## 1 Deep Eutectic Solvents (DESs)
These solvents are a mixture of two or more compounds that are generally solid at room temperature but, when they are combined in a specific molar ratio, form a liquid solution, i.e., a decrease in the melting point is observed for these mixtures because of the interaction between the molecules. In general, these mixtures present low vapor pressure and, therefore, low volatility, are non-flammable, and are compatible with water and, theoretically, environmentally friendly. DESs have sometimes been confused with ILs, and it has even been considered that the two types of mixture can be interchangeable [28]. Certainly, DESs are natural competitors of ILs, since they share properties. However, both types of solvent are very different, due mainly to two reasons: on the one hand, the nature of the starting materials is quite different (ILs are mixtures of organic cations and organic or inorganic anions, while DESs are combinations of one or more hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs); on the other hand, the methods used for their formation are also different: DESs can be prepared from single components via heating treatment, whereas ILs are normally synthesized using synthetic routes involving various reagents and solvents, consisting of two principal steps--cation formation, and anion exchange [29]. The nature of the components forming ILs and DESs also determines their behavior; for instance, ILs are dominated by ionic interactions, while DESs show strong hydrogen-bonding interactions. DESs have attracted the attention of the scientific community because of their potential applications. These mixtures can be used in organic synthesis, electrochemistry, extraction media [30; 31; 32; 33; 34], biotechnology or biodiesel [35; 36; 37] synthesis and separation processes [38; 39], as a solvent in biological assays or enzymatic reactions [40], in biocatalysis [41; 42], or in biomedical applications [43; 44; 45; 46]. Additionally, they have been used in the pharmaceutical industry as excipients for increasing the solubility of hydrophobic drugs, or in drug delivery formulations [47; 48; 49; 50; 51]. Thus, the number of scientific manuscripts related to DESs has been growing over the past several years (Figure 1). As mentioned previously, these mixtures are formed by a hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD) [52]. Several substances can act as hydrogen bond acceptors; the more typical chemicals are quaternary salts such as choline chloride or betaine, but others--such as thymol, menthol, and decanoic or lauric acids--have also been used [53]. On the other hand, urea, amino acids (alanine, serine, glutamic acid, proline), sugars (glucose, mannose, xylose, fructose, galactose, sucrose, or lactose), alcohols (glycerol, xylitol, sorbitol, ethylene glycol, 1,2-propylene glycol), amides (acetamide, benzamide), amines, or carboxylic acids (malonic, lactic, maleic, oxalic, citric, malic, tartaric) can be used as hydrogen bond donors [43; 46]. It is interesting to note that due to the massive amount of possible DESs, resulting from the abundance of possible combinations of raw materials (either hydrophilic or hydrophobic), it is possible to rationalize their use and select those that combine the best properties (chemical, toxicological, environmental, and safety) for a given application. However, this same versatility can present a problem, since it is not easy to unambiguously characterize and generalize their properties. It is worth mentioning that there are very few studies that have addressed the prediction of DESs' properties [54; 55]. This lack of predictive models is even more pronounced in the case of (eco)toxic behavior [56]. Regarding this topic, in general, DESs are considered to be nontoxic compounds [57]. Nevertheless, there are no systematic studies from the health and environmental toxicity points of view that confirm this point. For this reason, an exhaustive revision of this information was carried out in this article.