N-(n-Octyl)-2-pyrrolidone in Pesticide Formulations; Tolerance Exemption, 47773-47778 [2023-15679]
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[FR Doc. 2023–15697 Filed 7–24–23; 8:45 am]
BILLING CODE 9110–04–P
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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
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
This regulation establishes an
exemption from the requirement of a
tolerance for residues of N-(n-octyl)-2pyrrolidone (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 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 and the OPP
docket is (202) 566–1744. Please review
the visitor instructions and additional
information about the docket available
at https://www.epa.gov/dockets.
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: RDFRNotices@epa.gov.
SUPPLEMENTARY INFORMATION:
SUMMARY:
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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 Federal Register Office’s eCFR site at https://www.ecfr.gov/
current/title-40/chapter-I/subchapter-E/
part-180?toc=1.
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:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
online instructions for submitting
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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/where-sendcomments-epa-dockets#express.
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 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, https://
www.regulations.gov. There were no
comments received in response to the
notice of filing.
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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
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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
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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)-2pyrrolidone, including exposure
resulting from the exemption
established by this action. EPA’s
assessment of exposures and risks
associated with N-(n-octyl)-2pyrrolidone 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-observedadverse-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)-2pyrrolidone 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
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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
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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/pesticide-science-andassessing-pesticide-risks/overview-riskassessment-pesticide-program.
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
Exposure/scenario
Point of departure and
uncertainty/safety factors
RfD, PAD, LOC for risk
assessment
Study and toxicological effects
Acute dietary (General population including infants
and children).
An acute effect was not found in the database; therefore, an acute dietary assessment is not necessary.
Chronic dietary (All populations).
NOAEL= 90 mg/kg/day .....
UFA = 10 × ........................
UFH = 10 × ........................
FQPA SF = 1 × .................
NOAEL= 90 mg/kg/day .....
UFA = 10 × ........................
UFH = 10 × ........................
FQPA SF = 1 × .................
Dermal (or oral) study
NOAEL = 90 mg/kg/day
(dermal absorption rate
= 100%).
UFA = 10 × ........................
UFH = 10 × ........................
FQPA SF = 1 × .................
Inhalation (or oral) study
NOAEL = 90 mg/kg/day
(inhalation absorption
rate = 100%).
UFA = 10 × ........................
UFH = 10 × ........................
FQPA SF = 1 × .................
Incidental oral short-term (1
to 30 days).
Dermal short-term (1 to 30
days) and Dermal intermediate-term (1 to 6
months).
Inhalation short-term (1 to
30 days) and intermediate-term (1 to 6
months).
Cancer (Oral, dermal, inhalation).
Chronic RfD = 90 mg/kg/
day.
cPAD = 0.9 mg/kg/day.
LOC for MOE <100 ...........
[13-week oral Toxicity-dog] LOAEL = 240 mg/kg/day
based on neurological effects.
[13-week oral Toxicity-dog] LOAEL = 240 mg/kg/day
based on neurological effects.
LOC for MOE ....................
<100 ..................................
[13-week oral Toxicity-dog] LOAEL = 240 mg/kg/day
based on neurological effects.
LOC for MOE ....................
<100 ..................................
[13-week oral Toxicity-dog] LOAEL = 240 mg/kg/day
based on neurological effects.
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.
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).
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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
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occur from non-pesticidal uses but no
reliable information is available for nonpesticidal exposures. Therefore, EPA
assessed dietary exposures from
pesticidal uses of N-(n-octyl)-2pyrrolidone only. EPA assessed dietary
exposures from N-(n-octyl)-2pyrrolidone in food as follows:
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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.
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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-(noctyl)-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 https://
www.regulations.gov 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)-2pyrrolidone 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
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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-(noctyl)-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)-2pyrrolidone. 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 nonoccupational, non-dietary exposure
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(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)-2pyrrolidone, 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)-2pyrrolidone as a pesticide inert
ingredient only. The Agency assessed
pesticide products containing N-(noctyl)-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 postapplication 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)-2pyrrolidone 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)-2pyrrolidone to share a common
mechanism of toxicity with any other
substances, and N-(n-octyl)-2pyrrolidone 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 https://
www.epa.gov/pesticide-science-andassessing-pesticide-risks/cumulativeassessment-risk-pesticides.
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D. Safety Factor for Infants and
Children
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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-(noctyl)-2-pyrrolidone consists of a
developmental toxicity study and 1generation 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
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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)-2pyrrolidone 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)-2pyrrolidone 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 postapplication 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).
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Because EPA’s level of concern for N-(noctyl)-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-(noctyl)-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-(noctyl)-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)-2pyrrolidone 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
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47778
Federal Register / Vol. 88, No. 141 / Tuesday, July 25, 2023 / Rules and Regulations
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).
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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).
CropScience has requested these
tolerances under the Federal Food,
Drug, and Cosmetic Act (FFDCA).
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).
List of Subjects in 40 CFR Part 180
Environmental protection,
Administrative practice and procedure,
Agricultural commodities, Pesticides
and pests, Reporting and recordkeeping
requirements.
ADDRESSES:
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
1. The authority citation for part 180
continues to read as follows:
■
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Amend § 180.1130 by adding
paragraph (c) to read as follows:
■
§ 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
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[EPA–HQ–OPP–2022–0479; FRL–11131–01–
OCSPP]
Indaziflam; Pesticide Tolerance
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
This regulation establishes
tolerances for residues of indaziflam in
or on multiple commodities discussed
later in this document. Bayer
SUMMARY:
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The docket for this action,
identified by docket identification (ID)
number EPA–HQ–OPP–2022–0479, 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 and the OPP
Docket is (202) 566–1744. For the latest
status information on EPA/DC services,
docket access, visit https://
www.epa.gov/dockets.
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: RDFRNotices@epa.gov.
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 EPA’s tolerance
regulations at 40 CFR part 180 through
the Office of the Federal Register’s e-
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]]>Agencies
[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 [www.gpo.gov]
[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.
-----------------------------------------------------------------------
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 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 and the OPP docket is (202) 566-1744. Please review the
visitor instructions and additional information about the docket
available at https://www.epa.gov/dockets.
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:
[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 Federal Register Office's e-CFR site at https://www.ecfr.gov/current/title-40/chapter-I/subchapter-E/part-180?toc=1.
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:
Federal eRulemaking Portal: https://www.regulations.gov.
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.
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/where-send-comments-epa-dockets#express.
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 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, https://www.regulations.gov. 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 https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/overview-risk-assessment-pesticide-program.
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
----------------------------------------------------------------------------------------------------------------
Point of departure and
Exposure/scenario uncertainty/safety RfD, PAD, LOC for risk Study and toxicological
factors assessment effects
----------------------------------------------------------------------------------------------------------------
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.
----------------------------------------------------------------------------
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.........
----------------------------------------------------------------------------
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.
----------------------------------------------------------------------------------------------------------------
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 https://www.regulations.gov 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 https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides.
[[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
