Analytical chemistry, toxicology, epidemiology and health impact assessment of melamine in infant formula: recent progress and developments.

This review summarizes the most recent scientific literature and regulations regarding analytical chemistry, toxicology, epidemiology, exposure, and risk assessment of melamine in infant formula. For analyses, enzyme-linked immunosorbent assay, high-performance liquid chromatography, capillary electrophoresis, gas chromatography coupled with mass spectrometry and liquid chromatography coupled with tandem mass spectrometry have commonly been used. Organization of proficiency test programs provided good evidence to facilitate granting laboratories accreditation and to ascertain the measurement reliability of melamine methods. Metabolic studies demonstrated that melamine is predominantly restricted to blood or extracellular fluid and is not extensively distributed to organs and tissues. Studies of human renal histopathology and clinical diagnoses indicated that melamine-related obstructive nephropathy derives from melamine precipitation in the lower urinary tract, with stones that are thought to be melamine-uric acid complexes. Epidemiologic studies showed that the occurrence of melamine-related urolithiasis is related to both the concentration of melamine in ingested milk products and the duration of ingestion. Long-term follow-up cohort studies should be continued to further investigate the epidemic and chronic hazard of melamine-induced nephrotoxicity. The World Health Organization set a tolerable daily intake of 0.2 mg/kg bw/day to be applied to "the whole population including infants". Other authorities and research institutes have set/proposed lower values.