## 2 Natural Toxic Plant Alkaloids with Relevant Occurrence in Food
### Origin, Toxicity and Occurrence of Tropane Alkaloids (TAs)
In this sense, rainwater can contribute to this hypothetical horizontal transfer because of the high water solubility of TAs [38]. In 2013, an acute reference dose (ARfD) of 0.016 ug/kg body weight expressed as the sum of (\(-\))-hioscyamine and (\(-\))-scopolamine assuming equivalent potency was set by the European Food Safety Authority (EFSA). Likewise, the EFSA also recommended the collection of data on the presence of TAs in food, on atropine enantiomers, on TA toxicity, and on methodologies covering the analysis of TAs [31]. In 2015, the European Union (EU) recommended the monitoring of TAs in different plant-based foods, such ascereals and derived products, gluten-free products, tea and infusions, food supplements, legumes and derived products [39]. In addition, it was also indicated that at least atropine and scopolamine should be controlled and, if possible, the enantiomers of hyoscyamine. However, as for analytical reasons it is not always possible to differentiate between the enantiomers of hyoscyamine, maximum levels for scopolamine and atropine have been established, considering that the synthesis of TAs in plants leads to (\(-\))-hyoscyamine and (\(-\))-scopolamine. Accordingly, the EU has recently set maximum limits (0.2-50 \(\mathrm{\SIUnitSymbolMicro kg}\)) expressed as the sum of scopolamine and atropine for different products, including herbal teas, as well as processed and unprocessed cereals from sorghum, millet, corn and buckwheat [11]. Moreover, a maximum limit was set at 1 \(\mathrm{\SIUnitSymbolMicro kg}\) for scopolamine and 1 \(\mathrm{\SIUnitSymbolMicro kg}\) for atropine in processed cereal-based foods and baby foods for infants and young children [40]. However, it must be considered that this means overestimating the potential toxicity of the food, since it has been confirmed that the (+)-enantiomer can appear in the plant over time [32] and that some processing conditions also favor the racemization [41]. Regarding the foods more likely to be contaminated with TAs, almost 70% of the food alerts reported in the last 10 years have been notified in cereals and bakery products (Figure 1c), being millet and maize, the main cereals contaminated with high levels of these alkaloids. Currently, most of the publications related to the analysis of TAs focus on the development of analytical methodologies for their determination in plant-based foods, such as cereals [42], herbal teas [33; 43; 44], spices, aromatic herbs [45], vegetables [38; 46], processed cereal-based products (e.g., biscuits, breakfast cereals) [47; 48], etc. However, only a few of these works have evaluated the impact that food processing or culinary preparations may have on the TA content in contaminated samples. Nonetheless, most of these works only report the increase or reduction observed in the concentration levels of these alkaloids subjected to different procedures, but do not investigate the generation or appearance of transformation products [13]. One of the reasons is the lack of knowledge about the true toxicity of many of these alkaloids. Accordingly, the EFSA currently recommends an exhaustive study of thermal processing, transfer rate into infusion waters and degradation products generated by thermal processing along with toxicity studies [31; 35]. These topics represent new research lines in the TA field and, to date, only a few works have addressed them, as will be explained in the following sections.