Exemptions from Requirements of Tolerances:
Federal Register: March 30, 2011 (Volume 76, Number 61)
Rules and Regulations
Page 17556-17561
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
DOCID:fr30mr11-8
ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 180
EPA-HQ-OPP-2010-0097; FRL-8867-7
Sodium Ferric Ethylenediaminetetraacetate; 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 sodium ferric ethylenediaminetetraacetate (EDTA) in or on all food commodities when applied as a molluscicide and used in accordance with good agricultural practices. W. Neudorff GmbH KG submitted a petition to EPA under the
Federal Food, Drug, and Cosmetic Act (FFDCA), requesting an exemption from
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the requirement of a tolerance. This regulation eliminates the need to establish a maximum permissible level for residues of sodium ferric
EDTA under the FFDCA.
DATES: This regulation is effective March 30, 2011. Objections and requests for hearings must be received on or before May 31, 2011, 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-2010-0097. 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 Office of Pesticide Programs (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: John Fournier, Biopesticides and
Pollution Prevention Division (7511P), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: (703) 308-0169; e-mail address: fournier.john@epa.gov.
SUPPLEMENTARY INFORMATION:
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General Information
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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.
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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.gpoaccess.gov/ecfr. To access the harmonized test guidelines referenced in this document electronically, please go to http:// www.epa.gov/oscpp and select ``Test Methods and Guidelines.''
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How can I file an objection or hearing request?
Under FFDCA section 408(g), 21 U.S.C. 346a(g), any person may file an objection to any aspect of this regulation and may also request a hearing on those objections. You must file your objection or request a hearing on this regulation in accordance with the instructions provided in 40 CFR part 178. To ensure proper receipt by EPA, you must identify docket ID number EPA-HQ-OPP-2010-0097 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
May 31, 2011. Addresses for mail and hand delivery of objections and hearing requests are provided in 40 CFR 178.25(b).
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of the filing that does not contain any 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 a copy of your non-CBI objection or hearing request, identified by docket ID number EPA-HQ-OPP-2010-0097, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: 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.
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Background and Statutory Findings
In the Federal Register of September 30, 2010 (75 FR 60452) (FRL- 8837-2), 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 9F7668) by W. Neudorff GmbH KG, An der M[uuml]hle 3,
Postfach 1209, 31860 Emmerthal, Germany (c/o Walter G. Talarek, P.C., 1008 Riva Ridge Dr., Great Falls, VA 22066-1620). The petition requested that 40 CFR part 180 be amended by establishing an exemption from the requirement of a tolerance for residues of sodium ferric EDTA.
This notice referenced a summary of the petition prepared by the petitioner, W. Neudorff GmbH KG, which is available in the docket, http://www.regulations.gov. There were no comments 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 exemption 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 require 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.''
Additionally, section 408(b)(2)(D) of FFDCA requires that the Agency consider ``available information
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concerning the cumulative effects of a particular pesticide's residues'' and ``other substances that have a common mechanism of toxicity.''
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.
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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.
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Overview of Sodium Ferric EDTA
The pesticidal active ingredient, sodium ferric EDTA, is a molluscicide that has historically been used to control terrestrial slugs and snails in agriculture and on ornamental landscaping. The compound is comprised of iron in a sodium chelate. This chelate forms a soluble, complex molecule with iron ions, inactivating the ions so that they cannot normally react with other elements or ions to produce precipitates or scale. In this form, the iron is more bioavailable than in other mineral sources (Ref. 1). Bioavailability of iron is an essential quality of sodium ferric EDTA as the iron in this compound is responsible for controlling slugs and snails. That is, when slugs or snails ingest sodium ferric EDTA, the iron in the compound interacts with hemocyanin, a copper-based respiratory protein common to the blood of mollusks and responsible for their oxygen transport. This interaction with hemocyanin causes suffocation and eventually results in the death of slugs and snails. Iron does not have this interaction, however, in organisms that do not use hemocyanin for oxygen transport
(e.g., mammals).
Iron is a necessary nutrient for all mammals and other vertebrates because it is a component of hemoglobin, the oxygen transport protein found in red blood cells of vertebrates. It is the most abundant element on Earth and, as such, can be found in most soil and water. It is an essential nutrient listed as Generally Recognized as Safe (GRAS) by the Food and Drug Administration (FDA) for direct addition to food
(21 CFR 184.1375) and is added to commonly consumed, fortified foods such as enriched flour, bread, pasta, and grains. Sodium Ferric EDTA is allowed as a direct food additive by the FDA and is used as a source of iron for nutritional fortification in foods such as powdered meal replacements, flavored milk, and fruit-flavored beverages (Ref. 2), as well as soy, fish, teriyaki, and hoisin sauces (Ref. 3). The compound is also a common constituent of many cosmetic products and, despite being present at much higher concentrations than those found in sodium ferric EDTA end-use pesticide products used for control of slugs and snails, has an extensive history of safe use as an agricultural fertilizer.
In 2008, EPA registered the first sodium ferric EDTA-containing product for control of slugs and snails. EPA assessed the risks to human health and concluded that, when sodium ferric EDTA was used in accordance with widespread and commonly recognized practices, no unreasonable adverse effects on the environment were expected (Ref. 4).
At the time of this initial sodium ferric EDTA registration, the applicant did not petition EPA to establish a tolerance or tolerance exemption because all uses were non-food. On December 6, 2009, however,
EPA was petitioned by W. Neudorff GmbH KG to establish an exemption from the requirement of a tolerance for residues of sodium ferric EDTA in or on all food commodities. Accordingly, EPA has completed a risk assessment of mammalian toxicology data submitted in support of this request. The overall conclusions from these data are described in Unit
III.B., while more in-depth synopses of the study results can be found in the risk assessment and Biopesticides Registration Action Document provided as references in Unit IX. (Refs. 5 and 6).
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Biochemical Pesticide Human Health Assessment Data Requirements 1. Acute toxicity. Tier I acute toxicity studies of technical grade sodium ferric EDTA (Slugkil MP, containing 71.42% sodium ferric EDTA) showed that the active ingredient is a Toxicity Category III (slightly toxic) compound via the oral and dermal routes of exposure, a Toxicity
Category III (slightly irritating) compound via the dermal and eye routes of exposure, and a Toxicity Category IV (practically nontoxic) compound for inhalation exposure. Moreover, sodium ferric EDTA is not a dermal sensitizer. Given the results of these studies, no additional toxicity (i.e., Tiers II or III) or residue data are required to support food uses of this biochemical active ingredient. These acute toxicity studies confirm sodium ferric EDTA's low toxicity profile. i. The acute oral median lethal dose (LD50) for sodium ferric EDTA in rats was greater than 2,000 milligrams per kilogram (mg/ kg) and confirmed low toxicity through oral exposure (Master Record
Identification Number (MRID No.) 47942507). Sodium Ferric EDTA is classified as Toxicity Category III for acute oral toxicity. ii. The acute dermal LD50for sodium ferric EDTA in rats was greater than 2,000 mg/kg, which confirmed low dermal toxicity (MRID
No. 47942508). Sodium Ferric EDTA is classified as Toxicity Category
III for acute dermal toxicity. iii. The acute inhalation median lethal concentration
(LC50) for sodium ferric EDTA in rats was greater than 2.75 milligrams per liter (mg/L) and showed practically no inhalation toxicity (MRID No. 47942512). Sodium Ferric EDTA is classified as
Toxicity Category IV for acute inhalation toxicity. iv. A primary eye irritation study showed that exposure to sodium ferric EDTA will cause temporary, mild eye irritation (MRID No. 47942509). Accordingly, EPA has determined that sodium ferric EDTA is
Toxicity Category III for primary eye irritation. v. A primary dermal irritation study showed that exposure to sodium ferric EDTA is slightly irritating (MRID No. 47942510) and a skin sensitization study showed that sodium ferric EDTA is not a sensitizer to the skin (MRID No. 47942511). Accordingly, EPA has determined that sodium ferric EDTA is Toxicity Category III for dermal irritation. 2. Subchronic toxicity.--i. Submission of 90-day oral toxicity data was waived by EPA because the acute oral toxicity study demonstrated sodium ferric EDTA's low toxicity (LD50>2,000 .mg/kg). In their waiver rationale, the petitioner also cited information from
EPA's 2008 sodium ferric EDTA Biopesticides Registration Action
Document (BRAD):
No references for feeding studies using sodium ferric EDTA were located in the published literature. Rats fed low mineral diets with or without calcium disodium EDTA for four months had reduced weight gain, but their general condition was comparable to that of controls
(Ref. 7). Rats fed 1%, 5%, or 10% disodium salt of EDTA for 90 days had significantly lower food consumption and weight gain than controls (Ref. 8). Hematology was comparable among all groups, except that prothrombin time was increased in the 10% group. The only significant necropsy finding was pale livers in the 10% group.
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Mice fed 3,750 or 7,500 ppm trisodium EDTA for 103 weeks had no treatment-related clinical signs, and gross and microscopic pathology were unremarkable (Ref. 9). A companion study conducted by
NCI using rats produced the same results (Ref. 9). In a 12-month feeding study using dogs, Oser et al (1963) found no significant changes in hematology or urinalysis parameters, and no abnormal gross or microscopic findings in groups receiving up to 250 mg/kg body weight/day of calcium disodium EDTA (Ref. 10).
The information cited above refers to feeding studies using sodium EDTA and calcium disodium EDTA. The Agency has assessed the toxicity profile of these and other EDTA salts (Refs. 11 and 12), and concluded that they are closely related. This information sufficed for the assessment of toxicological risk characterization of sodium ferric EDTA.
Additionally, iron is an essential nutrient listed as GRAS by the
FDA, and both iron and sodium ferric EDTA are allowed as direct food additives to increase the nutritional content of food and food supplements. Sodium Ferric EDTA is also used in agriculture as a fertilizer. Given all of this information, EPA concluded that no subchronic oral toxicity is expected when this compound is used in accordance with good agricultural practices. ii. Submission of 90-day dermal toxicity data was waived by EPA because acute guideline studies demonstrated that sodium ferric EDTA has low dermal toxicity (LD50>2,000 mg/kg), is a slight dermal irritant, and is not a dermal sensitizer. Repeated dermal exposure, under conditions of product use at a concentration that could be toxic, is not anticipated. iii. Submission of 90-day inhalation data was waived by EPA because the acute inhalation toxicity study demonstrated sodium ferric EDTA's lack of toxicity (Toxicity Category IV). Repeated inhalation exposure, under conditions of product use at a concentration that could be toxic, is not anticipated. 3. Developmental toxicity and mutagenicity. Acceptable waiver requests were submitted to address the data requirements for
Developmental toxicity and Mutagenicity (OPPTS 870.3700). The Agency concluded that humans are regularly exposed to iron found abundantly in nature and from the use of sodium ferric EDTA as fertilizer. No negative effects of sodium ferric EDTA have been reported because of its low toxicity and low water solubility, which decreases its absorption in the intestine. Moreover, the active ingredient is not a mutagen nor is it related to any known classes of mutagens. After considering the aforementioned information and the extensive history of use of sodium ferric EDTA in agriculture and food without deleterious effects, EPA waived the requirement to submit developmental toxicity and mutagenicity data.
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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).
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Dietary Exposure 1. Food. The primary route of sodium ferric EDTA exposure to the general population will be through consumption of food; however, there is no reason to expect that practical use of sodium ferric EDTA, in accordance with good agricultural practices, will constitute any significant hazard.
Sodium Ferric EDTA is comprised of iron in a sodium chelate. Iron is abundant in nature, an essential nutrient, and listed as GRAS for direct addition to food (21 CFR 184.1375). Sodium Ferric EDTA is regarded as safe for use as a dietary supplement to increase iron bioavailability and prevent iron deficiency. In humans, iron is an essential nutrient that is vital to the processes by which cells generate energy. It is available to animals from food derived from other animals and plants.
When sodium ferric EDTA is ingested, the chelate holds the iron in the stomach until pH rises in the upper small intestine. As pH rises, the strength of the complex progressively diminishes, allowing exchange with other metals and iron for absorption. Iron dissociates from the
EDTA moiety and is released in the duodenum prior to absorption. Only a very small fraction of the sodium ferric EDTA complex (less than 1%) is absorbed intact. Intact EDTA metal complexes are rapidly excreted; they do not accumulate or undergo biotransformation (Ref. 13).
European Food Safety Authority Panel on Food Additives and Nutrient
Sources added to Food (2010) concluded that, when sodium ferric EDTA is used in food supplements at levels that provide 22.3 milligrams (mg) of iron/day for adults and 11.1 mg of iron/day for children, the use of sodium ferric EDTA as a source of iron in foods is of no safety concern as long as it does not lead to an exposure of EDTA above 1.9 mg/kg/day.
Exposure to EDTA and salts of EDTA already occurs through certain
FDA-approved uses as food additives, in sanitizing solutions, and in pharmaceutical products, or through their use in soaps, shampoos, or cosmetics. EDTA has also been administered safely under medical supervision as treatment for heavy metal poisoning. The results of toxicity testing and information found in public literature indicate that there is no risk to human health from residues of sodium ferric
EDTA in food crops. Furthermore, residues from the formulations in agricultural use sites (certified limits
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