1. Pharmacokinetic data reduce uncertainty in the acceptable daily intake for benzoic acid and its salts.
- Author
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Zu K, Pizzurro DM, Lewandowski TA, and Goodman JE
- Subjects
- Animals, Humans, No-Observed-Adverse-Effect Level, Rats, Recommended Dietary Allowances, Risk Assessment, Salts administration & dosage, Salts pharmacokinetics, Species Specificity, Uncertainty, Benzoic Acid administration & dosage, Benzoic Acid pharmacokinetics, Food Additives administration & dosage, Food Additives pharmacokinetics
- Abstract
The current acceptable daily intake (ADI) for benzoic acid and its salts as food additives is 0-5 mg/kg body weight. This accounts for a total uncertainty factor (UF) of 100, which includes a default factor of 10 for interspecies differences. Based on pharmacokinetic data in rodents and humans, we derived a chemical-specific adjustment factor (CSAF) of 2 for the pharmacokinetic component of the interspecies UF. Additional analyses indicate that this CSAF is conservative and interspecies differences between rats and humans are likely closer to unity. Human clinical studies indicate that the pharmacokinetics of benzoic acid and its salts are similar in children and adults, and that there is a lack of adverse events in humans at doses comparable to the no observed adverse effect level (NOAEL) in rodents; this suggests that the pharmacokinetic UF for intraspecies variability, as well as the pharmacodynamic components of the UFs, may also be reduced, although we did not calculate to what degree. In conclusion, the total UF can be reduced to 50 (2 for interspecies differences in pharmacokinetics, 2.5 for interspecies differences in pharmacodynamics, and 10 for intraspecies variability), which would increase the ADI to 0-10 mg/kg body weight., (Copyright © 2017 Gradient. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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