Physiologically based kinetic models for the alkenylbenzene elemicin in rat and human and possible implications for risk assessment.

S.J. van den Berg; A. Punt; A.E.M.F. Soffers; J.J.M. Vervoort; S. Ngeleja; B. Spenkelink; I.M.C.M. Rietjens

doi:10.1021/tx300239z

Physiologically based kinetic models for the alkenylbenzene elemicin in rat and human and possible implications for risk assessment.

S.J. van den Berg, A. Punt, A.E.M.F. Soffers, J.J.M. Vervoort, S. Ngeleja, B. Spenkelink, I.M.C.M. Rietjens

Research output: Contribution to journal › Article › Academic › peer-review

36 Citations (Scopus)

Abstract

The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene elemicin (3,4,5-trimethoxyallylbenzene) in rat and human, based on the PBK models previously developed for the structurally related alkenylbenzenes estragole, methyleugenol, and safrole. Using the newly developed models, the level of metabolic activation of elemicin in rat and human was predicted to obtain insight in species differences in the bioactivation of elemicin and read across to the other methoxy allylbenzenes, estragole and methyleugenol. Results reveal that the differences between rat and human in the formation of the proximate carcinogenic metabolite 1'-hydroxyelemicin and the ultimate carcinogenic metabolite 1'-sulfoxyelemicin are limited (

Original language	English
Pages (from-to)	2352-2367
Journal	Chemical Research in Toxicology
Volume	25
Issue number	11
DOIs	https://doi.org/10.1021/tx300239z
Publication status	Published - 2012

Keywords

unscheduled dna-synthesis
human liver-microsomes
post-labeling analysis
biokinetic pbbk model
in-vivo metabolism
carcinogen 1'-hydroxysafrole
alkenebenzene derivatives
mouse-liver
estragole bioactivation
safrole bioactivation

Access to Document

10.1021/tx300239z

PLANTLIBRA: PLANT food supplements: Levels of Intake, Benefit and Risk Assessment
1/06/10 → 31/05/14
Project: EU research project

Cite this

@article{5c1181b4aa674b89b500ed7e5d565b5c,

title = "Physiologically based kinetic models for the alkenylbenzene elemicin in rat and human and possible implications for risk assessment.",

abstract = "The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene elemicin (3,4,5-trimethoxyallylbenzene) in rat and human, based on the PBK models previously developed for the structurally related alkenylbenzenes estragole, methyleugenol, and safrole. Using the newly developed models, the level of metabolic activation of elemicin in rat and human was predicted to obtain insight in species differences in the bioactivation of elemicin and read across to the other methoxy allylbenzenes, estragole and methyleugenol. Results reveal that the differences between rat and human in the formation of the proximate carcinogenic metabolite 1'-hydroxyelemicin and the ultimate carcinogenic metabolite 1'-sulfoxyelemicin are limited (",

keywords = "unscheduled dna-synthesis, human liver-microsomes, post-labeling analysis, biokinetic pbbk model, in-vivo metabolism, carcinogen 1'-hydroxysafrole, alkenebenzene derivatives, mouse-liver, estragole bioactivation, safrole bioactivation",

author = "{van den Berg}, S.J. and A. Punt and A.E.M.F. Soffers and J.J.M. Vervoort and S. Ngeleja and B. Spenkelink and I.M.C.M. Rietjens",

year = "2012",

doi = "10.1021/tx300239z",

language = "English",

volume = "25",

pages = "2352--2367",

journal = "Chemical Research in Toxicology",

issn = "0893-228X",

publisher = "American Chemical Society",

number = "11",

}

TY - JOUR

T1 - Physiologically based kinetic models for the alkenylbenzene elemicin in rat and human and possible implications for risk assessment.

AU - van den Berg, S.J.

AU - Punt, A.

AU - Soffers, A.E.M.F.

AU - Vervoort, J.J.M.

AU - Ngeleja, S.

AU - Spenkelink, B.

AU - Rietjens, I.M.C.M.

PY - 2012

Y1 - 2012

N2 - The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene elemicin (3,4,5-trimethoxyallylbenzene) in rat and human, based on the PBK models previously developed for the structurally related alkenylbenzenes estragole, methyleugenol, and safrole. Using the newly developed models, the level of metabolic activation of elemicin in rat and human was predicted to obtain insight in species differences in the bioactivation of elemicin and read across to the other methoxy allylbenzenes, estragole and methyleugenol. Results reveal that the differences between rat and human in the formation of the proximate carcinogenic metabolite 1'-hydroxyelemicin and the ultimate carcinogenic metabolite 1'-sulfoxyelemicin are limited (

AB - The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene elemicin (3,4,5-trimethoxyallylbenzene) in rat and human, based on the PBK models previously developed for the structurally related alkenylbenzenes estragole, methyleugenol, and safrole. Using the newly developed models, the level of metabolic activation of elemicin in rat and human was predicted to obtain insight in species differences in the bioactivation of elemicin and read across to the other methoxy allylbenzenes, estragole and methyleugenol. Results reveal that the differences between rat and human in the formation of the proximate carcinogenic metabolite 1'-hydroxyelemicin and the ultimate carcinogenic metabolite 1'-sulfoxyelemicin are limited (

KW - unscheduled dna-synthesis

KW - human liver-microsomes

KW - post-labeling analysis

KW - biokinetic pbbk model

KW - in-vivo metabolism

KW - carcinogen 1'-hydroxysafrole

KW - alkenebenzene derivatives

KW - mouse-liver

KW - estragole bioactivation

KW - safrole bioactivation

U2 - 10.1021/tx300239z

DO - 10.1021/tx300239z

M3 - Article

SN - 0893-228X

VL - 25

SP - 2352

EP - 2367

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

IS - 11

ER -

Physiologically based kinetic models for the alkenylbenzene elemicin in rat and human and possible implications for risk assessment.

Abstract

Keywords

Access to Document

Fingerprint

Projects

PLANTLIBRA: PLANT food supplements: Levels of Intake, Benefit and Risk Assessment

Cite this