[Federal Register Volume 79, Number 37 (Tuesday, February 25, 2014)]
[Rules and Regulations]
[Pages 10353-10365]
[FR Doc No: 2014-03976]

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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; denial of request for a stay of effective date and
for a hearing; response to objections; confirmation of effective date.

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SUMMARY: The Food and Drug Administration (FDA or we) is responding to
objections and is denying requests that it received for a hearing on
the final rule that appeared in the Federal Register of August 22, 2008
(73 FR 49593), and that amended 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. After reviewing objections to the final rule and
requests for a hearing, we have concluded that the objections do not
raise issues of material fact that justify a hearing or otherwise
provide a basis for revoking or modifying the amendment to the
regulation. We are denying the request for a stay of the effective date
of the amendment to the food additive regulations. We are also
confirming the effective date of August 22, 2008, for the final rule.

DATES: Effective date of final rule published in the Federal Register
of August 22, 2008 (73 FR 49593) confirmed: August 22, 2008.

FOR FURTHER INFORMATION CONTACT: Teresa A. Croce, Center for Food
Safety and Applied Nutrition (HFS-265), Food and Drug Administration,
5100 Paint Branch Pkwy., College Park, MD 20740-3835,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Introduction

    In a notice published in the Federal Register of January 5, 2000
(65 FR 493), which was subsequently amended May 10, 2001 (66 FR 23943),
we announced that a food additive petition (FAP 9M4697), had been filed
by the National Food Processors Association (now merged into the
Grocery Manufacturers Association) on behalf of The Food Irradiation
Coalition, 1350 I St. NW., Suite 300, Washington, DC 20005
(petitioner). The petition proposed to amend the food additive
regulations in part 179, Irradiation in the Production, Processing and
Handling of Food (21 CFR part 179), 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 dose
of 4.5 kiloGray (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) and 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 fresh iceberg lettuce and fresh spinach up to a maximum dose of
4.0 kGy. In response to this request, we issued a final rule in the
Federal Register of August 22, 2008 (73 FR 49593), permitting the
irradiation of fresh iceberg lettuce and fresh spinach (hereafter
referred to as ``fresh lettuce and fresh spinach'') for control of
food-borne pathogens and extension of shelf life up to a maximum dose
of 4.0 kGy. We based our decision on data in the petition and in our
files. In the preamble to the final rule, we outlined the basis for our
decision and stated that objections to the final rule and requests for
a hearing were due within 30 days of the publication date (i.e., by
September 22, 2008).

II. Objections, Requests for a Hearing, and Request for a Stay of
Effective Date

    Section 409(f)(1) of the Federal Food, Drug, and Cosmetic Act (the
FD&C Act) (21 U.S.C. 348(f)(1)) provides that, within 30 days after
publication of an order relating to a food additive regulation, any
person adversely affected by such order may file objections,
``specifying with particularity the provisions of the order deemed
objectionable, stating reasonable grounds therefor, and requesting a
public hearing upon such objections.''
    Under 21 CFR 171.110 of the food additive regulations, objections
and requests for a hearing are governed by part 12 (21 CFR part 12) of
FDA's regulations. Under Sec.  12.22(a), each objection must meet the
following conditions: (1) Must be submitted on or before the 30th day
after the date of publication of the final rule; (2) must be separately
numbered; (3) must specify with particularity the provision of the
regulation or proposed order objected to; (4) must specifically state
each objection on which a hearing is requested; failure to request a
hearing on an objection constitutes a waiver of the right to a hearing
on that objection; and (5) must include a detailed description and
analysis of the factual information to be presented in support of the
objection if a hearing is requested; failure to include a description
and analysis for an objection constitutes a waiver of the right to a
hearing on that objection.
    Following publication of the final rule permitting the irradiation
of fresh lettuce and fresh spinach for control of food-borne pathogens
and extension of shelf life, we received numerous submissions with
objections to the rule within the 30-day objection period. The majority
of these submissions were form letters expressing concern regarding one
or more of the following issues: (1) Labeling of produce being
irradiated and (2) potential vitamin depletion resulting from
irradiation. Many of the form letters also expressed general opposition
to the final rule, or objected to the rule based on issues that are
outside the rule's scope such as the regulation and management of the
meat industry, the number of inspectors currently available to perform
inspections, and the proximity of cattle farms to produce farms.
Although most of these letters requested a hearing, no evidence was
identified in support of any of these objections that could be
considered in an evidentiary hearing (Sec.  12.22(a)(5)). Therefore,
these objections do not justify a hearing.\1\ We will not discuss these
submissions further.
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    \1\ FDA also received letters after the close of the objection
period that expressed general opposition to the fresh lettuce and
fresh spinach irradiation rule. Tardy objections fail to satisfy the
requirements of 21 U.S.C. 348(f)(1) and need not be considered by
the Agency (see ICMAD v. HEW, 574 F.2d 553, 558 n.8 (D.C. Cir.),
cert. denied, 439 U.S. 893 (1978)).
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    There were two submissions raising specific objections. One was a
letter from the Center for Food Safety (CFS) (letter to Docket No. FDA-
1999-F-2405; September 17, 2008) and the second was a letter from Food
& Water Watch (FWW) (letter to Docket No. FDA-1999-F-2405; September
22, 2008). The letter from CFS sought revocation of the final rule
pertaining to two areas, which were enumerated as five specific
objections. CFS requested a hearing on the issues

raised by each objection. The letter from FWW agreed with all
objections raised in the letter from CFS, and requested a hearing and
stay of effective date for one additional topic not described in the
CFS letter. A more detailed response to both CFS' and FWW's objections
is found in section IV. We also received two letters in support of the
fresh lettuce and fresh spinach rule.

III. Standards for Granting a Hearing

    Specific criteria for deciding whether to grant or deny a request
for a hearing are set out in Sec.  12.24(b). Under that regulation, a
hearing will be granted if the material submitted by the requester
shows, among other things, the following: (1) There is a genuine and
substantial factual issue for resolution at a hearing; a hearing will
not be granted on issues of policy or law; (2) the factual issue can be
resolved by available and specifically identified reliable evidence; a
hearing will not be granted on the basis of mere allegations or denials
or general descriptions of positions and contentions; (3) the data and
information submitted, if established at a hearing, would be adequate
to justify resolution of the factual issue in the way sought by the
requester; a hearing will be denied if the data and information
submitted are insufficient to justify the factual determination urged,
even if accurate; and (4) resolution of the factual issue in the way
sought by the person is adequate to justify the action requested; a
hearing will not be granted on factual issues that are not
determinative with respect to the action requested (e.g., if the action
would be the same even if the factual issue were resolved in the way
sought).
    A party seeking a hearing is required to meet a ``threshold burden
of tendering evidence suggesting the need for a hearing'' (Costle v.
Pac. Legal Found., 445 U.S. 198, 214 (1980), reh. denied, 446 U.S. 947
(1980), citing Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S.
609, 620-21 (1973)). An allegation that a hearing is necessary to
``sharpen the issues'' or to ``fully develop the facts'' does not meet
this test (Georgia-Pacific Corp. v. U.S. EPA, 671 F.2d 1235, 1241 (9th
Cir. 1982)). In judicial proceedings, a court is authorized to issue
summary judgment without an evidentiary hearing whenever it finds that
there are no genuine issues of material fact in dispute and a party is
entitled to judgment as a matter of law (see Fed. R. Civ. P. 56). The
same principle applies in administrative proceedings (see Sec.  12.24).
    A hearing request must not only contain evidence, but that evidence
should raise a material issue of fact ``concerning which a meaningful
hearing might be held'' (Pineapple Growers Ass'n v. FDA, 673 F.2d 1083,
1085 (9th Cir. 1982)). Where the issues raised in the objection are,
even if true, legally insufficient to alter the decision, we need not
grant a hearing (see Dyestuffs and Chemicals, Inc. v. Flemming, 271
F.2d 281, 286 (8th Cir. 1959), cert. denied, 362 U.S. 911 (1960)). A
hearing is justified only if the objections are made in good faith and
if they ``draw in question in a material way the underpinnings of the
regulation at issue'' (Pactra Industries v. CPSC, 555 F.2d 677, 684
(9th Cir. 1977)). A hearing need not be held to resolve questions of
law or policy (see Citizens for Allegan County, Inc. v. FPC, 414 F.2d
1125, 1128 (D.C. Cir. 1969); Sun Oil Co. v. FPC, 256 F.2d 233, 240-41
(5th Cir. 1958), cert. denied, 358 U.S. 872 (1958)).
    Even if the objections raise material issues of fact, we need not
grant a hearing if those same issues were adequately raised and
considered in an earlier proceeding. Once an issue has been so raised
and considered, a party is estopped from raising that same issue in a
later proceeding without new evidence. The various judicial doctrines
dealing with finality, such as collateral estoppel, can be validly
applied to the administrative process (see Pac. Seafarers, Inc. v. Pac.
Far East Line, Inc., 404 F.2d 804, 809 (D.C. Cir. 1968), cert. denied,
393 U.S. 1093 (1969)). In explaining why these principles ought to
apply to an Agency proceeding, the U.S. Court of Appeals for the
District of Columbia Circuit wrote: ``The underlying concept is as
simple as this: Justice requires that a party have a fair chance to
present his position. But overall interests of administration do not
require or generally contemplate that he will be given more than one
fair opportunity.'' (Retail Clerks Union, Local 1401 v. NLRB, 463 F.2d
316, 322 (D.C. Cir. 1972).) (See Costle v. Pac. Legal Found., 445 U.S.
at 215-20. See also Pac. Seafarers, Inc. v. Pac. Far East Line, Inc.,
404 F.2d 804 (D.C. Cir. 1968), cert. denied, 393 U.S. 1093 (1969).)
    In summary, a hearing request must present sufficient credible
evidence to raise a material issue of fact, and the evidence must be
adequate to resolve the issue as requested and to justify the action
requested.

IV. Analysis of Objections and Response to Hearing Requests

    The letter from CFS contains five numbered objections with requests
for a hearing on each of them, and also appears to have two broad
objections. FWW's letter agrees with all objections presented by CFS
and presents one additional objection; they request a hearing and stay
of effective date on each objection. We address CFS' two broad
objections first, followed by the specific objections, as well as the
evidence and information filed in support of each, comparing each
objection and the information submitted in support of it to the
standards for granting a hearing in Sec.  12.24(b).

A. CFS' Broad Objections

    Although CFS' letter was formatted as five numbered objections with
requests for a hearing on each, CFS appears to have two broad
objections to the final rule providing for the safe use of ionizing
radiation for control of food-borne pathogens and extension of shelf
life in fresh lettuce and fresh spinach. In brief, CFS claims that: (1)
We have improperly relied on studies in other fruits and vegetables and
(2) we have improperly relied on studies at doses below 4.0 kGy. CFS
appears to raise these objections to attempt to call into question our
assessment of the nutritional impact of the final rule and ultimately
our determination that the irradiation of fresh lettuce and fresh
spinach up to a maximum dose of 4.0 kGy is safe.
    We disagree that we have improperly relied on studies in other
fruits and vegetables. We have consistently taken the position that
various scientifically validated types of data may properly support a
safety determination for a proposed use of a food additive (see 21 CFR
170.20(a)). Further, we have consistently taken the position that data
obtained from specific foods irradiated under specific conditions may
be extrapolated and generalized to draw conclusions regarding the
safety of foods of a similar type irradiated under related conditions
(see 62 FR 64107 at 64110; December 3, 1997, and 70 FR 48057 at 48059;
August 16, 2005). Other scientific bodies have used this approach as
well. As explained in our final rule permitting the irradiation of
molluscan shellfish (70 FR 48057 at 48058), the World Health
Organization, in its review of the safety data on irradiated food,
found that safety data on one food type can be extrapolated to other
foods of similar composition and that individual studies of irradiated
foods can be integrated into one database (Ref. 1). In the fresh
lettuce and fresh spinach final rule, we concluded that the body of
data and information we considered in our review demonstrated the
safety of fresh lettuce and fresh spinach irradiated up to a maximum
dose of 4.0 kGy. CFS' suggestion that such information is not

sufficient to support a safety determination is unsupported by specific
data or other factual information.
    We also disagree that we improperly relied on studies at doses
below 4.0 kGy. In analyzing the nutritional adequacy of irradiated
fresh lettuce and fresh spinach, we evaluated the totality of evidence,
which included studies of plant-based foods irradiated at a wide range
of doses (i.e., doses above and below 4.0 kGy), information about the
susceptibility of vitamins in lettuce and spinach to irradiation,
information about the susceptibility of vitamins in plant matrices in
general to irradiation, and estimates of the significance of fresh
lettuce and fresh spinach as sources of these vitamins. For the
assessment of the significance of fresh lettuce and fresh spinach as
sources of vitamins, we considered the levels of the vitamins present
in food, published information about the relative contribution of fresh
lettuce and fresh spinach to the total dietary intake of these
vitamins, and published studies and reviews summarizing the limited
bioavailability of certain vitamins from green leafy vegetables.
Importantly, we noted that folate, provitamin A carotenoids, and
vitamin K all have limited bioavailability from green leafy vegetables;
hence the contribution of these foods to overall intake of these
vitamins is diminished, despite the presence of the vitamins in high
amounts in foods such as spinach (Ref. 2).\2\ For example, in 2001 the
Institute of Medicine (IOM) concluded that provitamin A bioavailability
from dietary sources (i.e., not supplemental forms) is half that
previously thought (Ref. 3), and that very low bioavailability (<10
percent) is associated with raw green leafy vegetables (Ref. 4).
Similar findings of limited bioavailability have been reported for
folate and vitamin K from green leafy vegetables, particularly relative
to supplements and other food sources, as discussed in our nutrition
memorandum (Ref. 2).
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    \2\ Only vitamin K is present in high amounts in iceberg
lettuce.
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    We considered studies performed at doses ranging from 0.5 kGy to 56
kGy to ascertain the relative amount of vitamin loss at those doses.
Specifically, we assessed studies performed at doses above 4.0 kGy for
folate, provitamin A carotenoids, vitamin K, and vitamin C. As such, we
did not rely solely on studies conducted below 4.0 kGy to perform the
nutritional assessment; rather we considered all available data
pertaining to potential nutrient loss for those vitamins. The available
data included information on the levels of vitamins following treatment
with doses below 4.0 kGy, information on the levels of vitamins
following treatment with doses above 4.0 kGy, information on the
limited bioavailability of certain vitamins and provitamins from green
leafy vegetables, and information pertaining to the relative
contribution of these sources to the total dietary intake of individual
vitamins. Our assessment of the available data does not provide reason
for a safety concern regarding potential vitamin loss from irradiating
fresh lettuce and fresh spinach up to a maximum dose of 4.0 kGy. CFS
provided no information to support its assertions that our reliance on
studies in other fruits and vegetables and studies performed at doses
below 4.0 kGy would call into question our assessment of the
nutritional impact of the final rule and ultimately our determination
that irradiated fresh lettuce and fresh spinach at 4.0 kGy is safe. A
hearing will not be granted on the basis of mere allegations or denials
or general descriptions of positions and contentions (Sec.
12.24(b)(2)). Therefore, we are denying CFS' objection and request for
a hearing based on this objection.

B. First Numbered Objection: CFS' Contention That FDA Failed To
Determine the Magnitude of Nutrient Losses at or Near the Maximum
Permitted Dose of 4.0 kGy

    The first objection raised by CFS contends that FDA ``fails to
determine the magnitude of nutrient losses to be expected from
irradiation of fresh spinach or iceberg lettuce at or near the upper
limit approved in the rule: 4 kGy.'' They expound upon this objection
by asserting that the majority of the studies cited in our nutrition
memorandum (Ref. 2) were performed at doses below 2 kGy and on fruits
and vegetables other than fresh spinach and fresh lettuce. The
objection includes CFS' assertions regarding the following
``nutrients'': Carotenoids/vitamin A,\3\ folate, vitamin K, and vitamin
C. CFS' discussion for each nutrient contains additional objections.
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    \3\ We note that while CFS refers to these components as
nutrients, not all carotenoids are vitamin A precursors and not all
carotenoids have been shown to be essential to the human diet.
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    CFS further contends that we failed to determine the magnitude of
nutrient losses to be expected from irradiating fresh spinach and fresh
lettuce at or near the petitioned maximum dose because we did not
address the synergistic effects of irradiation and heating. According
to CFS, we should have considered that ``irradiation-induced nutrient
losses will be superadded to those from other industrial or home food
processing methods.'' CFS' assertion that we failed to determine the
magnitude of nutrient losses at or near the petitioned maximum dose
ultimately attempts to call into question our determination that the
irradiation of fresh lettuce and fresh spinach up to a maximum dose of
4.0 kGy is safe.
    Contrary to CFS' contention and, as demonstrated in our nutrition
memorandum (Ref. 2), we evaluated both the extent of nutrient loss and
the nutritional importance of any such losses resulting from
irradiation of fresh lettuce and fresh spinach at doses up to 4.0 kGy.
Our review of a large body of data relevant to the nutritional adequacy
and wholesomeness of irradiated foods has demonstrated that irradiation
does not significantly alter the macronutrients (i.e., proteins, fats,
and carbohydrates) of the food at the petitioned doses. However, it has
been shown that some vitamins are susceptible to irradiation. The
susceptibility of a vitamin to irradiation depends on factors such as
the chemical structure of the vitamin, the conditions of processing,
the conditions and duration of storage, and the composition of food. To
determine whether or not partial vitamin loss is significant, it is
essential to consider the relative contribution of the vitamin from the
irradiated food to the total dietary intake of the vitamin and the
sensitivity of that vitamin to irradiation.
    Therefore, our analysis focused primarily on vitamins that are
present in relatively high amounts in fresh lettuce and/or fresh
spinach, which were identified using the criteria for nutrient content
claims (Sec.  101.54 (21 CFR 101.54)),\4\ and that contribute more than
a trivial amount to the total dietary intake of that vitamin (i.e.,
more than 1 to 2 percent). The nutrients which meet both criteria are:
Vitamin A, vitamin K, and folate. Therefore, our discussion of the
nutritional impact of the proposed conditions of irradiation on fresh
lettuce and fresh spinach focused on these three nutrients.\5\ For each
of these

nutrients, we evaluated the dietary requirements, dietary sources, and
susceptibility of vitamins to irradiation, and we found that there
would be no significant impact on the dietary intake of those
nutrients.
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    \4\ In accordance with Sec.  101.54(b), foods containing >= 20
percent of the Reference Daily Intake or Daily Reference Value per
reference amount customarily consumed, 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.
    \5\ Spinach contains high levels of vitamin C, but 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 in the United States (Ref. 5); hence, vitamin C was not an
area of focus in the final rule, although it was addressed in the
our nutrition memorandum.
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1. Provitamin A Carotenoids/Vitamin A
    In the analysis specific to irradiation-induced loss of provitamin
A, CFS objects to the use of six studies, five of which did not involve
the irradiation of fresh lettuce or fresh spinach. We have reviewed a
large body of data relevant to the safety of irradiated foods.\6\ When
evaluating the safety of a source of radiation to treat food intended
for human consumption, we address three general areas: (1) Potential
toxicity, (2) nutritional adequacy, and (3) effects on the
microbiological profile of the treated food. We have consistently taken
the position that various scientifically validated types of data may
properly support a safety determination for a proposed use of a food
additive. For example, in the case of food irradiation, we have taken
advantage of the extensive research and large body of knowledge
concerning the principles of radiation chemistry and the chemical
composition of foods. CFS' suggestion that data and information derived
from studies of analogous irradiated foods are not sufficient to
support a determination that irradiated fresh lettuce and fresh spinach
is safe is unsupported by specific data or other factual information.
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    \6\ 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. 6). In the 1990s, WHO reanalyzed the
safety data on irradiated foods, including additional studies (see
51 FR 13376 at 13378, April 18, 1986) and 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. 1).
Furthermore, our Bureau of Foods Irradiated Foods Committee assessed
hundreds of toxicology studies in our files and determined that
studies involving irradiated foods did not demonstrate adverse
effects (Ref. 7). These studies, taken as a whole, serve as an
independent method to assess toxicological safety. The studies
considered in that evaluation include those that have been relied on
by FDA in previous evaluations of the safety of irradiated foods,
including lettuce, spinach, molluscan shellfish, shell eggs, meat,
and poultry (see 73 FR 49593, August 22, 2008; 70 FR 48057, August
16, 2005; 65 FR 45280, July 21, 2000; 62 FR 64107, December 3, 1997;
55 FR 18538, May 2, 1990; and 51 FR 13376), along with additional
data and information from our files and from other information
available to us, including published reports regarding studies in
which animals were fed a wide variety of foods irradiated at
different doses.
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    Furthermore, vitamin A exists in food sources in two different
forms: (1) Preformed vitamin A (retinol) and (2) provitamin A
(carotenoids).\7\ Preformed vitamin A is found in some animal-derived
foods (e.g., organ meats, dairy products, eggs) and in fortified foods
such as ready-to-eat cereals, whereas provitamin A carotenoids are
found in foods such as dark-green vegetables, orange vegetables, orange
fruits, and red palm oil (Ref. 3). There is a diverse set of foods that
contributes to the total dietary intake of vitamin A in a balanced
diet, including vitamin A-rich foods and provitamin A carotenoid-rich
foods. Among the wide range of plant-based foods containing provitamin
A carotenoids, fresh lettuce and fresh spinach are among the poorer
dietary sources, due to limited bioavailability of carotenoids from
these foods, as discussed earlier and reviewed by the IOM (Ref. 4).
Hence, even for fresh spinach, which has a relatively high
concentration of provitamin A, the actual contribution of this food to
total vitamin A intake is minor due to limited bioavailability (Ref.
2). Therefore, considering the insensitivity of vitamin A and
provitamin A carotenoids found in spinach to irradiation and the
limited contribution of these particular foods to the total dietary
intake of vitamin A, the small losses of vitamin A that might result
from the irradiation of fresh lettuce or fresh spinach are not
nutritionally significant (Ref. 2).
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    \7\ There are also two types of carotenoids: Provitamin A
carotenoids that are vitamin A precursors, meaning that they
contribute to vitamin A activity, and nonprovitamin A carotenoids
that are not vitamin A precursors and, therefore, do not contribute
to vitamin A activity.
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    Additionally, CFS asserts that there is ``no discussion of the
apparent discrepancy between no carotenoid loss in carrots at 2 kGy and
`low to moderate losses in beta and alpha-carotene' * * * in carrots
irradiated at less than half that dose, 0.8 kGy.'' \8\ We were aware of
the discrepancies between the two studies during our review. However,
we concluded that differences in observed losses between the studies
did not call into question our assessment of the nutritional impact of
the final rule and determination that irradiating fresh lettuce and
fresh spinach up to a maximum dose of 4.0 kGy is safe. The two studies
differed in treatment dose but also other factors, including storage
time, temperature during irradiation and storage, and analysis of total
carotenoids (Ref. 8) versus individual carotenoids (Ref. 9), which
could impact the reported levels of carotenoids. Despite differences in
study design, losses of total carotenoids (alpha-carotene plus beta-
carotene) were less than 20 percent in both studies. Losses of alpha-
carotene (28 percent) were reported to be slightly higher than losses
of beta-carotene (8 percent) in the Baraldi et al. paper (Ref. 9);
however, it is important to note that alpha-carotene is present in
lower amounts than beta-carotene in carrots and has half the retinol
activity equivalence of beta-carotene (discussed further in this
document). Further, alpha-carotene is not present in meaningful amounts
in either spinach or iceberg lettuce; hence; this provitamin was not
highlighted in the nutrition memorandum.
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    \8\ The studies to which CFS refers are the Hajare et al. study
(Ref. 8) that looked at the loss in total carotenoids in carrots
irradiated at 2.0 kGy and the Baraldi et al. study that was reviewed
by Diehl (Ref. 9) and was conducted at 0.8 kGy showing low to
moderate losses in beta- and alpha-carotene. Our nutrition
memorandum (Ref. 2) notes that the study conducted at 0.8 kGy
showing low to moderate losses in beta- and alpha-carotene was
reviewed within the Diehl reference.
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    The nutritional significance of provitamin A carotenoids is that
provitamin A carotenoids, including alpha and beta-carotenes, are
precursors of vitamin A. Even at the highest observed losses in the
cited studies (28 percent for alpha-carotene), one would not expect
substantive losses of vitamin A in the total diet, in part due to
inefficient conversion of alpha-carotene to retinol and the limited
bioavailability of alpha-carotene from plant sources. In recognition of
these limitations, the IOM has established a retinol activity
equivalence of 24 micrograms of alpha-carotene (from food) to 1
microgram of retinol (meaning 24 micrograms of alpha-carotene in
carrots yield only 1 microgram of retinol in the body). In contrast,
the IOM estimates that 12 micrograms of food-borne beta-carotene yield
one microgram of retinol in the body. Despite the relatively high
concentration of beta-carotene in spinach, the bioavailability of beta-
carotene from green leafy vegetables is generally considered to be low
relative to other food sources of beta-carotene (even lower than raw
carrot) due to inhibitory effects of the food matrix (i.e., the
components of the food) on carotenoid release from food. Release of the
carotenoids from the food matrix is a step that precedes the
incorporation of carotenoids into mixed lipid micelles and their
subsequent absorption (Refs. 4 and 10). This topic has been addressed
in section IV.A and in an extensive review by the IOM (Ref. 3).
Considering the limited bioavailability of provitamin A carotenoids
from fresh lettuce and fresh spinach, the limited contribution

of these foods to the total dietary intake of vitamin A, and the
relative radiation resistance of plant-based carotenoids, we determined
that the loss of carotenoids would not be a safety concern. We also
note that although provitamin A carotenoids are susceptible to partial
losses due to irradiation, these losses are somewhat variable and can
be minimized by control of various irradiation conditions (e.g.,
temperature, packaging, headspace gas). Therefore, while there were
variable (but not extensive) losses observed in the two carrot studies,
this apparent discrepancy does not call into question the outcome of
this final rule. CFS' objection attempts to call into question our
assessment of the nutritional impact of the final rule and implies that
there is a safety issue due to a discrepancy in losses between the two
cited studies; however, they do not provide any information or data to
support their objection. We are therefore denying CFS' objection and
request for a hearing because a hearing will not be granted on the
basis of mere allegations or denials or general descriptions of
positions and contentions (Sec.  12.24(b)(2)).
    Further, CFS asserts that we failed to determine the magnitude of
nutrient losses from irradiating fresh lettuce and fresh spinach
because the discussion of carotenoids was limited to total carotenoid
levels as opposed to analyzing specific carotenoids with ``particular
nutritional relevance,'' such as lutein and zeaxanthin. To support this
objection, CFS cites a study performed by Semba and Dagnelie (Ref. 11),
that, according to CFS, demonstrates the nutritional relevance of
lutein and zeaxanthin because ``[l]ow dietary intake and plasma levels
of lutein and zeaxanthin have been associated with low macular pigment
density and increased risk of age-related macular degeneration, and on
this basis these carotenoids have been considered good candidates for
designation as a [sic] `conditionally essential' nutrients.'' CFS fails
to note that the same journal article states that these carotenoids
``may play a role in the pathogenesis of age-related macular
degeneration,'' that ``studies are beginning to suggest that they fit
the criteria for conditionally essential nutrients'' and that
``[s]hould controlled clinical trials show lutein and/or zeaxanthin
supplementation protects against the developments or progression of
ARMD [age-related macular degeneration] and other eye diseases, then
lutein and zeaxanthin could be considered as conditionally essential
nutrients for humans'' (emphasis added) (Ref. 11). Thus, none of these
statements supports CFS' claim that there currently is a scientific
basis which would provide a substantial rationale for us to perform
analysis on individual carotenoids. Furthermore, it should be noted
that both lutein and zeaxanthin are nonprovitamin A carotenoids,
meaning that neither contributes to vitamin A activity.
    Additionally, in the most recently published report from the IOM on
Dietary Reference Intakes (DRIs), which updated recommendations for the
intake of vitamin C, vitamin E, selenium, and discussed carotenoids,
the IOM stated: ``[a] large body of observational epidemiological
evidence suggests that higher blood concentrations of [beta]-carotene
and other carotenoids obtained from foods are associated with lower
risk of several chronic diseases. This evidence, although consistent,
cannot be used to establish a requirement for [beta]-carotene or
carotenoid intake because the observed effects may be due to other
substances found in carotenoid-rich food, or to other behavioral
correlates of increased fruit and vegetable consumption * * *
[a]lthough no DRIs are proposed for [beta]-carotene or other
carotenoids at the present time, existing recommendations for increased
consumption of carotenoid-rich fruits and vegetables are supported . .
.'' (Ref. 4).
    After reviewing the relevant scientific studies, the IOM did not
establish a requirement for carotenoid intake; therefore, unless the
carotenoids contributed to vitamin A levels in the diet, we did not
analyze specific carotenoids. For these reasons, there was no evidence
that individual carotenoids needed to be analyzed when we made our
safety decision on irradiation of fresh lettuce and fresh spinach at
the petitioned doses. Accordingly, we are denying CFS' objection and
request for a hearing because the data and information submitted by CFS
are insufficient to justify the factual determination urged, even if
accurate (Sec.  12.24(b)(3)).
2. Folate
    CFS offers three arguments to support their view that we
erroneously concluded that irradiation-induced folate loss in fresh
lettuce and fresh spinach is not nutritionally significant. First, CFS
asserts that we did not consider any studies of irradiation-induced
folate losses in iceberg lettuce. Second, CFS asserts that only one of
the cited studies pertained specifically to fresh spinach. Third, CFS
contends that we failed to discuss certain results from the study
performed by M[uuml]ller and Diehl (Ref. 12).
    First, CFS asserts that ``though iceberg lettuce contains
considerably less folate than spinach * * *, lettuces as a group supply
a larger percentage of folate than the spinach/greens groups to the
average American diet,'' and therefore we should have considered
studies of irradiation-induced folate losses in iceberg lettuce.
However, we note that iceberg lettuce is just one leafy vegetable
within the category of ``lettuces'' (which includes Romaine,
butterhead, green leaf, etc.); among the lettuces, iceberg lettuce
contains the lowest concentration of folate. In our nutrition
memorandum (Ref. 2), we explain that iceberg lettuce is not considered
to be a ``good source'' of folate in accordance with Sec.  101.54(c)
and that enriched and fortified foods (e.g., cereal grains and grain-
based products) make the greatest contribution to folate in the diet.
Furthermore, the form of folate used for fortification is more
bioavailable than naturally occurring food folates. While we did not
provide an analysis for iceberg lettuce, we did analyze the potential
folate loss in spinach, which is considered to contain relatively large
amounts of folate. We concluded that irradiation of spinach at doses up
to 4.0 kGy would not have a significant impact on the dietary intake of
folate in the U.S. diet. It follows that iceberg lettuce, which does
not meet the criteria for a ``good source'' of this nutrient, would not
have a significant impact on the dietary intake of folate either.
Therefore, the information provided by CFS that lettuces ``as a group''
supply a larger percentage of folate than the spinach/greens group is
not sufficient to demonstrate that we should have considered
irradiation-induced losses in iceberg lettuce. Accordingly, we are
denying CFS' objection and request for a hearing because the data and
information submitted by CFS are insufficient to justify the factual
determination urged, even if accurate (Sec.  12.24(b)(3)).
    Second, CFS asserts that only one study was presented that
considered irradiation-induced folate loss in fresh spinach. While we
cited two studies considering folate loss, CFS asserts that only one
study is relevant because it was performed in fresh spinach. In the
final rule, we explained our position that many scientifically valid
types of data may properly support a finding that a proposed use of a
food additive is safe. CFS has not provided any evidence that our
consideration of studies considering folate loss is inadequate to
determine the magnitude of nutrient losses from irradiating fresh
lettuce and fresh

spinach at the petitioned doses. CFS has also not provided any
additional studies that we should have considered in assessing folate
loss. We are therefore denying CFS' objection and request for a hearing
because a hearing will not be granted on the basis of mere allegations
or denials or general descriptions of positions and contentions (Sec.
12.24(b)(2)).
    Third, CFS contends that our discussion of the study performed by
M[uuml]ller and Diehl (Ref. 12) did not include certain results. CFS
asserts that the study reported a 12 percent loss of folate in fresh
spinach when irradiated at 2.5 kGy, but we did not discuss the 21
percent loss of folate in fresh spinach when irradiated at 5.0 kGy or
the 13 percent loss of folate when dehydrated spinach was irradiated at
10 kGy. The M[uuml]ller and Diehl study was included in the petition
and was analyzed by FDA when we made our safety assessment. We
acknowledge that a greater loss of folate was shown when fresh spinach
was irradiated at a higher dose (i.e., 5.0 kGy) when compared to the
lower dose of 2.5 kGy. The nutrition memorandum cited the 2.5 kGy
result, since it was within the range of doses under consideration in
the petition and highlighted the general stability of food folate. The
5.0 kGy dose, although greater than the dose under consideration in the
petition, still shows that nearly 80 percent of folate is maintained,
thus supporting the general stability of this vitamin to moderate doses
of irradiation. In our review of the petition, we considered the health
implications from folate loss in spinach at the maximum petitioned dose
(4.0 kGy), and concluded that such folate loss is not nutritionally
significant because: (1) Fresh lettuce and fresh spinach contribute
minimally to the dietary intake of folate; and (2) folate is found to
be consistently stable to irradiation under various conditions that
have been detailed in published studies.
    Therefore, the information provided by CFS that a greater loss of
folate was shown when fresh spinach was irradiated at a higher dose
does not call into question our assessment of the nutritional impact of
the final rule and determination that irradiating fresh lettuce and
fresh spinach up to a maximum dose of 4.0 kGy is safe. Accordingly, we
are denying CFS' objection and request for a hearing because the data
and information submitted by CFS are insufficient to justify the
factual determination urged, even if accurate (Sec.  12.24(b)(3)).
3. Vitamin K
    CFS objects to the final rule based on our nutrition memorandum for
vitamin K because CFS asserts that: (1) The Knapp and Tappel study
(Ref. 13) cited in the nutrition memorandum involved the irradiation of
pure vitamin K in an isooctane solution and not in a food matrix; (2)
the Richardson et al. study (Ref. 14) cited in the nutrition memorandum
involved indirect measurement of vitamin K activity in spinach and
other vegetables after freezing, irradiation at 28 or 56 kGy, or heat-
processing; (3) we ``failed to consider'' conflicting results in two
studies (Richardson et al. (Ref. 15) and Metta et al. (Ref. 16)) from
the same period as the Richardson et al. study (Ref. 14) cited in the
nutrition memorandum; and (4) we failed to consider the 2007 study by
Hirayama et al. (Ref. 17) that raises ``similar questions'' regarding
the nutritional impact of irradiating fresh lettuce and fresh spinach.
    First, CFS contends that the Knapp and Tappel study that involved
the irradiation of pure vitamin K in an isooctane solution rather than
a food matrix is of ``limited value for assessing irradiation-induced
loss of Vitamin K in irradiated spinach or iceberg lettuce.'' We
disagree with CFS' assessment. To the contrary, we maintain that this
study establishes vitamin K as one of the least sensitive fat-soluble
vitamins to irradiation, and therefore is relevant for assessing
irradiation-induced losses. Even though the study was performed in an
isooctane solution, the relative sensitivities of the vitamins to
irradiation do not change; rather, the food matrix can offer protection
to the vitamin, lessening the effects of irradiation because the
radiation effects will be distributed to all components of the food,
i.e., the principle of mutual protection (Ref. 18). We reviewed this
study and found it to be adequate to determine comparative
radiosensitivities under uniform conditions for vitamins A, D, E, K, as
well as carotene. Therefore, the information provided by CFS that the
Knapp and Tappel study involved the irradiation of vitamin K in an
isooctane solution rather than a food matrix does not call into
question the value of the Knapp and Tappel study in helping us assess
the nutritional impact of the final rule. We are denying CFS' objection
and request for a hearing because the data and information submitted by
CFS are insufficient to justify the factual determination urged, even
if accurate (Sec.  12.24(b)(3)).
    Second, CFS contends that the Richardson et al. study (Ref. 14) is
of limited value because the study ``estimated'' the vitamin K content
through indirect measurement of the prothrombin times of chick plasma,
and the study reported ``anomalous results.'' According to CFS, the
authors of the study reported an increase in vitamin K activity in
irradiated spinach over time in addition to variability in the values
obtained from different assays. CFS cites these findings to support its
contention that we erroneously determined the magnitude of vitamin K
loss from irradiation of fresh lettuce and fresh spinach under the
petitioned conditions.
    We disagree that the indirect measurement of vitamin K activity in
spinach precludes this study from being useful in the assessment of
potential nutrient losses. In our review of this study, we considered
the prothrombin time measurement in the chick bioassay, even though
indirect, to be relevant for assessing vitamin K activity in foods
since the chick is sensitive to dietary vitamin K deprivation.
Moreover, the prothrombin time measurement is a common parameter for
measuring vitamin K status for clinical purposes (Refs. 3 and 19).
Furthermore, we acknowledge the variability in the data cited by CFS;
however, CFS' objection fails to note that the authors of the study in
question concluded that ``regardless of the variability in results * *
* there was no appreciable loss of vitamin K activity in the foods
preserved by any process or when stored for 15 months'' (Ref. 14).
Variability in results is not grounds for a study to be ignored;
important information about general trends may still be gleaned from
this study, which consistently found vitamin K activity was not reduced
by irradiation relative to frozen or heat-processed controls. As part
of their objection, CFS specifically notes that vitamin K activity
after 15 months of storage was higher than directly after irradiation
at both irradiation doses; however, it should be noted that irradiation
may either accelerate or decelerate metabolic changes within the food,
a factor which may account for differences observed following storage
(Ref. 9). For example, it is known that vitamin K resides in the
chloroplasts and has tight association with the thylakoid membranes.
This tight association may account for the limited bioavailability of
vitamin K from green leafy vegetables (Ref. 20). Processing techniques
such as irradiation (particularly at high doses) may result in
disruption of thylakoid membranes, an

effect which may become more evident after long term storage and may
account at least in part for variability in observed vitamin K activity
after storage. As such, the information provided by CFS that the
Richardson et al. study involved indirect measurement of vitamin K
activity does not call into question the value of the Richardson et al.
study in helping us assess the nutritional impact of the final rule. We
are therefore denying CFS' objection and request for a hearing because
the data and information submitted by CFS are insufficient to justify
the factual determination urged, even if accurate (Sec.  12.24(b)(3)).
    Third, CFS contends that we failed to consider conflicting results
from two studies cited by CFS: A study performed by Richardson et al.
(Ref. 15); and a study performed by Metta et al. (Ref. 16). Although
neither of these studies was cited in our nutrition memorandum, we were
aware of both studies when evaluating the nutritional impact of
irradiating fresh lettuce and fresh spinach up to a maximum dose of 4.0
kGy. We disagree with CFS' conclusions that the Richardson et al. study
demonstrated that the ``Vitamin K activity of diets containing small
quantities of Vitamin K was markedly decreased by irradiation with
sterilizing doses of gamma rays.'' CFS' objection fails to note that,
in the experimental report, the authors concluded that ``practically
none of the vitamin K activity was lost by the irradiation process when
vitamin K1 was the source of the vitamin in the diet.'' The
article also concluded that ``[s]ince the incidence of hemorrhage was
higher in the chicks receiving the untreated spinach than it was in
those receiving the irradiated spinach, it was concluded that no
destruction of vitamin K occurred by the irradiation process.''
    In addition, the Metta et al. study (Ref. 16) reported vitamin K
deficiency in rats induced by the feeding of irradiated beef. However,
we deemed the study irrelevant to the assessment of vitamin K loss in
fresh lettuce and fresh spinach because the Metta et al. study assessed
the vitamin K destruction of the more labile form of vitamin K found in
meat (menaquinone). There are a number of different forms of vitamin K,
including, but not limited to: Phylloquinone (vitamin K1)--
the only important molecular form found in plants, menaquinones
(vitamin K2)--which refers to a series of compounds produced
by gut bacteria but also to a form of vitamin K2, termed
``menaquinone-4'' that is produced in animal tissues from conversion of
dietary vitamin K (K1, K3), and menadione
(vitamin K3), a synthetic form (Refs. 3, 21, and 22).
    Phylloquinone is the form of vitamin K that is found in spinach and
other leafy greens, whereas menaquinone, although present in minor
amounts, is the dominant form found in beef along with lesser amounts
of dietary phylloquinone. The radiosensitivities differ among various
forms of vitamin K. For example, Richardson et al. reported menadione
(vitamin K3) is more readily destroyed by ionizing radiation
than either phylloquinone (vitamin K1) or vitamin
K5 (a vitamin K analog) (Ref. 15). The Metta et al. study
assessed the destruction of vitamin K found in meat and the effect on
rats fed a limited diet; the lability of vitamin K in beef \9\ has been
noted in numerous published reviews, including those of WHO (Ref. 23),
Thayer et al. (Ref. 24); and Diehl et al. (Ref. 9). We determined that
the Metta et al. study was not relevant to the assessment of potential
irradiated-induced phylloquinone losses in fresh lettuce and fresh
spinach, and did not highlight this reference in our nutrition
memorandum.
---------------------------------------------------------------------------

    \9\ We note that although Metta et al. does not identify the
form of vitamin K in beef tissue, other studies have reported
menaquinone-4 as the predominant form of vitamin K in beef tissue.
---------------------------------------------------------------------------

    We do not agree with CFS' contention that our nutritional
assessment of irradiated fresh lettuce and fresh spinach is called into
question by these studies. Neither of these studies includes any
information or data that would call into question our findings
regarding the nutritional impact of irradiation under the petitioned
conditions. We are therefore denying CFS' objection and request for a
hearing because the data and information submitted by CFS are
insufficient to justify the factual determination urged, even if
accurate (Sec.  12.24(b)(3)).
    Lastly, CFS asserts that a study conducted by Hirayama et al. (Ref.
17) was not reviewed by FDA in the approval process to permit ionizing
radiation to treat fresh lettuce and fresh spinach, and therefore calls
into question our nutritional assessment and ultimately our safety
conclusion. In the Hirayama et al. study, germ-free mice were fed
pelleted, sterilized animal feed. According to CFS, vitamin
K3, a synthetic form of vitamin K, was eliminated when the
pure compound was added to the feed and irradiated at 50 kGy. CFS notes
that the study also showed that vitamin K1, the form found
in spinach, was reduced by approximately 68 percent after the pelleted
feed was exposed to irradiation doses of 50 kGy. CFS objects to the
final rule, asserting that this study demonstrates the need for more
research to determine the ``differential sensitivities'' of the two
forms of vitamin K. We do not agree that our nutritional assessment and
the safety of irradiated fresh lettuce or fresh spinach up to a maximum
dose of 4.0 kGy are called into question by this study.
    As previously mentioned in this document, research has demonstrated
that different forms of vitamin K have variable sensitivities to
irradiation. For example, the Richardson et al. study (Ref. 15) cited
by CFS investigated the effects of ionizing radiation on vitamin K when
different sources were used (i.e., probing the ``differential
sensitivities''). The sources of this vitamin were K1,
K3, K5, dehydrated alfalfa leaf meal, and fresh
spinach. The authors concluded that menadione (K3) was more
readily destroyed by irradiation than either vitamin K1 or
K5, and practically no destruction of vitamin K
(phylloquinone) occurred when the dietary source was natural (i.e.,
from alfalfa leaf meal and spinach). Clearly, it is understood that
different forms of vitamin K can have variable sensitivity to
irradiation, and we were aware of this fact when evaluating the
nutritional adequacy of irradiated lettuce and spinach (Ref. 25). In
addition, the petition proposes to irradiate spinach in its natural
form, and the Richardson et al. study, which provides the most
pertinent results (Ref. 15), demonstrated that there was practically no
destruction of vitamin K from this natural source. Furthermore, the WHO
report we evaluated during review of the petition contained information
regarding the varied properties of these different forms of vitamin K
(Ref. 20). Therefore, the Hirayama et al. study raised by CFS does not
call into question our assessment of the nutritional impact of the
final rule; we continue to conclude from all of the available evidence
that the irradiation of fresh lettuce and fresh spinach up to a maximum
dose of 4.0 kGy will have no significant impact on the total dietary
intake of vitamin K and is safe. We are denying CFS' objection and
request for a hearing because the data and information submitted by CFS
are insufficient to justify the factual determination urged, even if
accurate (Sec.  12.24(b)(3)).
4. Vitamin C
    CFS asserts that the final rule does not provide an assessment of
vitamin C loss from irradiation and further alleges that our assessment
of irradiation-induced vitamin C loss in our nutrition memorandum is
erroneous. CFS argues

that the studies we reviewed regarding irradiation-induced loss of
vitamin C showed varied results and that one source of variation in
that loss is whether ascorbic acid (AA) was measured or whether AA plus
dehydroascorbic acid (DHAA) was measured. Measuring AA plus DHAA yields
the total ascorbic acid (TAA). Specifically, CFS states that, in light
of the divergent data, experiments for irradiation of fresh lettuce and
fresh spinach should be conducted measuring TAA. CFS also contends that
a source of variation in vitamin C can arise from ``differential
Vitamin C loss in different fruits and vegetables.''
    We evaluated the vitamin C loss in irradiated fresh lettuce and
fresh spinach and the evaluation was provided in our nutrition
memorandum (Ref. 2). However, because fresh lettuce and fresh spinach
are not major contributors to vitamin C in the U.S. diet, the question
of vitamin C loss from these foods was not discussed in the final rule.
While spinach has a relatively high concentration of vitamin C, the
combined food group of ``spinach/greens'' contributes less than 2
percent to the total intake of vitamin C in the diet. Other major food
sources (e.g., citrus fruit, fortified juice drinks, tomatoes, peppers,
potatoes, broccoli) provide the majority of vitamin C in the U.S. diet.
We therefore determined that little if any reduction in intake of
vitamin C in the U.S. diet is expected to result from irradiation of
fresh lettuce and fresh spinach under the petitioned conditions of use.
    We agree that the studies cited in our nutrition memorandum appear
to report divergent results; however, for all these studies, we
provided an explanation for each set of differences. For example, our
nutrition memorandum states that, ``[m]any of the early studies of the
effects of irradiation on vitamin C levels measured AA levels only and
consequently reported artificially high decreases in vitamin C,'' and
``AA losses of irradiated foods relative to controls may be quite
different depending on whether AA levels are recorded immediately after
irradiation or after typical storage conditions.'' The memorandum also
states that, ``[i]n the most recent studies conducted on spinach and
iceberg lettuce, when irradiation has been conducted at doses
reflective of those that would be practical for maintaining acceptable
sensory properties, reported losses were minimal.'' Thus, the
information provided by CFS, that the studies we reviewed regarding
irradiation-induced loss of vitamin C showed varied results, does not
call into question our assessment of the nutritional impact of the
final rule or our conclusion that irradiating fresh lettuce and fresh
spinach up to a maximum dose of 4.0 kGy is safe. We evaluated the
totality of evidence and determined that the irradiation of fresh
lettuce and fresh spinach up to a maximum dose of 4.0 kGy was safe. We
are denying CFS' objection and request for a hearing because the data
and information submitted by CFS are insufficient to justify the
factual determination urged, even if accurate (Sec.  12.24(b)(3)).
5. Synergistic Effects of Irradiation and Heating
    CFS contends that we do not address the synergistic effects of
irradiation and heating, stating that nutrient losses would be even
greater for dual processing compared to irradiation alone. In support
of this objection, CFS cites a table in ``Safety of Irradiated Foods''
by Diehl (Ref. 9) specifically showing synergistic losses of vitamin E.
We are aware that synergistic losses have been noted for vitamin E and
thiamin, two vitamins that are particularly sensitive to irradiation;
however, synergistic effects have not been observed for all vitamins or
in all food types (Ref. 24). To determine the potential impact of
irradiation at levels up to 4.0 kGy on the nutritional value of fresh
lettuce and fresh spinach, we considered all vitamins known to be
present in these foods, and primarily focused on vitamins that are
present in relatively high amounts in one or both of these foods and
vitamins for which lettuce and spinach contribute more than a trivial
amount to the total dietary intake of those vitamins (i.e., more than 1
to 2 percent). There are a number of commonly consumed foods that are
substantial sources of vitamin E (e.g., certain nuts and oils,
margarines) (Ref. 5); these foods are discussed in the reference cited
by CFS. Substantial sources of thiamin include yeast breads, ready-to-
eat cereals, pastas and grains, certain meats, and milk (Ref. 5).
Neither of the two vitamins particularly sensitive to irradiation,
vitamin E and thiamin, has been identified as being present in
relatively high amounts in fresh lettuce and/or fresh spinach and as
contributing more than a trivial amount to the total dietary intake of
these vitamins. Therefore, the information provided by CFS, that
synergistic losses have been found for vitamin E, does not call into
question our assessment of the nutritional impact of the final rule and
determination that irradiating fresh lettuce and fresh spinach up to a
maximum dose of 4.0 kGy is safe. Accordingly, we are denying CFS'
objection and request for a hearing because the data and information
submitted by CFS are insufficient to justify the factual determination
urged, even if accurate (Sec.  12.24(b)(3)).

C. Second Numbered Objection: CFS' Assertion That FDA Underestimated
the Nutritional Contribution of Fresh Spinach and Fresh Lettuce to the
Diet

    CFS also objects that we underestimated the nutritional
contribution of fresh lettuce and fresh spinach to the diet.
Specifically, CFS states that we failed to consider spinach's
``dramatically rising nutritional contribution'' to the average
American diet over time and failed to consider subpopulations which
rely more heavily on spinach for nutrition than the statistically
average American. Thus, CFS attempts to call into question our
assessment of the nutritional impact of the final rule and ultimately
our determination that irradiating fresh lettuce and fresh spinach up
to a maximum dose of 4.0 kGy is safe.
    According to CFS, we employed two criteria to consider which
nutrients were assessed: (1) Nutrients for which spinach/iceberg
lettuce are an ``excellent source;'' and (2) nutrients for which
spinach/iceberg lettuce contribute greater than 1 to 2 percent of the
statistically average American's diet. CFS asserts that we should have
provided a rationale for considering only nutrients for which spinach
is an ``excellent source'' and should have considered vitamins for
which spinach is also a ``good source.'' CFS has mischaracterized the
criteria we used for our nutritional assessment, which was explained in
our nutrition memorandum (Ref. 2). We explained in the nutrition
memorandum that we considered all vitamins known to be present in
lettuce and spinach in relatively high amounts (greater than or equal
to 10 percent of the daily value for vitamins), including vitamins for
which lettuce and/or spinach were ``good'' or ``excellent'' sources,
and that contribute greater than 1 to 2 percent to the total dietary
intake of those vitamins. Vitamins that did not meet these two criteria
were not explicitly discussed in the nutrition memorandum. While fresh
spinach is a ``good source'' of vitamin E, vitamin B6, and
riboflavin, fresh spinach did not contribute more than 1 to 2 percent
to the total dietary intake of these vitamins. Therefore, we did not
explicitly discuss these nutrients in the nutrition memorandum. CFS has
not presented any evidence to call into question the criteria we used
for our nutritional assessment. Therefore, we are denying CFS'
objection and request

for a hearing because a hearing will not be granted on the basis of
mere allegations or denials or general descriptions of positions and
contentions (Sec.  12.24(b)(2)).
    In addition, CFS objects to our second criteria, asserting that we
rely on a ``13-year old `snapshot' that misses the growing importance
of [spinach] to the nutritional adequacy of American diets.'' In
support of this objection, CFS submitted a study performed by the
Economic Research Service (ERS) of the United States Department of
Agriculture (USDA) (Ref. 26). This study provides basic economic
information about the market distribution of spinach in the United
States. CFS points out that this study indicated an increase in the
consumption of spinach from the 1970s through 2002. Table 1 of the ERS
study presents ``per capita use'' \10\ of spinach in the United States.
The per capita use values for fresh market (i.e., fresh spinach) for
1994, 1995, and 1996 are 0.75, 0.67, and 0.63 pounds, respectively, and
the corresponding per capita use values for total spinach are 1.71,
1.66, and 1.77 pounds, respectively. While CFS focused on the value for
per capita use of total spinach, the fresh market value is more
pertinent to this discussion, as fresh spinach is the subject of this
regulation. The ERS study indicates that the total fresh market per
capita value for spinach increased from 0.75 pounds in 1994 to 1.49
pounds in 2002. CFS asserts that we did not consider this increase in
fresh spinach consumption in the nutritional assessment.
---------------------------------------------------------------------------

    \10\ ``Per capita use'' was calculated using two major datasets
on food consumption in the United States: (1) Food disappearance
data, which measures the flow of raw and semi-processed food
commodities through the U.S. marketing system, and (2) the
Continuing Survey of Food Intakes by Individuals, which records food
intake over a specific period and collects demographic information,
information on where a food item was purchased, how it was prepared,
and where it was eaten (Ref. 26).
---------------------------------------------------------------------------

    CFS further asserts that this rise in consumption of spinach could
be used to provide a rough approximation of the dietary and nutritional
contribution of spinach during these years (i.e., 1997 to 2002). CFS
provides estimations for percent contribution of spinach to vitamin A
and vitamin C intake and suggests that contributions of spinach to
vitamin E, riboflavin, and vitamin B6 intake may have
increased to provide more than 1 to 2 percent of the percent daily
value as well.
    However, we note that our nutritional assessment included a key
conservative assumption that compensates for the increase in fresh
spinach consumption cited by the ERS study. Specifically, we assumed
that all spinach and iceberg lettuce in the food supply would be
irradiated (i.e., 100 percent commercial application). For the years of
1994, 1995, and 1996, we conservatively estimated 100 percent
commercial application; values for total per capita use of spinach were
1.71, 1.66, and 1.77 pounds, respectively, during those years, and we
assumed all spinach could be irradiated when evaluating the nutritional
impact of irradiating fresh lettuce and fresh spinach. These values for
total per capita use of spinach each exceed the value for fresh market
consumption in 2002 and therefore, our assessment encompassed the
increased per capita use of fresh spinach through use of this
conservative approach. Since our approach did not underestimate fresh
spinach consumption in our nutritional assessment, the data and
information provided by CFS do not call into question our assessment of
the nutritional impact of the final rule and determination that
irradiating fresh lettuce and fresh spinach up to a maximum dose of 4.0
kGy is safe. Moreover, CFS' assertion that the rise in spinach
consumption indicates increased contributions of spinach to the dietary
intake of vitamins is not based on actual data. The estimates provided
by CFS are purely speculative; the estimates do not account for recent
changes in calculation of vitamin A equivalency and presume no other
changes in the U.S. diet (during the same time period) related to
intakes of other foods containing vitamin A and provitamin A and
certain water-soluble vitamins listed by CFS. Because the data and
information submitted by CFS are insufficient to justify the factual
determination urged, even if accurate (Sec.  12.24(b)(3)), and a
hearing will not be granted on the basis of mere allegations or denials
or general descriptions of positions and contentions (Sec.
12.24(b)(2)), we are denying CFS' objection and request for a hearing.
    CFS also objects to the final rule by alleging that we did not
consider atypical consumers of spinach such as Asian women, women 60
years of age or older, and vegetarians. We are aware that there is
variation in the amount of fresh spinach consumed by different U.S.
subpopulations; however, CFS provided no evidence that spinach is a
more significant source of certain vitamins for any particular
subpopulation. Indeed, to establish the contribution and significance
of spinach as a source of specific vitamins in the diet, the complete
diet must be considered. For example, when assessing the relative
contribution of spinach and other leafy greens to the vitamin A content
of the diet, the dietary intake of other major contributors of vitamin
A (including vitamin A rich foods such as organ meats and dairy
products) and provitamin A rich foods (such as carrots, tomatoes, and
fortified ready-to-eat cereals) should be included. In addition,
according to the IOM, bioavailability of provitamin A carotenoids
should be taken into account. In the absence of data on the complete
diet, it is not possible to determine the percent contribution of
spinach and lettuce to the dietary intake of vitamins for these
population subgroups and whether the relative contribution of spinach
and lettuce to the dietary intake of these vitamins varies for the
subpopulations cited by CFS. While the ERS study indicates that Asian
women and women 60 years of age or older consume a relatively greater
amount of fresh spinach compared to statistically average Americans,
CFS did not establish that the small losses of some vitamins that could
result from the petitioned use of irradiation of fresh spinach would be
nutritionally significant (i.e., exceed a trivial amount for the total
diet) for any of these population subgroups. Thus, the information
provided by CFS regarding certain subpopulations that consume more
spinach is not sufficient to support CFS' assertion that we failed to
protect ``atypical'' consumers and therefore underestimated the
nutritional contribution of fresh lettuce and fresh spinach to the
diet. We are denying CFS' objection and request for a hearing because
the data and information submitted by CFS are insufficient to justify
the factual determination urged, even if accurate (Sec.  12.24(b)(3)).

D. Third Numbered Objection: CFS' Contention That FDA Failed To Conduct
a Cumulative Assessment of Irradiation-Induced Nutrient Loss

    CFS also objects that we ``failed to conduct a cumulative
assessment of irradiation-induced nutrient losses in fresh spinach and
iceberg lettuce in combination with irradiation-induced nutrient losses
in other foods already approved for irradiation * * *.'' CFS contends
that by ``breaking out'' fresh lettuce and fresh spinach from the
original petition, the nutritional impact will appear lessened, even if
the impact of irradiating all the foods covered in the original
petition is significant. Accordingly, CFS believes that we should
conservatively assume that the entire supply of any given food will be
irradiated at the maximum permitted dose when approving a petition.
CFS'

contention therefore attempts to call into question our assessment of
the nutritional impact of the final rule and our determination that
irradiating fresh lettuce and fresh spinach up to a maximum dose of 4.0
kGy is safe.
    We explained in the final rule our criteria for evaluating whether
irradiation of fresh lettuce and fresh spinach up to a maximum dose of
4.0 kGy would have an adverse effect on the nutritional quality of the
diet. Our analysis focused on the effects of irradiation on those
nutrients for which at least one of these foods may be identified as an
``excellent source'' or a ``good source'' and for which they contribute
more than a trivial amount to the total dietary intake (i.e., the
nutrients that had the potential to impact the diet). We based our
decision on both the data and information submitted in the petition, as
well as other data and information in our files. We determined that,
based on the available data and information, the effects of irradiation
on nutrient levels in fresh lettuce and fresh spinach treated under the
proposed conditions will be insignificant and will not adversely affect
the nutritional quality of the overall U.S. diet.
    CFS alleges that ``breaking out'' fresh lettuce and fresh spinach
from the foods covered in the original petition lessens the apparent
overall nutritional impact of irradiated foods. However, the vitamin
loss resulting from this regulation is negligible and therefore will
not affect any cumulative assessment. CFS also asserts that we should
conservatively assume that the entire supply of any given food will be
irradiated at the maximum permitted dose during the approval of a
petition. We agree with CFS and have chosen to employ this approach
when assessing nutritional losses induced by irradiation. The nutrition
memorandum notes that we, in our reviews and analysis of nutritional
data, operate under the assumption that the entire supply of a given
food may be irradiated at the maximum permitted dose. Contrary to what
CFS appears to assert, the discussion of data at lower doses in the
nutrition memorandum does not negate this assumption; rather, it
reflects a review of published data on irradiation of various plant
foods at both lower and higher doses. CFS has not submitted sufficient
information to support the conclusion that nutrient loss in fresh
lettuce or fresh spinach irradiated under the petitioned conditions, in
combination with nutrient losses in other foods already approved for
irradiation, would call into question our assessment of the nutritional
impact of the final rule and would be a safety concern. Accordingly, we
are denying CFS' objection and request for a hearing because a hearing
will not be held on the basis of mere allegations or denials or general
descriptions of positions or contentions (Sec.  12.24(b)(2)).

E. Fourth Numbered Objection: CFS' Assertion That FDA Failed To
Determine Risk of Food-Borne Disease From Radiation Resistant Pathogens

    In another overall objection to the final rule, CFS objects to our
safety evaluation of irradiated fresh lettuce and fresh spinach,
stating that ``FDA has failed to determine whether irradiation of fresh
spinach and iceberg lettuce . . . will increase the risk of food-borne
disease from radiation-insensitive pathogens such as Clostridium
botulinum. . . .'' Specifically, CFS asserts that our analysis did not
adequately address the possibility that the suppression of radiation-
sensitive bacteria by irradiation might offer enhanced growth
conditions for pathogens that are more resistant to irradiation, such
as C. botulinum (the bacterium that produces the toxin which causes the
disease botulism). CFS presents three arguments to support this
objection: (1) We did not provide a discussion of radiation-insensitive
pathogens other than C. botulinum; (2) the study by Petran et al. (Ref.
27), which we cited to support our conclusion that irradiation will not
increase the risk of botulism, did not involve irradiation of fresh
lettuce or fresh spinach; and (3) the microbiology memorandum (Ref. 28)
contained contradictory statements. We will address each argument in
this document.
    First, CFS asserts that we erred by not evaluating irradiation's
potential effect on radiation-insensitive pathogens other than C.
botulinum. Historically, it has been our practice to evaluate
microbiological pathogens that have been identified as a potential
hazard for a specific type of food and which are also of public health
significance (see, for example, 70 FR 48057, August 16, 2005 (amending
the food additive regulations to provide for the safe use of ionizing
radiation for control of Vibrio species and other food-borne pathogens
in fresh or frozen molluscan shellfish); 65 FR 64605, October 30, 2000
(amending the food additive regulations to provide for the safe use of
ionizing radiation to control microbial pathogens in seeds for
sprouting); 65 FR 45280, July 21, 2000 (amending the food additive
regulations to provide for the safe use of ionizing radiation for the
reduction of Salmonella in fresh shell eggs); 62 FR 64107, December 3,
1997 (amending the food additive regulations to provide for the safe
use of a source of radiation to treat refrigerated or frozen uncooked
meat, meat byproducts, and certain meat food products to control food-
borne pathogens and extend product shelf life); 55 FR 18538, May 2,
1990 (amending the food additive regulations to provide for the safe
use of sources of ionizing radiation for the control of food-borne
pathogens in poultry); and 50 FR 29658, July 22, 1985 (amending the
food additive regulations to permit gamma radiation treatment of pork
to control Trichinella spiralis)). In the microbiology memorandum, we
provide a discussion of the food-borne disease outbreaks and pertinent
pathogens most commonly associated with the consumption of fresh
lettuce and fresh spinach. The microbiology memorandum identifies
Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella
enterica serovars as pathogens of public health significance, and
discussed these pathogens in detail. We also discuss C. botulinum in
the microbiology memorandum and in the final rule, not because C.
botulinum has been identified as a reasonable hazard for either fresh
lettuce or fresh spinach, but because this pathogen has been identified
as being both radiation-insensitive and of public health significance,
and to demonstrate the impact that elimination of native microflora may
have on the ability of this type of pathogen to proliferate and
elaborate toxin. However, it is not our burden to discuss possibly
irrelevant pathogens. CFS does not provide information related to
additional radiation-insensitive pathogens of public health
significance that may be present in fresh lettuce or fresh spinach that
we have not considered, and the objection contains no information that
would cause us to change our safety determination. We are therefore
denying CFS' objection and request for a hearing because a hearing will
not be granted on the basis of mere allegations or denials or general
descriptions of positions and contentions (Sec.  12.24(b)(2)).
    Second, CFS asserts that the Petran et al. study (Ref. 27), which
we cited in support of our conclusion that irradiation will not
increase the risk of botulism, did not involve irradiation of fresh
lettuce or fresh spinach, and therefore, did not address the safety
concern that irradiation may provide enhanced growing conditions for
radiation-insensitive pathogens due to the ``elimination'' of spoilage
and other

bacteria. CFS also objects to the final rule based on this study
because C. botulinum multiplies more rapidly on shredded cabbage than
romaine lettuce, asserting that this observation demonstrates that
pathogens can have markedly different growth patterns on different
vegetables, underscoring the illegitimacy of extrapolating from data on
one vegetable to another.
    The Petran et al. study (Ref. 27) assesses the potential for growth
and toxin production of heat-shocked C. botulinum spores in fresh-cut
romaine lettuce and shredded cabbage. While the produce was not
irradiated, the study was chosen because it offers a non-competitive
environment for C. botulinum elaboration, reflecting conditions that
would be generated if produce were irradiated in the presence of C.
botulinum spores. C. botulinum is a Gram-positive anaerobic
sporeformer, and this study examined the potential for outgrowth and
toxin production under conditions of temperature abuse in both aerobic
and anaerobic conditions. As stated in our microbiology memorandum,
there was no toxin production detected in either the vented or non-
vented packaging at 12.7 [deg]C (~55 [deg]F) or lower after 28 days.
Toxin was produced only under conditions of extreme temperature abuse
after all samples became unmistakably inedible, i.e., after 14 days at
21 [deg]C (~70 [deg]F). The study demonstrated that even under ideal
growth conditions for C. botulinum where the levels of native
microflora were greatly reduced, toxin production was not elaborated
until after the produce was clearly inedible. Moreover, CFS has not
presented evidence or a rationale that changes our conclusion that the
``growth and toxin expression by Gram-positive anaerobic sporeformers
would not present a likely additional hazard in this application of
irradiation.''
    CFS also objects to the use of the Petran et al. study because it
did not involve fresh lettuce or fresh spinach; rather, the study
explored the potential for growth and toxin production by C. botulinum
in samples of romaine lettuce and cabbage packaged in aerobic and
anaerobic conditions exposed to temperature abuse, which represent
ideal conditions for growth and toxin production by C. botulinum. CFS
uses the example of C. botulinum multiplying more rapidly on shredded
cabbage than on romaine lettuce as evidence that one cannot extrapolate
from data on one type of leafy green vegetable to draw conclusions
about other leafy green vegetables (i.e., fresh lettuce and fresh
spinach). We recognize that in the study, toxin was produced in the
non-vented cabbage sample after 7 days of storage at 21 [deg]C (nearly
70 [deg]F), a timeframe that was shorter than the timeframe for toxin
production in romaine lettuce. However, we do not agree that these
results indicate the illegitimacy of extrapolating data from one type
of leafy green vegetable to another leafy green vegetable. CFS fails to
note that all of the samples for which toxin production was observed
were clearly inedible prior to toxin production, and that toxin was not
produced for at least 28 days in any of the samples that were vented.
Indeed, the study demonstrated that it is extremely unlikely for an
anaerobic sporeformer to grow and produce toxin in lettuce products
that are handled properly (i.e., not stored at 70 [deg]F for 7 days)
and are of acceptable quality for consumption. Furthermore, all leafy
green vegetables (e.g., iceberg lettuce, spinach, romaine lettuce, and
cabbage) are grown and harvested under similar conditions and therefore
the probability of contamination with C. botulinum is similar. As
stated in the microbiology memorandum, this type of contamination is
unlikely. CFS did not provide any data to demonstrate that C. botulinum
has been identified as a hazard in green leafy vegetables or that the
likelihood of toxin production would be greater for either fresh
lettuce or fresh spinach than it is in romaine lettuce or cabbage. CFS'
objection did not include any new information or data that would call
into question our findings about this study. Accordingly, the
information provided by CFS, that the Petran et al. study did not
involve the irradiation of fresh lettuce or fresh spinach, is not
sufficient to call into question our determination that irradiating
fresh lettuce and fresh spinach up to a maximum dose of 4.0 kGy is
safe. We are therefore denying CFS' objection and request for a hearing
because the data and information submitted by CFS are insufficient to
justify the factual determination urged, even if accurate (Sec.
12.24(b)(3)).
    Further, it is important to note that the standards of
microbiological safety of fresh lettuce and fresh spinach are
independent of the final rule permitting the irradiation of fresh
lettuce and fresh spinach. Irradiation is just one potential control
contributing to the mitigation of food-borne pathogens, and its
intended technical effect is to reduce, not eliminate, spoilage and
pathogenic bacteria. Therefore, the final rule is not predicated on
irradiation, by itself, resulting in fresh lettuce and fresh spinach
that are pathogen-free.
    The final portion of the CFS objection contends that the our
microbiology memorandum contains contradictory statements, and
therefore, the question of whether the growth of C. botulinum or other
radiation-insensitive pathogens present on irradiated fresh lettuce or
fresh spinach would be enhanced by the suppression of competing
bacteria remains unanswered. CFS asserts that when discussing the
Petran et al. study, the microbiology memorandum states that the
spoilage microorganisms ``attain previous levels within days of
treatment,'' but when discussing the Zhang et al. study (2006) (Ref.
29), the memorandum states that ``relative reductions [in numbers of
viable bacteria during 9 days of storage] persisted . . .'' CFS
contends that these statements are contradictory and that our
conclusion that spoilage microorganisms ``attain previous levels within
days of treatment'' is erroneous.
    CFS' objection implies that both statements cannot be true and that
we misinterpreted the Zhang et al. study. However, we disagree that
either statement is false. The Zhang et al. study (Ref. 29) reported
substantially lower total bacterial counts for the irradiated samples
as compared to the unirradiated control on the same day. Our
microbiology memorandum's statement that ``relative reductions [in
numbers of viable bacteria during 9 days of storage] persisted . . .''
is, therefore, correct. However, while these lower levels of bacteria
persisted, the native microflora was also recovering as evidenced
through the increase in total bacterial counts over the storage period.
In the case of the 0.5 kGy and 1.0 kGy irradiation trials, bacterial
counts attained initial levels (i.e., the control level on day zero)
within days of treatment. For the 1.5 kGy sample, the total bacterial
counts did not reach the control level by the end of the 9-day storage
period, but the total bacterial counts increased as storage time
increased. The results of the 1.5 kGy sample therefore demonstrate the
veracity of both of the memorandum's statements: The native microflora
was able to recover and the substantially lower bacterial counts
persisted throughout the 9-day storage period. At the end of the 9-day
storage period, the unirradiated control was reported to have 7.60 Log
CFU/g \11\ or approximately 4 million colony forming units per gram,
which resulted in the spoilage of tissue. On the same day, the

sample irradiated at 1.5 kGy contained approximately 50 thousand colony
forming units per gram, which was lower than the unirradiated control,
but significantly larger than the nearly 200 colony forming units that
were present immediately following irradiation. Thus, the statements in
the microbiology memorandum are both correct, and we maintain that the
memorandum accurately and reliably reflects the information in the
cited publication. Accordingly, we are denying CFS' objection and
request for a hearing because the data and information submitted by CFS
are insufficient to justify the factual determination urged, even if
accurate (Sec.  12.24(b)(3)).
---------------------------------------------------------------------------

    \11\ The data were obtained by calculating the log of the colony
forming units per gram (LogCFU/g). Therefore, any whole number
reported is indicative of magnitude.
---------------------------------------------------------------------------

F. Fifth Numbered Objection: CFS' Contention That FDA Failed To
Consider Alternatives to Irradiation of Fresh Lettuce and Fresh Spinach

    CFS' final objection contends that we have failed to consider
alternatives to irradiation of fresh lettuce and fresh spinach.
However, we evaluate a particular food additive only for its safety.
Section 409(c)(1) of the FD&C Act requires FDA to establish a
regulation prescribing, with respect to one or more proposed uses of
the food additive involved, the conditions under which such additive
may be safely used. The FD&C Act does not require us to consider
alternatives as a factor in deciding whether to grant a food additive
petition. We evaluated the safety of irradiating fresh lettuce and
fresh spinach at a maximum dose not to exceed 4.0 kGy based on three
appropriate areas relevant to safety: (1) Potential toxicity; (2)
nutritional adequacy; and (3) effects on the microbiological profile of
the treated food. Based on the data and studies submitted in the
petition and other information in our files, we properly concluded that
the proposed use of irradiation to treat fresh lettuce and fresh
spinach with absorbed doses that will not exceed 4.0 kGy is safe.
Therefore, we are denying CFS' objection and request for a hearing
because CFS raises a factual issue that is not determinative with
respect to the action requested (e.g., the action would be the same
even if the factual issue were resolved in the way sought) (Sec.
12.24(b)(4)).

G. FWW's Assertion That FDA Failed To Address Potential Organoleptic
Degradation

    FWW submitted objections to the final rule in a letter dated
September 22, 2008, which concurred with objections put forth by CFS,
and included an additional objection. FWW asserts that there is a basis
to stay the approval of the final rule and to convene a public
evidentiary hearing on the issue of the quality of the irradiated
produce at the dose levels approved and whether there is technology
currently available to achieve the pathogen reduction desired while
still preserving the organoleptic properties of the produce. FWW
asserts that approval of this petition raises issues of safety and
deception to the consumer under section 409 of the FD&C Act because
irradiating fresh lettuce and fresh spinach at the petitioned doses may
result in organoleptic degradation and may not achieve pathogen
reduction.
    In support of its objection, FWW cites a 2008 study by Gomes et al.
(Ref. 30), which according to FWW, demonstrated that doses higher than
1 kGy were necessary to ensure elimination of food-borne pathogens from
bagged spinach leaves. Additionally, FWW quotes Dr. Mike Doyle,
Director of the Center for Produce Safety at the University of Georgia,
who stated that, ``in a commercial processing plant, products are
stacked in cartons for treatment, so the dose must be strong enough to
irradiate every part of the package and that could lead to some
products being `overly treated,' which could render the product
unappetizing.'' Thus, FWW asserts that pathogen reduction may require
strong irradiation doses that will result in organoleptic degradation.
    It appears from the objection that FWW has misinterpreted the
intended technical effect from irradiation of fresh lettuce and fresh
spinach to be the elimination of microbial contamination instead of the
control of microbial contamination, as stated in the final rule. FWW
provides no information to call into question our conclusions that the
irradiation of fresh lettuce and fresh spinach is safe and will achieve
the intended technical effect of controlling microbial contamination at
doses not to exceed 4.0 kGy. In addition, we acknowledge that
radiation-induced chemical changes, if sufficiently large, may cause
changes in the organoleptic properties of the food. However, such
organoleptic changes do not necessarily render the food unsafe, and FWW
has not provided any evidence that would establish a link between
organoleptic changes and the safety of irradiated foods. Moreover, food
processors have an incentive to minimize the extent of the chemical
changes in the food to avoid undesirable effects on taste, odor, color,
or texture. Therefore, we are denying FWW's objection and request for a
hearing because a hearing will not be granted on the basis of mere
allegations or denials or general descriptions of positions and
contentions (Sec.  12.24(b)(2)).
    FWW also asserted that irradiation is not effective against all
food-borne pathogens (e.g., viruses) and could lead consumers to an
incorrect conclusion that a product is safe even though it may still be
contaminated. While we recognize that irradiation is not effective
against viruses, the final rule permitting the irradiation of fresh
lettuce and fresh spinach up to a maximum dose of 4.0 kGy is not
predicated on the irradiation treatment eliminating all potential
pathogens. In the final rule, we concluded that the use of irradiation
up to a maximum dose of 4.0 kGy on fresh lettuce and fresh spinach was
safe. During the review, we considered chemical, toxicological,
nutritional, and microbiological effects resulting from the application
of ionizing radiation to fresh lettuce and fresh spinach. It was
demonstrated that the petitioned use of irradiation would not raise
safety concerns and that the treatment achieved its intended technical
effects (i.e., reduction of microorganisms and extension of shelf
life). Therefore, we are denying FWW's objection and request for a
hearing. FWW has not provided any evidence to demonstrate that the
final rule would lead consumers to an incorrect conclusion that a
product is safe even though it may still be contaminated; a hearing
will not be granted on the basis of mere allegations or denials or
general descriptions of positions and contentions (Sec.  12.24(b)(2)).
In addition, FWW's assertion that irradiation is not effective against
all food-borne pathogens is not determinative with respect to the
action requested; a hearing will not be granted unless resolution of
the factual issue in the way sought is adequate to justify the action
requested (Sec.  12.24(b)(4)).

V. Summary and Conclusion

    Section 409 of the FD&C Act requires that a food additive be shown
to be safe before marketing. Under 21 CFR 170.3(i), a food additive is
``safe'' if ``there is a reasonable certainty in the minds of competent
scientists that the substance is not harmful under the intended
conditions of use.'' In our August 22, 2008, final rule approving the
use of irradiation of fresh lettuce and fresh spinach up to a maximum
dose of 4.0 kGy, we concluded, based on our evaluation of the data
submitted in the petition and other relevant material, that the
petitioned use of irradiation is safe for its intended use for the
control of food-borne pathogens and extension of shelf life in fresh
lettuce and fresh spinach.

    The petitioner has the burden to demonstrate the safety of the
additive to gain FDA approval. However, once we make a finding of
safety in an approval document, the burden shifts to an objector, who
must come forward with evidence that calls into question our conclusion
(see section 409(f)(1) of the FD&C Act).
    CFS and FWW have not established that we overlooked or
misinterpreted significant information in the record to reach our
conclusion that the use of irradiation up to a maximum dose of 4.0 kGy
for control of food-borne pathogens and extension of shelf life in
fresh lettuce and fresh spinach is safe. Therefore, we have determined
that the final rule should not be modified or revoked based on the
objections. We are also denying the requests for a hearing because the
objections do not meet the standard for granting a hearing as discussed
in this document. In addition, FWW's request for a stay of the
effectiveness of the August 22, 2008, regulation until a hearing is
held is moot because we are denying all hearing requests. Thus, we are
confirming August 22, 2008, as the effective date of the regulation.

VI. 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 (HFA-305), Food and Drug Administration, 5630
Fishers Lane, Rm. 1061, Rockville, MD 20852, under Docket No. FDA-1999-
F-2405 (formerly 1999F-5522) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday, and are available
electronically at http://www.regulations.gov. References without
asterisks are not on display; they are available as published articles
and books.

1. WHO, ``Safety and Nutritional Adequacy of Irradiated Food,''
World Health Organization, Geneva, 1994.
*2. Memorandum for FAP 9M4697 from A. Edwards, FDA, to L.
Highbarger, FDA, dated July 16, 2008.
3. 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.
4. Institute of Medicine, Dietary Reference Intakes for Vitamin C,
Vitamin E, Selenium, and Carotenoids, National Academies Press, DC,
2000.
*5. Cotton, P. A., A. F. Subar, J. E. Friday, et al., ``Dietary
Sources of Nutrients Among U.S. Adults, 1994 to 1996,'' Journal of
the American Dietetic Association, 104:921-930, 2004.
6. FAO/IAEA/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.
*7. Memorandum to the file, FAP 4M4428, D. Hattan, Acting Director,
Division of Health Effects Evaluation, dated November 20, 1997.
*8. Hajare, S. C., V. S. Dhokane, R. Shashidhar, et al., ``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-S203,
2006.
9. Diehl, J. F., ``Nutritional Adequacy of Irradiated Foods,'' pp.
241-290 in Safety of Irradiated Foods, 2nd ed., Marcel Dekker, Inc.,
New York, 1995.
*10. Castenmiller, J. J. M., C. J. van de Poll, C. E. West, et al.,
``Bioavailability of Folate From Processed Spinach in Humans,''
Annals of Nutrition & Metabolism, 44:163-169, 2000.
*11. Semba, R. D. and G. Dagnelie, ``Are Lutein and Zeaxanthin
Conditionally Essential Nutrients for Eye Health?'' Medical
Hypotheses, 61(4):465-472, 2003.
*12. M[uuml]ller, H. and J. F. Diehl, ``Effect of Ionizing Radiation
on Folates in Food,'' Lebenson Wiss Technology-Food Science and
Technology, 29(1-2):187-190, 1996.
*13. Knapp, F. W. and A. L. Tappel, ``Comparison of the
Radiosensitivities of the Fat-Soluble Vitamins by Gamma
Irradiation,'' Agriculture and Food Chemistry, 9(6):430-433, 1961.
*14. Richardson, L. R., S. Wilkes, and S. J. Ritchey, ``Comparative
Vitamin K Activity of Frozen, Irradiated and Heat-Processed Foods,''
Journal of Nutrition, 73:369-373, 1961.
*15. Richardson, L. R., P. Woodworth, and S. Coleman, ``Effect of
Ionizing Radiation on Vitamin K,'' Federation Proceedings,
15(3):924-926, 1956.
*16. Metta, V. C., M. S. Mameesh, and B. C. Johnson, ``Vitamin K
Deficiency in Rats Induced by Feeding of Irradiated Beef,'' Journal
of Nutrition, 69:18-22, 1959.
*17. Hirayama, K., K. Uetsuka, Y. Kuwabara, et al., ``Vitamin K
Deficiency of Germfree Mice Caused by Feeding Standard Purified Diet
Sterilized by [gamma]-Irradiation,'' Experimental Animals,
56(4):273-278, 2007.
18. Diehl, J. F., ``Chemical Effects of Ionizing Radiation,'' pp.
43-88 in Safety of Irradiated Foods, 2nd ed., Marcel Dekker, Inc.,
New York, 1995.
19. Combs, G. F. Jr., The Vitamins. 3rd ed. Burlington: Elsevier
Academic Press, 2008.
20. FAO/WHO, ``Human Vitamin and Mineral Requirements,'' Report of a
Joint Food and Agriculture Organization/World Health Organization
Expert Consultation, Bangkok, Thailand. Rome: FAO/WHO, 2002.
*21. Booth, S. L. and J. W. Suttie, ``Dietary Intake and Adequacy of
Vitamin K,'' Journal of Nutrition, 128:785-788, 1998.
22. WHO IARC, ``Vitamin K Substances,'' IARC Monographs on the
Evaluation of Carcinogenic Risks to Humans, vol. 76, World Health
Organization, Lyon, France, 2001.
23. FAO/IAEA/WHO, ``High Dose Irradiation: Wholesomeness of Food
Irradiated With Doses Above 10kGy: Report of a Joint FAO/IAEA/WHO
Study Group,'' World Health Organization Technical Report Series,
No. 890, World Health Organization, Geneva, pp. 9-37, 1999.
24. Thayer, D. W., J. B. Fox, Jr., and L. Lakritz, ``Effects of
Ionizing Radiation on Vitamins.'' In: Thorne S., editor. Food
Irradiation. London: Elsevier Applied Science; pp. 285-325, 1991.
25. Thomas, M. H., ``Use of Ionizing Radiation to Preserve Food.''
In: Karmas, E. and R.S. Harris, editors. Nutritional Evaluation of
Food Processing. 3rd ed.: New York: Van Nostrand Reinhold; pp. 457-
501, 1988.
*26. Lucier, G., J. Allshouse, and B.-H. Lin, ``Factors Affecting
Spinach Consumption in the United States,'' USDA Economic Research
Service, VGS-300-01, January 2004.
*27. 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(6):624-627, 1995.
*28. Memorandum for FAP 9M4697 from R. Merker, FDA, to L.
Highbarger, FDA, dated June 11, 2008.
*29. Zhang, L., Z. Lu, F. Lu, et al., ``Effect of [gamma]
Irradiation on Quality-Maintaining of Fresh-Cut Lettuce,'' Food
Control, 17:225-228, 2006.
*30. Gomes, C. D., R. G. Moreira, M. E. Castell-Perez, et al., ``E-
Beam Irradiation of Bagged, Ready-to-Eat Spinach Leaves (Spinacea
oleracea): An Engineering Approach,'' Journal of Food Science,
73(2):E95-E102, 2008.

    Dated: February 19, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-03976 Filed 2-24-14; 8:45 am]
BILLING CODE 41640-01-P