With the World Health Organization (WHO) issuing an alert following the deaths of 66 children in The Gambia after they used cough syrups made by an Indian firm, two contaminants – diethylene glycol and ethylene glycol – are at the centre of investigations. This is not the first time these industrial solvents have caused fatalities.
Diethylene glycol (DEG) and ethylene glycol (EG) are colourless and viscous liquids which have a sweetish taste. While they are popularly used in industrial products such as paints, stationery ink, brake fluids and antifreeze, they have been involved in several mass poisoning cases dating as far back as 1937.
The United States passed stringent legislation in 1938 in reaction to a public health accident that occurred in 1937, when 105 people died from DEG poisoning, according to research published by WHO. Toxic effects of the chemical can include abdominal pain, vomiting, diarrhoea, bladder dysfunction, headache, altered mental state, and acute kidney injury, which may lead to death.
According to the US Centers for Disease Control (CDC), DEG and EG are often found as contaminants in glycerin, which is used as a sweetener in formulations of many pharmaceutical syrups ingested orally. “Complexities in the distribution of glycerin and other pharmaceutical raw materials that may involve many handlers (importers and exporters)” cause these contaminants to creep into such glycerin-based medical products, it said.
To be sure, DEG has also been used illegally as a cheap substitute solvent in drug manufacturing. DEG and EG have similar physical properties and both are often used in the adulteration process. What contribute to the risk of such adulteration are inadequate international regulations and the lack of analytical methods, according to scientists.
{{/usCountry}}To be sure, DEG has also been used illegally as a cheap substitute solvent in drug manufacturing. DEG and EG have similar physical properties and both are often used in the adulteration process. What contribute to the risk of such adulteration are inadequate international regulations and the lack of analytical methods, according to scientists.
{{/usCountry}}The four cough syrups manufactured by Indian company Maiden Pharmaceuticals Ltd – Promethazine Oral Solution, Kofexmalin Baby Cough Syrup, Makoff Baby Cough Syrup, and Magrip N Cold Syrup – are glycerin-based solutions that were exported to The Gambia.
“It is a preservative chemical to prolong shelf life of medications and prevent decomposition in adverse temperate conditions and to dissolve the components in cough syrup. It has a direct effect on kidney and brain when consumed above a certain quantity (or in accidental overdose situation as it is part of antifreeze and coolants for automobile industry and used as raw material in manufacture of polyester fibres) or excessive use of cough syrup, which normally can cause side effects such as shakiness, sedation, nausea, dryness of throat,” said Dr Praveen Khilnani, director, paediatric intensive care and senior consultant, Paediatric Pulmonology and Critical Care department, Madhukar Rainbow Children’s Hospital.
Despite the existence of several safeguards in India, 14 patients died in Mumbai in 1986 when they were given glycerin contaminated with DEG. A second episode of poisoning occurred in 1998 in India as a result of children ingesting DEG; at least 33 children are known to have died in that episode, according to local accounts and the UN health agency.
While traces of the two contaminants are sometimes found in glycerin-based medicines, WHO has said in its latest medical product alert that laboratory analysis of samples confirmed there were “unacceptable amounts of diethylene glycol and ethylene glycol as contaminants”.
“The Indian pharmaceutical industry has had a DEG poisoning problem for a long time now, with the first event being reported in 1972 in Madras. The reason that such poisoning events take place is because many pharma companies in India do not test all excipients before they are used in manufacturing drugs, despite the Good Manufacturing Practice code expressly requiring such testing,” public health activist Dinesh Thakur said, quoting from his upcoming book, The Truth Pill: The Myth of Drug Regulation in India.
The contaminants can result in renal and neurological toxicity if ingested, which, in simple terms, means they affect the brain and kidney functions. Acute kidney injury is usually the main cause of death, which occurs anywhere between 8 and 24 hours after exposure if the dose is high.
WHO has said that all batches of the four products listed by it should be considered unsafe until they can be analysed by the relevant national regulatory authorities.
While the UN agency said information received from India’s Central Drugs Standard Control Organisation (CDSCO) indicated that the manufacturer had only supplied the contaminated medications to The Gambia, hectic investigations are on in the country to determine the trail of the exports and how such contamination escaped the eye of the authorities.