Pharmacokinetic data reduce uncertainty in the acceptable daily intake for benzoic acid and its salts
| Autor: | Ke Zu, J.E. Goodman, T.A. Lewandowski, D.M. Pizzurro |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Acceptable daily intake No-observed-adverse-effect level Pharmacology Toxicology Recommended Dietary Allowances Risk Assessment 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Species Specificity Animals Humans Adverse effect Benzoic acid Potassium benzoate No-Observed-Adverse-Effect Level Chemistry Uncertainty General Medicine Benzoic Acid Rats 030104 developmental biology Pharmacodynamics Sodium benzoate Food Additives Salts 030217 neurology & neurosurgery |
| Zdroj: | Regulatory toxicology and pharmacology : RTP. 89 |
| ISSN: | 1096-0295 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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