虽然病理学同行评审/病理学工作组(PWG)模型长期以来一直用于哺乳动物毒理学病理学以确保准确性,一致性,组织病理学数据的客观性,到目前为止,这种范式在生态毒理学研究中的应用受到限制。在当前项目中,PWG方法用于评估ill的组织病理学切片,肝脏,肾,和/或来自三篇先前发表的鳟鱼双氯芬酸研究的肠道,其中报告的组织病理学发现存在实质性差异.这个审查过程的主要目标是调查和潜在的调和这些研究之间的差异,根据结果,建立适当的无观察效应浓度(NOEC)。由一位经验丰富的鱼类病理学家(病理学同行评审)对所有组织学切片和原始诊断进行完整检查后,我们进行了为期两天的PWG会议,让4人专家小组的成员确定3项鳟鱼研究中与治疗相关的发现程度.根据美国环境保护局(USEPA)农药法规(PR)94-5(EPA农药法规,1994).按照标准程序,PWG审查是由无表决权的主席以旨在最大程度地减少偏见的方式进行的,因此在评估过程中,四名投票小组成员不了解个体鱼的治疗组状态以及与组织学切片相关的原始诊断.根据这篇综述的结果,与双氯芬酸暴露有关的发现包括暴露于最高测试浓度(1,000μg/L)的鱼中,g丝尖端的增厚最小至略有增加,再加上之前未确诊的发现,肝糖原减少,这也发生在1,000μg/L剂量水平。专家小组发现几乎没有证据支持双氯芬酸在鳟鱼中的其他报道作用,因此,总NOEC被确定为>320μg/L。通过协商一致,PWG小组能够确定之前3项研究之间和内部的诊断不一致;因此,这项研究证明了病理学同行评审/PWG方法对于评估可能被监管机构用于风险评估的组织病理学结果可靠性的价值.
While the pathology peer
review/pathology working group (PWG) model has long been used in mammalian toxicologic pathology to ensure the accuracy, consistency, and objectivity of histopathology data, application of this paradigm to ecotoxicological studies has thus far been limited. In the current project, the PWG approach was used to evaluate histopathologic sections of gills, liver, kidney, and/or intestines from three previously published studies of diclofenac in trout, among which there was substantial variation in the reported histopathologic findings. The main objectives of this
review process were to investigate and potentially reconcile these interstudy differences, and based on the results, to establish an appropriate no observed effect concentration (NOEC). Following a complete examination of all histologic sections and original diagnoses by a single experienced fish pathologist (pathology peer
review), a two-day PWG session was conducted to allow members of a four-person expert panel to determine the extent of treatment-related findings in each of the three trout studies. The PWG was performed according to the United States Environmental Protection Agency (US EPA) Pesticide Regulation (PR) 94-5 (EPA Pesticide Regulation, 1994). In accordance with standard procedures, the PWG
review was conducted by the non-voting chairperson in a manner intended to minimize bias, and thus during the evaluation, the four voting panelists were unaware of the treatment group status of individual fish and the original diagnoses associated with the histologic sections. Based on the results of this
review, findings related to diclofenac exposure included minimal to slightly increased thickening of the gill filament tips in fish exposed to the highest concentration tested (1,000 μg/L), plus a previously undiagnosed finding, decreased hepatic glycogen, which also occurred at the 1,000 μg/L dose level. The panel found little evidence to support other reported effects of diclofenac in trout, and thus the overall NOEC was determined to be >320 μg/L. By consensus, the PWG panel was able to identify diagnostic inconsistencies among and within the three prior studies; therefore this exercise demonstrated the value of the pathology peer review/PWG approach for assessing the reliability of histopathology results that may be used by regulatory agencies for risk assessment.