Chemometric QSAR modeling of acute oral toxicity of Polycyclic Aromatic Hydrocarbons (PAHs) to rat using simple 2D descriptors and interspecies toxicity modeling with mouse

Ecotoxicology and Environmental Safety

Rugang Zhong¹  Yifan Zhang¹  Feifan Li²  Zhaoqi Hao²  Na Zhang²  Guohui Sun²  Yongzhen Peng²  Yao Mu²  Yuqing Lou²  Sha Xi²  Chuhan Chen²  Yachen Wang²  Jiayi Yun²  Luyu Pei²  Chen Li²  Lijiao Zhao² 

[1] Corresponding authors.;Beijing Key Laboratory of Environmental and Viral Oncology, College of Life Science and Chemistry, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, PR China;

关键词: PAHs;    Acute oral toxicity;    QSAR;    Interspecies toxicity model;    Toxicity prediction;   

DOI  :  

来源: DOAJ

【 摘 要 】

The information of the acute oral toxicity for most polycyclic aromatic hydrocarbons (PAHs) in mammals are lacking due to limited experimental resources, leading to a need to develop reliable in silico methods to evaluate the toxicity endpoint. In this study, we developed the quantitative structure-activity relationship (QSAR) models by genetic algorithm (GA) and multiple linear regression (MLR) for the rat acute oral toxicity (LD50) of PAHs following the strict validation principles of QSAR modeling recommended by OECD. The best QSAR model comprised eight simple 2D descriptors with definite physicochemical meaning, which showed that maximum atom-type electrotopological state, van der Waals surface area, mean atomic van der Waals volume, and total number of bonds are main influencing factors for the toxicity endpoint. A true external set (554 compounds) without rat acute oral toxicity values, and 22 limit test compounds, were firstly predicted along with reliability assessment. We also compared our proposed model with the OPERA predictions and recently published literature to prove the prediction reliability. Furthermore, the interspecies toxicity (iST) models of PAHs between rat and mouse were also established, validated and employed for filling data gap. Overall, our developed models should be applicable to new or untested or not yet synthesized PAHs falling within the applicability domain (AD) of the models for rapid acute oral toxicity prediction, thus being important for environmental or personal exposure risk assessment under regulatory frameworks.

【 授权许可】

Unknown