[Federal Register Volume 89, Number 210 (Wednesday, October 30, 2024)]
[Proposed Rules]
[Pages 86290-86305]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-25120]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 175, 176, 177, and 178

[Docket No. FDA-2016-F-1253]


Environmental Defense Fund, et al.; Response to Objections and 
Requests for a Public Hearing

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification; response to objections and denial of public 
hearing requests.

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SUMMARY: The Food and Drug Administration (FDA or we) received 
objections and requests for a public hearing submitted by the 
Environmental Defense Fund, Learning Disabilities Association of 
America, Center for Food Safety, Center for Environmental Health, 
Center for Science in the Public Interest, Breast Cancer Prevention 
Partners, Defend our Health, and Alaska Community Action on Toxics on 
the denial of a food additive petition (FAP

[[Page 86291]]

6B4815) requesting that we revoke specified regulations to no longer 
provide for the food contact use of 28 ortho-phthalates. We are 
overruling the objections and denying the requests for a public 
hearing.

DATES: October 30, 2024.

FOR FURTHER INFORMATION CONTACT: Jessica Urbelis, Office of Food 
Chemical Safety, Dietary Supplements, and Innovation, Human Foods 
Program, Food and Drug Administration, 5001 Campus Dr., College Park, 
MD 20740, 240-402-5187; or Carrol Bascus, Office of Policy, Regulations 
and Information, Human Foods Program, Food and Drug Administration, 
5001 Campus Dr., College Park, MD 20740, 240-402-2378.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of May 20, 2016 (81 FR 31877), we announced 
the filing of a food additive petition (FAP 6B4815) (petition) 
submitted by the Breast Cancer Fund (now Breast Cancer Prevention 
Partners), Center for Environmental Health, Center for Food Safety, 
Center for Science in the Public Interest, Clean Water Action, Consumer 
Federation of America, Earthjustice, Environmental Defense Fund, 
Improving Kids' Environment, Learning Disabilities Association of 
America, and Natural Resources Defense Council (hereinafter, 
petitioners).
    The petition, received March 18, 2016, initially requested that we 
amend or revoke specified food additive regulations under parts 175, 
176, 177, and 178 (21 CFR parts 175, 176, 177, and 178) to no longer 
provide for the food contact uses of 30 substances that the petition 
identified as ortho-phthalates. Additionally, petitioners requested 
that we amend regulations in part 181 (21 CFR part 181) related to 
prior-sanctioned uses of five ortho-phthalates and issue a new 
regulation in part 189 (21 CFR part 189) prohibiting the use of eight 
specific ortho-phthalates in food contact articles. We declined to file 
these portions of the submissions as a food additive petition because 
those requests were not within the scope of a food additive petition 
(81 FR 31877 at 31878).
    Following our May 20, 2016, announcement that we had filed the food 
additive petition, the petitioners provided supplementary information 
on October 8, 2016, and August 24, 2017 (see FAP 6B4815 regarding 
ortho-phthalates/Responses to September 1, 2016, request from Tom 
Neltner, Breast Cancer Fund, et al., dated October 8, 2016, and August 
24, 2017) (Supp., October 8, 2016, and Supp., August 24, 2017, 
respectively). In the October 8, 2016, supplement, the petitioners also 
requested that FDA remove two substances from the petitioner's original 
list of 30 substances, stating that they are not ortho-phthalates 
(Supp., October 8, 2016 at 2). Consequently, the subject of the food 
additive petition was limited to food additive regulations for 28 
ortho-phthalates. In addition, regarding the certain portions of the 
submissions that we declined to file as a food additive petition 
because those requests were not within the scope of a food additive 
petition, on April 19, 2016, the petitioners submitted a citizen 
petition containing those requests (see Citizen Petition from Nancy 
Buermeyer, Breast Cancer Fund, et al., submitted to the Dockets 
Management Staff, Food and Drug Administration, dated April 19, 2016 
(Comment ID FDA-2016-P-1171-0001) (citizen petition). Specifically, the 
citizen petition requested that we initiate rulemaking to remove the 
prior sanctions in part 181 for five ortho-phthalates and that we add a 
new section to part 189 prohibiting the use of eight ortho-phthalates 
(citizen petition at 1 through 2). On May 12, 2022, we denied the 
citizen petition.
    The core premise of FAP 6B4815 was that the 28 subject ortho-
phthalates are chemically and pharmacologically related and should 
therefore be treated as a class for purposes of evaluating their 
safety. The petitioners argued that a single purported acceptable daily 
intake (ADI) for one substance should be applied to the purported class 
of 28 ortho-phthalates and that the cumulative exposure to all 28 
ortho-phthalates significantly exceeded the purported ADI for the one 
substance petitioners selected, thereby rendering the entire purported 
class unsafe for use as food additives.
    In the Federal Register of May 20, 2022 (87 FR 31066), we announced 
that we were denying FAP 6B4815. In that Federal Register document 
(hereinafter, denial order), we explained that the petition did not 
provide sufficient information to support a finding that there is no 
longer a reasonable certainty of no harm for the authorized uses of the 
proposed class of 28 ortho-phthalates. As an additional matter, based 
on the information available to FDA, the denial order stated that we 
did not have a basis to conclude that dietary exposure levels from the 
authorized ortho-phthalates exceed a safe level (87 FR 31066 at 31075). 
The denial order advised that objections and requests for a hearing 
were due by June 21, 2022 (87 FR 31066). Subsequently, we received one 
submission from a group of eight objectors that raised several 
objections and requests for hearing in response to the denial order.
    Following receipt of FAP 6B4815 in March 2016, on June 25, 2018, we 
received a food additive petition (FAP 8B4820) submitted by the 
Flexible Vinyl Alliance (hereinafter, the abandonment petition). The 
abandonment petition proposed that we amend our food additive 
regulations in parts 175, 176, 177, and 178 to revoke the approvals of 
25 plasticizer substances that the petition identified as ortho-
phthalates for various food contact applications because such uses were 
permanently abandoned. In response to the abandonment petition, we 
issued a final rule on May 20, 2022 (87 FR 31080) amending the food 
additive regulations in parts 175, 176, 177, and 178 to revoke the 
authorization of the 25 substances that were the subject of the 
petition for various food contact applications (the abandonment final 
order). FDA issued the abandonment final order concurrently with its 
denial order for FAP 6B4815. On May 20, 2022, we also issued a request 
for information (RFI) seeking scientific data and information on 
current uses, use levels, dietary exposure, and safety data for ortho-
phthalates that remain authorized for use in food contact applications 
(87 FR 31090). The objections and requests for hearing we received 
refer to the denial order, citizen petition, abandonment final order, 
and RFI.
    Ortho-phthalates also are included on FDA's list of chemicals in 
the food supply that are under review (see https://www.fda.gov/food/food-chemical-safety/list-select-chemicals-food-supply-under-fda-review). We are committed to continuing the evaluation of all relevant 
scientific information and data to determine whether additional 
regulatory action regarding ortho-phthalates is warranted to ensure the 
safety of all authorized food contact uses of ortho-phthalates.

II. Objections and Requests for Hearing

    Section 409(f)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) (21 U.S.C. 348(f)(1)) provides that, within 30 days after 
publication of an order denying a food additive petition, any person 
adversely affected by such order may file objections, specifying with 
particularity the provisions of the order deemed objectionable, stating 
reasonable grounds therefor, and requesting a public hearing upon such 
objections.
    Under our regulations at 21 CFR 171.110, objections and requests 
for a hearing relating to food additive regulations are governed by 
part 12 (21 CFR part 12). Under Sec.  12.22(a), each

[[Page 86292]]

objection must: (1) be submitted on or before the 30th day after the 
date of publication of the final rule; (2) be separately numbered; (3) 
specify with particularity the provision of the regulation or proposed 
order objected to; (4) specifically state each objection on which a 
hearing is requested (failure to request a hearing on an objection 
constitutes a waiver of the right to a hearing on that objection); and 
(5) include a detailed description and analysis of the factual 
information to be presented in support of the objection if a hearing is 
requested (failure to include a description and analysis for an 
objection constitutes a waiver of the right to a hearing on that 
objection).
    We received one submission, on June 21, 2022, from the 
Environmental Defense Fund, Learning Disabilities Association of 
America, Center for Food Safety, Center for Environmental Health, 
Center for Science in the Public Interest, Breast Cancer Prevention 
Partners, Defend Our Health, and Alaska Community Action on Toxics 
(hereinafter, objectors) (see Objections and Request for Evidentiary 
Public Hearing Regarding FDA's Denial of Phthalates Food Additive 
Petition (FAP 6B4815)), submitted by Katherine K. O' Brien, 
Earthjustice, dated June 21, 2022, to the Dockets Management Staff, 
Food and Drug Administration (Comment ID FDA-2016-F-1253-0462) 
(Objections). The submission raises eight specific objections to the 
denial and requests hearings on six objections.

III. Standards for Granting a Hearing

    The criteria for granting a hearing are set out in Sec.  12.24(b). 
Under that regulation, a hearing will be granted if the material 
submitted by an objector shows that: (1) there is a genuine and 
substantial factual issue for resolution at a hearing (a hearing will 
not be granted on issues of policy or law); (2) the factual issue can 
be resolved by available and specifically identified reliable evidence 
(a hearing will not be granted on the basis of mere allegations or 
denials or general descriptions of positions and contentions); (3) the 
data and information submitted, if established at a hearing, would be 
adequate to justify resolution of the factual issue in the way sought 
by the objector (a hearing will be denied if the data and information 
submitted are insufficient to justify the factual determination urged, 
even if accurate); (4) resolution of the factual issue in the way 
sought by the objector is adequate to justify the action requested (a 
hearing will not be granted on factual issues that are not 
determinative with respect to the action requested, e.g., if the action 
would be the same even if the factual issue were resolved in the way 
sought); (5) the action requested is not inconsistent with any 
provision in the FD&C Act or any FDA regulation particularizing 
statutory standards (the proper procedure in those circumstances is for 
the person requesting the hearing to petition for an amendment or 
waiver of the regulation involved); and (6) the requirements in other 
applicable regulations, e.g., 21 CFR 10.20, 12.21, 12.22, 314.200, 
514.200, and 601.7(a), and in the document issuing the final regulation 
or the notice of opportunity for a hearing are met.
    In general, in an administrative proceeding under section 409(f) of 
the FD&C Act, FDA is authorized to issue a decision without holding a 
part 12 hearing when a party's objections do not raise a genuine and 
material issue of fact that, if proved in that party's favor, would 
suffice to warrant the relief requested (see Community Nutrition Inst. 
v. Young, 773 F.2d 1356, 1364 (D.C. Cir. 1985), cert. denied, 475 U.S. 
1123 (1986); see also Vermont Dep't of Pub. Serv. v. FERC, 817 F.2d 
127, 140 (D.C. Cir. 1987)). A party seeking a hearing must meet a 
``threshold burden of tendering evidence suggesting the need for a 
hearing'' (Costle v. Pacific Legal Foundation, 445 U.S. 198, 214-215 
(1980), citing Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 
609, 620-621 (1973)). An allegation that a hearing is necessary to 
``sharpen the issues'' or to ``fully develop the facts'' does not meet 
this test (Georgia Pacific Corp. v. EPA, 671 F.2d 1235, 1241 (9th Cir. 
1982)). If a hearing request fails to identify sufficient factual 
evidence that would be the subject of a hearing, there is no reason to 
hold one. In judicial proceedings, a court is authorized to issue 
summary judgment without an evidentiary hearing whenever it finds that 
there are no genuine issues of material fact in dispute, and a party is 
entitled to judgement as a matter of law (see Rule 56, Federal Rules of 
Civil Procedure). The same principle applies to administrative 
proceedings (Sec.  12.24). In reviewing whether an objecting party made 
``an adequate proffer of evidence'' to show that an ``actual dispute 
exist[s],'' courts consider whether the dispute lies in ``a highly 
technical area [within] the agency's expertise'' (see Cerro Wire & 
Cable Co. v. FERC, 677 F.2d 124, 129 (D.C. Cir. 1982)).
    A hearing request must not only contain evidence, but that evidence 
also must raise a material issue of fact ``concerning which a 
meaningful hearing might be held'' (Pineapple Growers Ass'n of Haw. v. 
FDA, 673 F.2d 1083, 1085 (9th Cir. 1982)). Where the issues raised in 
the objection are, even if true, legally insufficient to alter the 
decision, an agency need not grant a hearing (see Dyestuffs and 
Chemicals, Inc. v. Flemming, 271 F.2d 281, 286 (8th Cir. 1959), cert. 
denied, 362 U.S. 911 (1960)). A hearing is justified only if the 
objections are made in good faith and if they raise `` `material' 
issues of fact'' (Pineapple Growers Ass'n, 673 F.2d at 1085 (quoting 
Pactra Indus., Inc. v. CPSC, 555 F.2d 677, 684 (9th Cir. 1977)). The 
issues raised in objections ``must be material to the question 
involved; that is, the legality of the order attached'' (Pineapple 
Growers Ass'n, 673 F.2d at 1085 (quoting Dyestuffs and Chemicals, 271 
F.2d at 286)). A hearing need not be held to resolve questions of law 
and policy (see Kourouma v. FERC, 723 F.3d 274, 278 (D.C. Cir. 2013) 
(citing Citizens for Allegan County, Inc. v. FPC, 414 F.2d 1125, 1128 
(D.C. Cir. 1969)); Sun Oil Co. v. FPC, 256 F.2d 233, 240 (5th Cir. 
1958)).

IV. Analysis of Objections and Response to Hearing Requests

    The submission from the Environmental Defense Fund et al., contains 
eight numbered objections, some with multiple parts, and six requests 
for a hearing. We address each objection below, as well as any evidence 
and/or information filed in support of each. For each objection that 
requests a hearing, we evaluate whether the objection and any evidence 
and/or information submitted in support of it satisfies the standards 
for granting a hearing in Sec.  12.24(b).

A. Objection 1

    In Objection 1, the objectors argue that ``FDA unlawfully placed on 
the petitioners the burden of proving that the approved food-additive 
uses of phthalates are not safe'' (Objections at 8). The objectors 
assert that ``this legal error infected FDA's entire analysis and 
requires FDA to withdraw'' its order denying FAP 6B4815 (Objections at 
13). Because this objection raises a purely legal dispute, no hearing 
is warranted to adjudicate it (Sec.  12.24(b)(1)). Even if a hearing 
were available, the objectors did not request one with respect to this 
objection and, therefore, waive any right to a hearing (Sec.  
12.22(a)(4)). The only remaining issue on this objection, then, is 
whether it establishes that FDA's order denying FAP 6B4815 should be 
modified or revoked. As described below, we conclude that the objectors 
have not established a basis for modifying or revoking the denial 
order.

[[Page 86293]]

    In Objection 1, the objectors assert that FDA reviewed FAP 6B4815 
under an incorrect legal standard. The objectors argue that FDA must 
not expect revocation petitions to demonstrate the lack of safety of 
the food additives whose approvals the petitions seek to revoke. The 
objectors state that ``parties petitioning FDA to revoke approval of a 
food additive on safety grounds do not bear the burden of proving that 
the additive is unsafe, i.e., that it will cause harm to human health 
under the intended conditions of use'' (Objections at 9). Placing such 
a burden on the party seeking revocation would, the objectors assert, 
``be inconsistent with the Food Act's central premise for food-additive 
regulation, namely, that food additives are presumptively unsafe and 
may not be used unless the available evidence establishes with 
`reasonable certainty' that their use `will be safe' '' (id. (quoting 
section 409(c)(3)(A) of the FD&C Act)). (The reference to the ``Food 
Act'' is a reference to the FD&C Act.)
    The objectors also assert that FDA's basis for denying FAP 6B4815 
is inconsistent with our regulations. The objectors point to Sec.  
171.130 (21 CFR 171.130), which provides that petitions seeking 
amendments or repeals of existing food additive approvals 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 may justify its amendment or repeal'' (Objections at 10). 
The objectors interpret this regulation to mean that repeal petitions 
are required only to ``[tender] new information regarding a food 
additive's toxicity or otherwise demonstrating that amendment or repeal 
of the additive's authorization may be justified'' but do not bear 
``the burden of persuasion on the ultimate question of an additive's 
safety'' (id.). Therefore, the objectors contend, ``the burden of 
persuasion on the ultimate question of safety lies with the party 
advocating for continued authorization of the product'' (id. at 11). 
The objectors state that FDA applied an incorrect standard to 
evaluating FAP 6B4815 because ``FDA did not assess in the Order whether 
the petitioners provided `new information' regarding the `toxicity of 
the chemical[s]' at issue, as its regulations require, nor whether that 
information `establish[es] the existence of safety questions 
significant enough to support a finding that there is no longer a 
reasonable certainty of no harm from the currently approved uses' '' 
(id. at 12 (quoting Sec.  171.130(b) and the denial order at 87 FR 
31066 at 31067)).
    The objectors state that their position is consistent with League 
of United Latin Am. Citizens v. Regan, 996 F.3d 673 (9th Cir. 2021), a 
case involving the U.S. Environmental Protection Agency's (EPA's) 
regulation of pesticides (Objections at 10-11). The objectors further 
state their position is consistent with FDA's statement in a final rule 
concerning the food additive olestra (61 FR 3118, January 30, 1996) as 
well as the standard FDA applied in revoking food-additive 
authorizations for certain long-chain perfluorinated compounds (81 FR 
5, January 4, 2016) (Objections at 12).
    The crux of these arguments is that ``FDA unlawfully placed the 
burden of proof regarding the safety of the phthalate additives on the 
petitioners, asserting that FDA need only revoke a food additive 
authorization if presented with new evidence that `approved additives 
are in fact unsafe' '' (Objections at 12 (emphasis in original)).
    Finally, the objectors criticize FDA's approach in denying FAP 
6B4815 on the same day that we amended our regulations to no longer 
provide for most phthalates to be used in food contact applications 
because these uses were abandoned by industry (Objections at 12). The 
objectors state that the abandonment action ``significantly altered the 
scope of food-additive authorizations for phthalates that remain in 
effect, and for which a safety evaluation is still required'' (id.). 
The objectors state that our action ``reflects FDA's erroneous position 
that it may leave the extant food-additive authorizations in effect 
unless and until petitioners prove that they are in fact unsafe'' (id. 
at 12-13).
    FDA Response: We disagree with the assertion that FDA applied an 
incorrect legal standard in evaluating FAP 6B4815. It is fundamental 
that a food additive petition--whether requesting an authorization, 
modification, or repeal--must provide sufficient support for its 
request.
    We denied FAP 6B4815 because it failed to provide sufficient 
support for its request to revoke the authorization for the 28 ortho-
phthalates that were the subject of the petition. In reviewing FAP 
6B4815, we observed that the petition was premised on three distinct 
assertions (which, for ease of reference, we referred to as Assertions 
A, B, and C). Assertion A claimed that the 28 subject ortho-phthalates 
are chemically and pharmacologically related and should therefore be 
treated as a class for purposes of evaluating their safety. Under 
Assertion B, the petition proposed applying a purported ADI for di(2-
ethylhexyl) phthalate (DEHP) to all 28 ortho-phthalates (i.e., the 
petition proposed applying the proposed ADI to the entire purported 
class). Assertion C stated that the estimated daily intake (EDI) for 
the asserted class of 28 ortho-phthalates significantly exceeded the 
proposed ADI, thus rendering the purported class unsafe for their 
authorized uses as food contact substances. Our denial order explained 
in detail why the petition did not adequately support any of these 
three assertions. Consequently, we concluded that the petition did not 
contain sufficient data to support a finding that there is no longer a 
reasonable certainty of no harm from the approved uses (87 FR 31066 at 
31075). As an additional matter, we noted that, based on the 
information available to FDA, we did not have a basis to conclude that 
dietary exposure levels from authorized ortho-phthalates exceeded a 
safe level (id.). We stated that, as new information becomes available 
to us, we will continue to examine such data as appropriate to assess 
whether there remains a reasonable certainty of no harm (id.).
    Objection 1 rests on a flawed interpretation of the FD&C Act's 
legal framework governing food additives--in particular, its provisions 
concerning the premarket review of food additives. Under this 
framework, food additives are deemed unsafe and prohibited except to 
the extent FDA authorizes their use (see, e.g., sections 301(a), 
301(k), and 409(a) of the FD&C Act (21 U.S.C. 331(a), 331(k), and 
348(a))). Section 409 of the FD&C Act sets forth a process under which 
a person can submit a petition requesting that FDA issue a regulation 
prescribing the conditions under which a food additive may be safely 
used (see section 409(b)(1) of the FD&C Act). The statute specifies 
that a person must support such a petition by supplying the data 
specified in section 409(b)(2) of the FD&C Act. After a person submits 
a petition seeking approval of a food additive's use, FDA may issue a 
regulation authorizing the use only if the data before us establish 
that the proposed use of the food additive will be safe (see section 
409(c)(3)(A) of the FD&C Act).
    In addition to establishing the procedure for issuing regulations 
authorizing food additives, Congress directed FDA to establish a 
regulatory procedure prescribing how regulations authorizing food 
additives may be amended or repealed (see section 409(i) of the FD&C 
Act). Importantly, the

[[Page 86294]]

statute specifies that this regulatory ``procedure shall conform to the 
procedure provided in this section for the promulgation of such 
regulations'' (id.) (emphasis added) (section 409(i) of the FD&C Act). 
FDA's regulation at Sec.  171.130 establishes the procedure by which 
interested persons may petition FDA for amending or repealing a food 
additive authorization.
    FDA's approach to evaluating FAP 6B4815 was fully consistent with 
the legal framework described above. The provisions of section 409 of 
the FD&C Act make clear that the evidentiary burden to support 
authorization of a food additive's use lies with the petitioner seeking 
such authorization (see section 409(b) and (c) of the FD&C Act). Given 
the FD&C Act's directive that the regulatory procedure for amending or 
repealing an authorization ``shall conform'' to the statutory procedure 
for granting an authorization, it follows that a person seeking 
amendment or repeal likewise must provide a well-supported petition 
adequately justifying such action. See section 409(i) of the FD&C Act; 
In re Nat. Res. Def. Council, 645 F.3d 400, 403 (D.C. Cir. 2011) 
(``When a food additive petition seeks to amend an existing regulation, 
the petitioner must include full information on each proposed change'') 
(internal quotations and citations omitted). FDA's denial order 
thoroughly explained why the petition did not provide adequate evidence 
to support its requested postmarket remedy: the repeal of already-
authorized food additive uses. This conclusion did not conflict in any 
way with the premarket review framework invoked by the objectors.
    Moreover, to the extent the objectors contend that FDA disregarded 
any general statutory obligation to remove unsafe products from the 
market, we note that we have made no finding that the subject food 
additives are unsafe. Indeed, our denial order stated that we did not 
have a basis to conclude that dietary exposure levels from authorized 
ortho-phthalates exceeded a safe level (87 FR 31066 at 31075).
    The objectors' argument that FDA disregarded its own regulations is 
also in error. This argument relies on a portion of Sec.  171.130(b) 
providing that petitions for amendment or repeal must include an 
assertion of facts, supported by data, showing that new information 
exists. Citing this excerpt, the objectors maintain that this 
regulation ``establishes that petitioners seeking revocation of a food-
additive regulation bear a burden of production--specifically, the 
burden of tendering new information regarding a food additive's 
toxicity or otherwise demonstrating that amendment or repeal of the 
additive's authorization may be justified'' (Objections at 10). To the 
extent that the objectors assert that a repeal petition need only point 
to the existence of new toxicity data, this argument disregards the 
concluding sentence of Sec.  171.130(b).
    The concluding sentence provides that new data must be furnished in 
the form specified in Sec.  171.1 (21 CFR 171.1) for submitting 
petitions. Under Sec.  171.1(c), a petition must include ``full reports 
of investigations made with respect to the safety of the food 
additive.'' In addition, Sec.  171.1(c) provides that a petition ``may 
be regarded as incomplete unless it includes full reports of adequate 
tests reasonably applicable to show whether or not the food additive 
will be safe for its intended use.'' Further, under Sec.  171.1(c), for 
petitions seeking modification of existing regulations issued pursuant 
to section 409(c)(1)(A) of the FD&C Act (i.e., a regulation authorizing 
the use of a food additive under specified conditions), ``full 
information on each proposed change that is to be made in the original 
regulation must be submitted.'' Accordingly, petitions seeking 
revocation of a food additive regulation must do more than merely 
identify the existence of new toxicity studies. See also In re NRDC, 
645 F.3d at 403 (considering petition to repeal existing food additive 
authorization and citing Sec.  171.1 to conclude that food additive 
petitions seeking to amend existing food additive authorizations must 
include full information on each proposed change). Thus, FDA's 
regulations make clear that repeal petitions such as FAP 6B4815 must 
include adequate supporting information. We therefore acted 
consistently with our regulations when we evaluated FAP 6B4815 to 
determine whether its assertions were supported and whether the 
petition contained sufficient data to support a finding that there is 
no longer a reasonable certainty of no harm from the currently approved 
uses.
    Next, the objectors maintain that FDA's approach in evaluating FAP 
6B4815 was inconsistent with the following: (1) the League of United 
Latin Am. Citizens v. Regan, 996 F.3d 673 (9th Cir. 2021), a case 
involving EPA's regulation of pesticides; (2) an FDA statement in a 
food additive proceeding involving olestra; and (3) FDA's action on 
three specific perfluoroalkyl ethyl-containing food-contact substances. 
We address each of these in turn.
    First: The League of United Latin Am. Citizens (LULAC) case cited 
by the objectors is not germane because its holding was based on a 
distinct statutory scheme applicable to pesticides under section 408 of 
the FD&C Act (21 U.S.C. 346a) and factual circumstances different from 
the facts underlying this proceeding. In that case, EPA had received a 
petition asking the agency to prohibit foods that contained any residue 
of the insecticide, chlorpyrifos (996 F.3d at 673). EPA argued that the 
agency could leave in effect tolerances for the pesticide while the 
agency continued to evaluate the science (id. at 688). The LULAC court 
held that EPA has a continuing obligation under section 408 of the FD&C 
Act to ensure the safety of established pesticide tolerances that were 
previously found to be safe (id. at 691) (finding that EPA ``has its 
own continuing duty under [section 408 of the FD&C Act] to determine 
whether a tolerance that was once thought to be safe still is''). The 
court's conclusion regarding EPA's continuing obligation was based on 
statutory language in section 408 of the FD&C Act that is materially 
different from the language in section 409 of the FD&C Act at issue in 
this proceeding.
    Under section 408(b)(2)(A)(i) of the FD&C Act, EPA ``may establish 
or leave in effect a tolerance for a pesticide chemical residue in or 
on a food only if the Administrator determines that the tolerance is 
safe'' (emphasis added). In contrast, section 409 of the FD&C Act does 
not contain anything comparable to the ``leave in effect a tolerance . 
. . only if the Administrator determines that the [substance] is safe'' 
language in section 408, which was the linchpin for the LULAC court's 
conclusion that EPA had ``a continuous duty'' to determine whether a 
tolerance for a pesticide chemical reside is safe (id. at 692 
(``[Section 408 of the FD&C Act] imposes a continuous duty upon the EPA 
by permitting it to `leave in effect' a tolerance `only' if it finds it 
is safe. To `leave' something in effect means `to cause or allow [it] 
to be or remain in a specified condition. Denying the 2007 Petition 
caused the chlorpyrifos tolerances to remain in place . . . . But in so 
doing, the EPA did not `[determine] that the tolerance is safe.' '')) 
(Compare Sec. 409 of the FD&C Act).
    Further, unlike section 408 of the FD&C Act, section 409 of the 
FD&C Act directs FDA to establish procedures for repealing food 
additive authorizations that ``shall conform'' to the statutory 
procedure for promulgating authorizations, under which the evidentiary 
burden to support authorization of a food additive's use

[[Page 86295]]

lies with the petitioner seeking such authorization (see section 409(c) 
and (i) of the FD&C Act). Given the statutory framework established in 
section 409 of the FD&C Act and the ways in which it differs from the 
framework established in section 408 of the FD&C Act, it was entirely 
reasonable that FDA assessed the information in the objectors' repeal 
petition to determine whether there was sufficient data to establish 
the existence of safety questions significant enough to support a 
finding that there is no longer a reasonable certainty of no harm from 
the approved ortho-phthalates' uses. Furthermore, the factual 
circumstances are distinct. In LULAC, the record showed that EPA 
``repeatedly determined'' that the pesticide at issue was unsafe under 
the approved tolerance levels. Here, however, FDA has never determined 
the ortho-phthalates at issue in this proceeding to be unsafe. Instead, 
our denial order explained that FDA did not have a basis to conclude 
that dietary exposure levels from approved ortho-phthalates exceed a 
safe level (87 FR 31066 at 31075).
    Second: The objectors cite as support for their argument the 
following statement in the Federal Register document announcing FDA's 
decision to approve olestra: ``It is important to recognize that to 
institute a proceeding to limit or revoke the approval of olestra, FDA 
would not be required to show that olestra is unsafe. Rather, the 
agency would only need to show that based upon new evidence, FDA is no 
longer able to conclude that the approved use of olestra is safe, i.e., 
that there is no longer a reasonable certainty of no harm from the use 
of the additive'' (Objections at 11 (quoting 61 FR 3118 at 3169)). The 
objectors also refer to a statement in the olestra proceeding where FDA 
stated that ``in any proceeding to [withdraw] or limit the approval of 
olestra, Procter and Gamble would have the burden to establish the 
safety of the additive'' (Objections at 11, n. 39 (quoting 61 FR 3118 
at 3169); see also Sec.  12.87(c)). The objectors cite these excerpts 
from the olestra proceeding as support for the following proposition: 
``FDA has stated plainly that when FDA is in the position of raising 
concerns about the safety of a food additive or other product that it 
has previously authorized, the agency bears only an initial burden of 
producing new information that calls into question its previous safety 
finding; the burden of persuasion on the ultimate question of safety 
lies with the party advocating for continued authorization of the 
product'' (Objections at 11). However, contrary to the objectors' 
suggestion, FDA did not say or imply that we would initiate revocation 
proceedings based merely on new information that might ``[call] into 
question its previous safety finding,'' nor did FDA say or imply that 
we would be required to initiate such a proceeding upon being presented 
with such information. Instead, FDA stated that, to initiate the 
withdrawal process, we would ``need to show that based upon new 
evidence, FDA is no longer able to conclude that the approved use of 
olestra is safe, i.e., that there is no longer a reasonable certainty 
of no harm from the use of the additive'' (61 FR 3118 at 3169). 
Subsequently, in a hearing regarding the withdrawal of olestra, we 
stated that the sponsor, Procter and Gamble, would then have the burden 
of establishing safety (id. (citing Sec.  12.87(c)). Our review of FAP 
6B4815 was entirely consistent with the statements from the olestra 
proceeding cited by the objectors as to the evidence necessary to 
initiate the process of repealing a food additive authorization. In 
reviewing FAP 6B4815, we concluded that its assertions were not 
adequately supported, and therefore, the petition did not contain 
sufficient data to support a finding that there is no longer a 
reasonable certainty of no harm from the currently approved uses of the 
subject ortho-phthalate food additives (87 FR 31066 at 31075). 
Accordingly, we did not grant the petition's request that we institute 
proceedings to repeal the authorizations that were the subject of FAP 
6B4815.
    Third: Regarding FDA's action to revoke the authorizations for the 
food additive uses of three specific perfluoroalkyl-ethyl-containing 
food-contact substances (see 81 FR 5), the objectors state that FDA did 
so ``based on data raising `significant questions as to the safety of 
the authorized uses' '' (Objections at 9). However, the objectors' 
characterization of what FDA's perfluoroalkyl ethyl action was ``based 
on'' misunderstands the basis for that action. FDA stated in the 
perfluoroalkyl ethyl order that ``we conclude that there is no longer a 
reasonable certainty of no harm for the food contact use of these 
[substances]'' and that we were, therefore, taking the revocation 
action (81 FR 5 at 7).
    FDA did not state that the perfluoroalkyl ethyl revocation action 
was being instituted based on a finding of ``significant questions'' in 
isolation. Instead, FDA stated that ``[i]n order for FDA to grant a 
petition that seeks an amendment to a food additive regulation based 
upon new data concerning the toxicity of the food additive, such data 
must be adequate for FDA to conclude that there is no longer a 
reasonable certainty of no harm for the intended use of the substance'' 
(81 FR 5 at 7) (FDA's statements in the ortho-phthalates denial order 
were consistent, see 87 FR 31066 at 31067).
    Finally, the objectors criticize FDA's approach in denying FAP 
6B4815 on the same day that we amended our regulations to no longer 
provide for 25 ortho-phthalates to be used in food contact applications 
because these uses were abandoned by industry (i.e., the abandonment 
final order). We issued the abandonment final order in response to a 
separate food additive petition that was based on abandonment, not 
safety (see 87 FR 31080). While the objectors assert that our decision 
to take action based on abandonment ``reflects FDA's erroneous position 
that it may leave the extant food-additive authorizations in effect 
unless and until petitioners prove that they are in fact unsafe,'' this 
assertion is unsupported.
    We did not deny FAP 6B4815 for the reason that the petition failed 
to prove that the ortho-phthalates are in fact unsafe (i.e., they cause 
harm under their intended conditions of use); that was not the 
necessary showing. Instead, we denied FAP 6B4815 because the assertions 
in the petition were not adequately supported and the petition did not 
contain sufficient data to support a finding that there is no longer a 
reasonable certainty of no harm from the approved uses (i.e., FAP 
6B4815 did not contain sufficient data to support a finding that there 
is no longer a reasonable certainty in the minds of competent 
scientists that the substances are not harmful under the conditions of 
their intended use, see Sec.  170.3(i) (21 CFR 170.3(i)). Our denial 
order (87 FR 31066) correctly stated that a petition that seeks to 
amend or repeal existing regulations based on safety must contain 
sufficient data to establish the existence of safety questions 
significant enough to support a finding that there is no longer a 
reasonable certainty of no harm from the currently approved uses (see 
87 FR 31066 at 31067 (citing section 409(c) of the FD&C Act) 
(describing the data requirements); Sec. Sec.  171.1 through 171.130 
(prescribing food additive petition regulations)).
    For all these reasons, we disagree with the objectors' assertion 
that we committed any legal error that justifies modifying or revoking 
our denial order.

B. Objection 2

    In Objection 2, the objectors state that ``FDA unlawfully failed to 
evaluate the safety of the food-additive uses of phthalates that remain 
authorized'' (Objections at 13). The objectors refer to the fact that 
FDA issued the denial order

[[Page 86296]]

on the same day that we issued the abandonment final order, which 
amended our regulations to remove food additive authorizations for the 
use of 25, but not all, authorized ortho-phthalates that were the 
subject of FAP 6B4815 (see 87 FR 31080). FDA took this action based on 
evidence that the authorized food additive uses of most, but not all, 
of those ortho-phthalates were abandoned (id. at 31086). We did not 
receive evidence showing abandonment for the following five ortho-
phthalates that remain authorized as food additives for specified uses: 
diisononyl phthalate (DINP) (CAS No. 28553-12-0), diisodecyl phthalate 
(DIDP) (CAS No. 26761-40-0), di(2-ethylhexyl) phthalate (DEHP) (CAS No. 
117-81-7), dicyclohexyl phthalate (DCHP) (CAS No. 84-61-7), and diallyl 
phthalate (DAP) (CAS No. 131-17-9, for use as a monomer). Therefore, 
the food additive authorizations for these five ortho-phthalates remain 
in place.
    The objectors assert that FDA failed to meet its obligation to 
oversee the safety of the food supply by not conducting a new safety 
analysis for these five ortho-phthalates that remain authorized as food 
additives (Objections at 13). The objectors assert that FDA failed to 
satisfy its obligations to evaluate whether FAP 6B4815 contained `` 
`new data . . . that would justify amendment' of the applicable 
authorizations'' by assessing both ``the data and information in the 
petition and other available relevant material.' '' (id. at 14 (quoting 
81 FR 7, FDA's revocation of certain perfluoroalkyl ethyl-containing 
food-contact substances)). The objectors also state that FDA's separate 
RFI (87 FR 31090) regarding the still-authorized ortho-phthalates 
constituted an ``attempt to kick the proverbial can down the road'' 
that discredits FDA's assertion in its response to FAP 6B4815 that it 
had adequately assessed currently available research regarding 
phthalates, and that ``unlawfully . . . defer[red]'' consideration of 
an ``[issue] that FDA was required to address--years ago--in response 
to [FAP 6B4815]'' (id. at 15-16).
    The objectors do not request a hearing. Therefore, the objectors 
waive their right to a hearing on this objection (Sec.  12.22(a)(4)). 
The only remaining issue on Objection 2, then, is whether it 
establishes that FDA's order denying FAP 6B4815 should be modified or 
revoked. As described below, we conclude that the objectors have not 
established a basis for modifying or revoking the denial order.
    FDA Response: We do not agree with the objectors' assertions that 
FDA's response to FAP 6B4815 was unlawful because FDA did not conduct a 
new safety analysis of DINP, DIDP, DEHP, DCHP, and DAP; i.e., the five 
ortho-phthalates that were the subject of their petition that still 
have food additive authorizations in effect. When we originally 
authorized the use of these five additives, we concluded that the use 
of the food additives satisfied the statutory safety standard.
    FAP 6B4815 did not identify deficiencies with our original approval 
of phthalates for food contact use. Instead, FAP 6B4815 proposed a 
class-based grouping approach for evaluating the safety of the subject 
ortho-phthalates. In FAP 6B4815, the petitioners proposed that the 
authorizations should be revoked because, according to the petition: 
the subject ortho-phthalates share common chemical and pharmacological 
characteristics that justify grouping them as a class; a single ADI 
value from one ortho-phthalate should be applied to all members of the 
proposed class collectively; and both the EDI value for select 
phthalates as well as the cumulative estimated daily intake for the 
proposed class significantly exceeds the purported ADI value for the 
proposed class. In Objection 2, the objectors turn their attention to 
the phthalates that remain authorized as food additives. Regarding 
these ortho-phthalates that remain authorized, we conducted additional 
analysis by evaluating, in a supplementary memorandum, whether the core 
premise of FAP 6B4815 (i.e., the assertion that the subject ortho-
phthalates should be grouped as a class for purposes of a safety 
assessment) could be applied to the five still-authorized ortho-
phthalates. Our review used the information contained in the petition 
as well as other available information, including assessments from 
other regulatory bodies (Ref. 1). In that memorandum, which we made 
publicly available on the docket, we explained why the information 
before us did not support the grouping of these five substances for 
purposes of a safety assessment (id.). We based this conclusion on the 
structural variations and the differences in metabolites, metabolism, 
and toxicological endpoints across the substances. We described these 
differences and the scientific literature we reviewed in the memorandum 
(id.).
    Objection 2 urges us to disregard the very approach for analyzing 
food additive safety that the petitioners proposed in FAP 6B4815. 
Specifically, Objection 2 asserts that FDA committed legal error by not 
conducting a new safety assessment for the five still-authorized ortho-
phthalates even though FDA analyzed these substances in accordance with 
the class-grouping approach proposed by FAP 6B4815. Therefore, 
Objection 2 ignores the fact that we assessed the appropriateness of 
class grouping the five still-authorized ortho-phthalates (Ref. 1). 
Objection 2 largely recasts the arguments made in Objection 1 but with 
respect to the five still-authorized ortho-phthalates. It does this by 
citing FDA's statement in the Federal Register document in which we 
authorized olestra, where we referred to ``the agency's continuing 
obligation to oversee the safety of the food supply'' (61 FR 3118 at 
3168; see also Objections at 13-14 and 16).
    Our responses to Objection 1's assertions apply with equal force to 
Objection 2's assertions that we are required to conduct a new safety 
assessment with respect to the five still-authorized ortho-phthalates; 
as explained earlier, a petition that seeks to amend or repeal existing 
regulations based on safety must contain sufficient data to establish 
the existence of safety questions significant enough to support a 
finding that there is no longer a reasonable certainty of no harm from 
the currently approved uses. This standard for review is consistent 
with FDA's actions in the olestra proceeding. Moreover, the 
administrative record makes it clear that we satisfied our duties in 
reviewing FAP 6B4815. We reviewed the assertions in FAP 6B4815 in 
detail. In a separate memorandum, we evaluated the five still-
authorized ortho-phthalates, using the same core premise of class 
grouping proposed in FAP 6B4815 (Ref. 1).
    Objection 2 also accuses FDA of publishing its RFI (87 FR 31090) to 
``unlawfully . . . defer its evaluation of whether the agency's current 
authorizations for food-contact uses of phthalates are in fact safe'' 
(Objections at 15). However, our publication of the RFI, which sought 
scientific data and information on current uses, use levels, dietary 
exposure, and safety data of certain ortho-phthalates, was intended to 
seek any data that we do not possess, which ``may add to our knowledge 
of ortho-phthalates that remain authorized for use'' (see 87 FR 31090-
31091). The fact that we sought data from the public to inform our 
oversight of authorized ortho-phthalates does not reflect any 
deficiency in our evaluation of the specific assertions in FAP 6B4815 
based on the information that was in the record.
    Objection 2 also takes issue with FDA's response to a comment to 
the docket concerning FAP 6B4815, in which we stated that ``FDA is 
aware of

[[Page 86297]]

the research that has been conducted with respect to phthalates and 
that FDA considered `the research in its evaluation of the petition' '' 
(Objections at 14 (quoting 87 FR 31066 at 31076)). The objectors 
criticize FDA for not disclosing how we considered ``the research that 
has been conducted with respect to phthalates'' (Objections at 14). The 
objectors also assert that FDA's statement about having considered the 
research related to phthalates ``cannot be credited'' given that we 
issued the RFI on the same day that we denied FAP 6B4815. The 
statements that the objectors excerpt in Objection 2 were made in 
response to comments that referred to literature describing phthalates 
as hormone disrupting chemicals that are linked to certain adverse 
health outcomes (see 87 FR 31066 at 31076). We responded to the 
comments by stating that we are generally aware of the research on 
phthalates and considered the research cited in the comments (id.).
    The denial order, as well as the memoranda we made publicly 
available when we published the denial order (specifically, the 
chemistry memorandum, the toxicology memorandum, and the memorandum 
evaluating the five still-authorized ortho-phthalates), demonstrate 
that we considered the numerous research studies in the administrative 
record, including the research cited in the comments (Refs. 1, 3, and 
4). While we are generally aware of updated toxicological and use 
information that is publicly available, we published the RFI so that we 
could obtain a more complete picture of the data relevant to the 
general safety, dietary exposure, and usage of ortho-phthalates, which 
may include data that stakeholders have not made public (see 87 FR 
31090).
    Objection 2 also includes certain other arguments. In the last 
paragraph of Objection 2, the objectors repeat arguments they made in 
Objection 1 regarding the type of evidence that FAP 6B4815 was required 
to proffer (Objections at 16). Because we address these arguments in 
response to Objection 1, we do not repeat our evaluation of these 
arguments here. A footnote in Objection 2 also refers to the premarket 
review requirements for food additives (Objections at 14, n.48). 
However, as explained in response to Objection 1, FAP 6B4815 is a 
request for postmarket action, and our response to the petition did not 
conflict with the premarket review framework invoked by the objectors. 
Additionally, Objection 2 asserts that FDA should have evaluated FAP 
6B4815 to determine whether it presented new data (Objections at 16). 
As explained in our response to Objection 1 regarding the olestra 
proceeding, repeal petitions must do more than merely point to the 
existence of new data.
    For these reasons, we disagree with the objectors' assertion that 
we committed any legal error that justifies modifying or revoking our 
denial order.

C. Objection 3

    In Objection 3, the objectors argue that FDA's denial order ``fails 
to address new toxicity information that raises significant questions 
about the safety of the approved food-additive uses of phthalates'' 
(Objections at 17). In particular, the objectors state that new 
information became available since petitioners last supplemented the 
record for FAP 6B4815 in 2017. The objectors point to numerous studies 
and declarations concerning the health effects of ortho-phthalates. 
Most of these studies and declarations were submitted to the docket 
dedicated to their citizen petition addressing ortho-phthalates. In 
light of these studies and declarations, the objectors state that FDA 
should not have allowed DAP, DCHP, DEHP, DINP, and DIDP to remain 
authorized for food-contact use ``without addressing the substantial 
body of relevant toxicity information'' (Objections at 17).
    The information that the objectors identify in Objection 3 includes 
studies that they describe as linking DEHP exposure to developmental 
toxicity, developmental neurotoxicity, adult neurotoxicity, 
reproductive toxicity, endocrine disruption, hepatoxicity, metabolic 
toxicity, immunotoxicity, and epigenetic alterations (id. at 17-18). 
The objectors describe these studies as ``provid[ing] evidence for a 
number of DEHP-related adverse health outcomes, including altered adult 
sex behavior, delayed puberty, insulin sensitivity, obesity, 
hypothyroidism, cognitive impairment, and even depressive-link 
behaviors'' (Objections at 18). The objectors further assert that 
animal studies have linked DINP exposure to hepatoxicity and 
exacerbated nerve cell damages and decline in learning and memory, as 
well as elevated cholesterol (id.). In addition, the objectors assert 
that two studies ``found that phthalate mixtures induced reproductive 
tract malformations in male rats'' and point to epidemiological studies 
they describe as ``providing relevant toxicity information'' with 
respect to associations between DEHP and multiple adverse health 
outcomes (id. at 18). The objectors reference studies they describe as 
linking DINP and/or DEHP to insulin resistance, delayed puberty onset 
in boys, preterm birth, and neurodevelopmental harm (id. at 19). The 
objectors further point to certain publications by federal and European 
agencies (id.). Finally, the objectors point to the declarations they 
submitted to FDA that assert that phthalate exposure causes harm (id. 
at 20). The objectors request a hearing on Objection 3. They state that 
the hearing would address ``whether the many years' worth of data and 
information regarding the human health hazards of phthalates found in 
the diet presented in support of the Petition and Objections raise 
significant questions regarding the safety of the authorized food-
additive uses of DAP, DCHP, DEHP, DINP, and DIDP'' (Objections at 21).
    FDA Response: To justify a hearing on this objection, it is not 
enough for the objectors to simply name health effects linked to the 
still-authorized ortho-phthalates or to list publications and 
declarations that address the topic of ortho-phthalates generally. The 
objectors cite numerous recent studies and publications but do not 
provide meaningful analysis or explanation for why these materials 
support a finding that there are significant questions about the safety 
of the still-authorized ortho-phthalates for their currently authorized 
conditions of use. The objectors' mere citation of these studies and 
declarations is not adequate to justify resolution in the objectors' 
favor of the factual question about safety of the still-authorized food 
additive uses of ortho-phthalates; the existence of toxicity findings, 
alone, is insufficient to establish significant questions about whether 
there is no longer a reasonable certainty of no harm for an authorized 
use and is, therefore, insufficient to justify resolution of the 
factual question of safety (Sec.  12.24(b)(3)).
    All substances exhibit toxic effects at high enough exposure 
levels, and most substances exhibit an exposure threshold below which 
they do not exhibit a toxic effect. To support an assertion that the 
authorized use of a substance is unsafe or presents significant safety 
questions, it is not sufficient to cite studies that indicate that a 
substance is associated with a toxic effect; rather, that effect must 
be placed in the context of exposure. For this reason, when evaluating 
the safety of a substance, scientists will often determine the ``dose-
response'' relationship of substance exposure and toxic effect.
    To establish with reasonable certainty whether a food additive is 
harmful under its intended conditions of use, FDA considers the 
projected human dietary exposure to the food additive, the additive's 
toxicological data, and

[[Page 86298]]

other available relevant information (such as published literature). To 
determine safety, one approach we may use is to compare the estimated 
dietary intake of the food additive to an ADI level established by 
appropriate toxicological data. An ADI is the amount of a substance 
that is considered safe to consume each day over the course of a 
person's lifetime (Ref. 2). The ADI is typically based on an evaluation 
of toxicological studies to determine the highest appropriate 
experimental exposure dose level in animal studies that was shown to 
cause no adverse effect (also known as the no-observed-adverse-effect 
level, or NOAEL), divided by an appropriate safety factor (id.). A 
calculated dietary exposure to the food additive (i.e., the EDI) at or 
below the ADI is considered consistent with a reasonable certainty of 
no harm (id.).
    The objectors list publications of various animal and in vitro 
studies in Objection 3, yet they do not attempt to address whether the 
publications are relevant to assessing an appropriate ADI, calculating 
an EDI, or whether the dietary exposure could result in a toxic effect 
(i.e., the estimated daily exposure exceeds an appropriate ADI). The 
petitioners proposed an ADI in their underlying food additive petition, 
but our denial order explained why the proposed ADI was not supported 
and Objection 3 does not address or otherwise engage with FDA's 
identified concerns. Furthermore, the ADI that FAP 6B4815 proposed in 
the underlying petition was not based on any of the studies cited in 
Objection 3.
    The information provided in Objection 3 consists largely of studies 
that link some phthalates to certain identified health effects. Some 
studies are useful for hazard identification to determine additional 
hypotheses for future research, but these studies are not designed to 
provide information to show at which threshold level of dietary 
exposure these effects may occur. Such hazard identification is the 
first step in a risk assessment, but the existence of a possible effect 
does not necessarily mean that the effect is the appropriate endpoint 
to use for a risk assessment, that the effect will occur at the level 
of the substance in the diet, or that the substance is in fact unsafe 
for its intended use. As the hazard identification studies do not 
examine a dose-response relationship, these data are not adequate for 
identifying a NOAEL to perform a risk assessment for the food contact 
uses of the still-authorized phthalates. The data from such hazard 
identification studies are, therefore, not adequate to establish 
significant questions about whether there is no longer a reasonable 
certainty of no harm from the authorized uses and are insufficient to 
justify resolution of the factual question of safety.
    The other information the objectors cite in Objection 3 includes 
epidemiological studies. While epidemiological studies may suggest a 
possibility of occurrence of an effect, they are generally not useful 
for risk assessment due to a lack of control of confounders such as 
dietary, medical, and lifestyle factors, socioeconomic status, and 
characterization of past exposures. Some studies may also include self-
reported data by the test subjects which increases the potential for 
biases and inaccuracies, making it challenging to establish a 
consistent and reliable relationship between the cause and effect. 
Therefore, although epidemiological studies may be considered 
supplementary to the available toxicological data for conducting a 
safety evaluation, in general, they are not suitable to provide primary 
or sufficient basis for performing a risk assessment.
    The objection also cites the two declarations that were also 
submitted to the docket for the ortho-phthalates citizen petition. The 
declarations cite numerous epidemiological studies and a few animal 
studies that provide information on potential hazard identification. 
The declarations do not provide any dietary exposure estimates for the 
remaining five phthalates from their authorized food additive uses or 
additional supporting information for assessing the safety of the uses 
of the phthalates studied as food contact substances.
    The Federal and European publications cited in Objection 3 are the 
``Toxicological Profile for DEHP'' released by the Agency for Toxic 
Substances and Disease Registry (``ATSDR'') (Ref. 5), the ``Technical 
Report on the Toxicology and Carcinogenesis Studies of Di(2-
etyhylhexyl) Phthalate'' (Ref. 6) released by the National Toxicology 
Program (NTP), and an updated risk assessment of DEHP, DBP, BBP, DINP, 
and DIDP (Ref. 7) for use in food-contact materials released by the 
European Food Safety Authority (EFSA). Objection 3 states that these 
studies ``provide novel insights and weight of evidence analyses that 
are relevant to the safety reevaluations that FDA must conduct'' 
(Objections at 19). However, the objection does not provide any 
explanation for how these studies would be adequate to assess the 
safety of the substances' authorized food additive uses and, therefore, 
the objection does not establish that these studies create significant 
questions about whether there is no longer a reasonable certainty of no 
harm such that they would resolve the factual question of safety.
    The objection also cites two dose-response studies to state that 
``examining the cumulative effects of several phthalates (including 
DCHP and DEHP) found that phthalate mixtures induced reproductive tract 
malformations in male rats at doses well below those associated with 
harm from individual chemicals'' (Objections at 18). However, the 
objection fails to mention that, while the study referenced (Conley, et 
al. 2021) (Ref. 8) did include two of the five phthalates that still 
have food additive uses in the United States (DEHP and DCHP), the study 
examined effects using a mixture of nine phthalates and five non-
phthalate pesticides cumulatively, which cannot separate adverse 
effects caused by either a single phthalate, group of phthalates, or 
the non-phthalate pesticides. Similarly, the other study referenced 
(Conley, et al. 2018) (Ref. 12) dosed the rats using a mixture of 18 
chemicals, which included 9 phthalates (including DEHP and DCHP) and 
nine non-phthalate pesticides or drugs. Therefore, the two dose-
response studies cited in Objection 3 do not directly address the 
safety of the food contact uses of the five still-authorized ortho-
phthalate food additives.
    For these reasons, the objectors failed to demonstrate how the 
cited studies, publications, declarations, and facts asserted would be 
sufficient to justify resolution of the safety question in the 
objectors' favor. The objectors did not justify why the studies cited 
in Objection 3 would establish questions significant enough to support 
a finding that there is no longer reasonable certainty of no harm or 
that there are ``significant questions regarding the safety of the 
authorized food-additive uses of DAP, DCHP, DEHP, DINP, and DIDP.'' In 
other words, the objectors did not establish that the information in 
the record is adequate to justify their factual assertion regarding 
safety. Accordingly, Sec.  12.24(b)(3) supports denial of the request 
for the hearing. A hearing will not be granted when the information 
cited is not sufficient to support the factual assertion (Sec.  
12.24(b)(3)).
    Furthermore, a hearing will not be held unless resolution of the 
factual issue in the way sought by the objector is adequate to justify 
the action requested (Sec.  12.24(b)(4)). In Objection 3, the objectors 
alter the action requested from what they originally sought in FAP

[[Page 86299]]

6B4815, which was the revocation of food additive approvals for 28 
ortho-phthalates. They now seek a hearing ``regarding the safety of . . 
. DAP, DCHP, DEHP, DINP, and DIDP'' (Objections at 21)--the five ortho-
phthalates that remain authorized for use as food additives. This 
objection does not demonstrate how the outcome of the proceeding would 
be different if the factual issues addressed in this objection were 
resolved in the way sought, because this objection does not address the 
underlying requested action.
    The underlying requested action was that FDA revoke the food 
additive authorizations for the 28 subject ortho-phthalates based on 
their grouping as a class. The basis for the underlying requested 
action was that FDA should: (1) consider the 28 subject ortho-
phthalates to be a single class of chemically and pharmacologically 
related substances for safety evaluation; (2) apply FAP 6B4815's 
proposed ADI to the purported class; and (3) determine that the EDI for 
the class exceeds that ADI. However, Objection 3 focuses only on five 
of the 28 ortho-phthalates and asks that we take action with respect to 
these five. Thus, we are denying the request for a hearing in Objection 
3 because a hearing will not be granted on factual issues that are not 
determinative of the action requested in the proceeding (Sec.  
12.24(b)(4)).
    It is important to note that the objectors claim that our denial 
order was deficient because it did not address questions they failed to 
ask, and to take actions they failed to request, in the petition that 
is the subject of this proceeding.\1\ Such matters are outside the 
scope of the process set forth in section 409(f)(1) of the FD&C Act, 
which requires objections to ``[to specify] . . . the provisions of the 
[denial] order deemed objectionable.'' Because this objection and the 
corresponding request for a hearing seek determinations regarding 
issues that are outside the scope of the provisions of FDA's denial 
order, the objection and hearing request are improper. The assertions 
and information cited in Objection 3 regarding the health effects of 
the five still-authorized ortho-phthalate food additives would not 
change our conclusion that the requested action in FAP 6B4815 to remove 
the food contact authorizations for a purported class of 28 ortho-
phthalates was not adequately supported. A hearing will not be granted 
unless resolution of a factual issue in the way sought by the objector 
is adequate to justify the action requested (Sec.  12.24(b)(4)). This 
conclusion does not change the fact that FDA may, in the future, 
consider a subset of ortho-phthalates that remain authorized for use in 
food contact applications to be a single class of chemically and 
pharmacologically related substances for purposes of a safety 
evaluation.
---------------------------------------------------------------------------

    \1\ While FDA is denying this request for a hearing, we again 
note that, in the Federal Register of May 20, 2022, we issued an RFI 
seeking scientific data and information on current uses, use levels, 
dietary exposure, and safety data for ortho-phthalates that remain 
authorized for use in food contact applications (87 FR 31090). Any 
future evaluation may be informed by, among other things, 
appropriate scientific data and information submitted in response to 
the RFI.
---------------------------------------------------------------------------

D. Objection 4

    In Objection 4, the objectors take the position that we misapplied 
section 409(c)(5)(B) of the FD&C Act, which provides that, in 
determining whether a food additive is safe under section 409 of the 
FD&C Act, FDA is to ``consider among other relevant factors'' the 
cumulative effect of such additive in the diet of man or animals, 
taking into account any chemically or pharmacologically related 
substance or substances in such diet. The objectors assert that to 
``conduct the safety evaluations the Food Act demands, FDA must 
withdraw the Order and properly apply the statutory standard for 
chemically or pharmacologically related substances to account for the 
cumulative effects of all related phthalates in the diet'' (Objections 
at 26). Because this objection raises a purely legal dispute, no 
hearing is warranted to adjudicate it (Sec.  12.24(b)(1)). Even if a 
hearing were available, the objectors did not request one with respect 
to this objection and therefore waive any right to a hearing (Sec.  
12.22(a)(4)). The only remaining issue on Objection 4, then, is whether 
the objection establishes that FDA's order denying FAP 6B4815 should be 
modified or revoked. As described below, we conclude that the objectors 
have not established a basis for modifying or revoking of the denial 
order.
    The objectors assert that while the denial order ``does not 
articulate FDA's interpretation of what constitutes a `related' 
substance,'' FDA nevertheless ``applied an erroneous interpretation of 
`chemically or pharmacologically related' substances for which the Food 
Act mandates a cumulative effects analysis'' (Objections at 22). In 
describing our review of FAP 6B4815, the objectors assert that FDA 
``appeared to interpret'' this provision of the FD&C Act as only 
applying if substances that are known to share all of the following 
three factors: ``(1) well-defined similarities in chemical structure, 
and (2) a common defined toxicological endpoint, and (3) a common 
mechanism of action associated with that common endpoint'' (internal 
quotations omitted) (Objections at 23). The objectors disagree with 
this purported requirement and state that ``FDA's regulations make the 
focus on common effects, as opposed to a common mechanism of action'' 
(citing Sec.  170.18(a)) (Objections at 24). The objectors assert the 
proper focus is on common health effects (id.). The objectors state, 
``it would be irrational and contrary to the Food Act's safety mandate 
to ignore the cumulative effects of substances in the diet that are 
known to contribute to the same adverse health effect because the 
mechanism of action is not known to be the same for both substances or 
is not known at all'' (id.). Finally, the objectors assert in Objection 
4 that we ``erred in asserting that it is only required to consider the 
cumulative effects of substances that would be suitable for grouping 
into a single category for risk assessment'' (internal quotations 
omitted) (id.).
    FDA Response: Objection 4 questions FDA's evaluation of the claim 
made in FAP 6B4815 that the 28 subject ortho-phthalates are chemically 
and pharmacologically related and should therefore be treated as a 
class for purposes of evaluating their safety. In describing FDA's 
evaluation of this claim, the objectors assert that FDA required all of 
the following three factors to be satisfied: ``(1) well-defined 
similarities in chemical structure, and (2) a common defined 
toxicological endpoint, and (3) a common mechanism of action associated 
with that common endpoint'' (Objections at 23). As support for the 
proposition that FDA imposed such a requirement, Objection 4 cites to 
both the denial order and FDA's toxicology memorandum supporting the 
denial order (Ref. 4).
    There is no place in the denial order where we imposed such a 
requirement. In the denial order, we noted that other regulatory and 
scientific bodies have grouped phthalates based on these three 
considerations (87 FR 31066 at 31071). We also noted in our denial 
order that FAP 6B4815's approach to class grouping was not consistent 
with the approach taken by other regulatory and scientific bodies, 
given that FAP 6B4815 identified the work of those other bodies as a 
basis for the requested action (id.).
    To support their claim in Objection 4 that FDA required FAP 6B4815 
to satisfy the three factors that the objectors identify, the objectors 
cite page 10 of our toxicology memorandum for FAP 6B4815 (Ref. 4). The 
toxicology memorandum, however, did not suggest that FDA required the 
three factors as a

[[Page 86300]]

condition for grouping. Rather, this portion of the toxicology 
memorandum addressed the claim in FAP 6B4815 that the 28 subject ortho-
phthalates have similar health effects. In doing so, the toxicology 
memorandum noted that while FAP 6B4815 asserted that all ortho-
phthalates must be assumed to have ``reproductive/developmental, and 
endocrine health effects,'' the terms ``reproductive, developmental, 
and endocrine effects are broad terms that cover a wide range of 
toxicological effects that are not necessarily similar and can be 
caused by a variety of mechanisms.''
    The toxicology memorandum also noted that the endocrine system is a 
generic term which encompasses multiple organs and multiple hormonal 
pathways, and disruption of different hormonal pathways may not result 
in common health outcomes (i.e., are not related). The toxicology 
memorandum further stated that the proposed grouping of phthalates 
based on these broad terms was not consistent with the types of 
grouping undertaken by other scientific bodies. As with the denial 
order, the toxicology memorandum discussed the considerations 
underlying the groupings undertaken by these other scientific bodies 
because FAP 6B4815 pointed to the evaluations by these bodies as 
support for the requested action--not because FDA was presenting or 
imposing the three factors that the objectors identify. Thus, Objection 
4 is incorrect in asserting that FDA required the three factors the 
objectors identify.
    Likewise, the objectors mischaracterize FDA's denial order by 
stating that, in assessing whether the subject ortho-phthalates are 
pharmacologically related, we erred in assessing whether the 28 ortho-
phthalates exhibit a common mechanism of action; the objectors state 
that the more appropriate focus is whether there are common health 
effects (Objections at 24). According to Objection 4, ``it would be 
irrational and contrary to the Food Act's safety mandate to ignore the 
cumulative effects of substances in the diet that are known to 
contribute to the same adverse health effect because the mechanism of 
action is not known to be the same for both substances or is not known 
at all'' (id.). In fact, we did evaluate the claim in FAP 6B4815 
regarding common health effects, and our denial order explained why 
this claim was lacking. Specifically, our denial order explained that 
the generalized assertion in FAP 6B4815 that all the cited effects are 
pharmacologically related because they ``result from the effects of 
ortho-phthalates on the endocrine system'' does not acknowledge that 
the endocrine system is a generic term that encompasses multiple organs 
and multiple hormonal pathways (87 FR 31066 at 31070). A substance that 
exhibits activity in one hormonal pathway may not have any effect on a 
different hormonal pathway, and disruption of different hormonal 
pathways may not result in common health outcomes (id.).
    Our denial order also explained that the claim in FAP 6B4815 that 
all studied ortho-phthalates demonstrate similar effects on the 
endocrine system was directly contradicted by data cited in the 
petition (id.). We explained that one of the most commonly studied 
pharmacological effects for phthalates is antiandrogenicity and that 
the data cited in the petitioners' literature search indicates that, 
among the 12 phthalates with available toxicological information, seven 
phthalates exhibit antiandrogenic effects, but four phthalates have 
been shown to not exhibit antiandrogenic effects (id. at 31070 through 
31071). Thus, FDA's evaluation of FAP 6B4815 did, in fact, evaluate 
whether the 28 ortho-phthalates have common health effects. Objection 
4, therefore, errs in suggesting that FDA's evaluation was ``irrational 
and contrary to the Food Act'' by virtue of disregarding evidence that 
the 28 ortho-phthalates cause common health effects.
    Finally, Objection 4 is misplaced in asserting that FDA's denial 
order maintained that FDA ``is only required to consider the cumulative 
effects of substances that would be suitable for grouping into a single 
`category for risk assessment' '' (Objections at 24). FDA's denial 
document made no such statement. The internal quotation appears to 
refer to the following sentence in our denial order: ``the common 
functional group rationale should be supported with a discussion of any 
structural variations within that common functional group definition 
and an explanation of why the chemical-structural differences between 
members would not impact the suitability of the category for risk 
assessment'' (87 FR 31066 at 31069) (emphasis added). Contrary to the 
claim in Objection 4, this sentence does not announce any legal 
interpretation regarding when FDA may consider the cumulative effects 
of different food additives. Rather, it addresses one of the rationales 
offered by FAP 6B4815 for grouping the 28 ortho-phthalates: that the 
substances share a common functional group. In the sentence that 
petitioners quote from in Objection 4, we explain the type of 
scientific evidence that is recommended to support an assertion of a 
common functional group, as outlined in the Organization for Economic 
Co-operation and Development (OECD) guidance that the original petition 
cites as support of its assertion that the 28 ortho-phthalates share a 
common functional group (Ref. 9).
    For these reasons, we disagree with the assertion in Objection 4 
that FDA committed legal error that justifies modifying or revoking our 
denial order. We also note that, even if there was a legal error with 
FDA's application of section 409(c)(5)(B) of the FD&C Act, our 
resolution of FAP 6B4815 would have been the same. Our denial order did 
not rest solely on the question of whether the 28 ortho-phthalates 
should be considered a class for purposes of safety evaluation. Our 
denial order also rested on our conclusion that petitioners did not 
adequately support the other key assertions in FAP 6B4815 (i.e., the 
assertion proposing a purported ADI for DEHP, the assertion that the 
purported ADI should be applied to all 28 phthalates, and the assertion 
that the EDI for the asserted class of ortho-phthalates significantly 
exceeds the proposed ADI). Thus, even if FAP 6B4815 had established 
that there was sufficient evidence to support treating the 28 subject 
ortho-phthalates as a class, FDA would have denied the petition because 
it failed to establish the two subsequent assertions supporting the 
petition's request to revoke the authorizations of such substances.

E. Objection 5, 5-A, 5-B, and 5-C

    In Objection 5, the objectors argue that ``FDA acted arbitrarily 
and unlawfully'' by not considering the relatedness of smaller groups 
of ortho-phthalates (Objections at 26). The objection contends that the 
relatedness of different groups of ortho-phthalates would mean that 
``FDA must consider their cumulative effects'' (id. at 26). The premise 
of this objection is that FDA's denial order erred in analyzing the 
relatedness of all the 28 ortho-phthalates that were the subject of FAP 
6B4815, because on the same day that FDA issued the denial order we 
also issued the abandonment order. In Objection 5, the objectors assert 
that FDA's analysis of the relatedness of the 28 ortho-phthalates was 
``irrational on its face'' (id.). The objectors separate Objection 5 
into three separate sub-objections. In each sub-objection, the 
objectors propose that FDA grant a public hearing to determine that the 
proposed groupings of phthalates show that the phthalates are 
chemically or pharmacologically ``related.'' The

[[Page 86301]]

specific groupings proposed in Objection 5 are:
    (A) A group of nine ortho-phthalates, consisting of the five ortho-
phthalates that remain approved as food additives following FDA's 
abandonment order combined with four ortho-phthalates that are 
authorized for use as food-contact substances because they were 
sanctioned prior to the food additive amendments to the FD&C Act (i.e., 
they are prior sanctioned). A ``prior sanction'' is ``an explicit 
approval granted with respect to use of a substance in food prior to 
September 6, 1958,'' by the FDA or the United States Department of 
Agriculture, pursuant to the FD&C Act, the Poultry Products Inspection 
Act, or the Meat Inspection Act (Sec.  170.3(l)). The term ``prior 
sanction'' derives from section 201(s)(4) of the FD&C Act (21 U.S.C. 
321(s)(4)), which excepts from the definition of a ``food additive'' 
any substance ``used in accordance with a sanction or approval granted 
prior to'' September 6, 1958, the date of enactment of the Food 
Additives Amendment to the FD&C Act. Before that date, FDA had approved 
specific uses of various food-contact materials or food ingredients by 
issuing letters and other statements that stated that in FDA's view 
these substances were ``not considered unsafe,'' that they did ``not 
present a hazard,'' or that FDA ``did not object to their use.''
    The nine ortho-phthalates that are at issue in this sub-objection 
are Di(2-ethylhexyl) phthalate (DEHP), Dicyclohexyl phthalate (DCHP), 
Diisononyl phthalate (DINP), Diisodecyl phthalate (DIDP), Dialyl 
phthalate (DAP), Diethyl phthalate (DEP), Butyl phthalyl butyl 
glycolate (BPBG), Diisooctyl phthalate (DIOP), and Ethyl phthalyl ethyl 
glycolate (EPEG). The objectors assert that these nine ortho-phthalates 
should be grouped because they are ``chemically related'' and grouping 
them due to a common functional group would be consistent with the 
Organization for Economic Co-operation and Development (OECD) Guidance 
on Grouping Chemicals (Objections at 28).
    (B) A group of seven ortho-phthalates, which consist of a subgroup 
of the nine ortho-phthalates that remain either approved in our food 
additive regulations or authorized because they are prior sanctioned. 
These ortho-phthalates are DCHP, DEHP, DINP, DAP, DEP, DIDP, and DIOP. 
The objectors state that these ortho-phthalates are ``pharmacologically 
related substances on account of their common effect on developmental 
toxicity'' (Objections at 31).
    (C) A group of four ortho-phthalates, which consist of a subgroup 
of the nine ortho-phthalates that remain approved in our food additive 
regulations or authorized because they are prior sanctioned. These 
ortho-phthalates are DCHP, DEHP, DINP, and DIOP. The objectors state 
that these ortho-phthalates should be considered cumulatively ``based 
on their structural similarity and common antiandrogenic effects 
associated with the mechanism of action of reduced fetal testosterone 
production'' (Objections at 35).
    FDA Response: Even if the objectors' statements regarding the 
asserted relatedness of these different groups of ortho-phthalates were 
shown to be correct, the outcome of FDA's denial order would not be 
altered. FAP 6B4815 did not seek to establish the relatedness of these 
different groups of ortho-phthalates, consisting of both food additives 
and prior sanctioned substances, for purposes of safety assessment. 
Rather, FAP 6B4815 proposed that FDA take a different approach. 
Specifically, FAP 6B4815 requested that we treat 28 ortho-phthalates 
authorized for food contact use in our food additive regulations as a 
class, apply a single ADI to the purported class, and then compare 
exposure estimates for the 28-member class to the proposed ADI. FAP 
6B4815 did not ask us to consider these proposed groups of nine, seven, 
and four ortho-phthalates. As Objection 5 does not demonstrate how the 
outcome of this proceeding would be different based on the new 
assertions of the new proposed groupings, we deny the request for a 
hearing. A hearing will not be granted unless resolution of a factual 
issue in the way sought by the objector is adequate to justify the 
action requested (Sec.  12.24(b)(4)). As courts have recognized, the 
issues raised in objections ``must be material to the question 
involved; that is, the legality of the order attached'' (Pineapple 
Growers Ass'n of Haw., 673 F.2d at 1085).
    The objectors claim that our denial order was deficient because it 
did not address questions they failed to ask, and to take actions they 
failed to request, in the petition that is the subject of this 
proceeding. Such matters are outside the scope of the process set forth 
in section 409(f)(1) of the FD&C Act, which requires objections to 
``[to specify] . . . the provisions of the [denial] order deemed 
objectionable.'' The type of information necessary to consider for 
grouping chemicals for safety assessment is complex and proposing new 
groupings at the objection phase--when those groupings were not within 
the scope of the denial order--does not allow for full consideration of 
the complex scientific issues involved (see e.g., Ref. 1). Because 
Objection 5 and the corresponding request for a hearing seek 
determinations regarding issues that are outside the scope of the 
provisions of FDA's denial order, the objection and hearing request are 
improper.
    Separately, the objectors claim that FDA's review of FAP 6B4815 
failed to account for our abandonment order (Objections at 26). We 
disagree. On the same day that we issued our denial order, we published 
a detailed memorandum in which we addressed the purported relatedness 
of the five ortho-phthalates that remained approved as food additives 
following FDA's action on the abandonment petition (Ref. 1). FDA 
evaluated whether the five still-approved ortho-phthalates should be 
treated as a class for purposes of safety assessment and concluded that 
the five substances should not be grouped together for safety 
assessment. We based this conclusion on the structural variations and 
the differences in metabolites, metabolism, and toxicological endpoints 
across the substances. We described these differences in the memorandum 
that is in the docket (id.).

F. Objection 6

    In Objection 6, the objectors assert that FDA should have treated a 
group of eight ortho-phthalates as a class because the eight ortho-
phthalates, are ``antiandrogenic and are likely present in the diet'' 
(Objections at 38). The eight ortho-phthalates that Objection 6 
identifies for treatment as a class are Di(2-ethylhexyl) phthalate 
(DEHP), Dicyclohexyl phthalate (DCHP), Diisononyl phthalate (DINP), 
Diisooctyl phthalate (DIOP), Butyl benzyl phthalate (BBP), Dibutyl 
phthalate (DBP), Diisobutyl phthalate (DiBP), and Dihexyl phthalate 
(DnHexP). The eight ortho-phthalates are a subset of the 28 ortho-
phthalates that were the subject of FAP 6B4815. This proposed class 
consists of a subgroup of the ortho-phthalates that remain approved for 
food-contact use under our food additive regulations (DCHP, DEHP, and 
DINP), one that is prior sanctioned (DIOP), and four that are no longer 
authorized for food-contact use due to our abandonment order (DiBP, 
DBP, BBP, and DnHexP). The objection contends that the relatedness of 
these eight ortho-phthalates triggers FDA's obligation to take into 
account their cumulative effect, and the fact that FDA's denial order 
did not identify them as a class means that FDA acted ``contrary to the 
Food Act and its regulations by failing to account for the

[[Page 86302]]

cumulative effects of dietary exposure'' to this proposed group (id.).
    The objectors request a hearing on Objection 6. They state that the 
hearing would address ``whether FDA unlawfully failed to consider the 
cumulative effects of phthalates in the diet that are chemically or 
pharmacologically related to phthalates that remain approved for food-
additive use'' (internal quotations omitted) (Objections at 39 through 
40). The objectors state that at a hearing they would ``offer expert 
testimony regarding the presence of BBP, DBP, DIBP, and DnHP in the 
diet; the chemical and pharmacological relationship among these 
substances and DEHP, DINP, DCHP, and DIOP; and the approach or 
approaches FDA could take to appropriately account for the cumulative 
effects of these substances'' (id. at 40).
    FDA Response: Even if the objectors' asserted statements regarding 
the chemical and pharmacological relatedness of this group of eight 
ortho-phthalates were shown to be correct, the outcome of FDA's denial 
order would not be altered. The underlying proceeding did not address 
the relatedness of this smaller group of ortho-phthalates for purposes 
of safety assessment. FAP 6B4815 proposed that FDA take a different 
course of action. Specifically, as stated earlier, FAP 6B4815 requested 
that we group together 28 ortho-phthalates approved for food contact 
use in our food additive regulations, apply a single ADI to the 
purported class, and then compare exposure estimates for the 28-member 
class to the proposed ADI. FAP 6B4815 did not ask us to consider this 
new proposed group of eight ortho-phthalates.
    As Objection 6 does not demonstrate how the outcome of this 
proceeding would be different if the assertions regarding the new 
proposed grouping in Objection 6 were shown to be correct, we deny the 
request for the hearing. A hearing request will not be granted unless 
resolution of a factual issue in the way sought by the objector is 
adequate to justify the action requested (Sec.  12.24(b)(4)). As courts 
have recognized, the issues raised in objections ``must be material to 
the question involved; that is, the legality of the order attached'' 
(see Pineapple Growers Ass'n of Hawaii, 673 F.2d at 1085). With this 
Objection, petitioners would have us address a question that was not 
involved in the underlying proceeding. As noted earlier, the objectors 
claim that our denial order was deficient because it did not address 
questions they failed to ask, and to take actions they failed to 
request, in the petition that is the subject of this proceeding. 
However, such matters are outside the scope of the process set forth in 
section 409(f)(1) of the FD&C Act, which requires objections to ``[to 
specify] . . . the provisions of the [denial] order deemed 
objectionable.'' Because Objection 6 and the corresponding request for 
a hearing seek determinations regarding issues that are outside the 
scope of the provisions of FDA's denial order, the objection and 
hearing request are improper.
    Additionally, FDA did consider the relatedness of the 28 ortho-
phthalates that were the subject of FAP 6B4815 as well as the five 
ortho-phthalates that remain approved for food-contact use in our food 
additive regulations and did not find that the substances should be 
grouped as a class for purposes of safety assessment (87 FR 31066 at 
31075 and Ref. 1).

G. Objection 7

    In Objection 7, the objectors argue that ``FDA erred insofar as it 
required the petitioners to prove that current dietary exposure to the 
approved phthalates exceeds a safe level'' (Objections at 40). The 
objectors assert that FDA's evaluation of the information in FAP 6B4815 
related to exposure ``is contrary to the applicable statutory and 
regulatory provisions, the proper burden of proof, and FDA's past 
practice'' (Objections at 42). Because this objection raises a purely 
legal dispute, no hearing is warranted to adjudicate it (Sec.  
12.24(b)(1)). Even if a hearing were available, the objectors did not 
request one with respect to this objection and therefore waive any 
right to a hearing (Sec.  12.22(a)(4)). The only remaining issue on 
Objection 7, then, is whether this objection establishes that FDA's 
order denying FAP 6B4815 should be modified or revoked. As described 
below, we conclude that the objectors have not established a basis for 
modifying or revoking the denial order.
    In Objection 7, the objectors assert that, while FDA is to consider 
exposure data when approving new food additives, ``FDA's regulation 
governing petitions to amend or repeal food additive regulations does 
not require the petitioners to tender exposure data'' (Objections at 
40). The objectors contend that, rather than requiring repeal petitions 
to provide exposure data, FDA's regulations provide that repeal 
petitions ``may be based solely on `new data as to the toxicity of the 
chemical' or other `new information' showing `that experience with the 
existing regulation may justify its amendment or repeal' '' (quoting 
Sec.  171.130(b)) (id.). The objectors acknowledge that Sec.  
171.130(b) provides for new data to be furnished in the form specified 
in Sec.  171.1 but argue that ``[t]o the extent that the substantive 
requirements of section 171.1 are applicable to petitions seeking 
revocation or repeal of food additive regulations, that provision also 
does not require exposure data'' (Objections at 41). The objectors 
further state that ``to the extent that FDA interprets [Sec.  171.1] to 
require exposure information, it must apply that requirement in a 
manner that comports with the burden of production the Food Act places 
on petitioners seeking revocation of food additive authorizations based 
on safety concerns,'' such that ``FDA cannot lawfully require such 
petitioners to tender data proving that existing exposure to the 
additives at issue and related substances is unsafe'' (id. at 41). The 
objectors assert that FDA's action on certain long-chain perfluorinated 
compounds (81 FR 5) was consistent with this interpretation (id. at 41 
through 42).
    FDA Response: We disagree with the assertion that we applied an 
incorrect legal standard in evaluating FAP 6B4815. We reviewed the 
exposure information provided in FAP 6B4815 based on the petition's 
specific assertions. FAP 6B4815 asserted that the estimated dietary 
exposure for the asserted class of ortho-phthalates significantly 
exceeded the proposed ADI for the purported class, and the petition 
included dietary exposure estimates for select phthalates. In our 
denial order, we evaluated the proposed dietary exposure values and 
explained why they were not adequately supported. Specifically, we 
observed that FAP 6B4815 did not account for: (1) The imprecision of 
relying on exposures estimates derived from biomonitoring studies to 
assess dietary exposure; (2) the diverse parameters used in the cited 
dietary exposure analyses to determine which analysis, if any, most 
accurately reflects true U.S. dietary exposure; and (3) the 
contradiction in reported dietary exposure values between those 
analyses (87 FR 31066 at 31075; see also Ref. 3). Under our food 
additive regulations, petitioners must do more than request changes to 
FDA's food additive regulations. Petitioners must provide support for 
the requested changes. Food additive petitions seeking amendments to 
existing authorizations ``must include full information on each 
proposed change'' (In re Natural Resources Defense Council, 645 F.3d 
400, 403 (D.C. Cir. 2011) (internal quotations and citations omitted)). 
Here, FAP 6B4815

[[Page 86303]]

included dietary exposure estimates, and our denial order evaluated 
those estimates and explained why they were lacking. In doing so, we 
did not advance any new standards for the type of information that must 
be included in repeal petitions.
    Further, our denial order was not inconsistent with our action on 
long-chain perfluorinated compounds. In that action, we evaluated 
available exposure information and explained why we were not able to 
determine migration of the relevant food contact substances (FCSs) into 
food as a result of their approved food-contact use. For this reason, 
FDA was unable to calculate consumer exposure to the substances in a 
manner which would allow a quantitative assessment of the safety of 
that exposure. However, FDA's review noted that available data 
demonstrate that long-chain perfluorocarboxylic acids and fluorotelomer 
alcohols biopersist in animals and that this biopersistence also occurs 
in humans. Although available migration information did not allow a 
quantitative assessment of the safety of exposure to these FCSs, the 
reproductive and development toxicity of the three food contact 
substances could be qualitatively assessed in the context of 
biopersistence and the expectation that chronic dietary exposure to 
these substances would result in a systemic exposure to the substances 
or their metabolic by-products at levels higher than their daily 
dietary exposure (81 FR 5 at 7). There is not comparable evidence in 
the administrative record for FAP 6B4815 to allow FDA to conclude that 
there is no longer a reasonable certainty of no harm regarding the 
subject ortho-phthalates for their intended use in the absence of 
adequate exposure information. While FDA had a basis for qualitatively 
assessing exposure in the action on long-chained perfluorinated 
compounds, the record here does not support that approach.
    For these reasons, we disagree with the objectors' assertion that 
FDA committed any legal error that justifies modifying or revoking our 
denial order.

H. Objection 8

    The final objection argues that ``contrary to FDA's conclusion, the 
available exposure information raises serious safety questions 
regarding the approved food additive uses of phthalates'' (Objections 
at 43). The objectors request a hearing on Objection 8 and state that 
the hearing would address whether biomonitoring data from the National 
Health and Nutrition Examination Survey (NHANES) ``and other available 
exposure information together establish significant questions 
concerning the safety of the food additive uses of phthalates that 
remain approved'' (Objections at 49). The objectors state that ``FDA 
did not address this issue in the order. Instead, it dismissed the 
NHANES biomonitoring data provided with the Petition based on arguments 
that are legally and factually unsupported, and it did not evaluate the 
most recent NHANES data in conjunction with ATSDR's MRL for DEHP'' (id. 
at 49).
    FDA Response: A hearing will not be granted on factual issues that 
are not determinative with respect to the action requested (Sec.  
12.24(b)(4)). In this objection, the objectors challenge our evaluation 
of the information they provided in FAP 6B4815 related to exposure. 
However, our denial order made clear that our evaluation of exposure 
data was not the sole reason we denied FAP 6B4815. Instead, we based 
our denial on the lack of adequate support for each of the three 
assertions made in FAP 6B4815: (1) that the 28 ortho-phthalates should 
be treated as a class for purposes of evaluating their safety; (2) that 
a purported ADI for DEHP should be applied to all 28 ortho-phthalates 
that were the subject of the petition; and (3) that the EDI for the 
asserted class of ortho-phthalates significantly exceeded the proposed 
ADI, thus rendering the purported class unsafe for their use as food 
contact substances. Our denial order explained in detail why the 
petition did not adequately support any of these three assertions. 
Because we found that the petition was not adequately supported, we 
concluded that the petition did not contain sufficient data to support 
a finding that there is no longer a reasonable certainty of no harm 
from the approved uses (87 FR 31066 at 31075).
    To the extent that Objection 8 is based on the premise that FDA's 
evaluation of the exposure data was determinative to how we evaluated 
FAP 6B4815, that premise is incorrect. Even if FDA were to have found, 
as Objection 8 urges, that the data in the record show that the 
exposure to certain ortho-phthalates significantly exceeds the ADI 
proposed by FAP 6B4815 for the reference ortho-phthalate selected 
(DEHP), such a finding would not have answered the antecedent questions 
of whether the 28 ortho-phthalates should be treated as a class or 
whether the proposed ADI for the selected ortho-phthalate should be 
applied to the purported class of 28 ortho-phthalates. Because FDA's 
conclusion regarding exposure data in the record was not determinative 
with respect to the repeal action requested in FAP 6B4815, the 
objectors' request for a hearing on this subject is denied.
    In addition, we are denying the request for a hearing on this 
objection because the data and information identified by the objectors 
in support of the objection, even if established at a hearing, would 
not be adequate to justify the factual determination about unsafe 
exposure urged by the objectors (see Sec.  12.24(b)(3)). This is for 
two distinct reasons.
    First, Objection 8 claims that ``diet is a major, if not primary, 
source of exposure to the phthalates at issue'' (Objections at 43). The 
objection points to the 2014 report from the Chronic Hazard Advisory 
Panel on Phthalates and Phthalate Alternatives (CHAP report), two 
declarations that cite the CHAP report as support, and a statement in 
ATSDR's 2022 toxicological profile of DEHP that ``the principal route 
of human exposure to DEHP is oral,'' and that the ingestion of food 
accounts for the majority of total oral exposure to DEHP (Objections at 
45) (Ref. 10). The objectors state that FDA's denial order ``does not 
dispute the CHAP's conclusions regarding the primacy of diet as an 
exposure source for multiple approved phthalates and related 
substances'' and that FDA ``must qualitatively consider'' conclusions 
by CHAP or ATSDR that diet is a ``critically important source of 
exposure to DEHP and other phthalates at issue'' (id. at 45). This 
criticism is misplaced. Even if FDA were to reach the general 
conclusion that the diet is a major source of exposure to approved 
ortho-phthalates, that would not answer the question of whether or not 
a specific approved food additive use is safe. Regarding the CHAP 
report, it did not answer the question of whether specific food 
additive uses of ortho-phthalates are safe. To the extent that this 
objection asserts that FDA did not evaluate the CHAP report in 
responding to FAP 6B4815, that is not the case. The denial order and 
FDA's supporting memoranda discussed the CHAP report at length (Refs. 3 
and 4). Regarding ATSDR's report on DEHP, this report states that the 
intake approximations calculated for DEHP indicate that the general 
population is exposed to DEHP at levels that are 3-4 orders of 
magnitude lower than those observed to cause adverse health effects in 
animal studies. Accordingly, the ATSDR report does not justify 
resolution of the factual question about unsafe exposure in the 
objectors' favor.
    The second reason the data and information identified by the 
objectors in support of the objection, even if established at a 
hearing, would not be

[[Page 86304]]

adequate to justify resolution of the factual question about unsafe 
exposure relates to FDA's evaluation of biomonitoring studies. 
Objection 8 asserts that ``FDA irrationally dismissed the relevance of 
biomonitoring data from the CDC's NHANES, which tracks metabolites of 
DEHP, DCHP, DEP, and DINP, among other phthalates, in human urine'' 
(Objections at 45). The objectors assert that FDA's denial order was 
mistaken in stating that petitioners relied on biomonitoring data 
``alone'' as information presented in the petition established the 
primacy of diet as a source of exposure to multiple phthalates 
(Objections at 46). The objectors state that ``the NHANES biomonitoring 
data must be evaluated in light of evidence that most human exposures 
to these phthalates come from the diet'' (id.). Here, the objectors 
make several claims that are not supported. We did not, in fact, 
dismiss the potential relevance of biomonitoring evidence presented in 
the petition. Rather, our denial order specifically noted that human 
biomonitoring studies can be ``part of an appropriate postmarket 
approach to determine dietary exposure for a substance that is already 
authorized for use as a food contact substance'' (87 FR 31066 at 
31074). However, we also explained that ``many factors should be 
addressed to determine the suitability of any given dataset for 
determining dietary exposure'' (id.). We explained that the approach of 
directly comparing biomonitoring-based exposure values to a proposed 
ADI for the purpose of assessing the safety of a food additive is not 
scientifically appropriate (id.). Relying on biomonitoring data alone 
does not differentiate the amount of exposure that results from the 
diet compared to environmental and other sources (id.). Because FAP 
6B4815 did not account for these limitations by addressing how the 
biomonitoring data accounts for dietary exposure, we concluded that the 
petition's direct comparison of biomonitoring-based exposure values to 
the purported ADI was scientifically flawed. Our evaluation did not 
amount to a summary dismissal. We considered the information provided 
in the petition and found it lacking. The objectors' claim that we 
stated that FAP 6B4815 relied on biomonitoring data ``alone'' is also 
wrong. In our denial order, we discussed other evidence in FAP 6B4815 
that was related to exposure (and identified shortcomings with the 
petition's evaluation of that data) (id.). Thus, the record shows that 
we considered all relevant exposure-related data included in the 
petition.
    The objectors' claims regarding the primacy of the diet and FDA's 
dismissal of biomonitoring data, even if established at a hearing, 
would not be sufficient to justify resolution of the factual conclusion 
urged by the objectors (Sec.  12.24(b)(3)). These claims were intended 
to support a conclusion that the available exposure information raises 
serious safety questions regarding the approved food-additive uses of 
phthalates. The information presented to support these claims do not 
provide a factual basis for determining that any ortho-phthalates have 
unsafe dietary exposure levels or that there are significant safety 
questions regarding the dietary exposure levels because these claims do 
not proffer evidence of unsafe dietary exposure levels for any ortho-
phthalates with authorized uses. These arguments do not provide a basis 
for a hearing.
    A separate argument that objectors put forth in Objection 8 
purports to provide more direct data regarding exposure. The objectors 
described a new exposure analysis and provided a supporting memorandum 
(Objections at 48, n. 174) that calculated EDIs for 10 phthalates 
(DEHP, BBP, DBP, DIBP, DCHP, DEP, DIDP, DINP, DMP, and DnOP) using 
urinary metabolite concentrations from the most recent NHANES 
biomonitoring data (collection occurred from 2015 to 2016). The 
objectors state that the EDI estimate for DEHP (at the 90th and 95th 
percentiles) is above the 0.10 micrograms per kilogram body weight per 
day intermediate minimal risk level (MRL) for oral exposure established 
for DEHP by ATSDR in 2022 (id. at 48). The objectors state that this 
``indicate[s] unsafe exposure levels across the U.S. population'' 
(id.). As explained in our denial order and above, relying on 
biomonitoring data alone to calculate an exposure estimate does not 
differentiate the amount of exposure that results from the diet 
compared to other sources. Neither the objectors nor the supporting 
memorandum accounts for these limitations by addressing how the 
biomonitoring data is representative of an estimate to dietary exposure 
only. Furthermore, the MRL for DEHP cited by the objectors was 
determined based on a single study that used only one dose level and 
only a limited number of animals. Due to the use of a single dose and 
limited animals, there is not enough supporting information to rely on 
this value for the purposes of a safety assessment for DEHP or to apply 
it as a value for risk assessments of the other substances cited by the 
objectors.
    The objectors also assert that certain studies involving mixtures 
of ortho-phthalates ``underscore the need for FDA to consider the 
available exposure information in response to these objections, and the 
importance of cumulative effects analysis to that assessment'' 
(Objections at 49). The objectors state that ``EPA scientists [who] 
have documented the magnitude of the cumulative effect of mixtures of 
anti-androgenic ortho-phthalates, and mixtures of anti-androgenic 
ortho-phthalates and other substances with similar anti-androgenic 
effects. Collectively, these studies found that ortho-phthalates in 
mixtures with structurally and pharmacologically related substances 
induced anti-androgenic effects at doses that were orders of magnitude 
lower than those associated with anti-androgenic effects of individual 
phthalates'' (id. at 48). However, the objectors do not provide any 
dietary exposures to the proposed related anti-androgenic substances in 
the diet, nor do they identify what those related anti-androgenic 
substances are. While the Howdeshell (2017) (Ref. 11) and Conley et 
al., (2018 and 2021) (Refs. 8 and 12) studies demonstrate some additive 
effects of mixtures of anti-androgenic substances, the Conley et al., 
(2018 and 2021) studies also report a level of exposure of these 
phthalate and non-phthalate mixtures where no antiandrogenic effects 
were detected. Likewise, beyond the MRL for DEHP, the objectors do not 
provide a suitable safe level or a risk assessment value to compare 
that cumulative dietary exposure level for the purposes of conducting a 
safety assessment. The objectors do not demonstrate how determining 
that anti-androgenic effects from multiple substances may be additive 
would demonstrate Objection 8's assertion that the available exposure 
information raises serious safety questions regarding the approved 
food-additive uses of phthalates.
    Separately, the objectors contend that FDA committed legal error in 
evaluating the exposure information included in FAP 6B4815. The 
objectors assert that FDA evaluated their petition ``as if diet were 
the sole source of exposure to the approved phthalates,'' which 
Objection 8 describes as being in tension with the ``among other 
relevant factors'' text in section 409(c)(5) of the FD&C Act 
(Objections at 46). The applicability of the ``among other relevant 
factors'' text in section 409(c)(5) of the FD&C Act is a legal issue, 
and a hearing will not be granted on issues of law (Sec.  12.24(b)(1)). 
We note that, in determining whether a food additive is safe under 
section

[[Page 86305]]

409(c)(5) of the FD&C Act, FDA is to ``consider among other relevant 
factors'' the following: (1) probable consumption of the additive; (2) 
cumulative effect of such additive ``in the diet of man or animals, 
taking into account any chemically or pharmacologically related 
substance or substances in such diet;'' and (3) safety factors 
``generally recognized'' by qualified experts ``as appropriate for the 
use of animal experimentation data.''
    Section 409(c)(5) of the FD&C Act does not impose a ``legal 
obligation'' for FDA to consider exposure from non-dietary sources in 
determining safety. Rather, section 409(c)(5) of the FD&C Act makes 
clear that FDA has discretion to review a number of factors to 
determine whether a food additive is safe. Besides the factors 
enumerated in subparagraphs (A), (B), and (C), section 409(c)(5) of the 
FD&C Act gives us discretion to decide, in our scientific expertise, 
whether there are other factors that are ``relevant'' to the safety of 
a food additive in the context of a particular petition. Moreover, the 
text of subparagraphs (A) and (B), which contemplate FDA considering 
food-related uses in assessing safety, provides additional support that 
it is not required for FDA to consider exposure from non-dietary 
sources as a relevant factor. Specifically, subparagraph (A) states 
that in determining safety, the Secretary shall consider ``the probable 
consumption of the additive and of any substance formed in or on food 
because of the use of the additive,'' and subparagraph (B) refers to 
the diet of man or animals'' (emphasis added). Subparagraph 
409(c)(5)(C) of the FD&C Act, which directs FDA to consider safety 
factors that ``are generally recognized as appropriate for the use of 
animal experimentation data,'' does not suggest that FDA must consider 
exposure from non-dietary sources. Therefore, the objectors' argument 
that non-dietary exposure must be part of the safety analysis under 
section 409(c)(5) of the FD&C Act is incorrect. While the objectors 
state that other federal agencies ``frequently consider background 
exposures when evaluating and regulating harmful chemicals,'' we 
administer the FD&C Act and not authorities that are applicable to 
other Federal agencies.

V. Summary and Conclusions

    After evaluating the objections, we conclude that the submission 
does not provide a basis to support modifying or revoking the denial of 
FAP 6B4815. Therefore, we are overruling the objections and denying the 
requests for a public hearing.

VI. References

    The following references marked with an asterisk (*) are on display 
at the Dockets Management Staff, (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-
402-7500 and are available for viewing by interested persons between 9 
a.m. and 4 p.m., Monday through Friday; they also are available 
electronically at https://www.regulations.gov. References without 
asterisks are not on public display at https://www.regulations.gov 
because they have copyright restriction. Some may be available at the 
website address, if listed. References without asterisks are available 
for viewing only at the Dockets Management Staff. Although FDA verified 
the website addresses in this document, please note that websites are 
subject to change over time.

1. * FDA Memorandum from J. Urbelis to Administrative File for Food 
Additive Petition (FAP) 6B4815, May 11, 2022.
2. * FDA, Guidance for Industry, ``Toxicological Principles for the 
Safety Assessment of Food Ingredients: Redbook 2000,'' July 2007 
(available at https://www.fda.gov/media/79074/download).
3. * FDA Chemistry Memorandum from R. Brinas to J. Urbelis, May 11, 
2022.
4. * FDA Toxicology Memorandum from T-F. Cheng to J. Urbelis, May 
11, 2022.
5. * Agency for Toxic Substances and Disease Registry (ATSDR) 
``Toxicological Profile for Di(2-ethylhexyl) Phthalate (DEHP),'' 
January 2022.
6. * ``NTP Technical Report on the Toxicology and Carcinogenesis 
Studies of Di(2-ethylhexyl) Phthalate Administered in Feed to 
Sprague Dawley Rats,'' December 2021.
7. European Food Safety Authority Panel on Food Contact Materials, 
Enzymes and Processing Aids, ``Update of the Risk Assessment of Di-
Butylphthalate (DBP), Butyl-Benzyl-Phthalate (BBP), Bis(2-
ethylhexyl)Phthalate (DEHP), Di-Isononylphthalate (DINP) and Di-
Isodecylphthalate (DIDP) for Use in Food Contact Materials,'' 
European Food Safety Authority Journal, 17(12):5838, 2019.
8. Conley, J., C.S. Lambright, N. Evans, et. al., ``A Mixture of 15 
Phthalates and Pesticides Below Individual Chemical No Observed 
Adverse Effects Levels (NOAELs) Produces Reproductive Tract 
Malformations in the Male Rat,'' Environment International, 
156:106615, 2021.
9. ** 2014 Organization for Economic Cooperation and Development 
(OECD) Guidance on Grouping of Chemicals.
10. ** 2014 Chronic Hazard Advisory Panel (CHAP) on Phthalates and 
Phthalate Alternatives Final Report.
11. Howdeshell, K., A.K. Hotchkiss, L.E. Gray Jr., et al., 
``Cumulative Effects of Antiandrogenic Chemical Mixtures and Their 
Relevance to Human Health Risk Assessment,'' International Journal 
of Hygiene and Environmental Health 220 (2Pt A):179, 2017.
12. Conley, J., C.S. Lambright, N. Evans, et. al., ``Mixed 
Antiandrogenic Chemicals at Low Individual Doses Produce 
Reproductive Tract Malformations in the Male Rat,'' Toxicological 
Sciences 164(1):166, 2018.

    Dated: October 22, 2024.
Kimberlee Trzeciak,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2024-25120 Filed 10-29-24; 8:45 am]
BILLING CODE 4164-01-P