Risk assessment of small organoarsenic species in food
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Background to the risk assessment
- Risk managers need advice on the safety of food contaminants, such as arsenic, to establish maximum levels in foods that can be present without causing adverse health effects.
- Small organoarsenic species are compounds that contain methyl groups, but no other organic groups, bound to arsenic. Monomethylarsonic acid V (MMA(V)) and dimethylarsinic acid V (DMA(V)) are the most abundant of these compounds in food. The highest concentrations are found in rice, algae and seafood.
- In 2009, the European Food Safety Authority (EFSA) Panel on Contaminants in the Food Chain (CONTAM Panel) assessed the risks to human health related to the presence of arsenic in food.
- Because of a lack of data in 2009, EFSA only evaluated the risks for inorganic arsenic but could not assess the risks of small organoarsenic species or complex organoarsenic species such as arsenobetaine, arsenosugars or arsenolipids.
What was EFSA asked to do?
- The European Commission (EC) asked EFSA to provide four scientific opinions on arsenic in food, taking into account newly available scientific information since 2009, including new studies on the toxic effects of inorganic and organic arsenic.
- The first opinion, an updated risk assessment for inorganic arsenic in food, was published in January 2024. The risk assessment of small organoarsenic species is covered by this second opinion. The third and fourth opinions will be finalised by the beginning of 2025 and they will respectively cover the risk assessment of complex organoarsenic species and of the combined exposure to inorganic and organic arsenic.
How did EFSA carry out this work?
- EFSA first commissioned a comprehensive search and evaluation of the relevant literature. The report from this search (Licht et al., 2022) served as a starting point for the scientific opinion.
- Additional literature searches were conducted following established protocols. In addition, consumer exposure to MMA(V) and DMA(V) was estimated based on available consumption data from EFSA. This data was combined with occurrence data reported to EFSA and found in the literature.
- A draft of the opinion underwent public consultation from 26 March to 7 May 2024 and was finalised after considering the inputs received from stakeholders.
What were the limitations/uncertainties?
- The risk assessment was limited to MMA(V) and DMA(V) due to insufficient data on other small organoarsenic species. Nevertheless, these two are the predominant forms of small organoarsenic compounds found in food.
- The data on developmental toxicity, reproductive toxicity and neurotoxicity of MMA(V) and DMA(V) were incomplete and the mechanisms behind their genotoxicity remain unclear. Therefore, the Panel concluded that it is not appropriate to derive health-based guidance values and decided to apply a margin of exposure (MOE) approach for both compounds.
What were the outcomes and their implications?
General outcome:
- Rice and fish are the highest contributors to the exposure to MMA(V) and DMA(V) in the human diet.
Outcome for MMA(V):
- Studies in rats found that MMA(V) exposure at certain levels can lead to weight loss due to diarrhoea, which was identified as the critical health effect. The Reference Point (RP) for MMA(V) was set at 18.2 mg per kg of body weight per day (equivalent to 9.7 mg of arsenic per kg of body weight per day). This is a conservative estimate of the lowest dose that could be associated with increased weight loss due to diarrhoea after exposure to MMA(V).
- For substances that are neither genotoxic nor cause cancer, a minimum MOE of 100 is generally considered of low concern for human health. However, considering additional uncertainties in the data, the Panel applied a conservative 5-fold safety factor to the minimum MOE. Therefore, the Panel concluded that an MOE of 500 or higher is unlikely to be a health concern for MMA(V).
- For MMA(V), the MOEs were well above 500 for both average and high consumers in all age groups and thus did not raise health concerns.
Outcomes for DMA(V):
- Studies on rats found that DMA(V) exposure at certain levels increased the occurrence of urinary bladder tumours, which was identified as the critical health effect. The RP for DMA(V) was set at 1.1 mg per kg of body weight per day (equivalent to 0.6 mg of arsenic per kg of body weight per day). This is a conservative estimate of the lowest dose that could be associated with increased occurrence of urinary bladder tumours after exposure to DMA(V).
- There is convincing evidence that DMA(V) causes cancer and the Panel concluded that it is likely to be genotoxic. Therefore, following the recommendation of EFSA's Scientific Committee for substances that are genotoxic and carcinogenic, the Panel concluded that an MOE of 10,000 or higher is necessary for DMA(V) to be unlikely to pose a health concern.
- For DMA(V), calculated MOEs were below 10,000 in many cases across dietary surveys and age groups, in particular for some groups of high consumers. The Panel noted that these MOEs raise health concerns.
Implication:
- The outcomes of this opinion give the EC a scientific basis for potentially setting maximum levels for MMA(V) and DMA(V) in food.
What are the key recommendations?
Recommendations for the research community:
- Improve analytical methods: Develop robust, validated analytical methods to measure specific small organoarsenic species in food and their corresponding sulfur-containing forms.
- Standardise reference materials: Develop certified reference material for ensuring consistency and accuracy in measurements across laboratories.
Maintain consistent reporting: Report data on small organoarsenic species in food to EFSA as elemental arsenic concentrations to ensure comparable results. - Collect occurrence data: Continue the collection of data on small organoarsenic species in key foods (i.e. fish and seafood, rice), and collect data in breast milk and a wider range of foods (e.g. infant formula, mushrooms).
- Understand effects on human health: Improve understanding of the absorption, distribution, metabolism and excretion of small organoarsenic species in reference to human health.
- Perform toxicity, genotoxicity and mode of action studies: Carry out further research on the effects of small organoarsenic species on development, reproduction, nervous system, genotoxicity and effects on the body (mode of action).
Glossary
Genotoxicity: when a substance is capable of damaging the DNA in cells.
Inorganic arsenic: inorganic forms of arsenic are compounds that do not contain carbon-arsenic bonds. These include oxides, chlorides, sulfides, arsenites and arsenates, among others, and they occur naturally in soils and groundwater or as a result of human activity.
Margin of exposure (MOE): a tool used in risk assessment to explore safety concerns arising from the presence of a potentially toxic substance in food or animal feed. It is the ratio of the reference point (the dose at which a low but measurable adverse effect is observed) to the level of exposure to the substance in a given population.
Organic arsenic: organic forms of arsenic are compounds that contain carbon-arsenic bonds. These include methylated arsenic compounds, arsenobetaine, arsenolipids and arsenosugars, among others, and they are primarily found in seafood and marine environments.
Reference point (RP): the defined point of an experimental dose–response relationship denoting a critical effect, which is used to assess the potential risks of exposure to a given hazard. It is often used to establish a safe or acceptable level of exposure.
Disclaimer
- This plain language summary (PLS) is a simplified communication of EFSA’s Risk assessment of small organoarsenic species in food. The full EFSA opinion can be found here.
- The purpose of the PLS is to enhance transparency and inform interested parties on EFSA’s work on the topic using simplified language to present a summary of the main findings.
Reference
Risk assessment of small organoarsenic species in food.