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Published on: August 28, 2019
Quantification, cytotoxicity, and QSAR modeling of an emerging class of aromatic chlorobenzenediol DBPs in drinking
Wenshan Shi1, Xiaochen Liu2, Xinyi Weng2
1School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, Suzhou 215123, China; Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Abstract:
Chlorobenzenediols are a class of emerging aromatic disinfection byproducts (DBPs) that were identified in chlor(am)inated drinking water and exhibit great developmental toxicity. However, data on their cytotoxicity are lacking. This study updated their quantitative method, cytotoxicity, and quantitative structure-activity relationship (QSAR) modeling. The limits of quantification (LOQs) for chlorobenzenediols were 0.1-1 ng/L, which are 10-100 times lower than previously reported values (1-50 ng/L), enabling the quantification of chlorobenzenediols at trace levels. The LC50 values of the 15 chlorobenzenediols for CHO cells ranged from 6.1 to 1742.0 μM, with a median value of 19.0 μM, suggesting that their overall cytotoxicity was lower than that of chloroketones (median: 6.6 μM), but was higher than chloroacetaldehydes (median: 29.2 μM), chlorobenzoquinones (median: 31.1 μM), chloronitrophenols (median: 67.3 μM), chloroacetonitriles (median: 68.3 μM), chlorophenols (median: 244 μM), chloronitromethanes (median: 529 μM), chlorohydroxybenzonitriles (mean: 558 μM), chlorohydroxybenzoic acids (median: 447 μM), chloroacetamides (median: 1920 μM), chloroacetic acids (median: 2400 μM), and trichloromethane (9620 μM). 2,5-Dichlorobenzene-1,4-diol and 2‑chloro-1,4-benzenediol were the key drivers in drinking water leveraging the TIC-Tox method. The QSAR model revealed that the cytotoxicity of chlorobenzenediols was closely related to molecular parameters, especially EHOMO. The cytotoxicity of chlorobenzenediols is enhanced when hydroxyl group is substituted at the 2‑ or 4‑position of the benzene ring, but is reduced when a chlorine atom is located at the 2‑position. Although chlorobenzenediols are a class of highly cytotoxic aromatic DBPs compared to other DBPs, this study found their actual concentrations in drinking water to be orders of magnitude lower than their LC50 values (typically by a factor of 106 to 109), indicating a low probability of significant short-term health risks to the population.
