[Federal Register Volume 75, Number 3 (Wednesday, January 6, 2010)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-31280]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Choline chloride; Exemption from the Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of choline chloride (CAS Reg. No. 67-48-1)
applied pre-harvest on all raw agricultural commodities when applied/
used as a solvent. Loveland Products, Inc., submitted a petition to EPA
under the Federal Food, Drug, and Cosmetic Act (FFDCA), requesting an
exemption from the requirement of a tolerance. This regulation
eliminates the need to establish a maximum permissible level for
residues of choline chloride.
DATES: This regulation is effective January 6, 2010. Objections and
requests for hearings must be received on or before March 8, 2010, 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: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2008-0671. All documents in the
docket are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
FOR FURTHER INFORMATION CONTACT: Deirdre Sunderland, Registration
Division (7505P), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 603-0851; e-mail 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.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
B. How Can I Access Electronic Copies of this Document?
In addition to accessing electronically available documents at
http://www.regulations.gov, you may access this Federal Register
document electronically through the EPA Internet under the ``Federal
Register'' listings at http://www.epa.gov/fedrgstr. You may also access
a frequently updated electronic version of 40 CFR part 180 through the
Government Printing Office's e-CFR cite at http://www.gpoaccess.gov/ecfr.
C. Can I File an Objection or Hearing Request?
Under section 408(g) of FFDCA, 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. The EPA procedural regulations which
govern the submission of objections and requests for hearings appear in
40 CFR part 178. 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-2008-0671 in the subject line on the first page of
your submission. All requests must be in writing, and must be mailed or
delivered to the Hearing Clerk on or before March 8, 2010.
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 that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit your copies, identified by docket ID
number EPA-HQ-OPP-2008-0671, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket Facility's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Docket Facility telephone number is (703) 305-5805.
II. Background and Statutory Findings
In the Federal Register of December 3, 2008 (73 FR 73648) (FRL-
8391-3), EPA issued a notice pursuant to section 408 of FFDCA, 21
U.S.C. 346a, as amended by FQPA (Public Law 104-170), announcing the
filing of a pesticide petition (PP 8E7387 ) by Loveland Products, Inc.,
P.O. Box 1286, Greeley, CO 80632-1286. The petition requested that 40
CFR 180.920 be amended by establishing an exemption from the
requirement of a tolerance for residues of choline chloride when used
as an inert ingredient in pesticide formulations applied pre-harvest.
That notice included a summary of the petition prepared by the
petitioner. There were no comments received in response to the notice
Section 408(b)(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,
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
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. First, EPA determines the
toxicity of pesticides. Second, EPA examines exposure to the pesticide
through food, drinking water, and through other exposures that occur as
a result of pesticide use in residential settings.
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 ploymers 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. Toxicological Profile
Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the
available scientific data and other relevant information in support of
this action and considered its validity, completeness and reliability
and the relationship of this information 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. The nature of the toxic effects caused by choline
chloride are discussed in this unit. The following provides a brief
summary of the risk assessment and conclusions from the Agency's review
of choline chloride. The Agency's full decision document for this
action is available in the Agency's electronic docket (regulations.gov)
under the docket number EPA-HQ-OPP-2008-0671.
Choline chloride is a quaternary ammonium salt which dissociates in
water resulting in a positively charged quaternary hydroxyl
alkylammonium ion and a negatively charged chloride ion. Choline is an
essential component of the human diet and acts as a precursor to
acetylcholine, phospholipids, and the methyl donor betaine. It is
important for the structural integrity of cell membranes, cholinergic
neurotransmission, transmembrane signaling, methyl metabolism, and
lipid and cholesterol transport and metabolism.
Choline was officially made an ``essential nutrient'' in 1998 and
adequate intake (AI) levels were established (women-425 milligram/day
(mg/day), pregnant women-450 mg/day, men and lactating women-550 mg/
day). The Daily Upper Intake Level for choline is 3.5 grams for adults.
Research indicates that many individuals are not getting enough
choline, with daily intake levels far below the AI.
Chloride is a binary compound of chlorine; a salt of hydrochloric
acid. Chloride is the major extracellular anion and contributes to many
body functions including the maintenance of osmotic pressure, acid-base
balance, muscular activity, and the movement of water between fluid
compartments. The World Health Organization has performed two
assessments which determined that from a toxicological point of view,
there were no concerns for the chloride ion. It was considered to be
naturally-occurring and a normal participant of animal and human
Choline chloride has demonstrated a low acute oral toxicity with
LD50 values for rats ranging from 3,150 to >= 6,000
milligram/kilogram (mg/kg) and LD50 for mice in the range of
3,900 to 6,000 mg/kg. Although appropriate animal studies are lacking
for acute dermal toxicity, an in vitro percutaneous absorption study
performed under occluded and unoccluded conditions showed that choline
chloride is expected to have a low potential for percutaneous
absorption. Acceptable acute inhalation studies are not available.
Studies conducted in the early 1960's showed only slight transient
irritation of the skin and eye.
Repeat dose animal studies on choline chloride are limited. One
study in mice evaluated the impact of 200 mg/kg/day choline chloride
given orally or intranasally for 28 days. No adverse effects were
observed with regards to body weight, food and water consumption,
hematology, clinical biochemistry, or histopathology of various organs
(lung, heart, liver, spleen, and kidney). Results from intranasal
exposure to choline chloride were comparable with their respective
controls and to other treatment groups. The no adverse effects are
observed (NOAEL) for oral and intranasally administered choline
chloride is >= 200 mg/kg/day.
A 72-week feeding study in rats administered 500 mg/kg/day of
choline chloride and observed the animals for 30 weeks post exposure.
There were no significant difference between the control and treated
group in relation to body weights, relative liver weight, survival
rates, and the number of neoplastic liver nodules, hepatocellular
carcinomas, lung tumors, leukemia, or other tumors. This study resulted
in a NOAEL of 500 mg/kg/day (the highest dose tested).
Choline is a precursor to the vital neurotransmitter acetylcholine.
Studies show that choline has beneficial effects on the nervous system
and memory. Choline is necessary to promote proper development in the
fetus and infant and prevent cognitive problems. Choline chloride is
not expected to cause neurotoxicity and it is not a known endocrine
disruptor nor are its metabolites related to any class of known
endocrine disruptors. Based on the results of the in vitro and in vivo
studies the Agency concluded that choline chloride is not expected to
be carcinogenic or mutagenic.
Since the 1930's choline chloride has been used as a widespread
nutrient in animal feed without adverse effects reported on fertility
or teratogenicity. The Food and Drug Administration (FDA) requires
choline be added to non-milk based infant formulas at a minimum
concentration of 7 mg for every 100 kilocalories (21 CFR 107.100).
Although one study did show developmental effects, they were only seen
at very high doses (>=4,160 mg/kg/day) and only in the presence of
maternal toxicity. There were no observed adverse effects for both
mothers and pups exposed to 1,250 mg/kg/day. Based on this information
the Agency concluded that choline chloride, when used as an inert
ingredient, will not cause reproductive or developmental toxicity and
therefore, does not anticipate an increased risk to infants and
V. Aggregate Exposures
In examining aggregate exposure, section 408 of FFDCA directs EPA
to consider available information
concerning exposures from the pesticide residue in food and all other
non-occupational exposures, including drinking water from ground water
or surface water and exposure through pesticide use in gardens, lawns,
or buildings (residential and other indoor uses).
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.
Exposure from the use of choline chloride is expected through the
oral route via food and drinking water. Exposure via the dermal route
may occur for those individuals applying the product both
occupationally and residentially. Due to the rapid degradation of the
chemical and the natural presence of choline and chloride in the
environment, exposure from the use of choline chloride as an inert
ingredient in pesticide products is not expected to increase the
aggregate exposure to all subpopulation including infants and children
and therefore a quantitative exposure assessment has not been
VI. Cumulative Effects
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.''
Unlike other pesticides for which EPA has followed a cumulative
risk approach based on a common mechanism of toxicity, EPA has not made
a common mechanism of toxicity finding as to choline chloride and any
other substances, and these chemicals do not appear to produce a toxic
metabolite produced by other substances. For the purposes of this
tolerance action, therefore, EPA has not assumed that these chemicals
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 the policy statements released by EPA's Office of
Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a
common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/.
VII. Additional Safety Factor for the Protection of Infants and
Section 408 of FFDCA provides that EPA shall apply an additional
tenfold 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 that a different margin of safety will be safe for infants
and children. EPA concluded that the FQPA safety factor for choline
chloride should be reduced to 1X.
The database for choline chloride is adequate to make a
determination of safety for infants and children. Choline is a natural
component of a variety of commonly consumed foods. It has been added as
a supplement to infant formula in the United States for decades. In
addition to dietary consumption of choline and chloride, choline is
made endogenously in the human body. Choline is a precursor to the
vital neurotransmitter acetylcholine. Studies show that choline has
beneficial effects on the nervous system and memory. Choline is
necessary to promote proper development in the fetus and infant and
prevent cognitive problems. Choline chloride is not expected to cause
Chloride is also important for many biological functions. It helps
to maintain the fluid balance of cells, proper blood volume, blood
pressure, and the pH of body fluids. The World Health Organization has
performed two assessments which determined that from a toxicological
point of view, there were no concerns for the chloride ion. It was
considered to be naturally-occurring and a normal participant of animal
and human metabolism.
Choline chloride has been used as a widespread nutrient in animal
feed since the 1930's without adverse effects reported on fertility or
teratogenicity. Although one study in mice did show developmental
effects, they were only seen at very high doses (>=4,160 mg/kg/day) and
only in the presence of maternal toxicity. There were no observed
adverse effects for both mothers and pups exposed to 1,250 mg/kg/day.
Exposure to choline chloride is not expected to significantly
increase the pre-existing levels found in commonly eaten foods. Due to
the negligible anticipated crop residues and subsequent exposure, the
low toxicity of the chemical and its metabolites, the bodies need for
choline from a dietary source, and the beneficial role choline plays in
fetal development and memory; the safety factor has been reduced to 1
VIII. Determination of Safety for U.S. Population
In addition to its low toxicity, exposure to choline chloride will
be limited. The expected exposure pathway is via the oral and the
dermal routes. Humans are currently exposed to choline and chloride on
a daily basis through commonly eaten foods (both naturally occurring
and when added as a nutrient) and through the bodies natural ability to
synthesize the nutrient. It is unlikely that the exposure from choline
chloride, when used as an inert ingredient applied pre-harvest to food
commodities, will significantly increase the natural concentration of
choline and chloride in foods. Choline and chloride are also found
naturally in the environment. Choline chloride is readily biodegradable
and because of its high water solubility it is expected that most of
the inert will be washed from the plant prior to consumption. Once in
water, its preferred media, it will be broken into a quaternary
hydroxyl alkylammonium ion and a chloride ion.
Taking into consideration all available information on choline
chloride, it has been determined that there is a reasonable certainty
that no harm to any population subgroup, including infants and
children, will result from aggregate exposure to this chemical.
Therefore, the exemption from the requirement of a tolerance for
residues of choline chloride (CAS Reg. No. 67-48-1), when used as an
inert ingredient in pre-harvest applications, under 40 CFR 180.920 can
be considered safe under section 408(q) of the FFDCA.
IX. Other Considerations
A. Analytical Method(s)
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. International Tolerances
The Agency is not aware of any country requiring a tolerance for
choline chloride nor have any CODEX Maximum Residue Levels (MRLs) been
established for any food crops at this time.
Therefore, a tolerance exemption is established for choline
chloride (CAS Reg. No. 67-48-1) when used as inert ingredient in
pesticide formulations applied to growing crops only.
XI. Statutory and Executive Order Reviews
This final rule establishes a tolerance under section 408(d) of
FFDCA 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 final rule has been
exempted from review under Executive Order 12866, this final rule 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 final rule 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 section 408(d) of FFDCA, such as the exemption in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply.
This final rule 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 section 408(n)(4) of FFDCA. 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 final rule. In addition,
this final rule does not impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (Public Law 104-4).
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 of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272
XII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. 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 this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
Dated: December 24, 2009.
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. 180.920, the table is amended by adding alphabetically the
following inert ingredients:
Sec. 180.920 Inert ingredients used pre-harvest; exemptions from the
requirement of a tolerance.
Inert ingredients Limits Uses
* * * * *
Choline chloride (CAS Reg. No. ------------------ As a solvent
* * * * *
[FR Doc. E9-31280 Filed 1-5-10; 8:45 am]
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