FLUORIDE ACTION NETWORK PESTICIDE PROJECT
Return to FAN's Pesticide Homepage
Return to Flufenacet Index Page
Flufenacet (Bayer). April 10, 1998. Time-Limited Pesticide Tolerance. Final Rule. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/1998/April/Day-10/p9549.htm
[Federal Register: April 10, 1998 (Volume 63, Number 69)]
[Rules and Regulations]
[Page 17692-17699]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10ap98-12]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300636; FRL-5782-9]
RIN 2070-AB78
N-(4-fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-
1,3,4-thiadiazol-2-yl]oxy]acetamide; Time-Limited Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes a time-limited tolerances for the
combined 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 [hereafter referred to as flufenacet,
the proposed common chemical name] in or on certain raw agricultural
commodities. 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. 104-70). The tolerance will
expire on April 30, 2003.
DATES: This regulation is effective April 10, 1998. Objections and
requests for hearings must be received by EPA on or before June 9,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300636], 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-300636], 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, CM #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-300636]. 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: 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 April 2, 1997 (62
FR 15690)(5593-9), 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
[[Page 17693]]
tolerances by Bayer Corporation, 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 part 180 be amended by
establishing tolerances for combined residues of the herbicide, FOE
5043, N-(4-fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-
1,3,4-thiadiazol-2-yl]oxy]acetamide in or on field corn grain at 0.05
parts per million (ppm), field corn forage at 0.4 ppm, field corn
stover (fodder) at 0.4 ppm, soybean seed at 0.1 ppm, milk at 0.01 ppm,
meat at 0.05 ppm, and meat by-products at 0.05 ppm. Bayer subsequently
amended the petition by deleting the proposed milk, meat and meat by-
products tolerances. The tolerance expression is also being editorially
amended to read: 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.
The tolerances will expire and will be revoked on April 30, 2003.
I. Risk Assessment and Statutory Findings
New 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. First, EPA determines the
toxicity of pesticides based primarily on toxicological studies using
laboratory animals. These studies address many adverse health effects,
including (but not limited to) reproductive effects, developmental
toxicity, toxicity to the nervous system, and carcinogenicity. Second,
EPA examines exposure to the pesticide through the diet (e.g., food and
drinking water) and through exposures that occur as a result of
pesticide use in residential settings.
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 3
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,
[[Page 17694]]
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.
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
combined residues of flufenacet and its metabolites. 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 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
[[Page 17695]]
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
finds 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 10 X for inter-species extrapolation,
10 X for intra-species variation, 3 X required to protect infants and
children, and 3 X 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 mg/kg/day. This RfD is based on a 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 (10 X), intra-
species variability (10 X), and a lack of a NOEL in a critical study (3
X). An extra safety factor to protect infants and children is not
needed because the NOEL used in deriving the RfD is based on
methemoglobinema 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 not been established
(40 CFR part 180) previously for the residues of flufenacet, in or on
raw agricultural commodities. 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 and risks from flufenacet from the proposed use on
soybeans and field corn 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 (10 X), intraspecies variability (10 X), the lack of a
NOEL in the acute neurotoxicity study (3 X), and providing additional
protection to infants and children (3 X).
ii. Chronic exposure and risk. The Reference Dose (RfD) for
flufenacet is 0.004 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 (10
X), intraspecies variability (10 X), the lack of a NOEL in the rat
chronic feeding/carcinogenicity study (3 X).
A DRES chronic exposure analysis was conducted using tolerance
levels for field corn and soybeans and percent crop treated information
to estimate dietary exposure for the general population and 22
subgroups. The chronic analysis showed that exposure 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 (c) 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) of this preamble, 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) of this preamble, regional consumption information and
consumption information for significant
[[Page 17696]]
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 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.'' The Agency believes that ``available
information'' in this context might include not only toxicity,
chemistry, and exposure data, but also scientific policies and
methodologies for understanding common mechanisms of toxicity and
conducting cumulative risk assessments. For most pesticides, although
the Agency has some information in its files that may turn out to be
helpful in eventually determining whether a pesticide shares a common
mechanism of toxicity with any other substances, EPA does not at this
time have the methodologies to resolve the complex scientific issues
concerning common mechanism of toxicity in a meaningful way. EPA has
begun a pilot process to study this issue further through the
examination of particular classes of pesticides. The Agency hopes that
the results of this pilot process will increase the Agency's scientific
understanding of this question such that EPA will be able to develop
and apply scientific principles for better determining which chemicals
have a common mechanism of toxicity and evaluating the cumulative
effects of such chemicals. The Agency anticipates, however, that even
as its understanding of the science of common mechanisms increases,
decisions on specific classes of chemicals will be heavily dependent on
chemical specific data, much of which may not be presently available.
Although at present the Agency does not know how to apply the
information in its files concerning common mechanism issues to most
risk assessments, there are pesticides as to which the common mechanism
issues can be resolved. These pesticides include pesticides that are
toxicologically dissimilar to existing chemical substances (in which
case the Agency can conclude that it is unlikely that a pesticide
shares a common mechanism of activity with other substances) and
pesticides that produce a common toxic metabolite (in which case common
mechanism of activity will be assumed).
Flufenacet is structurally a thiadiazole. EPA is not aware of any
other pesticides with this structure. For flufenacet, EPA has not yet
conducted a detailed review of common mechanisms to determine whether
it is appropriate, or how to include this chemical in a cumulative risk
assessment. After EPA develops a methodology to address common
mechanism of toxicity issues to risk assessments, the Agency will
develop a process (either as part of the periodic review of pesticides
or otherwise) to reexamine these tolerance decisions. 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 these tolerance actions; therefore, EPA has not assumed
that flufenacet has a common mechanism of toxicity with other
substances.
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 the 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 to 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 flufencet 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 0.004 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 years.
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 (0.00400-0.00023 mg/kg bwt/day) for
children 1-6 years old (the group exposed to the highest level of
flufencet residues in both food and water).
The drinking water level of concerns (DWLOCs) for chronic exposure
to flufenacet in drinking water calculated for the U.S. population was
136 ppb assuming that an adult weighs 70 kg and consumes a maximum of 2
liters of water per day. 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
[[Page 17697]]
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
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 pesticide exposure during prenatal development
to one or both parents. 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 susceptiblity of the offspring in function/
neurological development. Therefore, EPA has required that a
developmental neurotoxicty study be conducted with flufenacet and a
threefold safety factor for children and infants will be used in the
aggregate dietary acute and chronic risk assessment. 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 factor should not be removed but instead reduced
because: (1) There was no assessment of susceptibility of the offspring
in functional/neurological developmental and reproductive studies. (2)
There is evidence of neurotoxicity in mice, rats, and dogs. (3) 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 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, 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. Office location and telephone
number: Room 119E, CM #2, 1921 Jefferson Davis Highway, Arlington, VA
22202, (703-305-5937).
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. EPA believes it is inappropriate to
establish permanent tolerances for the uses of flufenacet at this time
due to the exitence of data gaps. These data gaps are: (1) Data
regarding the stability of the glucoside conjugate and the
malonylalanine conjugate of thiadone and subsequent bioavailability of
any released free thiadone or thiadone glucuronide in meat, poultry,
eggs, and milk commodities. The glucoside and malonylalanine conjugates
of thiadone are metabolies of parent flufenacet that are present in
plant commodites. Data are needed to ensure that these metabolites are
not further converted to free thiadone or thiadone glucuronide in
animal commodities. (2) A revised analytical method incorporating
editorial changes specified in the Agency review. (3) Validation of the
product chemistry enforcement analytical methods. (4) Data for
additional rotational crops. (5) A developmental neurotoxicity study.
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.
No tolerances for inadvertent residues of flufenacet are required
in rotational crops. The restrictions that appear on the labeling
proposed for registration under the Federal Insecticide Fungicide and
Rodenticide Act (FIFRA), as amended, will prevent inadvertent residues
that may occur in rotational crops for the use on field corn and
soybeans.
IV. Conclusion
The analysis for flufenacet and its metabolites using crop
tolerances, percentage of crop estimates, and estimated drinking water
concentrations for all population subgroups examined by EPA shows the
use on soybeans and corn will not cause exposure at which the Agency
believes there is an appreciable risk during the period of time for the
time-limited tolerance. Therefore EPA concludes there is a reasonable
certainty of no harm from aggregate exposure to flufenacet. Based
[[Page 17698]]
on the information cited above, EPA has determined that establishing
time-limited tolerances for the combined 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 field corn grain at
0.05 ppm, field corn forage at 0.4 ppm, field corn stover at 0.4 ppm,
and soybean seed at 0.1 ppm will be safe. This time-limited tolerance
will expire on April 30, 2003. Therefore, the tolerances are
established as set forth below.
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 June 9, 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 Docket and Electronic Submissions
EPA has established a record for this rulemaking under docket
control number [OPP-300636] (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
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).
In addition, since these 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 General Accounting Office
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Bussiness 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 oher
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).
[[Page 17699]]
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: April 3, 1998.
Stephen L. Johnson,
Acting Director, 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. By adding Sec. 180.527, 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.
(a) General. (1) Time-limited tolerances are established for
combined 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:
------------------------------------------------------------------------
Parts per Expiration/
Commodity million Revocation Date
------------------------------------------------------------------------
Corn, field, forage..................... 0.05 4/30/03
Corn, field, grain...................... 0.4 4/30/03
Corn, field, stover..................... 0.4 4/30/03
Soybean seed............................ 0.1 4/30/03
------------------------------------------------------------------------
(2) Residues in these commodities not in excess of the established
tolerance resulting from the use described in paragraph (a) 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.
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 98-9549 Filed 4-7-98; 4:39 pm]
BILLING CODE 6560-50-F