## 2 Natural Toxic Plant Alkaloids with Relevant Occurrence in Food
### Origin, Toxicity and Occurrence of Opium Alkaloids (OAs)  
Opium alkaloids (OAs) are secondary metabolites found in the milky sap of opium poppy plant (_Papaver somniferum_ L.). Its latex (opium) derived from the capsules contains as many as 80 different Oas. However, from all these OAs, the most common are six of them, which can be divided into two groups according to their chemical structure: the phenanthrenes (morphine, codeine, oripavine and thebaine) and benzylisoquinolines (noscapine and papaverine) (Figure 2c) [49]. The phenanthrenes have an aromatic A ring, partially saturated B- and C-rings and a nitrogen-containing D-ring, spanning carbons 9 and 13 (Figure 2c). A common biosynthetic pathway is found; thebaine is the precursor of oripavine and codeine, which are both precursors of morphine. On the other hand, as the name suggests, the benzylisoquinolines consist of an isoquinoline and a benzyl part. They have one methylated nitrogen atom and oxygen functional groups (Figure 2c). The presence of these alkaloids in opium means that this traditional plant is widely used medicinally for its pharmacological properties. However, its consumption can result in false-positive drug tests and adverse consequences for health, such as nausea and vomiting, drowsiness, respiratory problems, and dependence, especially for the most vulnerable people and more severe cases of intoxication [8]. In recent years, the seeds of this plant have been increasingly used in some foods, such as bakery products (bread, rolls, cookies, etc. ), salads or yoghurt toppings, or even to produce teas and oil. Although poppy seeds do not naturally contain OAs, the problem is that they may be contaminated by the latex from this plant during harvesting or by insect damage [50]. However, due to the lack of control, numerous food alerts have been reported recently (23 since 2012) (Figure 1) noting high levels of morphine in poppy seeds, up to almost 400 ppm [9]. Therefore, due to the potential health risks described above, the European Commission has recently published Regulation (EU) 2021/2142, which came into effect on 1 July 2022 [12]. This regulation establishes maximum levels of OAs (expressed as morphine equivalents calculated as morphine + 0.2 \(\times\) codeine) in bakery products (1.5 mg/kg) and in poppy seeds (20 mg/kg) [12]. However, since 2018, the EFSA has claimed for new analytical methods that are effective in quantifying the six OAs in different food samples because, to date, most studies have focused on morphine and codeine, but the other OAs may be more toxic, as requested by the health authorities [49]. As a result, the number of studies related to this family of alkaloids has increased in recent years. These studies have been mainly performed on poppy seeds, in which considerably high concentrations above the established maximum limit have been found [51; 52; 53; 54]. For instance, recently the six main OAs have been studied in 11 commercial samples of seeds and it was found that all of them were present in all the samples analyzed, with concentrations in the range from 1.5 to 249.0 mg/kg for morphine, from <0.2 \(\upmu\)g/kg to 45.8 mg/kg for codeine, from <2.4 \(\upmu\)g/kg to 136.2 mg/kg for thebaine, from <0.2 \(\upmu\)g/kg to 27.1 mg/kg for papaverine, from <0.2 \(\upmu\)g/kg to 108.7 mg/kg for noscapine, and from <240 \(\upmu\)g/kg to 33.4 mg/kg for oripavine [54]. Likewise, some works have determined these alkaloids in bakery products [55; 56; 57; 51]. For example, [PERSON] et al. (2022) analyzed four slice breads and five breadsticks. In the case of breadsticks, the concentrations found were very low, while concentrations were higher in sliced bread, showing concentrations up to 8.3 \(\pm\) 0.5 of morphine and 2.4 \(\pm\) 0.2 mg/kg of codeine, respectively, exceeding the established EU maximum limits [55]. [PERSON] et al. (2018) analyzed two bakery products, in particular, two cakes, showing up to 0.6 mg/kg of morphine and <0.1 mg/kg of thebaine, codeine, noscapine and papaverine [51]. On the other hand, [PERSON] et al.