Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole
| Autor: | Reiko Kiwamoto, Amer J. Al_Malahmeh, Jacques Vervoort, Sebastiaan Wesseling, Ivonne M.C.M. Rietjens, Abdalmajeed M. Alajlouni, Ala′ A.A. Al-Subeihi, Ans E. M. F. Soffers |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Metabolite Biochemie Food Contamination Dioxoles Toxicology Biochemistry Activation Metabolic 03 medical and health sciences chemistry.chemical_compound Safrole Animals Humans Apiol Food science Mode of action Toxicologie VLAG Risk assessment Chemistry General Medicine Models Theoretical Margin of exposure Tumor formation Rats Kinetics PBK modelling 030104 developmental biology Food borne Read-across Petroselinum Food Science |
| Zdroj: | Food and Chemical Toxicology 89 (2016) Food and Chemical Toxicology, 89, 138-150 |
| ISSN: | 0278-6915 |
| Popis: | The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1′-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7–15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10−5 mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000–385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable. |
| Databáze: | OpenAIRE |
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