[Federal Register Volume 81, Number 250 (Thursday, December 29, 2016)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-31211]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2016-0007 and EPA-HQ-OPP-2016-0008; FRL-9950-40]
Isobutyl Acetate and Isobutyric Acid; Exemption From the
Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes exemptions from the requirement of
a tolerance for residues of isobutyl acetate (CAS Reg. No. 110-19-0)
and isobutyric acid (CAS Reg. No. 79-31-2) when used as inert
ingredients (solvent) in pesticide formulations applied to growing
crops and raw agricultural commodities after harvest. Technology
Sciences Group Inc. on behalf of Jeneil Biosurfactant Company submitted
a petition to EPA under the Federal Food, Drug, and Cosmetic Act
(FFDCA), requesting establishment of these exemptions from the
requirement of a tolerance. This regulation eliminates the need to
establish maximum permissible levels for residues of isobutyl acetate
and isobutyric acid.
DATES: This regulation is effective December 29, 2016. Objections and
requests for hearings must be received on or before February 27, 2017,
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 dockets for this action, identified by docket
identification (ID) numbers EPA-HQ-OPP-2016-0007 and EPA-HQ-OPP-2016-
0008, are available at http://www.regulations.gov or at the Office of
Pesticide Programs Regulatory Public Docket (OPP Docket) in the
Environmental Protection Agency Docket Center (EPA/DC), West William
Jefferson Clinton Bldg., Rm. 3334, 1301 Constitution Ave. NW.,
Washington, DC 20460-0001. The Public Reading Room is open from 8:30
a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays. The
telephone number for the Public Reading Room is (202) 566-1744, and the
telephone number for the OPP Docket is (703) 305-5805. Please review
the visitor instructions and additional information about the docket
available at http://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT: Michael Goodis, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington,
DC 20460-0001; main telephone number: (703) 305-7090; email address:
I. General Information
A. Does this action apply to me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
The following list of North American Industrial Classification System
(NAICS) codes is not intended to be exhaustive, but rather provides a
guide to help readers determine whether this document applies to them.
Potentially affected entities may include:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
B. How can I get electronic access to other related information?
You may access a frequently updated electronic version of 40 CFR
part 180 through the Government Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
C. How can I file an objection or hearing request?
Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an
objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2016-0007 or EPA-HQ-OPP-2016-0008 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 February 27, 2017. Addresses for mail and
hand delivery of objections and hearing requests are provided in 40 CFR
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-2016-0007 or EPA-HQ-
OPP-2016-0008, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider to be CBI or other
information whose disclosure is restricted by statute.
Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC
Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at http://www.epa.gov/dockets/contacts.html.
Additional instructions on commenting or visiting the docket, along
with more information about dockets generally, is available at http://www.epa.gov/dockets.
II. Petition for Exemption
In the Federal Register of April 25, 2016 (81 FR 24044) (FRL-9944-
86), EPA issued a document pursuant to FFDCA section 408, 21 U.S.C.
346a, announcing the filing of a pesticide petition (IN-10846 for
isobutyl acetate; IN-10852 for isobutyric acetate) by Technology
Sciences Group Inc., (1150 18th Street NW., Suite 1000, Washington, DC
20036) on behalf of Jeneil Biosurfactant Company (400 N. Dekora Woods
Blvd. Saukville, WI 53080). The petition requested that 40 CFR 180.910
be amended by establishing exemptions from the requirement of a
tolerance for residues of isobutyl acetate (CAS Reg. No. 110-19-0) and
isobutyric acid (CAS Reg. No. 79-31-2) when used as inert ingredients
(solvent) in pesticide formulations applied to growing crops and to raw
agricultural commodities after harvest. That document referenced the
summaries of the petitions prepared by Technology Sciences Group Inc.
on behalf of Jeneil Biosurfactant Company, the petitioner, which is
available in the docket, http://www.regulations.gov. A comment was
received on the notice of filing concerning petition #IN-10846. EPA's
response to this comment is discussed in Unit V.B.
III. Inert Ingredient Definition
Inert ingredients are all ingredients that are not active
ingredients as defined in 40 CFR 153.125 and include, but are not
limited to, the following types of ingredients (except when they have a
pesticidal efficacy of their own): Solvents such as alcohols and
hydrocarbons; surfactants such as polyoxyethylene polymers and fatty
acids; carriers such as clay 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
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(b)(2)(A)(ii) of FFDCA defines
``safe'' to mean that ``there is a reasonable certainty that no harm
will result from aggregate exposure to the pesticide chemical residue,
including all anticipated dietary exposures and all other exposures for
which there is reliable information.'' This includes exposure through
drinking water and in residential settings, but does not include
occupational exposure. Section 408(b)(2)(C) of FFDCA requires EPA to
give special consideration to exposure of infants and children to the
pesticide chemical residue in establishing a tolerance and to ``ensure
that there is a reasonable certainty that no harm will result to
infants and children from aggregate exposure to the pesticide chemical
residue. . . .''
EPA establishes exemptions from the requirement of a tolerance only
in those cases where it can be clearly demonstrated that the risks from
aggregate exposure to pesticide chemical residues under reasonably
foreseeable circumstances will pose no appreciable risks to human
health. In order to determine the risks from aggregate exposure to
pesticide inert ingredients, the Agency considers the toxicity of the
inert in conjunction with possible exposure to residues of the inert
ingredient through food, drinking water, and through other exposures
that occur as a result of pesticide use in residential settings. If EPA
is able to determine that a finite tolerance is not necessary to ensure
that there is a reasonable certainty that no harm will result from
aggregate exposure to the inert ingredient, an exemption from the
requirement of a tolerance may be established.
Consistent with FFDCA section 408(c)(2)(A), and the factors
specified in FFDCA section 408(c)(2)(B), EPA has reviewed the available
scientific data and other relevant information in support of this
action. EPA has sufficient data to assess the hazards of and to make a
determination on aggregate exposure for isobutyl acetate and isobutyric
acid including exposure resulting from the exemption established by
this action. EPA's assessment of exposures and risks associated with
isobutyl acetate and isobutyric acid 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 isobutyl acetate and isobutyric acid
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.
Only acute toxicity data are available on isobutyric acid and no
data are available on isobutyl acetate. However, upon ingestion,
isobutyl acetate is rapidly and completely hydrolyzed to isobutanol and
acetic acid. Isobutyric acid is a metabolic product of isobutanol.
Isobutanol is metabolized by alcohol dehydrogenase to form
isobutyric acid via conversion to isobutyraldehyde. Therefore, toxicity
data on isobutanol are considered suitable to assess repeated exposure
to isobutyl acetate and isobutyric acid. Since acetic acid is currently
exempted from tolerance under 40 CFR 180.910 without limitation, this
risk assessment focuses on toxicity data available on isobutanol.
The acute oral and dermal toxicities are low for isobutyric acid.
Isobutyric acid has an acute oral lethal dose (LD50) >=
2,230 milligram/kilogram (mg/kg) in rats and rabbits. The acute dermal
LD50 = 475 mg/kg in rabbits. The acute inhalation
LC50 > 9.59 milligram/liter (mg/L) in rats. It is corrosive
to the eye and skin in rabbits. Isobutyric acid is not a dermal
sensitizer in rabbits. Isobutanol has an acute oral LD50 >=
2,830 mg/kg in rats. The acute dermal acute LD50 >= 2,000
mg/kg in rabbits. The acute inhalation LC50 > 6,000 parts
per million (ppm) (approximately equivalent to 6,000 mg/L) in rats.
Isobutanol is severely irritating to the eye and minimally to
moderately irritating to the skin in rabbits.
Based on the subchronic data available, isobutanol is not toxic up
to the limit dose of 1,000 milligram/kilogram/day (mg/kg/day). In a 90-
day oral toxicity study via gavage in rats, hypo-activity, ataxia and
salivation were observed at 1,000 mg/kg/day of isobutanol. In another
90-day oral toxicity study with isobutanol via drinking water in rats,
no adverse effects were observed at doses up to 16,000 ppm
(approximately 1,450 mg/kg/day), the highest dose tested (HDT). The
study conducted via drinking water in rats is considered more relevant
to human exposure and therefore more reflective of potential human
In developmental toxicity studies with isobutanol via inhalation in
rats and rabbits, neither maternal nor developmental toxicity is seen
at doses up to 10,000 mg/m\3\ (approximately 3,060 mg/kg/day), the HDT
in both studies and above the limit dose of 1,000 mg/kg/day.
Similarly, no adverse effects are observed in a two-generation
reproductive study with isobutanol via inhalation in rats at doses up
to 2,500 ppm (approximately 2,326 mg/kg/day).
Carcinogenicity studies with isobutyl acetate, isobutyric acid or
isobutanol are not available. However, a chronic toxicity study in rats
treated with isobutantol in drinking water for 53-56 weeks did not show
any evidence of toxicity or tumors at doses as high as 200 mg/kg/day.
In addition, no toxicity is observed in other studies at doses below
1,450 mg/kg/day with isobutanol. Moreover, mutagenicity studies are
negative with isobutanol and isobutyric acid. An Ames test, unscheduled
DNA synthesis and mouse lymphoma assay are negative when tested with
isobutyric acid. The Ames test, mouse lymphoma, Comet and micronucleus
assays are negative when tested with isobutanol. Therefore, isobutyl
acetate and isobutyric acid are not expected to be carcinogenic.
A neurotoxicity screening battery with isobutanol via the
inhalation route of exposure in rats was available for review. Also,
neurotoxicity endpoints were evaluated in an acute toxicity study in
rats with isobutanol via the inhalation route of exposure. No adverse
effects were observed in the functional observational battery, motor
activity, schedule control operant behavior or neuropathology at doses
up to 1,500 ppm (approximately 1,408 mg/kg/day) and 2,500 ppm
(approximately 2,326 mg/kg/day) in rats in the neurotoxicity screening
battery and acute toxicity studies, respectively. EPA concluded that
isobutyl acetate and isobutyric acid are not expected to be neurotoxic.
Immunotoxicity studies with isobutyric acid and isobutanol are
available for review. Mouse cell-mediated immune response is not
modulated by isobutyric acid in a host-resistant assay using Listeria
monocytogenes. Humoral immunity is unaffected in mice as measured by
the antibody plaque-forming cell response to sheep erythrocytes. Also,
a lymphocyte mitogenesis test with isobutanol showed mitogenic activity
is not inhibited in stimulated B and T cells from mouse spleen.
Therefore, isobutyl acetate and isobutyric acid are not expected to be
Metabolism studies are not available for isobutyl acetate. Limited
data are available on isobutyric acid and isobutanol. A metabolism
study with a single dose of isobutyric acid via gavage in rats showed
that it is rapidly metabolized and the majority eliminated as expired
CO2. Less than 1.0% of the dose is found in feces and 3.21-
4.61% in urine. A metabolism study with isobutanol via gavage in
rabbits showed that it is rapidly metabolized. 0.5% is excreted in the
urine or exhaled air. Identified metabolites are isobutyraldehyde,
isobutyric acid, and isovaleric acid. There is no concern for the
metabolites isobutyraldehyde and isovaleric acid as they will be
conjungated and excreted.
B. Toxicological Points of Departure/Levels of Concern
The available toxicity studies indicate that isobutanol has very
low toxicity. The lowest NOAEL (316 mg/kg/day) in the database occurred
in a 90-day oral toxicity study with isobutanol via gavage in rats.
Hypo-activity, ataxia and salivation were seen at 1,000 mg/kg/day. In a
second study conducted for 90 days with isobutanol via drinking water
in rats, the aforementioned effects weren't seen at doses as high 1,450
mg/kg/day. The drinking water study in rats represents a more realistic
route for human exposure to isobutyric acid and isobutyl acetate, and
is considered more reflective of potential toxicity. Therefore, since
no signs of toxicity were observed at doses up to the limit dose in
oral and inhalation toxicity studies, an endpoint of concern for risk
assessment purposes was not identified. Since no endpoint of concern
was identified for the acute and chronic dietary exposure assessment
and short and intermediate dermal and inhalation exposure, a
quantitative risk assessment
for isobutyric acid and isobutyl acetate is not necessary.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to isobutyl acetate and isobutyric acid, EPA considered
exposure under the proposed exemption from the requirement of a
tolerance. EPA assessed dietary exposures from isobutyl acetate and
isobutyric acid in food as follows:
Under this exemption from the requirement of a tolerance, residues
of isobutyl acetate and isobutyric acid may be found on foods from
crops that were treated with pesticide formulations containing isobutyl
acetate and isobutyric acid. However, a quantitative dietary exposure
assessment was not conducted since a toxicological endpoint for risk
assessment was not identified.
2. Dietary exposure from drinking water. Since a hazard endpoint of
concern was not identified for the acute and chronic dietary
assessment, a quantitative dietary exposure risk assessment for
drinking water was not conducted, although exposures may be expected
from use on food crops.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., textiles (clothing and diapers), carpets, swimming
pools, and hard surface disinfection on walls, floors, and tables).
Isobutyl acetate and isobutyric acid may be used in pesticide
products and non-pesticide products that may be used in and around the
home. Based on the discussion in Unit IV.B., a quantitative residential
exposure assessment for isobutyl acetate and isobutyric acid was not
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.''
Based on the available data, isobutyl acetate and isobutyric acid
do not have a toxic mechanism; therefore, section 408(b)(2)(D)(v) does
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 (FQPA SF). 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.
As part of its qualitative assessment, the Agency did not use
safety factors for assessing risk, and no additional safety factor is
needed for assessing risk to infants and children. Based on an
assessment of isobutyl acetate and isobutyric acid, EPA has concluded
that there are no toxicological endpoints of concern for the U.S.
population, including infants and children.
E. Aggregate Risks and Determination of Safety
Because no toxicological endpoints of concern were identified, EPA
concludes that aggregate exposure to residues of isobutyl acetate and
isobutyric acid will not pose a risk to the U.S. population, including
infants and children, and that there is a reasonable certainty that no
harm will result to the general population, or to infants and children
from aggregate exposure to isobutyl acetate and isobutyric acid
V. Other Considerations
A. Analytical Enforcement Methodology
An analytical method is not required for enforcement purposes since
the Agency is establishing an exemption from the requirement of a
tolerance without any numerical limitation.
B. Response to Comments
A comment was received from a private citizen who was concerned
about the safety and impact pesticides on food on human health. The
Agency understands the commenter's concerns and recognizes that some
individuals believe that no residue of pesticides should be allowed.
However, under the existing legal framework provided by section 408 of
the Federal Food, Drug and Cosmetic Act (FFDCA), EPA is authorized to
establish pesticide tolerances or exemptions where persons seeking such
tolerances or exemptions have demonstrated that the pesticide meets the
safety standard imposed by the statute, which EPA has determined here.
Therefore, exemptions from the requirement of a tolerance are
established under 40 CFR 180.910 for residues of isobutyl acetate (CAS
Reg. No. 110-19-0) and isobutyric acid (CAS Reg. No. 79-31-2) when used
as inert ingredients (solvent) in pesticide formulations applied to
growing crops and raw agricultural commodities after harvest.
VII. Statutory and Executive Order Reviews
This action establishes tolerance exemptions 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 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
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
Dated: December 16, 2016.
Daniel J. Rosenblatt,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. In Sec. 180.910, add alphabetically the inert ingredients to the
table to read as follows:
Sec. 180.910 Inert ingredients used pre- and post-harvest; exemptions
from the requirement of a tolerance.
Inert ingredients Limits Uses
* * * * * * *
Isobutyl Acetate (CAS Reg. No. .................... Solvent.
Isobutyric Acid (CAS Reg. No. .................... Solvent.
* * * * * * *
[FR Doc. 2016-31211 Filed 12-28-16; 8:45 am]
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