Document ID: EPA-HQ-OPP-2006-0479-0004
Agency: epa
Document Type: Rule
Title: Ferric Citrate; Inert Ingredient; Exemption from the Requirement of a Tolerance
Posted Date: 2008-04-02T04:00Z

[Federal Register: April 2, 2008 (Volume 73, Number 64)]
[Rules and Regulations]               
[Page 17910-17914]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr02ap08-11]                         

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2006-0479; FRL-8347-9]

 
Ferric Citrate; Inert Ingredient; 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 under 40 CFR 180.910 for residues of ferric citrate (CAS 
Reg. No. 2338-05-8) in or on raw agricultural commodities when applied/
used as inert ingredients in pesticide formulations. The Shepherd 
Chemical Company submitted a petition to EPA under the Federal Food, 
Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality 
Protection Act of 1996, requesting an exemption from the requirement of 
a tolerance. This regulation eliminates the need to establish a maximum 
permissible level for residues of ferric citrate.

DATES: This regulation is effective April 2, 2008. Objections and 
requests for

[[Page 17911]]

hearings must be received on or before June 2, 2008, 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-2006-0479. To access the 
electronic docket, go to http://www.regulations.gov, select ``Advanced 
Search,'' then ``Docket Search.'' Insert the docket ID number where 
indicated and select the ``Submit'' button. Follow the instructions on 
the regulations.gov website to view the docket index or access 
available documents. All documents in the docket are listed in the 
docket index available in 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 either in the electronic docket at http://
www.regulations.gov, or, if only available in hard copy, at the Office 
of Pesticide Programs (OPP) Regulatory Public Docket in Rm. S-4400, One 
Potomac Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The 
hours of operation of this Docket Facility are 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: Kathleen Martin, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-2857; e-mail address: martin.kathleen@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. To determine 
whether you or your business may be affected by this action, you should 
carefully examine the applicability provisions in 40 CFR part 152. 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 an electronic copy of this Federal 
Register document through the electronic docket 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 pilot e-CFR site at http://
www.gpoaccess.gov/ecfr.

C. Can I File an Objection or Hearing Request?

    Under section 408(g) of FFDCA, as amended by FQPA, 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-2006-0479 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 June 2, 2008.
    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-2006-0479, 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'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 June 7, 2006 (71 FR 32955) (FRL-8071-2), 
EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 U.S.C. 
346a(d)(3), announcing the filing of a pesticide tolerance petition (PP 
6E7062) by The Shepherd Chemical Company, 4900 Beech Street; Norwood, 
OH 45212-2398. The petition requested that 40 CFR part 180 be amended 
by establishing an exemption from the requirement of a tolerance for 
residues of ferric citrate. No comments were received in response to 
the notice of filing.
    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. Pursuant to section 408(c)(2)(B) of FFDCA, in 
establishing or maintaining in effect an exemption from the requirement 
of a tolerance, EPA must take into account the factors set forth in 
section 408(b)(2)(C) of FFDCA, which 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

[[Page 17912]]

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. Provided below in 
Unit III is a brief summary and conclusions for the Agency's review of 
ferric citrate. The full Inert Ingredient Decision Document for this 
action is available on EPA's Electronic Docket at http://
www.regulations.gov/ under docket number EPA-HQ-OPP-2006-0479.

III. 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 ferric 
citrate is discussed in this unit.
    The Agency reviewed the available information on ferric citrate and 
determined that the toxicity database is sufficient. The toxicity 
studies summarized below are from the published literature; their full 
references are provided in the Decision Document. In summary, from what 
is known about the sulfates of iron (as opposed to the citrate), it 
appears that ferric citrate is not acutely toxic via the oral route. In 
subchronic toxicity using mice, no effects were noted at the maximum 
tolerated dose. In chronic toxicity testing, no effects were seen at 
1,200 parts per million (ppm). Ferric citrate has not been shown to be 
mutagenic or carcinogenic. Finally, no developmental and reproductive 
effects have been shown.
    Acute toxicity. No acute toxicity studies per se were identified 
for ferric citrate. In 2002 the Agency reassessed the tolerance 
exemptions for the mineral acids and their salts. Among the chemicals 
assessed were the iron sulfates. Acute toxicity values included: oral 
LD50 rat--1,487 to 2,102 milligrams/kilograms (mg/kg); oral 
LD50 mice--1,520 mg/kg; and dermal LD50 rabbit--
2,000 mg/kg. The National Academy of Sciences Institute of Medicine 
(IOM) discusses reports of acute toxicity resulting from overdoses of 
medicinal iron, especially in young children. Accidental iron overdose 
is the most common cause of poisoning deaths in children under six 
years of age in the U.S. The severity of iron toxicity is related to 
the amount of elemental iron absorbed. Gastrointestinal (GI) 
manifestations occur following the ingestion of 20 milligrams/kilograms 
body weight (mg/kg bw) and systemic toxicity may occur following the 
ingestion of 60 mg/kg bw. Vomiting and diarrhea characterize the 
initial stages of iron intoxication while later systemic effects can 
include those involving the heart, central nervous system, kidney, 
liver, and blood. IOM reports that in studies with adults, GI effects 
were seen at 50 milligrams/day (mg/day) of elemental iron; this finding 
is supported by other studies showing similar effects.
    Subchronic toxicity. The open literature reports a study where 
ferric citrate was administered to mice in drinking water at doses of 
0; 0.06; 0.12; 0.25; 0.5; or 1% (which is equivalent to 0; 600; 1,200; 
2,500; 5,000; or 10,000 ppm) for 13 weeks. The investigators determined 
that the maximum tolerated dose is 1,200 ppm.
    Mutagenicity. The open literature provides results of Ames testing 
(with S. typhimurium strains TA92, TA 1535, TA100, TA1537, TA94, and 
TA98) and chromosomal aberration testing (with Chinese hamster 
fibroblasts). In the Ames test using 25 milligrams/plate (mg/plate) of 
ferric citrate (the maximum dose), no significant increases in the 
number of revertant colonies were detected in any S. typhimurium 
strains. In the chromosomal aberration testing using 0.5 milligrams/
milliLiters (mg/mL) (the maximum dose), polyploidy was observed in 3% 
of the cells after 48 hours and structural aberration was observed in 
1% of the cells after 48 hours; the investigators concluded that these 
results were negative for chromosomal aberration.
    Chronic toxicity. In a study reported in the open literature, 
ferric citrate was administered to mice in drinking water at doses of 
0; 0.06; or 0.12% (which is equivalent to 0; 600 or 1,200 ppm) for 96 
weeks. No evidence of chronic toxicity or carcinogenicity was 
demonstrated in the study.
    Developmental and reproductive toxicity. To determine if toxic 
fetal serum iron levels are reached when maternal serum iron 
concentrations rise above what the body can homeostatically maintain, 
investigators dosed pregnant sheep with toxic doses of iron. 
Specifically, four gravid ewes were dosed with ferric chloride at 2 mg/
kg/bw via intravenous administration over 60 minutes; this route was 
chosen over the oral route because only a small amount of iron is 
absorbed from the gastrointestinal tract after overdose. A significant 
rise was observed in the maternal serum iron concentration but not in 
that of the fetuses. The investigators concluded that the fetus is 
protected from elevated maternal serum iron concentrations during the 
third trimester of pregnancy, a period when the fetus acquires most of 
the iron that it needs during the gestational period.

IV. Aggregate Exposures

    In examining aggregate exposure, FFDCA section 408 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 does not have information available to assess the potential for 
exposure to ferric citrate in consumer products. Nevertheless, given: 
The natural and ubiquitous occurrence of iron-containing compounds in 
the environment; iron's known role in human physiology; and its 
presence in various foods such as beef, soybeans, lentils, and spinach, 
it is unlikely that residential exposures of concern would result from 
the use of ferric citrate in nonpesticide products and as an ingredient 
in pesticide. Therefore, no further aggregate assessment is necessary.
    Dietary Exposure Food. EPA estimated dietary exposures for use of 
ferric citrate as an inert ingredient using DEEM\(tm)\, or Dietary 
Exposure Evaluation Model, a generic screening model that assumes that 
the inert ingredient is used on all commodities and that 100 percent of 
crops are treated with the inert ingredient. Generic chronic exposure 
for the overall U.S. population was estimated at 0.12 mg/kg/day.
    2. Drinking water exposure. Iron concentrations in groundwater have 
been reported to range <0.5 to 100 mg/L; higher values have been found 
in the absence of oxygen and in the presences of organic matter. In 
surface waters, iron concentrations can vary widely, ranging from 61 to 
2,680 milligrams/Liters (mg/L).

V. 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

[[Page 17913]]

``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 ferric citrate and any 
other substances and, this material does not appear to produce a toxic 
metabolite produced by other substances. For the purposes of this 
tolerance action, therefore, EPA has not assumed that ferric citrate 
has 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/.

VI. Determination of Safety for U.S. Population, Infants and Children

    Based on the information in this preamble, EPA concludes that there 
is a reasonable certainty of no harm from aggregate exposure to 
residues. Accordingly, EPA finds that exempting from the requirement of 
a tolerance will be safe.

VII. Other Considerations

A. Analytical Method

    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 
ferric citrate (CAS Reg. No. 2338-05-8), nor have any CODEX Maximum 
Residue Levels (MRLs) been established for any food crops at this time.

VIII. 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, 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 tolerance 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 6, 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).

IX. 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: March 21, 2008.
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. 180.910 the table is amended by adding alphabetically the 
following inert ingredient 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
------------------------------------------------------------------------
                              * * * * * * *
Ferric Citrate (CAS Reg. No.      ..................  Stabilizer
 2338-05-8)
                              * * * * * * *
------------------------------------------------------------------------

[[Page 17914]]

[FR Doc. E8-6818 Filed 4-1-08; 8:45 am]

BILLING CODE 6560-50-S