Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 15841 

SECURITIES AND EXCHANGE 

COMMISSION 

17 CFR Part 230 

General Rules and Regulations, 

Securities Act of 1933 

CFR Correction 

In Title 17 of the Code of Federal 

Regulations, Parts 200 to 239, revised as 

of April 1, 2010, on page 686, in 

§ 230.501, following paragraph (e)(3), 

reinstate the Note to paragraph (e) to 

read as follows: 

§ 230.501 Definitions and terms used in 

Regulation D. 

* * * * * 

(e) * * * 

NOTE: The issuer must satisfy all the 

other provisions of Regulation D for all 

purchasers whether or not they are 

included in calculating the number of 

purchasers. Clients of an investment 

adviser or customers of a broker or 

dealer shall be considered the 

‘‘purchasers’’ under Regulation D 

regardless of the amount of discretion 

given to the investment adviser or 

broker or dealer to act on behalf of the 

client or customer. 

* * * * * 

[FR Doc. 2011–6830 Filed 3–21–11; 8:45 am] 

BILLING CODE 1505–01–D 

DEPARTMENT OF HOMELAND 

SECURITY 

Bureau of Customs and Border 

Protection 

DEPARTMENT OF THE TREASURY 

19 CFR Part 141 

Entry of Merchandise 

CFR Correction 

In Title 19 of the Code of Federal 

Regulations, Parts 141 to 199, revised as 

of April 1, 2010, on page 6, the second 

general authority citation for part 141 is 

removed. 

[FR Doc. 2011–6840 Filed 3–21–11; 8:45 am] 

BILLING CODE 1505–01–D 

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. 

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 

§ 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 § 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 


Emcdonald on DSK2BSOYB1PROD with RULES
15842 Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 

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 

(§ 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 § 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 § 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 

§ 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 § 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 


Emcdonald on DSK2BSOYB1PROD with RULES
Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 15843 

1Fegley, 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. 

2The 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. 

3Fegley, 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. 

4FDA has established regulations for seafood 

HACCP in 21 CFR part 123. 

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

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.’’ 

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 (§ 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. 

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 


Emcdonald on DSK2BSOYB1PROD with RULES
15844 Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 

5 ‘‘Off-gassing’’ refers to volatile chemicals that 

may be emitted over time from a source. 

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 shelfstable. A hearing will not be granted on 

factual issues that are not determinative 

with respect to the action requested 

(§ 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 ‘‘peerreviewed 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 (§ 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 

(§ 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 irradiationsterilized 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 (§ 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 § 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 

§ 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 (§ 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 


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Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 15845 

6That 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. 

7Au, W., Susceptibility of Children to 

Environmental Toxic Substances, International 

Journal of Hygiene Environmental Health; 205:1–3, 

2002. 

shells, and the attenuation of irradiation 

effects from shell thickness. 

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 unirradiated 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 (§ 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

The applicability of § 170.22 is a legal 

issue, and a hearing will not be granted 

on issues of law. The Agency notes that 

§ 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 § 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 


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15846 Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 

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 § 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 

(§ 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 


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Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 15847 

8Toxicological 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). 

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 

(§ 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 

(§ 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 § 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 § 170.20(a)). Also citing 

§ 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 

§ 170.20 (a)). Third, the objections cite 

§ 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. 

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 


Emcdonald on DSK2BSOYB1PROD with RULES
15848 Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 

9Andrews, L. S., ‘‘Gamma Irradiation Processing 

to Reduce the Risk of Vibrio Infections from Raw 

Oysters,’’ (unpublished presentation at the 2002 

Annual Meeting), 2002. 

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 

§§ 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 § 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 

§ 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 nonirradiated 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 

§ 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 

§ 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 (§ 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. 

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 


Emcdonald on DSK2BSOYB1PROD with RULES
Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 15849 

10FAP 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. 

11FAP 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 

Continued 

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 

(§ 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 tumorpromoting 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 (§ 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 (§ 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 


Emcdonald on DSK2BSOYB1PROD with RULES
15850 Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 

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. 

12We note that recent studies have demonstrated 

that 2–ACBs are formed in certain foods that have 

not been irradiated (e.g., roasted nuts). 

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. 

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. 

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 

(§ 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 

((§ 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 Readyto-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). 


Emcdonald on DSK2BSOYB1PROD with RULES
Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 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 (§ 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 (§ 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 § 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 (§ 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. Delince ́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 Readyto-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. 


Emcdonald on DSK2BSOYB1PROD with RULES
15852 Federal Register / Vol. 76, No. 55 / Tuesday, March 22, 2011 / Rules and Regulations 

1 ‘‘Endangerment and Cause or Contribute 

Findings for Greenhouse Gases Under Section 

202(a) of the Clean Air Act.’’ 74 FR 66496 

(December 15, 2009). 

2 ‘‘Endangerment and Cause or Contribute 

Findings for Greenhouse Gases Under Section 

202(a) of the Clean Air Act.’’ 74 FR 66496 

(December 15, 2009). 

3 ‘‘Light-Duty Vehicle Greenhouse Gas Emission 

Standards and Corporate Average Fuel Economy 

Standards; Final Rule.’’ 75 FR 25324 (May 7, 2010). 

4 ‘‘Prevention of Significant Deterioration and 

Title V Greenhouse Gas Tailoring Rule; Final Rule.’’ 

75 FR 31514 (June 3, 2010). 

5 ‘‘Action to Ensure Authority to Issue Permits 

Under the Prevention of Significant Deterioration 

Program to Sources of Greenhouse Gas Emissions: 

Finding of Substantial Inadequacy and SIP Call; 

Final Rule.’’ 75 FR 77698 (December 13, 2010). 

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 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 52 

[EPA–R07–OAR–2010–0945; FRL–9281–6] 

Approval and Promulgation of 

Implementation Plans; Nebraska: 

Prevention of Significant Deterioration; 

Greenhouse Gas Permitting Authority 

and Tailoring Rule Revision 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: EPA is taking final action to 

approve revisions to the State 

Implementation Plan (SIP) for Nebraska, 

submitted by the Nebraska Department 

of Environmental Quality (NDEQ) to 

EPA for final processing on January 14, 

2011. These revisions cover two broad 

categories under Nebraska’s prevention 

of significant deterioration (PSD) 

preconstruction permitting program. 

The first applies to revisions relating to 

permitting of greenhouse gas (GHG) 

emissions under the PSD program. The 

second applies to revisions 

incorporating relevant aspects of EPA’s 

2002 new source review (NSR) reform 

rules, submitted by letter dated 

November 19, 2010. 

The GHG SIP revision, which 

incorporates updates to NDEQ’s air 

quality regulations, includes two 

significant changes impacting the 

regulation of GHGs under Nebraska’s 

PSD program. First, the SIP revision 

provides the State of Nebraska with 

authority to issue PSD permits 

governing GHGs. Second, the SIP 

revision establishes emission thresholds 

for determining which new stationary 

sources and modification projects 

become subject to Nebraska’s PSD 

permitting requirements for their GHG 

emissions. The first provision is 

required under the GHG PSD SIP call, 

which EPA published on December 13, 

2010, and which required the State of 

Nebraska to apply its PSD program to 

GHG-emitting sources. The second 

provision is consistent with the 

thresholds EPA established in the 

Tailoring Rule, published on June 3, 

2010. EPA is approving this SIP revision 

because this SIP revision meets the 

requirements of the GHG PSD SIP Call. 

In addition, in today’s action, EPA is 

also taking final action to approve 

Nebraska’s adoption of portions of 

EPA’s 2002 NSR Reform rules, 

published December 31, 2002. EPA has 

determined that Nebraska’s revisions 

track the Federal NSR Reform Rules. 

EPA previously determined that the 

implementation of the Federal NSR 

Reform Rules will be environmentally 

beneficial. 

DATES: This rule will be effective March 

22, 2011. 

ADDRESSES: EPA has established a 

docket for this action under Docket 

Identification No. EPA–R07–OAR– 

2010–0945. All documents in the docket 

are listed on the http:// 

www.regulations.gov Web site. Although 

listed in the index, some information is 

not publicly available, i.e., Confidential 

Business Information or other 

information whose disclosure is 

restricted by statute. Certain other 

material, such as copyrighted material, 

is not placed on the Internet and will be 

publicly available only in hard copy 

form. Publicly available docket 

materials are available either 

electronically through http:// 

www.regulations.gov or in hard copy at 

the Air Planning and Development 

Branch, Air and Waste Management 

Division, U.S. Environmental Protection 

Agency, Region 7, 901 North 5th Street, 

Kansas City, KS 66101. EPA requests 

that if at all possible, you contact the 

person listed in the FOR FURTHER

INFORMATION CONTACT section for further 

information. The Regional Office’s 

official hours of business are Monday 

through Friday, 8:30 to 4:30, excluding 

Federal holidays. 

FOR FURTHER INFORMATION CONTACT: For 

information regarding the Nebraska SIP, 

contact Mr. Larry Gonzalez, Air 

Planning and Development Branch, Air 

and Waste Management Division, U.S. 

Environmental Protection Agency, 

Region 7, 901 North 5th Street, Kansas 

City, Kansas 66101. Mr. Gonzalez’s 

telephone number is (913) 551–7041; email address: gonzalez.larry@epa.gov. 

SUPPLEMENTARY INFORMATION: 

Table of Contents 

I. What is the background for today’s final 

action? 

II. Analysis of Nebraska’s SIP Revision 

III. What is EPA’s response to comments 

received on the proposed action? 

IV. What is the effect of today’s final action? 

V. When is today’s action effective? 

VI. Final Action 

VII. Statutory and Executive Order Reviews 

I. What is the background for today’s 

final action? 

EPA has recently undertaken a series 

of actions pertaining to the regulation of 

GHGs that, although for the most part 

distinct from one another, establish the 

overall framework for today’s final 

action for the Nebraska SIP. The first 

four of these actions include, as they are 

commonly called, the ‘‘Endangerment 

Finding’’ and ‘‘Cause or Contribute 

Finding,’’ which EPA issued in a single 

final action,1 the ‘‘Johnson Memo 

Reconsideration,’’ 2 the ‘‘Light-Duty 

Vehicle Rule,’’ 3 and the ‘‘Tailoring 

Rule.’’ 4 Taken together, these actions 

established regulatory requirements for 

GHGs emitted from new motor vehicles 

and new motor vehicle engines; 

determined that such regulations, when 

they took effect on January 2, 2011, 

subject GHGs emitted from stationary 

sources to PSD requirements; and 

limited the applicability of PSD 

requirements to GHG sources on a 

phased-in basis. 

In a separate action, the ‘‘GHG PSD 

SIP Call,’’ 5 EPA called on the State of 

Nebraska and 12 other States with SIPs 

that do not provide authority to issue 

PSD permits governing GHGs to revise 

their SIPs to provide such authority. In 

that action, EPA took steps to ensure 

that in the 13 States that do not have 

authority to issue PSD permits to GHGemitting sources at present, either the 

State or EPA would have the authority 

to issue such permits by January 2, 

2011, or soon thereafter. EPA explained 

that although for most States, either the 

State or EPA is already authorized to 

issue PSD permits for GHG-emitting 

sources as of that date, Nebraska and the 

other 12 States have EPA-approved PSD 

programs that do not include GHGemitting sources and therefore do not 

authorize these States to issue PSD 

permits to such sources. Accordingly, 

EPA issued the GHG PSD SIP Call to 

require a SIP revision that applies 

Nebraska’s SIP PSD programs to GHGemitting sources. EPA also established a 

SIP submittal deadline. In the proposed 

SIP call, EPA had stated that the 

deadline could range from as little as 

three weeks after the final SIP call was 

signed to as long as 12 months after the 


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