What are okadaic acid toxins?
The okadaic acid group of toxins (OA-toxins) are the cause of diarrhoeic shellfish poisoning (DSP), a foodborne intoxication associated with the consumption of contaminated shellfish harvested from waters affected by growth of certain types of toxic algae. DSP is a non-lethal form of food poisoning with symptoms typical of gastroenteritis, especially diarrhoea. It has been known for around 35 years and is most common in Europe and Japan, but OA-toxins are being increasingly reported in shellfish from previously unaffected areas
The group of OA-toxins comprises OA itself, plus the dinophysis toxins, DTX1, DTX2 and DTX3, which are all analogues of OA. They are lipophilic, heat-stable polyether compounds.
What foods can be contaminated?
Most cases of DSP are related to bivalve molluscs, especially mussels, but also scallops, oysters and clams. These species are filter feeders and accumulate OA-toxins when the water contains sufficient levels of toxin-producing algae. Toxicity is seasonal and tends to be highest during the summer months in Europe and Japan, although DSP cases in Scandinavia have been reported in February and in October.
Predatory fish and other marine animals that prey on toxic shellfish may also accumulate OA-toxins, especially in liver tissue, but the significance of this for human health is uncertain.
OA-toxins are fat soluble and so tend to accumulate in the fatty tissue of affected shellfish. The highest levels are normally found in the viscera and shellfish can accumulate enough toxin to cause illness within hours when large populations of toxic algae are present in the water. OA-toxins may also be metabolised in the digestive gland (hepatopancreas) of contaminated shellfish, producing related toxic by-products. Toxin levels as high as 10 mg OA/g hepatopancreas have been reported in mussels grown in Japanese waters.
OA-toxin levels in shellfish do reduce naturally after they stop feeding on toxic algae, but there is little definite information on how this process occurs or on toxin retention times in different species. It is likely that some toxin is excreted in faeces before it can be assimilated.
How do they affect human health?
Two other marine biotoxins (pectenotoxins and yessotoxins) are often found in association with OA-toxins and were once thought to be involved in causing DSP. However, since neither group gives rise to diarrhoea, OA-toxins are now considered to be the principal cause of the intoxication.
OA-toxins are powerful phosphatase inhibitors and have been reported to act by disrupting the barrier function of the intestinal epithelial cells, making them more permeable. This property is associated with inflammation of the gut in humans, leading to fluid loss from intestinal cells and to diarrhoea. A minimum dose of OA for toxic effects to occur is estimated to be 48 μg, whereas for its derivative DTX1 the minimum it is 38.4 μg.
Levels of OA-toxins are commonly expressed as toxic equivalents of OA (mg OA eq/kg) or as Mouse Units (MU/kg) relating to a standard mouse bioassay method.
The onset of symptoms of DSP may occur between 30 minutes and 12 hours after ingestion of toxic shellfish. The main symptoms of DSP include diarrhoea, nausea and vomiting and abdominal pain. The severity of symptoms depends on the amount of OA-toxins ingested, but complete recovery typically occurs within three days. No fatalities caused by DSP have been reported to date and hospital treatment is not usually needed.
OA-toxins have also been shown to have other effects in animals and in cell cultures. For example OA and DTX1 are probable carcinogens, but the significance of this for human health is unknown.
How common is illness?
DSP mainly affects Western Europe and Japan, but OA-toxin contaminated shellfish and toxin-producing algae have been found in more widespread locations, including Canada, Mexico, South America, India, Thailand, China and Australia, and detections of OA-toxins seem to be increasing.
There have been a number of major outbreaks of DSP in Europe. Mussels imported from Denmark caused 415 cases of illness in France in 1990. In 1984, 10,000 people in France were affected by DSP symptoms caused by domestically produced mussels and a further 2,000 became ill the following year in a similar outbreak. 1984 also saw a major outbreak in Norway affecting at least 300 people. Over 5,000 cases of DSP-related gastroenteritis were reported in Spain in 1981, and OA-toxins have repeatedly been found at high levels in shellfish from the Galician region, resulting in prolonged disruption to local fisheries from 1993 onward. DSP cases were not reported in the UK until 1997, when 49 people were made ill after eating mussels in a London restaurant. Since then, the frequency of DSP events in UK waters has increased and shellfish harvesting has been restricted in several areas on a regular basis.
In Japan, cases of DSP were first reported in 1976 and 1977 when more than 150 people were affected by vomiting and diarrhoea. A total of at least 1,300 cases were reported between 1976 and 1981.
Elsewhere, outbreaks have been reported in Australia, Canada, Chile and the USA. Although the Northeast USA, especially New York and New Jersey, experienced large outbreaks of DSP-like illness between 1980 and 1985, outbreaks of human illness have not been reported since then, although OA-toxins have been found occasionally in US waters.
Where do they come from?
OA-toxins are produced by dinoflagellates of the genus Dinophysis. Seven species have been shown to produce the toxins. These are D. acuminata (Europe) D. acuta, D. fortii (Japan), D. mitra, D. norvegica (Scandinavia), D. rotundata and D. tripos. Three other species are also suspected of being able to produce toxins. Certain Prorocentrum species (P. concavum, P. lima and P. redfieldi) also produce OA-toxins.
If conditions are favourable, exponential growth of these species may occur resulting in an algal bloom. However, it is not necessary for visible blooms to occur for OA-toxins to be present at harmful levels. The production of toxins by different dinoflagellate species is highly variable and the same species may produce widely varying quantities of toxin in different locations. Some Dinophysis species can produce sufficient toxin in shellfish to cause illness in consumers at populations as low as 200 cells per litre. On other occasions much greater densities (more than 20,000 cells per litre) may be involved.
Are they stable in food?
OA-toxins are all relatively heat stable and are not destroyed by practical cooking processes.
Natural detoxification in shellfish does occur, but the rate of this process varies greatly with the species, the season (low water temperature slows toxin loss) and with the site of toxin accumulation. It has been reported that the retention time of OA-toxins in mussels can vary from one week to six months.
How can they be controlled?
The stability of OA-toxins and the variability of natural detoxification mean that neither depuration in clean water nor cooking processes are effective or economically viable methods of reducing the toxicity of affected shellfish to safe levels.
For enforcement agencies
The only effective controls available currently are the monitoring of the marine environment and the testing of shellfish flesh for OA-toxins. Regular inspection of the waters where shellfish are harvested, or produced by aquaculture, for the presence of toxic algae can be a useful source of data and indicate when a risk of toxicity is present. The routine testing of shellfish, especially mussels, for OA-toxins by chemical, immunological, or bioassay methods is the key prevention measure. However, the variability of toxin production by the algae and other factors must be taken into account when designing a suitable sampling plan
When toxic conditions are detected, bans on harvesting shellfish have to be imposed until toxicity can be shown to have returned to safe levels and contaminated shellfish should not be allowed to enter the human food chain.
Are there rules and regulations?
There are regulations relating specifically to OA-toxins in shellfish in a number of countries.
In the EU the European Commission has set a maximum limit for combined OA, DTXs and pectenotoxins in molluscs, echinoderms, tunicates and marine gastropods of 160 µg OA eq/kg of edible tissues. The grouping of OA-toxins with pectenotoxins is mainly due to their co-occurrence and the previously suspected role of pectenotoxins in DSP. This is now recognised as inappropriate and is under review. The mouse bioassay method is the official reference method of analysis, in association with a chemical detection method if required. Monitoring programmes for toxic dinoflagellates are in place in most European countries where shellfish are harvested.
Japan actively monitors both phytoplankton and shellfish and applies a tolerance level for OA-toxins of 5 MU/100g whole meat, when detected by the mouse bioassay method. This equates to approximately 0.2 μg/g.
In the USA, there is no current monitoring programme or limit for DSP toxins in shellfish, although monitoring is carried out in Canada.
Where can I learn more?
EFSA Scientific Opinion; marine biotoxins in shellfish – okadaic acid and analogues (2007)
US Centers for Disease Control & Prevention (CDC) – Marine toxins factsheet
FAO Food and Nutrition Paper 80 – Marine Biotoxins (2004)