###### Abstract  
Ozonation has been promoted as a successful methodology for recovering effluents from wastewater treatment plants, with special emphasis on wastewater contaminated with pharmaceutical and personal care products (PPCPs). Still, ozonation reactions may generate potentially toxic by-products, jeopardizing human health safety, a critical aspect considering the use of reclaimed water. We aimed at understanding the potential impacts of ozonation on the quality of reclaimed water for human use through cell viability assays with human skin keratinocytes (HaCaT cell line). Under this context, the cytotoxicity of synthetic effluents contaminated with methyl- and propylparaben, paracetamol, sulfamethoxazole, and carbamazepine, both individually and in mixtures, was assessed before and after ozonation. The viability of HaCaT cells decreased after exposure to untreated synthetic effluents, denoting the cytotoxicity of the tested PPCPs singly and more prominently in mixtures (especially in those combining two and three PPCPs). A similar pattern was observed when testing effluents treated with ozonation. Since the parent contaminants were fully removed during ozonation, the observed cytotoxicity relates to degradation by-products and interactive effects among them. This study suggests that ozonation is poorly efficient in reducing cytotoxicity, as required for the safe use of ozone-treated reclaimed water in activities involving direct contact with human skin. wastewater treatment; wastewater reuse; human health safety; HaCaT; cytotoxicity; parapabens; pharmaceuticals 2020  
life, and it is beginning to be considered an important component of water supply, e.g., in the irrigation of agricultural production [4] or even for human consumption mostly in recreational activities [5]. However, even after treatment, wastewaters can contain a wide variety of contaminants, usually at low concentrations, which include pharmaceutical and personal care products (PPCPs), among others [6]. This is because conventional wastewater treatment plants (WWTPs) are generally not designed to eliminate PPCPs, allowing them to easily reach surface waters through the treated effluent discharge [7], which has been largely confirmed by analytical surveys in such effluents (e.g., [8; 9]). Besides not being degraded during wastewater treatment, PPCPs are also hardly degraded naturally (e.g., [10]), raising concerns about PPCPs persistence in the aquatic compartment. In the environment, PPCPs are found in mixtures rather than individually [11; 12]. Although individual PPCPs may be present at low levels in the environment that would not have detrimental effects if acting alone, their mixture can entail interactions that may induce negative effects in exposed biological targets. The presence of these PPCPs in different water sources is concerning due to negative effects on human and ecosystem health, promoting in some cases antibiotic resistance. To minimize this environmental contamination pathway, there has been an increasing focus on the development of methodologies for PPCPs removal in WWTPs [13; 14], such as ozonation processes, ultimately promoting the safe use of reclaimed water [1; 6]. Ozonation has been gaining attention due to its ability to degrade a wide variety of contaminants [14; 15], including recalcitrant ones, provided by the strong oxidation capacity of molecular ozone [14; 16; 17] and hydroxyl radicals formed during ozone decomposition reactions. Furthermore, it has the advantage that ozone is easily produced from an oxygen source, allows high water recovery rates without significant waste production [15; 18], and can be easily adapted to the characteristics and conditions of the wastewater being treated [15]. However, there are disadvantages, namely the production of by-products through the selective oxidation of the initial contaminants by ozone, which sometimes make ozone-treated effluents more environmentally hazardous than the initial contaminated wastewaters [18; 19].