狄氏剂是一种有机氯杀虫剂，一直被广泛使用，直到 1970 年由于对小鼠肝脏有致癌作用而被禁止使用。一些长期的啮齿动物生物测定表明，狄氏剂会在几种小鼠品系中诱发肝肿瘤，但不会在大鼠中诱发肝肿瘤。本文回顾了有关狄氏剂肝脏影响的现有信息，并对这些肝脏发现的作用模式 (MOA) 和人类相关性进行了分析。科学证据强烈支持基于 CAR 激活的 MOA，导致基因表达的改变，从而导致肝细胞增殖增加、克隆扩张导致肝病灶改变，并最终形成肝细胞腺瘤和癌。相关事件包括肝脏重量增加、小叶中心肥大、Cyp2b10 表达增加及其导致的酶活性增加。其他相关事件包括细胞间间隙连接通讯和氧化应激的改变。对替代 MOA 进行了评估，结果表明其与狄氏剂施用无关。大量证据表明，狄氏剂不具有 DNA 反应性，不具有诱变性，并且总体上不具有遗传毒性。此外，其他相关核受体的激活，包括 PXR、PPARα、AhR 和雌激素，与狄氏剂诱导的肝肿瘤无关，也不存在肝细胞毒性。在之前的研究中，大鼠、狗和非人类灵长类动物在狄氏剂治疗后并未表现出细胞增殖或肿瘤前或肿瘤病变产生增加。因此，证据有力地表明，狄氏剂诱导的小鼠肝脏肿瘤是由于CAR激活所致，并且是小鼠特有的，这与人类肝癌的发生在性质上无关。因此，对人类不存在致癌风险。缺乏肝癌致癌性证据的积极流行病学发现也支持了这一结论。根据目前对狄氏剂诱发小鼠肝脏肿瘤的作用方式的了解，适当的结论是狄氏剂是小鼠特异性肝癌致癌物，不会对人类造成癌症风险。

Dieldrin is an organochlorine insecticide that was widely used until 1970 when its use was banned because of its liver carcinogenicity in mice. Several long-term rodent bioassays have reported dieldrin to induce liver tumors in in several strains of mice, but not in rats. This article reviews the available information on dieldrin liver effects and performs an analysis of mode of action (MOA) and human relevance of these liver findings. Scientific evidence strongly supports a MOA based on CAR activation, leading to alterations in gene expression, which result in increased hepatocellular proliferation, clonal expansion leading to altered hepatic foci, and ultimately the formation of hepatocellular adenomas and carcinomas. Associative events include increased liver weight, centrilobular hypertrophy, increased expression of Cyp2b10 and its resulting increased enzymatic activity. Other associative events include alterations of intercellular gap junction communication and oxidative stress. Alternative MOAs are evaluated and shown not to be related to dieldrin administration. Weight of evidence shows that dieldrin is not DNA reactive, it is not mutagenic, and it is not genotoxic in general. Furthermore, activation of other pertinent nuclear receptors, including PXR, PPARα, AhR, and estrogen are not related to dieldrin-induced liver tumors nor is there liver cytotoxicity. In previous studies, rats, dogs, and non-human primates did not show increased cell proliferation or production of pre-neoplastic or neoplastic lesions following dieldrin treatment. Thus, the evidence strongly indicates that dieldrin-induced mouse liver tumors are due to CAR activation and are specific to the mouse, which are qualitatively not relevant to human hepatocarcinogenesis. Thus, there is no carcinogenic risk to humans. This conclusion is also supported by a lack of positive epidemiologic findings for evidence of liver carcinogenicity. Based on current understanding of the mode of action of dieldrin-induced liver tumors in mice, the appropriate conclusion is that dieldrin is a mouse specific liver carcinogen and it does not pose a cancer risk to humans.