Federal Register / Vol. 79, No. 247 / Wednesday, December 24, 2014 / Rules and Regulations 77387 

constituent amino acids, phenylalanine 

and aspartic acid, and a small amount 

of methanol. By contrast, the primary 

metabolite of advantame is the deesterified form of advantame, namely N- 

[N-[3-(3-hydroxy-4- 

methoxyphenyl)propyl]-a-aspartyl]-Lphenylalanine. Because chemically 

these two sweeteners are different 

compounds, FDA’s safety decision on 

advantame was based solely on studies 

conducted on advantame. Therefore, we 

did not consider the health effects of 

aspartame in our safety decision on 

advantame. 

Regarding concerns about possible 

effects of advantame on the 

hypothalamus, the hypothalamus is 

involved with endocrine control via the 

pituitary gland. Therefore, any longlasting hypothalamic changes would 

affect the pituitary gland. For this 

reason, we recommend in our guidance 

‘‘Toxicological Principles for the Safety 

Assessment of Direct Food Additives 

and Color Additives Used in Food’’ that 

the pituitary gland from subchronic and 

long-term animal studies be assessed for 

treatment-related changes. Consistent 

with our guidance, the pituitary gland 

was one of the organs evaluated in the 

animal studies on advantame that were 

considered in the final rule, and there 

was no evidence of toxicologically 

significant changes. 

As previously noted, NRDC has 

requested that we withdraw our 

approval of advantame until we 

examine the brain tissues from the key 

advantame animal studies that were 

preserved for alteration of the 

hypothalamus and fully consider the 

implications on a child’s developing 

brain. NRDC has claimed that several 

studies on a different substance showed 

effects on the hypothalamus, but has not 

provided any information to support its 

view that additional histopathological 

examination of brain tissue samples is 

necessary to establish the safety of 

advantame. During our evaluation of the 

advantame petition, we thoroughly 

reviewed all of the data provided by the 

petitioner on the safety of advantame, 

including the results from a twogeneration study in rats, a chronic (52- 

week) dog study, a 104-week mouse 

carcinogenicity study, and a combined 

104-week rat carcinogenicity feeding 

study with in utero and chronic (52- 

week) phases, which included extensive 

histological evaluations of the brain, 

including the hypothalamus. In 

evaluating these studies, we applied the 

appropriate safety factors to extrapolate 

the findings from these animal studies 

to humans as required by section 

409(c)(5) of the FD&C Act. We also 

considered the potential intake of 

advantame at both the mean and 90th 

percentile of consumption for various 

age groups, including children. Based 

on this exposure and toxicological 

information, the estimated levels of 

daily intake for even high consumers of 

advantame were far below 

(approximately 200 times) the 

acceptable daily intake level, 

establishing that advantame is safe for 

the general population, including 

children. 

NRDC’s objection to the advantame 

final rule does not provide any new 

evidence or identify any evidence that 

we overlooked in our evaluation that 

would call into question FDA’s 

determination of safety for advantame. 

Moreover, NRDC has not provided a 

basis for concluding that the 

information we evaluated is inadequate 

to support a finding that the use of 

advantame as a non-nutritive sweetener 

in food is safe. Therefore, this objection 

does not provide a basis for us to 

reconsider our decision to issue the 

final rule on advantame. 

IV. Summary and Conclusion 

Section 409 of the FD&C Act requires 

that a food additive be shown to be safe 

before marketing. Under 21 CFR 

170.3(i), a food additive is ‘‘safe’’ if 

‘‘there is a reasonable certainty in the 

minds of competent scientists that the 

substance is not harmful under the 

intended conditions of use.’’ In our May 

21, 2014, final rule approving the use of 

advantame, we concluded that the data 

presented by the petitioner to establish 

safety of the additive demonstrate that 

advantame is safe for its intended use in 

food. 

The petitioner has the burden to 

demonstrate the safety of the additive to 

gain FDA approval. However, once we 

make a finding of safety, the burden 

shifts to an objector, who must come 

forward with evidence that calls into 

question our conclusion (see section 

409(f)(1) of the FD&C Act). After 

evaluating the objection from NRDC, we 

have concluded that the objection does 

not provide any basis for us to 

reconsider our decision to issue the 

final rule permitting the use of 

advantame as a non-nutritive sweetener 

and flavor enhancer in foods generally, 

except meat and poultry. Accordingly, 

we are not making any changes in 

response to the objection. 

Therefore, we have determined that 

the final rule should not be modified or 

revoked based on the objections. Thus, 

we are confirming May 21, 2014, as the 

effective date of the regulation. 

Dated: December 18, 2014. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2014–30144 Filed 12–23–14; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 860 

[Docket No. FDA–2013–N–1529] 

Medical Device Classification 

Procedures; Reclassification Petition: 

Content and Form; Technical 

Amendment 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final rule; technical 

amendments. 

SUMMARY: The Food and Drug 

Administration (FDA) is amending its 

regulations for petitioning for device 

reclassification to update mailing 

addresses for the petitions. This action 

is being taken to improve the accuracy 

of the regulations. 

DATES: This rule is effective December 

24, 2014. 

FOR FURTHER INFORMATION CONTACT: 

Nancy Pirt, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 4438, Silver Spring, 

MD 20993–0002, 301–796–6254. 

SUPPLEMENTARY INFORMATION: FDA is 

updating mailing addresses for device 

reclassification petitions (21 CFR 

860.123). For devices regulated by the 

Center for Devices and Radiological 

Health, the room number is now 4438. 

In addition, the Center for Biologics 

Evaluation and Research has moved to 

a new location at FDA’s White Oak 

Campus. The address remains the same 

for the Center for Drug Evaluation and 

Research. The regulations are being 

amended to ensure clarity and to 

improve the accuracy and readability of 

the regulations. 

Publication of this document 

constitutes final action on these changes 

under the Administrative Procedure Act 

(5 U.S.C. 553). FDA has determined that 

notice and public comment and a 

delayed effective date are unnecessary 

because these corrections are 

nonsubstantive. 

List of Subjects in 21 CFR Part 860 

Administrative practice and 

procedure, Medical devices. 

Therefore, under the Federal Food, 

Drug, and Cosmetic Act and under 

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77388 Federal Register / Vol. 79, No. 247 / Wednesday, December 24, 2014 / Rules and Regulations 

authority delegated to the Commissioner 

of Food and Drugs, 21 CFR part 860 is 

amended as follows: 

PART 860—MEDICAL DEVICE 

CLASSIFICATION PROCEDURES 

■ 1. The authority citation for 21 CFR 

part 860 continues to read as follows: 

Authority: 21 U.S.C. 360c, 360d, 360e, 

360i, 360j, 371, 374. 

■ 2. Revise § 860.123(b)(1) to read as 

follows: 

§ 860.123 Reclassification petition: 

Content and form. 

* * * * * 

(b) * * * 

(1) For devices regulated by the 

Center for Devices and Radiological 

Health, addressed to the Food and Drug 

Administration, Center for Devices and 

Radiological Health, Regulations Staff, 

10903 New Hampshire Ave., Bldg. 66, 

Rm. 4438, Silver Spring, MD 20993– 

0002; for devices regulated by the 

Center for Biologics Evaluation and 

Research, addressed to the Food and 

Drug Administration, Center for 

Biologics Evaluation and Research, 

Document Control Center, 10903 New 

Hampshire Ave., Bldg. 71, Rm. G112, 

Silver Spring, MD 20993–0002; for 

devices regulated by the Center for Drug 

Evaluation and Research, addressed to 

the Food and Drug Administration, 

Center for Drug Evaluation and 

Research, Central Document Control 

Room, 5901–B Ammendale Rd., 

Beltsville, MD 20705–1266, as 

applicable. 

* * * * * 

Dated: December 18, 2014. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2014–30141 Filed 12–23–14; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF THE TREASURY 

Internal Revenue Service 

26 CFR Part 1 

[TD 9707] 

RIN 1545–BM08 

Filing of Form 5472 

AGENCY: Internal Revenue Service (IRS), 

Treasury. 

ACTION: Final regulations. 

SUMMARY: This document contains final 

regulations concerning the manner of 

filing Form 5472, ‘‘Information Return 

of a 25% Foreign-Owned U.S. 

Corporation or a Foreign Corporation 

Engaged in a U.S. Trade or Business.’’ 

The final regulations affect certain 25- 

percent foreign-owned domestic 

corporations and certain foreign 

corporations that are engaged in a trade 

or business in the United States that are 

required to file Form 5472. 

DATES: Effective date: These regulations 

are effective on December 24, 2014. 

Applicability date: For dates of 

applicability, see §§ 1.6038A–1(n)(2) 

and (n)(3) and 1.6038A–2(g). 

FOR FURTHER INFORMATION CONTACT: 

Anand Desai at (202) 317–6939 (not a 

toll-free number). 

SUPPLEMENTARY INFORMATION: 

Background 

On June 6, 2014, the Department of 

the Treasury (Treasury Department) and 

the IRS published a notice of proposed 

rulemaking (REG–114942–14) in the 

Federal Register (79 FR 32687, 2014–26 

IRB 1117) under sections 6038A and 

6038C of the Internal Revenue Code 

(Code) (proposed regulations). The 

proposed regulations proposed 

removing a provision for timely filing 

Form 5472 separately from an income 

tax return that is untimely filed 

(‘‘untimely filed return provision’’). As 

a result, Form 5472 would be required 

to be filed in all cases only with the 

filer’s income tax return for the taxable 

year by the due date (including 

extensions) of that return. No public 

hearing was requested or held. The 

Treasury Department and the IRS 

received two written comments on the 

proposed regulations, which are 

available at www.regulations.gov. After 

consideration of the comments, this 

Treasury decision adopts the proposed 

regulations, without substantive change, 

as final regulations. 

Summary of Comments 

One comment recommended that the 

‘‘untimely filed return provision’’ be 

retained because the IRS may not timely 

receive the information required by 

Form 5472 if the untimely filed return 

provision is removed. The comment 

also recommended conforming changes 

to permit the filing of Form 5471, 

‘‘Information Return of U.S. Persons 

With Respect to Certain Foreign 

Corporations,’’ and Form 8865, ‘‘Return 

of U.S. Persons With Respect to Certain 

Foreign Partnerships,’’ separately from 

an income tax return that is untimely 

filed. 

The Treasury Department and the IRS 

decline to adopt this comment. The 

Treasury Department and the IRS have 

determined that tax administration 

generally is more efficient when forms 

(for example, Form 5471, Form 5472, 

and Form 8865) are filed with the filer’s 

timely filed income tax return. 

The second comment addressed 

issues unrelated to the proposed 

regulatory change. The final regulations 

do not incorporate the suggestions 

contained in this comment, which are 

outside the scope of the proposed 

regulations. 

Special Analyses 

It has been determined that these 

regulations are not a significant 

regulatory action as defined in 

Executive Order 12866, as 

supplemented by Executive Order 

13563. Therefore, a regulatory 

assessment is not required. It has also 

been determined that section 553(b) of 

the Administrative Procedure Act (5 

U.S.C. chapter 5) does not apply to these 

regulations, and because the regulations 

do not impose a collection of 

information, the Regulatory Flexibility 

Act (5 U.S.C. chapter 6) does not apply. 

Pursuant to section 7805(f) of the Code, 

the notice of proposed rulemaking 

preceding this regulation was submitted 

to the Chief Counsel for Advocacy of the 

Small Business Administration for 

comment on its impact on small 

business. 

Drafting Information 

The principal author of these 

regulations is Anand Desai, Office of 

Associate Chief Counsel (International). 

However, other personnel from the 

Treasury Department and the IRS 

participated in their development. 

List of Subjects in 26 CFR Part 1 

Income taxes, Reporting and 

recordkeeping requirements. 

Adoption of Amendments to the 

Regulations 

Accordingly, 26 CFR part 1 is 

amended as follows: 

PART 1—INCOME TAXES 

■ Paragraph 1. The authority citation 

for part 1 continues to read in part as 

follows: 

Authority: 26 U.S.C. 7805 * * * 

■ Par. 2. Section 1.6038A–1 is amended 

by revising the third sentence of, and 

adding a new fourth sentence to, 

paragraph (n)(2), and adding a third 

sentence to paragraph (n)(3), to read as 

follows: 

§ 1.6038A–1 General requirements and 

definitions. 

* * * * * 

(n) * * * 

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