Designing QSARs for Parameters of High-Throughput Toxicokinetic Models Using Open-Source Descriptors

The intrinsic metabolic clearance rate (Clint) and the fraction of the chemical unbound in plasma (f up) serve as important parameters for high-throughput toxicokinetic (TK) models, but experimental data are limited for many chemicals. Open-source quantitative structure–activity relationship (QSAR)...

Full description

Saved in:
Bibliographic Details
Published in:Environmental science & technology 2021-05, Vol.55 (9), p.6505-6517
Main Authors: Dawson, Daniel E, Ingle, Brandall L, Phillips, Katherine A, Nichols, John W, Wambaugh, John F, Tornero-Velez, Rogelio
Format: Article
Language:English
Subjects:
Biological activity
Chemicals
Computer Simulation
Data Science
Exposure
Mathematical models
Models, Biological
Parameters
Pesticides
Quantitative Structure-Activity Relationship
Structure-activity relationships
Toxicokinetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The intrinsic metabolic clearance rate (Clint) and the fraction of the chemical unbound in plasma (f up) serve as important parameters for high-throughput toxicokinetic (TK) models, but experimental data are limited for many chemicals. Open-source quantitative structure–activity relationship (QSAR) models for both parameters were developed to offer reliable in silico predictions for a diverse set of chemicals regulated under the U.S. law, including pharmaceuticals, pesticides, and industrial chemicals. As a case study to demonstrate their utility, model predictions served as inputs to the TK component of a risk-based prioritization approach based on bioactivity/exposure ratios (BERs), in which a BER < 1 indicates that exposures are predicted to exceed a biological activity threshold. When applied to a subset of the Tox21 screening library (6484 chemicals), we found that the proportion of chemicals with BER
ISSN:0013-936X
1520-5851
DOI:10.1021/acs.est.0c06117