Nolen G A, Baines D, Poynter J I, Weaver J E, Slough C L
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, OH 45239-8707.
Drug Chem Toxicol. 1989 Jun;12(2):111-21. doi: 10.3109/01480548908999148.
Weanling Charles River CD rats of both sexes were fed 300 mg/kg/day of Piroctone Olamine, an anti-bacterial agent, and were supplemented with 0, 50, 100 or 200 ppm dietary iron as FeSO4.7H2O for six weeks. However, analytical data indicated that Piroctone was degraded in the diet so that the rats received only 225 mg/kg/day. The rats given Piroctone Olamine without iron gained significantly less body weight and ate significantly less feed than controls, with the effect being more pronounced in the males. They also developed severe microcytic, hypochromic anemia. The rats supplemented with all three levels of dietary iron grew at a rate similar to controls. The rats supplemented with 50 ppm dietary iron had anemia with all of the hematological iron-associated factors being significantly depressed. The 100 ppm supplement restored all hematologic factors to normal in the females, but slight reductions remained in the males. The 200 ppm supplement of iron restored all parameters to values similar to the controls in both sexes. These results suggest that the mechanism of the toxicity of Piroctone Olamine is the prevention of dietary iron absorption by in situ chelation.
将断奶的雄性和雌性查尔斯河CD大鼠喂食300毫克/千克/天的抗真菌剂奥麦丁(Piroctone Olamine),并分别添加0、50、100或200 ppm作为FeSO₄·7H₂O的膳食铁,持续六周。然而,分析数据表明奥麦丁在饲料中会降解,因此大鼠实际摄入的剂量仅为225毫克/千克/天。与对照组相比,喂食奥麦丁但未补充铁的大鼠体重增加显著减少,采食量也显著降低,这种影响在雄性大鼠中更为明显。此外,它们还出现了严重的小细胞低色素性贫血。补充了所有三种膳食铁水平的大鼠生长速度与对照组相似。补充50 ppm膳食铁的大鼠出现贫血,所有与血液学铁相关的因子均显著降低。补充100 ppm铁后,雌性大鼠的所有血液学指标恢复正常,但雄性大鼠仍有轻微降低。补充200 ppm铁后,雌雄大鼠的所有参数均恢复到与对照组相似的值。这些结果表明,奥麦丁的毒性机制是通过原位螯合作用阻止膳食铁的吸收。