Aflatoxins, cattle and humans: Still a One Health challenge in the era of integrated toxicology

Background. Aflatoxins are a significant threat to food safety worldwide. Produced by Aspergillus flavus and A. parasiticus, they were first identified in the early 1960s following mass mortality events in turkeys and trout, providing the first insights into their hepatotoxicity and potential carcinogenicity in humans. Four major aflatoxins are known, and aflatoxin B1 (AFB1) is the most potent hepatotoxin, classified by the International Agency for Research on Cancer (IARC) as a Group 1 human carcinogen. Its widespread occurrence in staple commodities such as maize, peanuts, tree nuts, and spices, combined with its stability and resistance to food processing, makes AFB1 a priority concern for international food safety authorities. To confirm this, a recent analysis of the EU food and feed notifications (RASFF, 1999–2024) confirmed mycotoxins as the dominant cause of border rejection (42.94%), and AFB1 as the most frequently reported mycotoxin (49.15%). AFB1 is a critical concern in dairy cattle, because its hydroxylated metabolite aflatoxin M1 (AFM1) may be excreted in raw milk and in dairy products, raising significant concerns for human exposure. AFM1 is also classified as a Group 1 human carcinogen. Climate change is increasingly recognized as a critical factor influencing AFB1 contamination in feed and food commodities. Rising temperatures, prolonged droughts, and altered precipitation create optimal conditions for mold growth and AFB1 production. Regions previously at low risk, such as Southern and Central Europe, are now experiencing increased AFB1 contamination events. These changes may also compromise the effectiveness of current regulatory monitoring programs, calling for adaptive risk management strategies and enhanced surveillance systems to protect animal and human health. From a One Health perspective, AFB1 remains a critical food safety issue, as confirmed by a growing scientific interest: a PubMed search (April 2026) retrieved 3,306 and 360 articles related to AFB1 in humans and dairy cows, respectively. Furthermore, in the last five years (2021–2026) a total of 852 and 79 papers have been respectively published. In the following sections, the current and future challenges in the mitigation of AFB1 toxicity, based on recently published literature and personal data, are reported. Mitigation of AFB1. Mitigation strategies include pre- and post-harvest approaches. Physical and chemical methods, such as oxidation and adsorbent clays (bentonite, zeolite), are widely used. Despite mild cytotoxicity recorded in human enterocytes, EFSA considers bentonite safe for ruminants, consumers, and the environment under authorized conditions. Biological approaches are gaining increasing interest, particularly probiotic bacteria (Lactobacillus spp.) and yeasts (Saccharomyces spp.), studied for their ability to reduce AFB1 absorption and toxicity. AFB1 metabolism and transport in humans and cattle, and impact of gene variants. The cytochrome P450 1A2 (CYP1A2) and CYP3A4 are the foremost CYPs involved in AFB1 biotransformation in the human liver. Although kinetic characteristics are distinct and important, the major AFB1 derivative is the carcinogenic/genotoxic AFB1-8,9-exo-epoxide (AFBO), followed by AFM1, aflatoxin Q1 and P1 (AFQ1 and AFP1). In cattle liver, CYP1A1, CYP3A74, and CYP1B1 play key roles in AFB1 metabolism. CYP3A74 is the main enzyme responsible for the formation of AFBO, while CYP1A1 primarily drives AFM1 formation. CYP1B1 contributes to AFM1 and AFBO synthesis, with a possible coordinated regulation with CYP3A74. CYP genetic polymorphisms influence AFB1 toxicokinetics. In humans, CYP3A4 and CYP3A5 variants directly modulate AFBO adduct levels, while cattle CYP3A74 variants are likely to affect AFB1 metabolism. Overall, these data underscore the critical role of CYP polymorphisms in modulating AFB1 biotransformation, with implications for personalized risk assessment in humans and food safety monitoring in livestock. Concerning conjugative enzymes, glutathione S-transferases are primarily responsible for AFBO detoxification. Additionally, epoxide hydrolase and aflatoxin aldehyde reductase also play key roles in AFB1 detoxification in humans. However, cattle rely on a narrower and globally less efficient detoxification network, making them more vulnerable to AFB1 bioaccumulation and AFM1 transfer to animal-derived food products. Finally, in both species P-gp (encoded by the ABCB1 gene) and Breast Cancer Resistance Protein (BCRP, ABCG2) limit the absorption and promote the excretion of AFB1 and AFM1. BCRP plays a crucial role in AFM1 active secretion into milk. Like CYPs, genetic variants of these transporters may affect the overall AFB1 disposition. Circular economy and AFB1. Recovery of food loss and waste from agricultural and food supply chains provides major sources of bioactive compounds with antioxidant and anti-inflammatory properties. Driven by this potential, the feed antioxidants market size is projected to grow from USD 1.47 billion in 2026 to USD 1.93 billion by 2031. Polyphenols and natural essential oils are garnering attention to limit mycotoxin synthesis and reduce their presence in foods, and are promising means to reduce the AFB1 impact and toxic effects in farm animals and humans. Regarding cattle, available data suggest that natural polyphenolic antioxidants (e.g., curcumin) can reduce AFB1 cytotoxicity, alter its metabolite profiling, and alleviate its whole-transcriptome effects on exposed cells. Aflatoxin B1 and omics. In the last decade, whole-transcriptome profiling has deepened our knowledge of the molecular effects of AFB1 in humans and cattle, highlighting changes in pathways involved in the inflammatory response, oxidative stress, xenobiotic metabolism, ferroptosis, pyroptosis, and cancer. More recently, adverse outcome pathways (AOPs) and multi-omics approaches have been applied to refine AFB1 risk assessment and create a holistic view of the biological processes triggered by AFB1 in exposed organisms.