1,4-Dioxane, used widely as a solvent in the manufacture of chemicals and as a laboratory reagent, induced liver adenomas and carcinomas in mice and rats, and nasal tumors in rats in several long-term studies. 1,4-Dioxane has been reported to be non-genotoxic in vitro, and there is no clear conclusion concerning its in vivo genotoxicity in rodents. In the present study, we investigated the ability of 1,4-dioxane to induce micronuclei in the liver and bone marrow of rats. For the liver micronucleus test, we performed the juvenile animal method and two methods using partial hepatectomy (PH), dosing before PH or dosing after PH. We also evaluated the in vivo mutagenicity of 1,4-dioxane by Pig-a gene mutation assay using rat peripheral blood. As a result, all methods of liver micronucleus test showed an increase in the frequency of micronucleated hepatocytes by 1,4-dioxane. The dosing before PH, a suitable method for detecting structural chromosome aberration inducers, showed the clearest response for micronucleated hepatocytes induction among the three methods. This finding is consistent with a previous report that 1,4-dioxane induces mainly chromosome breakage in the liver. Negative results were obtained in the bone marrow micronucleus test and Pig-a gene mutation assay in our study. These results suggested that 1,4-dioxane is clastogenic in the liver but not genotoxic in the bone marrow of rats.

中文翻译：

---

通过大鼠肝脏和骨髓微核试验以及Pig-a试验评估1,4-二恶烷的体内遗传毒性。

1,4-二恶烷在许多长期研究中广泛用作制造化学品的溶剂和实验室试剂，可在小鼠和大鼠中诱发肝腺瘤和癌，以及在大鼠中诱发鼻腔肿瘤。据报道1，4-二恶烷在体外无遗传毒性，关于其在啮齿类动物体内的遗传毒性尚无明确结论。在本研究中，我们调查了1,4-二恶烷在大鼠肝脏和骨髓中诱导微核的能力。对于肝微核试验，我们进行了幼年动物方法和使用部分肝切除术（PH）的两种方法，即在PH前给药或在PH后给药。我们还通过使用大鼠外周血的Pig-a基因突变分析评估了1,4-二恶烷的体内致突变性。结果是，肝微核试验的所有方法均显示1,4-二恶烷增加了微核肝细胞的频率。在这三种方法中，PH之前的剂量是一种检测结构性染色体畸变诱导物的合适方法，显示出对微核肝细胞诱导最清晰的反应。这一发现与先前的报道一致，即1,4-二恶烷主要在肝脏中诱导染色体断裂。在我们的研究中，骨髓微核试验和Pig-a基因突变试验获得了阴性结果。这些结果表明1，4-二恶烷在大鼠肝脏中是可裂解的，但在大鼠骨髓中没有遗传毒性。在三种方法中，对微核肝细胞的诱导反应最清晰。这一发现与先前的报道一致，即1,4-二恶烷主要在肝脏中诱导染色体断裂。在我们的研究中，通过骨髓微核试验和Pig-a基因突变试验获得了阴性结果。这些结果表明1，4-二恶烷在大鼠肝脏中是可裂解的，但在大鼠骨髓中没有遗传毒性。在三种方法中，对微核肝细胞的诱导反应最清晰。这一发现与先前的报道一致，即1,4-二恶烷主要在肝脏中诱导染色体断裂。在我们的研究中，骨髓微核试验和Pig-a基因突变试验获得了阴性结果。这些结果表明1，4-二恶烷在大鼠肝脏中是可裂解的，但在大鼠骨髓中没有遗传毒性。