Scombrotoxin (Histamine)

What is Scombrotoxin?

Scombrotoxin, commonly known as histamine, is a biogenic amine that forms primarily in fish and other seafood products. This chemical is generated through the decarboxylation of histidine, an amino acid, by bacteria. In high levels, histamine becomes a public health concern due to its potential to cause scombroid poisoning.

Chemical Characteristics

Histamine is a low molecular weight compound that is soluble in water, making it easily dispersed throughout the tissue of fish. Because of its stability, it is heat-resistant and cannot be destroyed by cooking, freezing, or canning processes.

Importance in Food Safety

From a food safety standpoint, the presence of high levels of histamine in food products is undesirable and poses health risks. It is an indicator of microbial spoilage and poor handling conditions. The U.S. Food and Drug Administration (FDA) has set histamine levels at a maximum of 50 ppm (parts per million) in fish to deem it safe for consumption.

What Foods Can Be Contaminated?

Commonly Affected Foods

Histamine contamination is most frequently observed in fish that are rich in histidine, which is the precursor to histamine. These include:

  • Tuna
  • Mackerel
  • Mahi-mahi
  • Bluefish
  • Anchovies
  • Sardines
  • Herring

Other Potential Foods

Although less common, other fish and seafood products, such as shellfish, can also accumulate histamine under poor storage or handling conditions. Fermented foods like soy sauce, sauerkraut, and certain types of cheese may also contain low levels of histamine but generally are not a significant concern regarding scombrotoxin poisoning.

Processed Foods

Histamine contamination can also occur in processed foods that use histidine-rich fish as an ingredient, such as:

  • Canned tuna
  • Fish sauces
  • Smoked fish products
  • Sushi and sashimi

Cross-contamination Risks

Fish that are not usually associated with high levels of histamine can become contaminated through cross-contamination. This can happen if they are processed, stored, or transported with histamine-rich fish under suboptimal conditions.

How Does It Affect Human Health?

Acute Symptoms of Scombrotoxin Poisoning

When ingested in high amounts, histamine can induce a variety of symptoms that can range from mild to severe. These often resemble allergic reactions and can include:

  • Flushing and skin rash
  • Headache and dizziness
  • Nausea and vomiting
  • Abdominal cramps
  • Diarrhea

Timeframe for Onset

Symptoms usually manifest within 30 minutes to a few hours after consumption of contaminated food. They are generally self-limiting and subside within 12-48 hours.

Long-term Effects

While there are no long-term health effects directly associated with acute scombrotoxin poisoning, complications can arise in cases where other pre-existing health conditions are present. People with asthma or histamine intolerance may experience more severe symptoms.

Medical Treatment

The most common treatment for histamine poisoning is antihistamine medication, which can quickly alleviate symptoms. However, severe cases may require hospitalization for supportive care.

Interactions with Other Compounds

Histamine’s effect on the body can be exacerbated by alcohol and certain drugs, such as monoamine oxidase inhibitors (MAOIs). Thus, combining histamine-rich foods with these substances may heighten the risk and severity of poisoning.

The clinical diagnosis and management of scombrotoxin poisoning are guided by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO).

How Common Is Illness?

Prevalence of Scombrotoxin Poisoning

While it is challenging to accurately determine the frequency of scombrotoxin poisoning, it is generally considered rare. However, underreporting is a known issue; many cases may go unreported due to the self-limiting nature of the symptoms. The Centers for Disease Control and Prevention (CDC) estimates that for every single case of scombrotoxin poisoning reported, there might be up to 30 cases that go unreported.

Geographical Distribution

Scombrotoxin poisoning occurs worldwide, with cases more commonly reported in regions where fish consumption is high. Coastal areas and islands often report higher incidences.

Seasonal Trends

There appears to be a seasonal pattern to scombrotoxin poisoning, with higher cases often reported during warmer months. This may be due to increased bacterial activity that produces histamine more rapidly at elevated temperatures.

Risk Groups

Although scombrotoxin poisoning can affect people of all ages, those with a history of allergies, asthma, or histamine intolerance may be more susceptible to severe symptoms.

Where Does It Come From?

Microbial Origin

Histamine is produced when certain bacteria, such as Morganella morganii and Photobacterium spp., convert histidine to histamine through enzymatic decarboxylation. These bacteria are naturally present in the marine environment and can multiply on the fish post-catch.

Handling and Storage

According to the FDA, Improper handling and storage conditions, particularly failure to maintain low temperatures, can lead to rapid bacterial growth and consequently, higher histamine levels. Practices such as delayed icing, storing fish at temperatures above 32°F (0°C), or extended storage, even at refrigeration temperatures, can all contribute to histamine formation.

Processing and Preparation

Histamine formation can also occur during processing if cleanliness and temperature controls are not rigorously maintained. Cross-contamination during cutting, filleting, and packaging processes can also contribute to the spread of histamine-producing bacteria.

Industrial Contribution

In large-scale fishing operations, the time from catch to freezing or canning can be extended, increasing the risk of histamine formation. Inadequate sanitation measures in processing plants also contribute to this risk.

How Is It Affected By Environmental Factors?


Temperature is a crucial environmental factor affecting histamine formation. Bacteria that produce histamine are more active at warmer temperatures, thus increasing the risk of scombrotoxin poisoning during hot weather or due to inadequate refrigeration.

Oxygen Availability

Histamine-producing bacteria are usually facultative anaerobes, meaning they can grow in both the presence and absence of oxygen. However, these bacteria typically produce more histamine when oxygen levels are low, as is the case in vacuum-packed fish products.

pH Levels

Histamine formation is also affected by the pH levels of the food. Fish with a higher pH are more prone to bacterial growth and subsequent histamine production. However, bacterial activity generally slows as the pH becomes more acidic, making histamine formation less likely in such environments.

Salt and Water Activity

Salting fish can reduce water activity, thereby inhibiting bacterial growth. However, it is worth noting that salt alone is not sufficient to prevent histamine formation, especially if other environmental factors are favorable for bacterial growth. See more at Impact of Environmental Factors on Fish Spoilage.

Human Activities

Fishing practices, including the time from catch to initial processing and refrigeration, have a direct impact on histamine levels. Overfishing can also contribute indirectly by forcing ships to stay out longer, increasing the time before the fish are processed and stored properly.

How Can It Be Controlled?

Time-Temperature Control

The most effective way to control histamine formation is by maintaining a low temperature throughout the entire supply chain, from catching to consumption. The FDA recommends that fish be iced or refrigerated at temperatures of 32°F (0°C) or below immediately after being caught.

Good Manufacturing Practices (GMP)

Adhering to Good Manufacturing Practices in food processing environments can substantially reduce the risk of histamine formation. This includes maintaining clean surfaces, tools, and hands, as well as proper waste disposal.

Rapid Processing

Quickly processing fish post-catch can minimize the time for bacterial growth, thus reducing the potential for histamine formation.

Quality Control Testing

Conducting regular quality control tests for histamine can identify potential problems before the fish reach the consumer. High-performance liquid chromatography (HPLC) is a commonly used method for such testing.

Consumer Awareness

Educating consumers about the risks of histamine and how to properly store fish can help mitigate the risks of scombrotoxin poisoning. This includes advising against purchasing fish that has not been properly refrigerated or that has an off smell.

Treatment Methods

While heat treatment and radiation do not degrade existing histamine, they can reduce bacterial load, reducing the further formation of histamine. However, these methods are not foolproof and are not substitutes for proper cold storage.

Are There Rules and Regulations?

United States

In the United States, the Food and Drug Administration (FDA) sets the guidelines and regulations for histamine levels in fish. The maximum allowable level is 50 ppm for species where histamine is a concern. The FDA also has a Hazard Analysis and Critical Control Point (HACCP) plan that fish processors are required to follow to control histamine formation.

European Union

The European Union has similar guidelines, with Regulation (EC) No 2073/2005 setting the maximum limit for histamine at 200 mg/kg in fishery products from fish species associated with a high amount of histidine.

World Health Organization

The WHO provides global guidelines for food safety, including for scombrotoxin. While these are not legally binding, many countries refer to them when setting their own national standards.

Import and Export Regulations

Countries have their own set of regulations for importing fish products, and these usually include stringent histamine testing. Failure to meet these requirements can lead to the rejection of the entire batch, creating significant financial losses for the producers.

Enforcement and Penalties

Non-compliance with histamine regulations can result in a range of penalties, from fines to criminal charges. In some cases, failure to adhere to food safety guidelines can also result in the suspension or revocation of business licenses.

Future Directions

There is ongoing research to establish more efficient methods of histamine detection, as well as to update food safety guidelines to incorporate new scientific findings.

Resources and Further Readings

Scombrotoxin Poisoning and Decomposition

Scombrotoxin (Histamine) Formation

Scombroid poisoning: Causes, symptoms, and treatment

An Outbreak Investigation of Scombrotoxin Fish Poisoning

European Union Regulation (EC) No 2073/2005