Identification of mutagenic transformation products generated during oxidation of 3-methyl-4-nitrophenol solutions by orbitrap tandem mass spectrometry and quantitative structure–activity relationship analyses

Abstract

We used Ames assays to investigate the effects of ozonation (designated O), ozonation followed by chlorination (O/Cl), an advanced oxidation process (AOP, UV/HO), and AOP followed by chlorination (AOP/Cl) on the mutagenicity of solutions of 3-methyl-4-nitrophenol (3M4NP), a major environmental degradation product of the organophosphorus insecticide fenitrothion. Whereas O did not induce mutagenicity, O/Cl, AOP, and AOP/Cl converted 3M4NP into mutagenic transformation products (TPs). Using liquid chromatography-mass spectrometry, we detected a total of 138 peaks in the solutions subjected to O/Cl, AOP, and AOP/Cl. To elucidate the TPs responsible for the observed mutagenicity, we performed simple regression analyses of the relationship between the area of each peak and the observed mutagenicity of samples withdrawn periodically during each oxidation process. The area of each of 10 peaks was found to be positively correlated (r ≥ 0.8) with the observed mutagenicity, suggesting that the TPs corresponding to these peaks contributed to the mutagenicity. After taking into account the consistency of mutagenicity induction by the oxidation processes and analyzing the peaks by tandem mass spectrometry, we identified 3 TPs, corresponding to 6 peaks, as candidate mutagens. These TPs were assessed by means of 4 quantitative structure-activity relationship (QSAR) models, and all 3 were predicted to be mutagenic by at least one model. This result was consistent with our assumption that these TPs were mutagens. Ames assays of an authentic sample of one of the 3 TPs revealed that it did not contribute to the mutagenicity. This left 3-methoxy-4-nitrophenol and 2-[(E)-[(2,5-dihydroxyphenyl) methylidene]amino]-5-dihydroxybenzaldehyde on the list of mutagens suspected of contributing to the mutagenicity induced by AOP. No TPs were identified as candidate mutagens responsible for the mutagenicity induced by O/Cl and AOP/Cl.

Advanced Oxidation Processes for the Removal of Antibiotics from Water. An Overview

“…However, it is not infrequent that the oxidation leads to different byproducts that may have similar-or even higher-toxicity than the original pollutants themselves. Changes in the molecular structure of the pollutant may give rise to an entirely new kind of chemical toxicity or even to mutagenic [228] or estrogenic activity [229]. For instance, during ozonation, the bromide naturally occurring in wastewater can be oxidized to bromate [230], with increasing yields as ozone dose rises [231].…”

In silico environmental risk assessment of fate and effects of pharmaceuticals and their TPs generated and treated by coupling tertiary processes in hospital wastewater

“…Therefore, a better approach would be to evaluate the toxicological effects individually (for each TP), using in silico prediction models that avoid any need for TP analytical standards and enable rapid prediction of different endpoints for each TP. [18][19][20] In silico (quantitative) structure-activity relationship ((Q) SAR) prediction models are mathematical models that describe the relationship between molecular structures and their related properties, comparing the chemical structure of each studied compound with those of compounds included in databases that present results for endpoints with a high degree of certainty. 21 These in silico models offer easy applicability for the prediction of only one endpoint, such as biodegradability, 22 or a range of endpoints, such as toxicity towards different organisms, physicochemical parameters, carcinogenicity, and mutagenicity.…”

“…16,17 However, it is very difficult to evaluate the toxicities of the TPs in vitro due to the lack of analytical standards and, often, the presence of “mixtures” of TPs. 18 After an advanced treatment process, an ecotoxicity assessment of a mixture may indicate that the final mixture is less toxic than the initial mixture, giving a general indication of decreased effluent toxicity. This can sometimes lead to an incorrect conclusion since the concentrations of the chemical compounds, especially the initial compounds, have only been reduced or transformed by the treatment.…”

“…Therefore, a better approach would be to evaluate the toxicological effects individually (for each TP), using in silico prediction models that avoid any need for TP analytical standards and enable rapid prediction of different endpoints for each TP. 18–20…”

A Demonstration of Mass-spectrometric Exploration of Organic Ecotoxicants from Simulated Sewage-treatment-plant Effluents

“…Hogenboom et al [21] evaluated the toxicity of the leachates from polluted landfill soils with a zebrafish embryo toxicity test, and identified two causative ecotoxicants by a non-targeted mass spectrometric analysis with a LC-ESI-Orbitrap MS. In other reports [22][23][24][25][26][27][28][29][30][31], these inventions help us explore, elucidate or identify unknowns in water samples. Unfortunately, a large number of components are generally detected in STP effluents when analyses are conducted by a non-targeted mass spectrometric analysis by the nature of a precursor ion analysis (so-called a full scan).…”