EFSA publishes risk assessment of small organoarsenic species in food

In a recent study published in the EFSA Journal on July 2024, the European Commission tasked the European Food Safety Authority (EFSA) with conducting a comprehensive risk assessment of small organoarsenic species present in food. The study employed a revolutionary analytical technique: inductively coupled plasma mass spectrometry (ICPMS) combined with liquid chromatography (LC-ICPMS). This approach revolutionized the field of organoarsenic species detection by offering robust analysis, incredibly low detection limits (as low as 10 ng As/L), and significantly faster analysis times.  

While arsenic is highly toxic, certain forms, like monomethylarsonic acid (MMA) and dimethylarsonic acid (DMA), are more prevalent in our diet, and their toxicity varies depending on their methylation state: trivalent (III) or pentavalent (V).  

Trivalent forms are generally more toxic due to their higher reactivity and ability to interact with essential cellular processes, including mitochondrial function, generation of reactive oxygen species (ROS), and cellular signaling pathways. Methylated arsenicals also inhibit key enzymes like glutathione reductase and thioredoxin reductase, compromising the cell's antioxidant defenses.  

Due to limited toxicological databases for both compounds, EFSA applied a Margin of Exposure (MOE) approach to assess risk.  

The study found that MMA(V) decreases body weight due to diarrhea in rats. The highest exposures of MMA(V) were noted in high consumers of fish meat (infants) and processed fish (elderly). All MOEs were well above 500, suggesting no significant health concern.  

DMA(V) has been found to induce tumors, particularly in the urinary bladder of rats, with females being more sensitive. The highest chronic dietary exposure of DMA(V) was estimated in toddlers, primarily from rice and fish meat. MOEs were often below the benchmark of 10 000, especially at the 95th percentile exposure levels, indicating a potential health concern due to its genotoxic and carcinogenic properties.  

The mode of action for this carcinogenicity involves initial cytotoxicity followed by regenerative cell proliferation. The hypothesis suggests that a reactive metabolite is responsible for this cytotoxicity. Studies have demonstrated that antioxidants can mitigate the cytotoxic effects of DMA(III), supporting the involvement of oxidative stress in its mode of action.  

Beyond cancer, methylated arsenicals might contribute to cardiovascular issues. They may trigger blood clotting and programmed cell death in platelets, potentially impacting heart health. Additionally, animal studies suggest they may worsen plaque buildup in arteries.  

The assessment concludes that small organoarsenic species pose potential health risks, with trivalent forms likely being particularly harmful due to their higher toxicity, but more data is needed for a definitive assessment. However, DMA(V) shows evidence of carcinogenicity in rats and its ability to damage DNA raises a health concern, especially for toddlers who consume a lot of rice and fish. However, the exact role of DNA damage in its carcinogenicity remains unclear. Margin of Exposure (MOE) calculations indicate a potential health concern for DMA(V) at high exposure levels, but no significant risk for MMA(V). Further research is essential to elucidate the intricate mechanisms of toxicity of both trivalent and pentavalent species and develop targeted interventions to mitigate these risks, particularly for exposure in vulnerable populations.    



EFSA Journal