U. S. Food and Drug Administration
Center for Food Safety and Applied Nutrition
FDA Prime Connection
FEDERAL REGISTER NOTICE Decomposition and Histamine for Seafood
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
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Decomposition and Histamine-Raw, Frozen Tuna and Mahi-Mahi;
Canned Tuna; and Related Species; Revised Compliance Policy
Guide; Availability
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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 degs.C (30
degs.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
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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
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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.
YFR Doc. 95-19059 Filed 8-2-95; 8:45 am"
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