Federal Register / Vol. 73, No. 164 / Friday, August 22, 2008 / Rules and Regulations 49593 

§ 3550.61 Insurance (loans only). 

(a) Borrower responsibility. Any 

borrower with a secured indebtedness 

in excess of $15,000 at the time of loan 

approval must furnish and continually 

maintain hazard insurance on the 

security property, with companies, in 

amounts, and on terms and conditions 

acceptable to RHS including a ‘‘loss 

payable clause’’ payable to RHS to 

protect the Government’s interest. 

(b) Amount. The borrower is required 

to insure the dwelling and any other 

essential buildings in an amount equal 

to the insurable value of the dwelling 

and other essential buildings. However, 

in cases where the borrower’s 

outstanding secured indebtedness is less 

than the insurable value of the dwelling 

and other essential buildings, the 

borrower may elect a lower coverage 

provided it is not less than the 

outstanding secured indebtedness. If the 

borrower fails, or is unable, to insure the 

secured property, RHS will force place 

insurance and charge the cost to the 

borrower’s account. Force place 

insurance only provides insurance 

coverage to the Agency and does not 

provide any direct coverage or benefit to 

the borrower. The amount of the lenderplaced coverage will generally be the 

property’s last known insured value. 

* * * * * 

(d) * * * 

(1) Loss deductible clauses for 

required insurance coverage may not 

exceed the generally accepted 

minimums based on current industry 

standards and local market conditions. 

* * * * * 

■ 4. Section 3550.64 is revised to read 

as follows: 

§ 3550.64 Down payment. 

Elderly families must use any net 

family assets in excess of $20,000 

towards a down payment on the 

property. Non-elderly families must use 

net family assets in excess of $15,000 

towards a down payment on the 

property. Applicants may contribute 

assets in addition to the required down 

payment to further reduce the amount to 

be financed. 

Subpart C—Section 504 Origination 

and Section 306C Water and Waste 

Disposal Grants 

■ 6. Section 3550.103 is amended by 

revising paragraph (e) to read as follows: 

§ 3550.103 Eligibility requirements. 

* * * * * 

(e) Need and use of personal 

resources. Applicants must be unable to 

obtain financial assistance at reasonable 

terms and conditions from non-RHS 

credit or grant sources and lack the 

personal resources to meet their needs. 

In cases where the household is 

experiencing medical expenses in 

excess of three percent of the 

household’s income, this requirement 

may be waived or modified. Elderly 

families must use any net family assets 

in excess of $20,000 to reduce their 

section 504 request. Non-elderly 

families must use any net family assets 

in excess of $15,000 to reduce their 

section 504 request. Applicants may 

contribute assets in excess of the 

aforementioned amounts to further 

reduce their request for assistance. The 

definition of assets for this purpose is 

net family assets as described in 

§ 3550.54 of subpart B of this part, less 

the value of the dwelling and a 

minimum adequate site. 

* * * * * 

■ 7. Section 3550.110 is amended by 

revising paragraphs (a), (b) and (d)(1) to 

read as follows: 

§ 3550.110 Insurance (loans only). 

(a) Borrower responsibility. Any 

borrower with a secured indebtedness 

in excess of $15,000 at the time of loan 

approval must furnish and continually 

maintain hazard insurance on the 

security property, with companies, in 

amounts, and on terms and conditions 

acceptable to RHS including a ‘‘loss 

payable clause’’ payable to RHS to 

protect the Government’s interest. 

(b) Amount. The borrower is required 

to insure the dwelling and any other 

essential buildings in an amount equal 

to the insurable value of the dwelling 

and other essential buildings. However, 

in cases where the borrower’s 

outstanding secured indebtedness is less 

than the insurable value of the dwelling 

and other essential buildings, the 

borrower may elect a lower coverage 

provided it is not less than the 

outstanding secured indebtedness. If the 

borrower fails, or is unable to insure the 

secured property, RHS will force place 

insurance and charge the cost to the 

borrower’s account. Force place 

insurance only provides insurance 

coverage to the Agency and does not 

provide any direct coverage or benefit to 

the borrower. The amount of the lenderplaced coverage generally will be the 

property’s last known insured value. 

* * * * * 

(d) * * * 

(1) Loss deductible clauses for 

required insurance coverage may not 

exceed the generally accepted 

minimums based on current and local 

market conditions. 

* * * * * 

Dated: July 28, 2008. 

Russell T. Davis, 

Administrator, Rural Housing Service. 

[FR Doc. E8–19350 Filed 8–21–08; 8:45 am] 

BILLING CODE 3410–XV–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 179 

[Docket No. FDA–1999–F–2405] (formerly 

1999F–5522) 

Irradiation in the Production, 

Processing and Handling of Food 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final rule. 

SUMMARY: The Food and Drug 

Administration (FDA) is amending the 

food additive regulations to provide for 

the safe use of ionizing radiation for 

control of food-borne pathogens, and 

extension of shelf-life, in fresh iceberg 

lettuce and fresh spinach (hereinafter 

referred to in this document as ‘‘iceberg 

lettuce and spinach’’) at a dose up to 4.0 

kiloGray (kGy). This action is in partial 

response to a petition filed by The 

National Food Processors Association 

on behalf of The Food Irradiation 

Coalition. 

DATES: This rule is effective August 22, 

2008. Submit written or electronic 

objections and requests for a hearing by 

September 22, 2008. See section VI of 

this document for information on the 

filing of objections. 

ADDRESSES: You may submit written or 

electronic objections and requests for a 

hearing identified by Docket No. FDA–

1999–F–2405] (formerly 1999F–5522, by 

any of the following methods: 

Electronic Submissions 

Submit electronic objections in the 

following way: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the 

instructions for submitting comments. 

Written Submissions 

Submit written objections in the 

following ways: 

• FAX: 301–827–6870. 

• Mail/Hand delivery/Courier [For 

paper, disk, or CD-ROM submissions]: 

Division of Dockets Management (HFA–

305), Food and Drug Administration, 

5630 Fishers Lane, rm. 1061, Rockville, 

MD 20852. 

To ensure more timely processing of 

objections, FDA is no longer accepting 

objections submitted to the agency by email. FDA encourages you to continue 


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49594 Federal Register / Vol. 73, No. 164 / Friday, August 22, 2008 / Rules and Regulations 

1The temperature at which irradiation is 

conducted can also be a factor, with more radiationinduced changes occuring with increasing 

temperature. Temperature is less important, 

however, than the physical state of the food. 

to submit electronic objections by using 

the Federal eRulemaking Portal, as 

described in the Electronic Submissions 

portion of this paragraph. 

Instructions: All submissions received 

must include the agency name and 

docket number for this rulemaking. All 

objections received will be posted 

without change to http:// 

www.regulations.gov, including any 

personal information provided. For 

detailed instructions on submitting 

objections, see the ‘‘Objections’’ heading 

of the SUPPLEMENTARY INFORMATION

section of this document. 

Docket: For access to the docket to 

read background documents or 

objections received, go to http:// 

www.regulations.gov and insert the 

docket number(s), found in brackets in 

the heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Division of Dockets 

Management, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. 

FOR FURTHER INFORMATION CONTACT: 

Lane A. Highbarger, Center for Food 

Safety and Applied Nutrition (HFS–

255), Food and Drug Administration, 

5100 Paint Branch Pkwy., College Park, 

MD 20740, 301–436–1204. 

SUPPLEMENTARY INFORMATION: 

Table of Contents 

I. Background 

II. Safety Evaluation 

A. Radiation Chemistry 

B. Toxicological Considerations 

C. Nutritional Considerations 

D. Microbiological Considerations 

III. Comments 

A. 2-Alkylcyclobutanones 

B. List of Foods Covered by the Petition 

C. Toxicity Data 

D. Hardy Pathogens 

E. Effects on Organoleptic (Sensory) 

Properties 

IV. Conclusions 

V. Environmental Impact 

VI. Objections 

VII. References 

I. Background 

In a notice published in the Federal 

Register of January 5, 2000 (65 FR 493), 

and amended May 10, 2001 (66 FR 

23943), FDA announced that a food 

additive petition (FAP 9M4697) had 

been filed by The National Food 

Processors Association on behalf of The 

Food Irradiation Coalition, 1350 I St. 

NW., suite 300, Washington, DC 20005. 

The petition proposed that the food 

additive regulations in part 179, 

Irradiation in the Production, 

Processing, and Handling of Food (21 

CFR part 179), be amended to provide 

for the safe use of ionizing radiation for 

control of food-borne pathogens, and 

extension of shelf-life, in a variety of 

human foods up to a maximum 

irradiation dosage of 4.5 kGy for nonfrozen and non-dry products, and 10.0 

kGy for frozen or dry products, 

including: (1) Pre-processed meat and 

poultry; (2) both raw and pre-processed 

vegetables, fruits, and other agricultural 

products of plant origin; (3) certain 

multi-ingredient food products 

containing cooked or uncooked meat or 

poultry. Subsequently, in a letter dated 

December 4, 2007, the petitioner 

amended the petition to request a 

response to part of the original request 

while the remainder of the request 

would remain under review. 

Specifically, the petitioner requested a 

response regarding amending the food 

additive regulations to provide for the 

safe use of ionizing radiation for control 

of food-borne pathogens, and extension 

of shelf-life, in iceberg lettuce and 

spinach up to a maximum dose of 4.0 

kGy. This final rule is a partial response 

to the petition and addresses only the 

use of ionizing radiation on iceberg 

lettuce and spinach. The use of ionizing 

radiation on the remaining foods 

included in the petition remains under 

review. 

II. Safety Evaluation 

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 additive is not added to 

food literally, but is rather a source of 

radiation used to process or treat food 

such that, analogous to other food 

processing technologies, its use can 

affect the characteristics of the food. 

Importantly, 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 

testing and data required to establish the 

safety of an additive will vary 

depending on the particular additive 

and its intended use. 

In evaluating the safety of a source of 

radiation to treat food intended for 

human consumption, the agency must 

identify the various effects that may 

result from irradiating the food and 

assess whether any of these effects pose 

a public health concern. In doing so, the 

following three general areas need to be 

addressed: (1) Potential toxicity, (2) 

nutritional adequacy, and (3) effects on 

the microbiological profile of the treated 

food. Each of these areas is discussed in 

this document. Because an 

understanding of radiation chemistry is 

fundamental in addressing these three 

areas, key aspects of radiation chemistry 

relevant to the evaluation of the request 

that is the subject of this rulemaking are 

also discussed. FDA has fully 

considered the data and studies 

submitted in the petition as well as 

other data and information relevant to 

safety. 

A. Radiation Chemistry 

The term ‘‘radiation chemistry’’ refers 

to the chemical reactions that occur as 

a result of the absorption of ionizing 

radiation. In the context of food 

irradiation, the reactants are the 

chemical constituents of the food and 

initial radiolysis products that may 

undergo further chemical reactions. The 

chemistry involved in the irradiation of 

foods has been the subject of numerous 

studies over the years and scientists 

have compiled a large body of data 

regarding the effects of ionizing 

radiation on different foods under 

various conditions of irradiation. The 

basic principles are well understood 

(Refs. 1 to 4) and 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. The types and 

amounts of products generated by 

radiation-induced chemical reactions 

(‘‘radiolysis products’’) depend on both 

the chemical constituents of the food 

and on the specific conditions of 

irradiation. The principles of radiation 

chemistry also govern the extent of 

change, if any, in both the nutrient 

levels and the microbial loads of 

irradiated foods. 

In the next section, FDA will discuss 

important aspects of radiation chemistry 

and related topics as they apply 

specifically to iceberg lettuce, spinach, 

and foods of similar composition. 

1. Factors Affecting the Radiation 

Chemistry of Foods 

Apart from the chemical composition 

of the food itself, the specific conditions 

of irradiation 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., solid 

or frozen versus liquid or nonfrozen 

state, dried versus hydrated state), and 

the ambient atmosphere (e.g., air, 

reduced oxygen, and vacuum).1

The amounts of radiolysis products 

generated in a particular food are 

directly proportional to the radiation 

dose. Therefore, one can extrapolate 

from data obtained at high radiation 


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Federal Register / Vol. 73, No. 164 / Friday, August 22, 2008 / Rules and Regulations 49595 

doses to draw conclusions regarding the 

effects at lower doses. 

The radiation chemistry of food is 

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 nonfrozen state. This is because of the 

reduced mobility, in the frozen state, of 

the initial radiolysis products, which 

will tend to recombine rather than 

diffuse and react with other food 

components. Likewise, and for similar 

reasons, if all other conditions are the 

same, the extent of chemical change that 

occurs in the dehydrated state is less 

than the change that occurs in the fully 

hydrated state. 

The formation of radiolysis products 

in a given food also is affected by the 

ambient atmosphere. Irradiation in an 

atmosphere of high oxygen content 

generally produces both a greater 

variety, and greater amounts, of 

radiolysis products in the food than 

would be produced in an atmosphere of 

lower oxygen content. This is because 

irradiation initiates certain oxidation 

reactions that occur with greater 

frequency in foods with high fat content 

(Refs. 1 and 5). 

With few exceptions, the radiolysis 

products generated in a particular food 

are the same or very similar to the 

products formed in other types of food 

processing or under common storage 

conditions. These radiolysis products 

are also typically formed in very small 

amounts (Ref. 1). 

Radiation-induced chemical changes, 

if sufficiently large, however, may cause 

changes in the organoleptic properties 

of the food. Because food processors 

want to avoid undesirable effects on 

taste, odor, color, or texture, there is an 

incentive to minimize the extent of 

these chemical changes in food. Thus, 

the doses used to achieve a given 

technical effect (e.g., inhibition of 

sprouting, reduction in microorganisms) 

must be selected carefully to both 

achieve the intended effect and 

minimize undesirable chemical 

changes. Typically, the dose or dose 

range selected will be the lowest dose 

practical in achieving the desired effect. 

Irradiation also is often conducted 

under reduced oxygen levels or on food 

held at low temperature or in the frozen 

state. 

2. Radiation Chemistry of the Major 

Components of Iceberg Lettuce and 

Spinach 

The major components of iceberg 

lettuce and spinach, as with most fruits 

and vegetables, are water 

(approximately 91 to 96 percent) and 

carbohydrate (up to approximately 4 

percent), with protein also present as a 

minor component. The lipid content of 

both iceberg lettuce and spinach is quite 

low (less than 0.5 percent) (Ref. 6). 

Because of the high water content of 

iceberg lettuce and spinach, their 

radiation chemistry is dominated by the 

radiation chemistry of water, in which 

reactive hydroxyl and hydrogen radicals 

are the primary radiolysis products. 

These radicals are most likely to 

recombine to form water, hydrogen gas, 

or hydrogen peroxide; they may, 

however, also react with other 

components of iceberg lettuce and 

spinach (e.g., carbohydrates). While 

most of the chemical effects of 

radiation-processing on iceberg lettuce 

and spinach are expected to result from 

the reactions induced by hydroxyl and 

hydrogen radicals, other food 

components (e.g., carbohydrates, 

proteins, and lipids) may also absorb 

radiation directly and generate small 

amounts of other radiolysis products. 

a. Carbohydrates. Carbohydrates are 

molecules composed of sugar units, 

which are grouped and categorized 

according to their size. The simplest and 

smallest are the monosaccharides 

(simple sugars such as glucose) and 

disaccharides (such as sucrose). Larger 

complex carbohydrates (pectin, fiber, 

and starch) consist of chains of 

monosaccharide units and are referred 

to as polysaccharides. The main effects 

of ionizing radiation on carbohydrates 

in foods have been studied extensively 

and discussed at length in the scientific 

literature (Refs. 7 and 8), as well as in 

reviews by such bodies as the World 

Health Organization (WHO) (Ref. 9). In 

the presence of water, carbohydrates 

react primarily with the hydroxyl 

radicals generated by the radiolysis of 

water. The result is abstraction of 

hydrogen from the carbon-hydrogen 

bonds of the carbohydrate, forming 

water and a carbohydrate radical. Direct 

ionization of carbohydrates to form 

carbohydrate radicals also is possible, 

but occurs to a far lesser extent (Refs. 

10, 11, and 12). 

In polysaccharides, the links between 

constituent monosaccharide units may 

be broken, resulting in the shortening of 

polysaccharide chains. Starch may be 

degraded into dextrins, maltose, and 

glucose. Sugar acids, ketones, 

aldehydes, and other sugar 

monosaccharides may also be formed as 

a result of ionizing radiation. Various 

studies have reported that radiolysis 

products formed from starches of 

different origin are qualitatively similar. 

The nature and concentration of the 

main radiation-induced products 

showed no marked differences among 

the various starches. In addition, 40 

different products have been analyzed 

in irradiated starches and have been 

found to be produced by heat treatment 

or natural oxidation of starch during 

storage, as well as by irradiation (Refs. 

8 and 10). 

The overall effects of ionizing 

radiation on carbohydrates are basically 

the same as those caused by cooking 

and other food processing treatments 

(Refs. 1 and 10). Irradiation of 

carbohydrates at doses up to 10 kGy has 

minimal effect on the carbohydrate 

functionality and the resulting products 

are smaller carbohydrates or other 

compounds also produced from 

carbohydrates through oxidation and/or 

heat treatment. FDA concludes that no 

significant change in carbohydrate 

nutrient value or functionality is 

expected to occur in iceberg lettuce and 

spinach irradiated at doses up to 4 kGy. 

b. Proteins. FDA has previously 

provided detailed discussions of the 

radiation chemistry of proteins in its 

rulemakings on the use of ionizing 

radiation to treat meat and molluscan 

shellfish (‘‘the meat rule,’’ 62 FR 64107; 

December 3, 1997, and ‘‘the molluscan 

shellfish rule,’’ 70 FR 48057; August 16, 

2005, respectively). Studies conducted 

with high-protein foods (e.g., meat, 

poultry, and seafood), have established 

that most of the radiolysis products 

derived from food proteins have the 

same amino acid composition and are 

altered only in their secondary and 

tertiary structures (i.e., denatured). 

These changes are similar to those that 

occur as a result of heating, but in the 

case of irradiation, even at doses up to 

50 kGy, such changes are far less 

pronounced and the amounts of reaction 

products generated are far lower (62 FR 

64107; Refs. 10 and 13). FDA concludes 

that there will be few reaction products 

generated from the small amounts of 

protein in iceberg lettuce and spinach 

and that no significant change in the 

amino acid composition of these two 

foods is expected to result from 

irradiation at doses up to 4.0 kGy. 

c. Lipids. FDA also has previously 

provided a detailed discussion of the 

radiation chemistry of lipids in the meat 

and molluscan shellfish rules. In 

summary, a variety of radiolysis 

products derived from lipids have been 

identified, including fatty acids, esters, 

aldehydes, ketones, alkanes, alkenes, 

and other hydrocarbons (Refs. 1 and 14). 

Identical or analogous compounds are 

also found in foods that have not been 

irradiated. In particular, heating food 

produces generally the same types of 

compounds, but in amounts far greater 


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2Beef is generally composed of approximately 15 

to 25 percent fat, depending on the cut. Chicken, 

depending on the cut and whether skin is included, 

is approximately 5 to 19 percent fat. The palmitic 

acid content of the fat in beef and chicken is in the 

range of 22 to 25 percent (Ref. 6) 

3 Iceberg lettuce contains approximately 0.016 

percent palmitic acid, and spinach contains 

approximately 0.046 percent palmitic acid (Ref.6) 

4 During the early 1980s, a joint Food and 

Agriculture Organization/International Atomic 

Energy Agency, World Health Organization (FAO/ 

IAEA/WHO) Expert Committee evaluated the 

toxicological and microbiological safety and 

nutritional adequacy of irradiated foods. The Expert 

Committee concluded that irradiation of any food 

commodity at an average dose of up to 10 kGy 

presents no toxicological hazard (Ref. 24). In the 

1990s, at the request of one of its member states, 

WHO conducted a new review and analysis of the 

safety data on irradiated food. This more recent 

WHO 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 the 

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 concluded 

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. 9). 

5The irradiated fruits and vegetables in these 

studies included: Peaches, strawberries, bananas, 

cherries, prunes, potatoes, carrots, onions, black 

beans, corn, green beans, and cabbage. 

than the trace amounts produced from 

irradiating food (Refs. 10 and 15). 

There is, however, a class of 

radiolysis products derived from lipids, 

2-alkylcyclobutanones (2–ACBs), that 

has been reported to form in small 

quantities when fats are exposed to 

ionizing radiation, but not when they 

are exposed to heat or other forms of 

processing. The specific 2–ACBs formed 

will depend on the fatty acid 

composition of the food. For example, 2- 

dodecylcyclobutanone (2–DCB) is a 

radiation by-product of tryiglycerides 

with esterified palmitic acid. 

Researchers have reported that 2–DCB is 

formed in small amounts (less than 1 

microgram per gram lipid per kGy (μg/ 

g lipid/kGy) from irradiated chicken 

(Ref. 16) and in even smaller amounts 

from ground beef (Ref. 17). Both of these 

foods are of relatively high total fat and 

palmitic acid content.2

In the molluscan shellfish rule, the 

agency provided a detailed discussion 

of its assessment of the significance of 

the formation of 2–DCB to the safety 

evaluation of irradiated molluscan 

shellfish, a food which, like chicken and 

ground beef, contains significant 

amounts of triglycerides with esterified 

palmitic acid. In that assessment, FDA 

considered all of the available data and 

information, including the results of 

genotoxicity studies and previously 

reviewed studies in which animals were 

fed diets containing irradiated meat, 

poultry, and fish. All of these foods 

contain appreciable amounts of lipids 

that contain triglycerides with palmitic 

acid. While 2–DCB and other 

alkylcyclobutanones would be expected 

to be present in these irradiated foods, 

FDA found no evidence of toxicity 

attributable to their consumption. 

As noted previously in this document, 

iceberg lettuce and spinach contain 

little fat (less than 0.5 percent); neither 

food contains appreciable amounts of 

palmitic acid.3 Because of the low lipid 

content and the very low palmitic acid 

content of iceberg lettuce and spinach, 

FDA concludes that formation of 

alkylcyclobutanones generally, and 2–

DCB specifically, from irradiation of 

these foods would be in amounts much 

smaller than those formed from 

irradiation of foods of higher fat content 

and would not pose a toxicological 

concern. 

Overall, FDA concludes that no 

significant differences are expected to 

occur between the kinds and amounts of 

lipids and lipid byproducts in nonirradiated iceberg lettuce and spinach 

compared to iceberg lettuce and spinach 

irradiated at doses of 4.0 kGy. 

3. Consideration of Furan as a 

Radiolysis Product 

During the course of reviewing the 

chemical effects of irradiation as part of 

the evaluation of this and other 

petitions, FDA became aware of a report 

that suggested irradiating apple juice 

may produce furan (Ref. 18). Because 

furan has been shown to cause tumors 

in laboratory animals, FDA initiated 

research on whether the report was 

accurate and whether furan was a 

common radiolysis product in food. The 

petitioner also conducted testing and 

the United States Department of 

Agriculture (USDA) initiated additional 

research. FDA has confirmed that 

certain foods form furan in low 

quantities when irradiated. Studies 

conducted by FDA scientists and other 

researchers show that some foods form 

furan when heated and still other foods 

form furan during storage at 

refrigeration temperatures (Refs. 19 and 

20). Testing of irradiated lettuce and 

spinach show that if furan is formed 

when these foods are irradiated, it is 

formed at levels that are below the limit 

of detection in the tests, or below the 

background levels of natural furan 

formation during storage (Refs. 19, 21, 

and 22). Therefore, FDA concludes that 

the consumption of irradiated iceberg 

lettuce and spinach will not increase the 

amount of furan in the diet. 

B. Toxicological Considerations 

The available information from the 

results of chemical reactions described 

in section II.A of this document suggests 

that there is no reason to suspect a 

toxicological hazard due to 

consumption of an irradiated food. 

While chemical analyses have not 

identified the presence of radiolysis 

products in amounts that would raise a 

toxicological concern, the agency notes 

that the large body of data from studies 

where irradiated foods were fed to 

laboratory animals provides an 

independent way to assess toxicological 

safety. These studies include those 

relied on by the agency in previous 

evaluations of the safety of irradiated 

foods (see 70 FR 48057, 65 FR 45280, 62 

FR 64107, 55 FR 18538, and 51 FR 

13376) and additional data and 

information in FDA files or other 

published reports regarding studies in 

which animals were fed a wide variety 

of foods irradiated at different doses. 

The agency’s analysis incorporates the 

principles that toxicological data 

collected from studies on a given food 

may be applied to the toxicological 

evaluation of foods of similar generic 

class and that data from foods irradiated 

at high doses can be applied to the 

toxicological evaluation of foods of 

similar generic class receiving lower 

doses (62 FR 64107; Ref. 10). The 

agency’s analysis also draws upon the 

integrated toxicological database 

derived from the extensive body of work 

reviewed by the agency (Ref. 23) and by 

the WHO4 in previous evaluations of the 

safety of irradiated foods. Thus, the 

agency has re-examined the available 

data from toxicological studies that are 

particularly relevant to the safety of 

irradiated iceberg lettuce and spinach, 

specifically fruits and vegetables which, 

as a group, are relatively carbohydraterich foods of high water content. The 

agency’s analysis also takes into account 

the known effects of other conditions of 

irradiation to compare the results of 

different studies. 

FDA has evaluated a large number of 

studies in which various irradiated 

fruits or vegetables,5 alone or in 

combination with other irradiated foods, 

were fed to animals (Refs. 25 and 26). 

These studies were conducted in a 

variety of animal species, with foods 

irradiated at doses ranging from 0.15 to 

50 kGy. In the vast majority of these 

studies, no adverse effects were 

reported. Three studies reported 

observations that merit further 

discussion. FDA has concluded that the 

effects reported in these three studies 

were either not attributable to 


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6 Incidence of female sterility (percent), 

established fertility of males (percent), incidence of 

still births per litter, and pups born alive reaching 

weaning age (percent). 

7The effect was more pronounced in rats fed 

oranges irradiated at the lower of the two test doses, 

the opposite of what one would expect if the effect 

were related to irradiation. 

8 In accordance with 21 CFR 101.54(b), foods 

containing ≥ 20 percent of the Reference Daily 

Intake (RDI) or Daily Reference Value (DRV) per 

reference amount customarily consumed (RACC), 

the amount of food customarily consumed per 

eating occasion such as in one meal or snack) may 

be labeled as ‘‘excellent source of’’, ‘‘high in’’ or 

‘‘rich in’’ a given nutrient. By this criterion, spinach 

is an excellent source of vitamins A, C, K, and 

folate. Iceberg lettuce is an excellent source of 

vitamin K only. 

9Although spinach contains relatively high 

amounts of vitamin C, its contribution to the total 

dietary intake of this vitamin is negligible. The 

combined group of spinach and ‘‘greens’’ (e.g., kale, 

chard, chives) contributes less than 2 percent to the 

total dietary intake of vitamin C; the contribution 

of iceberg lettuce is essentially zero (Ref. 33). 

10The primary food sources of vitamin A 

(including provitamin A carotenoids) in the U.S. 

diet are carrots, organ meats, dairy products, eggs, 

and ready-to-eat cereals. Together, these food 

sources contribute approximately 60 percent of the 

total dietary intake of vitamin A (expressed in 

retinol equivalents). 

irradiation or were otherwise not of 

toxicological significance. 

In the first study, dogs fed a diet 

containing 10 percent onions (dry 

weight basis, irradiated at 0.25 kGy) for 

90 days were reported to develop 

anemia, as did control dogs fed 

nonirradiated onions (Ref. 27). Other 

effects such as increased spleen weights, 

myeloid metaplasia, and 

reticuloendothelial hyperplasia were 

reported but, again, in both control and 

treated dogs. FDA has concluded that 

the effects cannot be attributed to 

irradiation because similar effects were 

reported in both dogs fed irradiated 

onions and dogs fed non-irradiated 

onions (Ref. 25). 

The second study was a multigeneration reproduction study in which 

rats were fed a diet containing 35 

percent oranges (dry weight basis) (Ref. 

28). Animals in the control group were 

fed non-irradiated oranges; animals in 

the treated groups were fed oranges 

irradiated at 1.40 or 2.79 kGy. The 

authors reported decreased reproductive 

performance in the second breeding, as 

measured by several parameters,6 for 

rats fed irradiated oranges as well as 

those fed the control diet. Because the 

effects were observed in both animals 

fed irradiated food and animals fed nonirradiated food, FDA has concluded that 

they cannot be attributed to irradiation 

(Refs. 25 and 26). The authors also 

reported a small, but statistically 

significant difference in one additional 

parameter of reproductive performance 

in treated animals, body weight of pups 

at weaning. The pups made up for the 

weight depression after weaning. FDA 

has concluded that this reported effect 

is not of toxicological significance for 

the following two reasons: (1) It was a 

very small difference in the overall poor 

reproductive performance of all animals 

in the second breeding, and (2) the pups 

from the treated groups made up for the 

slight weight depression after weaning. 

In another segment of this study, the 

authors reported a small, but 

statistically significant reduction in 

body weight gain for third generation 

animals in the treated groups (but not 

the parent or second generation 

animals). FDA has concluded that this 

effect is not of toxicological significance 

for the following two reasons: (1) There 

was no apparent dose response,7 and (2) 

the differences in body weights were 

within the normal range of variation for 

feeding studies (Ref. 26). 

In a third study (Ref. 29), weanling 

rats fed a mixture of cabbage irradiated 

at 6 kGy and chicken stew irradiated at 

56 kGy for 19 days were reported to 

have reduced levels of alkaline 

phosphatase in duodenal tissue. In its 

evaluation of the safety of irradiated 

meat, FDA reviewed this study in detail 

and concluded that the effect observed 

was not of toxicological significance (62 

FR 64107 at 64113). 

In summary, FDA has reviewed a 

large body of data relevant to the 

assessment of potential toxicity of 

irradiated fruits and vegetables. While 

all of the studies are not of equal quality 

or rigor, the agency has concluded that 

the quantity and breadth of testing and 

the number and significance of 

endpoints assessed would have 

identified any real or meaningful risk. 

The overwhelming majority of studies 

showed no evidence of toxicity. On 

those few occasions when adverse 

effects were reported, FDA finds that 

those effects cannot be attributed to 

irradiation. Based on the totality of the 

evidence, FDA concludes that 

irradiation of iceberg lettuce and 

spinach under the conditions proposed 

in this petition does not present a 

toxicological hazard. 

C. Nutritional Considerations 

It is well known that the nutritive 

values of the macronutrients in the diet 

(protein, fats, and carbohydrates) are not 

significantly altered by irradiation at the 

petitioned doses (Refs. 30, 31, and 32). 

Minerals (e.g., calcium and iron) are 

also unaffected by irradiation. Levels of 

certain vitamins, on the other hand, may 

be reduced as a result of irradiation. The 

extent to which this reduction occurs 

depends on the specific vitamin, the 

type of food, and the conditions of 

irradiation. Not all vitamin loss is 

nutritionally significant, however, and 

the extent to which a reduction in a 

specific vitamin level is significant 

depends on the relative contribution of 

the food in question to the total dietary 

intake of the vitamin. 

Nutrition-related information relevant 

to fruits and vegetables submitted in the 

petition included analyses of 

consumption data for these broad 

categories and of vitamin levels in 

specific irradiated foods from these 

categories. The petitioner’s overall 

analysis focused on the the following 

vitamins the petitioner identified as 

being present in relatively high levels in 

fruits and vegetables generally: 

Thiamine; folate; and vitamins C, E, and 

A (the latter as provitamin carotenoids). 

Most of the studies with irradiated fruits 

or vegetables submitted in the petition 

focused on the levels of vitamin C or 

provitamin A carotenoids (sometimes 

also referred to as carotenes), because 

fruits and vegetables, as a combined 

category, are good sources of these 

micronutrients. Some studies of the 

effects of irradiation on the levels of 

vitamin E and on folate were also 

submitted. 

FDA has carefully reviewed the data 

and information submitted in the 

petition, as well as other data and 

information in its files, to determine 

whether irradiation of iceberg lettuce 

and spinach would have an adverse 

effect on the nutritional quality of the 

diet. FDA’s evaluation focused on the 

effects of irradiation on those nutrients 

for which at least one of these foods 

may be identified as an ‘‘excellent 

source’’8 and for which they contribute 

more than a trivial amount to the total 

dietary intake (i.e., greater than 1 to 2 

percent)9: Vitamin A (from betacarotene, a provitamin A carotenoid), 

vitamin K, and folate. FDA’s evaluation 

has also considered the relative 

radiation sensitivities of these vitamins. 

Many fruits and vegetables are good 

sources of vitamin A (including 

provitamin A carotenoids). Spinach is 

considered an excellent source of 

vitamin A based on its relatively high 

content of the provitamin A carotenoid 

beta-carotene. Nevertheless, it 

contributes no more than 3.5 percent to 

the total U.S. dietary intake of vitamin 

A10 (Refs. 33, 34 and 35). 

Although vitamin A has been 

identified as one of the most radiationsensitive of the fat-soluble vitamins, 

carotenoids in plant products 

demonstrate fairly high resistance to the 

effects of irradiation. One study of 

carrots irradiated at 2 kGy reported that 

carotenoids were stable to irradiation 


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11Other green vegetables such as broccoli, 

collards, salad greens, and kale contain substantial 

amounts of vitamin K. Other foods that also 

contribute to vitamin K intake include: Vegetable 

oils, grains, liver, cheese, and eggs. 

12One RACC of raw spinach (85 grams (g) can 

contain 41 percent of the RDA for folate. One RACC 

of iceberg lettuce, however, contains only about 6 

percent of the RDA for folate; iceberg lettuce is not 

considered a good source of this vitamin. (Ref. 6) 

13Enriched and fortified foods (e.g., cereal grains 

and grain-based products) make the greatest 

contribution to folate in the diet. 

14 D10 is the absorbed dose of radiation required 

to reduce a bacterial population by 90 percent. 

and that total carotenoid content of 

irradiated carrots did not differ from 

controls through 16 days of storage (Ref. 

36). In another study, carotenoid losses 

in mangoes and papayas irradiated at 

doses up to 2 kGy were reported to be 

negligible (0 to 15 percent) while 

considerable losses resulted from 

freezing or canning with various 

additives (Ref. 37). In other studies, 

minor carotenoid losses in broccoli 

irradiated at doses of 2 and 3 kGy were 

observed relative to controls on the day 

of treatment only, while no marked 

effects on total carotenoid content of 

irradiated samples were observed at 

days 4, 9, and 14 of storage (Ref. 38), 

and irradiation at doses up to 1 kGy did 

not affect the total carotenoid content of 

spinach stored under refrigeration for 15 

days (Ref. 39). In several studies, other 

processing or storage parameters were 

reported to affect the proportions of 

individual carotenoids more strongly 

than irradiation treatment (Ref. 31). FDA 

concludes that the small losses of 

vitamin A that might result from the 

proposed irradiation of iceberg lettuce 

or spinach will have little impact on the 

total dietary intake of this vitamin. 

Spinach and iceberg lettuce 

contribute approximately 12 percent 

and 8 percent, respectively, to the 

dietary intake of vitamin K (Ref. 40). 

Vitamin K is widely distributed in other 

plant and animal foods, however, and 

deficiencies of vitamin K in humans are 

extremely rare11 (Ref. 33). 

Vitamin K has also been identified as 

one of the least radiation sensitive of the 

fat-soluble vitamins (Ref. 41). In one 

study, which examined the effects of 

irradiation, freezing, and canning on 

vitamin K activity in spinach, along 

with other vegetables, there was no 

appreciable radiation-induced loss in 

Vitamin K activity at doses as high as 28 

or 56 kGy, doses much higher than the 

maximum dose requested in this 

petition (Ref. 42). FDA concludes that 

irradiation of iceberg lettuce and 

spinach up to a maximum dose of 4.0 

kGy will have no impact on the total 

dietary intake of vitamin K (Ref. 33). 

Spinach is an excellent source of 

folate.12 Nevertheless, in the context of 

the total diet, spinach contributes only 

a little more than 2 percent of the total 

dietary intake of folate (Refs. 33 and 

34).13 Studies that examined radiationinduced losses of folic acid in 

dehydrated asparagus irradiated to 5 

kGy or dehydrated spinach irradiated at 

10 kGy found no loss of folate as 

measured by compositional analysis or 

in a bioavailability assay in rats (Ref. 

43). Another recent study that examined 

the effects of irradiation of fresh 

vegetables at 2.5 kGy, reported folate 

losses of approximately 10 percent in 

fresh spinach, green cabbage, and 

Brussels sprouts (Ref. 44). The folate 

losses observed in this study are 

comparable to or less than the folate 

losses that have been reported for 

vegetables following various heat 

treatments (Refs. 45 and 46). FDA 

concludes that radiation-induced loss of 

folate in iceberg lettuce or spinach will 

have no significant impact on the 

dietary intake. 

In summary, based on the available 

data and information, FDA concludes 

that amending the regulations, as set 

forth below, to allow for the use of 

ionizing radiation to treat iceberg lettuce 

and spinach up to a maximum dose of 

4 kGy will not have an adverse impact 

on the nutritional adequacy of the 

overall diet. 

D. Microbiological Considerations 

Leafy green vegetables such as iceberg 

lettuce or spinach can serve as an ideal 

habitat for the growth of various 

microorganisms. Among the common, 

naturally-occurring microflora of 

vegetables, Pseudomonas, Enterobacter, 

and Erwinia species predominate. 

Various molds and yeasts may also be 

found on leafy green vegetables. 

Pathogens, which may also be present in 

the agricultural environment, can 

contaminate fresh produce that is 

grown, harvested, and in some cases 

undergoes preliminary processing (e.g., 

cutting or trimming) in that 

environment. Iceberg lettuce and 

spinach are often consumed raw and 

after only minimal preparation (e.g., 

rinsing) and, therefore, lack the final 

microbial elimination step provided for 

other foods by cooking. 

Contamination of fresh produce with 

several specific pathogens continues to 

be a public health problem. Infections 

from Salmonella enterica serovars and 

Escherichia coli O157:H7, for example, 

have not decreased since 1996. Most of 

the recent serious outbreaks of illness 

attributed to consuming lettuce or 

spinach have resulted from 

contamination by E. coli O157:H7. 

Three notable outbreaks involving this 

microorganism occurred in 2006; one of 

these was associated with bagged fresh 

spinach, the other two with lettuce used 

in fast food restaurants. Contamination 

of leafy greens with Listeria 

monocytogenes or Salmonella serovars 

also continues to be a public health 

problem. Even though other pathogens 

may be present, the three 

microorganisms named here are those 

that have been most commonly 

associated with recent outbreaks from 

the consumption of raw spinach or 

lettuce (Ref. 47). 

Data and information relevant to 

microbiological considerations 

presented in the petition included 

published studies of radiation-induced 

reductions in levels of different 

microorganisms in a variety of fruits and 

vegetables under different conditions of 

irradiation. Some of these studies also 

investigated the use of irradiation in 

combination with other antimicrobial 

treatments. FDA has evaluated the 

information in the petition, along with 

other data and information in its files 

and in the published literature in 

assessing the microbiological issues 

presented by the petitioner. 

There is a large body of work 

regarding the radiation sensitivities of 

non-pathogenic food spoilage 

microorganisms and pathogenic 

foodborne microorganisms. Generally, 

the common spoilage organisms such as 

Pseudomonas and the important 

pathogens in or on leafy greens are quite 

sensitive to the effects of ionizing 

radiation. Information in the petition 

and other information in FDA files 

shows that E. coli O157:H7 is highly 

sensitive to ionizing radiation, with 

published D10 values14 ranging from 

0.12 to 0.32 kGy, depending on the 

specific food matrix, physical state of 

the food, temperature, and other factors. 

Control of contaminating Salmonella 

serovars or Listeria spp. generally 

requires higher doses than for E. coli 

O157:H7. This is shown by the higher 

D10 values which are in the range of 0.16 

to 0.65 kGy, again, depending on the 

specific food, physical state, 

temperature, and other factors (Refs. 48 

to 51). 

Several recent studies have focused 

on the effects of ionizing radiation on 

pathogen levels in lettuce and spinach, 

specifically. In a series of studies by one 

group of researchers, the average D10

values for E coli O157:H7 and L. 

monocytogenes were reported to be 0.1 

kGy and 0.2 kGy, respectively and the 

D10 value for Salmonella reported to be 

ca. 0.25–0.3, depending on the lettuce 


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type (Refs. 52 and 53). In another study, 

treatment with ionizing radiation at a 

dose of 1.5 kGy produced a 4-log10

reduction in colony-forming units (CFU) 

on romaine lettuce and a 3-log10

reduction in CFU on baby spinach 

leaves (Ref. 54). Another recent study 

examined the effects of irradiation on 

bagged, ready-to-eat spinach leaves 

inoculated with E. coli O157:H7 and 

found that, for single leaves, doses as 

low as 0.9 kGy resulted in a 5- to 6-log10

reduction in the levels of this pathogen, 

while a dose of 1.2 kGy resulted in its 

reduction below the limits of detection 

of the test (Ref. 39). Collectively, these 

studies, together with earlier work, 

establish that levels of E. coli O157:H7, 

L. monocytogenes, and Salmonella 

serovars in or on iceberg lettuce or 

spinach will be reduced by irradiation 

at dose levels of 0.1 to 1.5 kGy, with the 

largest reductions occurring at the 

higher dose levels. 

Still other studies have examined the 

effects of irradiation on extension of 

shelf life and sensory attributes of 

various types of vegetables, including 

iceberg lettuce and spinach. In one 

study, the authors reported a reduction 

in total aerobic bacterial counts of over 

2-log10 CFU per gram (CFU/g) in freshcut lettuce irradiated at 1.0 kGy and 

over 3-log10 CFU/g reductions at 1.5 kGy 

(Ref. 55). In a separate study, the same 

researchers found similar results on 

total aerobic bacterial counts and 

significant reductions in coliform 

counts on fresh-cut lettuce when 

irradiated with similar doses. In this 

particular study, the authors also 

followed numbers of viable bacteria for 

9 days storage, noting that for irradiated 

samples, relative microbial reductions 

persisted while total numbers of 

bacteria increased by about 2-log10. Over 

the same storage period, coliforms 

remained below the level of detection in 

irradiated samples (Ref. 56). Recent 

studies by other researchers have 

examined the effects of irradiation on 

levels of pathogens and sensory 

attributes of fresh-cut iceberg lettuce, 

including studies in modified 

atmosphere packaging. One of these 

studies demonstrated deterioration in 

several sensory attributes (e.g., firmness, 

color) when iceberg lettuce is irradiated 

at levels of 3 or 4 kGy (Ref. 57). 

Additional related studies on iceberg 

lettuce and other vegetables by the same 

group of researchers indicate irradiation 

above 1.5 or 2 kGy (depending on the 

specific vegetable) can negatively affect 

sensory properties (Refs. 58 and 59). 

Taken together, the studies described 

above indicate that irradiation in the 

expected practical dose range will 

reduce, but not entirely eliminate, 

spoilage microorganisms. 

In evaluating the subject petition, 

FDA has carefully considered whether 

irradiation of iceberg lettuce and 

spinach under the conditions proposed 

in the petition could result in 

significantly altered microbial growth 

patterns such that these foods would 

present a greater microbiological hazard 

than comparable food that had not been 

irradiated. In considering this question, 

FDA has focused on whether the 

proposed irradiation conditions would 

increase the probability of significantly 

increased growth of, and subsequent 

toxin production by, Clostridium 

botulinum because this organism is 

relatively resistant to radiation as 

compared to non-spore-forming 

bacteria. FDA has concluded that the 

possibility of increased microbiological 

risk from C. botulinum is extremely 

remote because: (1) The conditions of 

refrigerated storage necessary to 

maintain the quality of iceberg lettuce or 

spinach are not amenable to the 

outgrowth and production of toxin by C. 

botulinum and, (2) sufficient numbers of 

spoilage organisms will survive such 

that spoilage will occur before 

outgrowth and toxin production by C. 

botulinum (Refs. 48 and 60). 

Based on the available data and 

information, FDA concludes that 

irradiation of iceberg lettuce and 

spinach conducted in accordance with 

good manufacturing practices will 

reduce or eliminate bacterial 

populations with no increased microbial 

risk from pathogens that may survive 

the irradiation process. 

III. Comments 

FDA has received numerous 

comments, primarily form letters, from 

individuals that state their opinions 

regarding the potential dangers and 

unacceptability of irradiating food. FDA 

has also received several comments 

from individuals or organizations that 

state their opinions regarding the 

potential benefits of irradiating food and 

urging FDA to approve the petition. 

None of these letters contain any 

substantive information that can be used 

in a safety evaluation of irradiated 

iceberg lettuce and spinach. 

Additionally, FDA received several 

comments from Public Citizen (PC) and 

the Center for Food Safety (CFS) 

requesting the denial of this and other 

food irradiation petitions. Overall, the 

comments were of a general nature and 

not necessarily specific to the requests 

in the individual petitions. Many of 

these comments from PC and CFS were 

also submitted to the docket for the 

agency rulemaking on irradiation of 

molluscan shellfish (Docket No. 1999F–

4372, FAP 9M4682). The topics raised 

in these comments included the 

following: Studies reviewed in the 1999 

FAO/IAEA/WHO report on high-dose 

irradiation; a review article that 

analyzed studies of irradiated foods 

performed in the 1950’s and 1960’s; the 

findings of a 1971 study in which rats 

were fed irradiated strawberries; the 

findings regarding reproductive 

performance in a 1954 study in which 

mice were fed a special irradiated diet; 

issues regarding mutagenicity studies; 

certain international opinions; issues 

related to ACBs, including purported 

promotion of colon cancer; the findings 

of certain studies conducted by the 

Indian Institute of Nutrition in the 

1970’s; general issues regarding toxicity 

data; FDA’s purported failure to meet 

statutory requirements; data from a 2002 

study purportedly showing an 

irradiation-induced increase in trans 

fatty acids in ground beef; studies 

regarding purported elevated 

hemoglobin levels and their 

significance; and an affidavit describing 

the opinions of a scientist regarding the 

dangers of irradiation and advocating 

the use of alternative methods for 

reducing the risk of foodborne disease. 

For a detailed discussion of the agency’s 

response to the above general 

comments, the reader is referred to the 

molluscan shellfish rule (70 FR 48057 at 

48062–48071). Because these comments 

do not raise issues specific to irradiated 

iceberg lettuce or spinach and because 

the agency has already responded to 

these comments in detail, they will not 

be addressed further here. 

FDA also received two letters from PC 

and CFS that were submitted only to the 

docket for this rulemaking (Docket No. 

FDA–1999–F–2405 (formerly Docket 

No. 1999F–5522), FAP 9M4697). Many 

of the issues raised in these letters were 

also raised in comments submitted by 

PC and CFS to the docket for the agency 

rulemaking on irradiation of molluscan 

shellfish. Other issues raised in these 

letters were specific to the request in 

FAP 9M4697; these particular 

comments were not responded to in the 

molluscan shellfish rule. Below, the 

agency responds to the specific 

comments raised in these two letters 

from PC and CFS that were not 

addressed in the molluscan shellfish 

rule. 

The agency also received an 

additional letter from Food and Water 

Watch (formerly PC) and CFS after the 

rule for the irradiation of molluscan 

shellfish published. The comments in 

this letter are also addressed below. 


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A. 2-Alkylcyclobutanones 

During the evaluation of this petition 

and several others requesting various 

applications of irradiation, the agency 

received several comments on issues 

related to 2–ACBs. The agency has 

previously addressed most of these 

comments in the molluscan shellfish 

rule (70 FR 48057 at 48062–48071), and 

that discussion will not be repeated 

here. However, after the publication of 

the molluscan shellfish rule, the agency 

received an additional comment on 2–

ACBs. This comment included a report 

that contained data on 2–ACBs present 

in irradiated turkey, hotdogs, and 

papayas. 

As noted in section II. A of this 

document, 2–ACBs are formed in small 

quantities when fats are exposed to 

ionizing radiation. Of the three foods 

examined in the study submitted with 

the comment, only papayas are from the 

same generic class as iceberg lettuce and 

spinach. (Turkey and hotdogs are foods 

high in protein and fat that have little 

in common with leafy greens.) The 

report presents data indicating that 2–

ACB concentrations in papaya flesh are 

indistinguishable from zero. There is no 

additional information in the paper 

other than concentrations of various 

alkylcyclobutanones in the three foods 

mentioned. 

As previously noted in this document 

and in the molluscan shellfish rule, 

FDA has reviewed studies in which 

animals were fed diets containing 

irradiated foods of high fat content 

(meat, poultry, and fish). The agency 

concluded that no adverse effects were 

associated with the consumption of 

these high fat foods. Iceberg lettuce and 

spinach contain far less fat than meat, 

poultry, fish or molluscan shellfish. As 

previously noted in section II.B of this 

document, FDA has reviewed studies in 

which animals were fed diets containing 

irradiated fruits and vegetables. No 

adverse effects were associated with 

consumption of these food types. The 

comment provides no additional 

information that would alter the 

agency’s conclusion that the 

consumption of irradiated iceberg 

lettuce and spinach does not present a 

health hazard. 

B. List of Foods Covered by the Petition 

One comment stated that ‘‘FDA has 

no definitive list of foods that are 

covered by the petition,’’ citing a 

personal communication of March 19, 

2001. The comment goes on to state that 

‘‘[a] Federal Register filing of May 10, 

2001, pertaining to the [abovereferenced] petition establishes that the 

FDA [sic] no understanding as to which 

specific foods are covered by the 

petition.’’

FDA disagrees with this comment. 

The Federal Register document of May 

10, 2001, corrected an inadvertent 

exclusion of certain foods from the 

scope of the original filing notice. FDA 

also notes that a listing of each and 

every food covered by a food additive 

petition has never been required and is 

not necessary. The agency frequently 

evaluates food additive petitions 

intended to cover broad categories of 

food types. Further, this partial response 

authorizing irradiation of iceberg lettuce 

and spinach up to a maximum dose of 

4.0 kGy addresses two specific foods, 

rendering the issue moot. 

C. Toxicity Data 

One comment states that the petition 

should be denied because ‘‘[t]he 

petitioner submitted no toxicology data 

on any of the products that are 

ostensibly covered by the petition.’’

FDA acknowledges that the petitioner 

did not submit new toxicological data 

specific to the foods in the petition. The 

petitioner made extensive reference to 

studies considered in earlier evaluations 

of the toxicological safety of irradiated 

foods by FDA, WHO, and others. As 

noted earlier, FDA has reviewed a large 

body of data relevant to the assessment 

of the potential toxicity of irradiated 

foods, including irradiated fruits and 

vegetables. There was no reason to 

submit additional copies of studies that 

had previously been reviewed by the 

agency. 

One comment states that the petition 

should be denied ‘‘because the validity 

of three of the studies referenced by the 

petitioner was questioned by the FDA’s 

Irradiated Foods Task Group (IFTG) in 

1982.’’ The comment lists three studies, 

one of which ‘‘was labeled ‘reject’ by the 

IFTG’’ and two of which were ‘‘labeled 

‘accept with reservation’ by the IFTG.’’

FDA does not disagree that the IFTG 

had questions regarding these three 

studies. FDA does not agree, however, 

that these 1982 findings by the IFTG 

provide a basis to deny the petition or 

the partial request that is the subject of 

this rulemaking. FDA has not relied on 

studies that were rejected by the IFTG 

in assessing the safety of irradiated 

iceberg lettuce and spinach or any other 

irradiated food. Some studies were 

accepted with reservation by the agency 

scientists on the IFTG because they did 

not meet modern standards in all 

respects; specifically, they may have 

used fewer animals, or examined fewer 

tissues than is common today. 

Nevertheless, these studies still provide 

important information that, when 

evaluated collectively, supports the 

conclusion that consumption of iceberg 

lettuce and spinach irradiated under the 

conditions proposed in this petition is 

safe. As noted earlier, FDA has reviewed 

a large body of data relevant to the 

assessment of the potential toxicity of 

irradiated fruits and vegetables, and to 

an assessment of the potential toxicity 

of irradiated iceberg lettuce and spinach 

specifically. The comment provides no 

basis to challenge FDA’s conclusion that 

iceberg lettuce and spinach irradiated 

under the conditions set forth in the 

regulations in this document are safe. 

Another comment stated that the 

petitioner claimed that a fourth study, 

conducted by Renner et al. (Ref. 61) 

‘‘provided [no] evidence of toxicity 

induced by irradiation.’’ The comment 

took issue with the petitioner’s 

characterization of this study, stating 

‘‘[t]he study found, however, 

‘significant’ effects on DNA synthesis 

and ‘significant loss of body weight’

among rodents that ate irradiated food 

compared to that that ate non-irradiated 

food.’’

The Renner et al. study consisted of 

six in vivo genetic toxicity tests that 

were carried out in several different 

animal species with irradiated or nonirradiated cooked chicken, dried dates, 

and cooked fish. FDA has previously 

evaluated the results of these tests and 

does not agree with comment’s 

characterization of the study findings, 

which appear to be presented out of 

context. 

In the Renner et al. study, the authors 

concluded that ‘‘[n]one of the tests 

provided any evidence of genetic 

toxicity induced by irradiation.’’

Further, the authors did not attribute a 

‘‘significant loss of body weight’’ to 

consumption of irradiated food, but 

stated, rather, that ‘‘[t]he nutritional 

effects of exposing Chinese hamsters for 

7 days to a diet consisting entirely of 

dried dates were evidenced by a 

significant reduction in food intake and, 

consequently, a significant loss of body 

weight.’’ The effect was observed in 

both animals fed non-irradiated dates 

and animals fed irradiated dates. The 

authors also reported various effects on 

DNA synthesis resulting from feeding 

Chinese hamsters diets consisting 

entirely of dried dates or cooked 

chicken, irradiated or not. Thus, the 

authors concluded that these effects 

were also not attributable to irradiation. 

Further, the authors state that ‘‘In only 

one case in the nine tests described in 

this report and in two previous 

papers* * *was an effect seen that 

could be attributed to an irradiated 

foodstuff. This was with irradiated fish 

in the DNA metabolism test.’’ The 

authors concluded that the specific 


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15Food irradiation processors are also subject to 

FDA’s regulation requiring Current Good 

Manufacturing Practice in Manufacturing, Packing, 

or Holding Human Food (CGMP) (21 CFR part 110) 

and other applicable regulations regarding proper 

food handling and storage conditions. 

effect observed with irradiated fish in 

the DNA metabolism test was not an 

indication of genotoxic activity, but 

rather, that it ‘‘* * *provided evidence 

for absence of genotoxic potential in fish 

so processed.’’ The comment provides 

no basis to conclude that the studies 

and information reviewed by the agency 

and discussed previously in this 

document are not adequate to assess the 

safety of irradiated iceberg lettuce and 

spinach. 

D. Hardy Pathogens 

One comment submitted a copy of a 

newsletter published by the Food Safety 

Consortium. The comment stated that 

‘‘when irradiation is applied to meat in 

commercial plants, the pathogens 

present have evolved to survive the 

irradiation better, thus the irradiation 

does not achieve the levels of decontamination that are predicted, and 

advertised, by the meat irradiation 

industry based on the lab studies.’’ The 

article in the newsletter states that 

pathogens in a food processing plant are 

generally more resistant to stressful 

conditions than laboratory grown 

bacteria. 

The comment provides no data that 

can be used in a safety assessment of 

irradiated food in general or irradiated 

iceberg lettuce and spinach, specifically. 

FDA also believes that the comment 

incorrectly characterizes the science 

behind the article in the newsletter. 

Scientists understand that bacteria 

grown under stressful conditions (e.g., 

high acidity, elevated temperatures) can 

manifest resistance to treatments that 

would be lethal to the same type of 

bacteria grown under less stressful 

conditions. Thus, any bacteria grown in 

nutrient-rich media under optimal 

conditions in the laboratory may be 

somewhat less resistant to any given 

treatment, including irradiation, than 

the same bacteria grown in nutrientpoor or other harsh conditions in a nonoptimal environment. 

FDA also notes that under the 

regulations set forth in § 179.25, 

radiation treatment of food must 

conform to a scheduled process, which 

is a written procedure to ensure that the 

radiation dose range selected by the 

food irradiation processor is adequate 

under commercial processing 

conditions (including atmosphere and 

temperature) for the radiation to achieve 

its intended effect on a specific product 

and in a specific facility.15 The 

regulations further require that the 

scheduled process be established by 

qualified persons having expert 

knowledge in radiation processing 

requirements of food and specific for 

that food and for the facility in which 

it is to be irradiated. 

E. Effects on Organoleptic (Sensory) 

Properties 

One comment argued that the petition 

should be denied because of 

‘‘organoleptic damage’’ that raises 

‘‘serious concerns about the general 

wholesomeness of irradiated foods.’’

The agency acknowledges that 

organoleptic changes can occur in 

irradiated foods. However, this 

comment provides no information that 

would establish a link between 

organoleptic changes in, and the safety 

of, irradiated foods. Consideration of 

organoleptic changes, in and of 

themselves, is beyond the scope of this 

rulemaking. 

IV. Conclusions 

Based on the data and studies 

submitted in the petition and other 

information in the agency’s files, FDA 

concludes that the proposed use of 

irradiation to treat iceberg lettuce and 

spinach with absorbed doses that will 

not exceed 4.0 kGy is safe, and 

therefore, the regulations in § 179.26 

should be amended as set forth below in 

this document. In accordance with 

§ 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 use of 

irradiation on iceberg lettuce and 

spinach in a partial response to the 

petition will be made available for 

inspection at the Center for Food Safety 

and Applied Nutrition by appointment 

with the information contact person (see 

FOR FURTHER INFORMATION CONTACT). As 

provided in § 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. 

This final rule contains no collections 

of information. Therefore, clearance by 

the Office of Management and Budget 

under the Paperwork Reduction Act of 

1995 is not required. 

V. Environmental Impact 

The agency has carefully considered 

the potential environmental effects of 

this action. The agency has determined 

under 21 CFR 25.32(j) that this action is 

of a type that does not individually or 

cumulatively have a significant effect on 

the human environment. Therefore, 

neither an environmental assessment 

nor an environmental impact statement 

is required. 

VI. Objections 

Any person who will be adversely 

affected by this regulation may file with 

the Division of Dockets Management 

(see ADDRESSES) written or electronic 

objections. 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 

are to be submitted and are to 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 Division of Dockets Management 

between 9 a.m. and 4 p.m., Monday 

through Friday. 

VII. References 

The following sources are referred to 

in this document. References marked 

with an asterisk (*) have been placed on 

display at the Division of Dockets 

Management (address above) and may 

be seen by interested persons between 9 

a.m. and 4 p.m., Monday through 

Friday. References without asterisks are 

not on display; they are available as 

published articles and books. 

*1. Diehl, J.F., ‘‘Chemical Effects of 

Ionizing Radiation,’’ pp. 43–88, in Safety of 

Irradiated Foods, 2d Ed., Marcel Dekker, Inc., 

New York, 1995. 

2. Elias, P.S. and A.J. Cohen, Recent 

Advances in Food Irradiation, Elsevier 

Biomedical, Amsterdam, 1983. 

*3. WHO, ‘‘High-Dose Irradiation: 

Wholesomeness of Food Irradiated With 

Doses Above 10kGy,’’ World Health 

Organization Technical Report Series, No. 

890, Geneva, pp. 9–37, 1999. 

4. Josephson, E.S. and M.S. Peterson, eds., 

Preservation of Food by Ionizing Radiation, 

vol. II, CRC Press, Boca Raton, FL, 1982. 

5. Diehl, J.F., ‘‘Radiolytic Effects in Foods,’’

pp. 279–357, in Preservation of Foods By 

Ionizing Radiation, vol. I, E.S. Josephson and 

M.S. Peterson, eds., CRC Press, Boca Raton, 

FL,1982. 


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Agricultural Research Service, USDA 

National Nutrient Database for Standard 

Reference, Release 20, Nutrient Data 

Laboratory Home Page, http:// 

www.ars.usda.gov/nutrientdata, 2007. 

*7. Adam, S., ‘‘Recent Developments in 

Radiation Chemistry of Carbohydrates,’’ pp. 

149–170, in Recent Advances in Food 

Irradiation, P.S. Elias and A.J. Cohen, eds., 

Elsevier Biomedical, Amsterdam, 1983. 

*8. Raffi, J., J.P. Agnel, C. Thiery, C. 

Frejaville, L. Saint-Lebe, ‘‘Study of Gamma 

Irradiated Starches Derived form Different 

Foodstuffs: A Way for Extrapolating 

Wholesomeness Data,’’ Journal of 

Agricultural and Food Chemistry, 29:1227–

1232, 1981. 

9. Safety and Nutritional Adequacy of 

Irradiated Food, World Health Organization, 

Geneva, 1994. 

*10. Memorandum for FAP 9M4697 from 

K. Morehouse, FDA, to L. Highbarger, FDA, 

dated August 10, 2001. 

*11. Raffi, J. and J.P. Agnel, ‘‘Influence of 

Physical Structure of Irradiated Starches on 

their ESR Spectra Kinetics,’’ Journal of 

Physical Chemistry, 87:2369–2373, 1983. 

*12. Thiery, J.M., J.P. Theiry, P. Angel, P. 

Vincent, C. Battesti, J. Raffi, and J.C. Evans, 

‘‘Electron Spin Resonance Study of SpinTrapped Radicals from Gamma Irradiation of 

Glucose Oligomers,’’ Magnetic Resonance In 

Chemistry, 28:594–600, 1990. 

*13. Merritt, C. 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 Biomedical, Amsterdam, 1983. 

*14. Nawar, W.W., ‘‘Volatiles from Food 

Irradiation,’’ Food Reviews International, 

2:45–78, 1986. 

*15. Nawar, W.W., ‘‘Comparison of 

Chemical Consequences of Heat and 

Irradiation Treatment of Lipids,’’ pp. 115–

127, in Recent Advances in Food Irradiation, 

P. S. Elias and A. J. Cohen, eds., Elsevier 

Biomedical, Amsterdam, 1983. 

*16. Crone, A.V.J., J.T.G. Hamilton, and 

M.H. Stevenson, ‘‘Effect of Storage and 

Cooking on the Dose Response of 2- 

Dodecylcyclobutanone, a Potential Marker 

for Irradiated Chicken,’’ Journal of the 

Science of Food and Agriculture, 58:249–252, 

1992. 

*17. Gadgil, P., K.A. Hachmeister, J.S. 

Smith, and D.H. Kropf, ‘‘2- 

Alkylcyclobutanones as Irradiation Dose 

Indicators in Irradiated Ground Beef Patties,’’

Journal of Agriculture and Food Chemistry, 

50:5746–5750, 2002. 

*18. Seibersdorf Project Report, 

International Programme on Irradiation of 

Fruit and Fruit Juices, Chemistry and 

Isotopes Department, National Centre for 

Nuclear Energy, Madrid, Spain, vol.8, 1966. 

*19. Memorandum for FAP 9M4697 from 

K. Morehouse, FDA, to L. Highbarger, FDA, 

dated February 20, 2008. 

*20. Locas, C., and V.A. Yaylayan, ‘‘Origin 

and Mechanistic Pathways of Formation of 

the Parent Furan-a Toxicant,’’ Journal of 

Agricultural and Food Chemistry, 52:6830–

6836, 2005. 

*21. Fan, X., and K.J.B. Sokorai, ‘‘Effect of 

Ionizing Radiation on Furan Formation in 

Fresh-Cut Fruits and Vegetables,’’ Journal of 

Food Science. 73(2): C79–C83, 2008. 

*22. Letter from petitioner for 9M4697 

dated 7/23/2007. 

*23. Memorandum to the file for FAP 

4M4428, from D. Hattan, FDA, dated 

November 20, 1997. 

24. 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. 

*25. Memorandum for 9M4697 from I. 

Chen, FDA, to L. Highbarger, FDA, dated 

December 21, 2001. 

*26. Memorandum to the file for 9M4697 

from I. Chen, FDA, and P. Hansen, FDA, 

dated June 20, 2008. 

*27. Gabriel, K.L., and R.S. Edmonds, ‘‘To 

Study the Effects of Radurized Onions When 

Fed to Beagle Dogs,’’ Food Irradiation 

Information, Food and Agriculture 

Organization/International Atomic Energy 

Agency, 6 (Suppl.)118, 1976. 

*28. Phillips, A. W., et al., ‘‘Long-Term Rat 

Feeding Studies: Irradiated Oranges,’’ Final 

Contract Report, Army Contract Report No. 

DA–49–007–MD–783, 1961. 

*29. Phillips, A.W., et al., ‘‘Long-term Rat 

Feeding Studies: Irradiated Chicken Stew 

and Cabbage,’’ Final Contract Report, Army 

Contract Report No. DA–49–007–MD–783, 

1961. 

*30. Underdal, B., J. Nordal, G. Lunde, and 

B. Eggum, ‘‘The Effect of Ionizing Radiation 

on the Nutritional Value of Fish (Cod) 

Protein,’’ Lebensmittel-Wissenschaft 

Technologie, 6:90–93, 1973. 

*31. Diehl, J.F., ‘‘Nutritional Adequacy of 

Irradiated Foods,’’ pp. 241–282, in Safety of 

Irradiated Foods, Marcel Dekker, New York, 

1995. 

*32. Josephson, E.S. and M. H. Thomas, 

‘‘Nutritional Aspects of Food Irradiation: An 

Overview,’’ Journal of Food Processing and 

Preservation, 2:299–313, 1978. 

*33. Memorandum for 9M4697 from A. 

Edwards, FDA, to L. Highbarger, FDA, dated 

July 16, 2008. 

*34. Cotton, P.A., A.F. Subar, J.E. Friday, 

and A. Cook, ‘‘Dietary Sources of Nutrients 

Among US Adults,’’ Journal of the American 

Dietetic Association, 104: 921–930, 2004. 

35. Institute of Medicine; Dietary Reference 

Intakes for vitamin A, vitamin K, arsenic, 

boron, chromium, copper, iodine, iron, 

manganese, molybdenum, nickel, silicon, 

vanadium, and zinc; National Academies 

Press, Washington, DC, 2001. 

*36. Hajare, S.N., V.S. Dhokane, R. 

Shashidhar, S. Saroj, A. Sharma, and J.R. 

Bandekar, ‘‘Radiation Processing of 

Minimally Processed Carrot (Daucus carota) 

and Cucumber (Cucumis sativus) to Ensure 

Safety: Effect on Nutritional and Sensory 

Quality,’’ Journal of Food Science, 

71(3):S198–203, 2006. 

*37. Beyers, M., and A.C. Thomas, 

‘‘Gamma-Irradiation of Subtropical Fruits, 4. 

Changes in Certain Nutrients Present in 

Mangoes, Papayas, and Litchis During 

Canning, Freezing, and Gamma-Irradiation,’’

Journal of Agricultural and Food 

Chemistry,27(1):48–51, 1979. 

38. Gomes, C. D., P. Da Silva, E. 

Chimbombi, J. Kim, E. Castell-Perez, and R.G. 

Moreira, ‘‘Electron-Beam Irradiation of Fresh 

Broccoli Heads (Brassica oleracea L. italica),’’

Lebensmittel-Wissenschaft Technologie, in 

press, 2008. 

*39. Gomes, C.D., R.G. Moreira, E. CastellPerez, J. Kim, P. Da Silva., and A. Castillo, 

‘‘E-Beam Irradiation of Bagged, Ready-To-Eat 

Spinach Leaves (Spinacea oleracea): an 

Engineering Approach,’’ Journal of Food 

Science, 73(2):E95–102, 2008. 

*40. Booth, S.L., J.A.T. Pennington, and 

J.A. Sadowski, ‘‘Food Sources and Dietary 

Intakes of Vitamin K–1 (Phylloquinone) in 

the American Diet: Data from the FDA Total 

Diet Study,’’Journal of the American Dietetic 

Association, 96:149–154, 1996. 

*41. Knapp, F.W. and A.L. Tappel, 

‘‘Comparison of the Radiosensitivities of the 

Fat-Soluble Vitamins by Gamma Irradiation,’’

Journal of Agricultural and Food Chemistry, 

9:430–433, 1961. 

*42. Richardson, R.L., S. Wilkes, and S.J. 

Ritchey, ‘‘Comparative Vitamin K Activity of 

Frozen, Irradiated, and Heat-Processed 

Food,’’ Journal of Nutrition, 73: 369–373, 

1961. 

*43. Pfeiffer, C., J.F. Diehl, and W. 

Schwack, ‘‘Effect of Irradiation on Folate 

Levels and of Bioavailability of Folates in 

Dehydrated Foodstuffs,’’ Acta Alimentaria, 

23:105–118, 1994. 

*44. Muller H., and J.F. Diehl, ‘‘Effect of 

Ionizing Radiation on Folates in Food,’’

Lebensmittel-Wissenschaft Technologie, 

29(1–2):187–190, 1996. 

*45. Stea, T.H., M. Johansson, M. Ja ̈gerstad, 

W. Fr<lich, ‘‘Retention of Folates in Cooked, 

Stored and Reheated Peas, Broccoli and 

Potatoes for Use in Modern Large-Scale 

Service Systems,’’ Food Chemistry, 

101(3):1095–1107, 2007. 

*46. Melse-Boonstra, A., P. Verhoef, E.J.M. 

Konings, M. Van Dusseldorp, A. Matser, 

P.C.H. Hollman, S. Meyboom, F.J. Kok, C.E. 

West, ‘‘Influence of Processing on Total, 

Monoglutamate and Polyglutamate Folate 

Contents of Leeks, Cauliflower, and Green 

Beans,’’ Journal of Agricultural and Food 

Chemistry, 50:3473–8, 2002. 

*47. Centers for Disease Control, 

‘‘Preliminary FoodNet Data on the Incidence 

of Infection with Pathogens Transmitted 

Commonly Through Food — 10 States, 

2006,’’ Morbidity and Mortality Weekly 

Report, 56, 336–339. 2007. 

*48. Memorandum for 9M4697 from R. 

Merker, FDA, to Lane Highbarger, FDA, dated 

June 11, 2008 

*49. Niemira, B. A. and X. Fan, ‘‘Low-Dose 

Irradiation of Fresh and Fresh-Cut Produce: 

Safety, Sensory, and Shelf Life,’’ pp. 169–

184, in Food Irradiation Research and 

Technology, C.H. Sommers, and X. Fan, eds., 

IFT Press, Chicago, 2006. 

*50. Prakash, A. and D. Foley, ‘‘Improving 

Safety and Extending Shelf Life* * *’’ pp. 

90–106, in Irradiation of Food and Packaging 

— Recent Developments, American Chemical 

Society, Washington, DC, 2004. 

*51. Monk, J.D., L.R. Beuchat, and M.P. 

Doyle, ‘‘Irradiation Inactivation of FoodBorne Microorganisms,’’ Journal of Food 

Protection, 58(2):197–208, 1995. 

*52. Niemira, B.A., C.H. Sommers, and X. 

Fan, ‘‘Suspending Lettuce Type Influences 

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Escherichia coli O157:H7,’’ Journal of Food 

Protection, 65:1388–1393, 2002. 

*53. Niemira, B.A., ‘‘Radiation Sensitivity 

and Recoverability of Listeria monocytogenes 

and Salmonella on 4 Lettuce Types,’’ Journal 

of Food Science, 68: 2784–2787, 2003. 

*54. Niemira, B.A., ‘‘Relative Efficacy of 

Sodium Hypochlorite Wash Versus 

Irradiation to Inactivate Escherichia coli 

O157:H7 Internalized in Leaves of Romaine 

Lettuce and Baby Spinach,’’ Journal of Food 

Protection, 70:2526–2532, 2007. 

*55. Zhang, L., Z. Lu, and H. Wang, ‘‘Effect 

of Gamma Irradiation on Microbial Growth 

and Sensory Quality of Fresh-Cut Lettuce,’’

International Journal of Food Microbiology, 

106:348–351, 2006. 

*56. Zhang, L., Z. Lu, F. Lu, and X. Bie, 

‘‘Effect of Gamma Irradiation on Quality 

Maintaining of Fresh-Cut Lettuce,’’ Food 

Control, 17:225–228, 2006. 

*57. Fan, X. and K.J. Sokorai, ‘‘Sensorial 

and Chemical Quality of Gamma-Irradiated 

Fresh-Cut Iceberg Lettuce in Modified 

Atmosphere Packages,’’ Journal of Food 

Protection, 65:1760–1765, 2002. 

*58. Fan, X. and K.J. Sokorai, ‘‘Assessment 

of Radiation Sensitivity of Fresh-Cut 

Vegetables Using Electrolyte Leakage 

Measurement,’’ Postharvest Biology and 

Technology, 36:191–197, 2005. 

*59. Fan, X., B.A. Niemira, and K.J. 

Sokorai, ‘‘Use of Ionizing Radiation to 

Improve Sensory and Microbial Quality of 

Fresh-cut Green Onion Leaves,’’ Journal of 

Food Science, 68:1478–1483, 2003. 

*60. Petran, R.L., W.H. Sperber, and A.B. 

Davis, ’’Clostridium botulinum Toxin 

Formation in Romaine Lettuce and Shredded 

Cabbage: Effect of Storage and Packaging 

Conditions,’’ Journal of Food Protection, 58, 

624–627, 1995. 

*61. Renner, H. W., U. Graf, F.E. Wurgler, 

H. Altmann, J.C. Asquith, and P.S. Elias, ‘‘An 

Investigation of the Genetic Toxicology of 

Irradiated Foodstuffs Using Short-Term Test 

Systems, III—in vivo Tests in Small Rodents 

and in Drosophila melangaster,’’ Food 

Chemistry and Toxicology, 30:867–878, 1982. 

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 

item ‘‘12.’’ under the headings ‘‘Use’’

and ‘‘Limitations’’ to read as follows: 

§ 179.26 Ionizing radiation for the 

treatment of food. 

* * * * * 

(b) * * * 

Use Limitations 

* * * * * * * 

12. For control of food-borne pathogens and extension of shelf-life in 

fresh iceberg lettuce and fresh spinach. 

Not to exceed 4.0 kGy. 

* * * * * 

Dated: August 19, 2008. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E8–19573 Filed 8–21–08; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Parts 314, 601, and 814 

[Docket No. FDA–2008–N–0032] (formerly 

Docket No. 2008N–0021) 

RIN 0910–ZA32 

Supplemental Applications Proposing 

Labeling Changes for Approved Drugs, 

Biologics, and Medical Devices 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final rule. 

SUMMARY: The Food and Drug 

Administration (FDA) is amending its 

regulations regarding changes to an 

approved new drug application (NDA), 

biologics license application (BLA), or 

medical device premarket approval 

application (PMA). This final rule 

provides that a supplemental 

application submitted under certain 

FDA regulations is appropriate to 

amend the labeling for an approved 

product to reflect newly acquired 

information and to add or strengthen a 

contraindication, warning, precaution, 

or adverse reaction if there is sufficient 

evidence of a causal association with 

the drug, biologic, or device, as defined 

in other FDA regulations and guidance 

documents. 

DATES: This rule is effective September 

22, 2008. 

FOR FURTHER INFORMATION CONTACT: 

For information regarding devices: 

Nicole Wolanski, Center for Devices 

and Radiological Health (HFZ–402), 

Food and Drug Administration, 

9200 Corporate Blvd., Rockville, 

MD 20850, 240–276–4010. 

For information regarding biologics: 

Christopher Joneckis, Center for 

Biologics Evaluation and Research 

(HFM–1), Food and Drug 

Administration, 1401 Rockville 

Pike, Rockville MD 20852, 301–

827–0373. 

For information regarding drugs: 

Laurie Burke, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 22, rm. 6462, 

Silver Spring, MD 20933, 301–796–

0900. 

SUPPLEMENTARY INFORMATION: 

I. Background 

In the Federal Register of January 16, 

2008 (73 FR 2848), FDA proposed 

amending its regulations regarding 

changes to an NDA, BLA, or PMA to 

codify the agency’s longstanding view 

concerning when a change to the 

labeling of an approved drug, biologic, 

or medical device may be made in 

advance of the agency’s review and 

approval of such change (the January 

2008 proposed rule). With respect to 

drugs, § 314.70(c)(6)(iii) (21 CFR 

314.70(c)(6)(iii)) provides that certain 

labeling changes related to an approved 

drug may be implemented upon receipt 

by the agency of a supplemental new 

drug application (sNDA) that includes 

the change. The corresponding 

regulation for biological products, 

§ 601.12(f)(2) (21 CFR 601.12(f)(2)), 

provides that products with certain 

labeling changes may be distributed 

before FDA approval. Similarly, with 

respect to devices, § 814.39(d) (21 CFR 

814.39(d)) provides that certain labeling 

changes may be placed into effect upon 

submission of a PMA supplement, but 

prior to the sponsor’s receipt of a 

written FDA order approving the 

supplement. The supplements described 

by §§ 314.70(c), 601.12(f)(2), and 

814.39(d) are commonly referred to as 

‘‘changes being effected supplements’’


yshivers on PROD1PC62 with RULES