Identification of a novel HLA-A24-restricted cytotoxic T lymphocyte epitope peptide derived from mesothelin in pancreatic cancer Identification of a novel HLA-A24-restricted cytotoxic T lymphocyte epitope peptide derived from mesothelin in pancreatic cancer

This letter is to comment on the study of Nahok, K. et al.

Previously a chemical-specific adjustment factor (CSAF) for human interindividual variation in kinetics (HK_AF) was defined for glutamates (E620-625) based on steady-state human plasma and brain glutamate levels. The present study defines this HK_AF based on kinetic data upon oral intake of monosodium glutamate (MSG) by human individuals in the absence or presence of food. Data on maximum plasma glutamate levels (C_max) following oral intake of MSG were obtained from literature. The median HK_AF values obtained amounted for the 95th, 97.5th and 99th percentile to 1.86, 1.98 and 2.13 for MSG exposure without food and to 1.86, 2.00 and 2.15 with food when assuming normal distributions for the Monte Carlo simulations and excluding studies with SE > 20 % of the mean. Assuming lognormal distributions the values amounted to 1.97, 2.29 and 2.65 without food and to 1.92, 2.21 and 2.54 with food. Corresponding average HK_AF values weighted for the number of study subjects were comparable. These values are in line with the HK_AF values previously obtained under steady-state conditions for plasma and brain-related data, and together point at an HK_AF for interindividual differences in kinetics of 2 to be used when deriving an acceptable daily intake (ADI) for glutamates.

The commonly used flavor enhancer monosodium glutamate (MSG) has been part of the human diet for many years and has undergone safety evaluation by several international scientific committees and regulatory agencies. Numerous studies exist on MSG but many of these studies are not consistent or representative of how humans are exposed to MSG (i.e., ingestion of food). Two GLP-compliant dietary rodent studies were summarized in evaluations performed by EFSA (2017) and JECFA (2022) but were never published. In the first study, groups of Sprague-Dawley rats (10 rats/sex/group) were fed diets containing 0 ppm (basal diet) or 50,000 ppm MSG for 29 days. In the second study, groups of Sprague-Dawley rats (20 rats/sex/group) were fed diets containing 0 (basal diet), 0.5, 1.5, or 5 % (w/w) MSG for 92-96 days. Animals in both studies underwent clinical examinations, hematology and biochemistry tests, full necropsies, and histopathological examination. No toxicologically significant findings were reported in either study. In the 28-day study, there were no adverse effects observed at 5100 mg/kg bw/day (males) and 4800 mg/kg bw/day (females). In the 90-day study, a no-observed-adverse-effect level (NOAEL) was identified as the highest dose tested of 3170 mg/kg bw/day (males) and 3620 mg/kg bw/day (females) or more.

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