[Federal Register Volume 76, Number 55 (Tuesday, March 22, 2011)]
[Rules and Regulations]
[Pages 15841-15852]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-6625]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 179

[Docket No. FDA-1999-F-0056; Formerly Docket No. 1999F-4372]


Irradiation in the Production, Processing, and Handling of Food; 
Confirmation of Effective Date

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule; denial of requests 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) is denying requests for 
a hearing on the final rule that amended the food additive regulations 
to provide for the safe use of ionizing radiation for the control of 
Vibrio species and other foodborne pathogens in fresh or frozen 
molluscan shellfish. After reviewing objections to the final rule and 
requests for a hearing, FDA has concluded that the objections do not 
justify a hearing or otherwise provide a basis for revoking the 
regulation. FDA also is denying the request for a stay of the effective 
date of the amendment to the food additive regulations.

DATES: The August 16, 2005, effective date for the final rule published 
at 70 FR 48057 is confirmed.

FOR FURTHER INFORMATION CONTACT: Lane A. Highbarger, Center for Food 
Safety and Applied Nutrition (HFS-255), Food and Drug Administration, 
5100 Paint Branch Pkwy., College Park, MD 20740, 301-436-1204.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Introduction
II. Objections, Requests for a Hearing, and Requests for a Stay
III. Standards for Granting a Hearing
IV. Analysis of Objections and Response to Hearing Requests
    A. Studies on Animals Fed Clams
    B. Microbiological Safety of Molluscan Shellfish
    C. Reasonable Certainty of No Harm
    D. Factors Unique to Molluscan Shellfish
    E. Application of 100-Fold Safety Margin for 2-
Alkylcyclobutanones
    F. Alleged Rejection of Published Evidence
    G. Alleged Warnings on Potential Risks
    H. Alleged Failure to Follow Critical Guidelines for Food 
Additives
    I. Wholesomeness
    J. FDA Review Memoranda
    K. Chemicals Formed in Irradiated Foods
V. Summary and Conclusion
VI. References

I. Introduction

    FDA published a notice in the Federal Register of October 19, 1999 
(64 FR 56351), announcing the filing of a food additive petition (FAP 
9M4682) by the National Fisheries Institute and the Louisiana 
Department of Agriculture and Forestry. In the Federal Register of 
August 16, 2005 (70 FR 48057), FDA issued a final rule permitting the 
irradiation of fresh or frozen molluscan shellfish for the control of 
Vibrio spp. and other food-borne pathogens. FDA based its decision on 
data in the petition and in its files. In the preamble to the final 
rule, FDA outlined the basis for its decision and responded to 
questions raised in several comments from Public Citizen and the Center 
for Food Safety (PC/CFS). The preamble to the final rule advised that 
objections to the final rule and requests for a hearing were due within 
30 days of the publication date (i.e., by September 15, 2005).

II. Objections, Requests for a Hearing, and Requests for a Stay

    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 therefore, and requesting a public hearing 
upon such objections.''
    Under part 171 (21 CFR part 171) in Sec.  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 or frozen molluscan shellfish for the

[[Page 15842]]

control of Vibrio spp. and other food borne pathogens, FDA received 
numerous submissions within the 30-day objection period. All but two of 
these timely submissions express general opposition to the final rule, 
and are form letters urging the FDA to conduct additional studies on 
irradiating molluscan shellfish specifically and food in general. 
Although most of these letters request a hearing, no evidence is 
identified in support of these objections that could be considered in 
an evidentiary hearing (Sec.  12.22(a)(5)). Therefore, they have waived 
their right to a hearing. The Agency will not discuss these submissions 
further. FDA received two submissions that met the requirements of 
Sec.  12.22(a), One of these two submissions is a letter sent jointly 
by PC/CFS containing 10 numbered objections to the final rule and 
requesting a hearing on each one. The second is a letter sent by Samuel 
Epstein (Dr. Epstein), containing six numbered objections, requesting a 
hearing on each. All but one of the issues raised by Dr. Epstein are 
identical to certain of those raised in the PC/CFS submission. Both PC/
CFS and Dr. Epstein also requested a stay of action on the final rule. 
FDA addresses the PC/CFS and Dr. Epstein objections and hearing 
requests in section IV of this document.
    FDA also received a large number of submissions after the close of 
the objection period; their content was identical or similar to the 
form letters expressing general opposition to the final rule. These 
tardy submissions failed to satisfy the requirements of 21 U.S.C. 
348(f)(1) and need not be considered further by the Agency (see ICMAD 
v. HEW, 574 F.2d 553, 558 n.8 (DC Cir), cert. denied, 439 U.S. 893 
(1978)).
    Additionally, most of the issues raised in the PC/CFS and Dr. 
Epstein objections are similar or identical to issues that have been 
raised previously and that have been previously addressed in the rule 
being objected to (70 FR 48057) and in other Agency rulemaking 
concerning irradiation. The Agency will address these issues briefly; 
please refer to the cited Federal Register documents for a more 
comprehensive discussion.

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 
requestor; 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. 
Pacific Legal Foundation, 445 U.S. 198, 214-215 (1980), reh. denied, 
446 U.S. 947 (1980), citing Weinberger v. Hynson, Westcott & Dunning, 
Inc., 412 U.S. 609, 620-621 (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)). If a hearing request fails to identify any 
factual evidence that would be the subject of a hearing, there is no 
point in holding one. 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 Rule 56, Federal 
Rules of Civil Procedure). The same principle applies in administrative 
proceedings (see Sec.  12.28).
    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 Association 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, the 
Agency 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)). FDA need not grant a hearing in each case where an objector 
submits additional information or posits a novel interpretation of 
existing information (see United States v. Consolidated Mines & 
Smelting Co., 455 F.2d 432 (9th Cir. 1971)). In other words, 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 (9th 
Cir. 1977)). Finally, courts have uniformly recognized that 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 (DC Cir. 1969); Sun Oil 
Co. v. FPC, 256 F.2d 233, 240 (5th Cir.), cert. denied, 358 U.S. 872 
(1958)).
    Even if the objections raise material issues of fact, FDA 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 can be validly applied to the administrative 
process. In explaining why these principles ``self evidently'' 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 a fair 
opportunity.'' Retail Clerks Union, Local 1401 v. NLRB, 463 F.2d 316, 
322 (DC Cir. 1972). (See Costle v. Pacific Legal Foundation, supra at 
215-220. See also Pacific Seafarers, Inc . v. Pacific Far East Line, 
Inc., 404 F.2d 804 (DC Cir. 1968), cert. denied, 393 U.S. 1093 (1969)).

IV. Analysis of Objections and Response to Hearing Requests

    The letter from PC/CFS contains 10 numbered objections and requests 
a hearing on each of them. The letter from Dr. Epstein includes six 
numbered objections and requests a hearing on each. The issues raised 
in five of the six objections in the letter from Dr. Epstein are 
identical to issues raised in the letter from PC/CFS; in those cases, 
the issues will be considered together. FDA addresses each of the 
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) as 
follows:.

A. Studies on Animals Fed Clams

    One objection raised by PC/CFS and Dr. Epstein states that the 
Agency failed

[[Page 15843]]

to consider two animal feeding studies that include toxicological 
evidence of harmful effects from consumption of irradiated molluscan 
shellfish. In support of this objection, PC/CFS submitted copies of 
brief summary reports of the two studies.
    The first study is a 1976 reproduction study \1\ in which 
irradiated (4 kiloGray (kGy) and 8 kGy) soft-shell clams were fed to 
chickens for 2 years. In a note appended to the summary report, the 
study authors state that the study was replicated (for differing 
durations) in the F1 and F2 generation birds (i.e., the second and 
third generation birds bred from the parent generation used in the 
original study). The objection notes that FDA did not include this 
study on chickens in the Agency's September 15, 1982, master 
bibliography of more than 400 studies on the safety of irradiated foods 
and, that therefore, this study was not assessed by the Task Group for 
the Review of Toxicology Data on Irradiated Food.\2\
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    \1\ Fegley, H.C. and Edmonds, R.E., in Food Irradiation 
Information, International Project in the Field of Food Irradiation, 
Karlsuhe, Germany, No. 6 (Supplement), 113-115, June 1976.
    \2\ The Bureau of Foods Irradiated Food Task Group consisted of 
toxicologists in the Bureau of Foods who reviewed many studies on 
food irradiation in the early 1980s.
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    The objection goes on to describe certain of the reported results 
from the study on chickens, specifically results in the F1 and F2 
generations, including the following: Higher hemoglobin values and 
smaller gonad weights in males of the F1 generation fed irradiated 
clams; and a decrease in ``hatchability'' of eggs, enlargement of 
kidneys in females (an effect that increased with increasing 
irradiation dose), decreases in egg fertility and embryonic viability, 
and lower body weights in females, in the F2 generation.
    FDA acknowledges that this study was not included in the inventory 
of studies reviewed by the Bureau of Foods Irradiated Food Task Group 
in the early 1980s, and agrees that the endpoints cited in the 
objection were reported by the study authors. However, the Agency does 
not agree that FDA's failure to assess the study calls into question 
the safety of irradiated molluscan shellfish, as the objectors contend. 
The objection fails to note that many of the findings cited in the 
experimental report were observed both in chickens fed irradiated clams 
and in chickens fed unirradiated clams, and that the report discusses 
the need to supplement the diets of the clam-fed chickens with 
thiamine. Therefore, the observed effects may have been related to the 
nutritional effects of feeding diets consisting of 50 percent wet-
weight of soft-shell clams to chickens. More importantly, if the 
negative effects cited by the objectors were due to the consumption of 
irradiated food, one would expect the findings to be reproducible in 
other studies on irradiated foods; however, such reproducibility is not 
seen in the large number of feeding studies that have been reviewed by 
FDA.
    The objection also cites a second paper by the same researchers \3\ 
describing a study on feeding clams irradiated at 4 kGy or 8 kGy to 
beagle dogs. According to the objection, the study showed a significant 
inverse correlation between the irradiation dose applied to the clams 
and the blood urea nitrogen (BUN) level of male dogs fed on them. PC/
CFS and Dr. Epstein both go on to state that ``[t]hough the researchers 
did not speculate, low blood urea nitrogen levels are usually a symptom 
of liver damage.''
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    \3\ Fegley, H.C. and Edmonds, R.E., in Food Irradiation 
Information, International Project in the Field of Food Irradiation, 
Karlsruhe, Germany, No. 6 (Supplement), 111-112, June, 1976.
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    The Agency included this beagle dog study in the review of 
toxicology studies conducted in the early 1980s. The FDA reviewer noted 
the reported BUN results and also noted that, although the researchers 
indicated that organs were weighed and examined histopathologically, no 
results of the histopathological examination were included in the 
report. This suggests that the researchers did not find any evidence of 
liver (or other organ) damage, and in fact the study report includes no 
information that supports the objectors' contention that liver damage 
was an underlying condition in the animals tested. Furthermore, the 
Agency, as part of its rulemaking pertaining to the irradiation of meat 
and meat products, re-examined the findings reported in this study. As 
stated in the December 3, 1997, final rule (62 FR 64107 at 64113), FDA 
concluded that the decrease in BUN levels in this study was not of 
toxicological significance, and laid out its reasoning in that document 
and in a memorandum to the record (Ref. 1). Thus, the Agency disagrees 
with PC/CFS' and Dr. Epstein's contention that this study ``* * * found 
serious toxicity concerns associated with irradiated molluscan 
shellfish.''
    A hearing will be denied if the data and information are 
insufficient to justify the factual determination urged, even if 
accurate (Sec.  12.24(b)(3)). FDA concludes the data and information 
are insufficient and, therefore, FDA is denying the request for a 
hearing on this issue.

B. Microbiologic Safety of Molluscan Shellfish

    PC/CFS' second objection asserts that the final rule fails to 
ensure that the irradiation of molluscan shellfish will result in a 
product that is microbiologically safe. In support of this objection, 
PC/CFS cites a 1996 PhD dissertation by Dustin W. Dixon on the effects 
of irradiation on Vibrio vulnificus in shellstock oysters (raw oysters 
in their shell) harvested in Florida and Texas (Ref. 2). The objection 
states that there is a potential for microbial outgrowth post-
irradiation, and cites Dixon's observation that the V. vulnificus count 
in oysters irradiated at 1.0 kGy and 3.0 kGy rose nearly to the level 
of that in unirradiated oysters after 2 and 9 days of storage, 
respectively. The objection states that Dixon concluded that ``* * * 
irradiation processing cannot be considered as a method to sterilize 
shellstock oysters, and provide a shelf-stable product.''
    The objection also notes the potential for improper temperature 
control of irradiated molluscan shellfish prior to consumption by the 
consumer. The objection states that there is no guarantee that 
temperature conditions will be properly maintained and asserts that FDA 
is assuming that Hazard Analysis and Critical Control Point (HACCP) 
plans \4\ will ensure consistent and adequate temperature control.
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    \4\ FDA has established regulations for seafood HACCP in 21 CFR 
part 123.
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    As noted by PC/CFS, the Dixon dissertation was submitted to the 
Agency as part of the molluscan shellfish petition. The stated 
objectives of the research presented in that document were to determine 
the effects of gamma irradiation on Florida and Texas shellstock 
oysters in terms of shelf life and microbial consequences. FDA does not 
dispute the findings of Dr. Dixon, and agrees that irradiation of 
molluscan shellfish to an absorbed dose of 5.5 kGy will not sterilize 
molluscan shellfish or create a shelf-stable product. FDA also agrees 
with Dr. Dixon's conclusion in his dissertation that irradiation may 
not be sufficient by itself to eliminate V. vulnificus in molluscan 
shellfish and that proper conditions of storage must be maintained 
after shellfish have been irradiated.
    FDA disagrees, however, with PC/CFS' assertion that the final rule 
must ``[en]sure the microbiological safety of fresh oysters.'' The 
standards for microbiological safety of molluscan

[[Page 15844]]

shellfish are independent of the final rule permitting the irradiation 
of molluscan shellfish. Irradiation is but one measure for the control 
of Vibrio spp. and other food-borne pathogens. The rule is not 
predicated on the approved treatment, by itself, resulting in shellfish 
that are sterile or shelf-stable. A hearing will not be granted on 
factual issues that are not determinative with respect to the action 
requested (Sec.  12.24(b)(4)). Therefore, FDA is denying the request 
for a hearing based on this objection.

C. Reasonable Certainty of No Harm

    PC/CFS' third objection states that ``there is no reasonable 
certainty in the minds of competent scientists that irradiation is not 
harmful as applied to molluscan shellfish.'' In support of this 
objection, PC/CFS makes several assertions. First, PC/CFS refers to 
several sets of comments that it submitted to the docket for the 
molluscan shellfish rulemaking. PC/CFS states that those comments cite 
11 ``peer-reviewed papers or other publications stating safety concerns 
associated with irradiated foods'' and that these comments refer to 
``at least 25 other highly `competent' Ph.D.s or MDs who have stated 
that they have safety concerns in published literature.'' The objection 
states that, although these comments and papers refer to irradiation of 
food types other than molluscan shellfish, the Agency should have 
specifically considered the statements of these authors. Second, PC/CFS 
asserts that FDA misstated what is contained in its literature 
reference numbered as ``Ref 20'' in the final rule. Third, PC/CFS, as 
well as Dr. Epstein, asserts that FDA mischaracterized the findings of 
the Raltech study. In support of this assertion, PC/CFS submitted a 
copy of two summary reports from the ``Raltech studies'' and a 1984 
trade press article that quotes Dr. Thayer of USDA. Finally, PC/CFS 
states that neither FDA's final rule nor the underlying petition 
actually contains data from, or references to, any toxicity studies on 
irradiated mollusks.
    As evidence that there is not a ``reasonable certainty of safety in 
the minds of competent scientists'' PC/CFS notes that they have 
submitted comments including journal articles and other publications 
that express concerns with food irradiation. However, the articles do 
not contain any evidence that could be resolved at a hearing, nor has 
PC/CFS pointed to any evidence in the cited articles. Nor has PC/CFS 
pointed to any specific factual information in the cited articles on 
foods analogous to molluscan shellfish, which the Agency has ignored 
and which would call into question the Agency's conclusions. A hearing 
will not be granted on the basis of mere allegations or general 
descriptions of positions and contentions (Sec.  12.24(b)(2)). 
Therefore, FDA is denying the request for a hearing based on this 
objection.
    The Agency agrees that reference 20 as cited in the final rule is 
incorrect. The proper reference is: S.G. Armstrong, S.G. Wylie, and D. 
N. Leach, ``Effects of Preservation by Gamma Irradiation on the 
Nutritional Quality of Australian Fish,'' Food Chemistry 50 (1994) 351-
357. This error does not demonstrate a lack of reasonable certainty of 
safety. A hearing will be denied if the information submitted is 
insufficient to justify the factual determination urged (Sec.  
12.24(b)(3)).
    The Agency disagrees with PC/CFS' and Dr. Epstein's assertion that 
the final rule mischaracterizes the findings of the ``Raltech study.'' 
The Raltech studies were sponsored by the United States Department of 
Agriculture and conducted by Raltech Scientific Services. In this 
series of studies, conducted in the late 1970s and early 1980s, 
irradiation-sterilized chicken (doses ranged from 45-59 kGy) was fed to 
various types of animals. PC/CFS alleges that there were several 
negative health effects seen in these studies, including a significant 
dose-related decrease in the number of offspring of Drosophila 
melanogaster (fruit flies), and a high incidence of testicular tumors 
and significantly reduced survival in mice.
    The Agency evaluated the results of the Raltech studies and has 
extensively discussed its conclusions regarding these studies in 
previous rulemaking documents (see 51 FR 13376 at 13386, 53 FR 53176 at 
53188, and 55 FR 18538 at 18540). The Agency specifically discussed the 
results of the feeding study in mice and the mutagenicity study in 
fruit flies (see, e.g., 55 FR 18538 at 18540). The Agency has described 
its reasoning in finding no evidence in any of the Raltech studies of 
adverse effects that could be attributed to consumption of irradiation-
sterilized chicken. The Agency has found that the quantity and breadth 
of testing and the number and significance of endpoints assessed would 
have identified meaningful risks, if any existed. On those few 
occasions where adverse effects were reported, FDA found that those 
effects were not attributable to irradiation. PC/CFS does not submit or 
otherwise identify any factual data that would cause the Agency to 
alter its conclusions about these studies. Accordingly, FDA is denying 
the request for a hearing based on this objection (Sec.  12.24(b)(2)).
    Finally, the Agency agrees that there were no toxicological studies 
conducted using irradiated molluscan shellfish submitted in the 
petition. As noted in the molluscan shellfish final rule (70 FR 48057 
at 48068), the Agency has reviewed a large body of data that are 
relevant to the assessment of the potential toxicity of irradiated 
flesh foods. FDA has 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 part 170 (21 
CFR part 170) in Sec.  170.20). For example, in the case of food 
irradiation, the Agency has taken advantage of the extensive research 
and large body of knowledge concerning the principles of radiation 
chemistry and the chemical composition of foods. PC/CFS' suggestion 
that data and information derived from studies of analogous irradiated 
foods are not sufficient to support a determination that irradiated 
molluscan shellfish are safe, is unsupported by specific data or other 
factual information. Further, the question of whether safety has been 
shown requires the application of the legal standard of safety as 
defined by FDA's regulations (``reasonable certainty of no harm'') to a 
set of facts (see Sec.  170.3(i)). As such, FDA concluded as a matter 
of law that the proposed use of irradiation to treat fresh and frozen 
molluscan shellfish with absorbed doses not to exceed 5.5 kGy is safe. 
A hearing will not be granted on issues of policy or law (Sec.  
12.24(b)(1)). Therefore, FDA is denying the request for a hearing based 
on this objection.

D. Factors Unique to Molluscan Shellfish

    PC/CFS objects to the molluscan shellfish final rule on the grounds 
that the Agency and the underlying petition failed to consider several 
factors that could make irradiated molluscan shellfish unsafe. These 
factors are: (1) Safety of irradiated salt water; (2) chemicals that 
irradiated molluscan shells may `off-gas' \5\; (3) effects of 
irradiation on undigested shellfish stomach contents such as plankton 
and algae; (4) attenuation of irradiation effects from shell thickness 
(i.e., that thicker shells may attenuate the effectiveness of 
irradiation); and (5) lack of data on furan creation from the shells. 
Dr. Epstein also objects on the basis of the issues relating to 
chemical byproducts from irradiated molluscan

[[Page 15845]]

shells, and the attenuation of irradiation effects from shell 
thickness.
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    \5\ ``Off-gassing'' refers to volatile chemicals that may be 
emitted over time from a source.
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    First, the Agency notes that there is no basis to suggest that the 
presence of salts in water will affect the irradiation of molluscan 
shellfish because ionizing radiation, under the petitioned conditions, 
does not affect inorganic salts (Ref. 3). Second, the objection 
provides no information to show that mollusk shells (composed of 
approximately 95 percent calcium carbonate and 5 percent protein), when 
irradiated, would produce any chemicals that may off-gas into the meat, 
nor is there any information to suggest that such chemicals, were they 
to be formed, would render the food unsafe. Third, the objection 
provides no evidence that the stomach contents of irradiated molluscan 
shellfish are materially different from any other irradiated food 
(i.e., composed predominantly of protein, fat, and carbohydrate). 
Fourth, the Agency agrees that varying shell thickness may attenuate 
the effectiveness of irradiation, and that this attenuation would 
increase with shell thickness. However, the objection provides no 
evidence that would cause the Agency to find that consumption of 
irradiated molluscan shellfish is not safe. As explained in section 
IV.B of this document, it is not necessary that irradiation ``[en]sure 
the microbiological safety of fresh oysters.'' Parties irradiating 
molluscan shellstock are responsible for ensuring that treated food 
receives the minimum irradiation dose reasonably required to accomplish 
its intended technical effect and not more than the maximum dose 
specified by the applicable regulation (see 21 CFR 179.25(b)) . 
Finally, the Agency discussed the potential generation of furan in the 
final rule (70 FR 48057 at 48059) and concluded that irradiated 
molluscan shellfish do not generate furan at a rate that is higher than 
the background generation of furan in un-irradiated molluscan shellfish 
(Ref. 4). Although in the final rule the Agency cited data concerning 
furan formation from shucked oysters, the objection points to no 
factual data to suggest that irradiation of mollusks in the shell 
(which is approximately 95 percent calcium carbonate) would lead to 
furan formation from irradiation of the shell.
    A hearing will not be granted on the basis of mere allegations or 
general descriptions of positions and contentions (Sec.  12.24(b)(2)). 
Neither PC/CFS nor Dr. Epstein has provided a basis for a hearing and 
FDA is denying the request for a hearing on this objection.

E. Application of 100-Fold Safety Margin for 2-Alkylcyclobutanones

    PC/CFS and Dr. Epstein cite 21 CFR 170.22 \6\ and object to the 
molluscan shellfish final rule (70 FR 48057) on the basis that FDA 
improperly failed to apply a 100-fold safety factor regarding the 
production of 2-alkylcyclobutanones (2-ACBs) from the irradiation of 
esterified fatty acids in considering the safety of irradiated 
molluscan shellfish. In support of their contention that the Agency 
should have applied a 100-fold safety factor to 2-ACBs, PC/CFS and Dr. 
Epstein make several assertions. First, the objection asserts that 2-
ACBs are found only in irradiated foods and are known to be potentially 
toxic at certain concentrations and to promote tumor formation in the 
presence of known carcinogenic substances. The objection also asserts 
that the flesh of molluscan shellfish is distinct from that of other 
flesh foods because it contains a ``unique combination'' of fatty acids 
and that these fatty acids, when irradiated, produce a unique 
combination of 2-ACBs. The objection, therefore, maintains that FDA's 
reliance on the Raltech study to address concerns about 2-ACBs is 
flawed because that study involved chicken which has a lower stearic 
acid content than oysters. Finally, the objection asserts that ``there 
are no adequate long-term safety studies that assist in assessing the 
overall health hazards that consuming 2-ACBs could pose, including 
likely variations in sensitivities to 2-ACBs among the human consumer 
population'' and refers particularly to children and other vulnerable 
populations. In relation to this last point, PC/CFS submitted a 
publication on the susceptibility of children to environmental 
substances by William Au.\7\
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    \6\ That section provides in relevant part that ``[e]xcept where 
evidence is submitted which justifies use of a different safety 
factor, a safety factor in applying animal experimentation data to 
man of 100 to 1, will be used. * * *'' 21 CFR 170.22.
    \7\ Au, W., Susceptibility of Children to Environmental Toxic 
Substances, International Journal of Hygiene Environmental Health; 
205:1-3, 2002.
---------------------------------------------------------------------------

    The applicability of Sec.  170.22 is a legal issue, and a hearing 
will not be granted on issues of law. The Agency notes that Sec.  
170.22 refers to safety factors to be used in determining whether a 
proposed use of a food additive will be safe. In the present instance, 
2-ACBs are not the food additive that is the subject of the rulemaking. 
Therefore, the 100-fold safety factor discussed in Sec.  170.22 does 
not apply to 2-ACBs. Further, as noted in the molluscan shellfish final 
rule (70 FR 48057 at 48066), applying a 100-fold safety factor to a 
processed food or to individual components of a processed food is not 
feasible or appropriate.
    The Agency agrees that 2-ACBs have been reported to be formed in 
small quantities as a result of irradiation of fats and that these 
compounds have been identified in irradiated meat and poultry. In the 
final rule permitting the irradiation of molluscan shellfish, the 
Agency described in detail its assessment of the significance of the 
formation of 2-ACBs to a safety assessment of molluscan shellfish, 
which like poultry and meat, contain appreciable amounts of 
triglycerides. This assessment included a discussion of the contentions 
that 2-ACBs may cause DNA damage and may be tumor promoters at certain 
concentrations (70 FR 48057 at 48065 to 48067). While the objection 
repeats assertions made in comments to the final rule about the 
toxicity of 2-ACBs and the failure of the Agency to apply a 100-fold 
safety factor for 2-ACBs, the objection includes no new information or 
analysis that would call into question the Agency's rationale for its 
decision.
    The objection states that molluscan shellfish contain a unique 
combination of fatty acids that differ from those in poultry, and that 
therefore, the Agency's reliance on the Raltech study to address 
concerns about 2-ACBs is flawed. In particular, the objection states 
that chicken meat contains less stearic acid than do oysters. It is 
true that the Agency considers the Raltech studies useful in assessing 
the effects of 2-ACBs in animals fed irradiated flesh foods (70 FR 
48057 at 48066). In the Raltech studies, animals were fed chicken 
irradiated at a dose approximately 10 times the dose permitted in the 
molluscan shellfish final rule, at a level of 35 percent of the diet, 
for their lifetime. Thus, although the concentration of stearic acid in 
chickens is lower than in molluscan shellfish, the amount of 2-ACBs in 
the diets of the animals in the Raltech studies, including those formed 
from irradiation of stearic acid is likely to be higher than the amount 
in the human diet from irradiated molluscan shellfish (70 FR 48057 at 
48066). As noted previously, there were no adverse toxicological 
effects seen in the Raltech studies that could be attributed to the 
consumption of irradiated chicken. In addition, it is important to note 
that the Agency has not relied solely on the Raltech studies in 
concluding that irradiation of molluscan shellfish under the conditions 
permitted in the final rule is safe. As pointed out in the final rule 
(70 FR 48057 at 48066), the Agency's review included studies in which 
animals were

[[Page 15846]]

fed diets containing irradiated beef, pork, poultry, horse meat, and 
fish, and found no evidence of toxicity attributed to the consumption 
of these foods, which contain various levels and combinations of fatty 
acids that may potentially form 2-ACBs. The objection has thus 
misrepresented the basis for the Agency's decision when it contends 
that the final rule relies on the Raltech studies to discount concerns 
about 2-ACBs in irradiated molluscan shellfish.
    In the molluscan shellfish final rule, the Agency noted that it had 
reviewed a multitude of studies on irradiated foods that would have 
contained radiolytic products including 2-ACBs, and which include long-
term safety studies. FDA noted that it had previously concluded that 
``The results of the available toxicological studies of irradiated 
flesh foods * * * demonstrate that a toxicological hazard is highly 
unlikely because no toxicologically significant adverse effects 
attributable to consumption of irradiated flesh foods were observed in 
any of these studies'' (62 FR 64107 at 64114). Although the objection 
alleges that there are no ``adequate long-term safety studies that 
assist in assessing the overall health hazards that consuming 2-ACBs 
could pose,'' the objection provides no factual information to call 
into question the studies on which the Agency has relied, nor does it 
provide any new information or data to refute the analysis set out in 
the molluscan shellfish final rule.
    The objection also cites the FDA's ``rejection'' of the 100-fold 
safety margin as inappropriate, given the need to ``protect children 
and other vulnerable consumers.'' The paper by Dr. Au, which was 
submitted in support of this objection, is a commentary discussing the 
need to consider data and information that indicate that children are 
more susceptible to toxic contaminants than are adults in setting 
guidelines for protecting children's health. The objection provides no 
evidence to show that the Agency's conclusion that molluscan shellfish, 
irradiated under the conditions permitted by the regulation, are safe, 
fails to protect children and other vulnerable consumers. The submitted 
commentary includes no information or data relevant to the safety of 
irradiated molluscan shellfish.
    In sum, the Agency is denying a hearing on the objection that FDA 
improperly rejected application of the 100-fold safety factor in Sec.  
170.22 to 2-ACBs produced in irradiated molluscan shellfish. The 
interpretation of the applicability of this regulation is a legal 
issue, and a hearing will not be granted on issues of law. Moreover, 
PC/CFS and Dr. Epstein have not presented any evidence supporting their 
contention that the potential levels of 2-ACBs in irradiated molluscan 
shellfish may render the food unsafe. PC/CFS' request for a hearing 
merely alleges that there is potential for harm, without providing any 
evidence that the Agency has not already considered. An objector must 
make an adequate proffer of evidence to support its allegations and to 
show that they provide a basis on which to call into question the 
Agency's conclusions (Sec.  12.24(b)(2)). Thus, neither PC/CFS nor Dr. 
Epstein has provided a basis for a hearing and FDA is denying their 
requests for a hearing based on this objection.

F. Alleged Rejection of Published Evidence

    PC/CFS cites their comment submitted on May 14, 2001, and repeats 
the assertion made in that comment that the Agency ignored or 
improperly discounted a number of positive in vivo and in vitro 
mutagenicity studies, including five peer-reviewed published studies 
performed by the Indian National Institute of Nutrition (NIN) in which 
purported mutagenic effects were found in mice, rats, and monkeys, and 
in malnourished children, consuming freshly-irradiated wheat. In 
support of the objection, PC/CFS submitted excerpts from 1987 
Congressional testimony by S.G. Srikantia, the former Director of NIN, 
who testified that FDA committed an error of judgment in accepting a 
report by a committee of Indian scientists discrediting the NIN studies 
(see 53 FR 53176 at 53182). The objection also asserts that FDA 
neglected to consider a statement made in 1988 by an Australian 
genotoxicity expert to a Committee of the Australian House of 
Representatives, stating that the malnourished children study's results 
seemed reasonable. In addition, the objection refers to two later 
publications by the NIN researchers rebutting criticisms of the study, 
and cites a statement by the former Director of NIN stating that the 
NIN's results were mirrored in a study on hamsters (Ref. 5) that found 
that polyploidy cells occurred five times more frequently in animals 
fed irradiated wheat in their diet, and that this increased incidence 
of polyploidy was related to irradiation dose.
    The Agency has previously considered all of the various in vitro 
and in vivo mutagenicity studies cited by PC/CFS and discussed its 
conclusions in detail in previous documents (see e.g., 51 FR 13376 at 
13383 and 13385; 53 FR 53176 at 53181-3 and 53191-2; 70 FR 48057 at 
48064 and 48067). Several of the studies cited in the comment refer to 
reports of in vitro mutagenicity of irradiated sugars in solution. The 
Agency previously has discussed in detail why it has concluded that the 
irradiation of simple sugars in solution is not a suitable model for 
predicting and extrapolating toxicity of irradiated foods. In the final 
rule permitting additional uses of ionizing radiation for the treatment 
of food, the Agency noted: ``In feeding studies where sugars are 
present in a typically complex food matrix there is no increase in 
mutagenicity after irradiation. Studies have demonstrated that when a 
food containing sugars is irradiated, the food does not produce the 
same toxic effects that occur when these sugars are irradiated in 
simple solution. Thus, the Agency concluded that irradiated aqueous 
sugar solutions are unsuitable models for predicting and extrapolating 
toxicity of irradiated foods and that there is no evidence that 
radiolytic products from sugars present in irradiated foods cause toxic 
effects to animals or humans (51 FR 13376 at 13383).''
    The objection provides no new evidence or rationale that provides a 
basis on which to find that FDA's conclusion on the relevance of these 
studies is incorrect.
    The Agency also has previously repeatedly addressed in detail the 
interpretation of the NIN studies using freshly irradiated wheat and 
concluded that none of the studies on polyploidy done at NIN were 
reliable and that the studies do not demonstrate that adverse effects 
would be caused by ingestion of irradiated foods (51 FR 13376 at 13385; 
53 FR 53176 at 53183; 70 FR 48057 at 48068). In the molluscan shellfish 
final rule, the Agency noted, citing earlier rulemaking: ``A committee 
of Indian scientists critically examined the techniques, the 
appropriateness of experimental design, the data collected, and the 
interpretations of NIN scientists who claimed that ingestion of 
irradiated wheat caused polyploidy in rats, mice, and malnourished 
children. After careful deliberation, this committee concluded that the 
bulk of these data are not only mutually contradictory, but are also at 
variance with well-established facts of biology. The committee was 
satisfied that once these data were corrected for biases that had given 
rise to these contradictions, no evidence of increased polyploidy was 
associated with ingestion of irradiated wheat.
    The Agency agreed with the conclusions of the committee of Indian 
scientists that the studies with irradiated foods do not demonstrate 
that

[[Page 15847]]

adverse effects would be caused by ingesting irradiated foods.'' (70 FR 
48057 at 44067 and 44068)
    Dr. Srikantia's testimony states that the FDA was wrong to accept 
the report of the committee of Indian scientists; he states that NIN 
has not repudiated the studies on polyploidy and that the Director of 
NIN submitted a rebuttal to the report of the committee of Indian 
scientists, and that ``[h]ad it seen the Institute's rejoinder to the * 
* * report, surely, it would have been in a better position to evaluate 
that report.'' FDA previously has addressed all issues raised in Dr. 
Srikantia's testimony (see e.g., 53 FR 53176 at 53182-3). As noted 
previously (53 FR 53176 at 53183) FDA did not state that NIN had 
repudiated the studies, nor did it base its own conclusions about the 
studies on a finding that the data were repudiated by NIN. FDA 
concluded that the available data from NIN did not provide an 
appropriate basis on which to conclude that increased polyploidy was 
caused by ingesting irradiated wheat. Furthermore, FDA in 1986 invited 
Dr. Srikantia to submit any information to FDA that would be relevant. 
Dr. Srikantia replied, but did not submit a copy of his rebuttal to the 
Indian government or any other report (see footnote 1, 53 FR 53176 at 
53183).
    The hamster study by Renner referenced by PC/CFS also has been 
discussed previously (53 FR 53176 at 53183 and 531834). The study 
involved the irradiation of hamster diets (composed primarily of 
carbohydrates) at high doses. The investigator concluded that at doses 
above 30 kGy there was a ``[* * *] transitory effect [* * *] as 
evidenced by an increased incidence of polyploidy cells'' but that 
``there was no evidence of any mutagenic effect being produced as a 
result of feeding an irradiated diet.'' He noted that no effects on 
incidence of polyploidy were seen at doses below 20 kGy. The objection 
contains no information that explains why this study is relevant to the 
molluscan shellfish (composed primarily of protein and fats) irradiated 
at doses up to 5.5 kGy.
    In summary, all of the studies referenced by PC/CFS have been 
considered previously by FDA and the Agency's rationale for its 
conclusions on those studies has been discussed at length in previous 
rulemakings. Neither the objection, nor the testimony of Dr. Srikantia, 
nor the statement of the Australian expert, includes any new 
information or data that would refute the Agency's findings about the 
studies. PC/CFS' request for a hearing merely alleges that there is 
potential for harm, without providing any evidence that the Agency has 
not considered previously. An objector must make an adequate proffer of 
evidence to support its allegations and to show that they provide a 
basis on which to call into question the Agency's conclusions (Sec.  
12.24(b)(2)). Thus, PC/CFS has not provided a basis for a hearing and 
FDA is denying PC/CFS' request for a hearing based on this objection.

G. Alleged Warnings on Potential risks

    PC/CFS' seventh objection alleges that the ``FDA misrepresents 
important published and unpublished warnings from qualified scientists 
calling for additional research on 2-ACBs.''
    The Agency previously has addressed the allegations of the 
potential harm of the long-term consumption of 2-ACBs that are produced 
from the irradiation of esterified fatty acids (70 FR 48057 at 48066) 
and the research performed on 2-ACBs. The Agency concluded: ``2-ACBs 
have been reported as radiolysis products of fats (Refs. 6 and 7). 
Studies performed by researchers have reported that certain 
alkylcyclobutanones can cause single strand DNA breaks detectable by 
the COMET assay (Ref. 8). Several animal feeding studies have been 
conducted with fat-containing foods irradiated at doses far higher than 
would be used on molluscan shellfish. If 2-ACBs, at the level present 
in irradiated foods, were of sufficient toxicity to cause significant 
DNA damage, one would expect to have seen adverse effects in those 
studies where animals were fed meat as a substantial part of their 
diet.''
    The objection provides no additional information on 2-ACBs that the 
Agency has not addressed previously. The Agency does not consider the 
statements in the cited papers on 2-ACBs to be warnings; rather, the 
comments are statements presented by the authors that research should 
continue on 2-ACBs. These statements do not affect the Agency's 
determination that 2-ACBs do not cause the food to be unsafe at levels 
present in irradiated food.
    Moreover, PC/CFS' request for a hearing merely alleges that there 
is potential for harm, without providing any evidence that the Agency 
has not already considered and determined did not demonstrate a 
potential for harm. An objector must make an adequate proffer of 
evidence to support its allegations and to show that they provide a 
basis on which to call into question the Agency's conclusions (Sec.  
12.24(b)(2)). Thus, PC/CFS has not provided a basis for a hearing and 
FDA is denying PC/CFS' request for a hearing based on this objection.

H. Alleged Failure To Follow Critical Guidelines for Food Additives

    PC/CFS and Dr. Epstein allege that FDA failed to follow ``critical 
guidelines'' for food additives. Specifically, the objections assert 
that although use of an irradiation source is statutorily defined as a 
food additive, 21 U.S.C. section 321(s), the final rule incorrectly 
characterizes irradiated molluscan shellfish as ``processed foods'' (70 
FR 48057 at 48069), and as such, applied a lower safety standard. 
Second, the objections cite Sec.  170.20 and assert that the Agency 
ignored provisions of that regulation. For example, the objections 
assert that the rule provides no evidence to support FDA's decision to 
ignore the current National Academy of Sciences-National Research 
Council (NAS-NRC) publication ``Risk Assessment/Safety Evaluation of 
Food Chemicals'' (see Sec.  170.20(a)). Also citing Sec.  170.20, the 
objections assert that the final rule provides no evidence that FDA 
gave due weight to anticipated levels and patterns of consumption of 
irradiated molluscan shellfish (see Sec.  170.20 (a)). Third, the 
objections cite Sec.  170.22 and state that the Agency failed to 
justify not using a 100-fold safety factor in the final rule. Fourth, 
the objection maintains that FDA failed to comply with the testing 
protocols set forth in the Redbook.\8\ Finally, the objections state 
that FDA ignored the recommendations put forth in 1980 by the Bureau of 
Foods Irradiated Foods Committee (BFIFC) regarding the evaluation of 
irradiated foods.
---------------------------------------------------------------------------

    \8\ Toxicological Principles for the Safety Assessment of Direct 
Food Additives and Color Additives Used in Food, ``Red Book II,'' 
U.S. Food and Drug Administration, Center for Food Safety and 
Applied Nutrition, (1993, revised 2001).
---------------------------------------------------------------------------

    A source of radiation used to process food is defined as a food 
additive in section 201(s) of the FD&C Act (21 U.S.C. 321(s)); the 
exposure of molluscan shellfish to ionizing radiation is what makes 
irradiated molluscan shellfish a processed food. The FD&C Act requires 
that a food additive, including a source of radiation used to process 
food, must be shown to be safe under the proposed conditions of use 
before the use can be approved. That is, the Agency must find that 
there is a reasonable certainty that consumption of an irradiated food 
is not harmful. FDA applied the same standards and guidelines that the 
Agency uses to evaluate all food additives to evaluate the safety of a 
source of ionizing radiation used to treat molluscan shellfish. The 
Agency's reference to

[[Page 15848]]

irradiated molluscan shellfish as a ``processed'' food in the final 
rule did not change the Agency's finding that such shellfish is safe.
    The Agency has previously addressed its reasoning in interpreting 
and applying its own regulations at Sec. Sec.  170.20 and 170.22 in the 
molluscan shellfish final rule, in response to comments submitted by 
PC/CFS (70 FR 48057 at 48066 and 48068). The regulation at Sec.  
170.20(a) reads in part: ``In reaching a decision on any petition filed 
under section 409 of the Act, the Commissioner will give full 
consideration to the specific biological properties of the compound and 
the adequacy of the methods employed to demonstrate safety for the 
proposed use, and the Commissioner will be guided by the principles and 
procedures for establishing the safety of food additives stated in 
current publications of the National Academy of Sciences-National 
Research Council. A petition will not be denied, however, by reason of 
the petitioner's having followed procedures other than those outlined 
in the publications of the National Academy of Sciences-National 
Research Council if, from available evidence, the Commissioner finds 
that the procedures used give results as reliable as, or more reliable 
than, those reasonably to be expected from the use of the outlined 
procedures. In reaching a decision, the Commissioner will give due 
weight to the anticipated levels and patterns of consumption of the 
additive specified or reasonably inferable.''
    In the molluscan shellfish final rule, the Agency explained that 
FDA has consistently taken the position that many scientifically valid 
types of data may properly support a finding that a proposed use of a 
food additive is safe. The Agency pointed out that NAS-NRC testing 
standards and guidelines have been stated in relatively general terms 
and that in practice, FDA has applied exposure and toxicological 
criteria that were current for the time, and appropriate for assessing 
the safety of a particular food additive (70 FR 48057 at 48068). In its 
objection, PC/CFS repeats its assertion that FDA failed to properly 
interpret its own regulation, but has provided no new information that 
would refute the Agency's reasoning. The objection implies that the 
Agency is obligated to explicitly discuss its consideration of NAS-NRC 
guidelines in its rules, but there is nothing in Sec.  170.20 that 
imposes such an obligation on the Agency. The regulation requires the 
Commissioner of Food and Drugs (the Commissioner) to make a finding 
that the procedures used by the petitioner give results that are as 
reliable as, or more reliable than, those reasonably expected from use 
of the NAS-NRC guidelines. Acceptance of a petition based on alternate 
procedures implies that the Commissioner has made such a finding.
    With respect to the assertion that FDA failed to give due weight to 
anticipated levels and patterns of consumption of irradiated molluscan 
shellfish, FDA previously has reviewed a large body of data relevant to 
the assessment of potential toxicity of irradiated flesh foods. In its 
evaluations of the safety of a source of radiation to treat food 
intended for human consumption, the Agency has identified three areas 
of concern to be addressed: (1) Potential toxicity, (2) nutritional 
adequacy, and (3) potential microbiological risk from treated foods. 
Each of these areas was discussed in detail in the molluscan shellfish 
final rule. FDA asserted that the Agency ``can draw conclusions about 
the amounts of radiolysis products expected to be generated at 
radiation doses relevant to the subject petition by extrapolating from 
data obtained at higher doses for foods of similar composition 
irradiated under similar conditions (70 FR 48057 at 48059).'' In its 
review of studies in which animals were fed diets containing beef 
irradiated at 56 kGy, fish at 6 kGy, horse meat at 6.5 kGy, fish at 56 
kGy, and others (62 FR 64107 at 64113), the Agency found no evidence of 
toxicity attributable to the consumption of these foods.
    FDA has concluded that products formed (typically oxidation 
products of food constituents) following irradiation of molluscan 
shellfish are the same as or similar to those found in non-irradiated 
foods after cooking. Further, radiolysis products in shellfish are 
essentially the same as those in red meat and poultry, since the 
composition is roughly the same. Additionally, shellfish make a smaller 
contribution to the average daily diet; therefore, exposure to 
radiolysis products from shellfish will be smaller than that from foods 
for which irradiation currently is regulated. Cooking and other heat 
processing methods remain the principle means for introducing such 
substances into the diet (Ref. 9). PC/CFS' assertion provides no basis 
to challenge FDA's assessment of the safety of irradiated molluscan 
shellfish.
    In like manner, the assertions that FDA failed to follow its 
regulation in Sec.  170.22, or to comply with recommendations in the 
Redbook or set forth by the BFIFC committee, have been raised 
previously by PC/CFS, Dr. Epstein, and others, and have been responded 
to by the Agency in the molluscan shellfish final rule (70 FR 48057 at 
48066 and 48069) and in other previous rulemakings (see e.g., 57 FR 
6667 at 6669; 62 FR 64102 at 64105; and Section IV.E., above). The 
Agency has described its reasoning for concluding that the data and 
information considered in the evaluation of the petition to permit the 
irradiation of molluscan shellfish, when considered in its entirety, 
are sufficient to support the safety of molluscan shellfish irradiated 
under the conditions specified in the regulation. Once the Agency makes 
a finding of safety in a listing document, the burden shifts to an 
objector to come forward with evidence that calls into question FDA's 
conclusion (see Sec.  12.24(b)(2)). PC/CFS and Dr. Epstein provide no 
new information on how the Agency failed to follow the regulations to 
establish the safety of irradiating molluscan shellfish to an absorbed 
dose of 5.5 kGy. A hearing will not be granted on the basis of mere 
allegations or general descriptions of positions and contentions (Sec.  
12.24(b)(2)). The objectors must, at a minimum, raise a material issue 
concerning which a meaningful hearing might be held. Neither PC/CFS nor 
Dr. Epstein has provided a basis for a hearing and FDA is denying their 
request for a hearing based on this objection.

I. Wholesomeness

    PC/CFS states that ``FDA's final rule fails to address recent 
studies in its possession indicating that irradiation at low dose 
levels in oysters may cause unpleasant--perhaps unwholesome--
byproducts.'' The objection discusses a report \9\ presented at the 
2002 annual meeting of the Institute of Food Technologists that 
suggests that molluscan shellfish irradiated at 2.0 kGy produced an 
``unpleasant yellow exudate.'' The objection goes on to discuss other 
potential organoleptic changes that may occur in irradiated molluscan 
shellfish (such as ``grassy'' and ``oxidized'' odors) as noted in 
Dixon's 1996 dissertation (Ref. 2). PC/CFS states that FDA's final rule 
failed to address these issues of ``wholesomeness,'' and requests a 
hearing on these issues.
---------------------------------------------------------------------------

    \9\ Andrews, L. S., ``Gamma Irradiation Processing to Reduce the 
Risk of Vibrio Infections from Raw Oysters,'' (unpublished 
presentation at the 2002 Annual Meeting), 2002.
---------------------------------------------------------------------------

    FDA previously has acknowledged that irradiation may cause 
organoleptic changes in foods (62 FR 64107 at 64110). Such organoleptic 
changes may make the food unappealing and unmarketable; however, 
undesirable organoleptic changes do not render the food unsafe. Neither 
the author of the

[[Page 15849]]

report cited by PC/CFS nor PC/CFS itself suggests that there is any 
evidence that the noted ``unpleasant yellow exudate'' or other 
organoleptic changes would render irradiated molluscan shellfish 
unsafe.
    PC/CFS' request for a hearing suggests that there is potential for 
harm from possible organoleptic changes from irradiation of molluscan 
shellfish, without providing any evidence to support this suggestion. 
An objector must make an adequate proffer of evidence to support its 
allegations and to show that they provide a basis on which to call into 
question the Agency's conclusions. A hearing will be denied if the 
Commissioner concludes that the data and information submitted are 
insufficient to justify the factual determination urged, even if 
accurate (Sec.  12.24(b)(3)). FDA concludes that the data and 
information are insufficient; therefore, FDA is denying the request for 
a hearing based on this objection.

J. FDA Review Memoranda

    PC/CFS alleges that there are errors in some of the FDA review 
memoranda used to support the final rule. The objection states that 
these errors call into question the adequacy of the Agency's review 
processes that led to the Agency's conclusion that irradiated molluscan 
shellfish are safe. There are four parts to this objection; the Agency 
will address each part below.
    Part one of this objection asserts that ``FDA significantly 
misrepresents published research on the tumor-promoting qualities of 2-
ACBs.'' Specifically, the objection states that an FDA memorandum in 
the record (Ref. 10) mischaracterizes the findings of a publication 
submitted by PC/CFS as part of a comment to the petition to irradiate 
molluscan shellfish (Ref. 11). The objection states that these alleged 
mischaracterizations ``severely bias the Agency's analysis of 2-ACBs.''
    The disputed memorandum included a discussion of the Raul et al. 
(2002) paper submitted to the Agency by PC/CFS as part of its comment 
to the molluscan shellfish petition; the memorandum also discussed a 
commentary on the paper that was submitted with the comment (Ref. 12). 
The objection cited three selected sentence fragments from the 
memorandum which PC/CFS maintains are incorrect. The memorandum 
discussed the authors' observations and the limitations of the Raul, et 
al. study and stated that those limitations and inconsistencies in the 
data made it difficult to draw conclusions from the study. In the final 
rule (70 FR 48057 at 48067) the Agency discussed the limitations of the 
study and its reasoning in concluding that the results of long-term 
feeding studies were more relevant to a finding of safety than the Raul 
et al. study.
    As FDA noted in the final rule (70 FR 48057 at 48067): ``Given the 
limitations of the animal model and study design, ambiguous data, and 
the absence of close relationship between the chemical exposure used in 
the study and the expected human exposure, the Agency finds that the 
comment provides no substantial or reliable scientific information to 
show that there is reason to believe that the consumption of 2-ACBs 
will promote colon cancer. Moreover, the Agency notes that long term 
feeding studies performed using irradiated foods that contain 2-ACBs 
did not show any promotion of colon cancer. The results of these latter 
long term feeding studies are more relevant than results from the Raul 
paper because 2-ACBs were fed in the diet as in human exposure and the 
levels of exposure would still have been increased over usual dietary 
levels.''
    The Agency maintains that the disputed memorandum taken as a whole, 
including the sentence fragments highlighted by PC/CFS, accurately and 
reliably reflects the information in the Raul and Rao publications. 
Importantly, the factual issues raised by the three disputed statements 
were not determinative in the Agency's overall conclusions about the 
relevance of the Raul et al. study or to its determination that the 
irradiated molluscan shellfish under the conditions of the regulation 
are safe. A hearing will not be granted on factual issues that are not 
determinative with respect to the action requested (Sec.  12.24(b)(4)). 
Thus, PC/CFS has not provided a basis for a hearing and FDA is denying 
PC/CFS' request for a hearing based on this objection.
    Part two of this objection asserts that FDA cites no evidence to 
dismiss the COMET assay as a valid technique for testing genetic 
toxicity. The objection asserts that the ``technique has broad support 
within the scientific community'' and quotes excerpts from several 
published reports that state that the COMET assay has utility, and is 
being increasingly used in the screening of various substances.
    The Agency does not dispute the statements quoted by the PC/CFS nor 
the fact that the COMET assay is being increasingly studied and used to 
study the cellular response to DNA damage and repair. In the final 
rule, the Agency has addressed its conclusions pertaining to the COMET 
assay results (70 FR 48057 at 48065), as they are presented with 
respect to 2-ACBs and has determined that, when the totality of 
evidence is examined with other more standard genotoxicity testing 
methods, ``the potential risk of 2-DCB, if any, is very low.'' The 
cited quotations do not provide any information related to the safety 
of consumption of 2-ACBs that may be present in irradiated molluscan 
shellfish that the Agency has not considered, and the objection 
contains no information that would cause the Agency to change its 
safety determination. A hearing will not be granted on factual issues 
that are not determinative with respect to the action requested (Sec.  
12.24(b)(4)).
    Part three of this objection states that certain FDA review 
memoranda (Chen to Highbarger, 12/21/2001, FAP 9M4697), (Morehouse to 
Highbarger, 6/l/2002, 9M4697), and (Chen to Highbarger, 4/7/2003, FAP 
9M4695) are irrelevant to the analysis of irradiated molluscan 
shellfish, because they were written as part of the review of other 
petitions to permit the irradiation of certain other foods. This 
objection also states that one of the memoranda (Chen to Highbarger, 
12/21/2001, FAP 9M4697) is inaccurate, because it states that ``the 
radiolysis products of irradiated lipids and proteins are either the 
same as, or structurally very similar to, compounds found in foods that 
have not been irradiated.'' PC/CFS state that ``numerous published 
articles show--and the FDA now admits--that 2-ACBs are fundamentally 
unique from any naturally occurring food component.'' Additionally, the 
objection states that this memorandum ignores the FDA Redbook's 
statement that genotoxicity tests can contribute to safety assessments.
    The Agency acknowledges that the review memoranda cited were 
written as part of the review of two petitions to permit the 
irradiation of certain foods (other than molluscan shellfish) that are 
pending at the Agency: FAP 9M4695, submitted by the U.S. Department of 
Agriculture (64 FR 71792) \10\ and FAP 9M4697, submitted by the 
National Food Processors Association on behalf of the Food Irradiation 
Coalition (65 FR 493 and 66 FR 23943).\11\ The objection

[[Page 15850]]

does not explain, however, why the information in those memoranda is 
irrelevant to the irradiation of molluscan shellfish to an absorbed 
dose of 5.5 kGy. These review memoranda describe chemistry and 
toxicology information related to the irradiation of protein, fat, and 
carbohydrate; these are components of molluscan shellfish. The Agency 
has repeatedly noted that its conclusions on safety of irradiating 
molluscan shellfish are based on the evaluation of the totality of 
evidence before it, and in particular, that information related to the 
irradiation of flesh foods is relevant to an evaluation of the safety 
of irradiated molluscan shellfish. The objection provides no 
information that would suggest the information in the cited memoranda 
is irrelevant to the molluscan shellfish final rule except to point out 
that they were written as part of the review of other petitions.
---------------------------------------------------------------------------

    \10\ FAP 9M4695 requests that 21 CFR part 179 be amended to 
provide for the safe use of a 4.5 kiloGray (kGy) maximum dose of 
ionizing radiation to treat unrefrigerated (as well as refrigerated) 
uncooked meat, meat products, and certain meat food products to 
reduce levels of foodborne pathogens and extend shelf-life.
    \11\ FAP 9M4697 requests that 21 CFR part 179 be amended to 
provide for the safe use of ionizing radiation for control of 
foodborne pathogens, and extension of shelf-life, in a variety of 
human foods up to a maximum irradiation dosage of 4.5 kGy for non-
frozen and non-dry products, and 10.0 kGy for frozen or dry 
products, including: (1) Pre-processed meat and poultry; (2) both 
raw and preprocessed vegetables, fruits, and other agricultural 
products of plant origin; (3) certain multi-ingredient food 
products. The notice stated that the petition does not cover 
products composed in whole or in part of raw meat, poultry, or fish 
nor does it cover ``ready-to-eat'' fish products or ingredients made 
from fish.
---------------------------------------------------------------------------

    The objection also cites a statement from a memorandum written in 
2001 that stated that `` * * * radiolysis products of irradiated lipids 
and proteins are either the same as, or structurally very similar to, 
compounds found in foods that have not been irradiated'' and points out 
that the Agency has since acknowledged that 2-ACBs have thus far not 
been found in food that has not been irradiated.\12\ As noted in the 
objection itself, there is no factual issue in dispute, and the 
objection points to no reason why the statement in the 2001 memorandum 
calls into question the Agency's subsequent conclusions about the 
safety of irradiated molluscan shellfish.
---------------------------------------------------------------------------

    \12\ We note that recent studies have demonstrated that 2-ACBs 
are formed in certain foods that have not been irradiated (e.g., 
roasted nuts).
---------------------------------------------------------------------------

    Finally, this part of the objection alleges that the 2001 
memorandum ignores the FDA Redbook's statement that genotoxicity tests 
can contribute significantly to safety assessments. The Agency agrees 
that genotoxicity testing can be useful in the assessment of the safety 
of food additives. In the molluscan shellfish final rule the Agency 
discussed the use of genotoxicity tests, and of long-term feeding 
studies, in the context of the safety assessment of irradiated foods 
(70 FR 48057 at 48064) concluding: ``The Bureau of Foods Irradiated 
Foods Committee (BFIFC) recommended that foods irradiated at a dose 
above 1 kGy be evaluated using a battery of mutagenicity tests to 
assess whether long-term feeding studies in animals were necessary 
(Ref. 36). Mutagenicity studies are primarily used to screen for 
potential mutagenic effects. Animal feeding studies are more reliable 
for determining the true mutagenic potential of a compound that is 
consumed in food. (Ref. 37). Moreover, one cannot draw valid 
conclusions from data simply by summing positive and negative results 
without fully evaluating the individual studies and assessing what 
conclusions such studies support and considering the totality of 
evidence. If the occasional report of a mutagenic effect were valid and 
significant to health, one should have seen consistent adverse 
toxicological effects in the many long term and reproduction studies 
with animals. This has not been the case.''
    Thus, the Agency has acknowledged the utility of genotoxicity 
tests, but also states that when long-term animal feeding studies are 
available, that these latter studies are more reliable for determining 
the mutagenic potential of a compound consumed in food. Nothing in the 
objection would suggest that the Agency's position is in contradiction 
to the recommendations in the Redbook.
    An objector must make an adequate proffer of evidence to support 
its allegations and to show that they provide a basis on which to call 
into question the agencies conclusions (Sec.  12.24(b)(2)). PC/CFS has 
not provided a basis for a hearing and FDA is denying PC/CFS' request 
for a hearing based on this objection.
    Finally, part four of the objection states that an FDA memorandum 
(Folmer-Jensen to Highbarger, 8/2/2002, FAP 9M4697) states that other 
food processing methods (such as freezing, canning and drying) can 
result in loss of vitamins, but neglects to consider the potential for 
additional vitamin reduction if irradiated foods were to be 
subsequently processed by freezing, canning or drying. This part 
further cites a 1986 trade press article as evidence that irradiation, 
when combined with other food processing techniques, has a greater 
effect on reducing levels of vitamins than each process individually. 
The objection then questions the Agency's conclusion that the 
contribution of thiamine, niacin and vitamin B6 from fish and shellfish 
represents an insignificant contribution to the nutritional needs of 
Americans. The objection cites two studies that showed a substantial 
reduction in thiamine level in irradiated cod.
    The Agency agrees that irradiation may reduce some vitamins in 
foods. Additionally, further processing may further reduce some 
vitamins in foods. The extent to which vitamin loss is nutritionally 
significant depends in part on the relative contribution of the food in 
question to the overall dietary intake of the vitamin. The Agency has 
concluded that the reductions of vitamins in molluscan shellfish will 
cause negligible changes in total dietary intake of the affected 
vitamins as a result of irradiating molluscan shellfish under the 
conditions of the regulation. The objection questions the Agency's 
analysis and conclusion, but offers no data or information to support a 
contention that permitting the irradiation of molluscan shellfish would 
have an adverse impact on the nutritional adequacy of the diet. 
Moreover, the objection contains no information that would cause the 
Agency to change its conclusion that the consumption of irradiated 
molluscan shellfish to an absorbed dose of 5.5 kGy is safe.
    A hearing will be denied if the Commissioner concludes that the 
data and information submitted are insufficient to justify the factual 
determination urged, even if accurate ((Sec.  12.24(b)(3)). FDA 
concludes that the data and information are insufficient; therefore, 
FDA is denying the request for a hearing based on this objection.

K. Chemicals Formed in Irradiated Foods

    One objection submitted by Dr. Epstein alleges that FDA has 
``ignore[d] the fact that irradiation can dramatically increase the 
concentration of many potentially toxic chemicals.'' Dr. Epstein 
specifically mentions benzene and toluene, quoting a statement from 
D.U. Ahn of Iowa State University: ``[B]enzene and toluene * * * could 
be formed from amino acids upon irradiation * * * Benzene has 
deleterious effects on human health (Ref. 13).'' In support of the 
quoted statement, the objection references a paper entitled ``Effects 
of Electron Beam Irradiation and Antimicrobials on the Volatiles, 
Color, and Texture of Ready-to-Eat Turkey Breast Roll.''
    The Agency acknowledges that benzene, toluene, and other compounds 
are formed, albeit in very small amounts, when meats are irradiated at 
sterilizing doses (Ref. 14.). The formation of benzene and other 
volatile compounds (including toluene) in irradiated foods and their 
possible risk to human health has been extensively evaluated by FDA and 
discussed in previous rulemaking (see 62 FR 64107 at 64110-64111, 55 FR 
18538 at 18542-18543 and 53 FR 53176 at 53197).

[[Page 15851]]

Regarding benzene specifically, the Agency has stated: ``The select 
Committee concluded that the small addition of benzene from radiation 
sterilized beef would contribute only a trivial increment to the normal 
body burden and is unlikely to increase significantly whatever hazard 
exists from other sources. FDA is not aware of any evidence that call 
this conclusion into question'' (53 FR 53176 at 53197).
    The objection identifies no evidence that the Agency overlooked, 
and does not provide any new evidence that would indicate benzene, 
toluene, or other chemicals are formed in irradiated molluscan 
shellfish in quantities that would pose a risk to human health. Thus, 
Dr. Epstein's request for a hearing based on this objection is denied 
because a hearing will not be granted on the basis of mere allegations 
or general descriptions of positions and contentions (Sec.  
12.24(b)(2)).
    The objection also criticizes the Agency for making ``[a] blanket 
statement which the Agency fails to explain further: ``FDA and food 
scientists worldwide have long agreed that the evaluation of the safety 
of irradiated foods requires consideration of the whole food, not the 
testing of each component.'' Dr. Epstein also takes issue with the 
Agency's statement that ``* * * identification of major radiolysis 
products will aid in the interpretation of data.''
    Contrary to Dr. Epstein's remarks, the Agency provided a detailed 
explanation of its statement about safety testing of irradiated whole 
foods versus the testing of individual components of those foods in the 
context of its response to a comment expressing a different view about 
requirements for testing irradiated food (see 70 FR 48057 at 48066). 
Additionally, the Agency has provided detailed discussions of the role 
of chemical identification of radiolysis products in the evaluation of 
data from safety testing (see 70 FR 48507 at 48059 and 62 FR 64107 at 
64110-64111 and section IV. H of this document).
    In conclusion, the submitted objection contains no evidence that 
the Agency has overlooked and no new evidence that would call into 
question the Agency's previous conclusion that consumption of 
irradiated molluscan shellfish is safe. The objection merely alleges 
that there may possibly be formation of benzene and toluene and alleges 
a potential of harm. 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, FDA is denying the request 
for a hearing based on this objection.

V. Summary and Conclusion

    The FD&C Act requires that a food additive be shown to be safe 
prior to marketing under section 409 of the FD&C Act. Under Sec.  
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 the Agency's 
August 16, 2005, final rule approving the use of irradiation on fresh 
or frozen molluscan shellfish, FDA concluded that the studies conducted 
to establish the safety of this additive demonstrate that this use of 
irradiation is safe for its intended use on fresh or frozen molluscan 
shellfish.
    The petitioner has the burden to demonstrate the safety of the 
additive to gain FDA approval. Nevertheless, once FDA makes a finding 
of safety in an approval document, the burden shifts to an objector, 
who must come forward with evidence that calls into question FDA's 
conclusion (American Cyanamid Co. v. FDA, 606 F.2d 1307, 1314-1315 (DC 
Cir. 1979)).
    Despite their many allegations, PC/CFS and Dr. Epstein have not 
established that FDA overlooked significant information in the record 
in reaching its conclusion that the use of irradiation on fresh or 
frozen molluscan shellfish is safe. In such circumstances, FDA has 
determined that the objections do not raise any genuine and substantial 
issue of fact that can be resolved by an evidentiary hearing (Sec.  
12.24(b)).
    Accordingly, FDA is denying the requests for a hearing. In 
addition, PC/CFS' and Dr. Epstein's requests for a stay of the 
effectiveness of the August 16, 2005, regulation until a hearing is 
held are moot because FDA is denying all hearing requests. Thus, FDA is 
confirming August 16, 2005, as the effective date of the final rule 
published at 70 FR 48057.

VI. References

    The following references are on display at the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20857, under Docket No. FDA-1999-F-0056 
(formerly 1999F-4372), and may be seen by interested persons between 9 
a.m. and 4 p.m., Monday through Friday.

1. Memorandum to the file, FAP 4M4428, from P. Hansen, FDA, dated 
October 31, 1997.
2. Dixon, D.W., ``The Influence of Gamma Radiation Upon Shellstock 
Oysters, and Culturable and Viable but Nonculturable Vibrio 
vulnificus,'' a dissertation presented to the Graduate School of the 
University of Florida, 1996.
3. Diehl, J.F., ``Safety of Irradiated Foods,'' second edition, 
Marcel Dekker, Inc., New York, 1995.
4. Memorandum for FAP 9M4682 from K. Morehouse, FDA, to L. 
Highbarger, FDA, July 15, 2005.
5. Renner, H.W., ``Chromosome Studies on Bone Marrow Cells of 
Chinese Hamsters Fed a Radiosterilized Diet,'' Toxicology, 8:213-
222, 1977.
6. Miesch, M., Ndiye, B., Hasselmann, C., and E. Marchioni, ``2-
Alkylcyclobutanones as Markers for Irradiated Food Stuffs--I. 
Synthesis of Saturated and Unsaturated Standards,'' Radiation 
Physics and Chemistry, 55:337-344, 1999.
7. Horvatovich, P., M. Miesch, C. Hasselmann, and E. Marchioni, 
``Supercritical Fluid Extractin of Hydrocarbons and 2-
Alkylcyclobutanones for the Detection of Irradiated Foodstuffs,'' 
Journal of Chromatography, 897:259-268, 2000.
8. Delinc[eacute]e H, B.L. Pool-Zobel, and G. Rechkemmer 
``Genotoxicity of 2-Dodecyclcyclobutanone,'' Food Irradiation: Fifth 
German Conference, Report BFE-R-99-01, Federal Nutrition Research 
Institute, Karlsruhe, Germany (unpublished, 1998).
9. Memorandum for FAP 9M4682 and FAP 1M4727, from D. Folmer, FDA, to 
L. Highbarger, August 2, 2002.
10. Memorandum for FAP 9M4682 from T. Twaroski, FDA, to L. 
Highbarger, FDA, July 14, 2005.
11. Raul, F., F. Gosse, H. Delincee, A. Hartwig, E. Marchioni, M. 
Miesch, D. Werner, and D. Burnouf, ``Food Borne Radiolytic Compounds 
(2-Alkylcyclobutanones) May Promote Experimental Colon 
Carcinogenesis,'' Nutrition and Cancer, 44(2):181-191, 2002.
12. Rao, C., ``Do Irradiated Foods Cause or Promote Colon Cancer?'', 
Division of Nutritional Carcinogenesis, Institute for Cancer 
Prevention, American Health Foundation--Cancer Center, Valhalla, NY 
(Unpublished, 2003), FDA notes that this article has now been 
published as a commentary in Nutrition and Cancer, 46(2):107-109, 
2003.
13. Bureau of Food Irradiated Foods Committee, ``Recommendations for 
Evaluation the Safety of Irradiated Food,'' prepared for the 
Director, Bureau of Foods, FDA, July 1980.
14. Toxicological Principles for the Safety Assessment of Direct 
Food Additives and Color Additives Used in Food, ``Red Book II,'' 
U.S. Food and Drug Administration, Center for Food Safety and 
Applied Nutrition, 1993, revised 2001.
15. Zhu, M.J., et al., ``Effects of Electron Beam Irradiation and 
Antimicrobials on the Volatiles, Color, and Texture of Ready-to-Eat 
Turkey Breast Roll,'' Journal of Food Science, 69(5):C382-C387, 
2004.
16. Federation of American Societies for Experimental Biology, Life 
Sciences Research Office, Evaluation of the Health Aspects of 
Certain Compounds Found in Irradiated Beef, Supplement 1979, 1977.


[[Page 15852]]


    Dated: March 15, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-6625 Filed 3-21-11; 8:45 am]
BILLING CODE 4160-01-P