Document ID: EPA-HQ-OPP-2008-0671-0003
Agency: epa
Document Type: Rule
Title: Choline chloride; Exemption from the Requirement of a Tolerance
Posted Date: 2010-01-06T05:00Z

[Federal Register: January 6, 2010 (Volume 75, Number 3)]
[Rules and Regulations]               
[Page 760-763]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06ja10-9]                         

[[Page 760]]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2008-0671; FRL-8802-4]

 
Choline chloride; Exemption from the Requirement of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes an exemption from the requirement 
of a tolerance for residues of 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) 
305-5805.

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: 
sunderland.deirdre@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. 
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 
CONTACT.

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 
of filing.
    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, 
including

[[Page 761]]

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 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 
ingredients.

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 
metabolism.
    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 
children.

V. Aggregate Exposures

    In examining aggregate exposure, section 408 of FFDCA directs EPA 
to consider available information

[[Page 762]]

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 
performed.

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 
Children.

    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 
neurotoxicity.
    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 
X.

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.

[[Page 763]]

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.

X. Conclusions

    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 
note).

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 
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: December 24, 2009.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority: 21 U.S.C. 321(q), 346a and 371.

0
2. In Sec. 180.920, 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
 67-48-1)
                                * * * * *
------------------------------------------------------------------------

[FR Doc. E9-31280 Filed 1-5-10; 8:45 am]

BILLING CODE 6560-50-S