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FOE 5043 Pesticide Petition Filing 4/97

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Notice of Filing of Pesticide Petitions 

AGENCY: Environmental Protection Agency (EPA). 

ACTION: Notice.
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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 
below:

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                                                         Office location/
Product Manager        telephone number                  Address
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Connie Welch (PM 21)   703-305-6226                      Rm. 227, CM #2,
                       e-mail:                           1921 Jefferson 
                       welch.connie@epamail.epa.gov      Davis Hwy,
                                                         Arlington, VA

Cynthia Giles-Parker (PM 22)                             Rm. 229, CM #2, 
                       703-305-5540                      Do. 
                       e-mail: 
                       giles-parker.cynthia@epamail.epa.gov.
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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: opp-docket@epamail.epa.gov

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

PP 6F4631

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 
(female).

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 
(female).

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 
response.

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 
satisfactory): 

------------------------------------------------------------------------ 
Population Group	Margin of Exposure
------------------------------------------------------------------------ U.S. 
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 -------------------
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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 
effects.

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 
residue method. 

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]