Flufenacet; Time-Limited Pesticide Tolerance

Note: EPA no longer updates this information, but it may be useful as a reference or resource.
 [Federal Register: September 23, 1998 (Volume 63, Number 184)]
[Rules and Regulations]               
[Page 50784-50791]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr23se98-14]

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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],

[[Page 50785]]

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

[[Page 50786]]

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 spleen

[[Page 50787]]

pigment 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

[[Page 50788]]

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

[[Page 50789]]

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.

[[Page 50790]]

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

[[Page 50791]]

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
Flufenacet; Time-Limited Pesticide Tolerance

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