Utilizing High-Throughput Screening Data, Integrative Toxicological Prioritization Index Score, and Exposure–Activity Ratios for Chemical Prioritization: A Case Study of Endocrine-Active Pesticides in Food Crops

Abstract

Endocrine-active chemicals can directly act on nuclear receptors and trigger the disturbances of metabolism and a homeostatic system, which are important risk factors for complicating chronic diseases in humans. The endocrine-active potentials of pesticides acting on estrogen, androgen, and thyroid hormone receptors have been extensively evaluated for pesticides; however, the effects on other receptors are less understood. This study aims to comprehensively characterize and prioritize the endocrine-active pesticides using an exposure–activity ratio (EAR) method and toxicological prioritization index (ToxPi). The aggregate exposure assessment of pesticides was performed using a computational exposure model [stochastic human exposure and dose simulation high-throughput model (SHEDS-HT)]. Minimum in vitro point of departure values were converted to human oral equivalent doses via in vitro-to-in vivo extrapolation. The overall endocrine-disrupting potentials of pesticides were evaluated via 76 assays, representing 11 nuclear receptors. EARs and ToxPi scores were then derived to prioritize 79 pesticides in food. This case study demonstrates that EAR profiling can inform the regulatory agencies for a relevant chemical prioritization, which would direct in-depth health risk assessments in the future.

Toxicity Prediction: An Application of Alternative Testing and Computational Toxicology in Contaminated Groundwater Sites in Taiwan

“…Therefore, this combined approach was performed in the current study to predict the groundwater sites that require immediate attention in a petrochemical district in Yunlin, Taiwan by integrating the chemical concentration and in vitro toxicity data of groundwater samples via the ToxPi tool. Currently, ToxPi is mostly applied for chemical prioritization using data available from libraries or databases (Chen et al, 2020;Danforth et al, 2020;Reif et al, 2010;Tilley et al, 2017) and for prioritizing of pollutants or contaminants in the environment (Danforth et al, 2020;Rogers et al, 2021;Tilley et al, 2017) and in food (dos Santos and Nardocci, 2019;Luo and Wu, 2021). Meanwhile, its use for the identification and prioritization of real environmental samples like the groundwater samples in the current study has emerged recently (Chen et al, 2021a(Chen et al, , 2021b.…”

Identification and Prioritization of Organic Pollutants in Human Milk from the Yangtze River Delta, China

“…The DFs of the compounds were also used to calculate the ToxPi scores. For PAHs and derivatives without in vitro ToxCast data, chemical read-across was performed using the OECD QSAR Toolbox (version 4.6) to fill in the data gaps (Text S3).…”

Editorial: Endocrine-active substances in food: identification, evaluation, and control

“…Diet is crucial in maintaining life, yet harmful substances can enter the human body via dietary exposure. Humans can be exposed to harmful substances indirectly from food contact materials [e.g., di(2-ethylhexyl)phthalate, DEHP] or directly from food [e.g., pesticides ( 1 , 2 ), soybean, and ultra-processed food]. Chronic exposure to these substances may lead to the development of chronic diseases; endocrine disruption is an early molecular event that plays an essential role in disease progression ( 3 ).…”