Organoarsenical Seafood Cocktail

Inorganic arsenic – arsenate or arsenite – is a Class I carcinogen that is heavily regulated in potable water. To monitor the concentration of these arsenic species, the determination of the total arsenic concentration of 0.01 mg/L is considered sufficient, since only traces of other arsenic species occur in water. However, arsenic forms rather stable carbon bonds and there are more than 100 organoarsenicals known to occur in biological tissues – mainly in marine organisms.

For example, the major organoarsenical in seafood is arsenobetaine, which is deemed non-toxic; while for most other organoarsenicals insufficient or no toxicological data exist. The determination of the total arsenic concentration in food is not relevant to establishing the toxicological potential of the food commodity, which complicates the analytical question, since inorganic arsenic needs to be determined solely amongst a plethora of organoarsenicals.

In June 2014, the United Nations’ World Health Organization (WHO) and Food and Agriculture Organization (FAO) recommended national authorities to implement regulations for a maximum level of inorganic arsenic rice and in June 2015 the EU implemented maximum level for different rice products, such as polished rice (0.2 mg/kg) or rice intended for baby food (0.1 mg/kg); this was the first regulation on that level for any food commodity. The inorganic arsenic contribution is relatively large and only a three organoarsenicals, such as dimethylarsinic acid (DMA), exist in rice. This makes the determination relatively easy and the analytical community was able to determine the inorganic arsenic concentration in rice samples
with confidence.

A worldwide proficiency test (1) showed that determination is method independent; however, the most commonly used technique was ion exchange chromatography coupled to inductively-coupled plasma mass spectrometry (IC-ICP-MS). Recently, more affordable methods, such as species-specific hydride generation coupled to ICP-MS (2) or atomic fluorescence spectrometry (AFS) (3), have shown to give complementary data without the use of chromatography. This is crucial since small laboratories don’t have the capability of hyphenating chromatography with ICP-MS.

However, seafood could contain a hundred times more total arsenic than rice. But so far, it is unregulated. The reason is the generally low contribution of inorganic arsenic amongst many known and some unknown organoarsenicals. However, it is expected that in the next few years the analytical community will develop reliable methods for inorganic arsenic based on the experience taken from the rice trials.

But are we really focusing on the right arsenic species? Should we be neglecting organoarsenicals? Clearly, complete monitoring would not be possible because of the vast number of different organoarsenicals species and the lack of a single method. But surely we must at least start making steps in the right direction.

We have recently started working in the growing field of lipid-soluble organoarsenicals, which contains more than 50 new compounds, such as arsenic containing fatty acids (AsFA), hydrocarbons (AsHC), phospholipids (AsPL), and fatty alcohols (AsFOH). Typically, the arsenic is dimethylated and occurs as an end-standing moiety of a longer carbon chain. Arsenolipids are present in the mg/kg range in commercial fish products, fish oils (4) and in algae products (5). And though many arsenolipids have been identified, determining those that may hydrolyze during extraction is still an analytical challenge (6, 7).

Two recent toxicology papers became the major justification for doing such sophisticated identification of novel lipid-soluble arsenic compounds. The Schwerdtle group (University of Potsdam, Germany) first discovered that highly purified, synthesized AsHC standards are cytotoxic in the micromolar range to two human cell lines in an in-vitro test (8) – mirroring the cytotoxic concentration range of arsenite, though through a different mode of action. In the group’s second paper, AsHC was shown to be detrimental to the late development stages of larvae of Drosophila (fruit flies) – once again toxicity was through a different mode of action but effective in the same concentration range as arsenite (9).

Ever since regulations were introduced worldwide for inorganic arsenic in rice, work on arsenic speciation in biological samples has become more important and rewarding. But don’t worry – there is still much more to be done by analytical chemists; for example, we need to establish robust methods that can be used routinely for inorganic arsenic in all food commodities. We also need to be vigilant for other ‘benign’ organoarsenicals that could turn out to be as toxic as inorganic arsenic. To conclude, we must continue developing tailored methods that make it possible to determine the real toxicological potential of organoarsenicals in food.