Chemical-specific adjustment factors (inter-species toxicokinetics) to establish the ADI for monosodium glutamate...

The EFSA's use of a default methodology for establishment of a health-based guidance value (HBGV) from a neurobehavioral study resulted in an acceptable daily intake (ADI) for glutamates (E620-625) of 30 mg/kg bw/day which is below the normal dietary glutamate intake, and lower than the intake of free glutamate by breast fed babies. To resolve this dilemma, the present study investigated the interspecies variability in plasma glutamate levels to define a chemical-specific adjustment factor (CSAF) for the interspecies variation in kinetics (AK_AF). Human, mouse and rat plasma glutamate levels available following the administration of MSG in a standard liquid diet (Sustagen) and water were analysed. The normalized Cmax values resulted in a AK_AF value of 1 following administration in food and 1.4 in water in a fasted state. The administration in a food vehicle being the more applicable mode of dietary consumption for MSG. Combining these numbers with the (HK_AF) for interindividual human differences in glutamate kinetics value of 2 and the default factors for interspecies and interindividual differences in dynamics of 2.5 and 3.16, results in an overall CSAF of 16. This CSAF results in a HBGV for glutamate that is no longer below the acceptable range of oral intake.