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Beside Fusarium toxins, Alternaria toxins are among the most commonly found mycotoxins in wheat and wheat products. Currently, investigations of possibilities of reduction of Alternaria toxins in the wheat-processing chain are limited. Therefore, the aim of this study was to explore the potency of cold atmospheric plasma treatments, as a new non-thermal approach, for reduction of alternariol (AOH), alternariol monomethyl ether (AME) and tentoxin (TEN) content in spiked white wheat flour samples. Samples were treated with plasma generated in the air during 30 s to 180 s, with an increment step of 30 s, and at four varying distances from the cold plasma source (6 mm, 21 mm, 36 mm and 51 mm). The reduction of the Alternaria toxins content in samples after treatment was monitored by high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The maximum reduction of the examined Alternaria toxins was obtained by treatment performed at 6 mm distance from the plasma source, lasting 180 s, resulting in reductions of 60.6%, 73.8% and 54.5% for AOH, AME and TEN, respectively. According to the obtained experimental results, five empirical models in the form of the second-order polynomials were developed for the prediction of AOH, AME and TEN reduction, as well as the temperature and the moisture content of the wheat flour, that gave a good fit to experimental data and were able to predict the response variables successfully. The developed second-order polynomial models showed high coefficients of determination for prediction of experimental results (between 0.918 and 0.961).