In 2007 there was a large outbreak of renal failure in cats and dogs in the USA associated with ingestion of pet food found to contain melamine and cyanuric acid. The melamine was added deliberately to one of the ingredients. Melamine alone is of low toxicity, however experimental studies have shown that combination with cyanuric acid leads to crystal formation and subsequent kidney toxicity. It is not known whether the cyanuric acid was also added deliberately or whether it was a by-product of the melamine preparation added. Analysis of the contaminated ingredient (gluten) responsible for this outbreak revealed the following triazine compounds: melamine 8.4%, cyanuric acid 5.3%, ammelide 2.3%, ammeline 1.7%, ureidomelamine and methylmelamine both <1% (Dobson et al 2008).
It appears that melamine can be found in a variety of milk and milk products at varying levels, from low ppb to ppm ranges. Following the pet food incident in 2007 preliminary risk assessments have been published by nationals/regional authorities. These form the basis for this preliminary guidance developed to assist in the decision-making process on possible health concern of melamine levels in food.
This preliminary guidance is proposed as a first pragmatic approach until more data become available that allow a more detailed assessment. It has to be noted that currently there are large uncertainties involved in the assessment which preclude a more detailed guidance and emphasize the need for more data.
WHO is presently initiating action to develop a more thorough assessment through meetings of international scientists.
Uses and possible human exposure
Melamine (CAS No. 108-78-1) is used in the production of melamine resins, typically by reaction with formaldehyde. It has many industrial uses, including in the production of laminates, glues, adhesives, moulding compounds, coatings and flame retardants.
In the US melamine is an indirect food additive for use only as a component of adhesives.
[21 CFR 175.105; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from: http://www.gpoaccess.gov/ecfr as of June 18, 2007 ]
Melamine was also found as a metabolite of the pesticide cyromazine in plants, goats, hens and rats (JMPR Report 2006). Melamine is also used in some fertilizers.
Outside the current food safety incident consumer exposure to melamine is considered to be low. Besides low levels of residues as consequence of cyromazine metabolism it may occur through the extraction of melamine from compression moulds by acidic foods, such as lemon or orange juice or curdled milk, at high temperature. Taking into account these sources the estimated oral uptake of melamine is around 0.007 mg melamine/kg body weight/day (OECD 1998).
Cyanuric acid (CAS No 108-80-5) is a structural analogue of melamine. It may be found as an impurity of melamine. Cyanuric acid is an FDA-accepted component of feed-grade biuret, a ruminant feed additive. It is also found in swimming pool water as the dissociation product of dichloroisocyanurates used for water disinfection. Consumer exposure may be through swallowing swimming pool water, through drinking water processed from surface water, and through fish which may accumulate this chemical (OECD 1999). When used in drinking water for disinfection purposes, sodium dichloroisocyanurate is rapidly dechlorinated to cyanurate.
Due to the widespread use of melamine, also in material in contact with food, low levels may be detected in food, not necessarily due to adulteration. Some countries have established legal limits in relation to migration of melamine from food contact material into foods.
Toxicity of Melamine
Melamine is not metabolized and is rapidly eliminated in the urine with a half life in plasma of around 3 hours (OECD 1998). The compound has a low acute toxicity, with an oral LD50 in the rat of 3161 mg/kg body weight (OECD 1998).
No human data could be found on the oral toxicity of melamine. Data are available from animal feeding studies carried out in rats, mice and dogs. The main toxic effects of dietary exposure to melamine in rats and mice were calculi formation, inflammatory reactions and hyperplasia in the urinary bladder (OECD 1998, Melnick et al 1984; Bingham et al 2001; IARC 1986 ). Melamine crystalluria has been reported in dogs (Bingham et al 2001).
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World Health Organization
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