DSM Nutritional Products AG, Wurmisweg 576, 4303, Kaiseraugst, Switzerland.
Charles River Laboratories Den Bosch BV, Hambakenwetering 7, 5231 DD 's, Hertogenbosch, the Netherlands.
Food Chem Toxicol. 2019 Jan;123:566-573. doi: 10.1016/j.fct.2018.11.010. Epub 2018 Nov 5.
3-NOP (3-nitroxy-propanol) is a new development compound which reduces methane emission from ruminating animals. For registration purposes with emphasis on EU and North America data requirements, mutagenic and genotoxic potential was assessed following OECD protocols and respective guidance documents. 3-NOP mutagenicity and genotoxicity testing raised no flags with regard to these endpoints. In silico assessment of 3-NOP and its major plasma metabolite NOPA (3-nitroxy-propionic acid) were predicted negative with regard to the bacterial reverse mutation (Ames) test. Ames test, mouse lymphoma assay, in vitro micronucleus test, and the oral in vivo micronucleus test using rat bone marrow were all negative. Exposure of the rat bone marrow was verified by the presence of 3-NOP and its metabolites NOPA and HPA (3-hydroxy-propionic acid) a naturally occurring substance in mammals) in plasma following oral dosing. It is therefore concluded that 3-NOP and its metabolites pose no mutagenic and genotoxic potential.
3-NOP(3-硝基氧基-1-丙醇)是一种新开发的化合物,可减少反刍动物的甲烷排放。为了在欧盟和北美数据要求方面进行注册,根据 OECD 方案和各自的指导文件,评估了致突变性和遗传毒性潜力。3-NOP 的致突变性和遗传毒性测试在这些终点方面没有发现任何问题。3-NOP 及其主要血浆代谢物 NOPA(3-硝基氧基-丙酸)的计算机评估预测对细菌回复突变(Ames)试验呈阴性。Ames 试验、小鼠淋巴瘤试验、体外微核试验和大鼠骨髓体内口服微核试验均为阴性。口服给药后,在血浆中检测到 3-NOP 及其代谢物 NOPA 和 HPA(哺乳动物中天然存在的物质 3-羟基丙酸),证实了大鼠骨髓的暴露。因此,可以得出结论,3-NOP 及其代谢物没有致突变性和遗传毒性潜力。