0842 Facts about melamine

Towards the end of September 2008 the Chinese authorities reported that >50 000 children had been hospitalised for complications associated with melamine ingestion. At least 150 had renal failure and four had died as a direct result. A concurrent report from Hong Kong revealed that 15017 children had attended designated clinics ; five had renal stones, four of which had a history of exposure during residence on the mainland. At this time it is well known that the problem originated as a result of milk producers diluting milk to increase volume, and then boosting nitrogen levels by adding melamine. Since usual tests for protein are only measuring nitrogen, the melamine creates a false impression of milk quality. The paediatric mini-epidemic followed an outbreak of renal failure and death in cats and dogs in 2007 when exported pet food was found to be contaminated with melamine. Victims in both these situations are at risk because of their sole or heavy dependence on the particular food sources for survival. But is it the melamine, and if so what is going on at tissue and organ level? Melamine itself is not metabolized and is fairly rapidly excreted by the kidneys. The compound is regarded as being of relatively low toxicity, with an oral lethal dose in the rat of >3g/Kg body weight. High dose ingestion appears to be associated with cystitis, crystalluria and stones rather than nephrolithiasis. Animal data therefore support the contention that melamine alone does not cause renal stones or renal failure. The problem of renal failure appears to arise when the melamine is associated with cyanuric acid, a structural analogue of melamine. The combination was found in the veterinary outbreak, but it was not clear whether the cyanuric acid had been added or was a by-product of the added melamine. While cyanuric acid on its own is also not particularly toxic, the combination is, affecting the kidneys through tubular damage (necrosis or hyperplasia of epithelium, neutrophil infiltration, mineralization and fibrosis). These changes are most likely caused by cyanurate or melamine-cyanuric acid co-crystals in the tubules. From the available Chinese data it is not absolutely clear whether the clinical problems observed are the result of chronic melamine exposure with renal problems following on bladder stones, or melamine-cyanuric acid exposure with more direct renal involvement.

Read more:
Lancet 2008; 372: 1444-5
Guidelines for Health Care Professionals www.phac-aspc.gc.ca
World Health Organisation http://www.who.int/foodsafety/fs_management/Melamine.pdf