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A chemical-specific adjustment factor for human interindividual differences in kinetics for glutamates (E620-625)
Ivonne McM Rietjens1, Takayuki Tanaka2, Yoko Masuzawa3
1Division of Toxicology, Wageningen University, Stippeneng 4, 6708, WE, Wageningen, the Netherlands.
Summary
A new chemical-specific adjustment factor (CSAF) for glutamates (E620-625) was developed to address health-based guidance values (HBGVs) that were too low. This factor ensures HBGVs align with normal dietary intake levels.
Area of Science:
- Toxicology
- Pharmacokinetics
- Nutritional Science
Background:
- Default methods for establishing health-based guidance values (HBGVs) for glutamates (E620-625) yielded an acceptable daily intake (ADI) below typical dietary consumption.
- This ADI was also lower than the free glutamate intake observed in breastfed infants, indicating a potential issue with the default methodology.
Purpose of the Study:
- To investigate interindividual human variability in plasma and brain glutamate levels.
- To define a chemical-specific adjustment factor (CSAF) for interindividual variation in glutamate kinetics (HKAF).
Main Methods:
- Collected and analyzed human clinical data on plasma glutamate levels from Mitsui Memorial Hospital.
- Utilized literature data on plasma and brain glutamate levels for comprehensive analysis.
- Calculated median HKAF values for both plasma and brain-derived glutamate levels.
Main Results:
- Median HKAF values were 2.62-2.74 and 2.33-2.52 for plasma, and 1.68-1.81 for brain-derived values.
- Combined HKAF with existing CSAFs for interspecies kinetics and dynamics factors (2.5 and 3.16).
- Derived an overall CSAF for glutamates ranging from 16 to 20.
Conclusions:
- The application of the derived CSAF ensures that the resulting HBGV for glutamate is within the acceptable range of oral intake (AROI).
- This approach rectifies the issue of HBGVs being set below normal dietary intake levels for glutamates.
- The study provides a more accurate and relevant HBGV for glutamates by accounting for human kinetic variability.
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