[Federal Register: August 22, 2008 (Volume 73, Number 164)]
[Rules and Regulations]               
[Page 49593-49603]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr22au08-2]                         

=======================================================================
-----------------------------------------------------------------------

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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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 e-mail. FDA encourages 
you to continue

[[Page 49594]]

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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&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 non-frozen 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\
---------------------------------------------------------------------------

    \1\ The temperature at which irradiation is conducted can also 
be a factor, with more radiation-induced changes occuring with 
increasing temperature. Temperature is less important, however, than 
the physical state of the food.
---------------------------------------------------------------------------

    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

[[Page 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 non-frozen 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

[[Page 49596]]

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 ([mu]g/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\
---------------------------------------------------------------------------

    \2\ Beef 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)
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \3\ Iceberg lettuce contains approximately 0.016 percent 
palmitic acid, and spinach contains approximately 0.046 percent 
palmitic acid (Ref.6)
---------------------------------------------------------------------------

    Overall, FDA concludes that no significant differences are expected 
to occur between the kinds and amounts of lipids and lipid byproducts 
in non-irradiated 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 
WHO\4\ 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 carbohydrate-rich 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.
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

    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

[[Page 49597]]

irradiation or were otherwise not of toxicological significance.
---------------------------------------------------------------------------

    \5\ The irradiated fruits and vegetables in these studies 
included: Peaches, strawberries, bananas, cherries, prunes, 
potatoes, carrots, onions, black beans, corn, green beans, and 
cabbage.
---------------------------------------------------------------------------

    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 multi-generation 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 non-irradiated 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).
---------------------------------------------------------------------------

    \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).
    \7\ The 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.
---------------------------------------------------------------------------

    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 beta-carotene, a provitamin A carotenoid), vitamin K, 
and folate. FDA's evaluation has also considered the relative radiation 
sensitivities of these vitamins.
---------------------------------------------------------------------------

    \8\ In accordance with 21 CFR 101.54(b), foods containing 
[gteqt] 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.
    \9\ Although 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).
---------------------------------------------------------------------------

    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 A\10\ (Refs. 33, 34 
and 35).
---------------------------------------------------------------------------

    \10\ The 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).
---------------------------------------------------------------------------

    Although vitamin A has been identified as one of the most 
radiation-sensitive 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

[[Page 49598]]

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 rare\11\ 
(Ref. 33).
---------------------------------------------------------------------------

    \11\ Other 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.
---------------------------------------------------------------------------

    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 radiation-induced 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.
---------------------------------------------------------------------------

    \12\ One 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)
    \13\ Enriched and fortified foods (e.g., cereal grains and 
grain-based products) make the greatest contribution to folate in 
the diet.
---------------------------------------------------------------------------

    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 values\14\ 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).
---------------------------------------------------------------------------

    \14\ D10 is the absorbed dose of radiation required 
to reduce a bacterial population by 90 percent.
---------------------------------------------------------------------------

    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

[[Page 49599]]

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 fresh-cut 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.

[[Page 49600]]

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 [above-referenced] 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 non-irradiated 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

[[Page 49601]]

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 de-contamination 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 nutrient-poor or other 
harsh conditions in a non-optimal environment.
    FDA also notes that under the regulations set forth in Sec.  
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.
---------------------------------------------------------------------------

    \15\ Food 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.
---------------------------------------------------------------------------

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 
Sec.  179.26 should be amended as set forth below in this document. 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 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 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.
    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.

[[Page 49602]]

    6. U.S. Department of Agriculture, Agricultural Research 
Service, USDA National Nutrient Database for Standard Reference, 
Release 20, Nutrient Data Laboratory Home Page, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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 Spin-Trapped 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. Castell-Perez, 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. J[auml]gerstad, W. 
Fr[oslash]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 Food-Borne Microorganisms,'' Journal of Food 
Protection, 58(2):197-208, 1995.
    *52. Niemira, B.A., C.H. Sommers, and X. Fan, ``Suspending 
Lettuce Type Influences Recoverability and Radiation Sensitivity of

[[Page 49603]]

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.

0
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

0
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.

0
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:


Sec.  179.26  Ionizing radiation for the treatment of food.

* * * * *
    (b) * * *

------------------------------------------------------------------------
                Use                              Limitations
------------------------------------------------------------------------
                              * * * * * * *
------------------------------------------------------------------------
12. For control of food-borne        Not to exceed 4.0 kGy.
 pathogens and extension of shelf-
 life in fresh iceberg lettuce and
 fresh spinach.
------------------------------------------------------------------------

* * * * *

    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