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

作者：Alajlouni Abdalmajeed M^*; Al Malahmeh Amer J; Kiwamoto Reiko; Wesseling Sebastiaan; Soffers Ans E M F; Al Subeihi Ala A A; Vervoort Jacques; Rietjens Ivonne M C M

来源：Food and Chemical Toxicology, 2016, 89: 138-150.

DOI：10.1016/j.fct.2016.01.018

• Apiol
• Safrole
• PBK modelling
• Read-across
• Risk assessment
• Margin of exposure

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 (BMDLio) 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 BMDLio value of 3 times the BMDLio for safrole. Based on an estimated BMDLio for apiol of 5.7-15.3 mg/kg body wt per day and an estimated daily intake of 4 x 10(-5) mg/1<g 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.

• 出版日期2016-3