Irradiation in the Production, Processing and Handling of Food

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.

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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.

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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\

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\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).

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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).

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\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).

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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

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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:

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\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.

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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.

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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.

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\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.

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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.

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\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.

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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

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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).

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\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.

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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.

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\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).

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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

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13384).\11\ The data showed that no treatment-related adverse effects

were observed with either irradiated food.

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\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.

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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\

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\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.

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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.

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\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.

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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.

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\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).

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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.

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\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.

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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.

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\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.

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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).

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\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).

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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\

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\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).

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[[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 -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-

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A. J. Cohen, eds., Elsevier, Amsterdam, 1977.

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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