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flufenacet Time-Limited Pesticide Tolerance 9/98


ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300712; FRL-6028-8] RIN 2070-AB78

Flufenacet; Time-Limited Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.
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SUMMARY: This regulation establishes a time-limited tolerance for indirect or 
inadvertent residues of N-(4-fluorophenyl)-N-(1-methylethyl)-2-[[5-
(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy]acetamide and its metabolites 
containing the 4-fluoro-N-methylethyl benzenamine moiety hereafter referred to 
as flufenacet, the proposed common chemical name, in or on certain raw 
agricultural commodities when present therein as a result of the application 
of flufenacet to field corn and soybeans as a herbicide. Bayer Corporation 
requested this tolerance under the Federal Food, Drug and Cosmetic Act 
(FFDCA), as amended by the Food Quality Protection Act of 1996 (Pub. L. 104-
170). The tolerance will expire on April 30, 2003.

DATES: This regulation is effective September 23, 1998. Objections and 
requests for hearings must be received by EPA on or before November 23, 1998.

ADDRESSES: Written objections and hearing requests, identified by the docket 
control number, [OPP-300712], must be submitted to: Hearing Clerk (1900), 
Environmental Protection Agency, Rm. M3708, 401 M St., SW., Washington, DC 
20460. Fees accompanying objections and hearing requests shall be labeled 
"Tolerance Petition Fees" and forwarded to: EPA Headquarters Accounting 
Operations Branch, OPP (Tolerance Fees), P.O. Box 360277M, Pittsburgh, PA 
15251. A copy of any objections and hearing requests filed with the Hearing 
Clerk identified by the docket control number, [OPP-300712], must also be 
submitted to: Public Information and Records Integrity Branch, Information 
Resources and Services Division (7502C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. In 
person, bring a copy of objections and hearing requests to Rm. 119, Crystal 
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.

    A copy of objections and hearing requests filed with the Hearing Clerk may 
also be submitted electronically by sending electronic mail (e-mail) to: opp-
docket@epamail.epa.gov. Copies of objections and hearing requests must be 
submitted as an ASCII file avoiding the use of special characters and any form 
of encryption. Copies of objections and hearing requests will also be accepted 
on disks in WordPerfect 5.1/6.1 file format or ASCII file format. All copies 
of objections and hearing requests in electronic form must be identified by 
the docket control number [OPP-300712]. No Confidential Business Information 
(CBI) should be submitted through e-mail. Electronic copies of objections and 
hearing requests on this rule may be filed online at many Federal Depository 
Libraries.

FOR FURTHER INFORMATION CONTACT: By mail: James A. Tompkins, Registration 
Division 7505C, Office of Pesticide Programs, Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460. Office location, telephone number, and 
e-mail address: Rm. 239, Crystal Mall #2, 1921 Jefferson Davis Hwy., 
Arlington, VA, (703) 305-5697, e-mail: tompkins.jim@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: In the Federal Register of June 23,1998 (63 FR 
34179)(FRL-5795-1), EPA, issued a notice pursuant to section 408 of the 
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e) announcing the 
filing of a pesticide petition (PP 6F4631) for tolerance by Bayer Corporation, 
8400 Hawthorn Road, P.O. Box 4913, Kansas City, MO 64120-0013. This notice 
included a summary of the petition prepared by Bayer Corporation, the 
registrant. There were no comments received in response to the notice of 
filing.

    The petition requested that 40 CFR 180.527 be amended by establishing 
tolerances for inadvertent residues of the herbicide, N-(4-fluorophenyl)-N-(1-
methylethyl)-2-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy]acetamide, 
flufenacet, and metabolites containing the 4-fluoro-N-methylethyl benzenamine 
moiety in or on the raw agricultural commodities of Crop Group 15 (cereal 
grains), Crop Group 16 (forage, stover and hay of cereal grains), Crop Group 
17 (grass forage, and grass hay), alfalfa forage, alfalfa hay, alfalfa seed, 
clover forage, and clover hay at 0.1 parts per million (ppm) when present 
therein as a result of the application of flufenacet to field corn and 
soybeans. This tolerance will expire on April 30, 2003.

I. Risk Assessment and Statutory Findings


    Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a tolerance 
(the legal limit for a pesticide chemical residue in or on a food) only if EPA 
determines that the tolerance is "safe." Section 408(b)(2)(A)(ii) 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. Section 
408(b)(2)(C) requires EPA to give special consideration to exposure of infants 
and children to the pesticide chemical residue in establishing a tolerance and 
to "ensure that there is a reasonable certainty that no harm will result to 
infants and children from aggregate exposure to the pesticide chemical 
residue...."

    EPA performs a number of analyses to determine the risks from aggregate 
exposure to pesticide residues. For further discussion of the regulatory 
requirements of section 408 and a complete description of the risk assessment 
process, see the Final Rule on Bifenthrin Pesticide Tolerances (62 FR 62961, 
November 26, 1997) (FRL-5754-7).

A. Toxicity

    1. Threshold and non-threshold effects. For many animal studies, a dose 
response relationship can be determined, which provides a dose that causes 
adverse effects (threshold effects) and doses causing no observed effects (the 
"no-observed effect level" or "NOEL").    Once a study has been evaluated and 
the observed effects have been determined to be threshold effects, EPA 
generally divides the NOEL from the study with the lowest NOEL by an 
uncertainty factor (usually 100 or more) to determine the Reference Dose 
(RfD). The RfD is a level at or below which daily aggregate exposure over a 
lifetime will not pose appreciable risks to human health. An uncertainty 
factor (sometimes called a "safety factor") of 100 is commonly used since it 
is assumed that people may be up to 10 times more sensitive to pesticides than 
the test animals, and that one person or subgroup of the population (such as 
infants and children) could be up to 10 times more sensitive to a pesticide 
than another. In addition, EPA assesses the potential risks to infants and 
children based on the weight of the evidence of the toxicology studies and 
determines whether an additional uncertainty factor is warranted. Thus, an 
aggregate daily exposure to a pesticide residue at or below the RfD (expressed 
as 100 percent or less of the RfD) is generally considered acceptable by EPA. 
EPA generally uses the RfD to evaluate the chronic risks posed by pesticide 
exposure. For shorter term risks, EPA calculates a margin of exposure (MOE) by 
dividing the estimated human exposure into the NOEL from the appropriate 
animal study. Commonly, EPA finds MOEs lower than 100 to be unacceptable. This 
hundredfold MOE is based on the same rationale as the hundredfold uncertainty 
factor.

    Lifetime feeding studies in two species of laboratory animals are 
conducted to screen pesticides for cancer effects. When evidence of increased 
cancer is noted in these studies, the Agency conducts a weight of the evidence 
review of all relevant toxicological data including short-term and 
mutagenicity studies and structure activity relationship. Once a pesticide has 
been classified as a potential human carcinogen, different types of risk 
assessments (e.g., linear low dose extrapolations or MOE calculation based on 
the appropriate NOEL) will be carried out based on the nature of the 
carcinogenic response and the Agency's knowledge of its mode of action.

    2. Differences in toxic effect due to exposure duration. The toxicological 
effects of a pesticide can vary with different exposure durations. EPA 
considers the entire toxicity data base, and based on the effects seen for 
different durations and routes of exposure, determines which risk assessments 
should be done to assure that the public is adequately protected from any 
pesticide exposure scenario. Both short and long durations of exposure are 
always considered. Typically, risk assessments include "acute," "short-term," 
"intermediate term," and "chronic" risks. These assessments are defined by the 
Agency as follows.

    Acute risk, by the Agency's definition, results from 1-day consumption of 
food and water, and reflects toxicity which could be expressed following a 
single oral exposure to the pesticide residues. High end exposure to food and 
water residues are typically assumed.    Short-term risk results from exposure 
to the pesticide for a period of 1-7 days, and therefore overlaps with the 
acute risk assessment. Historically, this risk assessment was intended to 
address primarily dermal and inhalation exposure which could result, for 
example, from residential pesticide applications. However, since enaction of 
FQPA, this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from food, 
water, and residential uses when reliable data are available. In this 
assessment, risks from average food and water exposure, and high-end 
residential exposure, are aggregated. High-end exposures from all three 
sources are not typically added because of the very low probability of this 
occurring in most cases, and because the other conservative assumptions built 
into the assessment assure adequate protection of public health. However, for 
cases in which high-end exposure can reasonably be expected from multiple 
sources (e.g. frequent and widespread homeowner use in a specific geographical 
area), multiple high-end risks will be aggregated and presented as part of the 
comprehensive risk assessment/characterization. Since the toxicological 
endpoint considered in this assessment reflects exposure over a period of at 
least 7 days, an additional degree of conservatism is built into the 
assessment; i.e., the risk assessment nominally covers 1-7 days exposure, and 
the toxicological endpoint/NOEL is selected to be adequate for at least 7 days 
of exposure. (Toxicity results at lower levels when the dosing duration is 
increased.)

    Intermediate-term risk results from exposure for 7 days to several months. 
This assessment is handled in a manner similar to the short-term risk 
assessment.

    Chronic risk assessment describes risk which could result from several 
months to a lifetime of exposure. For this assessment, risks are aggregated 
considering average exposure from all sources for representative population 
subgroups including infants and children.

B. Aggregate Exposure

    In examining aggregate exposure, FFDCA section 408 requires that EPA take 
into account available and reliable information concerning exposure from the 
pesticide residue in the food in question, residues in other foods for which 
there are tolerances, residues in groundwater or surface water that is 
consumed as drinking water, and other non-occupational exposures through 
pesticide use in gardens, lawns, or buildings (residential and other indoor 
uses). Dietary exposure to residues of a pesticide in a food commodity are 
estimated by multiplying the average daily consumption of the food forms of 
that commodity by the tolerance level or the anticipated pesticide residue 
level. The Theoretical Maximum Residue Contribution (TMRC) is an estimate of 
the level of residues consumed daily if each food item contained pesticide 
residues equal to the tolerance. In evaluating food exposures, EPA takes into 
account varying consumption patterns of major identifiable subgroups of 
consumers, including infants and children. The TMRC is a "worst case" estimate 
since it is based on the assumptions that food contains pesticide residues at 
the tolerance level and that 100% of the crop is treated by pesticides that 
have established tolerances. If the TMRC exceeds the RfD or poses a lifetime 
cancer risk that is greater than approximately one in a million, EPA attempts 
to derive a more accurate exposure estimate for the pesticide by evaluating 
additional types of information (anticipated residue data and/or percent of 
crop treated data) which show, generally, that pesticide residues in most 
foods when they are eaten are well below established tolerances.

    Percent of crop treated estimates are derived from Federal and private 
market survey data. Typically, a range of estimates are supplied and the upper 
end of this range is assumed for the exposure assessment. By using this upper 
end estimate of percent of crop treated, the Agency is reasonably certain that 
exposure is not understated for any significant subpopulation group. Further, 
regional consumption information is taken into account through EPA's computer-
based model for evaluating the exposure of significant subpopulations 
including several regional groups, to pesticide residues. For this pesticide, 
the most highly exposed population subgroup non-nursing infants was not 
regionally based.

II. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D), EPA has reviewed the available 
scientific data and other relevant information in support of this action, EPA 
has sufficient data to assess the hazards of flufenacet and to make a 
determination on aggregate exposure, consistent with section 408(b)(2), for a 
time-limited tolerance for indirect or inadvertent residues of flufenacet and 
its metabolites in certain raw agricultural commodities at 0.1 ppm when 
present therein as a result of the application of flufenacet to field corn and 
soybeans as a herbicide. EPA's assessment of the dietary exposures and risks 
associated with establishing the tolerance follows:

 A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its validity, 
completeness, and reliability as well as the relationship of the results of 
the studies to human risk. EPA has also considered available information 
concerning the variability of the sensitivities of major identifiable 
subgroups of consumers, including infants and children. The nature of the 
toxic effects caused by flufenacet are discussed below.

    1. A rat acute oral study with a LD<INF>50</INF> of 1,617 
milligrams (mg)/kilogram (kg) for males and 589 mg/kg for females.

    2. A 84-day rat feeding study with a No Observed Effect Level (NOEL) less 
than 100 ppm (6.0 mg/kg/day) for males and a NOEL of 100 ppm (7.2 mg/kg/day) 
for females and with a Lowest Observed Effect Level (LOEL) of 100 ppm (6.8 
mg/kg/day) for males based on suppression of thyroxine (T4) level and a LOEL 
of 400 ppm (28.8 mg/kg/day) for females based on hematology and clinical 
chemistry findings.

     3. A 13-week mouse feeding study with a NOEL of 100 ppm (18.2 mg/kg/day 
for males and 24.5 mg/kg/day) for females and a LOEL of 400 ppm (64.2 
mg/kg/day for males and 91.3 mg/kg/day) for females based on histopathology of 
the liver, spleen and thyroid.

    4. A 13-week dog dietary study with a NOEL of 50 ppm (1.70 mg/kg/day for 
males and 1.67 mg/kg/day for females) and a LOEL of 200 ppm (6.90 mg/kg/day 
for males and 7.20 mg/kg/day for females) based on evidence that the 
biotransformation capacity of the liver has been exceeded, (as indicated by 
increase in LDH, liver weight, ALK and hepatomegaly), globulin and 
spleenpigment in females, decreased T4 and ALT values in both sexes, decreased 
albumin in males, and decreased serum glucose in females.

    5. A 21-day rabbit dermal study with the dermal irritation NOEL of 1,000 
mg/kg/day for males and females and a Systemic NOEL of 20 mg/kg/day for males 
and 150 mg/kg/day for females and a Systemic LOEL of 150 mg/kg/day for males 
and 1,000 mg/kg/day for females based on clinical chemistry data (decreased T4 
and FT4 levels in both sexes) and centrilobular hepatocytomegaly in females.

    6. A 1-year dog chronic feeding study with a NOEL was 40 ppm (1.29 
mg/kg/day in males and 1.14 mg/kg/day in females) and a LOEL of 800 ppm (27.75 
mg/kg/day in males and 26.82 mg/kg/day in females) based on increased alkaline 
phosphatase, kidney, and liver weight in both sexes, increased cholesterol in 
males, decreased T2, T4 and ALT values in both sexes, and increased incidences 
of microscopic lesions in the brain, eye, kidney, spinal cord, sciatic nerve 
and liver.

     7. A rat chronic feeding/carcinogenicity study with a NOEL less than 25 
ppm (1.2 mg/kg/day in males and 1.5 mg/kg/day in females) and a LOEL of 25 ppm 
(1.2 mg/kg/day in males and 1.5 mg/kg/day in females) based on 
methemoglobinemia and multi-organ effects in blood, kidney, spleen, heart, and 
uterus. Under experimental conditions the treatment did not alter the 
spontaneous tumor profile.

     8. In a mouse carcinogenicity study the NOEL was less than 50 ppm (7.4 
mg/kg/day) for males and the NOEL was 50 ppm (9.4 mg/kg/day) for females and 
the LOEL was 50 ppm (7.4 mg/kg/day for males) and the LOEL was 200 ppm (38.4 
mg/kg/day) for females based on cataract incidence and severity. There was no 
evidence of carcinogenicity for flufenacet in this study.

     9. A two-generation rat reproduction study with a parental systemic NOEL 
of 20 ppm (1.4 mg/kg/day in males and 1.5 mg/kg/day in females) and a 
reproductive NOEL of 20 ppm (1.3 mg/kg/day) and a Parental Systemic LOEL of 
100 ppm (7.4 mg/kg/day in males and 8.2 mg/kg/day in females) based on 
increased liver weight in F<INF>1</INF> females and 
hepatocytomegaly in F<INF>1</INF> males and a reproductive LOEL of 
100 ppm (6.9 mg/kg/day) based on increased pup death in early lactation 
(including cannibalism) for F<INF>1</INF> litters and the same 
effects in both F<INF>1</INF> and F<INF>2</INF> pups 
at the high dose level of 500 ppm (37.2 mg/kg/day in F<INF>1</INF> 
males and 41.5 mg/kg/day in F<INF>1</INF> females, respectively).

     10. A rat developmental study with a maternal NOEL of 25 mg/kg/day and 
with a maternal LOEL of 125 mg/kg/day based on decreased body weight gain 
initially and a developmental NOEL of 25 mg/kg/day and a developmental LOEL of 
125 mg/kg/day based on decreased fetal body weight, delayed development mainly 
delays in ossification in the skull, vertebrae, sternebrae, and appendages, 
and an increase in the incidence of extra ribs.

     11. A rabbit developmental study with a maternal NOEL of 5 mg/kg/day and 
a maternal LOEL of 25 mg/kg/day based on histopathological findings in the 
liver and a developmental NOEL of 25 mg/kg/day and a developmental LOEL of 125 
mg/kg/day based on increased skeletal variations.

     12. An acute rat neurotoxicity study with a NOEL less than 75 mg/kg/day 
and a LOEL of 75 mg/kg/day based on decreased motor activity in males.

     13. A rat subchronic neurotoxicity study with a NOEL of 120 ppm (7.3 
mg/kg/day in males and 8.4 mg/kg/day in females) and a LOEL of 600 (38.1 
mg/kg/day in males and 42.6 mg/kg/day in females) based on microscopic lesions 
in the cerebellum/medulla and spinal cords.

     14. Flufenacet was negative for mutagenic/genotoxic effects in a Gene 
mutation/In vitro assay in bacteria, a Gene mutation/In vitro assay in chinese 
hamster lung fibroblasts cells, a Cytogenetics/In vitro assay in chinese 
hamster ovary cells, a Cytogenetics/In vivo mouse micronucleus assay, and an 
In vitro unscheduled DNA synthesis assay in primary rat hepatocytes.

    15. A rat metabolism study showed that radio-labeled flufenacet was 
rapidly absorbed and metabolized by both sexes. Urine was the major route of 
excretion at all dose levels and smaller amounts were excreted via the feces.

    16. A 55-day dog study with subcutaneous administration of thiadone 
flufenacet metabolite supports the hypothesis that limitations in glutathione 
interdependent pathways and antioxidant stress result in metabolic lesions in 
the brain and heart following flufenacet exposure.

B. Toxicological Endpoints

    1. Acute toxicity. EPA has concluded that a risk estimate is required 
based on the LOEL of 75 mg/kg/day established in the Acute Neurotoxicity 
Study. For this risk assessment a Margin of Exposure (MOE) of 900 is required 
based on 10X for inter-species extrapolation, 10X for intra-species variation, 
3X required to protect infants and children, and 3X for the use of a LOEL.

     2. Short-and intermediate-term toxicity. EPA has concluded that available 
evidence does not indicate any evidence of significant toxicity from short 
term and intermediate term dietary exposure.

     3. Chronic toxicity. EPA has established the RfD for flufenacet at 0.004 
milligrams/kilogram/day (mg/kg/day). This RfD is based on LOEL of 1.2 
mg/kg/day in the combined chronic toxicity/carcinogenicity study in rats with 
a 300-fold safety factor to account for inter-species extrapolation (10X), 
intra-species variability (10X), lack of a NOEL in a critical study (3X). An 
extra safety factor to protect infants and children is not needed because the 
NOEL used in deriving the RfD is based on Methemoglobinemia and multi-organ 
effects (not developmental or neurotoxic effects) in adult rats after chronic 
exposure and thus are not relevant for enhanced sensitivity to infants and 
children.

    4. Carcinogenicity. The Health Effects Division RfD/Peer Review Committee 
has classified flufenacet as "not likely" to be carcinogenic to humans based 
on the lack of carcinogenicity in rats and mice.

C. Exposures and Risks

    1. From food and feed uses. Tolerances have been established (40 CFR 
180.527 (63 FR 17692)(FRL-5782-9)) for the combined residues of N-(4-
fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-
yl]oxy]acetamide and its metabolites containing the 4-fluoro-N-methylethyl 
benzenamine moiety, in or on the raw agricultural commodities field corn and 
soybeans. There is no reasonable expectation of residues of flufenacet or its 
metabolites occurring in meat, milk, poultry, or eggs. Risk assessments were 
conducted by EPA to assess dietary exposures from flufenacet as follows:

    i.  Acute exposure and risk. Acute dietary risk assessments are performed 
for a food-use pesticide if a toxicological study has indicated the 
possibility of an effect of concern occurring as a result of a 1 day or single 
exposure. An acute dietary risk assessment was conducted for flufenacet and 
its metabolites containing the 4-fluoro-N-methylethyl benzenamine moiety based 
on the LOEL of 75.0 mg/kg/day from the acute neurotoxicity study. The acute 
analysis estimates the distribution of single-day exposures for the overall 
U.S. population and certain subgroups. The Margin of Exposure (MOE) is a 
measure of how closely the exposure comes to the LOEL and is calculated as a 
ratio of the LOEL to the exposure. The calculated MOE for acute risk of 
flufenacet and its metabolites for the General U.S. population was 50,000 and 
for the most exposed subgroups, Infants (< 1 year old) and Children (1-6 
years old), the MOE was 37,500. These figures are above the MOE of 900 which 
is the level of concern based on interspecies extrapolation (10X), 
intraspecies variability (10X), the lack of a NOEL in the acute neurotoxicity 
study (3X), and providing additional protection to infants and children (3X).

    ii. Chronic exposure and risk. The Reference Dose (RfD) for flufenacet is 
0.0004 mg/kg/day. This value is based on the systemic LOEL of 1.2 mg/kg/day in 
the rat chronic feeding/carcinogenicity study with a 300-fold safety factor to 
account for interspecies extrapolation (10X), intraspecies variability (10X), 
and the lack of a NOEL in the rat chronic feeding/carcinogenicity study (3X).

    A DRES chronic exposure analysis was conducted using tolerance levels for 
field corn, soybeans and rotated crops and percent crop treated information to 
estimate dietary exposure for the general population and 22 subgroups. The 
chronic analysis showed that exposures from the tolerances in or on field 
corn, soybeans and rotated crops for non-nursing infants (the subgroup with 
the highest exposure) would be 6.5% of the Reference Dose (RfD). The exposure 
for the general U.S. population would be 2.6% of the RfD.

    Section 408(b)(2)(F) states that the Agency may use data on the actual 
percent of food treated for assessing chronic dietary risk only if the Agency 
can make the following findings: (a) That the data used are reliable and 
provide a valid basis to show what percentage of the food derived from such 
crop is likely to contain such pesticide residue; (b) that the exposure 
estimate does not underestimate exposure for any significant subpopulation 
group; and if data are available on pesticide use and food consumption in a 
particular area, the exposure estimate does not understate exposure for the 
population in such area. In addition, the Agency must provide for periodic 
evaluation of any estimates used.

    The Agency used percent crop treated (PCT) information as follows. A 
routine chronic dietary exposure analysis for flufenacet was based on 16% of 
field corn crop treated and 26% of the soybean crop treated. The Agency 
believes that the three conditions listed above have been met. With respect to 
Unit II. B.1.ii.(a), EPA finds that the (PCT) information described above for 
flufenacet used on field corn is reliable and has a valid basis. Bayer 
Corporation's flufenacet production capacity does not exceed that needed to 
treat 16% of the total corn and 26% of the total soybean acres planted in the 
United States. at the average application rates for products containing 
flufenacet. Before the petitioner can increase production of product, 
permission from the Agency must be obtained. As to Unit II.B.1.ii.(b) and (c), 
regional consumption information and consumption information for significant 
subpopulations is taken into account through EPA's computer-based model for 
evaluating the exposure of significant subpopulations including several 
regional groups. Use of this consumption information in EPA's risk assessment 
process ensures that EPA's exposure estimate does not understate exposure for 
any significant subpopulation group and allows the Agency to be reasonably 
certain that no regional population is exposed to residue levels higher than 
those estimated by the Agency. Other than the data available through national 
food consumption surveys, EPA does not have available information on the 
regional consumption of food to which flufenacet may be applied in a 
particular area.

     2. From drinking water. Drinking water estimated concentrations (DWECs) 
for groundwater (parent flufenacet and degradate thiadone) were calculated 
from the monitoring data to be 0.18 parts per billion (ppb) for acute and 0.03 
ppb for chronic concentrations. The DWECs for surface water based on the 
computer models Pesticide Root Zone Method (PRZM) 2.3 and EXAMS 2.97.5 were 
calculated to be 17.0 ppb for the acute concentration and 14.2 ppb for chronic 
concentration (parent flufenacet and degradate thiadone).

    3.  From non-dietary exposure. There are no non-food uses of flufenacet 
currently registered under the Federal Insecticide, Fungicide and Rodenticide 
Act, as amended. No non-dietary exposures are expected for the general 
population.

    4. Cumulative exposure to substances with common mechanism of toxicity. 
Section 408(b)(2)(D)(v) requires that, when considering whether to establish, 
modify, or revoke a tolerance, the Agency consider "available information" 
concerning the cumulative effects of a particular pesticide's residues and 
"other substances that have a common mechanism of toxicity."

    EPA does not have, at this time, available data to determine whether 
flufenacet has a common mechanism of toxicity with other substances or how to 
include this pesticide in a cumulative risk assessment. Flufenacet is 
structurally a thiadiazole. Unlike other pesticides for which EPA has followed 
a cumulative risk approach based on a common mechanism of toxicity, flufenacet 
does not appear to produce a toxic metabolite produced by other substances. 
For the purposes of this tolerance action, therefore, EPA has not assumed that 
flufenacet has a common mechanism of toxicity with other substances. For 
information regarding EPA's efforts to determine which chemicals have a common 
mechanism of toxicity and to evaluate the cumulative effects of such 
chemicals, see the Final Rule for Bifenthrin Pesticide Tolerances (62 FR 
62961, November 26, 1997).

D. Aggregate Risks and Determination of Safety for U.S. Population

    1. Acute risk. The acute endpoint for flufenacet and its metabolites is 75 
mg/kg/day. The acute exposure for flufenacet and its metabolites is 0.0015 
mg/kg/day for the general U.S. population and 0.002 mg/kg/day for children 1-6 
years of age. The drinking water level of concerns (DWLOCs) for acute exposure 
to flufenacet in drinking water calculated for U.S. population was 2.87 ppm 
and for children (1-6 years old) was 813 ppb. These figures were calculated as 
follows. First, the acceptable acute exposure flufenacet in drinking water was 
obtained by subtracting the acute dietary food exposures from the ratio of the 
acute LOEL to the acceptable MOE for aggregate exposure. Then, the DWLOCs were 
calculated by multiplying the acceptable exposure to flufenacet in drinking 
water by estimated body weight (70 kg for adults, 10 kg for children) and then 
dividing by the estimated daily drinking water consumption (2 l/day for 
adults, 1 l/day for children). The Agency's SCI-Grow model estimates peak 
levels of flufenacet and its metabolite thiadone in groundwater to be 15.3 
ppb. PRZM/EXAMS estimates peak levels of flufenacet and its metabolite 
thiadone in surface water to be 17 ppb. EPA's acute drinking water level of 
concern are well above the estimated exposures for flufenacet in water for the 
U.S. population and subgroup with highest estimated exposure.

    2. Chronic risk. The chronic endpoint for flufenacet is 0.0004 mg/kg/body 
weight(bwt)/day. Using tolerance levels and percent crop treated, the residues 
in the diet (food only) are calculated to be 0.0001 mg/kg bwt/day or 2.6% of 
the RfD for the general U.S. population and 0.00023 mg/kg bwt/day or 5.8% of 
the RfD for children aged 1-6. Therefore, residues of flufenacet in drinking 
water may comprise up to 0.0039 mg/kg bwt/day (0.0040-0.0001 mg/kg bwt/day) 
for the U.S. population and 0.0038 mg/kg bwt/day (0.0040-0.00023 mg/kg 
bwt/day) for children 1-6 years old (the highest exposed group from residues 
of flufenacet in both food and water).

     The drinking water level of concerns (DWLOCs) for chronic exposure to 
flufenacet in drinking water calculated for U.S. population was 136 ppb 
assuming that an adult weighs 70 kg and consumes a maximum of 2 liters of 
water per day and for children (1-6 years old) the DWLOC was 37.7 ppb assuming 
that a child weighs 10 kg and consumes a maximum of 1 liter of water per day.

    The drinking water estimated concentration (DWECs) for groundwater (parent 
flufenacet and degradate thiadone) calculated from the monitoring data is 0.03 
ppb for chronic concentrations which does not exceed DWLOC of 37.7 ppb for 
children (1-6 years old). The DWEC for surface water based on the computer 
models PRZM 2.3 and EXAMS 2.97.5 was calculated to be 14.2 ppb for chronic 
concentration (parent flufenacet and degradate thiadone) which does not exceed 
the DWLOC of 37.7 ppb for children (1-6 years old).

     EPA concludes that there is a reasonable certainty that no harm will 
result from aggregate exposure to flufenacet residues.

E. Aggregate Risks and Determination of Safety for Infants and Children

    1. Safety factor for infants and children. In assessing the potential for 
additional sensitivity of infants and children to residues of flufenacet, EPA 
considered data from developmental toxicity studies in the rat and rabbit and 
a two-generation reproduction study in the rat. The developmental toxicity 
studies are designed to evaluate adverse effects on the developing organism 
resulting from maternal pesticide exposure gestation. Reproduction studies 
provide information relating to effects from exposure to the pesticide on the 
reproductive capability of mating animals and data on systemic toxicity.

    FFDCA section 408 provides that EPA shall apply an additional tenfold 
margin of safety for infants and children in the case of threshold effects to 
account for pre-and post-natal toxicity and the completeness of the database 
unless EPA determines that a different margin of safety will be safe for 
infants and children. Although there is no indication of increased sensitivity 
to young rats or rabbits following pre-and/or post-natal exposure to 
flufenacet in the standard developmental and reproductive toxicity studies, an 
additional developmental neurotoxicity study, which is not normally required, 
is needed to access the susceptibility of the offspring in 
functional/neurological development. Therefore, EPA has required that a 
developmental neurotoxicity study be conducted with flufenacet and a three 
fold safety factor for children and infants will be used in the aggregate 
dietary acute and chronic risk assessments. Although there is no indication of 
additional sensitivity to young rats or rabbits following pre-and/or post-
natal exposure to flufenacet in the developmental and reproductive toxicity 
studies; the Agency concluded that the FQPA safety factors should not be 
removed but instead reduced because: (a) There was no assessment of 
susceptibility of the offspring in functional/neurological development and 
reproductive studies, (b) there is evidence of neurotoxicity in mice, rats, 
and dogs, (c) there is concern for thyroid hormone disruption.

III. Other Considerations

A. Metabolism in Plants and Animals

    The nature of the residue in field corn, soybeans, rotational crops, and 
livestock is adequately understood. The residues of concern for the tolerance 
expression are parent and metabolites containing the 4-fluoro-N-methylethyl 
benzenamine moiety. Based on the results of animal metabolism studies it is 
unlikely that secondary residues would occur in animal commodities from the 
use on field corn and soybeans.

B. Analytical Enforcement Methodology

    An adequate analytical method, gas chromatography/mass spectrometry with 
selected ion monitoring, is available for enforcement purposes. Because of the 
long lead time from establishing these tolerances to publication of the 
enforcement methodology in the Pesticide Analytical Manual, Vol. II, the 
analytical methodology is being made available in the interim to anyone 
interested in pesticide enforcement when requested from: Calvin Furlow, PRRIB, 
IRSD (7502C), Office of Pesticide Programs, Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460. Office location and telephone number: Rm 
101FF, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, (703-
305-5229).

C. Endocrine Effects

    EPA is required to develop a screening program to determine whether 
certain substances (including all pesticides and inerts) "may have an effect 
in humans that is similar to an effect produced by a naturally occurring 
estrogen, or such other effect . . . " The Agency is currently working with 
interested stakeholders, including other government agencies, public interest 
groups, industry and research scientists in developing a screening and testing 
program and a priority setting scheme to implement this program. Congress has 
allowed 3 years from the passage of FQPA (August 3, 1999) to implement this 
program. At that time, EPA may require further testing of this active 
ingredient and end use products for endocrine disrupter effects. Based on the 
toxicological findings for flufenacet relating to endocrine disruption 
effects, flufenacet should be considered as a candidate for evaluation as an 
endocrine disrupter when the criteria are established.

D. Magnitude of Residues

    Based on the results of animal metabolism studies it is unlikely that 
significant residues would occur in secondary animal commodities from the use 
on corn and soybeans.

    Due to the following data gaps: (1) Data regarding the stability of the 
glucoside conjugate and the malonylalanine conjugate of thiadone and 
subsequent bioavailability of any release free thiadone or thiadone 
glucuronide; (2) a revised analytical method; (3) validation of the product 
chemistry enforcement analytical methods; (4) additional rotational crop data; 
(5) additional water monitoring data; and (6) a developmental neurotoxicity 
study; EPA believes it is inappropriate to establish permanent tolerances for 
the uses of flufenacet at this time. EPA believes that the existing data 
support time-limited tolerances to April 30, 2003. The nature of the residue 
in plants is adequately understood for the purposes of these time-limited 
tolerances.

 E. International Residue Limits

    There are no Codex Alimentarius Commission (Codex) Maximum Residue Levels 
(MRLs) for flufenacet.

F. Rotational Crop Restrictions

    Tolerances for indirect or inadvertent residues of flufenacet established 
by this regulation will cover any residues in the crops planted in treated 
soybean and corn fields in accordance with the restrictions that appear on the 
labeling proposed for registration under the Federal Insecticide, Fungicide, 
and Rodenticide Act (FIFRA), as amended.

IV. Conclusion

    Therefore, the tolerances are established for indirect or inadvertent 
residues of the herbicide, N-(4-fluorophenyl)-N-(1-methylethyl)-2-[[5-
(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy]acetamide and its metabolites 
containing the 4-fluoro-N-methylethyl benzenamine moiety in or on Crop Group 
15 (cereal grains), Crop Group 16 (forage, stover and hay of cereal grains), 
Crop Group 17 (grass forage, and grass hay), alfalfa forage, alfalfa hay, 
alfalfa seed, clover forage, and clover hay at 0.1 ppm when present therein as 
a result of the application of flufenacet to field corn and soybeans as a 
herbicide. These time-limited tolerances will expire on April 30, 2003

V. Objections and Hearing Requests

    The new FFDCA section 408(g) provides essentially the same process for 
persons to "object" to a tolerance regulation issued by EPA under new section 
408(e) and (l)(6) as was provided in the old section 408 and in section 409. 
However, the period for filing objections is 60 days, rather than 30 days. EPA 
currently has procedural regulations which govern the submission of objections 
and hearing requests. These regulations will require some modification to 
reflect the new law. However, until those modifications can be made, EPA will 
continue to use those procedural regulations with appropriate adjustments to 
reflect the new law.

    Any person may, by November 23, 1998, file written objections to any 
aspect of this regulation and may also request a hearing on those objections. 
Objections and hearing requests must be filed with the Hearing Clerk, at the 
address given above (40 CFR 178.20). A copy of the objections and/or hearing 
requests filed with the Hearing Clerk should be submitted to the OPP docket 
for this rulemaking. The objections submitted must specify the provisions of 
the regulation deemed objectionable and the grounds for the objections (40 CFR 
178.25). Each objection must be accompanied by the fee prescribed by 40 CFR 
180.33(i). If a hearing is requested, the objections must include a statement 
of the factual issues on which a hearing is requested, the requestor's 
contentions on such issues, and a summary of any evidence relied upon by the 
requestor (40 CFR 178.27). A request for a hearing will be granted if the 
Administrator determines that the material submitted shows the following: 
There is genuine and substantial issue of fact; there is a reasonable 
possibility that available evidence identified by the requestor would, if 
established, resolve one or more of such issues in favor of the requestor, 
taking into account uncontested claims or facts to the contrary; and 
resolution of the factual issues in the manner sought by the requestor would 
be adequate to justify the action requested (40 CFR 178.32). Information 
submitted in connection with an objection or hearing request may be claimed 
confidential by marking any part or all of that information as CBI. 
Information so marked will not be disclosed except in accordance with 
procedures set forth in 40 CFR part 2. A copy of the information 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.

VI. Public Record and Electronic Submissions

    EPA has established a record for this rulemaking under docket control 
number [OPP-300712] (including any comments and data submitted 
electronically). 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 public record is located in Room 
119 of the Public Information and Records Integrity Branch, Information 
Resources and Services Division (7502C), Office of Pesticide Programs, 
Environmental Protection Agency, Crystal Mall #2, 1921 Jefferson Davis 
Highway, Arlington, VA.

    Electronic comments may 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.

    The official record for this rulemaking, as well as the public version, as 
described above will be kept in paper form. Accordingly, EPA will transfer any 
copies of objections and hearing requests received electronically into 
printed, paper form as they are received and will place the paper copies in 
the official rulemaking record which will also include all comments submitted 
directly in writing. The official rulemaking record is the paper record 
maintained at the Virginia address in "ADDRESSES" at the beginning of this 
document.

VII. Regulatory Assessment Requirements

A. Certain Acts and Executive Orders

    This final rule establishes a tolerance under FFDCA section 408(d) in 
response to a petition submitted to the Agency. The Office of Management and 
Budget (OMB) has exempted these types of actions from review under Executive 
Order 12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 
1993). This final rule does not contain any information collections subject to 
OMB approval under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., 
or impose any enforceable duty or contain any unfunded mandate as described 
under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 
104-4). Nor does it require any prior consultation as specified by Executive 
Order 12875, entitled Enhancing the Intergovernmental Partnership (58 FR 
58093, October 28, 1993), or special considerations as required by Executive 
Order 12898, entitled Federal Actions to Address Environmental Justice in 
Minority Populations and Low-Income Populations (59 FR 7629, February 16, 
1994), or require OMB review in accordance with Executive Order 13045, 
entitled Protection of Children from Environmental Health Risks and Safety 
Risks (62 FR 19885, April 23, 1997).

B. Executive Order 12875

    Under Executive Order 12875, entitled Enhancing Intergovernmental 
Partnerships (58 FR 58093, October 28, 1993), EPA may not issue a regulation 
that is not required by statute and that creates a mandate upon a State, local 
or tribal government, unless the Federal government provides the funds 
necessary to pay the direct compliance costs incurred by those governments. If 
the mandate is unfunded, EPA must provide to the Office of Management and 
Budget (OMB) a description of the extent of EPA's prior consultation with 
representatives of affected State, local and tribal governments, the nature of 
their concerns, copies of any written communications from the governments, and 
a statement supporting the need to issue the regulation. In addition, 
Executive Order 12875 requires EPA to develop an effective process permitting 
elected officials and other representatives of State, local and tribal 
governments "to provide meaningful and timely input in the development of 
regulatory proposals containing significant unfunded mandates."

    Today's rule does not create an unfunded Federal mandate on State, local 
or tribal governments. The rule does not impose any enforceable duties on 
these entities. Accordingly, the requirements of section 1(a) of Executive 
Order 12875 do not apply to this rule.

C. Executive Order 13084

    Under Executive Order 13084, entitled Consultation and Coordination with 
Indian Tribal Governments (63 FR 27655, May 19,1998), EPA may not issue a 
regulation that is not required by statute, that significantly or uniquely 
affects the communities of Indian tribal governments, and that imposes 
substantial direct compliance costs on those communities, unless the Federal 
government provides the funds necessary to pay the direct compliance costs 
incurred by the tribal governments. If the mandate is unfunded, EPA must 
provide OMB, in a separately identified section of the preamble to the rule, a 
description of the extent of EPA's prior consultation with representatives of 
affected tribal governments, a summary of the nature of their concerns, and a 
statement supporting the need to issue the regulation. In addition, Executive 
Order 13084 requires EPA to develop an effective process permitting elected 
and other representatives of Indian tribal governments "to provide meaningful 
and timely input in the development of regulatory policies on matters that 
significantly or uniquely affect their communities."

    Today's rule does not significantly or uniquely affect the communities of 
Indian tribal governments. This action does not involve or impose any 
requirements that affect Indian Tribes. Accordingly, the requirements of 
section 3(b) of Executive Order 13084 do not apply to this rule.

    In addition, since tolerances and exemptions that are established on the 
basis of a petition under FFDCA section 408(d), such as the tolerance in this 
final rule, do not require the issuance of a proposed rule, the requirements 
of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.) do not apply. 
Nevertheless, the Agency has previously assessed whether establishing 
tolerances, exemptions from tolerances, raising tolerance levels or expanding 
exemptions might adversely impact small entities and concluded, as a generic 
matter, that there is no adverse economic impact. The factual basis for the 
Agency's generic certification for tolerance actions published on May 4, 1981 
(46 FR 24950) and was provided to the Chief Counsel for Advocacy of the Small 
Business Administration.

VIII. Submission to Congress and the Comptroller General

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the Small 
Business Regulatory Enforcement Fairness Act of 1996, generally provides that 
before a rule may take effect, the agency promulgating the rule must submit a 
rule report, which includes a copy of the rule, to each House of the Congress 
and to the Comptroller General of the United States. EPA will submit a report 
containing this rule and other required information to the U.S. Senate, the 
U.S. House of Representatives, and the Comptroller General of the United 
States prior to publication of the rule in the Federal Register. This rule is 
not a "major rule" as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and record keeping 
requirements.

    Dated: September 10, 1998.

James Jones,

Director, Registration Division, Office of Pesticide Programs.
    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

    1. The authority citation for part 180 continues to read as 
follows:
    Authority: 21 U.S.C. 346a and 371.

    2. In Sec. 180.527, by adding paragraph (d) to read as follows:

Sec.  180.527  N-(4-fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-
1,3,4-thiadiazol-2-yl]oxy]acetamide; tolerances for residues.

*      *      *      *      *

    (d) Indirect or inadvertent residues. (1) Time-limited tolerances are 
established for indirect or inadvertent residues of the herbicide, N-(4-
fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-
yl]oxy]acetamide and its metabolites containing the 4-fluoro-N-methylethyl 
benzenamine moiety in or on the following raw agricultural commodities from 
application of this herbicide to the raw agricultural commodities listed in 
paragraph (a)(1) of this section:

--------------------------------------------------------------------------
                                                      Parts    Expiration/
                     Commodity                         per     Revocation
                                                     million      Date
--------------------------------------------------------------------------
Alfalfa, forage...................................      0.1      4/30/03
Alfalfa, hay......................................      0.1      4/30/03
 Alfalfa, seed....................................      0.1      4/30/03
Clover, forage....................................      0.1      4/30/03
Clover, hay.......................................      0.1      4/30/03
Crop Group 15 (cereal grains).....................      0.1      4/30/03
Crop Group 16 (forage, stover and hay of cereal grains) 0.1      4/30/03
Crop Group 17 (grass forage, and grass hay).......      0.1      4/30/03
--------------------------------------------------------------------------

    (2) Residues in these commodities not in excess of the established 
tolerance resulting from the use described in paragraph (d)(1) of this section 
remaining after expiration of the time-limited tolerance will not be 
considered to be actionable if the herbicide is applied during the term of and 
in accordance with the provisions of the above regulation.

[FR Doc. 98-25451 Filed 9-22-98; 8:45 am]
BILLING CODE 6560-50-F
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