A chemical-specific adjustment factor for human interindividual differences in kinetics for glutamates (E620-625)

Food Chem Toxicol. 2021 Jan:147:111910. doi: 10.1016/j.fct.2020.111910. Epub 2020 Dec 10.

Abstract

Use of a default methodology for establishment of a health-based guidance value (HBGV) resulted in a group acceptable daily intake (ADI) for glutamates (E620-625) below the normal dietary glutamate intake, and also lower than the intake of free glutamate by breast fed babies. Use of a chemical-specific adjustment factor (CSAF) may overcome this problem. The present study investigates the interindividual human variability in glutamate plasma and brain levels in order to define a CSAF for the interindividual variation in kinetics, a HKAF, for glutamates. Human clinical data on plasma glutamate levels available from different groups of subjects at Mitsui Memorial Hospital as well as literature data on plasma and brain-related glutamate levels were collected and analysed. The median HKAF value obtained amounted to 2.62-2.74 to 2.33-2.52 for plasma derived values and to 1.68-1.81 for brain derived values. Combining these values with the CSAF for the interspecies differences in kinetics of 1 and the default factors for interspecies and interindividual differences in dynamics of 2.5 and 3.16 results in an overall CSAF of 16-20. Using this CSAF will result in a HBGV for glutamate that is no longer below the acceptable range of oral intake (AROI).

Keywords: CSAF for Interindividual variation in kinetics (HK(AF)); Chemical-specific adjustment factor (CSAF); Glutamate; Interindividual differences; Kinetics.

MeSH terms

  • Dose-Response Relationship, Drug
  • Food Additives
  • Glutamates / administration & dosage
  • Glutamates / metabolism
  • Glutamates / pharmacokinetics*
  • Guidelines as Topic
  • Humans
  • Kinetics
  • Models, Biological*
  • No-Observed-Adverse-Effect Level
  • Safety Management / standards

Substances

  • Food Additives
  • Glutamates