rman, Belgian, or Spanish subjects. In depth research on the biomarkers of FBs has been carried out based on their mode of action, specifically the inhibition from the biosynthesis of de novo sphingolipids. Ceramide synthase inhibition causes an elevation inside the Sa concentration and, CA I Inhibitor drug subsequently, a rise in the Sa-to-So ratio in a variety of animal species and in humans [72]. In Portugal, the evaluation of 68 human urine samples obtained from participants living inside the Central zone of the country, namely, a rural and an urban area, showed that the Sa/So ratio was 0.43 0.22 and 0.42 0.17, respectively; no significant variations have been identified among populations [82]. Moreover, a prior study performed in this area revealed that these populations, even the rural one, were undoubtedly below low exposure levels [82]. Data retrievedMolecules 2022, 27,8 offrom Portuguese HBM research comply with information discovered within the literature for French [83] and Italian [80,84] populations. Castegnaro et al. [83] investigated urine offered by 14 female and seven male wholesome French participants, and verified typical values from the Sa/So ratio. Nonetheless, a study in China [85] advocated that human sphingolipid metabolism is often influenced by the intake of FB1, and that the Sa/So ratio in urine may be beneficial for assessing high FB1 exposure, claiming that males are much more susceptible to FB1 inhibition of sphingolipid metabolism than females. In 2001, the potential function of FBs in endemic nephropathy, a chronic renal disease, was studied in Brodska Posavina, Croatia. The Sa/So ratio was evaluated in healthful participants and in patients from this endemic area. The outcomes, each in urine and in serum, revealed sphingolipid metabolism harm, possibly caused by FBs or fumonisin-like mycotoxins. Given that statistically considerable variations have been verified when comparing them to the participants not affected by endemic nephropathy, impairment in sphingolipid metabolism may possibly be regarded as an initial sign of this illness [86]. Concentrations of FBs have also been determined in other human biological samples like in serum [83,86] and plasma [84]. The average Sa/So ratio inside the serum of nine healthier female participants from France was 0.43 (0.18.78), whereas in nine male participants it was 0.31 (0.11.57). In South Africa, in 13 female participants the ratio was 0.22 (0.09.44), and in sufferers with esophageal cancer it was 0.23 (range 0.16.36). Consequently, despite the little quantity of cancer patients (n = 4), no L-type calcium channel Agonist supplier statistical difference was observed within the Sa/So ratio compared with the control group of esophageal cancer individuals [83]; these outcomes are also in accordance with those obtained in several other research. Notwithstanding the analytical progress made inside the determination of Sa and So, some inquiries remain to be addressed. The ratio has to be evaluated individually, together with FB exposure, and might only be useful in very exposed populations, with levels close to or above the established TDI. 3.4. Others Deoxynivalenol (DON) is a tricothecene made by F. graminearum and F. culmorum. Unmetabolized DON, as well as its glucuronide conjugate, is among the key compounds located in human urine. Even so, some reports have also shown the presence of the metabolite deepoxy-deoxynivalenol (DOM-1) in human urine [87,88]. In Portugal, the all-natural occurrence of DON and its metabolites in human urine samples in the north zone of Portugal was preliminary evaluated in 2012 in 13 volu