Using urinary solubility data to estimate the level of safety concern of low levels of melamine (MEL) and cyanuric acid (CYA) present simultaneously in infant formulas

Melamine (MEL) and cyanuric acid (CYA) may occur simultaneously in milk products. There is no health based guidance value for the mixture of MEL + CYA. Limited toxicological data indicate that MEL + CYA toxicity occurs at levels lower than the toxic doses of the single compounds. The key adverse effect of MEL + CYA is the formation of crystals in the urinary tract, which is dependent on the solubility of the MEL + CYA complex. Urinary concentrations resulting from oral doses of MEL + CYA and MEL alone have been calculated from published data from animal studies. A human exposure scenario assuming consumption of infant formula contaminated at a level of 1 ppm of MEL and CYA each (2 ppm of MEL + CYA) was also analyzed. Margins of more than two orders or magnitude were observed between estimated urine concentrations known to be without detectable effects in rats and calculated human urine concentrations. Because the hazard is related to the physico-chemical characteristics of the mixture, there would be a negligible concern associated with crystal formation if the urinary concentration of the complex is within the solubility range. The solubility of MEL + CYA was higher in urine than in water. A strong pH-dependency was observed with the lowest solubility found at pH 5–5.5. The calculated human urinary concentration was about 30 times less than the solubility limit for MEL + CYA in adult human urine. Altogether, these data provide preliminary evidence suggesting that the presence of 1 ppm of MEL and CYA each in infant formula is unlikely to be of significant health concern.