PLS: Update of the risk assessment of inorganic arsenic in food

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Disclaimer

  • This plain language summary (PLS) is a simplified communication of EFSA’s Update of the risk assessment of inorganic arsenic 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.

Background to the risk assessment update

  • Risk managers need advice on the safety of food contaminants, such as arsenic, to establish acceptable maximum levels that can be present without causing adverse health effects.
  • Chronic intake of inorganic arsenic via diet and/or drinking water is known to cause adverse health effects, including cancer of the skin, bladder, and lungs.
  • In 2009, EFSA’s Panel on Contaminants in the Food Chain (CONTAM) adopted a scientific opinion on the presence of arsenic in food and concluded that the minimum amount of inorganic arsenic that produces a clear, low-level health risk for these effects lies between 0.3 and 8 µg/kg of body weight (bw) per day.
  • In 2021, EFSA published an updated exposure assessment of inorganic arsenic in food (https://doi.org/10.2903/j.efsa.2021.6380).

What was EFSA asked to do?

  • The European Commission requested an updated assessment of the risks to human health associated with the presence of inorganic arsenic in food, taking into account the updated exposure assessment and newly available scientific information on the toxicity of inorganic arsenic.
  • In addition, EFSA was asked to provide risk assessments on small and complex organoarsenic compounds and to provide a risk assessment of combined exposure to inorganic and organic arsenic. These assessments will be finalised by the beginning of 2025.

How did EFSA carry out this work?

  • EFSA carried out a comprehensive literature review to identify human and animal toxicology publications relevant to the hazard assessment of inorganic arsenic, published since 2009.
  • Based on the biological differences between laboratory animals and humans, the CONTAM Panel decided to make use of only epidemiological (human) data for the hazard assessment of inorganic arsenic.
  • The CONTAM Panel developed an approach enabling the use of the results from epidemiological studies in dose-response modelling, which was needed to establish a safe or acceptable level of exposure.
  • EFSA held a public consultation from 24 July to 10 September 2023 and considered stakeholders’ comments when finalising the opinion. 

What were the limitations/uncertainties?

  • In some studies, exposure was estimated based on the levels of inorganic arsenic measured in urine, which reflects exposure from both drinking water and food. However, other studies reported the concentration of inorganic arsenic in drinking water. In these cases, the reported concentrations were transformed into exposure estimates using the average body weight of those exposed, their estimated daily water intake, and additional exposure from food. As such, this is a major source of uncertainty.
  • There is also uncertainty regarding the variability in susceptibility to inorganic arsenic toxicity due to genetic differences between individuals. As the hazard characterisation is based on the results of large epidemiological studies, individuals who are more susceptible to adverse health effects associated with inorganic arsenic exposure due to their genetics may not be sufficiently represented in these studies.

What were the outcomes and their implications?

  • The CONTAM Panel concluded that low to moderate exposure to inorganic arsenic can cause cancers of the skin, bladder and lung, spontaneous abortion, stillbirth, infant mortality, congenital heart disease, neurodevelopmental effects, ischaemic heart disease, respiratory disease, chronic kidney disease, atherosclerosis, decreased birth weight, and skin lesions.
  • EFSA’s risk assessment established a reference point of 0.06 µg/kg bw per day based on a case-control study on skin cancer. This is a conservative estimate of the lowest dose that could be associated with increased induction of skin cancer after exposure to inorganic arsenic.
    • This reference point is also protective against the other adverse health effects in humans.
    • This is lower than the range of reference points established in the scientific opinion of the CONTAM Panel in 2009, which was between 0.3 and 8 μg/kg bw per day.
  • As inorganic arsenic is a genotoxic carcinogen, a margin of exposure approach was applied in the risk characterisation, using the level of exposure from the 2021 exposure assessment.
    • In adults, the margins of exposure range between 2.0 and 0.4 for average consumers and between 0.9 and 0.2 for high consumers, respectively. 
    • Even considering the uncertainties of the risk assessment, the CONTAM Panel concluded that these margins of exposure raise a health concern. The experts are 69% certain that high consumers of inorganic arsenic (at the 95th percentile) may have an increased risk of developing skin cancer.
  • Overall, consumer exposure to inorganic arsenic in food raises a health concern. This finding corroborates the outcome of EFSA’s previous assessment of 2009.

What are the key recommendations?

  • The updated risk assessment identifies several data gaps and recommends further research and investigation regarding the following aspects:
    • It is known that arsenic can cause DNA damage, but the underlying molecular mechanism needs to be investigated.
    • Further understanding of the role of individual variations in the susceptibility to arsenic-related health conditions is needed.
    • How arsenic can lead to epigenetic alterations and the associated disease risk in exposed populations needs to be investigated.
    • The interplay between epigenetic and genetic alterations induced by inorganic arsenic deserves further investigation.
    • The health effects of pre- and perinatal exposure to arsenic and how arsenic-induced alterations occurring during early life can impact the risk of disease in adult life should be further investigated.
  • In addition, further guidance on the use of human data in risk assessments should be developed. This is particularly relevant when benchmark dose modelling of epidemiological data is carried out and when quantitative risk assessment for genotoxic carcinogens based on epidemiological data is needed.
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Glossary

Benchmark dose (BMD): the minimum dose of a substance that produces a clear, low level health risk, usually in the range of a 1-10% change in a specific toxic effect such as cancer induction.

Epigenetic alterations: changes surrounding the DNA in cells caused by external factors that affect the way genes are read without changing the underlying DNA sequence.

Genotoxic: when a substance is capable of damaging the DNA in cells.

Hazard assessment: the part of risk assessment that involves identifying and characterising potential hazards associated with biological, chemical and physical agents which may be present in food. The process should, if possible, involve an understanding of the doses involved and related responses.

Inorganic arsenic: inorganic forms of arsenic are compounds that do not contain carbon-arsenic bonds. These include oxides, chlorides, sulphides, arsenites and arsenates, among others, and they occur naturally in soils and groundwater or as a result of human activity.

Margin of exposure: 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): 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.

References

Update of the risk assessment of inorganic arsenic in food.
DOI: https://doi.org/10.2903/j.efsa.2024.8488