FOE 5043 Pesticide Petition Filing 4/97
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
SUMMARY: This notice announces the initial filing of pesticide petitions
proposing the establishment of regulations for residues of certain pesticide
chemicals in or on various agricultural commodities. DATES: Comments,
identified by the docket control number PF-723, must be received on or before
May 2, 1997.
ADDRESSES: By mail submit written comments to: Public Response and Program
Resources Branch, Field Operations Divison (7505C), Office of Pesticides
Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC
20460. In person bring comments to: Rm. 1132, CM #2, 1921 Jefferson Davis
Highway, Arlington, VA.
Comments and data may also be submitted electronically by following the
instructions under "SUPPLEMENTARY INFORMATION." No confidential business
information should be submitted through e-mail.
Information submitted as a comment concerning this document may be claimed
confidential by marking any part or all of that information as "Confidential
Business Information" (CBI). CBI should not be submitted through e-mail.
Information marked as CBI will not be disclosed except in accordance with
procedures set forth in 40 CFR part 2. A copy of the comment that does not
contain CBI must be submitted for inclusion in the public record. Information
not marked confidential may be disclosed publicly by EPA without prior notice.
All written comments will be available for public inspection in Rm. 1132 at
the address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: The product manager listed in the table
Product Manager telephone number Address
Connie Welch (PM 21) 703-305-6226 Rm. 227, CM #2,
e-mail: 1921 Jefferson
email@example.com Davis Hwy,
Cynthia Giles-Parker (PM 22) Rm. 229, CM #2,
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as follows
proposing the establishment and/or amendment of regulations for residues of
certain pesticide chemicals in or on various raw agricultural commodities
under section 408 of the Federal Food, Drug, and Comestic Act (FFDCA), 21
U.S.C. 346a. EPA has determined that these petitions contain data or
information regarding the elements set forth in section 408(d)(2); however,
EPA has not fully evaluated the sufficiency of the submitted data at this time
or whether the data supports grantinig of the petition. Additional data may be
needed before EPA rules on the petition.
The official record for this notice of filing, as well as the public version,
has been established for this notice of filing under docket control number PF-
723 (including comments and data submitted electronically as described below).
A public version of this record, including printed, paper versions of
electronic comments, which does not include any information claimed as CBI, is
available for inspection from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The official record is located at the address in
"ADDRESSES" at the beginning of this document.
Electronic comments can be sent directly to EPA at: firstname.lastname@example.org
Electronic comments must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Comment and data will also be
accepted on disks in Wordperfect 5.1 file format or ASCII file format. All
comments and data in electronic form must be identified by the docket number
(insert docket number) and appropriate petition number. Electronic comments on
this proposed rule may be filed online at many Federal Depository Libraries.
List of Subjects
Environmental protection, Agricultural commodities, Food additives, Feed
additives, Pesticides and pests, Reporting and recordkeeping requirements.
Dated: March 24, 1997.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Below summaries of the pesticide petitions are printed. The summaries of the
petitions were prepared by the petitioners. The petition summary announces the
availability of a description of the analytical methods available to EPA for
the detection and measurement of the pesticide chemical residues or an
explanation of why no such method is needed.
1. Bayer's Corporation
EPA has received a pesticide petition (PP 6F4631) from Bayer Corporation, 8400
Hawthorne Road, Kansas City, MO 64120-0013, proposing pursuant to section
408(d) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend
40 CFR Part 180 by establishing tolerances for residues of the herbicide, FOE
5043, N-(4-Fluorophenyl)-N-(1- methylethyl)-2[[5-(trifluoromethyl)-1,3,4-
thiadiazol-2-yl]oxy]acetamide in or on the raw agricultural commodities, field
corn grain at 0.05 parts per million (ppm), field corn forage at 0.4 ppm,
field corn stover (fodder) at 0.4 ppm, soybean seed at 0.1 ppm, milk at 0.01
ppm, meat at 0.05 ppm, and meat byproducts at 0.05 ppm. The proposed
analytical method is gas chromatography/mass spectrometry with selected ion
monitoring. (PM 22)
1. Chemical uses. FOE 5043 use on field corn and soybeans provides selective
weed control for a wide spectrum of annual grasses and small- seeded broadleaf
weeds, with exceptional strength on barnyard grass, large crabgrass, fall
panicum and foxtail species. Application technique: Products containing FOE
5043 can be applied preplant surface, preplant incorporated, or preemergence
for control of emerging weeds. Applications can be made up to 45 days before
planting. Applications may be made using standard low pressure ground
herbicide boom sprayers equipped with suitable nozzles and screens. The
products containing FOE 5043 may be applied either as a single or a split
application. Application rates range from 0.442 to 0.884 pounds active
ingredient (a.i.) of FOE 5043 per acre depending on the soil texture and soil
organic matter content. Tank mix combinations with selected products may
provide additional weed control.
2. FOE 5043 Safety. Bayer has submitted over 65 separate toxicology studies in
support of tolerances for FOE 5043. Among the submissions, a finding of
particular interest was the observation that in the long- term data compiled
for FOE 5043, provided no indications of a potential to induce either
carcinogenic or reproductive signs of toxicity. In addition, developmental no-
observed-adverse effects levels (NOAELs) of 25 milligrams body weight per day
(mg/kg bwt/day) were established for both the rat and rabbit.
The following mammalian toxicity studies have been conducted to support the
tolerance of AXIOM DF (contains FOE 5043 and metribuzin):
i. A rat acute oral study with an LD50 of 2,347 mg/kg (male) and 2,027 mg/kg
ii. A rabbit acute dermal with an LD50 of > 2,000 mg/kg.
iii. A rat acute inhalation with an LD50 of > 977 mg/m3.
iv. A primary eye irritation study in the rabbit which showed mild irritation.
v. A primary dermal irritation study which showed no irritation.
vi. A primary dermal sensitization study which showed no sensitization.
The following mammalian toxicity studies, derived from exposure to the
technical form of the chemical, have been conducted to support the tolerance
of FOE 5043:
i. A rat acute oral study with an LD50 of 1,617 mg/kg (male) and 589 mg/kg
ii. A rat acute dermal LD50 of 2,000 mg/kg bwt. iii. A rat acute inhalation
LC50 of 3,740 mg/m3 (male and female).
iv. A primary eye irritation study in the rabbit which showed no irritation.
v. A primary dermal irritation study which showed no irritation. vi. A primary
dermal sensitization study which showed no sensitization.
vii. An acute neurotoxicity study with a no-observed effect level (NOEL) for
FOB, motor and locomotor activity of 75 mg/kg bwt/day for males and females.
viii. A 90-day feeding study in the rat with a NOEL of 1.7 mg/kg bwt/day.
ix. A 90-day subchronic neurotoxicity study in the rat with a neurotoxicity
and overall NOEL of 120 ppm.
x. A 24-months chronic feeding/oncogenicity study in the rat with an overall
NOEL of 1.2 mg/kg bwt/day in males and females based on liver, kidney,
hematologic and thyroid effects. There was no evidence of an oncogenic
xi. A 90-day feeding study in dogs with a NOEL of 50 ppm, based on liver
hematology, and thyroid effects.
xii. A 12-month feeding study in dogs with a NOEL of 40 ppm, based on
hematology and thyroid effects.
xiii. A mouse oncogenicity study which provided no evidence of oncogenicity.
xiv. An oral teratology study in the rat with maternal and developmental
NOAELs of 25 mg/kg bwt/day.
xv. An oral teratology study in the rabbit with maternal and fetal NOELs of 5
and 25 mg/kg bwt/day respectively.
xvi. An two-generation reproduction study in the rat with a NOEL for
reproductive and parental toxicity of 500 and 20 ppm, respectively.
xvii. Ames assay: Negative
xviii. Unscheduled DNA synthesis: Negative xix. Mouse Micronucleus Assay:
Negative. 3. Threshold effects-- chronic effects. Based on the available
chronic toxicity data, Bayer believes the Reference Dose (RfD) for FOE 5043
should be 0.0114 mg/kg/day. The RfD for FOE 5043 is based on a 1 year chronic
toxicity study in the dog with a threshold No Observed Effect Level (NOEL) of
1.14 mg/kg/day and an uncertainty factor of 100.
Acute toxicity. EPA recently proposed a tiered approach to estimate acute
dietary exposure. The methods proposed by the EPA were reviewed and supported
by the FIFRA Scientific Advisory Panel (SAP, 1995). EPA's Tier 1 method is
based on the assumption that residue concentrations do not vary. The analysis
assumes that all residues have the same magnitude, typically the highest field
trial residue or tolerance value. This value is assumed for all points along
the consumption distribution, resulting in a distribution of dietary exposure.
For the acute analysis for FOE 5043, a Tier 1 analysis was conducted for the
overall U.S. population, infants, children 1 to 6 years of age, females 13
years and older, and males 13 years and older. Using the NOEL of 138 mg/kg
derived from the acute oral toxicity study in rats, the following margins of
exposure were calculated (margins of exposure of 100 or more are considered
Population Group Margin of Exposure
Population-All Seasons............... 94,741
Infants................................... 64,986 Children 1 to
6........................... 76,494 Women 13 to 50 years old..................
191,418 Men 13 years and older.................... 109,805 -------------------
4. Non-threshold Effects-- carcinogenicity. Using the Guidelines for
Carcinogen Risk Assessment, Bayer believes FOE 5043 to be in Group E for
carcinogenicity--no evidence of carcinogenicity--based on the results of
carcinogenicity studies in three species. There was no evidence of
carcinogenicity in an 18-month feeding study in mice, a 2- year feeding study
in rats, or a 1-year feeding study in dogs at the dose levels tested. The
doses tested are adequate for identifying a cancer risk. Thus, a cancer risk
assessment should not be necessary for FOE 5043.
5. Aggregate Exposure. For purposes of assessing the potential dietary
exposure under the proposed tolerances for FOE 5043, the estimated aggregate
exposure was based on the Theoretical Maximum Residue Concentrations (TMRC)
and the proposed tolerances (The TMRC is a worst case estimate of dietary
exposure since it is assumed that 100 % of all crops for which tolerances are
established are treated and that pesticide residues are present at the
tolerance levels.). Registration for FOE 5043 and AXIOM are currently being
sought on field corn and soybeans. FOE 5043 and AXIOM are not registered for
any uses. Tolerances are proposed (pesticide petition number 6F 4631) for FOE
5043 on the following Raw Agricultural Commodities (RAC); field corn grain
(0.05 ppm), forage (0.4 ppm) and stover (fodder) (0.4 ppm), soybean seed (0.1
ppm), milk (0.01 ppm), meat (0.05 ppm), and meat byproducts (0.05 ppm). The
TMRC is obtained by multiplying the tolerance level for these commodities by
consumption data which estimates the amounts of corn and soybean products
eaten by various human population subgroups. Tolerances are proposed for milk,
meat and meat byproducts because residues for FOE 5043 can be transferred from
corn and soybean based feeds through livestock to humans.
This dietary exposure estimate assumes that 100% of these crops are treated
with FOE 5043 and that the residues of FOE 5043 found in these crops would
occur at the proposed tolerance levels. These assumptions result in an
overestimate of exposure. In making a safety determination for these
tolerances this conservative exposure estimate has been taken into account.
Other potential sources of exposure of the general population to residues of
FOE 5043 are residues in drinking water and exposure from non-occupational
sources. In ongoing ground water monitoring studies, trace levels of FOE 5043
residues (less that 1 part per billion (ppb) total residues) have been
detected in ground water. These studies are being performed at sites with
vulnerable shallow aquifers and large amounts of irrigation are being applied
monthly. The highest residue level detected is well below the anticipated
life-time Health Advisory Level of 84 ppb. If residues of FOE 5043 do occur in
ground water used for drinking water they will be far below the level which
causes concern. Based on the available data, no significant residues of FOE
5043 are anticipated to occur in surface water used for drinking water. Since
registration is not being sought for any residential or homeowner uses no
other potential for exposure to FOE 5043 residues exists.
The toxicological profile for FOE 5043 is fundamentally characterized by
structural- and functional-related alterations in thyroid, hematologic and
hepatic parameters. These sort of changes are not uncommon among herbicides.
Since residues of FOE 5043 and its degradates will occur in raw agricultural
commodities and processed foods in the high parts per billion or low parts per
million range there is no compelling evidence that suggests a cumulative
effect (i.e., potentiated, additive, or synergistic response) might occur or
be anticipated in the human following exposure to multiple chemical agents
with similar toxicological profiles and/or mechanisms of toxicity.
6. Determination of safety for U.S. population--Reference dose (RfD). Using
the conservative exposure assumptions described above, based on the
completeness and reliability of the toxicity data, the aggregate exposure to
FOE 5043 will utilize 2.1% of the RfD for the U.S. population. EPA generally
has no concern for exposures below 100 % of the RfD. Therefore, based on the
completeness and reliability of the toxicity data and the conservative
exposure assessment, Bayer concludes that there is a reasonable certainty that
no harm will result from aggregate exposure to residues of FOE 5043, including
all anticipated dietary exposure and all other non-occupational exposures.
7. Determination of Safety for Infants and Children. The possibility of FOE
5043 induced developmental toxicity was suggested in preliminary and non-
definitive toxicity studies using rats (> 175 mg/kg bwt/day) and rabbits (>
125 mg/kg bwt/day). However NOAELs for developmental effects were ultimately
established in the definitive studies. Those values, as mentioned previously,
were 25 mg/kg bwt/day in the rat and 25 mg/kg bwt/day in the rabbit.
Reference Dose (RfD). Using the conservative exposure assumptions described
previously, Bayer has concluded that the percent of the RfD utilized by
aggregate exposure to residues of FOE 5043 ranges from 1.1 % for non-nursing
infants, up to 5.2 % for children 1 to 6 years old. EPA generally has no
concern for exposure below 100 % of the Reference Dose. Therefore, based on
the completeness and reliability of the toxicity data and the conservative
exposure assessment, Bayer concludes that there is a reasonable certainty that
no harm will result to infants and children from aggregate exposure to the
residues of FOE 5043, including all anticipated dietary exposure and all other
non- occupational exposures.
8. Estrogenic Effects. No specific tests have been conducted with FOE 5043 to
determine whether the pesticide may have an effect in humans that is similar
to an effect produced by a naturally occurring estrogen or other endocrine
9. Chemical Residue. The qualitative nature of the residues in plants and
animals is adequately understood for the purposes of registration. Residues of
FOE 5043 do concentrate slightly (1.6x) in the processed commodity of corn
grits. No tolerance has been proposed for residue of FOE 5043 in corn grits
because anticipated residues are less than two times the limit of quantitation
for the analytical method. There are no Codex maximum residue levels
established for residues of FOE 5043 on any crop. Bayer has submitted a
practical analytical method for detecting and measuring levels of FOE 5043 in
or on food with a limit of detection that allows monitoring of food with
residues at or above the proposed tolerance levels. EPA will provide
information on this method to FDA. The method is available to anyone who is
interested in pesticide residue enforcement from the EPA's Field Operations
Division, Office of Pesticide Programs.
Fifty-five separate residue trials have been conducted with FOE 5043 on corn
and soybeans. Analysis of these trials shows that the maximum total combined
residue for FOE 5043 and its major metabolites in any commodity will be
at/below 9.75 ppm. Residues occurred at this level in soybean dry hay.
However, no tolerances have been proposed for residues of FOE 5043 on soybean
hay because the proposed labels for products containing FOE 5043 do not allow
livestock to be fed with FOE 5043 treated soybean hay.
Tolerances have been requested for residues of FOE 5043 and its major
metabolites on field corn grain (0.05 ppm), forage (0.4 ppm) and stover
(fodder) (0.4 ppm) and soybean seed (0.1 ppm), milk (0.01 ppm), meat (0.05
ppm), and meat byproducts (0.05 ppm).
The proposed tolerance levels are adequate to cover residues likely to be
present from the proposed use of FOE 5043. Therefore, no special processing to
reduce the residues will be necessary.
There is no need for tolerances in poultry or eggs since there is no
reasonable expectation of residues in these materials based on the results of
poultry metabolism studies, as well as the corn and soybean metabolism and
rotational crop studies. Calculated transfer factors are extremely low and
maximum expected residues in poultry and eggs would be in the low parts per
billion or high parts per trillion range. The anticipated residues in poultry
tissues and eggs resulting from feeding poultry FOE 5043 treated corn and or
soybeans would be far below the limit of quantitation of the analytical
No FOE 5043 food additive tolerances are proposed for field corn starch (wet
milling), field corn refined oil (wet milling), field corn flour (dry milling)
and field corn refined oil (dry milling) because no residues were detected
above the limit of quantitation in this processed commodity.
Additionally, no FOE 5043 food additive tolerances are proposed in field corn
grits (dry milling) field corn meal (dry milling), soybean meal, soybean
hulls, and soybean refined oil because the measured concentration, when
adjusted for the exaggerated application rate, was less that two times the
limit of quantitation.
No feed additive tolerances are proposed for FOE 5043 in the aspirated grain
fractions of corn and soybeans. With pre-plant and or pre-emergent modes of
application for AXIOM DF and FOE 5043 DF, no residues were expected on the
seed surface in the corn and soybean magnitude of residue studies. Therefore,
no aspirated grain fractions were collected for analysis. A tolerance has not
been proposed for soybean forage because feeding soybean hay and forage
(silage) to livestock animals is not permitted by the proposed label.
Also, no feed additive tolerances are proposed for soybean meal or hulls since
the measured concentration in the soybean processing study for these feeds,
when adjusted for the exaggerated application rate, was less that two times
the limit of quantitation.
No tolerances are proposed for corn milled by-products. Table II (September
1995) advises use residue data for corn dry-milled processed commodities
having the highest residues, excluding oils. No residues were detected in the
dry-milled processed commodities above the limit of quantitation.
10. Environmental Fate. Laboratory studies indicate that FOE 5043 residue has
the potential to be moderately mobile in soil. However the results of field
dissipation studies performed in Wisconsin and North Carolina, both corn
and/or soybean producing states, indicate that downward movement of FOE 5043
residue is limited, with no quantifiable residues being found below 18 inches.
These studies were conducted under conditions conducive to downward movement
of FOE 5043 and degradates (very high sand content, low organic matter, and
large volumes of applied irrigation).
FOE 5043 has been found to be stable to chemical hydrolysis in the pH range of
environmental concern. The compound is also stable in water and soil when
exposed to artificial sunlight.
Microbial degradation is the principal means of dissipation in soil. Half-
lives for aerobic microbial degradation range from 10 to 34 days in varying
soil types at the anticipated field application rate. Degradation of FOE 5043
in soil under aerobic conditions occurs by cleavage of the thiadiazole ring to
form 3-trifluoromethyl-1,3,4- thiadiazol-2(3H)one (FOE thiadone) and the
corresponding alcohol, N-(4- flurophenyl)-2-hydroxy-N-(1-
methylethyl)acetamide. The FOE thiadone is further metabolized to CO2, and the
alcohol is subsequently oxidized to [4-flurophenyl)(1-
methylethyl)amino]oxoacetic acid. Another major degradation product of FOE
5043 is 4-fluoro-N-methylethylaniline- sulfoacetamide which is proposed to
form through the oxidation of a cysteine conjugate intermediate. (PM 22)
[FR Doc. 97-8397 Filed 4-1-97; 8:45 am]