Rule2023-15679
N-(n-Octyl)-2-pyrrolidone in Pesticide Formulations; Tolerance Exemption
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
July 25, 2023
Effective
July 25, 2023
Issuing agencies
Environmental Protection Agency
Abstract
This regulation establishes an exemption from the requirement of a tolerance for residues of N-(n-octyl)-2-pyrrolidone (CAS Reg. No. 2687-94-7) when used as an inert ingredient (solvent) in pesticide formulations containing prothioconazole as an active ingredient at a maximum concentration of 15% by weight. International Specialty Products submitted a petition to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA), requesting the exemption. This regulation eliminates the need to establish a maximum permissible level for residues of N-(n-octyl)-2-pyrrolidone, when used in accordance with the terms of the exemption.
Full Text
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<title>Federal Register, Volume 88 Issue 141 (Tuesday, July 25, 2023)</title>
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[Federal Register Volume 88, Number 141 (Tuesday, July 25, 2023)]
[Rules and Regulations]
[Pages 47773-47778]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-15679]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2021-0172; FRL-11166-01-OCSPP]
N-(n-Octyl)-2-pyrrolidone in Pesticide Formulations; Tolerance
Exemption
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 N-(n-octyl)-2-pyrrolidone (CAS Reg. No.
2687-94-7) when used as an inert ingredient (solvent) in pesticide
formulations containing prothioconazole as an active ingredient at a
maximum concentration of 15% by weight. International Specialty
Products submitted a petition to EPA under the Federal Food, Drug, and
Cosmetic Act (FFDCA), requesting the exemption. This regulation
eliminates the need to establish a maximum permissible level for
residues of N-(n-octyl)-2-pyrrolidone, when used in accordance with the
terms of the exemption.
DATES: This regulation is effective July 25, 2023. Objections and
requests for hearings must be received on or before September 25, 2023
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-2021-0172, is available at <a href="http://www.regulations.gov">http://www.regulations.gov</a> 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 and the OPP docket is (202) 566-1744. Please review the
visitor instructions and additional information about the docket
available at <a href="http://www.epa.gov/dockets">http://www.epa.gov/dockets</a>.
FOR FURTHER INFORMATION CONTACT: Charles Smith, Director, Registration
Division (7505T), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave. NW, Washington, DC 20460-
0001; main telephone number: (202) 566-1030; email address:
<a href="/cdn-cgi/l/email-protection#89dbcdcfdbc7e6fde0eaecfac9ecf9e8a7eee6ff"><span class="__cf_email__" data-cfemail="76243230243819021f1513053613061758111900">[email protected]</span></a>.
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:
<bullet> Crop production (NAICS code 111).
<bullet> Animal production (NAICS code 112).
<bullet> Food manufacturing (NAICS code 311).
<bullet> 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 Federal Register Office's e-CFR site at <a href="https://www.ecfr.gov/current/title-40/chapter-I/subchapter-E/part-180?toc=1">https://www.ecfr.gov/current/title-40/chapter-I/subchapter-E/part-180?toc=1</a>.
C. How can I file an objection or hearing request?
Under FFDCA section 408(g), 21 U.S.C. 346a(g), 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-2021-0172 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
September 25, 2023. 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-2021-0172, by one of
the following methods:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the online instructions for submitting
[[Page 47774]]
comments. Do not submit electronically any information you consider to
be CBI or other information whose disclosure is restricted by statute.
<bullet> Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave., NW, Washington, DC
20460-0001.
<bullet> Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at <a href="https://www.epa.gov/dockets/where-send-comments-epa-dockets#express">https://www.epa.gov/dockets/where-send-comments-epa-dockets#express</a>.
Additional instructions on commenting or visiting the docket, along
with more information about dockets generally, is available at <a href="https://www.epa.gov/dockets">https://www.epa.gov/dockets</a>.
II. Petition for Exemption
In the Federal Register of March 22, 2021 (86 FR 15162, FRL-10021-
44), EPA issued a document pursuant to FFDCA section 408, 21 U.S.C.
346a, announcing the filing of a pesticide petition (PP IN-11526) by
International Specialty Products, an Ashland Inc. Company, 1005 US 202/
206, Bridgewater, NJ 08807. The petition requested that 40 CFR 180.1130
be amended by establishing an exemption from the requirement of a
tolerance for residues of N-(n-octyl)-2-pyrrolidone (CAS Reg. No. 2687-
94-7) when used as an inert ingredient (solvent) in pesticide
formulations containing prothioconazole at a maximum concentration of
15%. That document referenced a summary of the petition prepared by the
petitioner, which is available in the docket, <a href="https://www.regulations.gov">https://www.regulations.gov</a>. There were no comments received in response to the
notice of filing.
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 and diatomaceous earth; 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.
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. When making a safety determination for an
exemption for the requirement of a tolerance FFDCA section 408(c)(2)(B)
directs EPA to take into account the considerations in section
408(b)(2)(C) and (D). 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. . . .'' Section 408(b)(2)(D) lists other factors for EPA's
consideration in making safety determinations, e.g., the validity,
completeness, and reliability of available data, nature of toxic
effects, available information concerning the cumulative effects of the
pesticide chemical and other substances with a common mechanism of
toxicity, and available information concerning aggregate exposure
levels to the pesticide chemical and other related substances, among
other factors.
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 harm 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 N-(n-octyl)-2-pyrrolidone,
including exposure resulting from the exemption established by this
action. EPA's assessment of exposures and risks associated with N-(n-
octyl)-2-pyrrolidone 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 N-(n-octyl)-2-pyrrolidone 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.
N-(n-octyl)-2-pyrrolidone has low acute toxicity via the oral and
dermal routes. N-(n-octyl)-2-pyrrolidone is considered extremely
irritating to the eyes and skin and is a dermal sensitizer. No acute
inhalation study was available in the database for N-(n-octyl)-2-
pyrrolidone alone; however, a product containing N-(n-octyl)-2-
pyrrolidone and prothioconazole showed low concern for acute inhalation
toxicity.
Clinical signs of neurotoxicity (e.g., increased salivation,
hunched posture, abnormal gait, and lethargy) are the most sensitive
and common effects observed throughout the database following repeated
dosing. These effects were observed in a 28-day study in rats, 13-week
study in dogs, and a developmental toxicity study in rats.
No carcinogenicity studies were available in the database for N-(n-
octyl)-2-pyrrolidone. The Agency used a qualitative structure activity
relationship (SAR) database, DEREK11, to determine if there were
structural alerts for potential carcinogenicity for N-(n-octyl)-2-
pyrrolidone. No structural alerts for carcinogenicity were identified
for N-(n-octyl)-2-pyrrolidone. In the
[[Page 47775]]
absence of any structural alerts and lack of mutagenicity in available
mutagenicity and genotoxicity studies, N-(n-octyl)-2-pyrrolidone is not
expected to be carcinogenic. The is no evidence of offspring
susceptibility, reproduction toxicity, or teratogenicity in the
available developmental toxicity study in rats and the 1-generation
reproduction toxicity study in rats.
No immunotoxicity or neurotoxicity studies were available in the
database for N-(n-octyl)-2-pyrrolidone. However, no evidence of
immunotoxicity was observed in the available database, and the selected
endpoints are protective of the neurotoxicity effects observed in the
database.
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 no adverse effects are observed (the NOAEL)
and the lowest dose at which adverse effects of concern are identified
(the LOAEL). 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 <a href="https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/overview-risk-assessment-pesticide-program">https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/overview-risk-assessment-pesticide-program</a>.
A summary of the toxicological endpoints for N-(n-octyl)-2-
pyrrolidone used for human risk assessment is shown in Table 1 of this
unit.
Table 1--Summary of Toxicological Doses and Endpoints for N-(n-Octyl)-2-Pyrrolidone for Use in Human Risk
Assessment
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Point of departure and
Exposure/scenario uncertainty/safety RfD, PAD, LOC for risk Study and toxicological
factors assessment effects
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Acute dietary (General population An acute effect was not found in the database; therefore, an acute dietary
including infants and children). assessment is not necessary.
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Chronic dietary (All populations).. NOAEL= 90 mg/kg/day... Chronic RfD = 90 mg/kg/ [13-week oral Toxicity-dog]
UFA = 10 x............ day. LOAEL = 240 mg/kg/day
UFH = 10 x............ based on neurological
effects.
FQPA SF = 1 x......... cPAD = 0.9 mg/kg/day..
Incidental oral short-term (1 to 30 NOAEL= 90 mg/kg/day... LOC for MOE <100...... [13-week oral Toxicity-dog]
days). UFA = 10 x............ LOAEL = 240 mg/kg/day
UFH = 10 x............ based on neurological
FQPA SF = 1 x......... effects.
Dermal short-term (1 to 30 days) Dermal (or oral) study LOC for MOE........... [13-week oral Toxicity-dog]
and Dermal intermediate-term (1 to NOAEL = 90 mg/kg/day <100.................. LOAEL = 240 mg/kg/day
6 months). (dermal absorption based on neurological
rate = 100%). effects.
UFA = 10 x............
UFH = 10 x............
FQPA SF = 1 x.........
Inhalation short-term (1 to 30 Inhalation (or oral) LOC for MOE........... [13-week oral Toxicity-dog]
days) and intermediate-term (1 to study NOAEL = 90 mg/ <100.................. LOAEL = 240 mg/kg/day
6 months). kg/day (inhalation based on neurological
absorption rate = effects.
100%).
UFA = 10 x............
UFH = 10 x............
FQPA SF = 1 x.........
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Cancer (Oral, dermal, inhalation).. Based on the lack of mutagenicity in N-(n-octyl)-2-pyrrolidone and the
absence of structural alerts in the DEREK analysis for N-(n-octyl)-2-
pyrrolidone, there is low concern for carcinogenicity.
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FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
of concern. mg/kg/day = milligram/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-
level. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. UF = uncertainty factor.
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among
members of the human population (intraspecies).
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to N-(n-octyl)-2-pyrrolidone, EPA considered exposure under
the proposed exemption from the requirement of a tolerance and existing
food uses. Dietary exposure may also occur from non-pesticidal uses but
no reliable information is available for non-pesticidal exposures.
Therefore, EPA assessed dietary exposures from pesticidal uses of N-(n-
octyl)-2-pyrrolidone only. EPA assessed dietary exposures from N-(n-
octyl)-2-pyrrolidone in food as follows:
i. Acute exposure. Quantitative acute dietary exposure and risk
assessments are performed for a food-use pesticide, if a toxicological
study has indicated the possibility of an effect of concern occurring
as a result of a 1-day or single exposure. Such effects were not
identified for N-(n-octyl)-2-pyrrolidone.
[[Page 47776]]
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment using DEEM-FCID, Version 4.02, EPA used food consumption
information from USDA's 2005-2010 NHANES/WWEIA. As to residue levels in
food, no residue data were submitted for N-(n-octyl)-2-pyrrolidone. In
the absence of specific residue data, EPA has developed an approach
which uses surrogate information to derive upper bound exposure
estimates for the subject inert ingredient. Upper bound exposure
estimates are based on the highest tolerance for a given commodity from
a list of high use insecticides, herbicides, and fungicides. A complete
description of the general approach taken to assess inert ingredient
risks in the absence of residue data is contained in the memorandum
entitled ``Update to D361707: Dietary Exposure and Risk Assessments for
the Inerts.'' (12/21/2021), which can be found at <a href="http://www.regulations.gov">http://www.regulations.gov</a> in docket ID number EPA-HQ-OPP-2018-0090.
In the dietary exposure assessment, the Agency assumed that the
residue level of the inert ingredient would be no higher than the
highest tolerance for a given commodity. Implicit in this assumption is
that there would be similar rates of degradation (if any) between the
active and inert ingredient and that the concentration of inert
ingredient in the scenarios leading to these highest levels of
tolerances would be no higher than the concentration of the active
ingredient. While the current request is for use of N-(n-octyl)-2-
pyrrolidone with the active ingredient prothioconazole at a limit of
15% in pesticide formulations, there are already existing food uses
with other active ingredients up to 20% in pesticide formulations. In
order to cover all possible exposure, the dietary exposure assessment
utilized the 20% limitation in pesticide formulations except for all
commodities except cotton, for which the assessment utilized a default
50% concentration.
The Agency believes the assumptions used to estimate dietary
exposures lead to an extremely conservative assessment of dietary risk
due to a series of compounded conservatisms. First, assuming that the
level of residue for an inert ingredient is equal to the level of
residue for the active ingredient will overstate exposure. The
concentrations of active ingredient in agricultural products are
generally at least 50 percent of the product and often can be much
higher. Further, pesticide products rarely have a single inert
ingredient; rather there is generally a combination of different inert
ingredients used which additionally reduces the concentration of any
single inert ingredient in the pesticide product in relation to that of
the active ingredient.
Second, the conservatism of this methodology is compounded by EPA's
decision to assume that, for each commodity, the active ingredient
which will serve as a guide to the potential level of inert ingredient
residues is the active ingredient with the highest tolerance level.
This assumption overstates residue values because it would be highly
unlikely, given the high number of inert ingredients, that a single
inert ingredient or class of ingredients would be present at the level
of the active ingredient in the highest tolerance for every commodity.
Finally, a third compounding conservatism is EPA's assumption that
all foods contain the inert ingredient at the highest tolerance level.
In other words, EPA assumed 100 percent of all foods are treated with
the inert ingredient at the rate and manner necessary to produce the
highest residue legally possible for an active ingredient. In summary,
EPA chose a very conservative method for estimating what level of inert
residue could be on food, then used this methodology to choose the
highest possible residue that could be found on food and assumed that
all food contained this residue. No consideration was given to
potential degradation between harvest and consumption even though
monitoring data shows that tolerance level residues are typically one
to two orders of magnitude higher than actual residues in food when
distributed in commerce.
Accordingly, although sufficient information to quantify actual
residue levels in food is not available, the compounding of these
conservative assumptions will lead to a significant exaggeration of
actual exposures. EPA does not believe that this approach
underestimates exposure in the absence of residue data.
2. Dietary exposure from drinking water. For the purpose of the
screening level dietary risk assessment to support this request for an
exemption from the requirement of a tolerance for N-(n-octyl)-2-
pyrrolidone, a conservative drinking water concentration value of 100
parts per billion (ppb) based on screening level modeling was used to
assess the contribution to drinking water for the chronic dietary risk
assessments for N-(n-octyl)-2-pyrrolidone. These values were directly
entered into the dietary exposure model.
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).
N-(n-octyl)-2-pyrrolidone may be used as an inert ingredient in
pesticide products that are registered for specific uses that may
result in residential exposure (e.g., products used in and around the
home). Although there are non-pesticidal uses for N-(n-octyl)-2-
pyrrolidone, no reliable exposure information is available for those
uses. Therefore, a conservative residential exposure and risk
assessment was completed for uses of N-(n-octyl)-2-pyrrolidone as a
pesticide inert ingredient only. The Agency assessed pesticide products
containing N-(n-octyl)-2-pyrrolidone using exposure scenarios that
represent conservative residential handler exposure.
Short-term and intermediate-term residential exposure for adults
combines high-end dermal and inhalation handler exposure from indoor
hard surface, aerosol sprays and results in a margin of exposure (MOE)
of 210. Short-term and intermediate-term high-end post-application
dermal exposure from contact with mopping/wiping results in an MOE of
520. Short-term residential exposure for children includes total
exposures associated with contact with indoor hard surface, aerosol
sprays result in an MOE of 250. Because EPA's level of concern (LOC)
for N-(n-octyl)-2-pyrrolidone is an MOE below 100, these MOEs are not
of concern.
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 N-(n-octyl)-2-pyrrolidone to share a common
mechanism of toxicity with any other substances, and N-(n-octyl)-2-
pyrrolidone does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance exemption,
therefore, EPA has assumed that N-(n-octyl)-2-pyrrolidone 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 <a href="https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides">https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides</a>.
[[Page 47777]]
D. Safety Factor for Infants and Children
1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the Food Quality
Protection Act safety factor. In applying this provision, EPA either
retains the default value of 10X, or uses a different additional safety
factor when reliable data available to EPA support the choice of a
different factor.
The Agency has concluded that the FQPA safety factor can be reduced
to 1x for N-(n-octyl)-2-pyrrolidone for all exposure scenarios for the
following reasons:
i. The toxicity database for N-(n-octyl)-2-pyrrolidone consists of
a developmental toxicity study and 1-generation reproduction study.
There is no evidence of effects on reproductive parameters in the 1-
generation reproduction study, and the offspring effects observed in
the database occurred at the same or higher doses than parental
effects. Therefore, there is no evidence of increased susceptibility in
the database.
ii. Additionally, the most sensitive endpoint selected, seen in the
13-week oral toxicity study on dogs, is protective of neurotoxic and
all other effects observed in the database.
iii. There are no residual uncertainties identified in the exposure
databases. As described earlier, EPA used worst case assumptions for
the dietary food exposure assessment. EPA made conservative
(protective) assumptions in the ground and surface water modeling used
to assess exposure to N-(n-octyl)-2-pyrrolidone in drinking water. EPA
used similarly conservative assumptions to assess residential post
application exposure of children as well as incidental oral exposure of
children 1-2. These assessments will not underestimate the exposure and
risks posed by N-(n-octyl)-2-pyrrolidone.
E. Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic dietary pesticide
exposures are safe by comparing aggregate exposure estimates to the
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA
calculates the lifetime probability of acquiring cancer given the
estimated aggregate exposure. Short-, intermediate-, and chronic-term
risks are evaluated by comparing the estimated aggregate food, water,
and residential exposure to the appropriate PODs to ensure that an
adequate MOE exists.
1. Acute risk. An acute aggregate risk assessment takes into
account acute exposure estimates from dietary consumption of food and
drinking water. No adverse effect resulting from a single oral exposure
was identified, and no acute dietary endpoint was selected. Therefore,
N-(n-octyl)-2-pyrrolidone is not expected to pose an acute risk.
2. Chronic risk. A chronic aggregate risk assessment takes into
account chronic exposure estimates from dietary consumption of food and
drinking water. Using the exposure assumptions described in this unit
for chronic exposure, EPA has concluded that chronic exposure to N-(n-
octyl)-2-pyrrolidone from food and water will utilize 45.9% of the cPAD
for children 1-2 years old, the population group receiving the greatest
exposure.
3. Short-term and intermediate-term risk. Short- and intermediate
term aggregate exposure takes into account short- and intermediate term
residential exposure plus chronic exposure to food and water
(considered to be a background exposure level).
N-(n-octyl)-2-pyrrolidone is currently used as an inert ingredient
in pesticide products that are registered for uses that could result in
short- and intermediate term residential exposure, and the Agency has
determined that it is appropriate to aggregate chronic exposure through
food and water with short- and intermediate term residential exposures
to N-(n-octyl)-2-pyrrolidone.
Using the exposure assumptions described in this unit for short-
and intermediate term exposures, EPA has concluded that the combined
short- and intermediate term food, water, and residential exposures
result in an aggregate MOE of 126 for adults. Adult residential
pesticide exposure combines high-end dermal and inhalation handler
exposure from indoor hard surface aerosol spray with high end post-
application dermal exposure from indoor mopping/wiping. EPA has
concluded that the combined short- and intermediate term food, water,
and residential exposures result in an aggregate MOE of 121 for
children. Children's residential pesticide exposure includes total
exposures associated with contact with treated indoor surfaces
(mopping/wiping; dermal and hand-to-mouth exposures). Because EPA's
level of concern for N-(n-octyl)-2-pyrrolidone is an MOE of 100 or
below, these MOEs are not of concern.
4. Aggregate cancer risk for U.S. population. Based on the absence
of structural alerts for potential carcinogenicity in the database and
the lack of mutagenicity concerns, N-(n-octyl)-2-pyrrolidone is not
expected to pose a cancer risk to humans.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, or to infants and children, from aggregate
exposure to N-(n-octyl)-2-pyrrolidone residues. More detailed
information on this action can be found in the document titled ``IN-
11526; N-(n-octyl)-2-pyrrolidone: Human Health Risk and Ecological
Effects Assessment of a Food Use Pesticide Inert Ingredient'' in docket
ID EPA-HQ-OPP-2021-0172.
V. Other Considerations
Analytical Enforcement Methodology
An analytical method is not required for enforcement purposes since
the Agency is not establishing a numerical tolerance for residues of N-
(n-octyl)-2-pyrrolidone in or on any food commodities. EPA is
establishing a limitation on the amount of N-(n-octyl)-2-pyrrolidone
that may be used in pesticide formulations. This limitation will be
enforced through the pesticide registration process under the Federal
Insecticide, Fungicide, and Rodenticide Act (``FIFRA''), 7 U.S.C. 136
et seq. EPA will not register any prothioconazole pesticide formulation
for food use that exceeds 15% N-(n-octyl)-2-pyrrolidone in the final
pesticide formulation.
VI. Conclusions
Therefore, an exemption from the requirement of a tolerance is
established for residues of N-(n-octyl)-2-pyrrolidone (CAS Reg. No.
2687-94-7) when used as an inert ingredient (solvent) in pesticide
formulations containing prothioconazole at a maximum concentration of
15% under 40 CFR 180.1130.
VII. Statutory and Executive Order Reviews
This action establishes an exemption from the requirement of a
tolerance 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 ``Regulatory Planning and Review'' (58 FR 51735,
October 4, 1993). Because this action
[[Page 47778]]
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) or Executive Order 13045, entitled
``Protection of Children from Environmental Health Risks and Safety
Risks'' (62 FR 19885, April 23, 1997). 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 exemptions 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: July 19, 2023.
Charles Smith,
Director, Registration Division, Office of Pesticide Programs.
Therefore, for the reasons stated in the preamble, the EPA amends
40 CFR chapter I as follows:
PART 180--TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES
IN FOOD
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. Amend Sec. 180.1130 by adding paragraph (c) to read as follows:
Sec. 180.1130 N-(n-Octyl)-2-pyrrolidone and N-(n-dodecyl)-2-
pyrrolidone; exemptions from the requirement of a tolerance.
* * * * *
(c) N-(n-Octyl)-2-pyrrolidone is exempt from the requirement of a
tolerance when used as a solvent in formulations containing
prothioconazole as an active ingredient at a concentration not to
exceed 15% by weight.
[FR Doc. 2023-15679 Filed 7-24-23; 8:45 am]
BILLING CODE 6560-50-P
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