[Federal Register Volume 60, Number 149 (Thursday, August 3, 1995)]
[Notices]
[Pages 39754-39756]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-19059]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES
[Docket No. 95D-0157]


Decomposition and Histamine--Raw, Frozen Tuna and Mahi-Mahi; 
Canned Tuna; and Related Species; Revised Compliance Policy Guide; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of revised Compliance Policy Guide (CPG) 7108.24, entitled 
``Decomposition and Histamine--Raw, Frozen Tuna and Mahi-Mahi; Canned 
Tuna; and Related Species.'' Revised CPG 7108.24 lowers the histamine 
level at which FDA may consider the fish subject to action under the 
Federal Food, Drug, and Cosmetic Act (the act) and states that the 
histamine defect action level (DAL) and the histamine action level (AL) 
now apply to raw, frozen tuna and mahi-mahi in addition to canned tuna. 
Furthermore, the revised CPG 7108.24 states that the AL also applies to 
related species of raw, frozen, and canned fish implicated in instances 
of histamine poisoning, such as bluefish, amberjack, and mackerel, in 
addition to tuna and mahi-mahi. Additionally, for these related 
species, levels of histamine less than the AL may be considered as 
evidence of decomposition on a case-by-case basis when supported by 
additional scientific data. The title of the revised CPG reflects these 
changes.

DATES: Written comments by September 5, 1995.

ADDRESSES: Submit written requests for single copies of CPG 7108.24, 
``Decomposition and Histamine--Raw, Frozen Tuna and Mahi-Mahi and 
Canned Tuna; and Related Species,'' and Laboratory Information Bulletin 
no. 3794 to the Director, Office of Constituent Operations, Industry 
Activities Staff (HFS-565), Food and Drug Administration, rm. 5827, 200 
C St. SW., Washington, DC 20204. Send two self-addressed adhesive 
labels to assist that office in processing your requests. Submit 
written comments on CPG 7108.24, ``Decomposition and Histamine--Raw, 
Frozen Tuna and Mahi-Mahi; Canned Tuna; and Related Species,'' to the 
Dockets Management Branch (HFA-305), Food and Drug Administration, rm. 
1-23, 12420 Parklawn Dr., Rockville, MD 20857. Requests and comments 
should be identified with the docket number found in brackets in the 
heading of this document. A copy of revised CPG 7108.24, 
``Decomposition and Histamine--Raw, Frozen Tuna and Mahi-Mahi; Canned 
Tuna; and Related Species,'' the Official Methods of Analysis of the 
Association of Official Analytical Chemists 15th Ed. (1990), section 
977.13, and Laboratory Information Bulletin no. 3794, and received 
comments are available for public examination in the Dockets Management 
Branch between 9 a.m. and 4 p.m., Monday through Friday.

FOR FURTHER INFORMATION CONTACT: Mary I. Snyder, Office of Seafood 
(HFS-416), Center for Food Safety and Applied Nutrition, Food and Drug 
Administration, 200 C St. SW., Washington, DC 20204, 202-418-3160.

SUPPLEMENTARY INFORMATION: Histamine is a chemical compound that forms 
postmortem in the muscle of scombroid fish, such as tuna, and in other 
species, such as mahi-mahi, by the action of certain bacteria that are 
common in fish. Bacteria that have the ability to form histamine do so 
by the decarboxylation of L-histidine, an amino acid found in the fish 
muscle. The decarboxylation reaction is catalyzed by an enzyme, 
histidine decarboxylase, produced by the bacteria. Fish species that 
are particularly vulnerable to the development of histamine are those 
with high levels of free L-histidine in their muscle tissues. 
Additional histidine may be released during decomposition and spoilage 
by proteolysis, whereby the protein structure is degraded, and amino 
acids are liberated (Ref. 1). The level of histamine produced in 
scombroid or other histidine-containing fish by these processes serves 
as an indicator of the decomposition that has occurred. When present at 
higher levels, histamine represents a health hazard. Therefore, FDA 
uses histamine to indicate that these fish are adulterated within the 
meaning of section 402(a)(1) and (a)(3) of the act (21 U.S.C. 342(a)(1) 
and (a)(3)).
    In the fishing industry, decomposition and bacterial histamine 
production are controlled primarily by the use of low temperature 
storage (Ref. 2). Significant decomposition and histamine formation can 
be avoided by good fish handling practices including icing or rapid 
immersion of the catch in water chilled to -1  deg.C (30  deg.F), 
followed by uninterrupted frozen storage. Under high temperature 
storage conditions, histamine may form before other indicators of 
decomposition are evident, especially the odor and appearance of 
decomposed fish (Ref. 3).
     Histamine also may form during low temperature storage conditions. 
However, in low temperature storage, the rate of histamine formation is 
slower, and it is usually accompanied by the typical odor of 
decomposition. Research sponsored by the Department of Health and Human 
Services has suggested that freezing may be more damaging to histamine-
forming bacteria than it is to nonhistamine producing spoilage bacteria 
(Ref. 4).
     Canned fish is frequently prepared from fish preserved by frozen 
storage before delivery to canneries. These fish are thawed before 
processing and are subjected to additional handling that may result in 
histamine levels in canned fish being somewhat higher than the levels 
observed in raw, freshly caught fish.
     Histamine is generally not uniformly distributed in a decomposed 
fish. A level of less than 50 parts per million (ppm) in one section 
may accompany a level in excess of 1,000 ppm elsewhere in the same 
fillet (Ref. 3). The anterior section of an individual fish generally 
is higher in histamine content than the posterior section, because the 
intestine, which is located in the forward end, is apparently the major 
source of the 

[[Page 39755]]
bacteria responsible for histamine formation. Postmortem disintegration 
of the intestine releases the microbial contents of the intestine which 
contaminate the anterior muscle tissue, making these sites particularly 
vulnerable to an accumulation of the amine (Refs. 5 and 6). The 
preponderance of scientific evidence demonstrates that the presence of 
histamine equal to or greater than 50 ppm, in a sample, is evidence 
that the fish is in a state of decomposition (Refs. 3, 5, and 6).

Defect Action Level for Decomposition

     Results of research conducted in the 1970's by FDA in cooperation 
with major universities, industry research associations, individual 
canners, and the National Marine Fisheries Service demonstrate that 
histamine levels in freshly caught tuna and mahi-mahi are less than 1 
ppm. Acceptable commercial fish generally contain about 5 ppm and 
rarely as much as 20 ppm histamine (Ref. 3). In a notice published in 
the Federal Register of September 14, 1982 (47 FR 40487), FDA stated 
that histamine levels in tuna that are judged to be of acceptable 
quality, based on organoleptic and physical analyses, are on the order 
of 10 to 20 ppm. FDA data from 1990 to 1992 show that the average 
histamine levels in acceptable commercial raw frozen fish (number of 
samples in parentheses) are 2 ppm for mahi-mahi (4), 4 ppm for albacore 
tuna (7), 2 ppm for yellowfin tuna (10), and 2 ppm for skipjack tuna 
(10) (Ref. 3). Other investigators also have reported that raw freshly 
caught scombroid fish contain very little histamine (Refs. 5 and 6).
     FDA conducted workshops in 1974 and 1976 in association with the 
Tuna Research Foundation. Test packs of canned tuna were prepared by 
the industry and classified by FDA experts using organoleptic 
evaluation. The average levels of histamine in the packs of canned tuna 
(numbers of cans in parentheses) found to be acceptable by organoleptic 
evaluation were 22 ppm for albacore (36), 12 ppm for skipjack (112), 
and 11 ppm for yellowfin (82). The average histamine level for all 230 
samples was 13 ppm. These tuna packs were not authentic packs but 
confirmed that commercially canned tuna of acceptable quality does not 
contain high levels of histamine. Similarly, commercially canned tuna 
collected from retail stores, in a survey conducted in 1981, was found 
to contain an average of approximately 6 ppm histamine (Ref. 3).
     The provisions of the current CPG 7108.24 announced in the 
September 14, 1982, notice, established a DAL of 200 ppm histamine for 
canned albacore, skipjack, and yellowfin tuna. The agency also stated 
that it would consider regulatory action against any canned tuna found 
to contain between 100 and 200 ppm histamine when a second indicator of 
decomposition (e.g., spoilage odors or honeycomb formation) is present.
     Since the studies on which the previous histamine DAL was based 
were conducted, the analytical methodology available for determination 
of histamine to 5 ppm levels has become standard practice. The official 
method for histamine detection published in 1977 (Ref. 7) was refined 
in 1993 (Ref. 8). The 1993 methodology has successfully undergone 
collaborative evaluation and testing. Refinement in the methodology for 
histamine determination and experience in using the methodology have 
made the determination of 50 ppm histamine levels a routine practice.
     Given the findings of these studies (Refs. 3, 5, and 6); the 
research that shows that the histamine levels in freshly caught fish 
are less than 2 ppm; the fact that commercially canned tuna classified 
as acceptable by FDA averages 6 ppm histamine; and the fact that levels 
at or above 50 ppm are only found in samples classified as decomposed 
by FDA organoleptic expert examination, the presence of 50 ppm 
histamine is evidence that raw, frozen, or canned tuna, and raw or 
frozen mahi-mahi, are in a state of decomposition. See United States v. 
1,200 Cases, Pasteurized Whole Eggs, 339 F. Supp. 131, 137 (N.D. Ga. 
1972). Therefore, when 50 ppm or more histamine is found in these types 
of fish, the agency may recommend regulatory action against the fish 
under section 402(a)(3) of the act.
     In the past two decades both industry and government have used 
organoleptic analysis of volatile odors for the detection of 
decomposition in raw and thermally processed fishery products. This 
analytical technique is acquired through extensive training and 
experience on samples and requires the analyst be periodically 
standardized in the application and performance of the analytical 
technique. However, organoleptic analysis is not quantifiable, and its 
application to stored and thermally processed commercial products, such 
as canned tuna, is difficult because the usual odors of decomposition 
found in raw product are often removed or altered during thermal 
processing. Unlike odors of decomposition, nonvolatile spoilage 
compounds such as histamine remain in the product and can be reliably 
measured by chemical analysis (Ref. 3). Therefore, confirmatory 
organoleptic examination for decomposition in regulatory samples would 
not be necessary when histamine levels at or above 50 ppm are detected 
by chemical analysis.
     Although the agency intends to use this DAL in deciding whether to 
recommend regulatory action, it does not consider that the fact that a 
fish or fishery product has a histamine level below 50 ppm establishes 
that the fish or fishery product is acceptable. Other spoilage 
mechanisms are possible that do not result in the formation of 
histamine. Thus a finding of histamine levels between 20 and 50 ppm 
should be viewed as indicating that the fish or fishery product has 
deteriorated and should cause a producer to further evaluate or test 
the product.

Histamine Formation in Species Other Than Tuna and Mahi-Mahi

    The agency's use of histamine level as a reliable indicator of 
decomposition is based primarily on agency experience with tuna and 
mahi-mahi. However, 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 equal to or 
greater than 50 ppm, the agency may determine that these fish are 
decomposed particularly when such a judgment is supported by other 
scientific data, including the presence of other amines associated with 
decomposition in these fish.

Action Level for Health Hazard

     In addition to being an indicator of decomposition, when ingested 
at sufficiently high levels histamine causes scombroid poisoning. The 
term ``scombroid fish poisoning'' developed because fish of the 
families Scombridae and Scomberesocidae are commonly implicated in 
instances of histamine poisoning deriving from advanced stages of 
decomposition in these fish. Tuna and mackerel are most frequently 
involved in instances of histamine poisoning, but this fact is 
attributable, in part, to the large amounts of these species that are 
consumed worldwide (Ref. 9).
     Nonscombroid fish, such as mahi-mahi (Coryphaena hippurus), is 
also involved in histamine poisoning. Bluefish (Pomatomus saltatrix) 
has been responsible for several scombroid poisoning outbreaks in the 
United States 

[[Page 39756]]
and has caused at least one outbreak in Australia. Pink salmon, 
redfish, yellowtail, marlin, and amberjack have also been implicated in 
scombroid poisoning outbreaks that have occurred in the United States. 
Outside the United States, 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 United 
States, and Great Britain (Ref. 9).
     From 1977 to 1981 there were 68 outbreaks of scombroid poisoning 
involving 461 illnesses (Ref. 10). In March 1980, the Centers for 
Disease Control and Prevention reported that mahi-mahi accounted for 40 
percent of the scombroid poisoning outbreaks reported in the United 
States. Since 1980, FDA has placed most shipments of mahi-mahi offered 
for entry into the United States on automatic detention because of the 
frequent occurrence of histamine levels exceeding 500 ppm (Ref. 11).
     Histamine is a poisonous or deleterious substance under section 
402 (a)(1) of the act because, when ingested at sufficiently high 
levels, it is known to cause scombroid poisoning (Ref. 12). In the 
September 14, 1982, notice, the agency established, on an interim 
basis, an AL of 500 ppm histamine in canned tuna (47 FR 40487). At this 
level, the agency considers histamine to present a hazard to public 
health. The agency is not changing the 500 ppm AL at this time because 
the threshold toxic dose of histamine is not known. However, the action 
level for canned tuna of 500 ppm will also apply to other species of 
raw, frozen, and canned fish, such as mahi-mahi, bluefish, amberjack, 
and mackerel, all fish that have been implicated in histamine poisoning 
outbreaks. Furthermore, the presence of other amine decomposition 
products in fish may have a synergistic effect on histamine toxicity. 
This synergism may dramatically lower the threshold toxic dose (Refs. 9 
and 10).

    Therefore, FDA is revising its histamine policy and announcing the 
availability of revised CPG 7108.24 ``Decomposition and Histamine--Raw, 
Frozen Tuna and Mahi-Mahi; Canned Tuna; and Related Species,'' which: 
(1) Includes a lower histamine DAL for decomposition, 50 ppm histamine 
rather than 100 ppm; (2) extends the application of the DAL of 50 ppm 
(5 mg per 100g) histamine for decomposition to raw and frozen tuna and 
mahi-mahi; (3) eliminates the provision that findings of less than 200 
ppm histamine need to be confirmed by organoleptic evaluation; (4) 
states that, on a case by case basis, histamine levels equal to or 
greater than 50 ppm, but less than 500 ppm, may be used as evidence of 
decomposition in other species commonly implicated in instances of 
histamine poisoning when supported by other scientific data; and (5) 
states that the AL of 500 ppm histamine now applies to other species of 
fish that have been implicated in histamine poisoning outbreaks.

 Title of Revised CPG 7108.24

     The title of CPG 7108.24 ``Decomposition and Histamine in Canned 
Albacore, Skipjack, and Yellowfin Tuna'' has been changed to 
``Decomposition and Histamine--Raw, Frozen Tuna and Mahi-Mahi; Canned 
Tuna; and Related Species'' to more accurately describe the contents of 
the revised CPG.

 References

     The following references have been placed on display in the 
Dockets Management Branch (address above) and may be seen by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday.
     1. Eitenmiller, R. R., and S. C. DeSouza, ``Enzymatic 
Mechanisms for Amine Formation in Fish,'' in Seafood Toxins, edited 
by E. P. Ragelis, American Chemical Society, Washington, DC, pp. 
431-442, 1984.
     2. Behling, A. R., and S. L. Taylor , ``Bacterial Histamine 
Production as a Function of Temperature and Time of Incubation,'' 
Journal of Food Science 47:1311-1314, and 1317, 1982.
     3. Memorandum from Division of Science and Applied Technology 
(HFS-425) to Division of Programs and Enforcement Policy (HFS-415), 
CFSAN, FDA, dated August 6, 1992.
     4. Baranowski, J. D., H. A. Frank, P. A. Brust, M. 
Chongsiriwatana, and R. J. Premaratne, ``Decomposition and Histamine 
Content in Mahi-Mahi (Coryphaena Hippurus),'' Journal of Food 
Protection 53:217-222, 1990.
     5. Frank, H. A., D. H. Yoshinaga, and W-K. Nip, ``Histamine 
Formation and Honeycombing During Decomposition of Skipjack Tuna, 
Katsuwonus pelamis, at Elevated Temperatures,'' Marine Fisheries 
Review 43:9-14, 1981.
     6. Frank, H. A., and Yoshinaga, ``Histamine Formation in Tuna'' 
in Seafood Toxins, edited by E.P. Ragelis, American Chemical 
Society, Washington, DC, pp. 443-451, 1984.
     7. Staruszkiewicz, W. F., ``Fluorometric determination of 
Histamine in Tuna: Collaborative Study'' in Journal of the 
Association of Official Analytical Chemists 60 (5) pp. 1131-1136, 
1977.
     8. Rogers, P. R., and W. F. Staruszkiewicz, ``Modification of 
GLC Method for Putrescine and Cadaverine and the Fluorometric Method 
for Histamine,'' Laboratory Information Bulletin no. 3794, July 
1993.
     9. Stratton, J. E., and S. L. Taylor, ``Scombroid Poisoning,'' 
in Microbiology of Marine Food Products, edited by Ward, D. R., and 
C. Hackney, Van Nostrand Reinhold, New York, pp. 333-344, 1991.
     10. Taylor, S. L., ``Marine Toxins of Microbial Origin,'' Food 
Technology 42(3):94-98, 1988.
     11. Regulatory Procedure Manual, part 9, Imports, Import Alert 
16-05--``Automatic Detention of Mahi-Mahi Because of Histamine and 
Decomposition,'' August 14, 1991.
     12. Taylor, S. L., J. Y. Hui, and D. E. Lyons, ``Toxicology of 
Scombroid Poisoning,'' in  Seafood Toxins, edited by E. P. Ragelis, 
American Chemical Society, Symposium Series, no. 262, pp. 417-430, 
1984.
    Interested persons may, on or before September 5, 1995, submit to 
the Dockets Management Branch (address above) written comments on the 
revised CPG 7108.24. Two copies of any comments are to be submitted, 
except that individuals may submit one copy. Comments are to be 
identified with the docket number found in brackets in the heading of 
this document. The revised CPG 7108.24 and received comments may be 
seen in the office above between 9 a.m. and 4 p.m., Monday through 
Friday.

    Dated: July 26, 1995.
Gary Dykstra,
Acting Associate Commissioner for Regulatory Affairs.
[FR Doc. 95-19059 Filed 8-2-95; 8:45 am]
BILLING CODE 4160-01-F