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.
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.
authors.affiliation: Aqaba International Laboratories/BENHAYYAN, ASEZA, Aqaba 77110, Jordan; Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands. Electronic address: abdul.alajlouni@wur.nl.
authors.forename: Abdalmajeed M
authors.initials: AM
authors.lastname: Alajlouni
authors.affiliation: Aqaba International Laboratories/BENHAYYAN, ASEZA, Aqaba 77110, Jordan; Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands.
authors.forename: Amer J
authors.initials: AJ
authors.lastname: Al Malahmeh
authors.affiliation: Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kiwamoto
authors.affiliation: Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Wesseling
authors.affiliation: Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands.
authors.forename: Ans E M F
authors.initials: AE
authors.lastname: Soffers
authors.affiliation: Philadelphia University, Faculty of Pharmacy, P.O. Box 1, Amman 19392, Jordan.
authors.forename: Ala A A
authors.initials: AA
authors.lastname: Al-Subeihi
authors.affiliation: Department of Biochemistry, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen, The Netherlands.
authors.forename: Jacques
authors.initials: J
authors.lastname: Vervoort
authors.affiliation: Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands.
authors.forename: Ivonne M C M
authors.initials: IM
authors.lastname: Rietjens
mesh_terms: D065767:Activation, Metabolic; D000818:Animals; D004149:Dioxoles / Q000633:toxicity*; D005506:Food Contamination; D006801:Humans; D007700:Kinetics; D008962:Models, Theoretical; D028528:Petroselinum; D051381:Rats; D012451:Safrole / Q000493:pharmacokinetics*; D000081248:Allylbenzene Derivatives
chemical_list: D004149:Dioxoles; D012451:Safrole; C446539:apiole; D000081248:Allylbenzene Derivatives
keywords: Apiol; Margin of exposure; PBK modelling; Read-across; Risk assessment; Safrole