BIOPESTICIDES REGISTRATION ACTION DOCUMENT
Sodium Ferric Ethylenediaminetetraacetate
(PC Code 139114)
U.S. Environmental Protection Agency
Office of Pesticide Programs
Biopesticides and Pollution Prevention Division
(Last updated November 20, 2008)
-------
Ferric Sodium Ethylenediaminetetraacetate Page 2 of 17
Biopesticides Registration Action Document
TABLE OF CONTENTS
I. EXECUTIVE SUMMARY: 5
II. ACTIVE INGREDIENT OVERVIEW 6
III. REGULATORY BACKGROUND 6
A. Classification 6
B. Food Clearances and Tolerances 6
IV. RISK ASSESSMENT 6
A. Active Ingredient Characterization 6
B. Human Health Assessment 7
1. Toxicology 7
2. Dose Response Assessment 10
3. Drinking Water Exposure and Risk
Characterization 7
4.. Occupational, Residential, School and Day Care Exposure and Risk
Characterization 10
5. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation
11
6. Cumulative Effects 11
7. Risk Characterization 11
C. ENVIRONMENTAL ASSESSMENT 11
1. Ecological Hazards 11
2. Environmental Fate and Ground Water Data 13
3. Ecological Exposure and Risk Characterization 13
4. Endangered Species Assessment 10
D. EFFICACY DATA 13
V. RISK MANAGEMENT DECISION 13
A. Determination of Eligibility for Registration Error! Bookmark not defined.
B. Regulatory Decision 14
VI. ACTIONS REQUIRED BY REGISTRANTS 14
A. Determination of Eligibility for Registration Error! Bookmark not defined.
B. Reporting of Hypersensitivity Incidents 15
-------
Ferric Sodium Ethylenediaminetetraacetate Page 3 of 17
Biopesticides Registration Action Document
VII. APPENDIX A. Data Requirements (40 CFR Part 158) 15
VIII. APPENDIX B. Product Specific Information 14
IX. APPENDIX C. References 17
-------
Ferric Sodium Ethylenediaminetetraacetate Page 4 of 17
Biopesticides Registration Action Document
BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM
Office of Pesticide Programs:
Biopesticides and Pollution Prevention Division
Biochemical Pesticides Branch (BPB)
Chief
Linda A. Hollis, M.S.
Health Effects/Non-target Organisms
Russell Jones, Ph.D.
Regulatory Action Leader
Leonard Cole, M.S.
Office of General Counsel
Laurel Scalise
-------
Ferric Sodium Ethylenediaminetetraacetate Page 5 of 17
Biopesticides Registration Action Document
I. EXECUTIVE SUMMARY:
Sodium Ferric ethylenediaminetetraacetate (Sodium Ferric EDTA) is a new active ingredient
that is used to make slug and snail control products. Currently, the only end use product is a
pelleted bait intended for use as a molluscicide in agricultural, nursery, greenhouse, and home
and garden applications. When Sodium Ferric EDTA is ingested by slugs or snails, the iron in
the compound interacts with the hemocyanin common to the blood of crustaceans, and
eventually causes death.
Adequate mammalian toxicology data on the technical grade active ingredient (TGAI) are
available to support registration of products containing Sodium Ferric EDTA. Acceptable acute
guideline studies were submitted, and waivers requested for mutagenicity, developmental
toxicity, and subchronic study requirements were granted by the Biopesticides and Pollution
Prevention Division (BPPD) based on submissions from the scientific literature. Adequate non-
target data were submitted to support the registration of this technical grade active ingredient.
Due to the selectivity of Sodium Ferric EDTA for copper-based blood systems, effects on non-
target insects are not expected.
The Agency considered human exposure to Sodium Ferric EDTA in light of the relevant safety
factors in FQPA and FIFRA. A determination has been made that no unreasonable adverse
effects to the U.S. population in general, and to infants and children. No significant exposure via
drinking water is expected when Sodium Ferric EDTA is used according to the product label
directions. The product is not to be applied directly to water or to areas where surface water is
present The active ingredient is toxic to aquatic invertebrates such as daphnids, but exposure
should not occur when the product is applied according to label directions.
Based on the information discussed above, the Agency has determined that registered use of
Sodium Ferric EDTA as an active ingredient will have No Adverse Effects (NAE) on threatened
and/or endangered species. Exposure to endangered or threatened terrestrial snails and
crustaceans (isopods) is not expected since the currently listed endangered or threatened species
pursuant to the Endangered Species Act of 1973, 16 U.S.C. 1531, et seq., are not found in
locations where the product is intended for use; i.e., home gardens, turf, and agricultural lands.
The Biopesticides and Pollution Prevention Division (BPPD) reviewed data requirements for
granting registration under Section 3(c)(5) of the Federal Insecticide, Fungicide and Rodenticide
Act (FIFRA). It was determined that the data/information submitted adequately satisfy current
guideline requirements (refer to 40 CFR Subpart U § 158.2000).
-------
Ferric Sodium Ethylenediaminetetraacetate Page 6 of 17
Biopesticides Registration Action Document
II. ACTIVE INGREDIENT OVERVIEW
Common Name: Ferric (III) EDTA Complex
Chemical Names: Ferric Sodium Ethylenediaminetetraacetate
Trade & Other Names: Slug & Snail Killer
CAS Registry Number: 15708-41-5
OPP Chemical Code: 139114
Type of Pesticide: Biochemical pesticide (Insecticide).
Application rates and methods vary depending on the product. For specific information
regarding the product(s) refer to Appendix B.
III. REGULATORY BACKGROUND
On December 17, 2004, the Agency received an application filed by Woodstream Corporation,
69 Locust Street, Litiz, PA 17543 (submitted by Technology Sciences Group, Inc., 1150 18th
Street, N.W., Suite 1000, Washington, DC 20036 to register the product Safer Brand Slug &
Snail Killer containing the new biochemical active ingredient Sodium Ferric
ethylenediaminetetraacetate (Sodium Ferric EDTA) at 5.87%. A notice of receipt of this
application was published in the Federal Register June 22, 2005 (70 FR 36153).
A. Classification
On May 16, 2001, the Biochemical Classification Committee determined that the active
ingredient Iron (formulated as an Fe-Na EDTA complex) qualified to be reviewed in BPPD. The
active ingredient was classified as "Not a biochemical, but eligible for a reduced data set". The
classification is based on the abundance of Iron in nature, its low toxicity, its use as a
nurtiritional supplement, and it low water solubility.
B. Food Clearances/Tolerances
Currently, this active ingredient is not registered for use on food or feed commodities because
applications must be away from food plants.. A tolerance or exemption from the requirement of
a tolerance is not relevant.
IV. RISK ASSESSMENT
A. Active Ingredient Characterization
Sodium Ferric EDTA is the active ingredient in products to control slugs and snails. The end use
product is a granular (pellet) formulation.
-------
Ferric Sodium Ethylenediaminetetraacetate Page 7 of 17
Biopesticides Registration Action Document
The descriptions of the product formulation and production process as well as the formation of
impurities were examined by BPPD and found to be acceptable in meeting current guideline
standards. A preliminary analysis to determine the Sodium Ferric EDTA content in the end use
product was not submitted, but results from analyses of 36 batches of the TGAI by the
manufacturer were provided and determined to be acceptable by BPPD. The analytical method
is high performance liquid chromatography (HPLC) with ultraviolet visible spectrophotometry
(UV-VIS).
All product chemistry data requirements for registration of Sodium Ferric EDTA (TGAI) have
been satisfied.
B. Human Health Assessment
1. Toxicology
Adequate mammalian toxicology data are available to support registration of products containing
the new active ingredient Sodium Ferric EDTA. Acceptable acute guideline studies were
submitted, and waivers requested for the mutagenicity, developmental toxicity, and subchronic
study requirements were granted by BPPD based on submissions from the scientific literature.
Sodium Ferric EDTA is a common chelating agent that immobilizes metal ions until they are in
an environment where they are available for uptake. Chelating agents are commonly applied to
agricultural commodities. EDTA is typically used as a chelating agent for trace elements,
including iron.
Iron is an essential element for nutrition and is used in nutritional supplements. Elemental iron
is listed as Generally Regarded as Safe (GRAS) by FDA (21 CFR 184.1375). Acute iron
toxicity in humans typically results from accidental ingestion of medicinal iron or ingestion of
adult iron supplements by children. Chronic toxicity in humans is generally limited to
individuals with inherited metabolic disorders that affect iron balance, such as human leukocyte
antigen-linked hereditary haemochromatosis.
A public literature review of toxicological and exposure data (Heimbach et al., 2000) concluded
that sodium Ferric EDTA possesses very low toxicity. Heimbach et al. (2000) determined the
upper bound estimated daily intake of EDTA from sodium Ferric EDTA to be 1.15 mg/kg body
wt/day, which is less than half the acceptable daily intake of 2.5 mg/kg body wt/day determined
by the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 1974).
Sodium Ferric EDTA dissociates in the gastrointestinal tract to form iron and an EDTA salt,
which are absorbed independently. The toxicologic effects of EDTA salts should be similar
regardless of the salt form. Since EDTA-metal complexes freely exchange in the digestive tract,
assessment of EDTA-metal complexes containing metals other than iron is relevant to the
assessment of sodium Ferric EDTA.
All toxicology data requirements for Sodium Ferric EDTA have been satisfied.
a. Acute Toxicity
Acute toxicity studies submitted in support of the EP are summarized in Table 3 below. Sodium
Ferric EDTA is classified in Toxicity Category IV for acute oral toxicity, acute dermal toxicity,
acute inhalation toxicity, and primary dermal irritation; Toxicity Category I for primary eye
irritation; and is not a dermal sensitizer. Based on the review and analysis of the information,
-------
Ferric Sodium Ethylenediaminetetraacetate
Biopesticides Registration Action Document
Page 8 of 17
guideline studies, and submitted literature discussed in detail in this section of the BRAD, no
additional toxicity data are required to support the nonfood use of this of this active ingredient.
TABLE 1. Acute toxicity and primary irritation data for Sodium Ferric EDTA
Study/ OPPTS
Guideline No.
Acute Oral Toxicity
870.1100
Acute Dermal Toxicity
870.1200
Acute Inhalation Toxicity
870.1300
Primary Eye Irritation
870.2400
Primary Dermal Irritation
870.2500
Skin Sensitization
870.2600
Hypersensitivity Incidents
Results
LD50 >5000 mg/kg in male rats.
LDgQ = 5719 mg/kg in female rats.
LD50 >5000 mg/kg in rats
LC50 >2.05 mg/L in rats
Maximum average score (Draize
method) was 11.7 @ 24 hours
Very slight erythema.
Irritation index =0.3
Not a sensitizer
No data
Toxicity category
IV
IV
IV
I
IV
Not a sensitizer
No data
MRIDNo.
45848103
45848104
45848105
45848106
45848107
45848108
No data
b. Subchronic Toxicity
Waivers requested for the subchronic [90-day feeding (OPPTS 870.3100), 90-day dermal
(OPPTS 870.3250), and 90-day inhalation (OPPTS 870.3465)] and immunotoxicity study
requirements were granted by BPPD, based on the rationales below.
No references for feeding studies using Sodium Ferric EDTA were located in the published
literature. Rats fed low mineral diets with or without added calcium disodium EDTA for four
months had reduced weight gain, but their general condition was comparable to that of controls
(Yang, 1964). Rats fed 1%, 5%, or 10% disodium salt of EDTA for 90 days had significantly
lower food consumption and weight gain than controls (Wynn, et al.1970). 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.
Mice fed 3750 or 7500 ppm trisodium EDTA for 103 weeks had no treatment-related clinical
signs, and gross and microscopic pathology were unremarkable (National Cancer Institute,
1977). A companion study conducted by NCI using rats produced the same results (National
Cancer Institute, 1977). 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.
The end use product containing Sodium Ferric EDTA is a pellet that does not produce any dust
and is applied directly to the ground. Therefore, it is unlikely that there will be any dermal
exposure when the product is applied according to the label use directions. Furthermore, Sodium
Ferric EDTA was demonstrated to be practically non-toxic (Toxicity Category IV) to rats in an
acute dermal toxicity guideline study (MRID 45848104).
Since the end use product is a pellet that does not produce any dust and is applied directly to the
ground, it is unlikely that there will be any inhalation exposure when the product is applied
according to the label use directions. Furthermore, Sodium Ferric EDTA was demonstrated to
-------
Ferric Sodium Ethylenediaminetetraacetate Page 9 of 17
Biopesticides Registration Action Document
be practically non-toxic (Toxicity Category IV) to rats in an acute inhalation toxicity guideline
study (MRID 45848105).
No literature was located suggesting that Sodium Ferric EDTA impacts the immune system.
FDA has approved calcium disodium EDTA and disodium EDTA as food additives, and these
materials are added to a wide range of processed foods at levels of 200 to 500 ppm. Based on
the use of EDTA and iron supplements as food ingredients, there do not appear to be any
concerns regarding immune response safety issues.
c. Developmental Toxicity and Mutagenicity
Sodium Ferric EDTA with and without S9 activation was found to be mutagenic in a L5178Y
tk+/tk- mouse lymphoma assay, but not mutagenic with or without S9 activation in an Ames
Salmonella assay (Dunkel et al., 1999). Heimbach et al. (2000) concluded that the positive
results seen for sodium Ferric EDTA in the mouse lymphoma assay conducted by Dunkel et al.
(1999) were most likely due to the sensitivity of L5178Y cells to the abnormally high iron
concentrations. No other references suggesting that Ferric iron has mutagenic potential were
found in the literature.
In a L5178Y tk+/tk- mouse lymphoma cell forward mutation assay using trisodium EDTA
(McGregor et al., 1988), no mutagenicity was seen with or without added S9. In another study,
Heindorff et al. (1983) reported that EDTA inhibits DNA synthesis and repair, and produces a
low degree of chromosomal damage and gene mutations in vitro. However, FDA scientists
(Lerner et al., 1986) concluded that these events were spurious indicators of genotoxic potential,
likely caused by chelation of cations that are important as enzymatic cofactors involved in DNA
synthesis in the cell. According to Heindorff et al. (1983) "the mechanism(s) by which EDTA
causes genetic effects is poorly understood. Most data support the idea that EDTA itself does not
induce genotoxic effects. Such effects are probably due to the cation deficiency induced by the
sequestering agent. Consequently, the ultimate cause of genotoxic effects would consist in
variation of the cation level."
The teratogenic potential of disodium EDTA has been investigated (Swenerton and Hurley,
1971; Gasset and Akaboshi, 1977; Kimmel, 1977) with variable results. The differences in
toxicity and teratogenicity shown in the scientific literature probably relate to several factors,
such as absorption differences, stress associated with the administration of treatments, different
species and strain susceptibility, and interaction with metals (Kimmel, 1977). Since it has been
shown that EDTA may chelate zinc (Swenterton and Hurley, 1971), the exchange of iron for zinc
is the predominant reaction of concern during pregnancy because of the potential effect of
disodium EDTA on zinc balance, and the high sensitivity of the developing embryo to zinc
deficiency (Hurley and Swenerton, 1966; Swenerton and Hurley, 1971; Kimmel, 1975; and
Kimmel and Sloan, 1975). Effects of EDTA on zinc balance depend on the EDTA:zinc ratio,
and the dietary dose range of 2.5 mg EDTA/kg bw/day recommended by the FAO/WHO Expert
Committed on Food Additives (JECFA, 1974) would not be expected to have detrimental effects
on zinc balance. Overall, many of the results found in the scientific literature, including
Schardein et al. (1981), indicated little or no teratogenic effect of disodium EDTA in rats and
rabbits. Based on the submitted data, the active ingredient is not likely to be teratogenic.
d. Chronic exposure and oncogenicity assessment
Repeated dose studies are conditionally required if the potential for adverse chronic effects are
indicated based on: 1) the subchronic effect levels established in Tier I subchronic oral,
inhalation, or dermal studies; 2) the pesticide use pattern; or 3) the frequency and the level of
-------
Ferric Sodium Ethylenediaminetetraacetate Page 10 of 17
Biopesticides Registration Action Document
repeated human exposure that is expected. Oncogen!city studies are required only if Tier I
studies show that the active ingredient or any of its metabolites, degradation products, or
impurities produce any morphologic effects in any organ that could potentially lead to neoplastic
changes. None of the results of the submitted studies triggered the need for chronic exposure or
oncogenicity testing. There are no reliable data documenting carcinogenicity of Sodium Ferric
EDTA.
e. Effects on the Endocrine System
The US Environmental Protection Agency (Agency) is required under the Federal Food, Drug,
and Cosmetics Act (FFDCA), as amended by Food Quality Protection Act, to develop a
screening program to determine whether certain substances (including all pesticide active and
other ingredients) "may have an effect in humans that is similar to an effect produced by a
naturally-occurring estrogen, or other such endocrine effects as the Administrator may
designate." Following the recommendations of its Endocrine Disrupter Screening and Testing
Advisory Committee (EDSTAC), EPA determined that there was scientific basis for including,
as part of the program, the androgen- and thyroid-hormone systems, in addition to the estrogen
hormone system. EPA also adopted EDSTAC's recommendation that the Program include
evaluations of potential effects in wildlife. For pesticide chemicals, the Agency will use FIFRA
and, to the extent that effects in wildlife may help determine whether a substance may have an
effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops
and resources allow, screening of additional hormone systems may be added to the Endocrine
Disrupter Screening Program (EDSP). Based on the weight of the evidence of available data, no
endocrine system-related effects have been identified for Sodium Ferric EDTA and none is
expected since it does not share any structural similarity to any known endocrine disrupter.
2. Dose Response Assessment
No toxicological endpoints were identified; therefore, a dose response assessment was not
required.
3. Drinking Water Exposure and Risk Characterization
No significant exposure via drinking water is expected when Sodium Ferric EDTA is used
according to the product label directions. The product is not to be applied directly to water or to
areas where surface water is present, and if used as labeled, is not likely to accumulate in
drinking water. In the unlikely event that exposure via drinking water did occur, the health risk
would be expected to be minimal, based on the low acute oral and dermal toxicity of Sodium
Ferric EDTA.
4. Occupational, Residential, School and Day Care Exposure and Risk Characterization
a. Occupational Exposure and Risk Characterization
Occupational exposure to Sodium Ferric EDTA is mitigated as long as the end-use product is
used according to label directions. Occupational exposures are not included under the FFDCA
in the assessment of aggregate exposures for the purpose of establishing tolerances and
exemptions from tolerance. The signal word on the end use product label is "Caution" and
-------
Ferric Sodium Ethylenediaminetetraacetate Page 11 of 17
Biopesticides Registration Action Document
precautionary statements include "Causes moderate eye irritation. Avoid contact with eyes or
clothing. Wash thoroughly with soap and water after handling." Since the product is applied
directly to soil as a pelleted bait, there is no potential for exposure via spray drift.
b. Residential, School and Day Care Exposure and Risk Characterization
Significant human exposure to Sodium Ferric EDTA is unlikely in residential, school and day
care areas when the end use product is used according to the label directions. The end use
product is a pelleted bait intended to be applied directly to soil. A public literature review of
toxicological and exposure data (Heimbach et al., 2000) concluded that sodium Ferric EDTA
may be generally regarded as safe. Should accidental exposure occur, the health risk is expected
to be minimal, based on the low acute oral, dermal, and inhalation toxicity of Sodium Ferric
EDTA.
5. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation
There is reasonable certainty that no harm to the US population will result from aggregate
exposure to residues of Sodium Ferric EDTA. This includes all exposures for which there is
reliable information. The Agency arrived at this conclusion based on the low level of toxicity of
Sodium Ferric EDTA and the current use of EDTA and iron supplements as food ingredients by
the general public without any reported adverse effects on human health. The risks from
aggregate exposure via oral, dermal and inhalation exposure are a compilation of three low-risk
exposure scenarios and are negligible. Since there are no threshold effects of concern, the
provision requiring an additional margin of safety does not apply. Therefore, the Agency has not
used a margin of exposure (safety) approach to assess the safety of Sodium Ferric EDTA.
6. Cumulative Effects
When used as proposed, residues of Sodium Ferric EDTA will not reach levels that are of
toxicological concern. Because of its low toxicity, cumulative effects with other substances that
share a common mechanism of toxicity are not expected.
7. Risk Characterization
The Agency considered human exposure to Sodium Ferric EDTA in light of the relevant safety
factors in FQPA and FIFRA. A determination has been made that no unreasonable adverse
effects to the U.S. population in general, and to infants and children in particular, will result from
the use of Sodium Ferric EDTA when label instructions are followed.
C. ENVIRONMENTAL ASSESSMENT
1. Ecological Hazards
Ecological effects data requirements for Sodium Ferric EDTA were fulfilled by data submitted
for acute avian toxicity and by submissions from the scientific literature to support waiver
requests pertaining to toxicity and effects on non-target organisms.
-------
Ferric Sodium Ethylenediaminetetraacetate Page 12 of 17
Biopesticides Registration Action Document
An avian acute oral toxicity study (OPPTS 850.2100) was conducted in which groups often
young adult northern bobwhite quail were administered a single oral dose of 0, 275, 454, 749,
1235, or 2038 mg Sodium Ferric EDTA/kg of body weight and observed for 14 days (MRID
45848109). Three often birds in the 2038 mg/kg group died by day 3 after displaying impaired
balance, low body carriage, and hypoactivity. No mortality or adverse clinical signs occurred in
any of the other test groups. Mean feed consumption was significantly lower in groups receiving
>454 mg/kg test material for days 0-3, but was comparable to that of controls afterward. Mean
body weight of the 2038 mg/kg group was significantly lower on days 3 and 7, but was
comparable to that of controls on day 14. The no observed effect level (NOEL) for mortality
was 1235 mg/kg, and the lowest lethal dose (LLD) was >1235 mg/kg. The LD50 was >2038
mg/kg, which is practically non-toxic to birds on an acute basis.
Waivers requested for the remaining non-target organism study requirements [avian dietary
toxicity (OPPTS 850.2200), fish acute toxicity (OPPTS 850.1075), aquatic invertebrate toxicity
(OPPTS 850.1010), non-target plant testing (OPPTS 850.4100), and non-target insect toxicity
(OPPTS 850.4340)] were granted by BPPD, based on the rationales described below.
FDA has approved the use of up to 240 ppm disodium EDTA as an additive in finished animal
feed (21 CFR § 573.360). Scott and Zeigler (1963) reported that the addition of 300 ppm EDTA
to prepared diet containing 5 ppm added zinc markedly improved chick growth, which was
nearly comparable to growth of chicks fed diet containing 60 ppm zinc without added EDTA.
The iron in Sodium Ferric EDTA interacts with the hemocyanin in the bloodstream of mollusks
and crustaceans. The blood of vertebrate animals contains hemoglobin, which is iron-based,
rather than the copper-based hemocyanin. There have been no reported effects of sodium Ferric
EDTA on vertebrates having iron-based blood systems. Since both birds and fish are vertebrate
animals, field application of Sodium Ferric EDTA at label rates should present little or no risk
from ingestion of the end use product pellets. Additionally, exposure offish should not occur
when label directions are followed, as the end use product is applied directly to soil, and is not
intended for use in aquatic environments.
Freshwater invertebrate testing is not required; as stated above, the iron in Sodium Ferric EDTA
would be toxic to Daphnia, since they are crustaceans. Exposure of daphnids and other
crustaceans is not likely to occur when label directions are followed, as the end use product is
applied directly to soil, and is not intended for use in aquatic environments.
EDTA is used in specialty fertilizers to chelate inorganic sources of iron and other elements. In
soil, EDTA is eventually degraded through microbial activity, and the cations released as a result
act as inorganic ions. Tomato plants grown for 130 days in hydroponic solution containing 14C-
labelled EDTA contained 14C-labelled amino acids in addition to the 14C-EDTA, indicating
EDTA was slowly decomposed by the plants (Matsuda, 1968). In another study using tomato
plants grown in solution containing labeled iron chelate (59Fe-14C-EDTA), Hill-Cottingham and
Lloyd-Jones (1961) reported that nearly all the iron, and only about 60% of the EDTA, was
recovered after 24 days, indicating that the EDTA was decomposed by the plants. No phytotoxic
effects were reported in this study.
Due to the selectivity of Sodium Ferric EDTA for copper-based blood systems, effects on non-
target insects are not expected. The registrant's testing of the effect of Sodium Ferric EDTA
-------
Ferric Sodium Ethylenediaminetetraacetate Page 13 of 17
Biopesticides Registration Action Document
pellets on insects showed that Melyrid beetles (Dicranolaius bellulus) ladybird beetles
(Harmonia conformis), and carabid beetles (Notonomus gravis) were not affected. Sodium
Ferric EDTA was found to be toxic to sowbugs (Oniscus asellus\ pillbugs (Armadillidium
vulgare), and common woodlice (Porcellio laevis); however, these are land-living crustaceans in
which the oxygen carrier is hemocyanin.
All non-target toxicology data requirements for Sodium Ferric EDTA have been satisfied.
2. Environmental Fate and Ground Water Data
The need for environmental fate and groundwater data was not triggered because Sodium Ferric
EDTA was practically non-toxic in the avian acute oral study, and the remaining Tier I studies
were waived.
3. Ecological Exposure and Risk Characterization
Based on the studies and rationales for the data waivers discussed above, exposure and risk from
the proposed use of Sodium Ferric EDTA are expected to be minimal for non-target organisms
(with the exception of pillbugs and sowbugs). The mode of action for Sodium Ferric EDTA
targets copper-based (hemocyanin) blood systems, which are found in mollusks and crustaceans.
The active ingredient is toxic to aquatic invertebrates such as daphnids, but exposure should not
occur when the product is applied according to label directions.
4. Endangered Species Assessment
Based on the information discussed above, the Agency has determined that registered use of
Sodium Ferric EDTA as an active ingredient will have No Adverse Effects (NAE) on threatened
and/or endangered species. Exposure to endangered or threatened terrestrial snails and
crustaceans (isopods) is not expected since the currently listed endangered or threatened species
pursuant to the Endangered Species Act of 1973, 16 U.S.C. 1531, et seq., are not found in
locations where the product is intended for use; i.e., home gardens, turf, and agricultural lands.
The habitats of currently listed threatened or endangered mollusks or crustacean species range
from isolated caves and streams to wood or forests. When the product is used according to label
use directions, there are no concerns for any non-target organisms.
D. PRODUCT PERFORMANCE DATA (EFFICACY)
Submission of product performance data (OPPTS 810.3000) is listed as a requirement for all
pesticide products. Customarily, the Agency requires efficacy data to be submitted for review
only in connection with the registration of products directly pertaining to the mitigation of
disease bearing human health organisms and certain designated quarantine pests, i.e., ticks,
mosquitoes, fleas, Mediterranean fruit flies, gypsy moths, Japanese beetles, etc. For a list of
organisms considered by the Agency as "public health pests", please refer to Pesticide
Registration Notice 2002-1 (http://www.epa.gov/PR_Notices/pr2002-l.pdf).
No efficacy data were required to be submitted with this pesticide application because the active
ingredient will not be used to control any disease bearing human health organisms and certain
designated quarantine pests as discussed above.
-------
Ferric Sodium Ethylenediaminetetraacetate Page 14 of 17
Biopesticides Registration Action Document
V. Risk Management Decision
A. Determination of Eligibility for Registration
Section 3(c)(5) of FIFRA provides for the registration of new active ingredients if it is
determined that (A) its composition is such as to warrant the proposed claims for it; (B) its
labeling and other materials required to be submitted comply with the requirements of FIFRA;
(C) it will perform its intended function without unreasonable adverse effects on the
environment; and (D) when used in accordance with widespread and commonly recognized
practice it will not generally cause unreasonable adverse effects on the environment.
The four criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied
by the science assessments supporting products containing active ingredient. Such products are
not expected to cause unreasonable adverse effects, and are likely to provide protection as
claimed when used according to label instructions. Therefore, Sodium Ferric EDTA is eligible
for registration for the labeled uses.
B. Regulatory Decision
The data submitted fulfill the requirements of registration for use of Sodium Ferric EDTA to
control slugs and snails. Refer to Appendix B for product-specific information.
1. Conditional/Unconditional Registration
All data requirements are fulfilled and EPA has determined that unconditional registration of
Sodium Ferric EDTA is appropriate.
C. Environmental Justice
EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of
all people, regardless of race, color, national origin, or income, in the development,
implementation, and enforcement of environmental laws, regulations, and policies. To help
address potential environmental justice issues, the Agency seeks information on any groups or
segments of the population who, as a result of their location, cultural practices, or other factors,
may have atypical, unusually high exposure to Sodium Ferric EDTA, compared to the general
population. Please comment if you are aware of any sub-populations that may have atypical,
unusually high exposure compared to the general population.
VI. ACTIONS REQUIRED BY REGISTRANTS
The Agency evaluated all of the data submitted in connection with the initial registration of
active ingredient and determined that these data are sufficient to satisfy current registration data
requirements. No additional data are required to be submitted to the Agency at this time. For
new uses and/or changes to existing uses, additional data may be required.
Not withstanding the information stated in the previous paragraph, it should be clearly
understood that certain, specific, data are required to be reported to the Agency as a requirement
for maintaining the Federal registration for a pesticide product. A brief summary of these types
of data are listed below.
-------
Ferric Sodium Ethylenediaminetetraacetate
Biopesticides Registration Action Document
Page 15 of 17
A. Reporting of Adverse Effects
Reports of all incidents of adverse effects to the environment must be submitted to the Agency
under the provisions stated in FIFRA, Section 6(a)(2).
B. Reporting of Hypersensitivity Incidents
Additionally, all incidents of hypersensitivity (including both suspected and confirmed incidents)
must be reported to the Agency under the provisions of 40 CFR Part 158.2050(d).
VII. Appendix A. Data Requirements (40 CFR Part 158-Subpart U)
*NOTE: MRID numbers listed in the following tables are representative of supporting data for
the original registration of the product containing this active ingredient. Subsequent to this
registration, there may be additional MRIDs that support registration of other products
containing this active ingredient.
TABLE 1. Product Chemistry Data Requirements for Active Ingredient (40 CFR §
OPPTS Guideline No.
830.1550
to
830.1670
830.1700
830.1750
830.1800
Study
Product identity;
Manufacturing
process;
Discussion of
formation of
unintentional
ingredients
Analysis of samples
Certification of
limits
Analytical method
158.2030)
Results (below are example results)
45848101
46758501
47315701
47302903
45848101
47434001
46954601
45848101
45848102
Table 2. Human Toxicology Data Requirements for Sodium Ferric EDTA (40 CFR § 158.2050)
Study/OPPTS Guideline No.
Acute oral toxicity (rat)
(870.1100)
Acute dermal toxicity (rat)
(870.1200)
Acute inhalation toxicity (rat)
(870.1300)
Primary eye irritation (rabbit)
(870.2400)
Primary dermal irritation (rabbit)
(870.2500)
Dermal sensitization (guinea pig)
(870.2600)
Hypersensitivity incidents
(885.3400)
Results
LD50 >5000 mg/kg in male rats.
LD^Q = 5719 mg/kg in female rats.
LD50 >5000 mg/kg in rats
LC50 >2.05 mg/L in rats
Maximum average score (Draize method) was 11.7
@ 24 hours
Very slight erythema.
Irritation index = 0.3
Not a sensitizer
No data
Toxicity
Category /Description
IV
IV
IV
I
IV
Not a sensitizer
-------
Ferric Sodium Ethylenediaminetetraacetate
Biopesticides Registration Action Document
Page 16 of 17
Table 3. Nontarget Organism, Fate and Expression Data Requirements for Sodium Ferric EDTA (40 CFR § 158.2060)
Study/OPPTS Guideline No.
Avian acute oral toxicity
(850.2100)
Avian Dietary Toxicity
(850.2200)
Fish Acute Toxicity - Freshwater and
Marine
(850.1075)
Aquatic Invertebrate Acute Toxicity
(850.1010)
Nontarget Plant Studies
(850.4100)
Nontarget Insect Studies
(880.4350)
Results
LD50 >2038 mg/kg
(practically non- toxic)
Waived
Waived
Waived
Waived
Waived
VIII. Appendix B.
For product specific information, please refer to http://www.epa.gov/pesticides/pestlabels
-------
Ferric Sodium Ethylenediaminetetraacetate Page 17 of 17
Biopesticides Registration Action Document
IX. Appendix C.
REFERENCES
Dunkel, V.C., R.H. San, H.E. Seifried, et al. 1999. Genotoxicity of iron compounds in Salmonella
typhimurium and L5178Y mouse lymphoma cells. Environmental and Molecular Mutagenesis 33:
28-41.
Gasset, A.R. and T. Akaboshi. 1977. Embryopathic effect of opthalmic EDTA. Investigations in
Ophthalmic and Visual Science 16:652-654.
Heimbach, J., S. Rieth, F. Mohamedshah, et al. 2000. Review. Safety assessment of iron EDTA
[sodium iron (Fe^+) ethylenediaminetetraacetic acid]: summary of toxicological fortification and
exposure data. Food and Chemical Toxicology 38:99-111.
Heindorff, K., O. Aurich, A. Michaelis, et al. 1983. Genetic toxicology of ethylenediaminetetraacetic
acid (EDTA). Mutation Research 115:149173.
Hill-Cottingham, D.G. and C.P. Lloyd-Jones. 1961. Absorption and breakdown of Fe
ethylenediaminetetraacetic acid by tomato plants. Nature 189:312.
Hurley, L.S. and H. Swenerton. 1966. Congenital malformations resulting from zinc deficiency in rats.
Proceedings of the Society for Experimental Biology and Medicine 123:692-696.
JECFA. 1974. Toxicological evaluation of some food additives including anticaking agents,
antimicrobials, antioxidants, emulsifiers, and thickening agents. Joint FAO/WHO Expert Committee
on Food Addictives. WHO Tech. Rep. Ser. No. 539.
Kimmel, C.A. 1975. Fetal gonad dysgenesis following EDTA administration. Teratology 11:26A.
Kimmel, C.A. 1977. Effect of route of administration on the toxicity and teratogenicity of EDTA in the
rat. Toxicology and Applied Pharmacology 40:299-306.
Kimmel, C.A. and C.S. Sloan. 1975. Studies on the mechanism of EDTA teratogenesis. Teratology
12:330-331.
Lerner, P., A. Milbert, A. Beloian, et al. 1986. A review of the current position of the U.S. Food and
Drug Administration on EDTA compounds, including sodium iron EDTA. Center for Food Safety
and Applied Nutrition. U.S. Food and Drug Administration, Washington, DC.
Matsuda, K. 1968. Effects of EDTA on crop plants. VI. Absorption and decomposition of EDTA by
crop plants. Nippon Dojo-Hiryogaku Zasshi 39: 310-313 (abstract only).
McGregor, D.B., A. Brown, and Cattanach, P. 1988. Responses of the L5178Y tk+/-tk mouse lymphoma
cell forward mutation assay: III. 72 coded chemicals. Environmental and Molecular Mutagenesis
12:85-154.
National Cancer Institute. 1977. Bioassay of trisodium ethylenediaminetetraacetate trihydrate (EDTA)
for possible carcinogenicity. NCI-CG-TR-11, PB 270 938.
------- |