(14 October 2008)
In September 2008 FSANZ became aware of media reports which indicated that m ore than 50 000 infants and young children in China had sought treatment for renal tube blockages and kidney stones following consumption of infant formula adulterated with melamine. The deliberate addition of melamine to food or infant formula is not approved anywhere in the world. Four deaths have now been reported and many thousands have been hospitalized with kidney problems. It is understood that melamine was added to infant formula to boost its apparent protein content.
Melamine has been commercially used for many years to produce melamine resins which are then used for kitchenware, plastic resins, flame retardant fibres and components of paper and cardboard. Although such resins may come into contact with food during food production usually only trace quantities of melamine are present in food. These trace quantities of melamine in food do not pose any risk to human health.
In 2007 in the United States there was a similar food adulteration incident involving melamine which resulted in the death of cats and dogs. An adulterated pet food ingredient (gluten) had been imported from China. Again, renal failure and death were observed in pet cats and dogs. A follow-up analysis of some adulterated pet food scraps detected melamine and a number of melamine-related compounds, ie. cyanuric acid, ammelide, and ammeline1.
In response to this incident the US Food and Drug Administration (FDA) prepared an i nterim risk assessment for melamine and related compounds analogues. This risk assessment established a tolerable daily intake (TDI) of 0.63 mg/kilogram body weight/day that included a 100-fold safety factor and considered the likely risk to humans arising from consumption of meat and eggs derived from animals that had eaten feed contaminated with melamine compounds. The risk assessment concluded that the dietary risk to humans from this source was very low2.
Investigations into the nature of the kidney stones which were present in the pets that had died in the 2007 incident revealed that they were composed of melamine-cyanurate. Furthermore, subsequent experimental tests reported in 2008 confirmed that cats fed pet food adultered with melamine and cyanuric acid (in combination) died because of kidney failure through intratubular obstruction caused by the presence of melamine-cyanurate kidney stones3. In contrast, cats did not die if fed either melamine or cyanuric acid separately at the equivalent concentration.
In view of this recent work showing that melamine and cyanuric acid could act synergistically (in combination) to produce an effect that was greater than each compound separately there is now some doubt about the adequacy of the melamine TDI for human health risk assessment purposes. The FDA has proposed to apply an additional 10-fold uncertainty factor to its risk assessment for exposure to melamine and its analogues in food. Based on its worst case exposure scenario the FDA has concluded that if 50% of the diet was contaminated with melamine and its analogues at a level of 2.5 mg melamine/kg of food a person’s daily exposure would be 0.063 mg/kg bw/day. Hence there is a 1000-fold difference between the estimated dietary exposure and the level of melamine that does not cause any toxicity in animals4.
It is recognised that trace quantities of melamine and related compounds that are of no toxicological importance may legitimately be present in food. This may arise during processing through leaching from food-grade melamine contact material. Published reports, which specify the likely leached levels of melamine in foods, are not available but there are studies reporting levels of melamine that can be leached from melamine kitchenware under very severe conditions. Melamine may be detected in beverages at levels of 0.5, 0.7, 1.4 and 2.2 mg/kg in coffee, orange juice, fermented milk and lemon juice respectively5. These levels originate from migration of melamine from the cup, made of melamine-formaldehyde resin, into the beverage under experimental hot and acidic conditions (95°C for 30 min). Given the extreme use conditions used to generate these data it is considered that a level of 2.5 mg melamine/kg food would represent the upper levels likely to be legitimately found in foods. Melamine levels in food exceeding 2.5 mg/kg would be indicative of food adulteration.
Dietary exposure assessment
Assuming a range of melamine contamination in milk powder, the amount of food containing dairy-based ingredients that would need to be consumed before the TDI is exceeded can be readily estimated. For infant formula, even at levels of adulteration of 100 mg/kg an infant will quickly exceed the TDI, if fed exclusively on formula. In products containing 10% milk powder, at melamine concentrations of 10 mg/kg unrealistic amounts of food would have to be consumed to exceed the TDI (e.g. 44 kg for a 70 kg adult). If food was contaminated with 100 mg/kg of melamine, a 20 kg child would have to eat more than 1 kg of that food before exceeding the TDI, and an adult more than 4 kg of the food. Assuming heavy adulteration with 1000 mg melamine per kg of food, adults would still have to consume over 400 g of food to exceed the TDI, and a 20 kg child 130 g.
FSANZ has undertaken a preliminary dietary exposure assessment using FSANZ’s Dietary Modelling computer program on melamine in soft confectionery for the whole population (Australians aged 2 years and above and New Zealanders aged 15 years and above) and the Australian population sub-groups of children aged 2-3 years and 4-8 years. Based on levels of melamine detected in White Rabbit Candy, a concentration of melamine of 180 mg/kg was assigned to foods similar to White Rabbit Candies, i.e. soft, chewy textured confectionery. In order to determine if the level of potential exposure to melamine will be a public health and safety concern, the estimated dietary exposures were compared to the TDI. For all adults and children 4-8 years dietary exposure was estimated to be below the TDI. For 2-3 year old children, dietary exposure was 115% TDI at the 90th percentile of melamine exposure. For a child weighing 30 kg about 105 g of these sweets would have to be consumed before the TDI was exceeded. However, in general, Chinese made sweets are likely to be infrequently consumed and in small amounts so they are not considered to be a high-risk food for ongoing dietary exposure to melamine.
Other Regulatory Agencies
The US FDA and Hong Kong have indicated that food, other than infant formula, containing in excess of 2.5 mg melamine/kg will not be permitted. The EU, Canada and China have a level of 2.5 mg melamine/kg for dairy-based foods. For infant formula a level of 1 mg melamine/kg will apply in Hong Kong, China and the US. In Canada the 1 mg melamine/kg maximum level applies to infant formula and sole nutrition products including meal replacement products. The EU and Australia are currently not permitting any importation of infant formula from China.
Risk assessments from the following countries can be accessed through the following links:
United States : http://www.fda.gov
- A maximum level of 1 mg/kg for melamine in infant formula is considered appropriate.
- A maximum level of 2.5 mg/kg for melamine in dairy-based foods and foods containing dairy-based ingredients is appropriate and acceptable.
- A level of melamine above 2.5 mg/kg is indicative of food adulteration.
- For infant formula, even at relatively low levels of adulteration an infant will quickly exceed the Tolerable Daily Intake for melamine, if consuming formula only.
- Foods with low levels of dairy-based ingredients, such as candies and biscuits, are likely to be infrequently consumed and in small amounts so they are not considered to be a high-risk food for potential dietary exposure to melamine even if the dairy ingredient has been adulterated.