Derivation of a Melamine Oral Reference Dose (RfD) and Drinking-Water Total Allowable Concentration

Abstract

Due to its high nitrogen content, melamine has been used to adulterate food to increase apparent protein content. In 2008, thousands of Chinese infants consumed reconstituted formula derived from melamine-adulterated milk. Urinary-tract stones (comprised of melamine and uric acid) accumulated in some victims and lead to acute renal failure or death. Premature infants and children (<2 yr) have an increased susceptibility to ingested melamine. Due to incomplete reporting, the human data were inadequate to identify a no-observed-adverse-effect level (NOAEL) for melamine-induced pediatric urolithiasis. Urolithiasis, urinary bladder cystitis, and ulcerations were observed in F344 rats after subchronic or chronic ingestion of melamine at > or =72 mg/kg-d. Bladder epithelial damage was followed by epithelial hyperplasia that progressed to bladder papillomas and carcinomas in male but not female F344 rats or male or female B6C3F1 mice. Short-term assays suggest, at best, weak genotoxic activity, and kinetic data show that melamine is not metabolized. Since reliable exposure information was lacking from the clinical reports, an oral reference dose (RfD) based on urolithiasis in male rats after 13 wk of continuous melamine ingestion was calculated as a 10% benchmark dose (38 mg/kg-d). Incorporation of 10-fold interspecies and intraspecies (for the increased susceptibility of infants) uncertainty factors and a threefold database uncertainty factor (for the lack of immunological, neurological and reproduction toxicity data) yields an oral RfD of 0.13 mg/kg-d. Assuming the 70-kg adult consumes 2 L of drinking water daily, a total allowable concentration of 0.9 mg/L (900 microg/L) was calculated for melamine in drinking water.

Acute and Subacute Safety Evaluation of Black Tea Extract (Herbt Tea Essences) in Mice

“…When humans are considered as the consumer of foods or medicines, the reference dose (RfD) is an instructive parameter [36]. Based on safety considerations, the evaluation of RfD is generally first conducted in animals (mainly mice or rats) [37,38]. The results on animals are then extrapolated to humans [39].…”

Selective extraction of melamine using 11-mercaptoundecanoic acid–capped gold nanoparticles followed by capillary electrophoresis

“…If the 70-kg adult consumes 2 L of drinking water daily, the permissible maximum level of melamine in drinking water is 0.9 mg/L [33]. Fig.…”