18
Apr
Widely Used Fungicide Mixed with Natural Mycotoxins Increases Toxicity of Treated Food Crops
(Beyond Pesticides, April 18, 2025) A recent study published in Foods assesses the ability of the fungicide azoxystrobin (AZX) and naturally occurring toxins produced by certain fungi, known as mycotoxins, to display effects of cytotoxicity (cell damage). These effects were evaluated using three common mycotoxins found in food, including ochratoxin A (OTA), deoxynivalenol (DON), and T-2 toxin as mixtures with AZX within human hepatocarcinoma (HepG2) cell cultures. In analyzing combinations of these compounds at sublethal concentrations, the authors find modified toxicological behavior and synergistic effects that highlight the complexities of chemical mixtures, and potential threats to liver health through dietary exposure to both toxicants and toxins, that are not adequately regulated for their interactions.
While fungicides, like azoxystrobin, are intended to prevent or control fungal diseases, resistance to these pesticides can increase the presence of fungi, and subsequent mycotoxins, on crops. This scenario allows for co-exposure of fungicides and mycotoxins within food products that present a risk to consumers. These chemicals can threaten human health individually, as the researchers confirm in their study, but present a greater threat in combination. The mixture of AZX with all three mycotoxins exhibits the highest toxicity, with synergistic effects at all tested concentration levels.
“These findings highlight that the co-occurrence of fungicides and mycotoxins in food commodities can lead to complex exposure scenarios that may result in combined toxic effects on the organism,†the researchers state. These simultaneous exposures, and the resulting heightened effects, better reflect real-world exposure where there is a constant stream of harmful compounds creating a chemical cocktail within the environment that all organisms are exposed to. As the authors point out, climate change is also of concern because it can exacerbate these threats, with “increasing global temperatures and shifting weather patterns, which result in higher rates of fungal diseases in crops.†(See study here.)
Through cell cultures and assays, the researchers test the effects of different mixtures of the compounds to find evidence of in vitro toxicity (within cells). This involves AZX and the three mycotoxins individually, in three binary combinations (AZX + DON, AZX + OTA, and AZX + T2), three tertiary combinations (AZX + DON + OTA, AZX + DON + T2, and AZX + OTA + T2), and a quaternary combination of all compounds (AZX + DON + OTA + T2). As the authors report, “The data obtained in the cytotoxicity tests were used to analyze the nature of the interactions between AZX and the mycotoxins DON, OTA, and T2.â€
As a result, the researchers find that all the compounds reduced cell viability in a concentration-dependent manner. AZX alone “significantly reduced HepG2 cell viability, with decreases ranging from 7% to 99% and 15% to 87%,†they state. The study also reveals significant differences between the varying combinations and individual compounds. For example, the mixture of AZX + DON displays higher cell viability reduction than AZX by itself. Similar results occurred with AZX combined with OTA and T2 in binary combinations as well, and the tertiary mixture of AZX + DON + OTA shows higher cytotoxic effects than when AZX is administered alone.
The most noteworthy effects occur with the combination of AZX and all three mycotoxins, which has the highest toxic effects on HepG2 cell viability. The authors state: “Of particular significance was the observation that the quaternary mixture of AZX, DON, OTA, and T2 exhibited a synergistic effect at all the concentration levels measured. This finding suggests that the toxicity of the assessment of cell viability of the quaternary combination is greater than that of the related individual mycotoxins.†These results highlight the threat of synergistic effects that can be exhibited with chemical mixtures, which, as the authors describe, “occur when the combined impact is greater than what would be expected from simply adding the individual effects together.â€
“Our results revealed that the interactions between AZX and the mycotoxins analyzed varied depending on the combination and concentration,†the researchers conclude. “This phenomenon could be attributed to a common occurrence observed between combinations of substances with different mechanisms of action.†While these mechanisms are not fully understood, scientific literature suggests that “AZX exhibits toxicity in human cells primarily through the generation of oxidative stress, mitochondrial dysfunction, and the induction of apoptosis [cell death].â€
The authors continue, saying: “Exposure to DON, T-2, or OTA has also been demonstrated to induce oxidative stress, mitochondrial dysfunction, apoptosis, DNA damage, and inflammatory responses in various cell types. One plausible explanation for the synergistic effect of the quaternary mixture could be the more complex composition of the mixture and the different mechanisms of action of each of the components, which may contribute to the increased cytotoxic effects… Thus, the available data suggest that the potential mode of action responsible for the cytotoxic effects observed in the synergistic interaction between simultaneous exposure to AZX, DON, T-2, and OTA may result from common metabolic processes, such as oxidative stress and energy metabolism.â€
When it comes to food crops, Maximum Residue Limits (MRLs) are set by regulatory bodies for the maximum permissible levels of pesticide residues. As the researchers share: “The MRLs established in the EU legislation are based on the potentially toxic effects of individual exposure to these chemicals and do not consider the presence of different classes of chemicals simultaneously… Most toxicity studies and risk assessments have focused on individual chemicals, failing to consider potential interactions between substances and leading to an underestimation of their overall impact on human health.†This also applies to the deficient protocols used by the U.S. Environmental Protection Agency (EPA). (See more on EPA failures here.)
The disregard for combined exposure to multiple compounds, especially when they can exhibit synergistic effects that enhance their toxicity, leaves the health of individuals at risk and “can lead to unpredictable health outcomes, including increased toxicity, reproductive and developmental disturbances, immune system impairment, or even cancer and neurodegenerative diseases.†(Learn more through the Pesticide-Induced Diseases Database.)
Exposure to harmful chemicals can occur through various routes, such as dermal contact, inhalation, and ingestion. The exposure to both agrochemicals and mycotoxins within food products represents a significant dietary risk for human health. As the authors note: “The most recent report from the Rapid Alert System for Food and Feed (RASFF) indicates that pesticide residues and mycotoxins have been consistently identified as the most prevalent hazard categories, occupying the first and third positions, respectively. Consumers can be simultaneously exposed to these compounds through various food products such as fruits, vegetables, nuts, nut products, and seeds, or sequentially because of mixed diets.â€
The increased risks to human health, as documented in this study, with combined exposure to multiple compounds showcases how crucial it is to evaluate chemical mixtures. The altered toxicological behavior and synergy that can occur with these interactions, currently not included in risk assessments, cannot be ignored. (See Action of the Week “FDA Must Establish Tolerances for Pesticides Used in Mixtures.â€) With incomplete assessment protocols, the safety of food products and human health are further threatened.
The only way to ensure that both health and the environment are protected is to adopt the holistic solution of organic agriculture and land management. (See more on health and environmental benefits here and here.) As previously reported by Beyond Pesticides, organic maintains a unique place in the food system because of its high standards, public input, inspection system, and enforcement mechanism. But, organic will only grow stronger if the public participates in voicing positions on key issues to the National Organic Standards Board (NOSB), a stakeholder advisory board.
The NOSB is responsible for guiding USDA in its administration of The Organic Foods Production Act (OFPA), including the materials allowed to be used in organic production and handling. The role of the NOSB is especially important as we depend on organic production to protect our ecosystem, mitigate climate change, and enhance our health. Contribute your voice to Keeping Organic Strong by submitting NOSB comments. Because of a shortened period for NOSB review, we urge the submission of comments as soon as possible, but no later than 11:59 pm EDT on April 28.
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Source:
Fuentes, C. et al. (2025) Combined Cytotoxic Effects of the Fungicide Azoxystrobin and Common Food-Contaminating Mycotoxins, Foods. Available at: https://www.mdpi.com/2304-8158/14/7/1226.
