## 3 Results and Discussion
### Considerations of General Health Risks Posed by Human Exposure to Aldehydic LOPs
#### 3.7.3. Carcinicities of Selected \(\alpha\),\(\beta\)-Unsaturated Aldehydes  
Currently, there is powerful evidence available that acrolein displays manifold key characteristics of carcinogens, which has been primarily acquired from human primary cell investigations, along with a range of experimental systems. This evidence has been strongly supported by human studies focused on structural molecular and bioanalytical explorations of acrolein's DNA adducts. Inhaled acrolein has been demonstrated to be carcinogenic in two species of rodent, it induces malignant lymphoma in female B6D2F1/Crj mice [90; 91], and has been shown to enhance the incidence of a composite of rare nasal cavity rhabdomyoma and squamous cell carcinoma in female F344/DuCrlCrl rats [89]. Acrolein readily reacts with DNA bases to form covalent DNA adducts, including cyclic \(\alpha\)- and \(\gamma\)-hydroxy-1,N\({}^{2}\)-propanodeoxyguanosine derivatives (the former is detectable in a variety of human biosamples, for example saliva, lung, brain liver, and urothelial mucosa) [92; 93]]. Upregulated concentrations of such DNA adducts have been observed in tobacco-smoking humans [94; 92], and also those with chronic inflammatory conditions. Similarly, there is \"strong\" evidence that crotonaldehyde exhibits multiple key characteristics of carcinogens, and again this arises from studies conducted in human primary cells and a wide range of experimental systems, which are supported by those focused on DNA adduct formation and proliferation in humans. Notwithstanding, to date there remains only \"limited\" evidence for its carcinogenicity in experimental animals. Nevertheless, one notable study from 1986 [95] reported that it increased the incidence of hepatocellular adenoma and carcinoma combined in male F344 rats when administered in drinking water. Moreover, this \(\alpha\),\(\beta\)-unsaturated aldehyde is genotoxic [96], and exerts clastogenic properties in human primary cells and human cell lines [96]. In November 2020, a Working Group representing the International Agency for Research on Cancer (IARC) finalized their evaluations of the carcinogenic potentials of acrolein and crotonaldehyde, along with arecoline (the primary active ingredient of the area'nut). Acrolein was classified as \"probably carcinogenic to humans\" (Group 2A) in view of \"sufficient\" evidence of carcinogenicity in experimental animals and \"strong\" mechanistic evidence. However, crotonaldehyde and arecoline were classified as \"possibly carcinogenic to humans\" (Group 2B) on the grounds of \"strong\" mechanistic evidence [97]. The deleterious toxicological effects of acrolein are further reviewed in detail in [98]. 7.4. Toxicological Significance of Dietary LOPs in CLOs and CLO-Loaded Fried Foods, and Its Frying Process Type-Dependence  
Although it appears that a significant level of the total aldehydes generated from PUFA and, to a much lesser extent, MUFA peroxidation processes in both thermally- stressed culinary oils, and via transference to foods fried therein, are depleted by their potential participation in Maillard and/or Michael addition chemical reactions with food matrix proteins and amino acids [13], these secondary LOPs clearly remain a major toxicological concern. Indeed, the above examples provided by [77; 83] report only the levels of 'free' aldehyde LOPs available for human consumption, and hence the total amount uptaken by the fried potato chip samples analyzed in these investigations may indeed be significantly or even substantially, greater. Moreover, such Maillard or Michael addition products could also serve as latent sources of bioavailable and bioactive aldehydes [99], a process which may promote or even prolong their deleterious toxic actions in vivo following ingestion. Similarly, chemical reactions of aldehydes with alcohols, polyols or even carbohydrates may yield hemiacetal and subsequently acetal species in fried foods; however, such reactions are readily reversible.