Federal Register: December 3, 1997 (Volume 62, Number 232)
Rules and Regulations
Page 64107-64121
From the Federal Register Online via GPO Access wais.access.gpo.gov
DOCID:fr03de97-22
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 179
Docket No. 94F-0289
Irradiation in the Production, Processing and Handling of Food
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is amending the food
additive regulations to provide for the safe use of a source of
radiation to treat refrigerated or frozen uncooked meat, meat
byproducts, and certain meat food products to control foodborne
pathogens and extend product shelf-life. This action is in response to
a petition filed by Isomedix, Inc.
Page 64108
DATES: Effective December 3, 1997; written objections and requests for
a hearing by January 2, 1998.
ADDRESSES: Submit written objections to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Patricia A. Hansen, Center for Food
Safety and Applied Nutrition (HFS-206), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-418-3093.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Introduction
II. Evaluation of Safety
III. Evaluation of the Safety of the Petitioned Use of a Source of
Radiation
A. General Framework
B. Radiation Chemistry
C. Toxicological Considerations
D. Nutritional Considerations
E. Microbiological Considerations
IV. Current Good Manufacturing Practice Considerations
V. Labeling
VI. Conclusion of Safety
VII. Environmental Impact
VIII. Objections
IX. References
I. Introduction
In a notice published in the Federal Register of August 25, 1994
(59 FR 43848), FDA announced that a food additive petition (FAP 4M4428)
had been filed by Isomedix, Inc., 11 Apollo Dr., Whippany, NJ 07891,
proposing that part 179 Irradiation in the Production, Processing and
Handling of Food (21 CFR part 179) be amended to provide for the safe
use of a source of radiation to treat the fresh or frozen raw edible
tissue of domesticated mammalian human food sources for purposes of
reduction of parasites and microbial pathogens, and extension of
product shelf-life.
Several letters, from members of academia and from a trade group,
were received in response to the filing of the petition. The letters
urged FDA to approve irradiation of beef and other meats, and expressed
the belief that the use of irradiation could benefit public health and
improve the safety of meat by controlling foodborne pathogens. Because
the letters expressed general support for the agency's action, but
provided no substantive information, these comments will not be
addressed further.
The comments illustrate, however, a heightened public awareness of
the health threat posed by pathogens in or on meat. Among these,
Escherichia coli O157:H7, Salmonella sp., and Clostridium perfringens
are of primary concern from a public health standpoint; E. coli O157:H7
because of the severity of the illness associated with the organism,
and Salmonella and C. perfringens because of the high number of
outbreaks and individual cases of foodborne illness associated with
these pathogens (Refs. 1 and 2).\1\
---------------------------------------------------------------------------
\1\ E. coli O157:H7 causes hemorrhagic colitis, a severe
illness, the symptoms of which include high fever, vomiting, and
bloody diarrhea, with consequent dehydration. In patients with
weakened or immature immune systems, the infection can progress to
hemolytic uremic syndrome (HUS), a life-threatening kidney disease
with a mortality rate of 6 percent (Ref. 3). The number of outbreaks
in the United States reported to be associated with E. coli O157:H7
has increased from 4 in 1992 to 30 in 1994; E. coli O157:H7 has been
estimated to cause more than 20,000 infections and 250 deaths each
year (Ref. 4).
Salmonella sp. are a leading reported cause of foodborne
bacterial diseases (Ref. 5) and have been reported to be associated
with 48 percent of beef-related outbreaks (Ref. 2). C. perfringens
is also an important agent of foodborne microbial disease, with a
projected incidence of 652,000 cases and 7.6 deaths per year. During
1973 to 1987, beef accounted for 30 percent of all C. perfringens
type A food poisoning outbreaks (Ref. 6).
---------------------------------------------------------------------------
Although proper handling practices and cooking to recommended
internal temperatures are effective interventions in preventing
foodborne illness associated with meat products, much effort has gone
into the development of other interventions aimed at reducing microbial
pathogens. Irradiation has been proposed as one such additional tool.
The subject petition requests that FDA amend the food additive
regulations to authorize the use of ionizing radiation to ``control
microbial pathogens in raw, fresh-chilled, and frozen intact and
comminuted edible tissue of the skeletal muscle and organ meat of
domesticated mammalian food sources; with concomitant control of
infectious parasites, and, extension of acceptable edible/marketable
life of chilled/refrigerated and defrosted meat through the reduction
in levels of spoilage microorganisms.'' The petition also specifies
that the proposed foods are to be ``primarily from bovine, ovine,
porcine, and equine sources.'' The petition requests that a maximum
dose of 4.5 kiloGray (kGy) be established for the irradiation of fresh
(chilled, not frozen) meat, and that a maximum dose of 7.0 kGy be
established for the irradiation of frozen meat.
In this final rule, FDA is adding refrigerated and frozen uncooked
meat, meat byproducts (e.g., edible organs such as the liver and the
kidneys) and certain meat food products (e.g., ground beef and
hamburger) to the list of foods that are authorized (under
Sec. 179.26(b)) for treatment with ionizing radiation. In addition, FDA
is establishing 4.5 kGy as the maximum permitted dose for irradiation
of refrigerated meat, meat byproducts, and certain meat food products
;
and 7.0 kGy as the maximum permitted dose for irradiation of frozen
meat, meat byproducts and certain meat food products.
The foods that are set forth in the regulation below are all
subject to the Federal Meat Inspection Act (21 U.S.C. 601, et seq.),
and are defined by the U.S. Department of Agriculture/Food Safety and
Inspection Service (USDA/FSIS) in title 9 of the Code of Federal
Regulations. These foods include meat, as defined by USDA/FSIS in 9 CFR
301.2(rr),\2\ meat byproducts, as defined by USDA/FSIS in 9 CFR
301.2(tt),\3\ and certain meat food products\4\ from among those
defined by USDA/FSIS in 9 CFR 301.2(uu).
---------------------------------------------------------------------------
\2\ Meat. (1) The part of the muscle of any cattle, sheep,
swine, or goats, which is skeletal or which is found in the tongue,
or in the diaphragm, or in the heart, or in the esophagus, with or
without the accompanying and overlying fat, and the portions of
bone, skin, sinew, nerve, and blood vessels which normally accompany
the muscle tissue and which are not separated from it in the process
of dressing. It does not include the muscle found in the lips,
snout, or ears. This term, as applied to products of equines, shall
have a meaning comparable to that provided in this paragraph with
respect to cattle, sheep, swine, and goats.
(2) The product derived from the mechanical separation of the
skeletal muscle tissue from the bones of livestock using the
advances in mechanical meat/bone separation machinery and meat
recovery systems that do not crush, grind, or pulverize bones, and
from which the bones emerge comparable to those resulting from hand-
deboning (i.e., essentially intact and in natural physical
conformation such that they are recognizable, such as loin and rib
bones, when they emerge from the machinery) which meets the criteria
of no more than 0.15 percent or 150 mg/100 gm of product for calcium
(as a measure of bone solids content) within a tolerance of 0.03
percent or 30 mg.
\3\ Meat byproduct. Any part capable of use as human food, other
than meat, which has been derived from one or more cattle, sheep,
swine, or goats. This term, as applied to products of equines, shall
have a meaning comparable to that provided in this paragraph with
respect to cattle, sheep, swine, and goats.
\4\ Specifically, those meat food products within the meaning of
9 CFR 301.2(uu), with or without nonfluid seasoning, that are
otherwise composed solely of intact or ground meat and/or meat
byproducts (e.g., ground beef as in 9 CFR 319.15(a); hamburger as in
9 CFR 319.15(b); certain defatted beef or pork products as in 9 CFR
319.15(e) and 9 CFR 319.29(a), respectively; mechanically separated
(species) as in 9 CFR 319.5).
---------------------------------------------------------------------------
In the text of this document, the term ``meat'' will be used to
refer collectively to meat, meat byproducts, and applicable meat food
products. When, in the text of this document, the discussion is also
applicable to foods that might, in common usage, be referred to as a
meat or as a type of meat (e.g., chicken, turkey, or fish), but that
Page 64109
do not conform to the definitions of meat, meat byproducts, or meat
food products in title 9 of the Code of Regulations, the term ``flesh
food(s)'' will be used instead.
II. Evaluation of Safety
Under section 201(s) of the Federal Food, Drug, and Cosmetic Act
(the act) (21 U.S.C. 321(s)), a source of radiation used to treat food
is defined as a food additive:
* * * The term ``food additive'' means any substance the
intended use of which results or may reasonably be expected to
result, directly or indirectly, in its becoming a component or
otherwise affecting the characteristics of any food (including any
substance intended for use in producing, manufacturing, packing,
processing, preparing, treating, packaging, transporting, or holding
food; and including any source of radiation intended for any such
use) * * *.
Under section 409(c)(3)(A) of the act (21 U.S.C. 348(c)(3)(A)), a
food additive cannot be approved for a particular use unless a fair
evaluation of the evidence establishes that the additive is safe for
that use. The concept of safety embodied in the Food Additives
Amendment of 1958 (the Amendment) is explained in the legislative
history of the provision: ``Safety requires proof of a reasonable
certainty that no harm will result from the proposed use of the
additive. It does not--and cannot--require proof beyond any possible
doubt that no harm will result under any conceivable circumstance'' (H.
Rept. 2284, 85th Cong., 2d sess. 4 (1958)). This concept of safety has
been incorporated into FDA's food additive regulations (21 CFR
170.3(i)).
The legislative history of the Amendment clearly reflects that
Congress recognized that it is impossible to establish with complete
certainty the absolute harmlessness of any chemical substance. The
concept of safety contained in the Amendment has, as its focus, the
reduction of uncertainty about the safety of an additive to the point
where the agency can reasonably conclude that no harm will result from
its proposed use.
The statute does not prescribe the safety tests to be performed but
leaves that determination to the discretion and scientific expertise of
FDA. Not all food additives require the same amount or type of testing.
The amount and type of testing required to establish the safety of an
additive will vary depending on the particular additive and its
intended use.
In this particular case, the additive is not, literally, added to
food. Instead, a source of radiation is used to process or treat food
such that, analogous to other food processes, its use can affect the
characteristics of the food. In the subject petition, the intended
technical effect is a change in the microbial load of the food,
specifically, a reduction in the numbers of microorganisms, both
pathogenic and nonpathogenic, in or on meat. It is important to
realize, however, that the petitioner is not required to show, nor is
FDA permitted to consider, that irradiation of meat has benefits,
health or otherwise, for consumers of irradiated meat. The legislative
history of the Amendment is clear on this point:
The question of whether an additive produces such a technical
effect (or how much of an additive is required for such an effect)
is a factual one, and does not involve any judgement on the part of
the Secretary whether such effect results in any added `value' to
the consumer of such food or enhances the marketability from a
merchandising point of view.
S. Rept. 2422, 85th Cong., 2d sess. 7 (1958). Accord: H. Rept. 2284,
85th Cong., 2d sess. 6 (1958)
Thus, in evaluating the safety of a source of radiation to treat
meat intended for human consumption, FDA cannot consider the possible
benefits to consumers or to food processors. Instead, the agency must
identify the various effects that can result from irradiating this food
and assess whether any of these effects may pose a human health risk.
In this regard, three areas of concern need to be addressed: potential
toxicity, nutritional adequacy, and potential microbiological risk.
Each of these areas is discussed in detail in section III of this
document.
III. Evaluation of Safety of the Petitioned Use of a Source of
Radiation
The petitioner submitted a large number of published articles and
other study reports containing data and information in the areas of
radiation chemistry,\5\ dietary consumption patterns, toxicology,
nutrition, and microbiology. FDA has reviewed the data and studies
submitted in the petition, as well as other information in its files
relevant to the safety and nutritional adequacy of meat treated with
ionizing radiation. Specifically, the agency evaluated information
concerning:
---------------------------------------------------------------------------
\5\ The term ``radiation chemistry'' refers to the chemical
reactions that occur as a result of the absorption of ionizing
radiation. Like all chemical reactions, these radiation-induced
reactions depend on the nature of the reactants and on the energy
supplied to the system. In the context of food irradiation, the
radiation-induced reactions depend on the chemical constituents of
the food and such factors as the ambient atmosphere (which also
contains potential reactants), the physical state of the food, the
ambient temperature, and the radiation dose. Radiation-induced
chemical reactions can affect the detailed chemical composition of
the food and the cellular components of the microorganisms in or on
the food.
---------------------------------------------------------------------------
1. Studies of the radiation chemistry of food components and whole
foods, including chemical analyses of irradiated flesh foods.
2. Toxicity studies of flesh foods, including studies of irradiated
beef, pork, horse meat, chicken, and fish.
3. Studies of nutrient levels in, and information regarding dietary
consumption patterns of, irradiated flesh foods.
4. Studies of the effects of irradiation on both pathogenic and
nonpathogenic microorganisms.
A. General Framework
To determine whether the use of a food additive is safe, FDA
typically considers the chemical identity and amount of the additive
that will be ingested in light of what is known regarding its toxicity.
In the case of substances added directly to food, the agency estimates
the amount of the additive that will be ingested from the proposed use
levels of the additive in particular foods or food types along with
consideration of consumption patterns of those foods. Information about
the chemical structure of an additive and an assessment of the likely
consumption levels of the additive, together with information obtained
from toxicological testing, forms the basis for evaluating safety.
In the case of food irradiation, the effects of this form of
processing on the characteristics of the treated foods are a direct
result of the chemical reactions induced by the absorbed radiation.
Research has established that the types and amounts of products
generated by radiation-induced chemical reactions (hereinafter referred
to as ``radiolytic products'') depend on the chemical constituents of
the food and on the conditions of irradiation. Information regarding
the chemical structures and the amounts of radiolytic products in
particular food types, together with the information obtained from
toxicological testing, forms a sound basis for evaluating the
toxicological safety of an irradiated food.
In the case of food irradiation, the nutritional adequacy and the
microbiological safety of the treated foods must also be evaluated.
Research has shown that the principles of radiation chemistry govern
the extent of changes both in the nutrient levels and in the microbial
load of irradiated foods. Key factors include the specific nutrient or
microorganism of interest, the food, and the conditions of irradiation.
Page 64110
B. Radiation Chemistry
Scientists have compiled an enormous body of data regarding the
effects of ionizing radiation on different foods under various
conditions of irradiation. Because of the complexity in the composition
of any food and the large numbers of specific radiation-induced
reactions that can occur, the agency will limit its discussion here to
the broad principles that are applicable to this decision.\6\ These
broad principles provide the basis for extrapolation and generalization
from data obtained in specific foods irradiated under specific
conditions to draw conclusions regarding foods of a similar type
irradiated under different, yet related, conditions.
---------------------------------------------------------------------------
\6\ Several books provide more detailed discussions of radiation
chemistry with references to the large number of original research
studies, particularly in the area of food irradiation. Sources that
can be consulted for further information include, but are not
limited to: Radiation Chemistry of Major Food Components, edited by
P. S. Elias and A. J. Cohen, Elsevier, Amsterdam, 1977; Recent
Advances in Food Irradiation, edited by P. S. Elias and A. J. Cohen,
Elsevier, Amsterdam, 1983; and Diehl, J. F., ``Chemical Effects of
Ionizing Radiation,'' Ch. 3 in Safety of Irradiated Foods, Marcel
Dekker, New York, 1995.
---------------------------------------------------------------------------
1. Factors Affecting the Radiation Chemistry of Foods
Apart from the chemical composition of the food itself, the
factors, or irradiation conditions, that are most important in
considering the radiation chemistry of a given food include the
radiation dose, the physical state of the food (e.g., the solid or
frozen versus the liquid or nonfrozen state), and the ambient
atmosphere (air, reduced oxygen, vacuum, etc.).
With respect to dose, the amounts of radiolytic products generated
in a particular food have been shown to be directly proportional to the
radiation dose (Refs. 7, 8, and 9). Thus, it is entirely sound to
extrapolate from data obtained at high radiation doses to draw
conclusions regarding the amounts of radiolytic products expected to be
generated at lower doses.
The radiation chemistry of food is also strongly influenced by the
physical state of the food. If all other conditions, including dose and
ambient atmosphere, are the same, the extent of chemical change that
occurs in a particular food in the frozen state is less than the change
that occurs in the same food in the nonfrozen state. This is a result
of the reduced mobility, in the frozen state, of the initial products
of irradiation (free radicals, which are highly energetic, unstable
molecules). Because of their reduced mobility, these free radicals tend
to recombine to form the original substance rather than to diffuse
through the food to react with other components of the food matrix and
thereby form different substances (Refs. 9 and 10). Thus, both the
types and the amounts of radiolytic products are affected by the
physical state of the food, and, for a given food, higher radiation
doses are needed to effect the same degree of chemical change in frozen
versus nonfrozen food. Higher radiation doses are also needed to
accomplish the same antimicrobial technical effect in a frozen food
versus a nonfrozen food of the same type.
The formation of radiolytic products in a given food is also
affected by the ambient atmosphere. Irradiation in an atmosphere of
high oxygen content generally produces both a greater variety, and
greater amounts, of radiolytic products in the food than would be
produced in an atmosphere of lower oxygen content. This is because
irradiation initiates certain oxidation reactions, reactions that occur
with greater frequency in foods with high fat content (Refs. 11 and
12). The final products of radiation-induced oxidation reactions in
foods are similar to those produced by oxidation reactions induced by
other processes (e.g., storage or heating in air).
In general, the types of products generated by irradiation are
similar to those produced by other food processing methods. Radiation-
induced chemical changes, if sufficiently large, however, may cause
changes in the organoleptic properties of the food. Because food
processors wish to avoid undesirable effects on taste, odor, color, or
texture, there is an incentive to minimize the extent of these chemical
changes in the food. Thus, irradiation is often conducted under reduced
oxygen levels or on food in the frozen state.
2. Radiation Chemistry of the Major Components of Flesh Foods
The major components of all foods are water, carbohydrates,
proteins, and lipids. Flesh foods, as a group, have very little
carbohydrate content, and are comprised primarily of water, proteins,
and lipids. The radiation chemistry of these components is well
established.
In foods of relatively high water content, such as flesh foods,
free radicals produced by radiolysis of water form the majority of the
initial products of the radiation-induced chemical reactions. These
free radicals, in turn, react with the other components of the food to
form the final, stable, radiolytic products.
With respect to proteins, several types of reactions can occur as a
result of irradiation. One type of reaction is the breaking of a small
number of peptide bonds to form polypeptides of shorter length than the
original protein (Refs. 13 and 14).\7\ Radiation-induced aggregation or
cross-linking of individual polypeptide chains can also occur; these
processes result in protein denaturation (Refs. 13 through 16). In
irradiated flesh foods, most of the radiolytic products derived from
proteins have the same chemical composition but are altered in their
secondary and tertiary structures. These changes are similar to those
that occur as a result of heating, but in the case of irradiation, such
changes are far less pronounced and the amounts of reaction products
generated are far lower.
---------------------------------------------------------------------------
\7\ Proteins are composed of amino acids joined by peptide
bonds. The characteristic sequence of amino acids in a particular
protein is known as the primary structure. The extent and nature of
the coiling or pleating of different segments of the protein is
known as the secondary structure. The three dimensional shape of the
coiled or pleated protein is known as the tertiary structure.
Denaturation refers to structural changes that result in a loss of
biological properties; these are usually changes in the secondary or
tertiary structures.
---------------------------------------------------------------------------
A third type of reaction that can occur when proteins are
irradiated involves the reaction of amino acids in the polypeptide
chain with the free radicals produced from water, without the breaking
of peptide bonds (Refs. 17 and 18). The compounds produced by such
reactions, like the other radiolytic products derived from proteins,
are similar or identical to those found in foods that have not been
irradiated. The radiolytic products resulting from this third type of
reaction occur in very small amounts; various studies have established
that there is little change in the amino acid composition of flesh
foods irradiated at doses below 50 kGy (Refs. 19 and 20), a dose
approximately seven times greater than the highest dose set forth in
the regulation below.
The radiation chemistry of lipids (fats) is also well
established.\8\ Numerous studies have been performed with various oils
and fats and also on the lipid fraction of irradiated foods (see, e.g.,
Refs. 21 through 25). A variety of radiolytic products derived from
lipids have been identified, including fatty acids, esters, aldehydes,
ketones, alkanes, alkenes, and other hydrocarbons (Refs. 7, 22, 23, 25,
and 26a through 26c).\9\ All of these types of
Page 64111
compounds are also found in foods that have not been irradiated. These
types of compounds are also produced by heating foods, and, in the case
of heating, are produced in amounts far higher than the trace amounts
that result from irradiating foods (Refs. 23 and 27).
---------------------------------------------------------------------------
\8\ The fat in meat is composed primarily of triglycerides, each
molecule of which contains three fatty acids. The predominant fatty
acids in the triglycerides of flesh foods are oleic, palmitic,
linoleic, and stearic acid.
\9\ One major effort to determine whether radiolytic products in
a flesh food presented any risk to human health is described in a
report entitled ``Evaluation of the Health Aspects of Certain
Compounds Found in Irradiated Beef,'' prepared by the Life Sciences
Research Office of the Federation of American Societies for
Experimental Biology under contract with the U.S. Army (``the FASEB/
LSRO report'' and supplements, Refs. 26a through 26c).
This report presented the results of chemical analyses performed
on frozen beef irradiated under vacuum at a dose of 56 kGy. Sixty-
five volatile radiolytic products were identified, most of which
originated from the lipid fraction. This study established that
these 65 radiolytic products were either identical or structurally
similar to substances found in foods that have not been irradiated,
and that these individual radiolytic products were produced in very
small amounts (generally 1 to 700 parts per billion of irradiated
beef), even at a radiation dose eight times higher than the highest
dose requested in the petition.
---------------------------------------------------------------------------
In summary, the results obtained from chemical analyses of
irradiated flesh foods establish that there would be very small amounts
of individual radiolytic products generated by radiation doses
comparable to those proposed in the petition. In addition, most of
these radiolytic products are either the same as, or structurally very
similar to, compounds found in foods that have not been irradiated.
Because of their structural similarities to compounds found in foods
that have not been irradiated, these radiolytic products would be
expected to be toxicologically similar to such compounds as well. Thus,
the available information regarding the radiation chemistry of the
major components of flesh foods supports the proposition that there is
no reason to suspect a toxicological hazard due to consumption of an
irradiated flesh food.
3. Flesh Foods as a Generic Class
As noted above, flesh foods are comprised primarily of water,
proteins, and lipids.\10\ While the proportions of the individual amino
acids in the proteins and the individual fatty acids in the lipid
fraction vary somewhat among the different flesh foods, the same
chemical components provide the basis for any chemical reactions in
flesh foods caused by the absorption of ionizing radiation. Because of
this, the same compounds (in slightly varying proportions) will
constitute the majority of radiolytic products in all irradiated flesh
foods.
---------------------------------------------------------------------------
\10\ The proximate composition of flesh foods does not vary
widely. Beef and lamb, for example, are composed of approximately 17
to 20 percent protein, 15 to 25 percent fat, and 56 to 65 percent
water, depending on the cut. Chicken, depending on the cut and
whether the skin is included, is approximately 18 to 25 percent
protein, 5 to 19 percent fat, and 57 to 75 percent water. Fish,
depending on the species, is approximately 16 to 27 percent protein,
1 to 20 percent fat, and 60 to 75 percent water.
The predominant fatty acids in the triglycerides of flesh foods
are oleic, palmitic, linoleic, and stearic acid. The saturated fatty
acids (palmitic and stearic acid) contribute approximately 8 to 12
percent of the fat content in both beef and lamb. The fat in chicken
(skin on) and pork is composed of approximately 2 to 9 percent
saturated fatty acids. The amino acid content of flesh foods also
does not vary widely. In beef, pork, lamb, and chicken, tryptophan
contributes the smallest weight percentage and lysine the greatest
weight percentage to the amino acid content (see Refs. 28 and 29).
---------------------------------------------------------------------------
The large number of studies on the radiation chemistry of food and
food components, taken together, support this conclusion regarding
commonality in the chemistry and predictability of the types and
amounts of radiolytic products (see, e.g., Refs. 14, 18, and 30).
Accordingly, it is scientifically sound to generalize from the data
obtained in studies of a variety of specific irradiated flesh foods to
draw conclusions regarding the irradiation of flesh foods as a class
(Ref. 30). Because of the foregoing, FDA has determined that, to
evaluate the safety of foods that are the subject of this petition
(i.e., meat and meat byproducts as defined in 9 CFR 301.2(rr) and (tt),
and certain meat food products from among those defined in 9 CFR
301.2(uu)), it is entirely appropriate to consider the available data
from all flesh foods, irradiated under a variety of conditions. Details
of the agency's analysis are presented below.
C. Toxicological Considerations
As discussed previously, all of the available information from the
results of chemical analyses suggests that there is no reason to
suspect a toxicological hazard due to consumption of an irradiated
food. However, while chemical analyses have not identified the presence
of any particular radiolytic products in amounts that would raise a
toxicological concern, the agency notes that the large body of data
from studies where irradiated flesh foods were fed to laboratory
animals provides an independent way to assess toxicological safety.
Thus, the agency has also examined all the available data from
toxicological studies that are relevant to the safety of irradiated
meat, namely, all of those with flesh foods.
This includes the data relied on by the agency in its previous
evaluation of the safety of poultry irradiated at doses up to 3 kGy
(discussed in the Federal Register of May 2, 1990 (55 FR 18538)), as
well as additional data in FDA files from studies of irradiated meat,
poultry, and fish. The agency's analysis incorporates the principle
that toxicological data collected from studies on foods irradiated at
high doses can be applied to the toxicological evaluation of foods of
the same generic class receiving lower doses (Refs. 14 and 30). The
agency's analysis also takes into account the known effects of other
conditions of irradiation, such as the physical state of the food and
the ambient atmosphere, to compare the results of different studies. A
summary of that analysis is presented below.
1. Toxicity Studies of Flesh Foods Relied Upon by FDA in Previous
Safety Evaluations
In the early 1980's, as part of a regulatory initiative on
irradiation of minor dry ingredients (e.g., spices and seasonings) and
foods irradiated at low doses, the agency conducted a review of all
toxicological studies of irradiated foods that were available at that
time. In order to come to timely closure on that rulemaking, the agency
limited its analysis to whether individual studies could stand alone to
support a safety decision and to whether the studies showed any
evidence of toxicity attributable to irradiation. The agency found no
evidence of toxicity that could be attributed to irradiation of food
and amended its regulations to authorize the use of irradiation on
foods at low doses (no greater than 1 kGy) and on minor dry ingredients
at doses no greater than 30 kGy (51 FR 13376 at 13378, April 18, 1986).
However, FDA concluded that it could not, at that time, expand
approval to higher doses for foods other than minor dry ingredients
because most of the individual studies had limitations in design or
conduct. The agency did not attempt to determine whether the available
toxicological studies, taken as a whole, could complement each other
and thus compensate for weaknesses in any individual study or whether
additional information could be obtained to supplement the available
reports. In addition, FDA had not, at that time, assessed the
nutritional and microbiological ramifications of irradiating major
dietary components at doses above 1 kGy.
Although, as noted, many of the animal feeding studies were not
fully adequate by modern toxicology standards, the agency found that
several studies were fully adequate in design and conduct and could
stand alone in support of safety. One of these studies examined the
effects of feeding an irradiated flesh food to animals; specifically,
rats were fed beef stew or evaporated milk, each food irradiated at
27.9 and 55.8 kGy (51 FR 13376 at
Page 64112
13384).\11\ The data showed that no treatment-related adverse effects
were observed with either irradiated food.
---------------------------------------------------------------------------
\11\ Although the agency cited this as one study, it would be
more accurately described as one report where the results of two
chronic feeding studies of irradiated beef stew, one in rats and one
in dogs, and two chronic studies of irradiated evaporated milk, also
one in rats and one in dogs, were described. The two studies in rats
were fully accepted by the agency. The two studies in dogs were not
fully accepted in the agency's early review solely because of the
small number of animals used.
---------------------------------------------------------------------------
Subsequent to the agency's review of all animal feeding studies,
discussed above, FDA further evaluated a series of feeding studies of
irradiated poultry, obtaining additional information on some of the
studies and analyzing the results in greater detail.\12\ The agency has
previously discussed the findings of, and its conclusions regarding,
these studies in its decision authorizing the irradiation of poultry at
doses no greater than 3 kGy (55 FR 18538, May 2, 1990).\13\ Briefly,
the agency concluded that three animal feeding studies of high quality
(a multigeneration study in rats, a chronic study in rats, and a 1-year
study in beagle dogs), in which chicken was irradiated at 3 or 6 kGy
and administered at a level of 35 percent of the diet, showed no
evidence of adverse toxicological effects attributable to irradiation
(55 FR 18538 at 18539 and 18540). At that time, the agency also
reviewed all other toxicity data on irradiated poultry and found the
results to be consistent with a conclusion that irradiated poultry does
not present a toxicological hazard.\14\
---------------------------------------------------------------------------
\12\ The earlier review had not fully accepted some of these
studies because the reports did not contain a complete discussion of
all relevant details. In addition, FDA had not fully addressed the
possible significance of the use of an antioxidant to prevent
rancidity from developing during drying of the meat for storage. The
agency subsequently concluded that the studies were acceptable after
receiving additional information from the laboratory, and after
determining that the antioxidant could not have changed the effects
due to irradiation because it was added after the chicken was
irradiated (see 55 FR 18538 at 18539 and 18540).
\13\ Following publication of the final rule, FDA received
several letters and two submissions within the 30-day objection
period. The submissions sought revocation of the final rule and
requested a hearing. Elsewhere in this issue of the Federal
Register, FDA is denying the objections and requests for a hearing
because they do not raise issues of material fact that justify a
hearing or otherwise provide a basis for revoking the final rule.
\14\ The agency evaluated several other studies in which animals
were fed radiation-sterilized chicken and one in which mice were fed
chicken irradiated at 7 kGy. No treatment-related adverse effects
were seen in any of these studies (55 FR 18538 at 18540). However,
because, in the studies of radiation-sterilized chicken, the
conditions of irradiation were different from what would be used in
commerce under the regulation sought by the petitioner, and because
of deficiencies in the data from the study of chicken irradiated at
7 kGy, FDA did not rely explicitly on these studies.
---------------------------------------------------------------------------
In summary, the agency has previously found that the following
toxicological studies of irradiated flesh foods, tested in fully
adequate animal feeding studies, demonstrated no adverse health effects
that could be attributed to irradiation: beef (as a component of stew)
irradiated at doses of 27.9 and 55.8 kGy and tested in a chronic study
in rats; chicken irradiated at doses of 3 kGy and 6 kGy and tested in a
three generation reproduction study in rats, a chronic study in rats,
and a 1-year study in dogs.
2. Additional Analyses of Toxicity Data
In 1980, a Joint FAO/IAEA/WHO Expert Committee\15\ concluded that
irradiation of any food commodity at an average dose of up to 10 kGy
presents no toxicological hazard (Ref. 31). Based in part on the Expert
Committee's conclusion regarding the absence of toxicological hazard
(as well as conclusions on the nutritional adequacy and microbiological
safety of irradiated foods), the Codex Alimentarius Commission (Codex),
in 1984, recommended that member nations adopt the Codex finding that
the ``wholesomeness of foods irradiated so as to have absorbed an
overall average dose of up to 10 kGy, is not impaired'' (Ref. 32). FDA
did not adopt the Codex recommendation in its 1986 rulemaking because,
as noted, it had not yet analyzed the issues of nutritional adequacy
and microbiological safety in a sufficiently comprehensive way and had
not pursued the analysis of toxicity data beyond the examination of
individual studies.
---------------------------------------------------------------------------
\15\ FAO is the Food and Agriculture Organization of the United
Nations, IAEA is the International Atomic Energy Agency, and WHO is
the World Health Organization.
---------------------------------------------------------------------------
Subsequently, WHO, at the request of one of its member States,
conducted a new review and analysis of the safety data on irradiated
food (Ref. 33). WHO considered the extent to which data on one food
type can be extrapolated to other foods and the extent to which
individual studies of irradiated foods can be integrated into one large
database to be evaluated as a whole, as opposed to separate evaluations
of a series of individual studies.
This review included all the studies in FDA's files that the agency
considered as reasonably complete, as well as those studies that
appeared to be acceptable but had deficiencies interfering with
interpretation of the data (see 51 FR 13376 at 13378). The WHO review
also included data from USDA and from the Federal Research Centre for
Nutrition at Karlsruhe, Germany. WHO explicitly documented, in detail,
the data relied on for its conclusion that the integrated toxicological
database is sufficiently sensitive to evaluate safety and that no
adverse toxicological effects due to irradiation were observed in the
dose ranges tested (Ref. 33).
FDA has previously reviewed the individual studies that are cited
in the WHO report and found no evidence of toxicity attributable to
irradiation. FDA has now also reexamined these studies to determine
whether the integrated toxicological database derived from this body of
work, together with the information regarding radiation-induced
chemical changes, establishes the toxicological safety of meat
irradiated under the conditions set forth in the regulation below.
FDA finds that, while many of these studies cannot individually
establish safety,\16\ they still provide important information that,
evaluated collectively, supports a conclusion that there is no reason
to believe that irradiation of flesh foods presents a toxicological
hazard (Refs. 34a and 34b). The overwhelming majority of studies
reported no adverse toxicological effects due to consumption of
irradiated flesh foods; equally important, the few effects observed
were not reproduced in other studies.\17\ In addition, FDA notes that
many of the feeding studies were conducted using flesh foods irradiated
at doses far higher than those proposed in the petition, providing some
exaggeration in terms of the amounts of radiolytic products consumed.
---------------------------------------------------------------------------
\16\ For example, the number of animals used in many of the
early studies is smaller than that commonly used today. Complete
histopathology was not always done or reported. For some studies,
the data are available only in brief summary form.
\17\ If the radiolytic products in flesh foods irradiated under
test conditions were of any toxicological significance, consistent
effects, particularly in those tests where the foods were irradiated
at comparable doses and under comparable conditions, should have
been observed. It is also important to note that at the time many of
these studies were conducted, scientists did not fully understand
the nutritional ramifications of modifying an animal's diet by
feeding it large amounts of foods not normally consumed by
laboratory animals. The few adverse effects observed in certain of
the studies are consistent with what one could expect based on the
nutritional composition of the test diet (Refs. 33 and 35).
---------------------------------------------------------------------------
Details regarding the important features of both WHO's and FDA's
recent analyses are presented below. FDA has evaluated all relevant
data to ensure that any potential evidence of toxicity would not be
overlooked. However, because of the large number of studies in the
total database, this document focuses on the types of
Page 64113
studies of irradiated flesh foods that provide the greatest opportunity
for detecting a treatment-related effect rather than attempting an
exhaustive discussion of all the available studies.\18\ In addition,
this document concentrates on those studies that were conducted at
radiation doses greater than, or comparable to, the doses requested in
the subject petition.
---------------------------------------------------------------------------
\18\ Chronic toxicity studies and reproductive toxicity studies
are generally considered to be the most sensitive tools for
detecting treatment-related toxicological effects when there is no
basis, a priori, to expect a particular adverse effect. This is
because treatment over the lifetime of the animal in a chronic study
allows the longest time for a subtle effect to be manifested, and
because the developing organism in reproduction and teratology
studies can be particularly sensitive to toxic effects.
---------------------------------------------------------------------------
3. Chronic Feeding Studies
Both FDA and WHO evaluated chronic studies in which various flesh
foods, irradiated at doses ranging from 6 to 74 kGy, were fed to
animals (Ref. 36). These include those studies, discussed previously,
on which FDA has relied in previous safety evaluations of irradiated
foods. The studies in which no adverse effects were reported include
the following: (1) Studies in which rats were fed beef irradiated at 56
kGy; pork at 56 kGy; chicken at 6 kGy; fish at 6 kGy; horse meat at 6.5
kGy; fish at 56 kGy; beef stew at 56 kGy; a mixture of beef, pork,
fish, and other foods at 28 kGy; pork brain and egg at 93 kGy; and pork
at 74 kGy; (2) studies in which mice were fed chicken irradiated at 59
kGy; bacon and bacon fat at 56 kGy; chicken at 7 kGy; fish and beef at
56 kGy; pork brain and egg at 93 kGy; and pork and chicken at 56 kGy;
and (3) studies in which dogs were fed chicken irradiated at 59 kGy;
chicken, beef, and jam at 56 kGy; bacon and cabbage at 56 kGy, beef at
56 kGy; and chicken at 6 kGy.
In addition to the studies listed above, four chronic studies
reported observations that merit further discussion. FDA has concluded
that the effects reported in these four studies were either not
attributable to irradiation or were otherwise not of toxicological
significance.
In one study (Ref. 37), weanling rats fed a mixture of radiation-
sterilized (56 kGy) chicken stew and irradiated (6 kGy) cabbage for 19
days were reported to have reduced levels of alkaline phosphatase in
duodenal tissue. However, this effect was not seen in weanling rats fed
either (but not both) radiation-sterilized chicken stew or irradiated
cabbage for 19 days and was not seen in other rats that were fed the
irradiated chicken stew/cabbage mixture for 150 days. Additionally, no
adverse histopathological findings that would indicate a toxic effect
were reported. FDA concludes that the observed decrease in alkaline
phosphatase levels in weanlings is not of toxicological significance
for three reasons: (1) The effect observed in weanling rats was not
observed in rats maintained on the same diet into adulthood, (2) the
effect was not reproduced when either of the two irradiated foods was
fed individually, and (3) no other reported observations indicate a
toxic effect (Ref. 38).
In a second study (Ref. 39), a diet composed of a mixture of nine
foods, including bacon, beef, ham, and fish was radiation-sterilized
(56 kGy) and fed to rats. This study reported a decreased weight gain
for third generation females, but not for males. FDA has concluded that
this effect cannot be attributed to irradiation because it was
accompanied by breeding problems that significantly reduced the sizes
of the groups of rats fed the control diet as well as the groups of
rats fed the irradiated diet, an observation that is indicative of
overall dietary deficiencies unrelated to radiation treatment (Ref.
35).
A third study (Ref. 40) reported a significant increase in heart
lesions (auricular dilatations) in mice fed radiation-sterilized (56
kGy) pork and chicken. FDA has determined that this effect cannot be
attributed to the irradiated flesh foods because a replicate study with
nearly 5,000 mice of the same strains showed no such lesions. (Refs.
34a and 38).
Finally, a chronic study in dogs fed irradiated (8 kGy) soft shell
clams reported a decrease in blood urea nitrogen (BUN) in the males but
not in the females (Ref. 41). FDA has concluded that the decreased BUN
levels in this study were not of toxicological significance for the
following reasons. FDA notes that, while an elevated BUN level could be
a sign of kidney malfunction (urea is a metabolite of protein excreted
by the kidney), a decrease in BUN level may simply indicate less
protein consumed. No significant findings were reported, however, with
respect to clinical chemistry parameters other than BUN levels, or in
the histopathological examinations. Moreover, given that the normal
range of BUN levels in dogs is quite wide, the observed decrease in BUN
level is likely to represent an artifact of the low statistical power
of the study and is not of toxicological significance (Ref. 38).
In summary, a large number of chronic feeding studies have been
conducted in rats, mice, and dogs with flesh foods irradiated at doses
between 6 and 74 kGy. In these studies, no toxic effects that can be
attributed to radiation treatment were consistently observed.
4. Reproduction and Teratology Studies
FDA has also reviewed the following reproduction/teratology studies
(Ref. 42) in which flesh foods, irradiated at doses of 6 kGy or higher,
were fed to laboratory animals: (1) Studies in which rats were fed pork
irradiated at 56 kGy; chicken and green beans irradiated at 59 kGy; and
fish irradiated at 6 kGy (two separate studies with fish); (2) a
multigeneration reproduction study and a teratology study in which mice
were fed chicken irradiated at 59 kGy and 45 kGy, respectively; (3) two
studies in which dogs were fed beef irradiated at 56 kGy; (4) a study
in which hamsters were fed chicken irradiated at 45 kGy; and (5) a
study in which rabbits were fed chicken irradiated at 45 kGy.
All of these studies, except one, showed no adverse effects. In one
of the two studies in which fish irradiated at 6 kGy was fed to rats
(``the Shillinger study,'' Ref. 43), rats in the treated group were
reported to have an increased incidence of testicular atrophy and
prolonged estrous cycles, among other findings. The authors reported no
significant difference between experimental and control groups with
regard to such standard indices of reproductive function as time of
first births, fertility index, number of offspring in the litter, or
weight of offspring at birth or at 1 month of age. In addition, no
toxic effects on the growth or development of three generations were
reported. The authors stated that some of the findings point to a
protein deficiency.\19\ However, the second reproduction study with
fish irradiated at the same dose (``the Hickman study,'' Ref. 44)
reported no adverse effects. FDA has concluded that the effects
reported in the Shillinger study are not attributable to irradiation
for three reasons: (1) The irradiated fish was stored under
inappropriate conditions, (2) the results of measurements of blood
protein levels
Page 64114
are consistent with a nutritionally inadequate diet, and (3) similar
effects were not seen in the Hickman study.
---------------------------------------------------------------------------
\19\ Although the irradiated fish was not irradiated at a
sterilizing dose or treated to inactivate enzymes that could lead to
decomposition, it was stored under refrigeration for up to 2 months.
Fish fed to the control group, however, was stored frozen until
incorporated into the diet. Irradiated fish, stored under
refrigeration, had greater opportunity to undergo decomposition or
other spoilage before consumption. The authors did not report
addition of vitamins or minerals to the diets and did not report
actual nutrient levels in the diet. The authors also reported a
higher incidence of pneumonia and parasitic infections in the
treated group, varying blood and liver enzyme activities in the
different generations, and a lower albumin/globulin ratio (a sign of
protein deficiency) in the treated group.
---------------------------------------------------------------------------
In summary, the agency concludes that the available studies of
irradiated flesh foods show no adverse effects on reproductive or
developmental endpoints that can be attributed to radiation treatment.
5. Genetic Toxicity Studies
Although chronic feeding studies are the primary basis for
assessing potential carcinogenicity of a substance, genetic toxicity
tests are often used to screen for possible carcinogenic effects. A
large variety of genetic toxicity studies with irradiated chicken, ham,
beef, or fish have been conducted (Ref. 45). All of these studies
report that no genotoxic effects were observed. FDA agrees that these
studies demonstrate that irradiated flesh foods are not genotoxic.
6. Summary of the Toxicological Assessment
As noted previously, chemical analyses and toxicity studies provide
independent means for assessing whether there is a reasonable certainty
that irradiation of meat will not present a toxicological hazard.
Chemical analyses are used to identify substances produced by
irradiation that might present a risk. Animal feeding studies and
genetic toxicity studies are used to determine whether toxicants may be
present in irradiated foods, even if not identified, at levels that
would be harmful.
The agency has carefully reviewed the data and information
submitted in the petition. The agency has also considered all the
available data and studies in its files regarding the radiation-induced
chemical changes in flesh foods and the toxicological effects of
irradiated meat and other irradiated flesh foods (e.g., chicken and
fish) when consumed in the diet.
All the available results of chemical analyses of irradiated flesh
foods support the conclusion that a toxicological hazard due to
consumption of irradiated flesh foods is highly unlikely, because no
substance resulting from irradiation has been found at levels that
would suggest any reason for toxicological concern. The results of the
available toxicological studies of irradiated flesh foods also
demonstrate that a toxicological hazard is highly unlikely because no
toxicologically significant adverse effects attributable to consumption
of irradiated flesh foods were observed in any of these studies. Thus,
the results of the chemical analyses and the toxicological studies are
entirely consistent. The agency therefore concludes, based on all the
evidence before it, that irradiation of meat under the conditions set
forth in the regulation does not present a toxicological hazard.
D. Nutritional Considerations
The nutritional adequacy of an irradiated food may be affected by
radiation-induced reductions in the amounts of essential nutrients in
the food. FDA has carefully reviewed the data and information submitted
in the petition, as well as other information in its files, to
determine whether irradiation would have an adverse effect on the
nutritional value of meat.
1. Nutrients in Meat
Flesh foods are consumed primarily as sources of protein. The so-
called ``red meats,'' beef in particular, are also rich sources of iron
and phosphorus. Flesh foods, including red meats, also contribute
significantly to the dietary intake of B vitamins, except for thiamine.
Most individual flesh foods, including meats, provide only a minor
portion of the dietary intake of thiamine (Ref. 46). The exception to
this rule is pork, which contributes approximately 9 percent of the
thiamine in the American diet (Refs. 46 and 47). The largest
contributors to thiamine intake in the human diet, however, are grains
in various foods (e.g., cereals; flour in bread, other baked goods, and
pasta) and legumes.
2. Effects of Irradiation on the Nutrients in Meat
It is well known that the nutrient value of the macronutrients in
the diet (proteins, fats, and carbohydrates) is not significantly
altered by irradiation at the petitioned doses (Refs. 19, 48, and 49).
Minerals (e.g., iron, phosphorus, and calcium) are also unaffected by
irradiation (Refs. 48 and 49).
Levels of certain vitamins may be reduced, however, as a result of
irradiation. The extent to which this occurs depends on the specific
vitamin, the food type, and the conditions of irradiation. Not all
vitamin loss is significant, however. The extent to which a reduction
in a specific vitamin level is significant depends on the relative
contribution from the food in question to the dietary intake of the
vitamin.
Most of the nutrition-related studies submitted in the petition
presented analyses of vitamin levels in irradiated flesh foods. These
studies covered a wide range of foods, vitamins, and irradiation
conditions. Most of these studies focused on the levels of B vitamins
because, as noted, meats and certain edible organs (e.g., the liver and
the heart) are better sources of B vitamins than of other vitamins,
such as vitamins C or D, for example. For the same reason, FDA's
evaluation of the nutritional adequacy of irradiated meat and meat
byproducts, which considered all relevant vitamins, focused on the
effects of irradiation on the levels of B vitamins. In FDA's
evaluation, thiamine levels received particular attention because
thiamine is one of the vitamins most susceptible to radiation (Refs. 46
and 50).
In general, the available studies have reported insignificant
effects on the levels of B vitamins other than thiamine when flesh
foods were irradiated at dose levels comparable to those proposed in
the subject petition (Refs. 50, 51, and 52). For example, pork
irradiated at a dose of 6.7 kGy showed no detectable loss in cobalamin
level and, when irradiated at 5 kGy, showed no detectable loss in
niacin level (``the first Fox study,'' Ref. 47). Similar results have
been obtained in studies of the effects of irradiation on other B
vitamins such as pyridoxine and pantothenic acid (Ref. 52).
Another recently conducted study by Fox et al., (``the second Fox
study,'' Ref. 53) compared radiation-induced reductions in B vitamin
levels in beef, lamb, pork, and turkey, all of which were irradiated at
5 deg.C in the presence of oxygen, conditions which would tend to
maximize vitamin loss. The authors reported that, even under such
conditions, losses of riboflavin resulting from irradiation were
virtually undetectable at radiation doses up to 3 kGy and that the
losses did not differ significantly among the various flesh foods. The
average incremental loss of riboflavin at radiation doses above 3 kGy
was reported to be 2.5 percent per kGy, which was judged by the authors
as insignificant. FDA agrees that this reduction in riboflavin is
insignificant in the context of the total diet (Refs. 46 and 51).
Losses in thiamine levels resulting from irradiation were also
measured in the second Fox study. Thiamine losses were detectable at
all irradiation doses tested and differed among the flesh foods tested,
but the range was fairly narrow: from a low of 8 percent loss per kGy
in lamb to a high of 16 percent loss per kGy in beef. The incremental
thiamine loss in pork was approximately 11 percent per kGy above 3 kGy
when irradiated at 5 deg.C in the presence of oxygen. These results
were consistent with the results of the first Fox study in which pork
irradiated at 4.5 kGy at 0 deg.C (frozen) sustained losses
Page 64115
in thiamine levels of circa (ca.) 40 percent (Ref. 47).
Other studies of the effect of irradiation on thiamine levels in
flesh foods, conducted under a variety of irradiation conditions, show
losses ranging from approximately 10 to 50 percent over a dose range of
0.6 to 7.3 kGy (Refs. 46, 52, 54, and 55), which is comparable to the
dose range that could, in actual practice, be used under the
limitations set forth in the regulation. It is important to note that
the highest thiamine losses (ca. 50 percent for some, but not all,
flesh foods) have occurred when foods were irradiated at the higher
doses in this range (ca. 7 kGy), in the nonfrozen state, and/or in the
presence of oxygen.
Irradiation of meat is likely to be carried out on products that
are in prepackaged form. Meat is commonly packaged under vacuum or
reduced oxygen levels at the wholesale level and stored and shipped
either refrigerated or frozen (Ref. 2). As discussed previously,
irradiation of food in the frozen state (or at reduced temperatures)
and under reduced oxygen levels tends to minimize vitamin losses (Ref.
48). Thus, irradiation of most meat, which is likely to be carried out
in an atmosphere of reduced oxygen content and at low temperature or in
the frozen state, will tend to result in thiamine losses that are far
less than 50 percent.
Nevertheless, the agency has conducted an ``extreme case''
assessment of the potential effect on the dietary intake of thiamine
that would result if all flesh foods (i.e., meat, poultry, and fish)
were irradiated under conditions that would tend to maximize thiamine
loss (i.e., such that thiamine levels in all these foods would be
reduced by 50 percent). The agency has determined that even in such
extreme and unlikely circumstances, the average thiamine intake would
still be above the recommended daily allowance (RDA) and, thus, there
would be no deleterious effect on the total dietary intake of thiamine
as a result of irradiating flesh foods, including meat (Ref. 46).
3. Summary of the Nutritional Assessment
As discussed, FDA has concluded that the effects of irradiation on
thiamine, under the conditions set forth in the regulation below, will
not result in an adverse effect on the dietary intake of thiamine.
Because the effects of irradiation on B vitamins other than thiamine
are far less than the effects on thiamine, FDA also concludes that
there will be no deleterious effect on the total dietary intake of
these other B vitamins (e.g., riboflavin, niacin, cobalamin). In
addition, as noted, irradiation does not affect mineral levels, nor, at
the doses set forth in the regulation, the nutritional quality of the
protein in meat.
FDA therefore concludes, based on all the evidence before it, that
irradiation of meat under the conditions set forth in the regulation
below will not have an adverse impact on the nutritional adequacy of a
person's diet.
E. Microbiological Considerations
Irradiation at the doses requested in the petition will reduce, but
not entirely eliminate, the microorganisms in or on meat. Further,
because different microorganisms are affected by irradiation to
different degrees, irradiation of meat will change the relative amounts
of different microorganisms present (the microbiological profile). The
microbiological profile and the storage conditions of meat influence
the growth patterns of the various microorganisms found in or on this
food. Because microorganisms remaining in food after irradiation
processing can multiply, FDA has assessed whether irradiation of meat
under the conditions set forth in the regulation is likely to alter the
growth patterns of any surviving microorganisms in such a way as to
result in an increased microbiological hazard (from increased growth of
pathogens) compared to meat that has not been irradiated.
1. Microbiological Profile of Raw Meat
Meat is a nutrient-rich substrate that can support the growth of a
variety of microorganisms. During the initial processing steps (e.g.,
slaughter, skinning, cutting of primals) these microorganisms are
diverse. They include a wide variety of nonpathogenic spoilage
bacteria, including organisms from the Pseudomonas-Moraxella-
Acinetobacter group, Lactobacillus sp., and others. Pathogenic
(illness-causing) microorganisms, including Salmonella sp., E. coli
O157:H7, Listeria monocytogenes, Staphylococcus aureus, and others,
have also been isolated from raw meat, generally at relatively low
levels (see Refs. 2, 56, and 57).
Spores\20\ of certain other pathogenic microorganisms have been
isolated from raw meat as well. The most commonly occurring spores in
meat are those of C. perfringens (Refs. 2 and 6). Spores of Clostridium
botulinum have also been isolated from raw meat; the available data
indicate that both the incidence and the numbers of C. botulinum spores
are extremely low (Refs. 58, 59, and 60).
---------------------------------------------------------------------------
\20\ Spores are the so-called ``resting stage'' of certain
bacteria in which the bacterial cell becomes enclosed in a tough,
resistant coat as a response to adverse environmental conditions. On
return to less adverse conditions, the spore can germinate and
revert to the normal vegetative form of the organism. Under
favorable conditions, the vegetative cells can multiply and, in the
case of certain spore-forming bacteria, produce toxin. Growth rates
of the vegetative cells are influenced by several factors including
temperature, ambient oxygen level, pH, and the size of the spore
inoculum (numbers of spores present).
---------------------------------------------------------------------------
Fungal species (i.e., yeasts and molds) have also been isolated
from the surfaces of raw meat, presumably as a result of airborne
contamination. Various parasites, including Toxoplasma gondii and
Trichinella spiralis, both of which can cause serious foodborne
illness, may also be found in meat.
2. Effects of Irradiation on Microorganisms in or on Meat
The petitioner provided reports and published articles describing
the effects of irradiation on the microorganisms in or on flesh foods.
These reports and published articles provide data on several
microorganisms of relevance, including various species of Salmonella;
E. coli O157:H7; C. perfringens; S. aureus; L. monocytogenes; Bacillus
cereus; Campylobacter jejuni; and the protozoan parasite T. gondii.
Taken together, the available reports and published articles establish
that the radiation dose necessary to reduce the initial population of
any of the bacterial pathogens by 90 percent (i.e., the ``D value'')
ranges from 0.1 kGy to just under 1 kGy. For any individual pathogen,
the D value varies depending on such factors as the specific food,
physical state (frozen versus nonfrozen) of the food, temperature, and
ambient oxygen level.
The D value for Salmonella, for example, ranges from approximately
0.4 kGy to 0.8 kGy, depending on the microbial strain and the other
factors mentioned above (Refs. 61, 62, 63, and 64). E. coli O157:H7 is
more radiation sensitive than Salmonella, with a D value range of
approximately 0.2 to 0.4 kGy, depending on the type of flesh food and
the conditions of irradiation (Refs. 62, 63, and 65). Other studies of
a variety of different pathogens in different flesh foods yield
comparable results.\21\
---------------------------------------------------------------------------
\21\ For example, the D values of both L. monocytogenes and S.
aureus fall in the range of 0.40 to 0.48 kGy when irradiated in
beef, pork, or lamb at 5 deg.C (see, e.g., Refs. 62 and 66). C.
jejuni is more radiation sensitive, with D values in the range of
0.16 to 0.24 kGy depending on the particular meat and the conditions
of irradiation (see, e.g., Refs. 63 and 67).
T. gondii tissue cysts are inactivated at a radiation dose of
approximately 0.4 kGy (Ref. 68).
---------------------------------------------------------------------------
Page 64116
D values for the principal nonpathogenic microorganisms (spoilage
bacteria) commonly found in or on meat cover a wide range, from
approximately 0.3 to 2.0 kGy (Refs. 69, 70, and 71). Lactobacillus sp.
are among the more radiation-resistant nonpathogenic spoilage bacteria;
the D values for these bacteria range from approximately 1 to 2 kGy,
depending on the microbial strain and the conditions of irradiation
(Ref. 71).
In the case of spore-forming bacteria, the spores and vegetative
cells are affected by irradiation to different degrees. Spores are
generally more resistant to the effects of radiation than vegetative
cells. For example, the D values for vegetative cells of various
strains of C. perfringens range from 0.6 to 0.8 kGy (Refs. 72 and 73),
comparable to the D values for most of the pathogens discussed above,
while the D values for the spores of C. perfringens range from 1.2 to
1.8 kGy (Ref. 74). The spores of C. botulinum are more radiation-
resistant; the D values for the spores of various strains of C.
botulinum range from approximately 2 to 4 kGy (Refs. 60 and 74).
The agency has reviewed the data and information described
previously as well as other information in its files and has determined
that irradiation at doses of up to 4.5 kGy for refrigerated product and
doses of up to 7.0 kGy for frozen product will significantly reduce the
number of pathogenic microorganisms in or on meat (Ref. 75). Under the
conditions set forth in the regulation below, reductions in Salmonella
levels, for example, could be approximately 100,000-fold in
refrigerated beef irradiated at 4.5 kGy. Because E. coli is more
sensitive to the effects of irradiation, reductions in the levels of
that microorganism would be even greater in beef irradiated under these
same conditions. The levels of most spoilage microorganisms on meat
will also be significantly reduced at the petitioned doses, resulting
in an extension of the shelf-life of the product.
However, while irradiation at the petitioned doses significantly
reduces the numbers of many pathogenic and spoilage bacteria, its
effect in reducing the numbers of relatively radiation-resistant spores
of other pathogenic bacteria (e.g., C. botulinum, with D values of
approximately 2 to 4 kGy), is less. Therefore, FDA has carefully
examined the effects of radiation-induced changes in the
microbiological profile of meat on the growth patterns of surviving
microorganisms to determine whether the microbiological safety of meat
irradiated under the conditions set forth in the regulation would be
adversely affected. In FDA's evaluation, C. botulinum received
particular attention both because C. botulinum spores are the most
radiation-resistant of the pathogens found in meat and because the
illness induced by botulinal toxin is so severe.
3. Growth Patterns of Microorganisms in or on Raw Meat
As noted previously, meat is a substrate that can, in principle,
support the growth of a variety of microorganisms. The conditions under
which meat is stored (e.g., temperature, ambient atmosphere, pH)
influence the growth patterns of different microorganisms, however,
affecting both the types and numbers of different microorganisms that
are likely to be found in or on meat at any given time.
Meat is chilled and subsequently stored under refrigeration
(generally 37 to 45 deg.F) immediately following the initial
processing steps. During cold storage, the predominant microorganisms
are the spoilage bacteria, primarily Pseudomonas sp., that are capable
of growth at these temperatures. If the chilled meat is packaged in an
environment of reduced oxygen content, other spoilage bacteria, such as
Lactobacillus sp., Brochothrix thermosphacta, and other lactic acid-
producing microorganisms, predominate (Refs. 2 and 56).
The growth of C. perfringens, Salmonella, and E. coli is well
controlled by cooling meat quickly after slaughter and maintaining the
product at refrigerated temperatures during subsequent transport and
storage. None of these pathogens is normally capable of growth in meat
stored under refrigeration. In addition, competition with the more
numerous and faster-growing spoilage bacteria that predominate at
refrigeration temperatures further inhibits the growth of these
pathogens. Both Salmonella and E. coli O157:H7 are capable of
significant growth, however, in meat stored above refrigeration
temperatures (``temperature abuse'' conditions; above 50 deg.F).
Temperature control is thus a primary tool in reducing the growth of,
and consequently, the risk from, these pathogens.
Growth of C. botulinum is influenced by several factors in addition
to temperature, including the availability of oxygen, pH of the food,
and the numbers of C. botulinum spores in relation to the types and
numbers of competing microorganisms. Temperature control is, however,
the single most important factor in controlling the growth of the
strains of C. botulinum that have been most frequently (albeit still
rarely and in low numbers) isolated from meat in the United States
(Refs. 59, 60, and 76) In this regard, the same temperature control
regimen used to control the growth of other pathogens such as
Salmonella, E. coli O157:H7, and C. perfringens also works well to
inhibit growth of, and toxin production by, C. botulinum in meat.
Temperature abuse can lead to growth and toxin production by C.
botulinum; however, this typically takes several weeks to occur, even
at temperatures of approximately 60 deg.F. By this time, signs of
spoilage (e.g., putrid odor, slimy texture), produced primarily by the
faster-growing and more numerous nonpathogenic spoilage bacteria, are
evident. The objectionable odor and texture of spoiled meat is a signal
that typically inhibits consumers from eating the product. Reports of
botulism resulting from consumption of such meat are rare and,
generally, have been limited to ethnic groups that favor these foods
(see Refs. 59, 76, and 77).
In summary, maintaining meat at low storage temperatures is the
primary method for controlling the growth of pathogenic microorganisms
and, thus, for reducing the risk of disease from pathogenic
microorganisms in or on meat.
4. Effects of Irradiation on Growth Patterns of Microorganisms in or on
Meat
As noted above, radiation-induced changes in the microbiological
profile of meat have the potential to affect the growth patterns of the
various microorganisms in or on meat. FDA has evaluated whether
irradiation would result in significantly altered microbial growth
patterns in meat (e.g., significantly increased growth of pathogens)
such that irradiated meat would present an increased microbiological
hazard compared to meat that had not been irradiated. The agency has
reviewed data and information submitted in the petition, as well as
other information in its files, regarding the effects of irradiation,
temperature abuse conditions, and ambient oxygen levels on the
microbiological profile of meat.
Because C. botulinum spores are the most resistant to the effects
of irradiation and would thus be more likely to survive irradiation
than other pathogens and most spoilage bacteria, and because the
illness associated with botulinal toxin is so severe, FDA, in its
evaluation, focused particularly on the effects of irradiation on the
probability of significantly increased growth of, and subsequent toxin
production by, C. botulinum.
Page 64117
With respect to most of the significant pathogens found in or on
meat, other than C. botulinum (e.g., Salmonella and E. coli O157:H7),
FDA concludes that the probability of significant growth of these
pathogens in irradiated meat stored under adequate temperature control
is extremely remote for two reasons. First, these pathogens typically
require temperatures of 50 deg.F or higher for significant growth.
Second, as noted above, most of the pathogens in or on meat are more
sensitive to the effects of irradiation than many of the common
spoilage microorganisms (e.g., Lactobacillus, with D values of 1 to 2
kGy). Because these pathogens are sensitive to the effects of
irradiation, FDA expects that irradiation under the conditions set
forth in the regulation below will reduce the numbers of these
pathogens to a far greater extent than it will reduce the numbers of
the faster-growing spoilage microorganisms that compete with, and
inhibit the growth of, pathogens at refrigeration temperatures.
Nevertheless, FDA has also considered the effects of temperature
abuse on growth of these pathogens (e.g., Salmonella, E. coli O157:H7,
C. perfringens) in irradiated meat. In one of the studies submitted in
the petition (Ref. 72), pork was packaged and irradiated at 1.75 kGy
under a modified atmosphere containing no oxygen following inoculation
with high levels of any one of several pathogens. In this study, the
authors reported that growth of these pathogens (Salmonella, E. coli,
and C. perfringens, among others), was, in fact, decreased by
irradiation even when temperature conditions were favorable for growth
(approximately 60 deg.F).
With respect to C. botulinum, FDA concludes that the probability
for significant growth of, and toxin production by, C. botulinum in
irradiated meat stored under adequate temperature control (properly
refrigerated or frozen) is extremely remote for several reasons. First,
as noted, C. botulinum spores occur with extremely low frequency and in
extremely low numbers in meat; these numbers will be further reduced by
irradiation at the petitioned doses. Research has established that the
size of the spore inoculum (numbers of spores present in the food) is
an important factor in the growth of, and toxin production by, C.
botulinum; reduced numbers of spores generally result in a decreased
probability that growth sufficient for toxin production will occur
(Ref. 59).
Second, most strains of C. botulinum that have been found in meat
do not grow and produce toxin under refrigeration conditions
appropriate for transport and storage of flesh foods. The available
data show that growth and subsequent toxin production by C. botulinum
in meat requires significantly elevated temperatures (50 to 55 deg.F,
or higher) (Refs. 59, 60, and 77). Even under reduced ambient oxygen
levels (conditions that favor the growth of C. botulinum), elevated
temperatures are still required for significant growth and toxin
production. Irradiation does not enable C. botulinum to grow at
refrigeration temperatures; elevated temperatures on the order of 50 to
55 deg.F are required, whether meat is irradiated or not.
Nevertheless, the agency has also considered whether, in the absence of
temperature control, irradiation could increase the likelihood that C.
botulinum could grow and produce toxin without the signs of spoilage
familiar to the consumer that discourage consumption of spoiled meat.
One study submitted in the petition (Ref. 78) investigated the
effect of irradiation, at a dose of 3 kGy, on the patterns of microbial
growth and spoilage in vacuum-packaged pork loins stored under
conditions of proper refrigeration (2 to 4 deg.C to simulate wholesale
storage, and 5 to
7 deg.C to simulate retail storage) and under conditions of severe
temperature abuse (24 to 25 deg.C). Shelf-life of pork stored under
refrigeration conditions was extended by irradiation. The authors found
that both irradiated pork and pork that had not been irradiated spoiled
rapidly under conditions of severe temperature abuse and that the same
types of microorganisms were responsible for spoilage in both
irradiated pork and pork that had not been irradiated. The authors
concluded that the concurrent and similar increases that they observed
in the numbers of lactobacilli and other bacteria in the temperature-
abused, vacuum-packaged irradiated pork indicated that sufficient
spoilage organisms survived irradiation to bring about spoilage after
severe temperature mishandling. FDA concurs in these conclusions (Ref.
77).
In several other studies submitted in the petition (``the Lambert
studies,'' Refs. 79a through 79c), pork was packaged and irradiated at
a dose of 1 kGy under reduced ambient oxygen levels following
inoculation with high levels of C. botulinum spores. In these studies,
storage at elevated temperatures, equivalent to approximately 60
deg.F, was required for C. botulinum to grow and produce toxin; no
toxin was detected in pork stored at approximately 41 deg.F . The
authors concluded that irradiation at 1 kGy significantly delayed toxin
production by C. botulinum (Refs. 79a and 79b). The authors of these
studies also reported that signs of spoilage in the irradiated pork
appeared at least 1 week before, and under certain conditions, up to 5
weeks before, toxin was detected (Ref. 79a).
The data and information in the Lambert studies show that even when
the levels of C. botulinum spore inoculum are high and the ambient
oxygen level low (conditions that, as noted, would tend to increase
growth and toxin production), toxin production was preceded by signs of
spoilage in the irradiated meat. These data also demonstrate that
storage at sustained elevated temperatures, for several weeks, are
required for growth of, and toxin production by, C. botulinum in
irradiated pork.
Third, other data and information also show that various species of
other microorganisms commonly found on meat, particularly spoilage
bacteria (e.g., Lactobacillus sp.\22\ and others), survive irradiation
in sufficient numbers to grow and inhibit growth of, and toxin
production by, C. botulinum in both refrigerated and temperature-abused
irradiated meats (Refs. 71, 80, and 81).
---------------------------------------------------------------------------
\22\ In the case of Lactobacillus, production of lactic acid,
which lowers the pH of the meat, is a contributing factor in
inhibiting the growth of various pathogens, including C. botulinum
(see, e.g., Refs. 59 and 71).
---------------------------------------------------------------------------
5. Summary of the Microbiological Assessment
FDA has reviewed the data and information submitted in the petition
and has considered all the available data and information in its files
relevant to an assessment of the microbiological safety of the
irradiation of meat. In particular, FDA has carefully examined the
effects of radiation-induced changes in the microbiological profile of
meat on the growth patterns of any surviving microorganisms, including
C. botulinum, to determine whether the microbiological safety of meat
would be adversely affected by irradiation under the conditions set
forth in the regulation below.
As discussed previously in this document, the agency has determined
that irradiation of meat and meat byproducts under the conditions set
forth in the regulation below will not result in any additional health
hazard from C. botulinum (Ref. 75). Likewise, as discussed previously,
FDA has also determined that irradiation will not result in any
additional hazard from common pathogens other than C. botulinum.
Therefore, the agency concludes, based on all the evidence before it,
that irradiation of meat under
Page 64118
the conditions set forth in the regulation below will not result in a
microbiological hazard.
IV. Current Good Manufacturing Practice Considerations
As noted, the proper processing, handling, and storage of meat and
meat byproducts, irradiated or not, are necessary to ensure their
safety. With respect to the processing and handling of both meat and
poultry, USDA/FSIS has recently established specific requirements
applicable to meat and poultry establishments designed to reduce the
occurrence and numbers of pathogenic microorganisms on meat and poultry
products and thus, to reduce the incidence of foodborne illness
associated with these products (61 FR 38806, July 25, 1996). Among
other things, these new regulations require that each meat and poultry
establishment develop and implement written standard operating
procedures for sanitation (Sanitation SOP's, SSOP's) and that each
establishment also develop and implement a system of preventive
controls, known as HACCP (Hazard Analysis and Critical Control Points),
which is designed to improve the safety of their products.
FSIS has stated that it intends to use HACCP systems as a framework
for the modernization of the meat and poultry inspection system (61 FR
33806). HACCP systems are not intended to replace good manufacturing
practices (GMP's), but rather to be used as the basis of an approach to
food safety that focuses on hazard prevention and control. HACCP,
GMP's, SSOP's, and other tools and interventions all have a place in
ensuring the safety of meat. FSIS has stated that it anticipates that
the adoption of HACCP systems by the meat industry as a whole will
significantly increase the safety of meat products and reduce the risk
of foodborne illness (61 FR 33806).
A. Temperature control
As noted previously, proper temperature control is critical in
ensuring the safety of meat, meat byproducts, and meat food products,
whether or not they are irradiated. FDA's regulations regarding CGMP's
(part 110 (21 CFR part 110)) stipulate that the temperature of
refrigerated foods not exceed 45 deg.F (Sec. 110.80(b)(3)(i)). With
respect to meat products specifically, FDA's Model Food Code, which is
offered for adoption by States and other government entities that
exercise primary regulatory authority over food service, retail food
stores, and food vending machine operations, recommends that meat
products be stored at 41 deg.F or less. There are no data or other
information that suggest that, in order to ensure their safety,
irradiated meat products require different temperature controls than
meat products that have not been irradiated.
Moreover, FSIS, under its regulatory authority over meat processing
plants, can establish specific requirements with respect to temperature
control of irradiated meat, meat byproducts, and meat food
products.\23\ FDA concludes that its regulation should allow for
flexibility in this regard. Therefore, the regulation does not
establish specific requirements with respect to temperature control of
irradiated meat, meat byproducts, and meat food products.
---------------------------------------------------------------------------
\23\ In the preamble to the rule that established the new
requirement for the development and implementation of HACCP systems
in meat and poultry plants, FSIS addressed the need for cooling and
chilling requirements for raw meat and poultry. In the final rule,
FSIS stated that, with respect to regulation of time and temperature
control, it would be best to have, as a performance standard, a
maximum temperature for products being shipped into commerce, and at
which raw products in commerce must be maintained. This standard
would be applicable to all persons who handle such product before
the product reaches the consumer. FSIS concluded, however, that
development of such a performance standard required the acquisition
of additional information, and indicated that it would engage in
further rulemaking in this area.
---------------------------------------------------------------------------
B. Consideration of the Need for Establishment of a Minimum Dose
FDA has established, in Sec. 179.25, general provisions defining
CGMP for the use of irradiation in the treatment of food. This
regulation discusses requirements such as recordkeeping and the need
for a scheduled process for food irradiation. Among other things,
Sec. 179.25 also requires that ``Food treated with ionizing radiation
shall receive the minimum radiation dose reasonably required to
accomplish its intended effect * * *.'' (Section 179.25(b).)
FDA notes that the minimum dose necessary to control pathogenic
organisms on food can vary with the particular microorganism, the
specific food, and with the microbial load on the food. In its decision
to permit the irradiation of poultry at doses up to 3 kGy, FDA
explicitly considered these facts and noted that FSIS, based on its
regulatory authority over poultry processing plants, could establish a
minimum dose, consistent with CGMP, for controlling pathogenic
organisms in or on the products processed in such plants. The agency
also concluded that FSIS should be free to do so without having to
submit a new petition for an amendment to the regulation, as long as
any requirements complied with the applicable sections of part 179.
Similarly, with respect to the processing of meat, meat byproducts,
and meat food products, FDA is not establishing a minimum required
dose. The agency concludes that different doses could be appropriate,
in different circumstances, for achieving the desired technical effect
and that FDA's regulation should allow for flexibility in this regard.
Moreover, FSIS, under its regulatory authority over meat processing
plants, can establish a minimum dose, consistent with GMP, for
controlling pathogenic organisms in or on the products processed in
these plants. FSIS should be free to do so without having to submit a
petition for an amendment to FDA's regulation, as long as any FSIS
requirements comply with the applicable sections of part 179.
V. Labeling
Meat, meat byproducts, and meat food products are subject to the
Federal Meat Inspection Act (21 U.S.C. 601 et seq.). Therefore, the
labeling of these products irradiated under the conditions set forth in
the regulation must comply with any requirements imposed by USDA/FSIS
under its authority to approve the labeling of such products.
VI. Conclusion of Safety
FDA has evaluated the data in the petition and other material in
its files relevant to the proposed use of a source of radiation to
treat meat, meat byproducts, and certain meat food products. Based on
all the evidence before it, FDA concludes that irradiation of these
products under the conditions set forth in the regulation below will
not present a toxicological hazard, will not present a microbiological
hazard, and will not adversely affect the nutritional adequacy of such
products. Therefore, the agency concludes that irradiation of meat,
meat byproducts, and meat food products under the conditions set forth
in the regulation below is safe. Accordingly, FDA has determined that
part 179 should be amended.
In accordance with Sec. 171.1(h) (21 CFR 171.1(h)), the petition
and the documents that FDA considered and relied upon in reaching its
decision to approve the petition are available for inspection at the
Center for Food Safety and Applied Nutrition by appointment with the
listed contact person. As provided in Sec. 171.1(h), the agency will
delete from the documents any materials that are not available for
public disclosure before making the documents available for inspection.
Page 64119
VII. Environmental Impact
The agency has carefully considered the potential environmental
effects of this action. FDA has concluded that the action will not have
a significant impact on the human environment, and that an
environmental impact statement is not required. The agency's finding of
no significant impact and the evidence supporting that finding,
contained in an environmental assessment, may be seen in the Dockets
Management Branch (address above) between 9 a.m. and 4 p.m., Monday
through Friday.
VIII. Objections
Any person who will be adversely affected by this regulation may at
any time on or before January 2, 1998 file with the Dockets Management
Branch (address above) written objections thereto. Each objection shall
be separately numbered, and each numbered objection shall specify with
particularity the provisions of the regulation to which objection is
made and the grounds for the objection. Each numbered objection on
which a hearing is requested shall specifically so state. Failure to
request a hearing for any particular objection shall constitute a
waiver of the right to a hearing on that objection. Each numbered
objection for which a hearing is requested shall include a detailed
description and analysis of the specific factual information intended
to be presented in support of the objection in the event that a hearing
is held. Failure to include such a description and analysis for any
particular objection shall constitute a waiver of the right to a
hearing on the objection. Three copies of all documents shall be
submitted and shall be identified with the docket number found in
brackets in the heading of this document. Any objections received in
response to the regulation may be seen in the Dockets Management Branch
between 9 a.m. and 4 p.m., Monday through Friday.
IX. References
The following sources are referred to in this document. References
marked with an asterisk (*) 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. References without an
asterisk are not on display; they are available as published articles
and books.
1. Weingold, S. E., J. J. Guzewich, and J. F. Fudala, ``Use of
Foodborne Disease Data for HACCP Risk Assessment,'' Journal of Food
Protection, 57:820-830, 1994.
2. National Advisory Committee on Microbiological Criteria for
Foods, ``Generic HACCP for Raw Beef,'' Food Microbiology, 10:449-
488, 1993.
3. Griffin, P. M. and R. V. Tauxe, ``The Epidemiology of
Infections Caused by Escherichia coli O157:H7, Other
Enterohemorrhagic E. coli, and the Associated Haemolytic Uraemic
Syndrome,'' Epidemiology Reviews, 13:60-98, 1991.
4. Boyce, T. G., D. L. Swerdlow, and P. M. Griffin,
``Escherichia coli O157:H7 and the Hemolytic-Uremic Syndrome,'' New
England Journal of Medicine, 333(6):364-368, 1995.
5. D'Aoust, J. Y.,``Salmonella Species,'' pp. 129-158, in Food
Microbiology: Fundamentals and Frontiers, M. P. Doyle, L. R.
Beuchat, and T. J. Montville, eds., ASM Press, Washington, DC, 1997.
6. McClane, B. A., ``Clostridium perfringens,'' pp. 305-326, in
Food Microbiology: Fundamentals and Frontiers, M. P. Doyle, L. R.
Beuchat, and T. J. Montville, eds., ASM Press, Washington, DC, 1997.
7. Merritt, C., Jr., ``Qualitative and Quantitative Aspects of
Trace Volatile Components In Irradiated Foods and Food Substances,''
Radiation Research Reviews, 3:353-368, 1972.
*8. Morehouse, K. M., ``The Quantitative Determination of
Radiolytically Generated Hydrocarbons in Meats,'' final report for
U.S. Army, Natick Research Development and Engineering Center,
Sustainability Directorate, under Interagency Agreement FDA 224-93-
2448.
9. Merritt, C., Jr., et al., ``Effect of Radiation Parameters on
the Formation of Radiolysis Products in Meat Substances,'' Journal
of Agricultural and Food Chemistry, 26:29-35, 1978.
10. Taub, I. A. et al., ``Factors Affecting Radiolytic Effects
In Food,'' Radiation Physics and Chemistry, 14:639-653, 1979.
11. Diehl, J. F., ``Radiolytic Effects in Foods,'' pp. 279-357,
in Preservation of Foods By Ionizing Radiation, Vol. 1, E. S.
Josephson and M. S. Peterson, eds., CRC Press, Boca Raton, Fl.,
1982.
12. Diehl, J. F., ``Chemical Effects of Ionizing Radiation,''
pp. 43-88, in Safety of Irradiated Foods, Marcel Dekker, New York,
1995.
13. Taub, I. A. et al., ``Effect of Irradiation on Meat
Proteins,'' Food Technology, pp. 184-193, May 1979.
14. Merritt, C., Jr., and I. A. Taub, ``Commonality and
Predictability of Radiolytic Products In Irradiated Meats,'' pp. 27-
58, in Recent Advances In Food Irradiation, P. S. Elias and A. J.
Cohen, eds., Elsevier, Amsterdam, 1983.
15. Delincee, H., ``Recent Advances in the Radiation Chemistry
of Proteins,'' pp. 129-148, in Recent Advances in Food Irradiation,
P. S. Elias and A. J. Cohen, eds., Elsevier, Amsterdam, 1983.
16. Urbain, W. M., ``Radiation Chemistry of Proteins,'' pp. 63-
130, in Radiation Chemistry of Major Food Components, P. S. Elias
and A. J. Cohen, eds., Elsevier, Amsterdam, 1977.
17. Simic, M. G., ``Radiation Chemistry of Water Soluble Food
Components,'' pp. 1-73, in Preservation of Food by Ionizing
Radiation, Vol. 2, E. S. Josephson and M. S. Peterson, eds., CRC
Press, Boca Raton, Fl., 1982.
18. Taub, I. A., ``Reaction Mechanisms, Irradiation Parameters,
and Product Formation,'' pp. 125-166, in Preservation of Food by
Ionizing Radiation, Vol. 2, E. S. Josephson and M. S. Peterson,
eds., CRC Press, Boca Raton, Fl., 1982.
19. Underdal, B., et al., ``The Effect of Ionizing Radiation on
the Nutritional Value of Fish (Cod) Protein,'' Lebensmittel-
Wissenschaft Technologie, 6:90-93, 1973.
20. Josephson et al., ``Nutritional Aspects of Food Irradiation:
An Overview,'' Journal of Food Processing and Preservation, 2:299-
313, 1979.
21. Nawar, W. W., ``Radiation Chemistry of Lipids,'' pp. 21-62,
in Radiation Chemistry of Major Food Components, P. S. Elias and A.
J. Cohen, eds., Elsevier, Amsterdam, 1977.
22. Nawar, W. W., ``Volatiles from Food Irradiation,'' Food
Reviews International, 2:45-78, 1986.
23. Nawar, W. W., ``Radiolysis of Nonaqueous Components of
Foods,'' pp. 75-124, in Preservation of Food by Ionizing Radiation,
Vol. 2, E. S. Josephson and M. S. Peterson, eds., CRC Press, Boca
Raton, Fl., 1982.
24. Morehouse, K. M. and Yuoh Ku, ``Gas Chromatographic and
Electron Spin Resonance Investigations of <greek-g>-Irradiated
Shrimp,'' Journal of Agricultural and Food Chemistry, 40:1963-1971,
1992.
25. Delincee, H., ``Recent Advances in the Radiation Chemistry
of Lipids,'' pp. 89-114, in Recent Advances in Food Irradiation, P.
S. Elias and A. J. Cohen, eds., Elsevier, Amsterdam, 1983.
*26a. Chinn, H. I. (Chairman, Select Committee on Health Aspects
of Irradiated Beef), ``Evaluation of Health Aspects of Certain
Compounds Found in Irradiated Beef,'' Federation of American
Societies for Experimental Biology (FASEB), Bethesda, MD, 1977.
*26b. Chinn, H. I., ``Supplement I. Further Toxicological
Considerations of Volatile Compounds,'' FASEB, Bethesda, MD, 1979.
*26c. Chinn, H. I., ``Supplement II. Possible Radiolytic
Compounds,'' FASEB, Bethesda, MD, 1979.
27. Nawar, W. W., ``Thermal Degradation of Lipids. A Review,''
Journal of Agricultural and Food Chemistry, 17(1):18-21, 1969.
28. Watt, B. K. and A. L. Merrill, Composition of Foods,
Agriculture Handbook No. 8, Consumer and Food Economics Institute,
Agriculture Research Service, United States Department of
Agriculture, Washington, DC, 1975.
29. Krause, M. V. and M. A. Hunscher, Food, Nutrition, and Diet
Therapy, W. B. Saunders Co., Philadelphia, 1972, pp. 665-677, (table
adapted from ``Amino Acid Content of Foods,'' Home Economics
Research Report No. 4, U.S. Department of Agriculture, 1968.)
*30. Brunetti, A. P., et al., ``Recommendations for Evaluating
the Safety of Irradiated Foods,'' final report prepared for the
Director, Bureau of Foods, FDA, July 1980.
*31. WHO, ``Wholesomeness of Irradiated Food: Report of a Joint
FAO/IAEA/WHO Expert Committee,'' World Health Organization Technical
Report Series, No. 659, World Health Organization, Geneva, 1981.
Page 64120
*32. FAO, ``Codex General Standard for Irradiated Foods and
Recommended International Code of Practice for the Operation of
Radiation Facilities for the Treatment of Foods,'' Codex
Alimentarius Commission, FAO/WHO, CAC/Vol. XV, Ed.1, Rome, 1984.
*33. WHO, ``Safety and Nutritional Adequacy of Irradiated
Food,'' World Health Organization, Geneva, 1994.
*34a. Memorandum to the file, FAP 4M4428, from D. Hattan, FDA,
dated November 18, 1997.
*34b. Memorandum from H. Irausquin, FDA, to P. Hansen, FDA,
dated April 20, 1995.
*35. Memorandum from Food Additives Evaluation Branch, FDA, to
Petitions Control Branch, FDA, dated December 28, 1982, with
attached Tab A, dated September 15, 1982.
*36. Memorandum to the file, FAP 4M4428--References for long-
term feeding studies, from W. Trotter, FDA, dated November 10, 1997.
*37. Phillips, A. W., R. Newcomb, and D. Shanklin, ``Long-term
Rat Feeding Studies: Irradiated Chicken Stew and Cabbage,'' U.S.
Army Unpublished Contract Report No. DA-49-007-MD-783, 1961.
*38. Memorandum to the file, FAP 4M4428, from P. Hansen, FDA,
dated October 31, 1997.
*39. Read, M. S., H. F. Kraybill, and N. F. Witt, ``Successive
Generation Rat Feeding Studies with a Composite Diet of Gamma-
Irradiated Foods,'' Toxicology and Applied Pharmacology, 3:153,
1961.
*40. Monsen, H., ``Heart Lesions in Mice Induced by Feeding
Irradiated Foods,'' Federation Proceedings, 19:1031, 1960.
*41. Fegley, H. C. and R. E. Edmonds, ``To Examine the
Wholesomeness of Irradiated Soft-Shell Clams (Mya Arenaria) in
Dogs,'' Food Irradiation Information, Food and Agriculture
Organization/International Atomic Energy Agency, 6 (Suppl.):111,
1976.
*42. Memorandum to the file, FAP 4M4428--References for
reproduction and teratology studies, from W. Trotter, FDA, dated
November 10, 1997.
*43. Shillinger, I. and I. N. Osipova, ``The Effect of Fresh
Fish, Exposed to Gamma Radiation on the Organism of Albino Rats,''
Voprosy Pitanija, 29(5):45, 1970.
*44. Hickman, J. R., ``Studies on the Wholesomeness of
Irradiated Fish, Reproduction,'' Harwell, U.K. Atomic Energy
Authority, Technical Report AERE-R-6016, 1969.
*45. Memorandum to the file, FAP 4M4428--References for the
mutagenicity and genotoxicity studies, from W. Trotter, FDA, dated
November 10, 1997.
*46. Memorandum from J. Vanderveen, FDA, to P. Hansen, FDA,
dated March 11, 1996.
47. Fox, J. B., Jr., et al., ``Effect of Gamma Irradiation on
the B Vitamins of Pork Chops and Chicken Breasts,'' International
Journal of Radiation Biology, 55:689-703, 1989.
48. Diehl, J. F., ``Nutritional Adequacy of Irradiated Foods,''
pp. 241-282, in Safety of Irradiated Foods, Marcel Dekker, New York
1995.
49. Josephson, E. S. and M. H. Thomas, ``Nutritional Aspects of
Food Irradiation: An Overview,'' Journal of Food Processing and
Preservation, 2:299-313, 1978.
50. Tobback, P.P., ``Radiation Chemistry of Vitamins,'' pp. 187-
220 in Radiation Chemistry of Major Food Components, P. S. Elias and
A. J. Cohen, eds., Elsevier, Amsterdam, 1977.
*51. Memorandum from S. Carberry, FDA, to P. Hansen, FDA, dated
January 12, 1995.
52. Thayer, D. W., J. B. Fox, Jr., and L. Lakritz, ``Effects of
Ionizing Radiation on Vitamins,'' pp. 285-325, in Food Irradiation,
S. Thorne, ed., Elsevier Applied Science Publishers, London, 1991.
53. Fox, J. B., et al., ``Effect of Gamma Radiation on Thiamin
and Riboflavin in Beef, Lamb, Pork, and Turkey,'' Journal of Food
Science, 60(3):596-598, 1994.
54. Srinivas, H. et al., ``Nutritional and Compositional Changes
in Dehydro-Irradiated Shrimp,'' Journal of Food Science, 39:807-811,
1974.
55. Kennedy, T. S. and F. J. Ley, ``Studies on the Combined
Effect of Gamma Radiation and Cooking on the Nutritional Value of
Fish,'' Journal of Science Food and Agriculture, 22:146-148, 1971.
56. Lambert, A. D., J. P. Smith, and K. L. Dodds, ``Shelf Life
Extension and Microbiological Safety of Fresh Meat: A Review,'' Food
Microbiology, 8:267-297, 1991.
57. Doyle, M. P. and J. L. Schoeni, ``Isolation of Escherichia
coli O157:H7 from Retail Fresh Meats and Poultry,'' Applied and
Environmental Microbiology, 53:2394-2396, 1987.
58. Dodds, K. L., ``Clostridium botulinum in Foods,'' pp. 53-68
in Clostridium botulinum: Ecology and Control in Foods, A. H. W.
Hauschild, and K. L. Dodds, eds., Marcel Dekker, New York, 1993.
59. Lucke, F-K. and T. A. Roberts, ``Control in Meat and Meat
Products,'' pp. 177-207, in Clostridium botulinum: Ecology and
Control in Foods, A. H. W. Hauschild, and K. L. Dodds, eds., Marcel
Dekker, New York, 1993.
60. International Commission on Microbiological Specification
for Foods, Microorganisms in Foods 5. Characteristics of Microbial
Pathogens, Blackie Academic and Professional, London, 1996.
61. Thayer, D. W., et al., ``Radiation Resistance of
Salmonella,'' Journal of Industrial Microbiology, 5:383-390, 1990.
62. Thayer, et al., ``Variations in Radiation Sensitivity of
Foodborne Pathogens Associated with the Suspending Meat,'' Journal
of Food Science, 60(1):63-67, 1994.
63. Clavero, M. R. S., et al., ``Inactivation of Escherichia
coli O157:H7, Salmonellae and Campylobacter jejuni in Raw Ground
Beef by Gamma Irradiation,'' Applied and Environmental Microbiology,
60:2069-2075, 1994.
64. Han, L.-B., M.-H. Liew, and L.-T. Yeh, ``Preservation of
Grass Prawns by Ionizing Radiation,'' Journal of Food Protection,
55:198-202, 1992.
65. Thayer, D. W. and G. Boyd, ``Elimination of Escherichia coli
O157:H7 in Meats by Gamma Irradiation,'' Applied and Environmental
Microbiology, 59:1030-1034, 1993.
66. Monk, D. J., et al., ``Irradiation Inactivation of Listeria
monocytogenes and Staphylococcus aureus in Low- and High-fat, Frozen
and Refrigerated Ground Beef,'' Journal of Food Protection, 57:969-
974, 1994.
67. Lambert, J. D. and R. B. Maxcy, ``Effects of Gamma Radiation
on Campylobacter jejuni,'' Journal of Food Science, 49:665-667,
1984.
68. Dubey, J. P. and D. W. Thayer, ``Killing of Different
Strains of Toxoplasma gondii Tissue Cysts by Irradiation Under
Defined Conditions,'' Journal of Parasitology, 80(5): 764-767, 1994.
69. Ingram, M. and J. Farkas, ``Microbiology of Foods
Pasteurized by Ionizing Radiation,'' Acta Alimentaria, 6:123-185,
1977.
70. Tallentire, A., ``The Spectrum of Microbial Radiation-
Sensitivity,'' Radiation Physics and Chemistry, 15:83-89, 1980.
71. Hastings, J. W., W. H. Holzapfel, and J. G. Niemand,
``Radiation Resistance of Lactobacilli Isolated from Radurized Meat
Relative to Growth and Environment,'' Applied and Environmental
Microbiology, 52(4):898-901, 1986.
72. Grant, I. R. and M. F. Patterson, ``Effect of Irradiation
and Modified Atmosphere Packaging on the Microbiological Safety of
Minced Pork Under Temperature Abuse Conditions,'' International
Journal of Food Science and Technology, 26:521-533, 1991.
73. Grant, I. R. and M. F. Patterson, ``Sensitivity of Foodborne
Pathogens to Irradiation in the Components of a Chilled Ready
Meal,'' Food Microbiology, 9:95-103, 1992.
74. Grecz, N., D. B. Rowley, and A. Matsuyama, ``The Action of
Radiation on Bacteria and Viruses,'' pp. 167-218, In Preservation of
Food by Ionizing Radiation, Vol. 2, E. S. Josephson and M. S.
Peterson, eds., CRC Press, Boca Raton, Fl., 1982.
*75. Memorandum from J. Madden and L. Bluhm, FDA, to P. Hansen,
FDA, dated January 20, 1995.
76. Tompkin, R. B., ``Botulism from Meat and Poultry Products-A
Historical Perspective,'' Food Technology, pp. 229-236, May, 1980.
77. Dodds, K. L. and J. W. Austin, ``Clostridium botulinum,''
pp. 288-304, in Food Microbiology: Fundamentals and Frontiers, M. P.
Doyle, L. R. Beuchat, and T. J. Montville, eds., ASM Press,
Washington, DC, 1997.
78. Lebepe, S., et al., ``Changes in Microflora and Other
Characteristics of Vacuum-Packaged Pork Loins Irradiated at 3.0
kGy,'' Journal of Food Science, 55(4):918-924, 1990.
79a. Lambert, A. D., J. P. Smith, and K. L. Dodds, ``Combined
Effect of Modified Atmosphere Packaging and Low-Dose Irradiation on
Toxin Production by Clostridium botulinum in Fresh Pork,'' Journal
of Food Protection, 54(2):94-101, 1991.
79b. Lambert, A. D., J. P. Smith, and K. L. Dodds, ``Effect of
Headspace CO2 Concentration on Toxin Production by Clostridium
botulinum in MAP, Irradiated Fresh Pork,'' Journal of Food
Protection, 54(8):588-592, 1991.
79c. Lambert, A. D., J. P. Smith, and K. L. Dodds, ``Effect of
Initial O2 and CO2 and Low-Dose Irradiation on Toxin Production by
Page 64121
Clostridium botulinum in MAP Fresh Pork,'' Journal of Food
Protection, 54(12):939-944, 1991.
80. Niemand, J. G., et al., ``Radurization of Prime Beef Cuts,''
Journal of Food Protection, 44:677-681, 1981.
81. Ehioba, R. M., et al., ``Identification of Microbial
Isolates from Vacuum-Packaged Ground Pork Irradiated at 1 kGy,''
Journal of Food Science, 53:278-282, 1988.
List of Subjects in 21 CFR Part 179
Food additives, Food labeling, Food packaging, Radiation
protection, Reporting and record keeping requirements, Signs and
symbols.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
179 is amended as follows:
PART 179--IRRADIATION IN THE PRODUCTION, PROCESSING AND HANDLING OF
FOOD
1. The authority citation for 21 CFR part 179 continues to read as
follows:
Authority: 21 U.S.C. 321, 342, 343, 348, 373, 374.
2. Section 179.26 is amended in the table in paragraph (b) by
adding a new entry ``8.'' under the headings ``Use'' and
``Limitations'' to read as follows:
Sec. 179.26 Ionizing radiation for the treatment of food.
* * * * *
(b) * * *
------------------------------------------------------------------------
Use Limitations
------------------------------------------------------------------------
* * * *
* * *
8. For control of foodborne pathogens Not to exceed 4.5 kGy maximum
in, and extension of the shelf-life for refrigerated products; not
of, refrigerated or frozen, uncooked to exceed 7.0 kGy maximum for
products that are meat within the frozen products.
meaning of 9 CFR 301.2(rr), meat
byproducts within the meaning of 9 CFR
301.2(tt), or meat food products
within the meaning of 9 CFR 301.2(uu),
with or without nonfluid seasoning,
that are otherwise composed solely of
intact or ground meat, meat
byproducts, or both meat and meat
byproducts..
------------------------------------------------------------------------
* * * * *
Dated: November 26, 1997.
Michael A. Friedman,
Lead Deputy Commissioner for the Food and Drug Administration.
FR Doc. 97-31740 Filed 12-2-97; 8:45 am
BILLING CODE 4160-01-F