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. (March 2016)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Food and chemical toxicology. Volume 89(2016)
• Page Start: 138
• Page End: 150
• Publication Date: 2016-03
• Subjects: Apiol -- Safrole -- PBK modelling -- Read-across -- Risk assessment -- Margin of exposure; ADD 4-allyl-3, 6-dimethoxybenzene-1, 2-diol -- BMDL10 the lower confidence limit of the benchmark dose resulting in a 10% extra cancer -- DHA 2′, 3′-di hydroxyapiol -- DMSO dimethyl sulfoxide -- EFSA European Food Safety Authority -- GI gastrointestinal -- HA 1′-hydroxyapiol -- HAG 1′-hydroxyapiol glucuronide -- HAO 1′-oxoapiol -- HES 1′-sulfoxyapiol -- L liver -- MOE Margin of Exposure -- PAPS 3′-phosphoadenosine-5′-phosphosulfate -- PBK physiologically based kinetic -- SC sensitivity coefficient incidence -- TFA trifluoroacetic acid -- UDPGA uridine 5′-diphosphoglucuronic acid -- UPLC ultra-performance liquid chromatography; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2016.01.018
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: 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. Graphical abstract: Highlights: Physiologically-based kinetic (PBK) models for the alkenylbenzene apiol are defined. Risk assessment for apiol is done by PBK-based read-across from safrole. Formation of the 1′-sulfoxy metabolite is 3 times lower for apiol than for safrole. The MOE estimated for apiol indicates a low priority for risk management. PBK modelling can contribute to the development of alternatives for animal testing.