Internal Exposure Levels and Health Risk Assessment of Melamine and Organophosphate Metabolites in Urine: Research Progress and Prospects

With the widespread use of emerging contaminants such as melamine (MEL) and organophosphate esters (OPEs) as alternatives to traditional flame retardants, their ubiquitous presence in the environment has raised concerns about human internal exposure and health risks. Urine, as a critical matrix for biomonitoring, enables accurate assessment of internal exposure to these contaminants and their metabolites. This review systematically summarizes the research progress on urinary biomonitoring of MEL and its derivatives (cyanuric acid (CYA), ammeline (AMN), ammelide (AMD)) and OPE metabolites. It covers analytical methods (sample pretreatment including enzymatic hydrolysis and extraction, instrumental detection via HPLC-MS/MS/UPLC-MS/MS, and method validation), exposure characteristics (global spatial differences, population disparities among sensitive groups like children and e-waste workers, and temporal variations such as postprandial peaks), and health risk assessments. Results show that MEL and CYA are widely detected in urine (detection rates > 97%), with CYA dominating total MEL (66.2-80%); OPE metabolites exhibit regional compositional differences, e.g., bis(2-chloroethyl) phosphate (BCEP) in Shenzhen and diphenyl phosphate (DPHP) in New York. Current exposure levels are generally safe, but 2-12% of sensitive individuals face potential risks. This review highlights key challenges (method standardization, limited hydroxylated OPE standards) and provides directions for future research to establish a comprehensive exposure-health risk evaluation system.