December 23, 2021
FDA is announcing the availability of a draft Compliance Policy Guide entitled “Sec. 540.525 Scombrotoxin (Histamine)-forming Fish and Fishery Products--Decomposition and Histamine.” The draft guidance, when finalized, will replace existing guidance for FDA staff on adulteration associated with decomposition and histamine identified during surveillance sampling and testing of fish and fishery products susceptible to histamine formation.
Decomposition in fish, such as tuna and mahi-mahi, is detected by organoleptic evaluation. It is also indicated by elevated histamine levels in the muscle tissue. The presence of 50 ppm (5 mg/100 g) or more histamine is indicative of decomposition in these fish whether or not organoleptic examination detects decomposition.
Histamine forms postmortem by bacterial action on the amino acid, L-histidine. Histamine is heat-stable and survives thermal processing. It is therefore a useful indicator of decomposition in scombroid and certain other fish because odors that normally signal decomposition to the organoleptic analyst may be modified, reduced, or eliminated by thermal processing.
In addition to being an indicator of decomposition, when ingested at sufficiently high levels histamine causes scombroid poisoning. Cases of scombroid poisoning have been traced to the consumption of raw, frozen, and canned tuna and raw and frozen mahi-mahi. The term, "scombroid fish poisoning," developed because fish of the families Scombridae and Scomberesocidae are implicated in instances of histamine poisoning derived from decomposition in these fish. Tuna and mackerel are most frequently involved in instances of histamine poisoning, but this fact may be partly the result of the rate of consumption of these species worldwide.
From 1977 to 1981 there were 68 outbreaks of scombroid poisoning involving 461 illnesses. In the United States (U.S.), from the period of 1968-1986, a total of 188 outbreaks of histamine poisoning were reported. Certain nonscombroid fish such as mahi-mahi (Coryphaena hippurus) may also be involved in histamine poisoning. In March 1980, the Centers for Disease Control and Prevention stated that mahi-mahi accounted for 40 percent of the scombroid poisoning outbreaks reported in the U.S. Bluefish (Pomatomus saltatrix) have been responsible for several outbreaks in the U.S. and have caused at least one outbreak in Australia. Outbreaks have also occurred in the U.S., implicating pink salmon, redfish, yellowtail, marlin, and amberjack. Outside the U.S., pilchards, herring, anchovies, bluefish, and sardines have been involved in a number of cases. Sardines and pilchards have become a major source of histamine poisoning in Great Britain. Japan had an outbreak associated with black marlin, and anchovies have been implicated in single incidents in Japan, the U.S. and Great Britain.
The agency's use of histamine levels as reliable indicators of decomposition is based primarily on agency experience with tuna and mahi-mahi. However, as noted above, other species have been implicated in a significant number of incidents of histamine poisoning. These other species also contain high levels of free L-histidine in their muscle tissue and are known to form histamine as they decompose. Therefore, on a case by case basis, when these other species contain levels of histamine of less than 500 ppm but equal to or greater than 50 ppm, the agency may determine that these fish are decomposed. In these instances, FDA determination that the fish is decomposed may be based not only on the histamine level but also on other scientific data, including the presence of other amines associated with decomposition in these fish.
In addition, FDA intends to use the action level for canned tuna of 500 ppm in considering whether fish of other species that previously have been implicated in histamine poisoning outbreaks are adulterated.
REGULATORY ACTION GUIDANCE:
The following represents criteria for recommending legal action to CFSAN/Office of *Compliance*/Division of Enforcement (HFS-605). Histamine values used to support a recommendation, at a minimum, need to be accompanied by the information described in the compliance program or assignment. The appropriate program or assignment will provide correct information on: sample size, number or subsamples to examine preparation and analytical procedure. Submit the original and check results with the recommendation for action.
Criteria for recommending regulatory action for the presence of decomposition in canned tuna are usually based on a sample size of 24 cans (subsamples). In deciding whether to authorize seizure, HFS-605 will expect to see that a minimum of two subsamples must contain evidence of decomposition when up to 24 cans, but not necessarily all 24 cans, are analyzed. For example, to support a recommendation for regulatory action, if 18 cans are analyzed, two cans found to contain evidence of decomposition. However, when more than 24 cans are analyzed, the number of cans that would be expected to contain evidence of decomposition to justify regulatory action is proportionately higher. For example, if 36 cans are examined, HFS-605 would expect that 3 cans be found to contain decomposition to support a recommendation for regulatory action. Similarly, for raw and frozen fish, a minimum of 2 subsamples would generally be expected to contain evidence of decomposition when up to 24 subsamples are examined if regulatory action is to be authorized.
Decomposition, tuna and mahi-mahi
Samples of tuna or mahi-mahi found to meet criterion a., b., or c. (below) should be considered adulterated within the meaning of 21 U.S.C. 342(a)(3).
- Histamine level equal to or greater than 50 ppm in at least two subsamples by both the original and check analyses.
- Organoleptic evidence of decomposition, except honeycombing in canned tuna, is found in at least two subsamples by an analyst qualified in organoleptic testing and the findings are confirmed by a national expert in organoleptic testing.
- Honeycombing is found in two subsamples by an analyst qualified in organoleptic testing and confirmed by a national expert in organoleptic testing.
Decomposition, species other than tuna and mahi-mahi
Samples of fish previously implicated in instances of histamine poisoning found to meet criterion a. or b. (below) may be considered adulterated within the meaning of 21 U.S.C. 342(a)(3) when supported by other scientific data.
- Histamine level equal to or greater than 50 ppm but less than 500 ppm in at least two subsamples by both original and check analyses.
- Organoleptic evidence of decomposition is found in at least two subsamples by an analyst qualified in organoleptic testing and the findings are confirmed by a national expert in organoleptic testing.
Danger to Health
Samples of fish implicated in an instance of histamine poisoning that have been found to meet either criterion a. or b. (below) should be considered adulterated within the meaning of 21 U.S.C. 342(a)(1).
- Histamine level equal to or greater than 500 ppm in one subsample by both the original and check analyses, or
- Documented evidence of an illness associated with the fish irrespective of histamine content.
*Material between asterisks is new or revised*
Revised: 10/30/89, 3/95, 7/26/95, 5/2005
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