict pulsed exposure effects in which concentration, duration, and frequency of pulses change through time. The underlying theory of the dose-response models used to calculate LC50 values, stochastic versus individual effective dose (IED) theory, has not been tested rigorously either.; In this study, the effects of exposure duration and concentration on mortality during and after exposures, and the effects of recovery time between two pulses on mortality during a second pulse were quantified. The influences of toxicant modes of action were discussed. The underlying theory for survival distribution models was further explored. Survival analysis was used to incorporate these factors into predictive models and to circumvent some of the aforementioned shortcomings. The experiments were conducted with two contrasting toxicants, copper sulfate (CuSO4) and sodium pentachlorophenol (NaPCP). The amphipod, Hyalella azteca, was used as the model organism.; Latent mortality is significantly affected by exposure concentration and an integral part of the lethal effects of toxicants that cause cumulative damage. For toxicants that cause minimal cumulative damage during the exposure, the latent mortality is not significant and can be ignored. Exposure duration did not show any significant effect on latent mortality for either toxicant. It is recommended that for other experimental conditions the effect still needs to be considered. Recovery time had significant effect on mortality during the second pulse for both toxicants. To recover to a similar background level mortality, the time an exposed organism needed to return to a stage similar to its original resistance was much longer for CuSO4 than for NaPCP. The hypothesis that IED is the dominant explanation for the dose-response models was rejected for both toxicants. By effectively incorporating exposure duration and other factors, survival analysis better predicted pulsed exposure consequences than did the conventional LC50 methods.
机译:生态毒理学家采用了哺乳动物毒理学中值致死浓度(LC50)方法。这种常规的LC50方法具有缺点。固定暴露时间并选择50%死亡率会导致所有其他时间产生的与生态相关的信息丢失。它还忽略了暴露结束后可能出现的潜在死亡率。结果,它不能充分预测脉冲浓度,持续时间和频率随时间变化的脉冲曝光效果。用于计算LC50值的剂量反应模型的基础理论,即随机与个人有效剂量(IED)理论,也未经过严格测试。在这项研究中,量化了暴露时间和浓度对暴露期间和暴露后死亡率的影响,以及两个脉冲之间的恢复时间对第二个脉冲期间死亡率的影响。讨论了有毒物质作用方式的影响。进一步探讨了生存分布模型的基础理论。生存分析用于将这些因素纳入预测模型,并规避某些上述缺点。实验使用两种有毒的对比毒物:硫酸铜(CuSO4)和五氯苯酚钠(NaPCP)。两栖动物,透明质酸菌,用作模型生物。潜在的死亡率受到暴露浓度和引起累积损害的有毒物质致死作用的重要组成部分的显着影响。对于在暴露过程中造成最小累积损害的有毒物质,潜在死亡率并不重要,可以忽略不计。暴露时间对两种毒物的潜在死亡率均未显示任何显着影响。建议对于其他实验条件,仍然需要考虑效果。对于两种有毒物质,恢复时间对第二次脉冲期间的死亡率都有重要影响。为了使死亡率恢复到相似的背景水平,暴露的生物体需要返回到与其原始抗药性相似的阶段的时间要比NaPCP长得多。两种有毒物质都拒绝使用IED是剂量反应模型的主要解释的假设。通过有效地结合暴露时间和其他因素,生存分析比传统的LC50方法更好地预测了脉冲暴露的后果。

著录项

  • 作者

    Zhao, Yuan.;

  • 作者单位

    The College of William and Mary.;

  • 授予单位 The College of William and Mary.;
  • 学科 Health Sciences Toxicology.; Biology Biostatistics.; Environmental Sciences.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 127 p.
  • 总页数 127
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 毒物学(毒理学);生物数学方法;环境科学基础理论;
  • 关键词

  • 入库时间 2022-08-17 11:42:39

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