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土壤熏蒸剂 1,3-二氯丙烯的体内致突变性评价。

In vivo mutagenicity evaluation of the soil fumigant 1,3-dichloropropene.

机构信息

Exponent, Inc., Center for Health Sciences, Alexandria, VA, USA.

Research and Development, Corteva Agriscience, Indianapolis, IN, USA.

出版信息

Mutagenesis. 2020 Dec 1;35(5):437-443. doi: 10.1093/mutage/geaa015.

DOI:10.1093/mutage/geaa015
PMID:33511997
Abstract

1,3-Dichloropropene (1,3-D; CAS No. 542-75-6) is a soil fumigant used for the control of nematodes in agriculture. There is an extensive database on the genotoxicity of 1,3-D and many of the published studies are confounded by the presence of mutagenic stabilisers in the test substance. Mixed results were obtained in the in vitro assays, often due to the purity of the 1,3-D sample tested. In order to get further clarity, the mutagenic potential of 1,3-D was investigated in vivo in the transgenic Big Blue rodent models. Inhalation exposure of 150 ppm 1,3-D (×2.5 tumourigenic dose) to transgenic male B6C3F1 mice did not induce lacI mutations in either the lung (tumour target tissue) or liver. Similarly, dietary administration of 1,3-D up to 50 mg/kg/day to transgenic male Fischer 344 rats did not increase the cII mutant frequency in either the liver (tumour target) or kidney. These results, along with other available in vivo data, including the absence of DNA adducts and clastogenic/aneugenic potential, support the conclusion that 1,3-D is efficiently detoxified in vivo and, as such, does not pose a mutagenic hazard or risk.

摘要

1,3-二氯丙烯(1,3-D;CAS No. 542-75-6)是一种土壤熏蒸剂,用于农业防治线虫。关于 1,3-D 的遗传毒性有广泛的数据库,许多已发表的研究因测试物质中存在诱变稳定剂而受到混淆。在体外试验中得到了混合的结果,这往往是由于测试的 1,3-D 样品的纯度所致。为了进一步明确,在转基因 Big Blue 啮齿动物模型中体内研究了 1,3-D 的诱变潜力。150 ppm 1,3-D(×2.5 致癌剂量)的吸入暴露对转基因雄性 B6C3F1 小鼠的肺部(肿瘤靶组织)或肝脏均未诱导 lacI 突变。同样,给转基因雄性 Fischer 344 大鼠喂食高达 50 mg/kg/天的 1,3-D,也未增加肝脏(肿瘤靶)或肾脏中 cII 突变体的频率。这些结果以及其他可用的体内数据,包括缺乏 DNA 加合物和致裂/致畸潜力,支持以下结论:1,3-D 在体内被有效解毒,因此不会造成遗传毒性危害或风险。

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