TY - JOUR
T1 - Development of physiologically based toxicokinetic models for 3-monochloropropane-1,2-diol and glycidol
AU - Jia, Wei
AU - Jiang, Jiahao
AU - Ke, Xing
AU - Zhang, Lange
AU - Li, Yaoran
AU - Wan, Xuzhi
AU - Jiao, Jingjing
AU - Zhang, Yu
N1 - Funding information:
This work was financially supported by the Zhejiang Provincial Natural Science Foundation of China (Grant No. LZ20C200001) and the National Key Research and Development Program of China (Grant No. 2017YFC1600500).
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2023/2
Y1 - 2023/2
N2 - 3-Monochloropropane-1,2-diol (3-MCPD), glycidol, together with their fatty acid esters are commonly presented in various food and have shown carcinogenicity in various laboratory animals. Public health risk assessment of 3-MPCD and glycidol exposure relies on quantitative tools that represent their in vivo toxicokinetics. In order to better understand the absorption, distribution, metabolism, and excretion profiles of 3-MCPD and glycidol in male rats, a physiologically based pharmacokinetic (PBTK) model was developed. The model's predictive power was evaluated by comparing in silico simulations to in vivo time course data obtained from experimental studies. Results indicate that our PBTK model successfully captured the toxicokinetics of both free chemicals in key organs, and their metabolites in accessible biological fluids. With the validated PBTK model, we then gave an animal-free example on how to extrapolate the toxicological knowledge acquired from a single gavage to a realistic dietary intake scenario. Three biomarkers, free compound in serum, urinary metabolite DHPMA, and glycidol-hemoglobin adduct (diHOPrVal) were selected for in silico simulation following constant dietary intakes, and their internal levels were correlated with proposed external daily exposure via reverse dosimetry approaches. Taken together, our model provides a computational approach for extrapolating animal toxicokinetic experiments to biomonitoring measurement and risk assessment.
AB - 3-Monochloropropane-1,2-diol (3-MCPD), glycidol, together with their fatty acid esters are commonly presented in various food and have shown carcinogenicity in various laboratory animals. Public health risk assessment of 3-MPCD and glycidol exposure relies on quantitative tools that represent their in vivo toxicokinetics. In order to better understand the absorption, distribution, metabolism, and excretion profiles of 3-MCPD and glycidol in male rats, a physiologically based pharmacokinetic (PBTK) model was developed. The model's predictive power was evaluated by comparing in silico simulations to in vivo time course data obtained from experimental studies. Results indicate that our PBTK model successfully captured the toxicokinetics of both free chemicals in key organs, and their metabolites in accessible biological fluids. With the validated PBTK model, we then gave an animal-free example on how to extrapolate the toxicological knowledge acquired from a single gavage to a realistic dietary intake scenario. Three biomarkers, free compound in serum, urinary metabolite DHPMA, and glycidol-hemoglobin adduct (diHOPrVal) were selected for in silico simulation following constant dietary intakes, and their internal levels were correlated with proposed external daily exposure via reverse dosimetry approaches. Taken together, our model provides a computational approach for extrapolating animal toxicokinetic experiments to biomonitoring measurement and risk assessment.
KW - 3-monochloropropane-1,2-diol
KW - Biomarker
KW - Glycidol
KW - Physiologically based toxicokinetic model
KW - Risk assessment
UR - http://www.scopus.com/inward/record.url?scp=85144254634&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2022.113555
DO - 10.1016/j.fct.2022.113555
M3 - Journal article
C2 - 36493944
AN - SCOPUS:85144254634
SN - 0278-6915
VL - 172
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
M1 - 113555
ER -