Babu Ch Kishore, Khanna Subhash K, Das Mukul
Food Toxicology Laboratory, Industrial Toxicology Research Centre, P.O. Box # 80, M.G. Marg, Lucknow 226001, India.
Food Chem Toxicol. 2006 Jul;44(7):1151-7. doi: 10.1016/j.fct.2006.02.003. Epub 2006 Feb 28.
Epidemic dropsy is a disease caused by the consumption of mustard oil contaminated with argemone oil (AO). During 1998 dropsy in New Delhi, which is so far the largest with more than 3000 victims and over 60 deaths, it was enquired at various scientific and regulatory meetings about the maximum tolerated dose of AO. Hence, the present study was aimed to investigate the safety levels of AO in rats. Animals were given AO in diet at a dose of 0.001%, 0.01%, 0.1%, 0.5% and 1% daily for 90 days and the two control groups received the standard diet with and without 1% mustard oil. A decrease in body weight gain (28-31%) was observed in 0.5% and 1% AO groups; while significant increases in relative lungs and liver weight was noticed in respective doses of 0.01% and 0.1% AO groups as well as in higher dosage animals. Reduction in RBC count and hemoglobin content (p<0.05) was noticed in 0.01% and 0.1% AO exposed animals. This effect was more pronounced in higher AO doses. Serum marker enzymes including alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) were found to be significantly elevated in 0.01-1% AO groups. Further, a decrease in albumin/globulin ratio (42-78%) was observed in the serum of 0.01% to higher AO dose groups. The levels of serum triglycerides and VLDL cholesterol were found to be enhanced (p<0.05) in AO treated (0.01-1.0%) animals. Histopathological changes in lung were observed at 0.01% dose of AO while liver, kidney and heart produced changes at 0.1% AO and above doses. None of the parameters were found to be affected in 0.001% AO treated animals. These results suggest that the no observed adverse effect level (NOAEL) dose of AO is 0.001% in rats and considering a factor of 100 for humans for highly toxic compound, the safe limit of 0.00001% (100 ppb or 100 ng AO/g oil) AO can be implicated which shall contain only 0.55% of sanguinarine equivalent to 0.6 ng sanguinarine per gram oil. However, the minimum detectable limit of AO is 5 ppm (equivalent to 5 microg sanguinarine per gram oil) with the present existing HPLC method, thereby suggesting that mustard oil should be absolutely free from AO contamination.
流行性水肿是一种因食用被白屈菜红碱油（AO）污染的芥子油而引发的疾病。1998年新德里发生的水肿疫情是迄今为止规模最大的一次，有3000多名受害者，60多人死亡。在各种科学和监管会议上，人们探讨了AO的最大耐受剂量。因此，本研究旨在调查大鼠体内AO的安全水平。给动物喂食含0.001%、0.01%、0.1%、0.5%和1% AO的饲料，持续90天，两个对照组分别喂食含1%芥子油和不含1%芥子油的标准饲料。0.5%和1% AO组的体重增加有所下降（28 - 31%）；而在0.01%和0.1% AO组以及高剂量组中，相对肺和肝脏重量显著增加。在接触0.01%和0.1% AO的动物中，红细胞计数和血红蛋白含量降低（p<0.05）。这种影响在更高AO剂量下更为明显。在0.01 - 1% AO组中，血清标志物酶包括丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）和碱性磷酸酶（ALP）显著升高。此外，在0.01%至更高AO剂量组的血清中，白蛋白/球蛋白比值下降（42 - 78%）。在接受AO处理（0.01 - 1.0%）的动物中，血清甘油三酯和极低密度脂蛋白胆固醇水平升高（p<0.05）。在0.01% AO剂量下观察到肺部有组织病理学变化，而在0.1% AO及以上剂量下，肝脏、肾脏和心脏出现变化。在接受0.001% AO处理的动物中，未发现任何参数受到影响。这些结果表明，大鼠体内AO的未观察到有害作用水平（NOAEL）剂量为0.001%，考虑到高毒化合物对人类的安全系数为100，可得出AO的安全限量为0.00001%（100 ppb或100 ng AO/g油），其中血根碱含量仅为0.55%，相当于每克油含0.6 ng血根碱。然而，采用现有的高效液相色谱法，AO的最低检测限为5 ppm（相当于每克油含5 μg血根碱），这表明芥子油应绝对不含AO污染。
