
[Federal Register Volume 82, Number 85 (Thursday, May 4, 2017)]
[Proposed Rules]
[Pages 20847-20859]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-08987]



[[Page 20847]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 170, 177, and 189

[Docket No. FDA-2015-F-0537]


Natural Resources Defense Council et al.; Denial of Food Additive 
Petition

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification; denial of petition.

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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is 
denying a petition, submitted by the Natural Resources Defense Council, 
Center for Food Safety, Clean Water Action, Children's Environmental 
Health Network, Center for Science in the Public Interest, Breast 
Cancer Fund, Center for Environmental Health, Environmental Working 
Group, and Improving Kids' Environment, requesting that we revoke the 
Threshold of Regulation (TOR) exemption No. 2005-006 to no longer 
exempt from our food additive regulations the use of sodium perchlorate 
monohydrate as a conductivity enhancer in antistatic agents for use in 
finished articles in contact with dry foods; issue a new FDA regulation 
to prohibit the use of perchlorates in antistatic agents for use in 
food-contact articles; and amend our food additive regulations to no 
longer provide for the use of potassium perchlorate as an additive in 
closure-sealing gaskets for food containers.

DATES: This notification is effective May 4, 2017; except as to any 
provisions that may be stayed by the filing of proper objections. See 
Section VI of this document for information on the filing of 
objections. Submit either electronic or written objections and requests 
for a hearing by June 5, 2017. Late, untimely filed objections will not 
be considered. The https://www.regulations.gov electronic filing system 
will accept comments until midnight Eastern Time at the end of June 5, 
2017. Objections received by mail/hand delivery/courier (for written/
paper submissions) will be considered timely if they are postmarked or 
the delivery service acceptance receipt is on or before that date.

ADDRESSES: You may submit either electronic or written objections and 
requests for a hearing identified by Docket No. FDA-2015-F-0537, by any 
of the following methods:

Electronic Submissions

    Submit electronic objections in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Objections submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your objection will be 
made public, you are solely responsible for ensuring that your 
objection does not include any confidential information that you or a 
third party may not wish to be posted, such as medical information, 
your or anyone else's Social Security number, or confidential business 
information, such as a manufacturing process. Please note that if you 
include your name, contact information or other information that 
identifies you in the body of your objection, that information will be 
posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the objection as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper objections submitted to the Division of 
Dockets Management, FDA will post your objection, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2015-F-0537 for ``Natural Resources Defense Council et al.; Denial 
of Food Additive Petition.'' Received objections, those filed in a 
timely manner (see DATES), will be placed in the docket, and except for 
those submitted as ``Confidential Submissions,'' publically viewable at 
https://www.regulations.gov or at the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit an objection with 
confidential information that you do not wish to be made publicly 
available, submit your objections only as a written/paper submission. 
You should submit two copies total. One copy will include the 
information you claim to be confidential with a heading or cover note 
that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' We 
will review this copy, including the claimed confidential information, 
in our consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
objections received, go to https://www.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Hui-Chen (Anita) Chang, Center for 
Food Safety and Applied Nutrition (HFS-275), Food and Drug 
Administration, 5001 Campus Dr., College Park, MD 20740-3835, 240-402-
1161.

SUPPLEMENTARY INFORMATION: 

I. Introduction

    In a document published in the Federal Register of March 16, 2015 
(80 FR 13508), we announced that we filed a food additive petition (FAP 
4B4808) (``petition'') submitted by the Natural Resources Defense 
Council, 1152 15th St. NW., Suite 300, Washington, DC 20005; the Center 
for Food Safety, 303 Sacramento St., Second Floor, San Francisco, CA 
94111; Clean Water Action, 144 I St. NW., Suite 400, Washington, DC 
20005; the Center for Science in the Public Interest, 1220 L St. NW., 
Suite 300, Washington, DC 20005; Children's Environmental Health 
Network, 110 Maryland Ave. NE., Suite 402, Washington, DC 20002; the 
Breast Cancer Fund, 1388 Sutter St., Suite 400, San Francisco, CA 
94109-5400; the Center for Environmental Health, 2201 Broadway, Suite 
302, Oakland, CA 94612; Environmental Working Group, 1436 U St. NW., 
Suite 100, Washington,

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DC 20009; and Improving Kids' Environment, 1915 West 18th St., 
Indianapolis, IN 46202 (collectively, ``petitioners''). In the March 
2015 document, we requested comments on the petition under Sec.  
189.1(c) (21 CFR 189.1(c)). The petition included submissions dated 
July 31, 2014, October 15, 2014, and December 5, 2014. The October 15, 
2014, submission included a resubmission of the entire July 31, 2014, 
original petition with the inclusion of some additional information. 
The December 5, 2014, submission contained additional information to 
that provided in the October 15, 2014, submission. Any references to 
specific parts of the petition are to the October 15, 2014, submission 
while specific references to the December 5, 2014, submission will 
refer to the date of that document.
    The petition asked FDA to take three separate regulatory actions: 
(1) Revoke its 2005 approval of TOR exemption No. 2005-006 allowing as 
much as 1.2 percent sodium perchlorate monohydrate in dry food 
packaging; (2) issue a new Sec.  189.301 (21 CFR 189.301) prohibiting 
the use of perchlorate as a conductivity enhancer in the manufacture of 
antistatic agents to be used in food contact articles; and (3) remove 
potassium perchlorate as an allowed additive in sealing gaskets for 
food containers in existing Sec.  177.1210 (21 CFR 177.1210). For 
accuracy, we will refer to the petition's second request as a request 
to issue a new regulation under part 189 because a regulation already 
exists at Sec.  189.301. The petition asserted that the allowed food-
contact uses of perchlorate are not safe because there is no longer a 
reasonable certainty that the perchlorate is not harmful under the 
intended conditions of use considering: (1) The probable consumption of 
perchlorate; (2) the cumulative effect of perchlorate after taking into 
account pharmacologically-related substances, such as thiocyanate and 
nitrate, in the diet; and (3) additional safety factors necessary to 
protect the developing brain of fetuses and infants from irreversible 
harm. The petition also asserted that new exposure data are available 
that support the requested revocation of TOR exemption No. 2005-006.
    Both food contact substances that are the subject of the petition--
sodium perchlorate monohydrate and potassium perchlorate--belong to a 
class of chemicals termed ``perchlorates.'' Perchlorates are both 
naturally-occurring and man-made chemicals with a wide variety of 
industrial and some medical applications. Perchlorates are ionic salts 
that contain the perchlorate anion (chemical structure 
ClO4-). In this notification, the term 
``perchlorates'' refers to the class of chemicals while the term 
``perchlorate'' refers to the perchlorate ion.

II. Background

A. Statutory and Regulatory Background

    The petition asked FDA to take actions related to three different 
types of FDA regulations.
1. Food Additive Regulation
    The Federal Food, Drug, and Cosmetic Act (the FD&C Act) authorizes 
us to regulate ``food additives'' (see section 409(a) of the FD&C Act 
(21 U.S.C. 348(a)). The FD&C Act defines ``food additive,'' in relevant 
part, as any substance the intended use of which results or may 
reasonably be expected to result, directly or indirectly, in its 
becoming a component of food (see section 201(s) of the FD&C Act (21 
U.S.C. 321(s))). Food additives can include both substances added 
directly to food and ``food contact substance[s]'' (i.e., substances 
intended for use in materials that come into contact with food, for 
instance in food packaging or manufacturing, but which are not intended 
to have any technical effect in the food (see Sec.  170.3(e)(3) (21 CFR 
170.3(e)(3))). Food additives are deemed unsafe and prohibited except 
to the extent that we approve their use (see, e.g., section 301(a) and 
(k) (21 U.S.C. 331(a) and (k)) and 409(a) of the FD&C Act).
    The FD&C Act provides a process through which persons who wish to 
use a food additive may submit a petition proposing the issuance of a 
regulation prescribing the conditions under which the additive may be 
safely used (see section 409(b)(1) of the FD&C Act). Such a petition is 
referred to as a ``food additive petition.'' When we conclude that a 
proposed use of a food additive is safe, we issue a regulation called a 
``food additive regulation'' authorizing a specific use of the 
substance.
    The specific food additive regulation at issue in the petition, 
Sec.  177.1210, lists substances allowed as indirect additives (also 
called food contact substances) in closures with sealing gaskets for 
food containers. Potassium perchlorate is one of the listed substances 
authorized for this use under Sec.  177.1210.
    The FD&C Act provides that we must by regulation prescribe the 
procedure by which a food additive regulation may be amended or 
repealed (see section 409(i) of the FD&C Act). Our regulation specific 
to the administrative actions for food additives provides that the 
Commissioner of Food and Drugs (the Commissioner), on his own 
initiative or on the petition of any interested person, may propose the 
issuance of a regulation amending or repealing a regulation pertaining 
to a food additive (see Sec.  171.130(a) (21 CFR 171.130(a))). Our 
regulation, at Sec.  171.130(b), further provides that any such 
petition must include an assertion of facts, supported by data, showing 
that new information exists with respect to the food additive or that 
new uses have been developed or old uses abandoned, that new data are 
available as to toxicity of the chemical, or that experience with the 
existing regulation or exemption may justify its amendment or repeal.
    FDA has issued administrative regulations for food additive 
petitions in part 171. These regulations apply to food additive 
petitions requesting either that we authorize the new use of a food 
additive or that we amend or repeal an existing food additive 
regulation.
2. TOR Exemption
    The food additive petition process generally applies to substances 
used in food packaging or processing when the proposed use will cause 
the substance to become part of the food at a level that exceeds a 
minimum ``threshold of regulation'' (see Sec.  170.39 (21 CFR 170.39)). 
Our determination that a use of a substance is at or below the 
``threshold of regulation'' is referred to as a ``threshold of 
regulation'' exemption, or a TOR exemption. Regardless of whether the 
use of a substance is at or below the threshold of regulation, we 
reserve the right to apply the food additive petition process in those 
cases in which available information establishes that the proposed 
food-contact use may pose a public health risk (see Sec.  170.39(b)).
    We established the procedures set forth in Sec.  170.39 to exempt 
certain substances used in food-contact articles (e.g., food-packaging 
(such as a cereal bag) or food-processing equipment) that migrate or 
may be expected to migrate into food at negligible levels from 
regulation as a food additive. Eligible substances must become a 
component of food at levels that are at or below the threshold of 
regulation, must not have been shown to cause cancer in humans or 
animals or be suspected carcinogens, and must meet other criteria in 
Sec.  170.39. If we determine the criteria are met, we inform the 
requestor by letter that the intended use of a substance in food-
contact articles is exempt from regulation as a food additive. 
Therefore, when we issue a TOR exemption, the intended use of the 
substance does not require a regulation authorizing its food

[[Page 20849]]

additive use under section 409 of the FD&C Act (also referred to as a 
``listing regulation'') or food additive petition (see Sec. Sec.  
170.3(e)(2) and 171.8). We issued TOR exemption No. 2005-006 in 2005. 
We maintain a list of TOR exemptions on our Web site (Ref. 1).
    Our regulations provide that if we receive significant new 
information that raises questions about the dietary concentration or 
the safety of a substance that is the subject of a TOR exemption, we 
may reevaluate the substance (see Sec.  170.39(g)). Our regulations, at 
Sec.  170.39(g), state that if we tentatively conclude that the 
available information no longer supports an exemption for the use of 
the food-contact material from the food additive regulations, we will 
notify any persons that requested an exemption for the substance of our 
tentative decision and will provide them with an opportunity to show 
why the use of the substance should not be regulated under the food 
additive provisions of the FD&C Act. If the requestors fail to 
adequately respond to the new evidence, we notify them that further use 
of the substance in question for the particular use will require a food 
additive regulation (see Sec.  170.39(g)). Thus, anyone who seeks to 
use such substance as a food additive would need to submit a food 
additive petition seeking such a regulation or obtain authorization 
through a food contact notification. We also notify other 
manufacturers, by means of a notice published in the Federal Register, 
of our decision to revoke a TOR exemption issued for a specific use of 
a substance in a food-contact article (see Sec.  170.39(g)).
3. Regulation Under Part 189
    Our regulations at Sec.  189.1(a) provide that ``food ingredients'' 
may be prohibited from uses in human food based on a determination that 
the food ingredients present a potential risk to the public health or 
have not been shown by adequate scientific data to be safe for use in 
human food. Additionally, Sec.  189.1(c) provides that the 
Commissioner, either on his own initiative or on the petition of any 
interested person, may publish a proposal to establish, amend, or 
repeal a regulation under this section on the basis of new scientific 
evaluation or information. We established part 189 to: (1) Provide, for 
reference purposes, a partial listing of substances prohibited from use 
in human food and (2) create an administrative process through which we 
can prohibit by rulemaking the use of substances in human foods because 
of a determination that they present a potential risk to the public 
health or have not been shown by adequate scientific data to be safe 
for use in human foods (see 39 FR 34172, September 23, 1974).

B. Abandonment of Use of Potassium Perchlorate Authorized Under 21 CFR 
Sec.  177.1210

    In a document published in the Federal Register on June 30, 2016 
(81 FR 42585), we announced that we filed a food additive petition (FAP 
6B4816) (``abandonment petition'') that proposed that we amend Sec.  
177.1210 to no longer provide for the use of potassium perchlorate as 
an additive in closure-sealing gaskets for food containers because the 
use has been intentionally and permanently abandoned. Elsewhere in this 
issue of the Federal Register, we have published a final rule 
concluding that the use of potassium perchlorate authorized under Sec.  
177.1210 has been permanently and completely abandoned. The final rule 
amends Sec.  177.1210 to no longer authorize the use of potassium 
perchlorate as an additive in closure-sealing gaskets for food 
containers.
    Because the final rule issued in response to the abandonment 
petition removes potassium perchlorate as an allowed additive in 
sealing gaskets for food containers--thereby taking the third action 
requested in the petition--the petition's third request is moot, and it 
is neither necessary nor an efficient use of our resources to address 
the petitioners' assertions regarding the safety of the food additive 
use of potassium perchlorate that is no longer authorized. Where 
helpful for clarity, this notification will describe the petition's 
arguments regarding the food additive use of potassium perchlorate in 
the course of reviewing the petition's requests to revoke TOR exemption 
No. 2005-006 and to issue a new regulation under part 189.

C. The Scope of a Food Additive Petition

    The petitioners designated their petition as a ``food additive 
petition.'' A food additive petition must either propose the issuance 
of a regulation prescribing the conditions under which a food additive 
may be safely used (see section 409(b)(1) of the FD&C Act), or propose 
the amendment or repeal of an existing food additive regulation (see 
section 409(i) of the FD&C Act).
    Only one of the petition's requested actions falls within the 
statutory scope of a food additive petition: Amending Sec.  177.1210 to 
remove potassium perchlorate as an allowed additive in sealing gaskets 
for food containers, the action we are taking in response to the 
abandonment petition. Because the petition's other two requests--the 
revocation of TOR exemption No. 2005-006 and the issuance of a 
regulation under part 189 prohibiting the use of perchlorate in the 
manufacture of antistatic agents to be used in food-contact articles--
are not directed at regulations issued under the food additive petition 
process, they are governed by different regulations and are not subject 
to the statutory processes for food additive petitions.
    TOR substances, i.e., substances used in food-contact articles that 
become a component of food at levels that are below the threshold of 
regulation and meet the criteria in Sec.  170.39, are exempt from 
regulation as food additives and do not require a listing regulation or 
food additive petition (see Sec. Sec.  170.3(e)(2) and 171.8). As noted 
in the filing notice for this petition, the procedures for reevaluating 
and revoking a TOR exemption are set forth in Sec.  170.39(g). These 
procedures are distinct from the food additive petition process. A 
request to revoke a TOR exemption is the proper subject of a citizen 
petition submitted under 21 CFR 10.30.
    The petition's request that we issue a new regulation under part 
189 also falls outside the scope of a food additive petition. A 
proposed part 189 regulation does not propose the issuance of a new 
food additive regulation or the amendment or repeal of an existing food 
additive regulation (see sections 409(b)(1) and (i) of the FD&C Act). 
Under part 189, an interested person can use the citizen petition 
process to request a regulation prohibiting a substance from human food 
(see Sec.  189.1(c) (referring to 21 CFR part 10, which sets forth 
FDA's citizen petition process)).
    Although the requests to revoke the approval of TOR exemption No. 
2005-006 and to issue a new regulation under part 189 are outside the 
scope of a food additive petition, for reasons of administrative 
efficiency, we initially considered these requests in conjunction with 
the petition's request to amend Sec.  177.1210 to remove potassium 
perchlorate as an allowed additive in sealing gaskets for food 
containers. Because the food additive use of potassium perchlorate has 
been removed from Sec.  177.1210 in response to the abandonment 
petition, it is neither necessary nor an efficient use of resources to 
address the petition's assertions regarding this use of perchlorate. 
Nonetheless, because we considered all of these requests together for 
purposes of administrative efficiency, we are addressing the

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petition's requests to revoke the approval of TOR exemption No. 2005-
006 and to issue a new regulation under part 189 in this document. 
However, although we are addressing these requests in connection with 
our denial of a food additive petition, we emphasize that these 
requests are not the proper subject of a food additive petition. Our 
denial of these two requests is a final Agency decision, but is not an 
order under section 409(c)(1)(B) of the FD&C Act.

D. Background on Perchlorate

    Perchlorate can interfere with the normal functioning of the 
thyroid gland by competitively inhibiting the transport of iodide into 
the thyroid. Iodide is an important component of two thyroid hormones, 
T4 and T3, and the transfer of iodide from the blood into the thyroid 
is an essential step in the synthesis of these two hormones. Iodide 
transport into the thyroid is mediated by a protein molecule known as 
the sodium (Na+)-iodide (I-) symporter (NIS). NIS 
molecules bind iodide with high affinity, but they also bind other ions 
that have a similar shape and electric charge, such as perchlorate. The 
binding of these other ions to the NIS can inhibit iodide transport 
into the thyroid, which can result in intrathyroidal iodide deficiency 
and consequently decreased synthesis of T4 and T3 (73 FR 60262, 60266, 
October 10, 2008). In fetuses, infants, and young children, thyroid 
hormones are critical for normal growth and development. Id. at 60275. 
For example, sustained thyroid hormone decrement in a pregnant mother 
could lead to adverse neurodevelopmental effects in the fetus. Id. at 
60266. Research in this area is ongoing.
    As part of its discussion asserting that new information is 
available that raises question as to the safety of the allowed food-
contact uses of perchlorates, the petition cited two reviews on 
perchlorate requested by the Environmental Protection Agency (EPA): A 
2005 National Research Council (NRC) review (Ref. 2) and the 2013 
report of the EPA's Scientific Advisory Board (SAB) (Ref. 3). The 2005 
NRC report noted that thyroid iodide uptake inhibition (IUI) is the 
only effect that has been consistently documented in humans exposed to 
perchlorate. Therefore, as part of its review, the NRC utilized a 
hypothetical mode-of-action (MOA) framework, which represents a 
continuum of possible biological effects resulting from perchlorate 
exposure, to describe the potential pathway of events following 
perchlorate exposure. This MOA framework hypothesized that IUI could 
induce thyroid hormone changes to an extent that could ultimately 
result in neurodevelopmental effects in fetuses and infants. The SAB 
utilized a similar MOA framework. In both MOA frameworks, IUI is the 
determinant, non-adverse precursor effect, which must occur prior to 
any later adverse effect.
1. 2005 NRC Review
    The 2005 NRC report was prepared in response to a request from the 
EPA that the National Academy of Sciences review the science regarding 
potential adverse effects of disruption of thyroid function and provide 
recommendations to apply this information to a risk assessment for 
environmental contamination from perchlorate. The report recommended 
that EPA derive a reference dose (RfD) for perchlorate by applying a 
tenfold intraspecies uncertainty factor to a no observed effect level 
(NOEL) based on the initiation of IUI as determined in a human study 
(Ref. 4). (The RfD is an estimate (with uncertainty spanning perhaps an 
order of magnitude) of a daily oral exposure to the human population 
(including sensitive subgroups) that is likely to be without an 
appreciable risk of deleterious effects during a lifetime. The NOEL is 
an exposure level at which there are no statistically or biologically 
significant increases in frequency or severity of any effect between 
the exposed population and its appropriate control.) The NRC stated 
that this approach was conservative and protective of health given that 
the NOEL is based on the non-adverse effect of IUI, which precedes the 
continuum of possible adverse effects as a result of perchlorate 
exposure. According to the NRC, the application of the uncertainty 
factor accounts for differences in sensitivity between the healthy 
human subjects of the determinant clinical study and ``even the most 
sensitive populations'' for perchlorate exposure, which the NRC 
identified as fetuses of pregnant women who may have hypothyroidism or 
iodide deficiency. (Hypothyroidism is a condition where ``the thyroid 
gland does not produce enough thyroid hormones to meet the body's 
needs'' (Ref. 5)). EPA adopted the NRC's recommendations resulting in 
an RfD of 0.7 micrograms perchlorate/kilogram body weight/day ([mu]g/kg 
bw/d) (Ref. 6).
2. 2013 EPA SAB Report
    The 2013 SAB report was developed in response to a request by EPA 
for guidance on a suitable approach to utilize relevant available 
information to derive a maximum contaminant level goal (MCLG) for 
perchlorate in drinking water. The Safe Drinking Water Act defines an 
MCLG as the level of a contaminant in drinking water ``at which no 
known or anticipated adverse effects on the health of persons occur and 
which allows for an adequate margin of safety.'' 42 U.S.C. 300g-
1(b)(4). An MCLG is a nonenforceable public health goal. EPA generally 
derives an MCLG using the RfD and specific chemical exposure factors. 
(Ref. 7). Rather than this default approach, the SAB recommended that 
EPA expand existing physiologically-based pharmacokinetic/
pharmacodynamics (PBPK/PD) models to relate perchlorate exposure, in 
combination with iodide intake, beyond IUI to downstream MOA framework 
effects, such as resultant thyroid hormone perturbations and potential 
adverse neurodevelopmental outcomes. The SAB also recommended that the 
sensitive populations for exposure to perchlorate that EPA should 
consider when determining an MCLG are the fetuses of hypothyroxinemic 
pregnant women (hypothyroxinemia means that the free thyroxine (fT4) 
value is at lower end of the normal range with normal levels of thyroid 
stimulating hormone (Ref. 8)) and infants exposed to perchlorate 
through either water-based formula preparations or the breast milk of 
lactating women.

III. Review of the Petition

    The petition asserted that the original request for TOR exemption 
No. 2005-006 contained errors that should have made the request 
ineligible for a TOR exemption under Sec.  170.39. The petition also 
asserted that we made additional errors in exempting the proposed use 
of sodium perchlorate monohydrate from regulation as a food additive. 
The petition also identified four categories of ``significant new 
information that raises questions about the dietary concentration or 
the safety of a substance that [FDA] has exempted from regulation,'' 
that it contends warrant reevaluation of TOR exemption No. 2005-006 
under Sec.  170.39(g). Lastly, the petition asserted that infants are 
likely to be disproportionately impacted by perchlorate, and that we 
have an obligation under Executive Order 13045 (see 62 FR 19885, April 
23, 1997) to address risks to infants from perchlorate exposure. The 
petition also requested that FDA issue a new regulation under part 189 
to prohibit the use of perchlorate as a conductivity enhancer in the 
manufacture of antistatic agents to be ``applied to food contact 
articles.''
    We will first address the petition's arguments regarding the review 
of TOR exemption No. 2005-006, then address

[[Page 20851]]

the petition's arguments based on ``significant new information,'' then 
subsequently address the assertions pertaining to our obligation under 
Executive Order 13045, and finally, the request that we issue a new 
regulation under part 189.

A. Arguments Regarding Review of TOR Exemption No. 2005-006

    The petition claimed that multiple errors were made in the original 
calculation of dietary exposure resulting from the use allowed by the 
TOR exemption No. 2005-006 and that assumptions used in that 
calculation were either improperly applied or have been shown to be 
flawed based on new information available after the TOR exemption 
became effective. The petition stated further that if these alleged 
errors were addressed, the dietary exposure resulting from the use 
allowed by the TOR exemption No. 2005-006 would exceed the TOR 
exemption criteria.
    We describe the background for TOR exemption No. 2005-006 in 
section III.A.1. The issues raised in the petition concerning alleged 
errors in the original calculation and assumptions used in that 
calculation, as well as our responses to those issues, are discussed in 
sections III.A.2 through III.A.6.
1. Background for TOR Exemption No. 2005-006
    Our regulations, at Sec.  170.39(a)(2), provide the exposure 
criteria for a TOR exemption. As stated in Sec.  170.39(a)(2)(i), the 
use of a substance will be exempted from regulation as a food additive 
if the use in question is shown to result in or may be expected to 
result in dietary concentrations at or below 0.5 parts per billion 
(ppb), corresponding to dietary exposure levels at or below 1.5 
[micro]g of substance/person/day (based on a diet of 1,500 grams (g) of 
solid food and 1,500 g of liquid food per person per day). As noted in 
section II.A.2, Sec.  170.39(g) sets forth the procedures for 
reevaluating and revoking a TOR exemption.
    We have issued guidance documents to help interested parties when 
preparing premarket submissions for food contact substances. Our 
guidance document specific to chemistry recommendations for food 
contact substances (Ref. 9) (``chemistry guidance'') provides 
recommendations for: (1) Migration protocols to determine or estimate 
the concentration of a food contact substance in the specific food that 
contacts a given food-contact article containing the substance as a 
result of the intended use of that substance (``the migration of a 
substance'') and (2) how to use this information to calculate the 
resultant total dietary exposure to the substance as a result of its 
intended use. Our chemistry guidance provides general protocols for 
food-contact articles intended for single use, as well as general 
recommendations for articles intended for repeated use.
    The chemistry guidance also provides recommended migration 
protocols for certain specific use applications, including articles 
intended for use only with non-fatty, dry foods (termed ``Food Type 
VIII'' in our chemistry guidance). Specific to non-fatty, dry foods, 
the recommended protocol includes an assumption that a food contact 
substance migrates into non-fatty, dry foods at a level of 50 [micro]g 
substance per kilogram food, or 50 ppb. To determine total dietary 
exposure to a substance as a result of its intended use, the chemistry 
guidance recommends the application of a consumption factor to the 
concentration in food determined from the migration protocol. The 
consumption factor describes the fraction of the daily diet expected to 
contact a specific type of packaging material. Consumption factors are 
derived using information on the types of food consumed, the types of 
food contacting each packaging surface, the number of food packaging 
units in each food packaging category, the distribution of container 
sizes, and the ratio of the weight of food packaged to the weight of 
the package (Ref. 9).
    The request for TOR exemption No. 2005-006 was submitted to FDA by 
Ciba Specialty Chemicals Corporation (Ciba) on June 17, 2005. Although 
Ciba calculated exposure for sodium perchlorate monohydrate, in this 
document we convert Ciba's exposure numbers to exposure to the 
perchlorate anion (the substance of toxicological concern is the 
perchlorate anion and EPA's RfD for perchlorate is expressed on a 
perchlorate anion basis). To determine the concentration of perchlorate 
anion (i.e., ``perchlorate'') in food that contacts finished articles 
containing sodium perchlorate monohydrate as a result of TOR exemption 
No. 2005-006, Ciba applied the percentage of sodium perchlorate 
monohydrate in the finished food-contact article to the 50 ppb 
migration concentration assumption for non-fatty, dry foods listed in 
our chemistry guidance. This resulted in a sodium perchlorate 
monohydrate concentration in food of 0.6 ppb, which corresponds to a 
concentration of 0.4 ppb for perchlorate in food. To determine a total 
dietary concentration for perchlorate as a result of this specific use, 
Ciba then applied our consumption factor for substances that may be 
used in all polymers but only for specific uses (0.05) to this 
concentration value. This resulted in a total dietary concentration for 
sodium perchlorate monohydrate of 0.03 ppb, or 0.02 ppb for 
perchlorate. For comparison against the TOR exemption exposure criteria 
stipulated in Sec.  170.39(a)(2)(i), Ciba subsequently multiplied this 
total dietary concentration by FDA's assumption that an individual 
consumes 3 kg of food per day. This resulted in a dietary exposure of 
0.09 [micro]g sodium perchlorate monohydrate/person/day, or 0.063 
[micro]g perchlorate/person/day. A review that we conducted before TOR 
exemption 2005-006 became effective determined that the provided 
information demonstrated that the use would result in a dietary 
exposure below the 1.5 [micro]g/person/day TOR exemption criteria (Ref. 
10).
2. Issues Pertaining to Calculations Based on FDA's Chemistry Guidance
    The petition asserted that Ciba deviated from the recommendations 
provided in FDA's chemistry guidance when calculating the exposure to 
perchlorate that results from the intended use for the TOR exemption 
No. 2005-006. Specifically, the petition asserted that applying the 
percentage of sodium perchlorate monohydrate in the finished food-
contact article to the 50 ppb migration concentration assumption 
deviates from the recommended migration protocol for non-fatty, dry 
foods and improperly made Ciba's intended use for sodium perchlorate 
monohydrate eligible for a TOR exemption. Furthermore, the petition 
said that the original TOR exemption submission did not account for the 
recommendations presented in FDA's chemistry guidance for substances in 
food-contact articles intended for repeated-use.
    a. Applying the percentage of sodium perchlorate in the finished 
food-contact article to the 50 ppb migration concentration assumption. 
The petition asserted that Ciba ``varied'' from our chemistry guidance 
when it ``inserted the amount of perchlorate in the formulation (4%) 
and the amount of formulation in the packaging (30%) into'' the 
equation for calculating the dietary concentration of sodium 
perchlorate monohydrate. Specifically, Ciba applied the percentage of 
sodium perchlorate monohydrate in the finished food-contact article (4% 
x 30% = 1.2%) to the 50 ppb migration concentration assumption.
    We acknowledge that our chemistry guidance does not specifically 
discuss a procedure for applying the percentage of

[[Page 20852]]

a substance in the finished food-contact article to the 50 ppb 
migration concentration assumption for the food contact substance, but 
applying such a percentage to a migration concentration assumption does 
not deviate from that guidance. The migration protocol for Food Type 
VIII is written at a general level and does not preclude scientifically 
appropriate calculations based on the percentage of a food contact 
substance when using the 50 ppb migration concentration assumption. We 
believe it was scientifically appropriate for Ciba to apply the 
percentage of the food contact substance in the finished packaging to 
the 50 ppb migration concentration assumption. Ciba's calculation noted 
that sodium perchlorate monohydrate represents only a small fraction of 
the antistatic agent in which it is used (4 percent), and the 
antistatic agent itself represents only a fraction of the finished 
food-contact article in which it is used (30 percent). Therefore, 
absent contradictory data, it is scientifically reasonable to assume 
that sodium perchlorate monohydrate migrates to Food Type VIII at the 
level that it is present in the finished food-contact article (i.e., 
1.2 percent of the 50 ppb migration concentration assumption). Such 
percentages have been applied to migration concentration assumptions in 
other submissions that have been approved or become effective (Ref. 
11).
    We also note that the chemistry guidance states that dry foods with 
the surface containing no free fat or oil typically exhibit little or 
no migration, and cites volatile or low molecular weight adjuvants as 
examples of substances that would be expected to migrate into non-
fatty, dry foods. Sodium perchlorate monohydrate is an ionic compound 
with low volatility and therefore would not be expected to migrate from 
food-contact materials into non-fatty, dry foods (Ref. 11). Therefore, 
there is no scientific basis to suggest that sodium perchlorate 
monohydrate would migrate into non-fatty, dry foods at a higher 
percentage of the 50 ppb migration concentration assumption than its 
percentage in the food-contact article.
    The appropriateness of Ciba's approach of applying the percentage 
of sodium perchlorate monohydrate in the finished food-contact article 
to the 50 ppb migration concentration assumption is supported by 
available analytical data provided in comments to the docket for the 
petition. The migration protocol specific to non-fatty, dry foods 
provided in our chemistry guidance recommends either the estimation of 
the migration of a substance using the 50 ppb migration concentration 
assumption or the determination of the actual migration via appropriate 
migration studies. Comments submitted to the docket for the petition 
include a migration study for sodium perchlorate monohydrate from a 
worst-case polymeric resin into a simulant for non-fatty, dry foods 
(see Docket Nos. FDA-2015-F-0537, Supplemental Comments from BASF 
Corporation (Keller and Heckman LLP) (FDA-2015-F-0537-18), BASF Corp 
Migration Report (Redacted) re: Supplemental Comments from BASF 
Corporation (Keller and Heckman LLP) (FDA-2015-F-0537-19), BASF 
Corporation Appendix A--Analysis Method (Redacted) re: Supplemental 
Comments from BASF Corporation (Keller and Heckman LLP) (FDA-2015-F-
0537-20), BASF Corporation Appendix B--Detailed Sample Analysis Data 
(Redacted) re: Supplemental Comments from BASF Corporation (Keller and 
Heckman LLP) (FDA-2015-F-0537-21), BASF Corporation Appendix C--
Chromatograms (Redacted) re: Supplemental Comments from BASF 
Corporation (Keller and Heckman LLP) (FDA-2015-F-0537-22), and BASF 
Corporation Appendix D--Spiking Validation at Low Perchlorate 
(Redacted) re: Supplemental Comments from BASF Corporation (Keller and 
Heckman LLP) (FDA-2015-F-0537-23)). We reviewed this study and 
determined that it is adequate to determine worst-case migration of 
perchlorate into non-fatty, dry foods as a result of the use specified 
in the TOR exemption No. 2005-006 (Ref. 11). As such, the migration 
concentration in food for perchlorate as determined from this migration 
study can be used to verify the appropriateness of Ciba's approach of 
applying the percentage of sodium perchlorate monohydrate in the 
finished food-contact article to the 50 ppb migration concentration 
assumption.
    The migration study reported its results on a basis of grams of 
perchlorate per surface area of test sample. To convert this reporting 
basis to grams of perchlorate per gram of food, we applied our standard 
assumption for the food mass-to-surface area ratio for consumer 
packaging (10 g of food contacting each square inch of food-contact 
article) to the results of the migration study. This results in a 
migration concentration of 0.5 nanogram (ng) perchlorate/g food, or 0.5 
ppb. This value is substantially less than the 50 ppb migration 
concentration assumption provided in our chemistry guidance and is 
essentially equivalent to the 0.4 ppb concentration for perchlorate in 
food calculated using Ciba's approach in its TOR submission. The 
dietary exposure to perchlorate calculated using the concentration for 
perchlorate in food obtained from the migration study (0.075 [mu]g/
person/day) is also essentially equivalent to that calculated using 
Ciba's approach (0.063 [micro]g/person/day) and is lower than the TOR 
exemption criteria of 1.5 [mu]g/person/day. The results of the 
migration study confirm that Ciba's approach to calculating migration 
was scientifically appropriate. Both the migration study and Ciba's 
approach resulted in dietary exposure figures for sodium perchlorate 
monohydrate that were lower than the TOR exemption criteria. Therefore, 
the petition's assertion that the intended use of sodium perchlorate 
monohydrate would not be eligible for a threshold of regulation 
exemption if migration had been properly calculated is unfounded.
    b. Calculation of dietary exposure based on migration protocol. As 
discussed in section III.A.1, FDA's chemistry guidance discusses 
general protocols for food-contact articles intended for single-use 
(e.g., a disposable paper cup), as well as for articles intended for 
repeated-use (e.g., a reusable ceramic mug). Part I.C.5 of the petition 
noted that Ciba's calculation of dietary exposure ``did not rely'' on 
the recommended migration protocol in our chemistry guidance for food-
contact articles intended for repeated use. Related to this argument, 
in the December 5, 2014, submission, the petitioners asserted that 
Ciba's use of a single-use protocol, rather than a repeated-use 
protocol, does not account for the release of perchlorate over time 
``as the plastic degrades or is flexed.''
    Using the single-use protocol results in a higher exposure value 
than using the repeated-use protocol because: (1) The factors applied 
to the migration value to determine exposure in the single-use protocol 
are exaggerative and (2) exposure values from repeated-use articles are 
typically very small in comparison to single-use articles. Therefore, 
when a food contact substance will be used in both single- and 
repeated-use articles, it is more conservative and protective to use 
the single-use protocol to determine exposure than it is to use the 
repeated-use protocol. Accordingly, where, as here, a food contact 
substance is intended to be used in both single- and repeated-use food-
contact articles, we use the single-use protocol to determine exposure. 
We only use the repeated-use protocol for food contact substances that 
are only used in repeated-use food-contact articles. As Ciba's intended 
use

[[Page 20853]]

of sodium perchlorate monohydrate was not limited to repeated-use food-
contact articles, its use of the single-use protocol, rather than the 
repeated-use protocol, was appropriate.
    i. Background on migration protocols. The migration protocols in 
the chemistry guidance provide recommendations on: (1) How to determine 
the total migration of a substance from a given food-contact surface 
area (migration value) and (2) how to use that migration value to 
determine dietary exposure to the migrating substance based upon the 
mass of food the food-contact surface area will come into contact with 
and the percentage of the diet that mass of food constitutes. The 
single-use and repeated-use protocols both provide similar 
recommendations on how to determine the total amount of migration of a 
substance from a given food-contact surface area; however, they differ 
in the assumptions used to determine dietary exposure from that 
migration value. Specifically, to determine dietary exposure, the 
single-use protocol applies the following factors to the migration 
value: (1) FDA's standard assumption of the amount of food in contact 
with a given surface area of a single-use articles (10 g of food 
contacting each square inch of food-contact article); (2) food-type 
distribution factors to account for the variable nature of the food 
contacting each food-contact article (when applicable); and (3) 
consumption factors (i.e., the fraction of the daily diet expected to 
contact a specific type of packaging material). Ciba's calculation did 
not use food-type distribution factors, and we will not discuss such 
factors further. By comparison, the repeated-use protocol recommends 
that dietary exposure be determined by applying to the migration value 
an estimate of the total mass of food contacting a known food-contact 
surface area over the service life of the article.
    ii. Use of the single-use protocol for substances in both single- 
and repeated-use articles. We consider the exposure calculated from the 
single-use protocol to address the exposure to a food contact substance 
used in both single- and repeated-use articles for several reasons, 
including that: (1) The factors applied to the migration value to 
determine exposure in the single-use protocol are exaggerative and (2) 
exposure values from repeated-use articles are typically very small in 
comparison to single-use articles.
    We consider the factors applied to the migration value to determine 
exposure in the single-use protocol to be exaggerative for several 
reasons. For instance, the use of a consumption factor in the single-
use protocol assumes that the food contact substance will be used in 
all food-contact articles that utilize the specific type of material to 
which the consumption factor applies (as discussed in section III.A.1, 
consumption factors are specific to a material--e.g., glass, paper, or 
plastic--in that the consumption factor describes the fraction of the 
daily diet expected to contact packaging that utilizes that type of 
material). This is an exaggerative assumption. Food contact substances 
are used in food-contact articles to perform a specific technological 
function. It is highly unlikely that all food-contact articles that use 
the type of packaging material to which a specific consumption factor 
applies will require that technological function. In addition, the use 
of a consumption factor does not account for the use of alternative 
food contact substances that perform the same technological function. 
The following example illustrates the exaggerative nature of the use of 
a consumption factor: Under the single-use protocol one could use FDA's 
consumption factor for colored plastics to determine exposure to a 
black pigment intended to be added to plastic food packaging. FDA's 
consumption factor for colored plastics describes the fraction of the 
daily diet expected to contact packaging that consists of colored 
plastic, regardless of the color of that plastic. However, not all 
colored plastic is black, and, therefore, a black pigment would not be 
added to all colored plastics. In addition, there are multiple black 
pigments that are authorized to color food-contact articles. Given that 
alternative black pigments are available for the same purpose, it is 
unlikely that all black colored plastic packaging would use the 
particular black pigment at issue.
    We also note that exposure values from repeated-use articles are 
typically very small in comparison to single-use articles because 
individual repeated-use articles come into contact with significantly 
larger amounts of food over their service lifetime than individual 
single-use articles. This results in a much greater food mass-to-
surface area ratio for repeated-use articles than the 10 g of food 
contacting each square inch of food-contact article assumption for 
single-use articles. The greater food mass-to-surface area ratio for 
repeated-use articles means that the total amount of migration of a 
substance from a given food-contact surface area (the migration value) 
is diluted across a much larger amount of food in comparison to a 
single-use article, resulting in a significantly lower dietary 
concentration.
    In conclusion, we consider the exposure to a food contact substance 
used in both single- and repeated-use articles to be addressed by the 
exaggerative exposure calculated via the single-use protocol. 
Therefore, we apply the single-use protocol to food contact substances 
intended to be used in both single-use and repeated-use food-contact 
articles.
    iii. Applying worst-case assumptions to available migration 
information. In any event, we note that the migration study described 
in section III.A.2.a followed equivalent or more stringent 
specifications than those recommended in the single- and repeated-use 
protocols. In section III.A.3, we explain that, even if the absolute 
worst-case assumptions for both the single- and repeated-use protocols 
discussed in the chemistry guidance--that each square inch of food-
contact article will come into contact with 10 g of food, and that the 
article will come into contact with all food in a consumer's diet (in 
other words, no consumption factors or food type distribution factors 
are applied to the migration value)--are applied to the migration value 
determined from this study, the calculated dietary exposure to 
perchlorate would still fall within the TOR exposure exemption 
criteria. As such, the petitioners' assertions that Ciba did not follow 
the repeated-use protocol discussed in the chemistry guidance document 
and that use of a single-use protocol did not account for the release 
(i.e., migration) of perchlorate over time if the finished article 
degrades or is flexed, do not support the conclusion that TOR exemption 
No. 2005-006 should be revoked.
3. Issues Pertaining to the Use of a Consumption Factor When 
Calculating Dietary Exposure
    The original calculation of dietary exposure resulting from the use 
allowed by the TOR exemption No. 2005-006 used FDA's consumption factor 
for substances that may be used in all polymers but only for specific 
uses. The petition asserted that the use of a consumption factor in 
this instance is inappropriate for a variety of reasons, including that 
the consumption factor does not account for the use of sodium 
perchlorate monohydrate in all antistatic agents and all polymers, nor 
in reusable bulk packaging for raw materials which the petition said 
result in finished articles containing sodium perchlorate monohydrate 
coming into contact with food ingredients that will later be used in 
the production of

[[Page 20854]]

processed foods which are not limited to non-fatty, dry foods.
    To address the petition's assertions regarding the appropriateness 
of the use of a consumption factor, we used the results of the 
migration study provided in comments submitted to the docket for the 
petition (discussed in section III.A.2.a) to calculate the dietary 
exposure to perchlorate from the use allowed by TOR exemption No. 2005-
006 without the use of a consumption factor (Ref. 11). This approach 
overestimates the dietary exposure from the use allowed by TOR 
exemption No. 2005-006 because it assumes that finished articles 
containing sodium perchlorate monohydrate will come into contact with 
all foods in a consumer's diet instead of coming into contact with just 
non-fatty, dry foods. This approach also assumes that all food will 
come into contact with articles containing sodium perchlorate 
monohydrate at the maximum allowed use level, which is a conservative 
assumption because it can be expected that not all finished articles 
would utilize the substance at the maximum allowed use level. In 
addition, this calculation utilizes our food mass-to-surface area ratio 
assumption for consumer (single use) packaging, even though it can be 
expected that food-contact articles used in food processing and raw 
material storage have a much larger food mass-to-surface area ratio 
than consumer packaging (see discussion in section III.A.2.b.ii).
    Using this conservative approach, we calculated a perchlorate 
exposure of 1.5 [micro]g/person/day, which falls within the TOR 
exemption criteria specified in Sec.  170.39(a)(2)(i) even without the 
use of a consumption factor. This calculation demonstrates that the 
assertions raised in the petition pertaining to the use of a 
consumption factor do not support a conclusion that TOR exemption No. 
2005-006 is no longer supportable under Sec.  170.39(g).
4. Inclusion of Use in Contact With Infant Formula and Food for 
Children Younger Than Two Years Old
    As discussed in section III.A.1, the original submission for TOR 
exemption No. 2005-006 calculated the dietary exposure to perchlorate 
from the intended use of sodium perchlorate monohydrate. This 
calculation used several factors, including a consumption factor as 
well as an assumption of a total food consumption of 3 kg of food per 
day. Section I.C.3 of the petition stated that because these factors 
are specific to adults, exposure calculated using these factors could 
underestimate perchlorate exposure for infants relying on powdered 
formula as their sole source of nutrition if sodium perchlorate 
monohydrate was used in infant formula packaging as a result of TOR 
exemption No. 2005-006. The petition stated that many infants rely on 
infant formula as their sole source of nutrition, whereas adults 
consume a diverse diet. The petition also stated that infants consume 
more food per bodyweight than adults.
    a. Section 170.39(a)(2)(i) and the use of specific factors to 
calculate exposure. As discussed in section III.A.1, Sec.  
170.39(a)(2)(i) requires that dietary exposure be calculated using a 
specified assumption of 3 kg of food per day, which is an assumption 
for the general adult population. In addition, Sec.  170.39(a)(2)(i) 
requires that dietary exposure be expressed on a per person basis 
([micro]g/person/day), which does not account for the fact that infants 
consume more food per bodyweight than adults. To account for the fact 
that infants consume more food per bodyweight than adults, infant 
dietary exposure would need to be expressed on a bodyweight basis 
([micro]g/kg bodyweight/day). Section 170.39(a)(2)(i) does not preclude 
the use of a consumption factor when calculating exposure; as discussed 
in section III.A.3, the use of a consumption factor refines exposure by 
taking into account the fraction of the daily diet expected to contact 
a specific type of packaging material rather than assuming a given food 
contact substance will be used in contact with all food in a consumer's 
diet. However, in section III.A.3 we also demonstrate that the dietary 
exposure to perchlorate that results from the intended use subject to 
TOR exemption 2005-006 falls within the TOR exemption criteria even if 
that exposure is calculated without the use of a consumption factor.
    b. Section 170.39(b) and infant exposure to perchlorate from the 
TOR use. Although the intended use for TOR exemption No. 2005-006 
results in an exposure of 1.5 [mu]g/person/day or less using the 
assumptions specified in Sec.  170.39(a)(2)(i), under Sec.  170.39(b) 
we can decline to grant a TOR exemption in those cases where the 
available information establishes that the proposed use may pose a 
public health risk. In certain circumstances, we believe that infants' 
dietary exposure to a substance may be relevant to whether the proposed 
use of a substance may pose a public health risk under Sec.  170.39(b). 
Therefore, to address the petition's argument that the use of adult-
specific exposure assumptions could underestimate perchlorate exposure 
for infants that solely consume reconstituted powdered formula, we 
calculated a potential exposure to perchlorate in powdered formula from 
the intended use allowed by TOR exemption No. 2005-006. We calculated 
this potential infant dietary exposure by applying infant-specific 
exposure assumptions articulated in FDA's draft guidance for food 
contact notification submissions for food contact substances that 
contact infant formula or human milk (Ref. 12), to data from the 
migration study provided in comments submitted to the docket for the 
petition (discussed in Section III.A.2.). These infant-specific dietary 
exposure assumptions include an assumption that an infant (aged 0 to 6 
months) consumes 900 g of liquid formula per day (data from the 
National Health and Nutrition Examination Survey indicate that the 
highest mean intake for infants 0-6-months is for 2-month old infants, 
which have an intake of 900 grams/day). FDA also used the corresponding 
mean body weight of 2-month olds of 6.3 kg bodyweight/infant. The 
infant-specific potential dietary exposure estimate excludes the use of 
a consumption factor, because infants aged 0 to 6 months frequently 
consume human milk and/or infant formula exclusively. Using this 
approach, we calculated a potential infant dietary exposure to 
perchlorate in powdered formula from the intended use allowed by TOR 
exemption No. 2005-006 of 0.019 [micro]g/kg bodyweight/day (Ref. 11). 
As discussed in section III.B, the petition discusses the safety of 
perchlorate exposure in the context of the RfD for perchlorate, as well 
as a value derived from a preliminary, biologically based dose-response 
model. This calculated potential perchlorate exposure for powdered 
formula is less than both the RfD for perchlorate (0.7 [micro]g/kg 
bodyweight/day) and the value derived from the model (0.42 [micro]g/kg 
bodyweight/day). Thus, the petition does not demonstrate that there is 
a public health risk to infants under Sec.  170.39(b) as a result of 
the intended use of perchlorate allowed by TOR exemption No. 2005-006.
5. Consideration of Exposure From Other Sources
    The petition asserted that section 409(c)(5)(B) of the FD&C Act and 
Sec.  170.3(i)(2) require consideration of cumulative exposure to 
perchlorate in the review of TOR exemption No. 2005-006 and that, if 
these exposures are considered when calculating the dietary exposure 
for the TOR exemption, the resultant exposure may exceed the TOR 
exemption criteria of dietary exposure at or below 1.5 [micro]g/person/
day. Specifically, the petition stated that the

[[Page 20855]]

original calculation of dietary exposure resulting from the use allowed 
by TOR exemption No. 2005-006 did not consider dietary exposure to 
perchlorate as a result of the approved food-contact use of potassium 
perchlorate listed in Sec.  177.1210, nor as a result of environmental 
contamination of the food supply.
    The use of a food contact substance that is exempted from 
regulation as a food additive under FDA's TOR regulation is not subject 
to the factors that apply to the proposed use of a food additive under 
section 409(c)(5)(B) of the FD&C Act and Sec.  170.3(i)(2). Rather, 
when we exempt a food-contact use of a substance from regulation as a 
food additive, our TOR regulation ensures the safety of this food-
contact use by setting extremely low limits on migration levels so that 
its proposed use results in a negligible dietary concentration, and 
requiring that the substance not be a carcinogen. A premise of the TOR 
regulation is that if a substance meets these requirements, it presents 
no other health or safety concerns (see Sec.  170.39(a)(2)). In 
determining whether the use of a substance qualifies for a TOR 
exemption, cumulative exposure to a substance is not considered under 
the TOR regulation because the dietary exposure from the use of a 
substance that is at or below the threshold of regulation is 
negligible. Thus, Sec.  170.39(a)(2)(i) provides that the only dietary 
exposure that is relevant to whether the use of a substance qualifies 
for a TOR exemption from regulation as a food additive is the dietary 
exposure resulting from the use in question.
    We established the threshold of regulation set forth in Sec.  
170.39(a)(2)(i) based on available toxicological data showing that it 
was feasible to establish a threshold level below which dietary 
exposures to substances used in food-contact articles are so negligible 
as to pose no public health or safety concerns (see 60 FR 36582, July 
17, 1995). In the preamble to the proposed TOR rule, we explained that 
our analysis of toxicological data on a large number of representative 
compounds demonstrated that the noncarcinogenic toxic effects caused by 
the majority of unstudied compounds would be unlikely to occur below 
1,000 ppb (58 FR 52719 at 52722, October 12, 1993). To provide an 
adequate safety margin, we selected 0.5 ppb as the threshold for 
regulation, which is 2,000 times lower than the dietary concentration 
at which the vast majority of studied compounds are likely to cause 
noncarcinogenic toxic effects (see 58 FR 52719 at 52722). We also 
analyzed potency data on a large number of known carcinogens to 
determine that the 0.5 ppb dietary concentration level would result in 
negligible risk, even in the event that a substance that is exempted 
from regulation as a food additive were later shown to be a carcinogen 
(see 58 FR 52719 at 52722).
    Consistent with Sec.  170.39(a)(2)(i), we do not calculate 
cumulative exposure to a substance in evaluating whether the use of the 
substance qualified for a TOR exemption. As we explained in an April 
2002 guidance for industry entitled, ``Preparation of Food Contact 
Notifications for Food Contact Substances: Toxicology 
Recommendations,'' at the time the TOR process was established, FDA 
determined that, because of the conservative assumptions ordinarily 
applied in estimating exposure, the cumulative exposure from a limited 
number of trivial food additive uses is not likely to be more than 
negligible. Accordingly, in the case of the TOR exposure levels, it was 
not necessary to utilize cumulative exposure levels. FDA believes that 
the determination made in establishing its TOR is still sound (Ref. 
13).
    Therefore, contrary to the petition's assertions, under FDA's TOR 
regulations, the dietary exposures to perchlorate that are not a result 
of the use specified in the TOR exemption No. 2005-006 are not 
considered under the exposure criteria for the TOR exemption.
6. Inconsistencies Between the Intended Use Reviewed by FDA and That 
Listed on Our Inventory of Effective TOR Exemptions
    We maintain an inventory of effective TOR exemptions on our Web 
site (Ref. 1). The originating submission for TOR exemption No. 2005-
006 requested a use for sodium perchlorate monohydrate in antistatic 
agents at a maximum level of 4 percent by weight. The antistatic agent 
would be used in finished plastic at a maximum level of 30 percent by 
weight. The finished plastic would be used in contact with non-fatty, 
dry foods (Food Type VIII) only. This is the intended use that we 
considered in 2005 when we determined that the information provided in 
the originating request demonstrated that the use would result in a 
dietary exposure at or below the 1.5 [micro]g/person/day criteria. The 
petition asserted that this intended use was expanded in the final 
letter for the TOR exemption No. 2005-006 to permit the finished 
article to be used in contact with all dry foods. The petition also 
asserted that the intended use was further expanded in the listing on 
our inventory of effective TOR exemptions, to include the use of sodium 
perchlorate monohydrate in all types of food contact materials at a 
maximum use level of 4 percent by weight in the finished article.
    We agree that the intended use for TOR exemption No. 2005-006 was 
inaccurately described in the final letter for the TOR exemption No. 
2005-006 and the inventory of effective TOR exemptions. On August 17, 
2015, we corrected the listing for TOR exemption No. 2005-006 on the 
inventory of effective TORs on our Web site to be consistent with the 
intended use reviewed by FDA when the TOR exemption became effective 
and thereby address the petition's assertions regarding the description 
of the intended use for TOR exemption No. 2005-006. We further revised 
the listing for TOR exemption No. 2005-006 on September 19, 2016, to 
clarify that TOR exemption No. 2005-006 allows the use of perchlorate 
in the manufacture of antistatic agents for use in all polymeric food-
contact articles and not only polymeric food packaging.

B. Arguments Based on ``Significant New Information''

    Part I.D. of the petition identified the following four categories 
of ``significant new information'' that has become available after TOR 
exemption No. 2005-006 became effective: ``First, additional research 
shows that the endpoint used in the decision was not the most 
appropriate or sensitive one to protect fetuses and infants from 
permanent brain damage. Second, it is now known that nitrates and 
thiocyanates are pharmacologically-related to perchlorate and, 
therefore, must be considered in any safety evaluation of perchlorate 
as an additive. Third, in 2011, FDA acknowledged that the 50 ppb 
migration to dry-food default assumption (``virtually nil'' migration) 
may be flawed based on research evidence from Europe. Fourth, FDA has 
demonstrated that there is widespread contamination of the food supply 
with perchlorate that must be considered.'' The petition asserted that 
this new information warrants a reevaluation of TOR exemption No. 2005-
006 under Sec.  170.39(g).
    We will first address the petition's arguments regarding 
hypothyroxinemia and its proposed acceptable daily intake level, then 
discuss the petition's arguments pertaining to perchlorate in the food 
supply and pharmacologically related substances, and finally the 
arguments pertaining to our 50 ppb migration concentration assumption.

[[Page 20856]]

1. Proposed Acceptable Daily Intake Level Based on Hypothyroxinemia
    The petition proposed an acceptable daily intake (ADI) value in 
place of the RfD for perchlorate and argues that the exposure from the 
TOR use exceeds the ADI proposed in the petition. The petition stated 
that the ADI proposed in the petition better accounts for 
hypothyroxinemia as a potential result of perchlorate exposure than 
does the RfD. However, under our TOR regulations, because a substance 
is expected to migrate into food at negligible levels, a non-
carcinogenic endpoint such as hypothyroxinemia is not relevant unless 
the use of the substance may pose a public health risk under Sec.  
170.39(b). As discussed further in this section, the information in the 
petition does not support such a conclusion under Sec.  170.39(b) 
because: (1) Even if hypothyroxinemia were relevant, the petition does 
not demonstrate that the proposed ADI better accounts for the potential 
for perchlorate to cause hypothyroxinemia than the RfD for perchlorate; 
(2) the proposed ADI is based on the results of a preliminary model; 
and (3) even if it were appropriate to base an ADI on the results of 
the preliminary model, the resulting ADI would still be above the 
exposure from the TOR use.
    a. Summary of petition's discussion on hypothyroxinemia. The 
petition asserted that new information, available since TOR exemption 
No. 2005-006 became effective, demonstrates that exposure to 
perchlorate can result in hypothyroxinemia. As noted in section I.D.2, 
hypothyroxinemia means that the fT4 value is at the lower end of the 
normal range with normal levels of TSH in the blood. The petition 
asserted that the SAB report, which was issued after the TOR exemption 
became effective, identified the potentially sensitive population for 
perchlorate exposure to be fetuses of hypothyroxinemic pregnant women. 
This is in contrast to the NRC report, which identified the potentially 
sensitive population for perchlorate exposure to be fetuses of pregnant 
women with hypothyroidism or iodide deficiency (both the SAB report and 
the NRC report are discussed in section I.D.2). Based upon this 
difference, the petition asserted that the RfD, which was based on the 
NRC review, does not provide sufficient protection to susceptible 
populations. The petition also asserted that IUI, which is the basis of 
the RfD, is a less sensitive endpoint than hypothyroxinemia.
    The petition proposed an ADI of 0.042 [micro]g/kilogram bodyweight/
day for perchlorate based on the amount of perchlorate exposure that 
may result in hypothyroxinemia in iodide-deficient pregnant women as 
reported by FDA scientists in a 2013 Lumen et al. article (Ref. 14). 
Lumen et al. summarizes the results of a proof-of concept, biologically 
based dose-response (BBDR, also known as a PBPK/PD) model that is 
specific to near-term human mothers and fetuses. This model used PBPK/
PD data to predict perchlorate intake levels that could produce thyroid 
hormone perturbations at varying levels of maternal iodide intake. The 
petition derived its proposed ADI by applying two ten-fold uncertainty 
factors to the results presented in the Lumen et al. article. One ten-
fold uncertainty factor is applied to account for intraspecies 
variability, while the second tenfold uncertainty factor is applied to 
account for the assertion that the perchlorate exposure value provided 
in the Lumen et al. article is based on a lowest observed adverse 
effect level (LOAEL) rather than a no observed adverse effect level 
(NOAEL). (The petition also stated that additional, unquantified 
uncertainty factors should be applied to its proposed ADI to account 
for deficiencies in the model, but it does not include these factors in 
its calculation of the proposed ADI.) The petition subsequently 
compared its proposed ADI to a dietary exposure to perchlorate 
resulting from the use allowed by TOR exemption No. 2005-006 as 
calculated in the petition. As the exposure to perchlorate calculated 
in the petition is higher than the derived ADI, the petition asserted 
that TOR exemption No. 2005-006 should be revoked.
    b. FDA's consideration of the petition's discussion on 
hypothyroxinemia. First, the petition contended that its proposed ADI 
accounts for the potential for perchlorate to cause hypothyroxinemia 
while the RfD for perchlorate does not. However, the petition does not 
adequately support its assertion that the RfD for perchlorate fails to 
account for the potential for perchlorate to cause hypothyroxinemia 
(Ref. 15). The SAB's and NRC's identification of different sensitive 
populations for perchlorate exposure is not a basis for concluding that 
the RfD provides insufficient protection to the sensitive population 
identified by the SAB, nor that the RfD does not account for the 
potential for perchlorate to cause hypothyroxinemia. The RfD for 
perchlorate is based on the IUI. As previously stated, the basis of the 
MOA framework for perchlorate is that IUI must first occur prior to any 
resultant thyroid hormone perturbations such as hypothyroxinemia or 
hypothyroidism. This contradicts the petition's assertion that IUI is a 
less sensitive endpoint than hypothyroxinemia. The NRC and SAB used the 
MOA framework for perchlorate in determining their recommendations. The 
MOA framework was also used in the development of the Lumen et al. BBDR 
model cited by the petitioners (Ref. 14). Furthermore, the tenfold 
intraspecies uncertainty factor utilized by the NRC in the derivation 
of the RfD is a default value that is intended to account for the 
entire range of sensitivity among humans to perchlorate exposure. The 
petition did not provide support for its contention that this default, 
intraspecies uncertainty factor is not inclusive of fetuses of pregnant 
women with hypothyroxinemia.
    Second, the 2013 Lumen et al. BBDR model that forms the basis of 
the ADI proposed by the petitioners is a preliminary model (Ref. 15) 
that FDA believes is not appropriate to use in a quantitative risk 
assessment as presented in the petition. Because FDA does not believe 
that the model should be used for a quantitative risk assessment due to 
the preliminary nature of the analysis, consideration of the 
appropriateness of the uncertainty factors proposed by the petitioners 
is premature at this time. Since the 2013 Lumen et al. article, we have 
worked with EPA scientists to further develop the model cited by the 
petitioners. On January 10 and 11, 2017, EPA's contractor conducted an 
independent, scientific public peer review of EPA's draft BBDR model 
and report. EPA is currently considering peer reviewer comments. EPA 
intends to seek peer review of a second report that evaluates methods 
to apply the final BBDR model to develop a maximum contaminant level 
goal for perchlorate in drinking water (see 81 FR 87553, December 5, 
2016).
    Third, we note that even if the approach taken in the petition were 
appropriate--i.e., to calculate a risk assessment value based on the 
results of the preliminary model referenced in the petition, and to 
apply both 10-fold uncertainty factors specified in the petition (one 
to account for a LOAEL and one to account for intraspecies variability) 
to the amount of perchlorate exposure that may result in 
hypothyroxinemia in iodide-deficient pregnant women as reported in the 
Lumen et al. article--the resultant ADI calculated in the petition is 
0.042 [mu]g/kg bodyweight/day. This risk assessment value is higher 
than the exposure to

[[Page 20857]]

perchlorate as a result of TOR exemption No. 2005-006 as determined by 
Ciba (0.063 [mu]g per chlorate/person/day, which equates to 0.001 
[mu]g/kg bodyweight/day utilizing FDA's assumption of 60 kg bodyweight 
for adults as described in the chemistry guidance), as well as the 
exposures determined from the migration study discussed in section 
II.A.2 (for adults: 0.075 [mu]g/person/day which equates to 0.001 
[mu]g/kg bodyweight/day; and for infants: 0.019 [mu]g/kilogram 
bodyweight/day--see section II.A.4). Therefore, even if deriving a risk 
assessment value based on the results presented in the Lumen et al. 
article were appropriate, the exposure to perchlorate as a result of 
TOR exemption No. 2005-006 is lower than the resulting risk assessment 
value, and therefore would not support the assertion by the petitioners 
that the results presented in the Lumen et al. article ``raises 
questions about the safe level of exposure to perchlorate relied on by 
Ciba when the Agency approved TOR No. 2005-006.''
2. Argument Related to Cumulative Dietary Exposure From Perchlorate, 
and Substances Pharmacologically Related to Perchlorate, in the Food 
Supply
    The petition asserted that new information has become available, 
since FDA issued the listing regulation for potassium perchlorate in 
Sec.  177.1210 and TOR exemption No. 2005-006, that nitrate and 
thiocyanate are pharmacologically related to perchlorate, and that 
perchlorate contamination of the food supply is widespread. The 
petition also asserted that we are required to take into account the 
cumulative effect of these substances in the diet.
    As discussed in section III.A.5, under Sec.  170.39(a)(2)(i), we do 
not calculate cumulative dietary exposure to a substance or 
pharmacologically related substances in evaluating whether the use of 
the substance qualifies for a TOR exemption from regulation as a food 
additive. Under Sec.  170.39(a)(2)(i), the only dietary exposure that 
is relevant to whether the use of a substance qualifies for a TOR 
exemption from regulation as a food additive is the dietary exposure 
resulting from the use in question. Therefore, the petition's argument 
regarding cumulative dietary exposure to perchlorate or 
pharmacologically related substances does not support a conclusion that 
TOR exemption No. 2005-006 is no longer supportable.
3. Alleged Flaws in FDA's 50 ppb Migration Concentration Assumption
    The petition stated that FDA, in a 2011 speech by an FDA scientist, 
acknowledged potential flaws in the 50 ppb migration concentration 
assumption for migration to non-fatty, dry foods (Food Type VIII). To 
support this statement, the petition cited a 2011 article which 
summarizes the speech given by the FDA scientist (Ref. 16). The 
petition also asserted that the 50 ppb migration assumption is 
particularly flawed for perchlorate, which is used in packaging to 
neutralize the static charge on dry food.
    The migration study provided in comments submitted to the docket 
for the petition (discussed in section III.A.2.a) found that 
perchlorate migrated into a simulant for non-fatty, dry foods at a 
concentration of 0.5 ng perchlorate/g food, or 0.5 ppb. As noted, this 
value is substantially less than the 50 ppb migration concentration 
assumption provided in our chemistry guidance and indicates that the 50 
ppb migration concentration assumption does not understate migration 
from the intended use of sodium perchlorate monohydrate into non-fatty, 
dry foods. As a result, the petition's contentions regarding alleged 
flaws in the 50 ppb migration concentration assumption, both generally 
and as applied to perchlorate, do not support a conclusion that TOR 
exemption No. 2005-006 is no longer supportable.

C. Alleged Disproportionate Impact of Perchlorate on Children's Health 
and FDA's Obligation Under Executive Order 13045

    Executive Order 13045, ``Protection of Children from Environmental 
Health Risks and Safety Risks'' (see 62 FR 19885, April 23, 1997), 
provides in part that, ``to the extent permitted by law and 
appropriate, and consistent with the agency's mission,'' each Federal 
Agency ``shall ensure that its policies, programs, activities, and 
standards address disproportionate risks to children that result from 
environmental health risks or safety risks,'' which are defined as 
``risks to health or to safety that are attributable to products or 
substances that the child is likely to come in contact with or ingest 
(such as the air we breath [sic], the food we eat, the water we drink 
or use for recreation, the soil we live on, and the products we use or 
are exposed to).'' The petition asserted that, because perchlorate has 
a disproportionate impact on infants, the Executive Order warrants the 
use by FDA of additional safety factors beyond those provided in Sec.  
170.22 (21 CFR 170.22) when considering the safety of the food-contact 
uses of perchlorate. Specifically, the petition contended that safety 
factors in addition to the 100-fold safety factor stated in Sec.  
170.22 are necessary due to deficiencies in the Lumen et al. BBDR model 
(discussed in section III.B.1) and because a pregnant woman's short-
term exposure to perchlorate can cause irreversible harm to the fetal 
brain if the woman has low iodine intake.
    We note that Sec.  170.22 pertains to safety factors used in 
applying animal experimentation data to man. As the safety arguments 
presented in the petition utilize data obtained from human subjects, 
and the petition discusses specific safety factors for each argument, 
Sec.  170.22 is not relevant to the safety arguments presented in the 
petition. Furthermore, in the December 5, 2014, submission the petition 
stated that the tenfold safety factor utilized to derive the RfD for 
perchlorate is consistent with Executive Order 13045.
    With respect to the petition's request to apply additional safety 
factors, section III.B.1 explains that FDA believes the results of the 
BBDR model are preliminary in nature and not an appropriate basis for a 
quantitative risk assessment as presented in the petition. A discussion 
of whether or not uncertainty factors should be applied is premature at 
this time. For these reasons, we believe that our analysis of the 
potential health effects of perchlorate satisfies Executive Order 13045 
and that the use of additional safety factors is not necessary.

D. Request To Issue a New Regulation Under 21 CFR Part 189

    Part II of the petition asserted that, if FDA were to revoke TOR 
exemption No. 2005-006, publication of the notice of revocation in the 
Federal Register would be insufficient to alert industry, and therefore 
requested that we issue a new regulation under part 189. The requested 
regulation would prohibit the use of perchlorates in the manufacture of 
antistatic agents to be used in food-contact articles, which is the use 
of perchlorate allowed by TOR exemption No. 2005-006.
    Because we conclude that TOR exemption No. 2005-006 remains 
supportable under Sec.  170.39, we decline to propose a regulation 
under part 189 prohibiting this use of perchlorate.

IV. Comments on the Filing Notice

    We received very few comments on the petition. Those comments that 
discussed the safety of the use of perchlorate in food contact 
applications did not provide any additional data to that presented in 
the petition.
    In this section we discuss the issues raised in the remaining 
comments. We preface each comment discussion with a numbered 
``Comment'' and each

[[Page 20858]]

response by the word ``Response'' to make it easier to identify 
comments and our responses. We have numbered each comment to help 
distinguish among different topics. The number assigned is for 
organizational purposes only and does not signify the comment's value, 
importance, or the order in which it was received.
    (Comment 1) One comment provided a migration study for sodium 
perchlorate monohydrate from a worst-case polymeric resin into a dry 
food simulant.
    (Response) This study is discussed in section III.A.2.
    (Comment 2) Several comments stated that the use of potassium 
perchlorate as an additive in closure-sealing gaskets for food 
containers has been abandoned.
    (Response) The abandonment of potassium perchlorate as an additive 
in closure-sealing gaskets is the subject of a separate food additive 
petition, 6B4816, which we address elsewhere in this edition of the 
Federal Register.
    (Comment 3) Another comment stated that the petition's request that 
FDA add perchlorate to the list of prohibited substances contained in 
part 189 is based upon the identification of a hazard relating to a 
class of chemical substances. The comment asserted that an approach to 
safety assessment based on hazard identification is a departure from 
FDA's practice of evaluating the safety of food contact materials based 
on their intended use.
    (Response) As we are declining to propose a regulation under part 
189 prohibiting the use of perchlorates as a food contact substance in 
antistatic agents (see section V), it is not necessary to respond to 
this comment.

V. Conclusion

    We reviewed the petition and with respect to the petition's first 
request, we have determined that the dietary exposure to sodium 
perchlorate monohydrate as a result of the use allowed by the TOR 
exemption No. 2005-006 does not exceed the TOR exemption criteria in 
Sec.  170.39(a)(2)(i) and that the data and information provided do not 
support a conclusion that TOR exemption No. 2005-006 is no longer 
supportable. With respect to the petition's second request, we decline 
to propose a regulation under part 189 prohibiting the use of 
perchlorates as a food contact substance in antistatic agents because 
proposing such a regulation would be inconsistent with our conclusion 
that the data and information provided in the petition do not support a 
conclusion that TOR exemption No. 2005-006 is no longer supportable. 
With respect to the petition's third request, which is the sole request 
that is the proper subject of a food additive petition, the food 
additive use of potassium perchlorate has been removed from Sec.  
177.1210 in a final rule published elsewhere in this issue of the 
Federal Register and we decline to address the petitioners' assertions 
regarding the safety of the food additive use. Therefore, we are 
denying all three requests, and we are denying the petition in full.

VI. Objections

    Any person that may be adversely affected by this order may file 
with the Division of Dockets Management (see ADDRESSES) either 
electronic or written objections. You must separately number each 
objection, and within each numbered objection you must specify with 
particularity the provision(s) to which you object, and the grounds for 
your objection. Within each numbered objection, you must specifically 
state whether you are requesting a hearing on the particular provision 
that you specify in that numbered objection. If you do not request a 
hearing for any particular objection, you waive the right to a hearing 
on that objection. If you request a hearing, your objection must 
include a detailed description and analysis of the specific factual 
information you intend to present in support of the objection in the 
event that a hearing is held. If you do not include such a description 
and analysis for any particular objection, you waive the right to a 
hearing on the objection.
    It is only necessary to send one set of documents. Identify 
documents with the docket number found in brackets in the heading of 
this document. Any objections received in response to the regulation 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at 
https://www.regulations.gov. We will publish notice of the objections 
that we have received or lack thereof in the Federal Register.
    As explained in section II.C, only the petition's request to amend 
Sec.  177.1210 is within the scope of a food additive petition under 
section 409(b) of the FD&C Act. The remaining two requests are not 
within the scope of a food additive petition and our denial of these 
requests is not an order under section 409(c)(1)(B) of the FD&C Act. 
Therefore, the provision for objections and public hearing under 
section 409(f) of the FD&C Act does not apply to these two requests.

VII. References

    The following references are on display in the Division of Dockets 
Management (see ADDRESSES) and are available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also 
available electronically at https://www.regulations.gov. FDA has 
verified the Web site addresses, as of the date this document publishes 
in the Federal Register, but Web sites are subject to change over time.

1. FDA. ``Threshold of Regulation Exemptions.'' Available at https://www.fda.gov/Food/IngredientsPackagingLabeling/PackagingFCS/ThresholdRegulationExemptions/default.htm.
2. National Research Council. 2005. ``Health Implications of 
Perchlorate Ingestion.'' Washington, DC. National Academies Press. 
ISBN 0-309-09568-9. Available at https://www.nap.edu/catalog/11202/health-implications-of-perchlorate-ingestion.
3. EPA. 2013. ``SAB Advice on Approaches to Derive a Maximum 
Contaminant Level Goal for Perchlorate.'' EPA-SAB-13-004. Available 
at https://yosemite.epa.gov/sab%5CSABPRODUCT.NSF/
86E44EE7F27EEC1A85257B7B0060F364/$File/EPA-SAB-13-004-unsigned2.pdf.
4. Greer, M.A., G. Goodman, R.C. Pleus, et al. 2002. ``Health Effect 
Assessment for Environmental Perchlorate Contamination: The Dose 
Response for Inhibition of Thyroidal Radioiodide Uptake in Humans.'' 
Environmental Health Perspective. 110:927-937.
5. National Institutes of Health, ``Hypothyroidism (Underactive 
Thyroid).'' Available at https://www.niddk.nih.gov/health-information/endocrine-diseases/hypothyroidism.
6. EPA. ``Perchlorate (ClO4) and Perchlorate Salts.'' 
Available at https://cfpub.epa.gov/ncea/iris2/chemicalLanding.cfm?substance_nmbr=1007.
7. EPA. ``White Paper: Life Stage Considerations and Interpretation 
of Recent Epidemiological Evidence to Develop a Maximum Contaminant 
Level Goal for Perchlorate.'' 2012. Available at https://
yosemite.epa.gov/sab/sabproduct.nsf/
d21b76bff879fa0a8525735a00766807/D3BB75D4297CA4698525794300522ACE/
$File/Final+Perchlorate+White+Paper+05.29.12.pdf.
8. Stedman, T.L. 2006. ``Stedman's Medical Dictionary.'' 
Philadelphia: Lippincott Williams & Wilkins. 28th ed. ISBN 978-
0781733908.
9. FDA. ``Guidance for Industry: Preparation of Premarket 
Submissions for Food Contact Substances: Chemistry 
Recommendations.'' Available at https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/IngredientsAdditivesGRASPackaging/ucm081818.htm.

[[Page 20859]]

10. FDA Memorandum from J. Smith, September 15, 2005.
11. FDA Memorandum from R. Costantino to P. Honigfort, March 31, 
2017.
12. FDA. ``Draft Guidance for Industry: Preparation of Food Contact 
Notifications for Food Contact Substances in Contact with Infant 
Formula and/or Human Milk.'' December 2016. Available at https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm528215.htm.
13. FDA. ``Guidance for Industry: Preparation of Food Contact 
Notifications for Food Contact Substances: Toxicology 
Recommendations.'' Available at https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm081825.htm.
14. Lumen A., D.R. Mattie, and J.W. Fisher. ``Evaluation of 
Perturbations in Serum Thyroid Hormones During Human Pregnancy Due 
to Dietary Iodide and Perchlorate Exposure Using a Biologically 
Based Dose-Response Model.'' Toxicological Sciences. 133(2):320-41, 
2013.
15. FDA Memorandum from G. Patton, P. Honigfort, and J. Aungst to 
Administrative File, March 31, 2017.
16. Clapp, S., ``FDA Chemist Says Agency's Food Contact Advice is 
`Showing Its Age.' '' Food Chemicals News. 53(30): 11-12, 2011.

    Dated: April 28, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-08987 Filed 5-3-17; 8:45 am]
 BILLING CODE 4164-01-P


