[Federal Register Volume 63, Number 152 (Friday, August 7, 1998)]
[Rules and Regulations]
[Pages 42249-42257]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-20899]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Parts 180 and 185

[OPP-300697; FRL-6021-7]
RIN 2070-AB78


Flutolanil; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes time-limited tolerances, to expire 
on December 31, 2000, for residues of the fungicide flutolanil N-(3-(1-
methylethoxy)phenyl)-2-(trifluoromethyl)benzamide and its metabolites 
converted to 2-(trifluoromethyl)benzoic acid and calculated as 
flutolanil in or on the raw agricultural commodities rice grain at 2.0 
parts per million (ppm) and rice straw at 8.0 ppm and in or on the 
processed food or feed commodities rice hulls at 7.0 ppm and rice bran 
at 3.0 ppm when present therein as a result of application of the 
fungicide to growing crops. AgrEvo USA Company requested the tolerances 
under the Federal Food, Drug and Cosmetic Act (FFDCA), as amended by 
the Food Quality Protection Act of 1996 (Pub. L. 104-170).

DATES: This regulation is effective August 7, 1998. Objections and 
requests

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for hearings must be received by EPA on or before October 6, 1998.

ADDRESSES: Written objections and hearing requests, identified by the 
docket control number, [OPP-300697], 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-300697], 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: <a href="/cdn-cgi/l/email-protection#bad5caca97ded5d9d1dfcefadfcadbd7dbd3d694dfcadb94ddd5cc"><span class="__cf_email__" data-cfemail="83ecf3f3aee7ece0e8e6f7c3e6f3e2eee2eaefade6f3e2ade4ecf5">[email protected]</span></a>. 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 or 
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-300697]. 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: Mary L. Waller, 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, Rm 247, 1921 
Jefferson Davis Hwy., Arlington, VA, (703) 308-9354, e-mail: 
<a href="/cdn-cgi/l/email-protection#5225333e3e37207c3f33202b123722333f333b3e7c3722337c353d24"><span class="__cf_email__" data-cfemail="f285939e9e9780dc9f93808bb29782939f939b9edc978293dc959d84">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION: In the Federal Register of June 23, 1998 (63 
FR 34176)(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 pesticide petition (PP) 4F4380 for tolerances 
by AgrEvo USA Co., Little Falls Centre One, 2711 Centerville Rd., 
Wilmington, DE 19808. This notice included a summary of the petition 
prepared by AgrEvo USA Co., the registrant. There were no comments 
received in response to the notice of filing.
    The petition requested that 40 CFR 180.484 be amended by 
establishing tolerances for residues of the fungicide flutolanil N-(3-
(1-methylethoxy)phenyl)-2-(trifluoromethyl)benzamide and its 
metabolites converted to 2-(trifluoromethyl)benzoic acid and calculated 
as flutolanil in or on the raw agricultural commodities rice grain at 
2.0 ppm and rice straw at 8.0 ppm and in or on the processed food or 
feed commodities rice hulls at 7.0 ppm and rice bran at 3.0 ppm when 
present therein as a result of application of the fungicide to growing 
crops.

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,

[[Page 42251]]

and based on the effects seen for different durations and routes of 
exposure, determines which risk assessments should be done to assure 
that the public is adequately protected from any pesticide exposure 
scenario. Both short and long durations of exposure are always 
considered. Typically, risk assessments include ``acute'', ``short-
term'', ``intermediate term'', and ``chronic'' risks. These assessments 
are defined by the Agency as follows.
    Acute risk, by the Agency's definition, results from 1-day 
consumption of food and water, and reflects toxicity which could be 
expressed following a single oral exposure to the pesticide residues. 
High end exposure to food and water residues are typically assumed.
    Short-term risk results from exposure to the pesticide for a period 
of 1-7 days, and therefore overlaps with the acute risk assessment. 
Historically, this risk assessment was intended to address primarily 
dermal and inhalation exposure which could result, for example, from 
residential pesticide applications. However, since enaction of FQPA, 
this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from 
food, water, and residential uses when reliable data are available. In 
this assessment, risks from average food and water exposure, and high-
end residential exposure, are aggregated. High-end exposures from all 
three sources are not typically added because of the very low 
probability of this occurring in most cases, and because the other 
conservative assumptions built into the assessment assure adequate 
protection of public health. However, for cases in which high-end 
exposure can reasonably be expected from multiple sources (e.g. 
frequent and widespread homeowner use in a specific geographical area), 
multiple high-end risks will be aggregated and presented as part of the 
comprehensive risk assessment/characterization. Since the toxicological 
endpoint considered in this assessment reflects exposure over a period 
of at least 7 days, an additional degree of conservatism is built into 
the assessment; i.e., the risk assessment nominally covers 1-7 days 
exposure, and the toxicological endpoint/NOEL is selected to be 
adequate for at least 7 days of exposure. (Toxicity results at lower 
levels when the dosing duration is increased.)
    Intermediate-term risk results from exposure for 7 days to several 
months. This assessment is handled in a manner similar to the short-
term risk assessment.
    Chronic risk assessment describes risk which could result from 
several months to a lifetime of exposure. For this assessment, risks 
are aggregated considering average exposure from all sources for 
representative population subgroups including infants and children.

B. Aggregate Exposure

    In examining aggregate exposure, FFDCA section 408 requires that 
EPA take into account available and reliable information concerning 
exposure from the pesticide residue in the food in question, residues 
in other foods for which there are tolerances, residues in groundwater 
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or 
buildings (residential and other indoor uses). Dietary exposure to 
residues of a pesticide in a food commodity are estimated by 
multiplying the average daily consumption of the food forms of that 
commodity by the tolerance level or the anticipated pesticide residue 
level. The Theoretical Maximum Residue Contribution (TMRC) is an 
estimate of the level of residues consumed daily if each food item 
contained pesticide residues equal to the tolerance. In evaluating food 
exposures, EPA takes into account varying consumption patterns of major 
identifiable subgroups of consumers, including infants and children.The 
TMRC is a ``worst case'' estimate since it is based on the assumptions 
that food contains pesticide residues at the tolerance level and that 
100% of the crop is treated by pesticides that have established 
tolerances. If the TMRC exceeds the RfD or poses a lifetime cancer risk 
that is greater than approximately one in a million, EPA attempts to 
derive a more accurate exposure estimate for the pesticide by 
evaluating additional types of information (anticipated residue data 
and/or percent of crop treated data) which show, generally, that 
pesticide residues in most foods when they are eaten are well below 
established tolerances.
    Percent of crop treated estimates are derived from federal and 
private market survey data. Typically, a range of estimates are 
supplied and the upper end of this range is assumed for the exposure 
assessment. By using this upper end estimate of percent of crop 
treated, the Agency is reasonably certain that exposure is not 
understated for any significant subpopulation group. Further, regional 
consumption information is taken into account through EPA's computer-
based model for evaluating the exposure of significant subpopulations 
including several regional groups, to pesticide residues. For this 
pesticide, the most highly exposed population subgroup 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 
flutolanil and to make a determination on aggregate exposure, 
consistent with section 408(b)(2), for time-limited tolerances for 
residues of flutolanil N-(3-(1-methylethoxy)phenyl)-2-
(trifluoromethyl)benzamide and its metabolites converted to 2-
(trifluoromethyl)benzoic acid and calculated as flutolanil in or on the 
raw agricultural commodities rice grain at 2.0 ppm and rice straw at 
8.0 ppm and in or on the processed food or feed commodities rice hulls 
at 7.0 ppm and rice bran at 3.0 ppm. EPA's assessment of the dietary 
exposures and risks associated with establishing the tolerance follows.

A. Toxicological Data Base

    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 flutolanil are 
discussed below.
    1.  Acute studies. Acute toxicity studies, except for the acute 
dermal study, were classified as Toxicity Category IV. The acute dermal 
study places technical flutolanil in Toxicity Category III (Caution). 
Data show minimal to slight irritation to the eye. Flutolanil is not a 
dermal sensitizer and is non-irritating to skin.
    2.  Subchronic toxicity testing. i. A subchronic feeding study in 
rats was conducted for 3 months. Flutolanil was orally administered at 
dose levels of 0, 500, 4,000 or 20,000 ppm (0, 37, 299 or 1,512 
milligrams/kilograms/day (mg/kg/day) in males and 0, 44, 339 or 1,743 
mg/kg/day in females). The systemic Lowest Observed Effect Level (LOEL) 
is 299 mg/kg/day based on increased absolute and relative liver 
weights. The systemic No Observed Effect Level (NOEL) is 37 mg/kg/day.
    ii. A subchronic oral toxicity study in dogs was conducted for 90 
days. Flutolanil was administered orally via

[[Page 42252]]

gelatin capsules at dose levels of 0, 80, 400 or 2,000 mg/kg/day. The 
LOEL for this study was 400 mg/kg/day based on systemic signs of 
toxicity in the form of enlarged livers and increased severity of 
glycogen deposition in both males and females. The NOEL was 80 mg/kg/
day.
    iii. In a 21-day repeated dose dermal toxicity study, flutolanil 
was administered dermally to rats in 15 applications at doses of 0 or 
1,000 mg/kg/day. No LOEL was established for systemic or dermal 
toxicity. The NOEL for dermal effects was > 1,000 mg/kg/day (limit 
dose) and the systemic toxicity NOEL was also > 1,000 mg/kg/day (limit 
dose).
    3.  Chronic toxicity studies. A 2-year dog feeding study was 
conducted using doses of 0, 50, 250, or 1,250 mg/kg/day. The LOEL is 
250 mg/kg/day based on evidence of systemic toxicity in the form of 
increased incidence of clinical toxic signs (emesis, salivation and 
soft stool), lower body weight gains and decreased food consumption. 
The NOEL is 50 mg/kg/day.
    4. Carcinogenicity. i. In a 2-year combined chronic toxicity/
carcinogenicity study, technical grade flutolanil was administered in 
the diet to rats at dose levels of 0, 40, 200, 2,000, or 10,000 ppm (0, 
1.8, 8.7, 86.9, or 460 mg/kg/day for males and 0, 2.1, 10, 103.1 or 
535.8 mg/kg/day for females. The LOEL for systemic toxicity for males 
is 460.5 mg/kg/day and 535.8 mg/kg/day for females based on reduced 
body weight and body weight gain in males, along with decreased 
absolute and relative weights in females. The NOEL for systemic 
toxicity is 86.9 mg/kg/day for males and 103.1 mg/kg/day for females. 
Flutolanil was not carcinogenic under the conditions of this study.
    ii. A carcinogenicity study in mice was conducted for 78 weeks in 
which technical flutolanil was administered in the diet at 0, 300, 
1,500, 7,000 or 30,000 ppm (0, 32, 162, 735, or 3,333 mg/kg/day for 
males and 0, 34, 168, 839, or 3,676 mg/kg/day for females). The LOEL 
for systemic toxicity is 3,333 mg/kg/day in males and 839 mg/kg/day for 
females based on significant decreases in body weight gains in the high 
dose tested. The NOEL is 735 mg/kg/day in males and 162 mg/kg/day in 
females. Flutolanil was not carcinogenic under the conditions of this 
study.
    5. Developmental toxicity. i. In a developmental toxicity study in 
rats, flutolanil was administered orally via oral gavage at dose levels 
of 0, 40, 200 or 1,000 mg/kg/day on gestational days (GDs) 6-15, 
inclusive. No maternal toxicity was observed at any dose level. No 
compound-related effects were observed at any dose level for 
developmental toxicity. No Maternal LOEL was established. The maternal 
NOEL is > 1,000 mg/kg/day (limit dose). A developmental LOEL was not 
established. The developmental NOEL is > 1,000 mg/kg/day (limit dose).
    ii. In a developmental toxicity study, rabbits were administered 
flutolanil via oral gavage at dose levels of 0, 40, 200 or 1,000 mg/kg/
day on GDs 6-18, inclusive. No significant maternal or developmental 
toxicity was noted at the dose levels tested. The maternal toxicity 
NOEL is > 1,000 mg/kg/day, the developmental toxicity LOEL is > 1,000 
mg/kg/day and the developmental toxicity NOEL is > 1,000 mg/kg/day.
    6. Reproductive toxicity. i. In a three-generation reproduction and 
developmental study, flutolanil was administered in the diet to rats at 
0, 1,000 or 10,000 ppm (equivalent to 0, 63.7 or 661.8 mg/kg/day in 
males and 0, 86.3 or 880.8 mg/kg/day for females). For the reproduction 
segment of this study, flutolanil at the highest levels produced 
offspring systemic toxicity in the form of reduced pup body weights and 
body weight gains in both males and females. There was no treatment 
related clinical toxicity signs, mortality, differences in food 
consumption or efficiency and water consumption. No treatment related 
effects were noted on mating performance, duration of pregnancy and 
litter size. Provided gross examination data was limited. Organ weights 
showed increases in absolute and relative liver weights in the high 
dose males and females across generations. This effect is consistent 
with observations found in other chronic toxicity studies. The 
offspring systemic toxicity LOEL is 661.8 mg/kg/day. The offspring 
systemic toxicity NOEL is 63.7 mg/kg/day. For the developmental 
segment, there may have been an effect in both dose groups in the form 
of reduced fetal body weights. Fetal examinations showed no treatment 
related effects on gross or skeletal examinations. Visceral examination 
revealed a possible treatment related increase in enlargement of the 
renal pelvis (statistically significant in the high dose group). These 
studies were classified as supplementary due to deficiencies. A 
discussion of the study is included because the reference dose (RfD) 
was established based on this study.
    ii. In a two-generation reproductive toxicity study, technical 
flutolanil was administered daily in the diet to rats at 0, 200, 2,000 
or 20,000 ppm (during premating, for males 0, 16, 159, or 1,625 mg/kg/
day and for females 0, 19, 190, or 1,936 mg/kg/day. No compound-related 
parental effects were observed in either sex or generation. 
Consequently, the LOEL for parental toxicity was not determined and the 
NOEL for parental toxicity is > 1,625 mg/kg/day (exceeds limit dose).
     7.  Mutagenicity. Mutagenicity studies included: In vitro 
Aberrations in Don Cells, Mouse Micronucleus, Mammalian Cells in 
Culture Cytogenetics Assay in Human Lymphocytes, Salmonella and E. coli 
Reverse Mutation Assays, In vitro Unscheduled DNA Synthesis Assays in 
Primary Rat Hepatocytes, and Gene Mutation in Cultured Mammalian Cells 
(Mouse Lymphoma Cells). The In vitro Aberrations in Don Cells study was 
positive for inducing chromosomal aberrations in cultured Chinese 
hamster lung cells in the presence of metabolic activation. All other 
studies were negative.
     8. Metabolism. In a metabolism study in rats, disposition and 
metabolism of 14C-flutolanil was investigated at a low oral dose of 20 
mg/kg/day, repeated low oral doses of 20 mg/kg for 14 days, and a 
single high dose of 1,000 mg/kg. Absorption of flutolanil was 
incomplete at the single low and high doses, but appeared to be 
increased after repeated low oral dosing. There were no appreciable 
tissue levels of flutolanil at study termination. At the single low 
oral dose, excretion in urine and feces was equivalent, with 
approximately 40% of an administered dose excreted via each route in 
male and female rats. Repeated low dosing resulted in an increased 
percentage in urine (approximately 70%) with a corresponding decrease 
in fecal excretion. At the single high dose, the majority of the 
radioactivity (66-78%) was excreted via the feces, with less than 10% 
found in urine. Identification of urinary and fecal metabolites by TLC 
showed the presence of the major metabolite M4 (desisopropylflutolanil) 
in urine in all dose groups. In feces, radioactivity was excreted 
mainly as parent compound, with limited conversion to M4.
     9.  Neurotoxicity. There have been no clinical neurotoxic signs or 
other types of neurotoxicity observed in any of the evaluated 
toxicology studies.
     10. Other toxicological considerations. Flutolanil has a complete 
data base and no other toxicological concerns have been identified in 
the evaluated studies.

B. Toxicological Endpoints

    1. Acute toxicity. EPA has determined that data do not indicate the 
potential for adverse effects after a single dietary exposure.
     2. Short - and intermediate - term toxicity. No appropriate 
endpoints were

[[Page 42253]]

identified for short - term (1-7 days), or intermediate-term (1 week to 
several months) exposure.
     3. Chronic toxicity. EPA has established the Reference dose (RfD) 
for flutolanil at 0.63 mg/kg/day. This RfD is based on the reproductive 
toxicity study in rats with a NOEL of 63 mg/kg/day and an uncertainty 
factor of 100.
    4. Carcinogenicity. Using its Guidelines for Carcinogen Risk 
Assessment published September 24, 1986 (51 FR 33992), EPA has 
classified flutolanil as a Group E chemical--``Evidence of Non-
carcinogenicity for Humans'' --based on the results of carcinogenicity 
studies in two species. The doses tested are adequate for identifying a 
cancer risk.

C. Exposures and Risks

    1. From food and feed uses. Tolerances have been established (40 
CFR 180.484 and 185.3385) for flutolanil N-(3-(1-methylethoxy)phenyl)-
2-(trifluoromethyl)benzamide and its metabolites converted to 2-
(trifluoromethyl)benzoic acid and calculated as flutolanil in or on the 
raw agricultural commodities peanuts, peanut hay and hulls, meat, milk, 
poultry and eggs and the processed food commodity peanut meal. Time-
limited tolerances were previously established for the raw agricultural 
commodities rice grain and rice straw and for the processed food 
commodities rice hulls and rice bran. These time-limited tolerances 
expired and are being reestablished in today's action. Risk assessments 
were conducted by EPA to assess dietary exposures and risks from 
flutolanil 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. EPA did not identify an acute dietary 
toxicological endpoint and thus, flutolanil is not considered to pose 
an acute dietary risk.
    ii. Chronic exposure and risk. Chronic dietary (food only) exposure 
analyses were performed using tolerance level residues and 100 percent 
crop treated information to estimate the Theoretical Maximum Residue 
Contribution (TMRC) for the general population and 22 subgroups. The 
existing flutolanil tolerances and the added tolerances for rice 
commodities result in an exposure that is equivalent to 0.2% of the RfD 
for the U.S. population and 0.5% for children (1-6 years old). Even 
without refinement, the chronic dietary risk exposure to flutolanil 
appears to be minimal for use of flutolanil on rice and does not exceed 
the RfD for any of the subgroups.
    2. From drinking water. There is no established Maximum Contaminant 
Level for residues of flutolanil in drinking water. No Health Advisory 
Levels for flutolanil in drinking water have been established. The 
``Pesticides in Groundwater Database'' has no information concerning 
flutolanil. Estimates of ground and surface water concentrations for 
flutolanil were determined based on a maximum annual application rate 
of 1.0 pound active ingredient/acre. The surface water numbers are 
based on the results of a Generic Environmental Concentration (GENEECX/
beta version) model. The modeling results indicated that flutolanil has 
the potential to contaminate surface waters through erosion of soil 
particles to which flutolanil is adsorbed or through off-site draining 
of rice paddy water containing the chemical. The ground water numbers 
are based on a screening tool, SCI-GROW, which tends to overestimate 
the true concentration in the environment. These modeling results 
indicate that flutolanil will not be found in significant 
concentrations in groundwater. For acute effects, the surface water 
estimated environmental concentration (EEC) was determined to be 565 
parts per billion (ppb). For chronic effects the surface water EEC was 
542 ppb. The estimated groundwater concentration for both acute and 
chronic effects is 0.399 ppb
    i. Acute exposure and risk.  No acute risk is expected from 
exposure to flutolanil.
    ii. Chronic exposure and risk. Chronic exposure is calculated based 
on surface water. Chronic exposure from ground water is lower. Chronic 
exposure (mg/kg/day) is calculated by multiplying the concentration in 
water in mg/l by the daily consumption (2l/day for male and female 
adults and 1l/day for children) and dividing this figure by average 
weight (70 kg for males, 60 kg for females and 10 kg for children). For 
adult males, exposure is 0.015 mg/kg/day; for adult females, 0.018 mg/
kg/day; and for children, 0.054 mg/kg/day. Chronic risk (non-cancer) 
from surface water, using EPA's conservative model for estimating 
exposure through surface water, was calculated to be 2.4% of the Rfd 
for males, 2.9% for females and 8.6% for children.
    3. From non-dietary exposure. Flutolanil is not currently 
registered for use on non-food sites. Therefore, acute, short - and 
intermediate-term and chronic (non-cancer) occupational or residential 
risk assessments are not required
    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).
    EPA does not have, at this time, available data to determine 
whether flutolanil has a common mechanism of toxicity with other 
substances or how to include this pesticide in a cumulative risk 
assessment. Unlike other pesticides

[[Page 42254]]

for which EPA has followed a cumulative risk approach based on a common 
mechanism of toxicity, flutolanil 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 flutolanil has a 
common mechanism of toxicity with other substances.

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

    1. Acute risk. No acute dietary risks were identified.
    2. Chronic risk. Using the unrefined exposure assumptions described 
above, EPA has concluded that aggregate exposure to flutolanil from 
food will utilize 0.2% of the RfD for the U.S. population. The major 
identifiable subgroup with the highest aggregate exposure is children 
(1-6 years old) which is discussed below. EPA generally has no concern 
for exposures below 100% of the RfD because the RfD represents the 
level at or below which daily aggregate dietary exposure over a 
lifetime will not pose appreciable risks to human health. Despite the 
potential for exposure to flutolanil in drinking water, EPA does not 
expect the aggregate exposure to exceed 100% of the RfD.
    3. Short- and intermediate-term risk. Short- and intermediate-term 
aggregate exposure takes into account chronic dietary food and water 
(considered to be a background exposure level) plus indoor and outdoor 
residential exposure. No short- or intermediate-term risk is expected 
from the use of flutolanil.
    4. Aggregate cancer risk for U.S. population. Flutolanil is 
classified as Category E: not carcinogenic in two acceptable animal 
studies. Since flutolanil is not carcinogenic, there would be no 
expected risk of cancer in humans from the use of flutolanil.
    5.  Conclusion. EPA concludes that there is a reasonable certainty 
that no harm will result from aggregate exposure to flutolanil 
residues.

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

    1. Safety factor for infants and children-- i. In general. In 
assessing the potential for additional sensitivity of infants and 
children to residues of flutolanil, EPA considered data from 
developmental toxicity studies in the rat and rabbit and a three-
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 during 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. Margins of 
safety are incorporated into EPA risk assessments either directly 
through use of a MOE analysis or through using uncertainty (safety) 
factors in calculating a dose level that poses no appreciable risk to 
humans. EPA believes that reliable data support using the standard 
uncertainty factor (usually 100 for combined inter- and intra-species 
variability) and not the additional tenfold MOE/uncertainty factor when 
EPA has a complete data base under existing guidelines and when the 
severity of the effect in infants or children or the potency or unusual 
toxic properties of a compound do not raise concerns regarding the 
adequacy of the standard MOE/safety factor.
    ii. Developmental toxicity studies-- a.  Rats. No maternal toxicity 
was observed at any dose level. No compound-related effects were 
observed at any dose level for developmental toxicity. A maternal LOEL 
was not established. The maternal NOEL is <gr-thn-eq> 1,000 mg/kg/day 
(limit dose). A developmental LOEL was not established. The 
developmental NOEL is <gr-thn-eq> 1,000 mg/kg/day (limit dose).
    b. Rabbits. In the developmental toxicity study in rabbits, no 
significant maternal or developmental toxicity was noted at the dose 
levels tested. The maternal toxicity LOEL is > 1,000 mg/kg/day and the 
maternal toxicity NOEL is <gr-thn-eq> 1,000 mg/kg/day. The 
developmental toxicity LOEL is > 1,000 mg/kg/day and the developmental 
toxicity NOEL is <gr-thn-eq> 1,000 mg/kg/day.
    iii. Reproductive toxicity study-- a.  Rats. In the 3-generation 
reproduction and development study in rats, systemic toxicity was noted 
in offspring at the highest dose in the form of reduced pup body 
weights and body weight gains during the lactation period and 
subsequent reduced adult body weights in both males and females. There 
were no treatment related clinical toxicity signs, mortality, 
differences in food consumption or efficiency and water consumption. No 
treatment related effects were noted on mating performance, duration of 
pregnancy and litter size. Organ weights showed increases in absolute 
and relative liver weights in the high dose males and females across 
generations. This effect is consistent with observations found in other 
chronic toxicity studies. The offspring systemic toxicity LOEL is 661.8 
mg/kg/day. The offspring systemic toxicity NOEL is 63.7 mg/kg/day. For 
the developmental segment, there may have been an effect in both dose 
groups in the form of reduced fetal body weights. Fetal examinations 
showed no treatment related effects on gross or skeletal examinations. 
Visceral examination revealed a possible treatment related increase in 
enlargement of the renal pelvis in the high dose group.
    b. Rats. In a two-generations reproductive toxicity study, no 
compound-related parental effects were observed in either sex or 
generation. The LOEL for parental toxicity was not determined and the 
NOEL for parental toxicity is > 1,625 mg/kg/day (exceeds limit dose).
    iv. Pre- and post-natal sensitivity. The pre- and post-natal 
toxicology data base for flutolanil is complete with respect to current 
toxicological data requirements. Based on the developmental and 
reproductive toxicity studies discussed above, there does not appear to 
be an extra sensitivity for pre- or post-natal effects.
    v. Conclusion. EPA concludes that reliable data support use of the 
hundredfold uncertainty factor and that an additional tenfold factor is 
not needed to ensure the safety of infants and children from dietary 
exposure.
    2. Acute risk. No acute dietary risk has been identified.
    3. Chronic risk. Using the conservative exposure assumptions 
described above, EPA has concluded that exposure to flutolanil from 
food will utilize 0.2% of the Rfd for the U.S. population and 0.5% for 
children 1-6 years old. EPA generally has no concern for exposures 
below 100% of the RfD because the RfD represents the level at or below 
which daily aggregate dietary exposure over a lifetime will not pose 
appreciable risks to human health. Despite the potential for exposure 
to flutolanil in drinking water and from non-dietary, non-occupational 
exposure, EPA does not expect the aggregate exposure to exceed 100% of 
the RfD. EPA concludes that there is a reasonable certainty that no 
harm will result to infants and children from aggregate exposure to 
flutolanil residues.
    4. Short- or intermediate-term risk. No appropriate endpoints were 
identified for short- or intermediate-term exposure, therefore, no 
unreasonable adverse effects are expected to result from the use of 
flutolanil.

[[Page 42255]]

    5. Conclusion. EPA concludes that there is a reasonable certainty 
that no harm will result to infants and children from aggregate 
exposure to flutolanil residues.

III. Other Considerations

A. Endocrine Disrupter 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 endocrine 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.

B. Metabolism In Plants and Animals

    1. Plants. Based on the three metabolism studies on peanuts, rice 
and cucumbers (which indicate a similar metabolic route for crops in 
three different crop groups), the nature of the residues is adequately 
understood. The residues of concern for flutolanil consist of 
flutolanil N-(3-(1-methylethoxy)phenyl)-2-trifluoromethyl)benzamide and 
identified metabolites containing the common moiety, 2-trifluoromethyl 
benzanilide. The tolerance expression takes cognizance of this and is 
expressed in the terms of the analytical derivative of this common 
moiety. The residue of concern in plants consists of flutolanil and 
metabolites convertible to the methyl ester of 2-trifluoromethyl 
benzoic acid.
    2. Animals. The nature of the residue in animals is adequately 
understood. The residues of concern in animal commodities are 
flutolanil and identified metabolites containing the common moiety, 2-
trifluoromethyl benzanilide and that can be converted to the methyl 
ester of 2-trifluoromethyl benzoic acid. .

C. Analytical Enforcement Methodology

     The residue analytical method will be forwarded to FDA for 
publication after the Agency has concluded its review of the 
independent validation of the method which is currently under review. 
This method is available for limited distribution from: By mail, 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: Crystal Mall #2, Rm. 101FF, 1921 
Jefferson Davis Hwy., Arlington, VA 22202 (703) 305-5229. The method 
has the following disclaimer: This method is for use only by 
experienced chemists who have demonstrated knowledge of the principles 
of trace organic analysis; and have proven skills and abilities to run 
a complex residue analytical method obtaining accurate results at the 
part per billion level. Users of this method are expected to perform 
additional method validation prior to using the method for either 
monitoring or enforcement. The method can detect gross misuse.

D. Magnitude of Residues

    The residues of flutolanil and its metabolites converted to 2-
(trifluoromethyl)benzoic acid resulting from the use on rice will not 
exceed 2.0 ppm in rice grain, 8.0 ppm in rice straw, 7.0 ppm in rice 
hulls or 3.0 ppm in rice bran. Residue data for animal commodities 
indicated that the currently established tolerances are adequate to 
cover the use of flutolanil on rice.

E. International Residue Limits

    There are no Codex, Canadian or Mexican residue limits established 
for flutolanil on rice. Therefore, no compatibility problems exist for 
the proposed tolerances on rice.

F. Rotational Crop Restrictions.

    Rotational crop restrictions for rice include: 240 day restriction 
for soybeans or grain sorghum and 12 months for all other crops except 
peanuts and rice.

IV. Conclusion

    Therefore, time-limited tolerances, to expire on December 31, 2000, 
are established for the residues of the fungicide flutolanil N-(3-(1-
methylethoxy)phenyl)-2-(trifluoromethyl)benzamide and its metabolites 
converted to 2-(trifluoromethyl)benzoic acid and calculated as 
flutolanil in or on the raw agricultural commodities rice grain at 2.0 
ppm and rice straw at 8.0 ppm and in or on the processed food or feed 
commodities rice hulls at 7.0 ppm and rice bran at 3.0 ppm when present 
therein as a result of application of the fungicide to growing crops. 
The tolerances are time-limited to allow the Agency adequate time to 
review additional residue studies and to review the method validation 
for flutolanil which have already been submitted.

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 October 6, 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 
Confidential Business Information (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

[[Page 42256]]

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-300697] (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:
    <a href="/cdn-cgi/l/email-protection#98f7e8e8b5fcf7fbf3fdecd8fde8f9f5f9f1f4b6fde8f9b6fff7ee"><span class="__cf_email__" data-cfemail="68071818450c070b030d1c280d180905090104460d1809460f071e">[email protected]</span></a>.

    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 time-limited tolerances 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 time-limited tolerances 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 was 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

40 CFR Part 180

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

40 CFR Part 185

    Environmental protection, Food additives, Pesticides and pests.

    Dated: July 29, 1998.

Arnold E. Layne,

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

PART 180 --[AMENDED]

    1. In part 180:
    a. The authority citation for part 180 continues to read as 
follows:

    Authority: 21 U.S.C. 346a and 371.


    b. Section 180.484 is amended as follows:
    i. By adding a paragraph heading ``General'' to paragraph (a).
    ii. By redesignating the text in paragraph (a) as paragraph (a)(1), 
``Permanent tolerances.''
    iii. By adding paragraph (a)(2).
    iv. By adding a heading to paragraph (b) and removing and reserving 
the text of the paragraph.
    v. By adding paragraphs (c) and (d) with headings and reserving the 
text of those paragraphs.
    The added text reads as follows:


Sec. 180.484  Flutolanil; tolerances for residues.

    (a) General -- (1) Permanent tolerances. *  *  *
    (2) Time-limited tolerances.  Time-limited tolerances are 
established for the residues of the fungicide flutolanil N-(3-(1-
methylethoxy)phenyl)-2-(trifluoromethyl)benzamide and its metabolites 
converted to 2-(trifluoromethyl) benzoic acid and calculated as 
flutolanil in or on the following agricultural commodities:

------------------------------------------------------------------------
                                                  Parts     Expiration/ 
                   Commodity                       per      Revocation  
                                                 million       Date     
------------------------------------------------------------------------
Rice, grain....................................      2.0        12/31/00
Rice, straw....................................      8.0        12/31/00
Rice, bran.....................................      3.0        12/31/00
Rice, hulls....................................      7.0        12/31/00
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c)  Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]

PART 185 --[AMENDED]

    2. In part 185:
    a. The authority citation for part 185 continues to read as 
follows:


[[Page 42257]]


    Authority: 21 U.S.C. 348.


Sec. 180.3385 [Removed]

    b. In Sec. 185.3385, in the table to paragraph (a), the entry for 
``peanut meal'' is transferred and alphabetically added to the table in 
paragraph (a)(1) of Sec. 180.484. The remainder of Sec. 185.3385 is 
removed.
[FR Doc. 98-20899 Filed 8-6-98; 8:45 am]
BILLING CODE 6560-50-F .


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