What is scombrotoxin?
Scombrotoxin is a foodborne toxin most often associated with the consumption of fish, particularly species belonging to the Scombridae and Scomberesocidae families (scombroid fish), such as mackerel and tuna. It can cause a mild, though sometimes distressing, form of foodborne intoxication (scombroid or scombrotoxic food poisoning) when ingested in sufficient quantities.
Scombrotoxic poisoning is also known as histamine poisoning, since histamine is considered to be the principal toxic component of scombrotoxin, although other compounds may be involved. Histamine (C5H9N3) is a biogenic amine and can be produced during processing and/or storage in fish and certain other foods, usually by the action of spoilage bacteria.
What foods can be contaminated?
Scombrotoxin is most often associated with scombroid fish, especially tuna, skipjack, bonito and mackerel, but other non-scombroid fish, such as sardines, herring, pilchards, marlin and mahi-mahi have been involved in outbreaks of illness. There are also reports that scombrotoxin could occur in salmon species. Generally, fast swimming and migratory finfish species with red coloured meat are more likely to develop high histamine levels that whitefish species.
The toxin is not limited to fresh and frozen fish. It may be present in canned and cured fish products at high enough concentrations to cause illness.
The concentration of histamine can vary considerably between different sampling sites in a single fish, or between individual cans in a single lot. Levels of more than 3,000 ppm have been recorded in fish products implicated in outbreaks of scombrotoxic poisoning.
Histamine can also be produced at levels toxic to humans by bacterial action in other foods, notably Swiss cheese.
How does it affect human health?
Scombrotoxic (histamine) poisoning is a chemical intoxication, in which symptoms typically develop rapidly (from 10 minutes to two hours) after ingestion of food containing toxic histamine levels.
The range of symptoms experienced is quite wide, but may include an oral burning or tingling sensation, skin rash and localised inflammation, hypotension, headaches and flushing. In some cases vomiting and diarrhoea may develop and elderly or sick individuals may require hospital treatment. The symptoms usually resolve themselves within 24 hours.
The evidence for histamine as the active toxin in scombrotoxic poisoning is strong, but the condition is very difficult to replicate in humans using pure histamine and a clear dose-response effect is lacking. Scombroid poisoning is therefore not now considered to be simple histamine poisoning. A number of possible toxicity mechanisms have been proposed, but the true cause remains uncertain. One possibility is that other biogenic amines in spoiled fish, such as putrescine and cadaverine, may act as potentiators for histamine toxicity.
Because of the uncertainty over the mechanism of toxicity, the threshold toxic level for histamine remains unclear. Individuals also vary in the severity of their response to histamine in fish. Analysis of outbreaks suggests that levels of histamine above 200 ppm are potentially toxic. Although histamine occurs naturally in the human body, exposure to large doses can rapidly produce the symptoms of toxicity.
How common is illness?
The symptoms of histamine poisoning resemble an allergic reaction and there is potential for misdiagnosis. Furthermore, since symptoms are usually mild, it is likely that the illness is considerably under-reported. Nevertheless, it is thought that histamine poisoning is one of the commonest forms of fish-related toxicity.
The highest numbers of cases are reported in the USA, Japan and the UK, but this may be a reflection of reporting systems rather than incidence. Between 1992 and 2009, England and Wales reported 71 outbreaks affecting 336 people. Outbreaks were more common in summer than in winter. In the USA, between 1968 and 1980, 103 outbreaks involving 827 people were reported and in Japan over the same period, 42 outbreaks affecting 4,122 people. A more recent report (2008) stated that scombroid poisoning accounted for 38% of all seafood-related poisoning outbreaks in the USA.
Large outbreaks also occur. In 1973, at least 200 US consumers became ill after eating domestic canned tuna.
In the first six months of 2005 an unusual increase in incidence was reported in England and Wales, with 16 outbreaks affecting 38 people. This was thought to be associated with poor temperature control and hygiene in certain catering premises. A similar trend was reported in 2010.
Where does it come from?
Histamine in fish and other foods is produced by the decarboxylation of the amino acid histidine and fish species that have high levels of free histidine in their tissues are most likely to develop toxic histamine levels. This is usually the result of the action of the enzyme histidine decarboxylase, which is found in a number of bacterial species that may occur on fish.
Bacteria such as Vibrio species, Pseudomonas species and Photobacterium species are found in the marine environment and occur naturally on fish. Others, especially the Enterobacteriaceae, are contaminants that are introduced post-harvest. It is this second group that is considered most important in the development of histamine. Species such as Morganella morganii, Raoultella planticola and Hafnia alvei are able to produce high levels of histamine very rapidly at mesophilic temperatures (20-30oC). For this reason, histamine is more often produced during spoilage in this temperature range, although high levels can also develop at temperatures as low as 0-5oC over time. Recently, significant histamine production has been found in psychrotolerant species, such as Morganella psychrotolerans and Photobacterium phosphoreum.
In tropical waters the indigenous microflora may be more important histamine-producing organisms, particularly when fishing methods such as long-lining are used, where the fish may die before landing. Under these conditions, it is possible for histamine to be formed before the fish is landed and chilled.
There is evidence that histidine decarboxylase remains active at chill temperatures, even though the bacteria themselves are not active. Therefore once the enzyme has been formed at higher temperatures, it may continue to produce histamine even when the fish is properly chilled.
It is also possible for histamine to form after cooking or canning if the fish subsequently becomes contaminated with histidine decarboxylase-producing bacteria. This can happen when canned fish is handled under conditions of poor hygiene.
Is it stable in food?
Histamine is extremely stable once formed and is not affected by cooking. It can survive canning and retorting processes and is not reduced during freezing or frozen storage. Furthermore, high histamine levels may not be accompanied by other signs of spoilage and may be undetectable other than by chemical analysis.
The enzyme histidine decarboxylase is inactivated by cooking and further histamine will not then be produced unless recontamination occurs.
How can it be controlled?
For primary producers
The key measure for the control of histamine production in fish is rapid chilling as soon as possible after death, particularly where the fish has been exposed to warm water. This will inhibit the formation of bacterial histidine decarboxylase. Once the enzyme is present control options are very limited.
Accepted guidelines (FDA 2011) recommend that fish exposed to air or water temperatures of 28.3oC or less should be placed in ice, chilled seawater or brine at 4.4oC or less as soon as possible, but not more than 9 hours of the time of death. If the fish have been exposed to air or water temperatures above 28.3oC they should be chilled to 4.4oC or less as soon as possible, but not more than 6 hours from the time of death. Fish gutted and gilled before chilling should be chilled to 4.4oC or less as soon as possible, but not more than 12 hours from the time of death. Very large fish such as tuna that are eviscerated before chilling also should have the body cavity packed with ice.
Further chilling to a temperature as close to the freezing point as possible is desirable to prevent less rapid formation of histidine decarboxylase at lower temperatures. Even rapid chilling to 4.4oC or less may only give a safe shelf life of 5-7 days.
Once frozen, the fish can be stored safely for extended periods and further histidine decarboxylase will not be formed. However, enzyme produced before freezing will not be destroyed and will continue to produce histamine after thawing.
Hygiene and handling
Good hygienic practice on board fishing vessels, especially during landing and processing, is important to minimise contamination with non-indigenous histamine producing bacterial species.
Careful handling of fish to avoid damage to muscle tissue is also important in preventing contamination. For example, puncture wounds in fish can introduce contaminating bacteria into deep tissue where large concentrations of histidine are available. Histamine production may then happen much more quickly.
For food processors and caterers
Cooking will destroy both histamine producing bacteria and bacterial decarboxylases, but not histamine itself. Cooked fish therefore can be stored safely for longer periods and canned fish can be kept almost indefinitely.
It is important to note that once cooked or canned fish becomes recontaminated with histamine producing bacteria, temperature control again becomes critical to prevent a hazard. For example, canned tuna that is not consumed immediately after opening should be stored at less than 5oC as soon as possible.
Good hygiene at processing and preparation stages in the supply chain, such as cutting and packing or in catering operations, is also important to prevent contamination of fresh fish, or recontamination of frozen and cooked fish.
Histamine is only detectable by analysis and the sensory characteristics of affected fish may appear satisfactory. Testing by chemical methods such as HPLC, or by ELISA and other immunological techniques can provide some assurance that toxic levels of histamine are not present, but the variability in histamine levels in a single fish mean that very large numbers of samples must be taken. For this reason, chemical testing cannot be relied upon to demonstrate adequate control of the hazard, but can be useful as a HACCP verification tool. Rapid ‘dipstick’ type methods have been developed recently and may be valuable screening tests for fish processors.
Are there rules and regulations?
European legislation states that fish species belonging to families known to contain large amounts of histidine (e.g. Scombridae, Clupeidae etc) in their tissues should be tested for the presence of histamine. Nine samples should be tested from each lot and the mean value should be 100 ppm or less. The lot is considered unsatisfactory if more than two samples give results of between 100 and 200 ppm, or if any sample gives a result of 200 ppm or more.
In the USA the Food and Drug Administration has issued guidelines for tuna and related fish establishing a ‘defect action level’ of 50 ppm in any sample. This is said to be indicative of spoilage and may mean that toxic levels are present in other samples. A separate toxicity level of 500 ppm is also given.
The international Codex standard for fish also includes histamine levels as indicators of decomposition and hygiene and handling. A maximum average level of not more than 100 ppm is considered satisfactory in relation to decomposition, while an upper limit of 200 ppm in any one sample is applied for hygiene and handling.
Australia and New Zealand also apply a maximum limit of 200 ppm for histamine in fish or fish products.
Where can I learn more?
FDA Fish and Fishery Products Hazards and Controls Guidance Fourth Edition April 2011. Chapter 7: Scombrotoxin (Histamine) Formation