|Title||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|
|Author(s)||Alajlouni, A.M.; Al-Malahmeh, A.J.; Kiwamoto, Reiko; Wesseling, Sebastiaan; Soffers, A.E.M.F.; Al-Subeihi, A.A.A.; Vervoort, Jacques; Rietjens, I.M.C.M.|
|Source||Food and Chemical Toxicology 89 (2016). - ISSN 0278-6915 - p. 138 - 150.|
Sub-department of Toxicology
|Publication type||Refereed Article in a scientific journal|
|Keyword(s)||Apiol - Margin of exposure - PBK modelling - Read-across - Risk assessment - Safrole|
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.