What is ethylene glycol and why is it dangerous?
In December 2022, it became known about deaths among children in neighboring countries associated with taking an Indian drug in the form of cough syrup called Doc-1 Max. Ethylene glycol was found in one of the series of this drug. What is this substance and what is its danger?
Ethylene glycol is a vicinal (containing two OH groups) diol.
The range of doses of ethylene glycol that cause severe human poisoning is quite wide. In most cases, lethal doses were 100-150 ml of liquids containing this compound. According to other sources, lethal doses in terms of a pure substance were 1.5 – 5.0 ml / kg. Probably, there are significant differences in individual sensitivity to the poison, since in some cases the intake of 30 – 60 ml of pure ethylene glycol led to the death of the victims, while in others – the intake of 240 – 280 ml was not fatal.
When ethylene glycol is taken orally, the following happens: in the stomach, ethylene glycol is quickly absorbed into the blood and distributed relatively evenly in organs and tissues. The maximum concentration of this substance in the blood of various animal species (rats, dogs, monkeys) and humans is observed 1 to 4 hours after its oral intake.
Ethylene glycol is quickly excreted from the body and after a few hours (according to some authors – after 1 hour) after administration, its concentration in the urine becomes significantly higher than in the blood. Poison does not accumulate in organs and tissues.
The mechanism of toxic action of ethylene glycol is rather complicated. It is customary to highlight the effects caused by the action of the unchanged ethylene glycol molecule and the products of its biotransformation (metabolism, “digestion”). Currently, the prevailing point of view is that the toxicity of ethylene glycol is determined mainly by the products of its biotransformation.
The toxicity of the main products of ethylene glycol biotransformation is distributed as follows: glyoxylic acid > glycolic aldehyde > oxalate > glycolic acid. All of these substances are capable of inhibiting respiration, oxidative phosphorylation and protein synthesis. However, at present, most authors, without denying the very high toxicity of glyoxylic acid, nevertheless believe that in ethylene glycol poisoning, the main carrier of toxicity is glycolic acid, which, due to slower destruction, accumulates in the body in concentrations exceeding the level of glyoxylic acid in 1300 – 1400 times. This theory is also supported by the fact that large doses of ethylene glycol suppress the processes responsible for the metabolism of glycolic acid, and the direct dependence of mortality on the level of its concentration in the urine.
The clinical picture of ethylene glycol poisoning includes manifestations of toxic encephalopathy (excitation, stupor, coma), lesions of the gastrointestinal tract (abdominal pain, nausea, vomiting, etc.), metabolic acidosis (“acidification” of the body), and later – toxic nephro – or hepatonephropathy with acute renal or renal-hepatic insufficiency.
Coming back to the tragedy with the drug “Doc-1 Max”, it is important to note that the concentration of ethylene glycol in this drug exceeded the permissible by 300 times. All production activities of Marion Biotech, the manufacturer of this drug, have been suspended.