Abass, K., Reponen, P., Alsanie, W. F., Rautio, A., & Pelkonen, O. (2022). Metabolic profiling and in vitro-in vivo extrapolation of furathiocarb in mammalian hepatic microsomes. Toxicology Reports, 9, 750–758. https://doi.org/10.1016/j.toxrep.2022.03.030
Metabolic profiling and in vitro-in vivo extrapolation of furathiocarb in mammalian hepatic microsomes
|Author:||Abass, Khaled1,2,3; Reponen, Petri2; Alsanie, Walaa F.4;|
1Arctic Health, Faculty of Medicine, University of Oulu, P.O. Box 7300, FI-90014, Finland
2Pharmacology and Toxicology Unit, Research Unit of Biomedicine, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland
3Department of Pesticides, Menoufia University, P.O. Box 32511, Egypt
4Department of Clinical Laboratory Sciences, The Faculty of Applied Medical Sciences & Centre of Biomedical Sciences Research (CBSR), Taif University, Saudi Arabia
5Thule Institute, University of the Arctic, FI-90014 Oulu, Finland
|Online Access:||PDF Full Text (PDF, 3.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022101161611
|Publish Date:|| 2022-10-11
Furathiocarb is a carbamate insecticide found in marine ecosystems as well as river water and sediments. The aim of this study was to characterize species differences in the in vitro metabolism of furathiocarb in seven mammalian species (human, monkey, minipig, rat, mouse, dog, rabbit) analyzed by LC-TOF-MS/MS, in order to provide qualitative and quantitative chemical-specific data to enhance toxicological risk assessment. Furathiocarb was mainly biotransformed to carbofuran metabolic pathway via (N-S) bond-cleavage. Two hydroxylated and sulfoxidated metabolites of furathiocarb were also detected (oxidation pathway). No unique human metabolites were detected. The carbofuran metabolic pathway was more predominant than the furathiocarb oxidation pathway in all species studied; differences based on hepatic clearance rates (CLH), were up to 9.4-fold in monkey and 7-fold in rats, while it was 4.3-fold in human. Animal to human differences in the carbofuran pathway are within the default toxicokinetic uncertainty factor, except for mouse (3.9-fold). Our findings on metabolic profiling and in vitro-in vivo extrapolations are helpful for the interpretation of toxicological findings and chemical risk assessment of furathiocarb.
|Pages:||750 - 758|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This research was supported by the European Union's Horizon 2020 program EDCMET (grant number 825762). Walaa F. Alsanie would like to acknowledge Taif University for support No. TURSP (2020/53).
|EU Grant Number:||
(825762) EDCMET - Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways
Supplementary data associated with this article can be found in the online version at doi:10.1016/j.toxrep.2022.03.030.
© 2022 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).