Roxarsone (ROX) remains to be as an organoarsenical feed additive used widely in developing countries. However, most of the ROX is excreted unchanged in manure, which could be readily photodegraded into inorganic arsenic derivatives. In this study, the comparative cytotoxicity and arsenic accumulation were evaluated after the exposure of Tetrahymena thermophila (T. thermophila) cell model to ROX and its photodegradates. The cytotoxic effects were estimated according to the relevant cell growth curves, morphologies and MTT assays. The 36 h median effective concentrations for ROX and its photodegradates at various photolysis times (10, 20, and 30 min) are 39.0, 2.08, 1.88, and 1.82 mg (total arsenic) L-1, respectively. In parallel, the cellular arsenic uptakes were determined by hydride generation-atomic fluorescence spectrometry. Phospholipid layer as basic membrane structure was mimicked to assess the correlation between membrane permeability and cytotoxicity. The biocompatibility of ROX was dependent on its tendency to interact with cell membrane while the cytotoxicity was induced by the trans-membrane of the inorganic arsenic species present in the photodegradates of ROX. Furthermore, the photodegradates of ROX-associated alterations of intracellular protein profiles were analyzed using a proteomic approach. Overall, the significance was clarified that the control of arsenic emission caused by the application of ROX needs to be imposed. (C) 2015 Elsevier B.V. All rights reserved.