Clinical parameters, postmortem analysis and estimation of lethal dose in victims of a massive intoxication with diethylene glycol.
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.
Ferrari
Luis A
LA
Laboratory of Toxicology and Legal Chemistry, Court of Justice of the Province of Buenos Aires, 41 and 119, 1900 La Plata, Argentina. laferrari@unimoron.edu.ar
Giannuzzi
Leda
L
D000136:Acid-Base Equilibrium; D058186:Acute Kidney Injury / Q000139:chemically induced; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D001002:Anuria / Q000139:chemically induced; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001219:Aspartate Aminotransferases / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose; D005026:Ethylene Glycols / Q000032:analysis / Q000506:poisoning*; D005260:Female; D005410:Flame Ionization; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007958:Leukocyte Count; D008099:Liver / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D011429:Propolis / Q000737:chemistry; D012131:Respiratory Insufficiency / Q000139:chemically induced; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000097:blood
D005026:Ethylene Glycols; C013484:diethylene glycol; D011429:Propolis; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase