Although frequently examined as a target organ for non-endocrine toxicity, histopathological evaluation of the liver is becoming a routine component of endocrine disruption studies that utilize various fish species as test subjects. However, the interpretation of microscopic liver findings can be challenging, especially when attempting to distinguish adverse changes associated with endocrine disrupting substances from those caused by systemic or direct hepatic toxicity. The purpose of this project was to conduct a critical assessment of the available peer-reviewed and grey literature concerning the histopathologic effects of reproductive endocrine active substances (EAS) and non-endocrine acting substances in the livers of fish models, and to determine if liver histopathology can be used to reliably distinguish endocrine from non-endocrine etiologies. The results of this review suggest that few compound-specific histopathologic liver effects have been identified, among which are estrogen agonist-induced increases in hepatocyte basophilia and proteinaceous intravascular fluid in adult male teleosts, and potentially, decreased hepatocyte basophilia in female fish exposed to substances that possess androgenic, anti-estrogenic, or aromatase inhibitory activity. This review also used published standardized methodology to assess the credibility of the histopathology data in each of the 117 articles that reported liver effects of treatment, and consequently it was determined that in only 37% of those papers were the data considered either highly credible or credible. The outcome of this work highlights the value of histopathologic liver evaluation as an investigative tool for EAS studies, and provides information that may have implications for EAS hazard assessment.

尽管经常被检查为非内分泌毒性的靶器官，但是肝脏的组织病理学评估已成为利用各种鱼类作为测试对象的内分泌干扰研究的常规组成部分。然而，微观肝脏发现的解释可能具有挑战性，尤其是在试图将与内分泌干扰物相关的不利变化与全身或直接肝毒性引起的不良变化区分开来时。该项目的目的是对鱼类模型肝脏中生殖内分泌活性物质（EAS）和非内分泌作用物质的组织病理学影响的现有同行评审灰色文献进行严格评估，并确定肝脏组织病理学是否可用于可靠地区分内分泌病因和非内分泌病因。这篇综述的结果表明，几乎没有发现化合物特异性的组织病理学肝效应，其中包括雌激素激动剂诱导的成年雄性硬骨鱼肝细胞嗜碱性和蛋白质性血管内液的增加，以及潜在地降低了暴露于该物质的雌鱼的肝嗜碱性细胞的降低。具有雄激素，抗雌激素或芳香酶抑制活性。这篇综述还使用了公开发表的标准化方法来评估117篇报道肝脏治疗的文章中每篇的组织病理学数据的可信度，因此确定只有37％的论文被认为是高度可信或可信的数据。 。