Nicotinamide; Exemption From the Requirement of a Tolerance, 52775-52778 [2019-20528]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[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 https://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 https://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 
https://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: https://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 https://www.epa.gov/dockets/contacts.html. Additional 
instructions on commenting or visiting the docket, along with more 
information about dockets generally, is available at https://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, https://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 https://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 https://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.


0
 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
----------------------------------------------------------------------------------------------------------------
 
                                                  * * * * * * *
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]
 BILLING CODE 6560-50-P