Dataset Information

Physiologically based kinetic modelling-facilitated reverse dosimetry to predict in vivo red blood cell acetylcholinesterase inhibition following exposure to chlorpyrifos in the Caucasian and Chinese population.

ABSTRACT: Organophosphates (OPs) have a long history of use as insecticides over the world. The aim of the present study was to investigate the interethnic differences in kinetics, biomarker formation and in vivo red blood cell (RBC) acetylcholinesterase (AChE) inhibition of chlorpyrifos (CPF) in the Chinese and the Caucasian population. To this purpose, PBK models for CPF in both the Chinese and Caucasian population were developed, and used to study time- and dose-dependent interethnic variation in urinary biomarkers and to convert concentration-response curves for RBC AChE inhibition to in vivo dose-response curves in these two populations by reverse dosimetry. The results obtained revealed a marked interethnic difference in toxicokinetics of CPF, with lower urinary biomarker levels at similar dose levels and slower CPF bioactivation and faster CPO detoxification in the Chinese compared with the Caucasian population, resulting in 5- to 6-fold higher CPF sensitivity of the Caucasian than the Chinese population. These differences might be related to variation in the frequency of single-nucleotide polymorphisms (SNPs) for the major biotransformation enzymes involved. To conclude, the interethnic variation in kinetics of CPF may affect both its biomarker-based exposure assessment as well as its toxicity and risk assessment and that PBK modelling facilitates the characterisation and quantification of these interethnic variations.

SUBMITTER: Zhao S

PROVIDER: S-EPMC6736452 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Physiologically Based Kinetic Modeling-Facilitated Reverse Dosimetry to Predict In Vivo Red Blood Cell Acetylcholinesterase Inhibition Following Exposure to Chlorpyrifos in the Caucasian and Chinese Population.

Zhao Shensheng S Kamelia Lenny L Boonpawa Rungnapa R Wesseling Sebastiaan S Spenkelink Bert B Rietjens Ivonne M C M IMCM

Toxicological sciences : an official journal of the Society of Toxicology 20190901 1

Organophosphates have a long history of use as insecticides over the world. The aim of the present study was to investigate the interethnic differences in kinetics, biomarker formation, and in vivo red blood cell acetylcholinesterase inhibition of chlorpyrifos (CPF) in the Chinese and the Caucasian population. To this purpose, physiologically based kinetic models for CPF in both the Chinese and Caucasian population were developed, and used to study time- and dose-dependent interethnic variation ...[more]

PMID: 31214721

Similar Datasets

Project description:Human biomonitoring (HBM) data can provide insight into co-exposure patterns resulting from exposure to multiple chemicals from various sources and over time. Therefore, such data are particularly valuable for assessing potential risks from combined exposure to multiple chemicals. One way to interpret HBM data is establishing safe levels in blood or urine, called Biomonitoring Equivalents (BE) or HBM health based guidance values (HBM-HBGV). These can be derived by converting established external reference values, such as tolerable daily intake (TDI) values. HBM-HBGV or BE values are so far agreed only for a very limited number of chemicals. These values can be established using physiologically based kinetic (PBK) modelling, usually requiring substance specific models and the collection of many input parameters which are often not available or difficult to find in the literature. The aim of this study was to investigate the suitability and limitations of generic PBK models in deriving BE values for several compounds with a view to facilitating the use of HBM data in the assessment of chemical mixtures at a screening level. The focus was on testing the methodology with two generic models, the IndusChemFate tool and High-Throughput Toxicokinetics package, for two different classes of compounds, phenols and phthalates. HBM data on Danish children and on Norwegian mothers and children were used to evaluate the quality of the predictions and to illustrate, by means of a case study, the overall approach of applying PBK models to chemical classes with HBM data in the context of chemical mixture risk assessment. Application of PBK models provides a better understanding and interpretation of HBM data. However, the study shows that establishing safety threshold levels in urine is a difficult and complex task. The approach might be more straightforward for more persistent chemicals that are analysed as parent compounds in blood but high uncertainties have to be considered around simulated metabolite concentrations in urine. Refining the models may reduce these uncertainties and improve predictions. Based on the experience gained with this study, the performance of the models for other chemicals could be investigated, to improve the accuracy of the simulations.

Dataset Information

Physiologically based kinetic modelling-facilitated reverse dosimetry to predict in vivo red blood cell acetylcholinesterase inhibition following exposure to chlorpyrifos in the Caucasian and Chinese population.

Publications

Physiologically Based Kinetic Modeling-Facilitated Reverse Dosimetry to Predict In Vivo Red Blood Cell Acetylcholinesterase Inhibition Following Exposure to Chlorpyrifos in the Caucasian and Chinese Population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets