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二甘醇大规模中毒受害者的临床参数、尸检分析及致死剂量估算

Clinical parameters, postmortem analysis and estimation of lethal dose in victims of a massive intoxication with diethylene glycol.

作者信息

Ferrari Luis A, Giannuzzi Leda

机构信息

Laboratory of Toxicology and Legal Chemistry, Court of Justice of the Province of Buenos Aires, 41 and 119, 1900 La Plata, Argentina.

出版信息

Forensic Sci Int. 2005 Oct 4;153(1):45-51. doi: 10.1016/j.forsciint.2005.04.038.

Abstract

This work analyzes a massive intoxication that occurred in 1992 in Argentina as a result of the use of propolis syrup as a popular upper respiratory infection medicinal agent. The intoxicating agent was diethylene glycol (DEG), which caused metabolic acidosis, anuria, renal failure and death in 15 out of the 29 studied victims. DEG poisoning cases were classified in three groups according to survival time: Group 1-patients that survived up to 3 days; Group 2-patients that survived between 4 and 5 days; Group 3-patients that survived between 6 and 21 days. Patients from Group 1 showed the highest values of anion gap, the lowest measures of base excess (BE) and more severe clinical manifestations. Correlation between pH and BE was r(2) = 0.68, 0.99 and 0.55 for Groups 1, 2 and 3, respectively. A methanolic extraction was performed on the fatal victims' viscera and blood, with subsequent concentration and purification. The semi-crystalline fraction obtained retained DEG by means of co-dissolution and adsorption as demonstrated by thin lay chromatography/flame ionisation detection (TLC/FID). In 3 out of the 15 fatal cases (from Group 1), DEG was isolated from viscera and blood (femoral venous), between 48 and 72 h post ingestion. The concentration relation (DEG)viscera/(DEG)blood ranged from 1.45 to 1.55 with a coefficient correlation r(2)=0.96 (n=3). In the other victims, DEG could not be detected. The reason for this could be the long survival period of the victims after their ingestion of the syrup. Additionally, putrefying mechanisms could have been operating. Samples of the propolis syrup of each victim were studied by means of nuclear magnetic resonance (NMR) and quantified by gas chromatography/flame ionisation detection (GC/FID). Results showed that syrup samples contained 65.0% (w/v) of diethylene glycol (DEG) and 32.0% (w/v) of propylene glycol (PG). A good correlation between the amount of DEG ingested and the anion gap (r(2)=0.63) for the 15 victims studied could be observed. The lethal dose for human beings estimated in this work ranged from 0.014 to 0.170 mg DEG/kg body weight. This is a lower lethal dose than reported in a separate incident in Haiti. These results may contribute to the understanding of DEG's metabolic pathway and provides data from lethal doses in humans.

摘要

这项研究分析了1992年在阿根廷发生的一起大规模中毒事件,中毒原因是人们将蜂胶糖浆作为一种常用的上呼吸道感染药物使用。中毒剂为二甘醇(DEG),在29名受研究的受害者中,有15人因二甘醇导致代谢性酸中毒、无尿、肾衰竭并死亡。根据存活时间,二甘醇中毒病例分为三组:第1组——存活时间达3天的患者;第2组——存活时间在4至5天之间的患者;第3组——存活时间在6至21天之间的患者。第1组患者的阴离子间隙值最高,碱剩余(BE)测量值最低,临床表现也更严重。第1、2、3组患者的pH值与BE值之间的相关性分别为r(2)=0.68、0.99和0.55。对死亡受害者的内脏和血液进行了甲醇萃取,随后进行浓缩和提纯。通过薄层色谱/火焰离子化检测(TLC/FID)证明,所获得的半结晶部分通过共溶解和吸附保留了二甘醇。在15例死亡病例中的3例(第1组),摄入后48至72小时内从内脏和血液(股静脉)中分离出了二甘醇。内脏与血液中二甘醇的浓度关系(DEG)viscera/(DEG)blood在1.45至1.55之间,相关系数r(2)=0.96(n = 3)。在其他受害者中未检测到二甘醇。原因可能是受害者摄入糖浆后的存活时间较长。此外,可能已经发生了腐败机制。通过核磁共振(NMR)对每位受害者的蜂胶糖浆样本进行了研究,并通过气相色谱/火焰离子化检测(GC/FID)进行了定量分析。结果显示,糖浆样本中含有65.0%(w/v)的二甘醇(DEG)和32.0%(w/v)的丙二醇(PG)。对于所研究的15名受害者,可以观察到摄入的二甘醇量与阴离子间隙之间具有良好的相关性(r(2)=0.63)。这项研究中估计的人类致死剂量范围为0.014至0.170毫克二甘醇/千克体重。这一比海地另一起单独事件中报告的致死剂量更低。这些结果可能有助于理解二甘醇的代谢途径,并提供人类致死剂量的数据。

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