[Federal Register Volume 84, Number 192 (Thursday, October 3, 2019)]
[Rules and Regulations]
[Pages 52775-52778]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-20528]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2017; FRL-9994-70]
Nicotinamide; Exemption From the Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of nicotinamide (CAS Reg. No. 98-92-0) when
used as an inert ingredient (corrosion inhibitor) on growing crops only
and limited to 5.0% in a pesticide formulation. Dow AgroSciences LLC
submitted a petition to EPA under the Federal Food, Drug, and Cosmetic
Act (FFDCA), requesting an amendment to an existing requirement of a
tolerance. This regulation eliminates the need to establish a maximum
permissible level for residues of nicotinamide.
DATES: This regulation is effective October 3, 2019. Objections and
requests for hearings must be received on or before December 2, 2019
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: The docket for this action, identified by docket
identification (ID) number EPA-HQ-OPP-2017-0046, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory
Public Docket (OPP Docket) in the Environmental Protection Agency
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334,
1301 Constitution Ave. NW, Washington, DC 20460-0001. The Public
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through
Friday, excluding legal holidays. The telephone number for the Public
Reading Room is (202) 566-1744, and the telephone number for the OPP
Docket is (703) 305-5805. Please review the visitor instructions and
additional information about the docket available at http://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT: Michael L. Goodis, Registration
Division (7505P), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave. NW, Washington, DC 20460-
0001; main telephone number: (703) 305-7090; email address:
[email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this action apply to me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
The following list of North American Industrial Classification System
(NAICS) codes is not intended to be exhaustive, but rather provides a
guide to help readers determine whether this document applies to them.
Potentially affected entities may include:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
B. How can I get electronic access to other related information?
You may access a frequently updated electronic version of 40 CFR
part 180 through the Government Publishing Office's e-CFR site at
http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
C. How can I file an objection or hearing request?
Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an
objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2017-0046 in the subject line on the first
page of your submission. All objections and requests for a hearing must
be in writing and must be received by the Hearing Clerk on or before
December 2, 2019. Addresses for mail and hand delivery of objections
and hearing requests are provided in 40 CFR 178.25(b).
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing (excluding any Confidential Business Information (CBI)) for
inclusion in the public docket. Information not marked confidential
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without
prior notice. Submit the non-CBI copy of your objection or hearing
request, identified by docket ID number EPA-HQ-OPP-2017-0046, by one of
the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider to be CBI or other
information whose disclosure is restricted by statute.
Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW, Washington, DC
20460-0001.
Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at http://www.epa.gov/dockets/contacts.html. Additional
instructions on commenting or visiting the docket, along with more
information about dockets generally, is available at http://www.epa.gov/dockets.
II. Petition for Exemption
In the Federal Register of June 8, 2017 (82 FR 26641) (FRL-9961-
14), EPA issued a document pursuant to FFDCA section 408, 21 U.S.C.
346a, announcing the filing of a pesticide petition (IN-11012) by Dow
AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 46268. The
petition requested that 40 CFR 180.920 be amended by establishing an
exemption from the requirement of a tolerance for residues of
nicotinamide (CAS Reg. No. 98-92-0) when used as an inert ingredient
(corrosion inhibitor) in pesticide formulations applied to growing
crops, limited to 5% in the pesticide formulation. That document
referenced a summary of the petition prepared by Dow AgroSciences LLC,
the petitioner, which is available in the docket, http://www.regulations.gov. Comments were received on the notice of filing.
EPA's response to these comments is discussed in Unit V.B.
III. Inert Ingredient Definition
Inert ingredients are all ingredients that are not active
ingredients as defined in 40 CFR 153.125 and include, but are not
limited to, the following types of ingredients (except when they have a
pesticidal efficacy of their own): Solvents such as alcohols and
hydrocarbons; surfactants such as polyoxyethylene polymers and fatty
acids; carriers such as clay; thickeners such as carrageenan and
modified cellulose; wetting, spreading, and dispersing agents;
propellants in aerosol dispensers; microencapsulating agents; and
emulsifiers. The term ``inert'' is not intended to imply nontoxicity;
the ingredient may or may not be chemically active. Generally, EPA has
exempted inert ingredients from the requirement of a tolerance based on
the low toxicity of the individual inert ingredients.
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IV. Aggregate Risk Assessment and Determination of Safety
Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an
exemption from the requirement for a tolerance (the legal limit for a
pesticide chemical residue in or on a food) only if EPA determines that
the tolerance is ``safe.'' Section 408(c)(2)(A)(ii) of FFDCA defines
``safe'' to mean that ``there is a reasonable certainty that no harm
will result from aggregate exposure to the pesticide chemical residue,
including all anticipated dietary exposures and all other exposures for
which there is reliable information.'' This includes exposure through
drinking water and in residential settings, but does not include
occupational exposure. Section 408(c)(2)(B) requires EPA to take into
account the considerations set forth in subparagraphs (C) and (D) of
subsection (b)(2) when making this exemption safety determination.
Section 408(b)(2)(C) of FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical residue. . .
.''
EPA establishes exemptions from the requirement of a tolerance only
in those cases where it can be clearly demonstrated that the risks from
aggregate exposure to pesticide chemical residues under reasonably
foreseeable circumstances will pose no appreciable risks to human
health. In order to determine the risks from aggregate exposure to
pesticide inert ingredients, the Agency considers the toxicity of the
inert in conjunction with possible exposure to residues of the inert
ingredient through food, drinking water, and through other exposures
that occur as a result of pesticide use in residential settings. If EPA
is able to determine that a finite tolerance is not necessary to ensure
that there is a reasonable certainty that no harm will result from
aggregate exposure to the inert ingredient, an exemption from the
requirement of a tolerance may be established.
Consistent with FFDCA section 408(c)(2)(A), and the factors
specified in FFDCA section 408(c)(2)(B), EPA has reviewed the available
scientific data and other relevant information in support of this
action. EPA has sufficient data to assess the hazards of and to make a
determination on aggregate exposure for nicotinamide including exposure
resulting from the exemption established by this action. EPA's
assessment of exposures and risks associated with nicotinamide follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered their
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. Specific information on the studies received and the nature
of the adverse effects caused by nicotinamide as well as the no-
observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-
effect-level (LOAEL) from the toxicity studies are discussed in this
unit.
Nicotinamide is a water-soluble B-complex vitamin which is present
naturally in animal products, whole cereals and legumes. Together with
nicotinic acid (niacin), nicotinamide belongs to vitamin B3 and is
required as a nutrient to prevent niacin deficiency disorders such as
pellagra. It functions as a coenzyme or co-substrate in many biological
reduction and oxidation reactions required for energy metabolism in
mammalian systems. It is used as a nutritional supplement, therapeutic
agent, skin and hair conditioning agent in cosmetics and a constituent
of consumer, household solvent and cleaning products.
As a nutritional supplement and vitamin, recommended daily dietary
allowances and maximum daily doses have been established by the
Institute of Medicine (US) Standing Committee on the Scientific
Evaluation of Dietary Reference Intakes and its Panel on Folate, Other
B Vitamins, and Choline. The committee also established the tolerance
upper intake level at 35 mg/day based on flushing as a critical adverse
effect. The level applies to all forms of niacin added to foods or
taken as supplements, including nicotinamide. Although nicotinamide is
not associated with flushing effects, a UL for nicotinic acid based on
flushing is protective against the other effects seen in the available
toxicity studies.
Nicotinamide exhibits low levels of acute toxicity. The rat acute
oral lethal dose (LD50) is 3,000-7,000 milligrams/kilogram
(mg/kg). The acute dermal LD50 for rabbits is > 2,000 mg/kg.
Nicotinamide is negative for skin sensitization in the guinea pig. It
is not irritating to rabbit skin. Nicotinamide is considered irritating
to rabbit eyes.
In a 4-week oral toxicity via gavage, no adverse effects were
observed in female rats at dose levels below treated with 1,000 mg/kg/
day of nicotinamide.
In a developmental toxicity study involving exposure to nicotinic
acid, no effects in the dams (decreased body weight gains and
significantly decreased placental weights) and fetuses (significantly
lower body weights in male offspring) were observed at dose levels
below 1,000 mg/kg/day. The NOAEL for maternal and developmental
toxicity is 200 mg/kg/day (198 mg/kg/day for nicotinamide). This study
is deemed relevant to the assessment of nicotinamide since nicotinamide
converts to nicotinic acid in the gut.
Nicotinamide was negative in Ames tests, micronucleus tests, with
and without metabolic activation. No chromosomal effects were reported
in mammalian cells. Positive results were seen in a sister chromatid
exchange induction study. However, it was noted that activity was only
seen at excessively high concentrations. Based on the weight of
evidence, nicotinamide is considered negative for mutagenicity.
Nicotinamide is not carcinogenic. No increased incidence of tumors
was observed in a lifetime carcinogenicity study with Swiss mice
receiving 1.0% (equivalent to 66.3 and 100 mg/kg/day in female and male
rats, respectively) nicotinamide in the diet.
There were no data directly regarding the potential for
neurotoxicity or immunotoxicity of nicotinamide. However, there is no
evidence of potential neurotoxicity or immunotoxicity in the available
data.
Metabolism of nicotinamide in humans is well understood.
Nicotinamide is necessary for lipid metabolism, tissue respiration and
glycogenolysis. It is readily absorbed in the gastrointestinal (g.i.)
tract. In vivo, nicotinamide is formed from the conversion of nicotinic
acid (niacin), while some dietary nicotinamide is oxidized to nicotinic
acid and then to nicotinamide. Nicotinamide is incorporated into two
coenzymes: Nicotinamide adenine dinucleotide (NAD) and nicotinamide
adenine dinucleotide phosphate (NADP) which act as hydrogen-carrier
molecules in glycogenolysis, tissue respiration and lipid metabolism.
It can be incorporated into NADP either directly or after deamidation,
or metabolized in the liver and excreted in the urine. The primary
metabolites are N-methylniacinamide and N-methyl-2-pyridone-5-
carboxamide, though it may also be excreted unchanged.
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B. Toxicological Points of Departure/Levels of Concern
Once a pesticide's toxicological profile is determined, EPA
identifies toxicological points of departure (POD) and levels of
concern to use in evaluating the risk posed by human exposure to the
pesticide. For hazards that have a threshold below which there is no
appreciable risk, the toxicological POD is used as the basis for
derivation of reference values for risk assessment. PODs are developed
based on a careful analysis of the doses in each toxicological study to
determine the dose at which the NOAEL and the LOAEL are identified.
Uncertainty/safety factors are used in conjunction with the POD to
calculate a safe exposure level--generally referred to as a population-
adjusted dose (PAD) or a reference dose (RfD)--and a safe margin of
exposure (MOE). For non-threshold risks, the Agency assumes that any
amount of exposure will lead to some degree of risk. Thus, the Agency
estimates risk in terms of the probability of an occurrence of the
adverse effect expected in a lifetime. For more information on the
general principles EPA uses in risk characterization and a complete
description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
The available toxicity studies indicate that nicotinamide has a
very low overall toxicity. No effects are observed below 1,000 mg/kg/
day, the limit dose. Since signs of toxicity were not observed below
the limit dose an endpoint of concern for risk assessment purposes was
not identified.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to nicotinamide, EPA considered exposure expected under the
proposed exemption from the requirement of a tolerance as well as from
the existing approved uses. EPA assessed dietary exposures from
nicotinamide in food as follows:
Nicotinamide is already approved for use (synergist) on growing
crops. The current request (for use as a corrosion inhibitor) increases
dietary exposure (food and drinking water) to nicotinamide that can
occur following ingestion of foods with residues from treated crops. In
addition, dietary exposure to nicotinamide may also occur through foods
that contain it naturally, such as grains, meat and milk; fortified
foods, and dietary supplements. However, a quantitative dietary
exposure assessment was not conducted since a toxicological endpoint
for risk assessment was not identified.
2. Dietary exposure from drinking water. Since a hazard endpoint of
concern was not identified for the acute and chronic dietary
assessment, a quantitative dietary exposure risk assessment for
drinking water was not conducted, although exposures may be expected
from use on food crops.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., textiles (clothing and diapers), carpets, swimming
pools, and hard surface disinfection on walls, floors, tables).
Nicotinamide may be used as an inert ingredient in pesticide
products that are registered for specific uses that may result in
residential exposure, such as pesticides used in and around the home,
and in non-pesticide products such as household products, personal care
products and cosmetics. However, based on the lack of a hazard endpoint
of concern, a quantitative residential exposure assessment for
nicotinamide was not conducted.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
EPA has not found nicotinamide to share a common mechanism of
toxicity with any other substances, and nicotinamide does not appear to
produce a toxic metabolite produced by other substances. For the
purposes of this tolerance action, therefore, EPA has assumed that
nicotinamide does not have a common mechanism of toxicity with other
substances. For information regarding EPA's efforts to determine which
chemicals have a common mechanism of toxicity and to evaluate the
cumulative effects of such chemicals, see EPA's website at http://www.epa.gov/pesticides/cumulative.
D. Safety Factor for Infants and Children
Based on the lack of threshold effects, EPA has not identified any
toxicological endpoints of concern and is conducting a qualitative
assessment of nicotinamide. The qualitative assessment does not use
safety factors for assessing risk, and no additional safety factor is
needed for assessing risk to infants and children. Based on an
assessment of nicotinamide, EPA has concluded that there are no
toxicological endpoints of concern for the U.S. population, including
infants and children.
E. Aggregate Risks and Determination of Safety
Because no toxicological endpoints of concern were identified, EPA
concludes that aggregate exposure to residues of nicotinamide will not
pose a risk to the U.S. population, including infants and children, and
that there is a reasonable certainty that no harm will result to the
general population, or to infants and children from aggregate exposure
to nicotinamide residues.
V. Other Considerations
A. Analytical Enforcement Methodology
An analytical method is not required for enforcement purposes since
the Agency is establishing an exemption from the requirement of a
tolerance without any numerical limitation.
B. Response to Comments
Two comments were received concerning the safety and impact of
pesticides on food and human health. Although the Agency recognizes
that some individuals believe that no residue of pesticides should be
allowed in or on food, the existing legal framework provided by section
408 of the FFDCA authorizes the establishment of pesticide tolerances
or exemptions where the Agency determines that tolerance or exemption
meets the safety standard imposed by the statute. EPA has sufficient
data to support a safety determination for the exemption from the
requirement of a tolerance for nicotinamide. The commenters have
provided no additional information supporting a determination that the
exemption is not safe.
VI. Conclusions
Therefore, an exemption from the requirement of a tolerance is
established under 40 CFR 180.920 for nicotinamide (CAS Reg. No. 98-92-
0) when used as an inert ingredient (corrosion inhibitor) in pesticide
formulations applied to growing crops, limited to 5.0% in a pesticide
formulation.
VII. Statutory and Executive Order Reviews
This action establishes a tolerance exemption under FFDCA section
408(d) in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled
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``Regulatory Planning and Review'' (58 FR 51735, October 4, 1993).
Because this action has been exempted from review under Executive Order
12866, this action is not subject to Executive Order 13211, entitled
``Actions Concerning Regulations That Significantly Affect Energy
Supply, Distribution, or Use'' (66 FR 28355, May 22, 2001); Executive
Order 13045, entitled ``Protection of Children from Environmental
Health Risks and Safety Risks'' (62 FR 19885, April 23, 1997); or
Executive Order 13771, entitled ``Reducing Regulations and Controlling
Regulatory Costs'' (82 FR 9339, February 3, 2017). This action does not
contain any information collections subject to OMB approval under the
Paperwork Reduction Act (PRA) (44 U.S.C. 3501 et seq.), nor does it
require any special considerations under Executive Order 12898,
entitled ``Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations'' (59 FR 7629, February 16,
1994).
Since tolerances and exemptions that are established on the basis
of a petition under FFDCA section 408(d), such as the exemption in this
final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.), do not apply.
This action directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4). As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled ``Federalism'' (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
``Consultation and Coordination with Indian Tribal Governments'' (65 FR
67249, November 9, 2000) do not apply to this action. In addition, this
action does not impose any enforceable duty or contain any unfunded
mandate as described under Title II of the Unfunded Mandates Reform Act
(UMRA) (2 U.S.C. 1501 et seq.).
This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act (NTTAA) (15 U.S.C. 272 note).
VIII. Congressional Review Act
Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.),
EPA will submit a report containing this rule and other required
information to the U.S. Senate, the U.S. House of Representatives, and
the Comptroller General of the United States prior to publication of
the rule in the Federal Register. This action is not a ``major rule''
as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: September 11, 2019.
Michael Goodis,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
0
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
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2. In Sec. 180.920, revise the inert ingredient ``Nicotinamide (CAS
Reg. No. 98-92-0)'' in the table to read as follows:
Sec. 180.920 Inert ingredients used pre-harvest; exemptions from the
requirement of a tolerance.
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Inert ingredients Limits Uses
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* * * * * * *
Nicotinamide (CAS Reg. No. 98-92-0) Not to exceed 0.5% by weight of pesticide Synergist, Corrosion
formulation as synergist; not to exceed 5% by Inhibitor
weight of pesticide formulation as corrosion
inhibitor.
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[FR Doc. 2019-20528 Filed 10-2-19; 8:45 am]
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