[Federal Register Volume 65, Number 180 (Friday, September 15, 2000)]
[Rules and Regulations]
[Pages 55911-55921]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-23773]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-301005; FRL-6589-3]
RIN 2070-AB


Difenoconazole; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a tolerance for residues of 
difenoconazole [(2S,4R)/(2R/4S)]/[(2R/4R)/(2S,4S) 1-(2-[4-(4-
chlorophenoxy)-2-chlorophenyl]-4-methyl-1,3-dioxolan-2-yl-methyl)-1H-
1,2,4-triazole in or on canola, seed. Novartis Crop Protection, Inc. 
requested this tolerance under the Federal Food, Drug, and Cosmetic 
Act, as amended by the Food Quality Protection Act of 1996.

DATES: This regulation is effective September 15, 2000. Objections and 
requests for hearings, identified by docket control number OPP-301005, 
must be received by EPA on or before November 14, 2000.

ADDRESSES: Written objections and hearing requests may be submitted by 
mail, in person, or by courier. Please follow the detailed instructions 
for each method as provided in Unit VI. of the ``SUPPLEMENTARY 
INFORMATION.'' To ensure proper receipt by EPA, your objections and 
hearing requests must identify docket control number OPP-301005 in the 
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, 
Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., 
NW.,Washington, DC 20460; telephone number: (703) 305-7740; and e-mail 
address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer, or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         Potentially
                                                       Affected Entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically.You may obtain electronic copies of this 
document, and

[[Page 55912]]

certain other related documents that might be available electronically, 
from the EPA Internet Home Page at http://www.epa.gov/. To access this 
document, on the Home Page select ``Laws and Regulations'' and then 
look up the entry for this document under the ``Federal Register--
Environmental Documents.'' You can also go directly to theFederal 
Register listings at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number OPP-301005. The official record 
consists of the documents specifically referenced in this action, and 
other information related to this action, including any information 
claimed as Confidential Business Information (CBI). This official 
record includes the documents that are physically located in the 
docket, as well as the documents that are referenced in those 
documents. The public version of the official record does not include 
any information claimed as CBI. The public version of the official 
record, which includes printed, paper versions of any electronic 
comments submitted during an applicable comment period is available for 
inspection in the Public Information and Records Integrity Branch 
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy., 
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.

II. Background and Statutory Findings

    In the Federal Register of May 5, 1999 (64 FR 24153) (FRL-6072-7), 
EPA issued a notice pursuant to section 408 of the Federal Food, Drug, 
and Cosmetic Act (FFDCA), 21 U.S.C. 346a as amended by the Food Quality 
Protection Act of 1996 (FQPA) (Public Law 104-170) announcing the 
filing of a pesticide petition (PP) for tolerance by Novartis Crop 
Protection, Inc. This notice included a summary of the petition 
prepared by Novartis Crop Protection, Inc., the registrant. There were 
no comments received in response to this notice of filing.
    The petition requested that 40 CFR 180.475 be amended by 
establishing a tolerance for the fungicide, difenoconazole [(2S,4R)/
(2R/4S)]/[(2R/4R)/(2S,4S) 1-(2-[4-(4-chlorophenoxy)-2-chlorophenyl]-4-
methyl-1,3-dioxolan-2-yl-methyl)-1H-1,2,4-triazole, in or on canola, 
seed at 0.01 ppm.
    Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable 
certainty that no harm will result from aggregate exposure to the 
pesticide chemical residue, including all anticipated dietary exposures 
and all other exposures for which there is reliable information.'' This 
includes exposure through drinking water and in residential settings, 
but does not include occupational exposure. Section 408(b)(2)(C) 
requires EPA to give special consideration to exposure of infants and 
children to the pesticide chemical residue in establishing a tolerance 
and to ``ensure that there is a reasonable certainty that no harm will 
result to infants and children from aggregate exposure to the pesticide 
chemical residue....''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 and a complete description of 
the risk assessment process, see the final rule on Bifenthrin Pesticide 
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).

III. 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 and to 
make a determination on aggregate exposure, consistent with section 
408(b)(2), for a tolerance for residues of difenoconazole [(2S,4R)/(2R/
4S)]/[(2R/4R)/(2S,4S) 1-(2-[4-(4-chlorophenoxy)-2-chlorophenyl]-4-
methyl-1,3-dioxolan-2-yl-methyl)-1H-1,2,4-triazole in or on canola, 
seed at 0.01 ppm. 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 difenoconazole are 
discussed in this unit.
    Difenoconazole possesses low acute toxicity. Technical 
difenoconazole had the following acute toxicology endpoints and 
toxicity categories. The acute oral toxicity Lethal Dose 50% 
(LD50) was 1,453 milligrams per kilogram (mg/kg) (Toxicity 
Category III). The acute dermal toxicity LD50 was >2,010 mg/
kg (Toxicity Category III). The acute inhalation Lethal Concentration 
50% (LC50) was >3,300 milligrams per cubic meter (mg/
m3; 4 hours of exposure; Toxicity Category IV). The primary 
eye irritation results were mild eye irritation, reversible in 7 days 
(Toxicity Category III). The primary skin irritation results were 
slight irritation (Toxicity Category IV). The dermal sensitization 
results were negative.
    Subchronic studies in mice and rats manifested decreased body 
weights, decreased body weight gains, and effects on the liver at 200 
ppm and higher. Microscopic examination of the eyes of dogs at 3,000 
ppm revealed unilateral and bilateral lenticular cataracts in both 
sexes of animals. Decreased body weights, body weight gains, and food 
consumption were reported in a 21-day rabbit dermal study at the lowest 
observed adverse effect level (LOAEL) of 100 mg/kg/day.
    Chronic studies in rats revealed decreased body weight gains and 
increased liver weights along with hepatocellular hypertrophy. Clinical 
chemistry data supported the liver pathology data suggesting that the 
liver was the primary target organ. There were no treatment-related 
neoplastic effects. The LOAEL was 500 ppm (equal to 24.12 and 32.79 
milligrams per kilogram per day (mg/kg/day) for males and females, 
respectively) and the no observed adverse effect level (NOAEL) was 20 
ppm (equal to 0.96 and 1.27 mg/kg/day for males and females, 
respectively).
    Chronic feeding studies in mice showed decreased body weight gains 
in male and female mice at termination. Treatment-related non-
neoplastic lesions were confined to the liver and were supported by the 
clinical chemistry data at a level of 300 ppm (46.29 and 57.79 mg/kg/
day for males and females, respectively). Liver tumors were observed in 
mice at 300 ppm and higher; however, based on the excessive toxicity 
observed at the two highest doses of 2,500 and 4,500 ppm (females 
terminated after 2 weeks due to excessive toxicity resulting in 
moribundity and death), the absence of tumors at the two lower doses of 
10 and 30 ppm, and the absence of genotoxic effects, the Cancer Peer 
Review Committee (CPRC) recommended for a cancer classification of C 
(possible human carcinogen) and advocated a Margin of Exposure (MOE) 
approach to risk assessment utilizing the NOAEL of 30 ppm (4.7 and 5.6 
mg/kg/day in males and females, respectively) and the LOAEL of 300 ppm 
(46.3 and 57.8 mg/

[[Page 55913]]

kg/day in males and females, respectively) from the mouse study, using 
only those biological endpoints which were related to tumor development 
(i.e., hepatocellular hypertrophy, liver necrosis, fatty changes in the 
liver, and bile stasis).
    The chronic study in beagle dogs revealed decreased body weight 
gains throughout the study at 500 ppm and increased levels of alkaline 
phosphatase at 1,500 ppm (equal to 51.2 and 44.3 mg/kg/day for males 
and females, respectively). The LOAEL was 500 ppm (equal to 16.4 and 
19.4 mg/kg/day for males and females respectively) and the NOAEL was 
100 ppm (equal to 3.4 and 3.7 mg/kg/day for males and females, 
respectively).
    The results of the 2-generation and developmental studies did not 
demonstrate increased sensitivity to infants and children.
    Neurotoxicity studies are not applicable as this chemical is not a 
cholinesterase inhibitor and there is no evidence in the available data 
base that difenoconazole possesses neurotoxic properties. It is not 
structurally related to known neurotoxic compounds.
    Mutagenicity studies indicated that difenoconazole was not 
mutagenic under the test conditions.
    Metabolism studies in rats indicated that peak absorption occurred 
between 28 and 48 hours post-dosing. Elimination in the feces ranged 
between 78% and 94% and in the urine between 8% and 21%. Difenoconazole 
did not accumulate to any appreciable extent, since tissues contained 
less than 1.0% of the radioactivity after 7 days post-dosing. 
Difenoconazole undergoes successive oxidation and conjugation 
reactions. There is saturation of the metabolic pathway at high doses. 
The distribution, metabolism, and excretion of difenoconazole are not 
sex-dependent.
    The overall quality of the toxicology data base is good. Confidence 
in the hazard and dose response assessment is also good. There are no 
toxicology data gaps.

B. Toxicological Endpoints

    An inhalation dose/endpoint was not identified by the Agency 
because there is minimal concern for potential inhalation exposure/risk 
based on the low acute toxicity (Toxicity Category IV), application 
rate, application method, and number of applications (one time).
    1. Acute toxicity. An acute Reference Dose (RfD) for difenoconazole 
of 0.25 mg/kg was established for the subpopulation group females 13+ 
years old, based on a NOAEL of 25 mg/kg from a developmental toxicity 
study in the rabbit. Effects at the next higher dose level of 75 mg/kg 
(the LOAEL) were based on post-implantation loss and resorptions per 
dose and a significant decrease in fetal body weight. These effects are 
presumed to occur after a single exposure in utero and therefore are 
considered to be appropriate for this risk assessment. The 10x FQPA 
Safety Factor, to provide increased protection for infants and children 
where this is needed, was reduced to 1x because there is no evidence 
that infants and children have an increased sensitivity to 
difenoconazole. As a result, the acute RfD and the acute Population 
Adjusted Dose (aPAD) are the same: 0.25 mg/kg. An acute dose and 
endpoint were not selected for the general population group (including 
infants and children) because there were no effects oberved in oral 
toxicology studies including maternal toxicity in the developmental 
toxicity studies in rats and rabbits that are attributable to a single 
exposure (dose).
    2. Short- and intermediate-term toxicity. For difenoconazole, the 
short-term dermal dose/endpoint was chosen from a developmental rabbit 
study. An oral NOAEL of 25 mg/kg/day was selected, based on post-
implantation loss, increased resorptions per dose, and decreased body 
weight seen at 75 mg/kg/day (LOAEL). An intermediate-term dermal 
endpoint was chosen from a rat 2-generation reproduction study. The 
Agency chose an oral NOAEL of 1.25 mg/kg/day based on decreased pup 
weight on day 21 at 12.5 mg/kg/day (LOAEL).
    3.Chronic toxicity (non-cancer). EPA established an oral chronic 
RfD for difenoconazole at 0.01 mg/kg/day. This RfD is based on a 2-year 
chronic feeding/oncogenicity study in the rat, where the NOAEL of 0.96 
mg/kg/day (statistically equal to 1.0 mg/kg/day) was based on 
cumulative decreases in body weight gains at the LOAEL of 24.12 mg/kg/
day (500 ppm). This RfD was originally established by the Agency in 
1994, and reconfirmed by the Agency in 1998. The chronic Population 
Adjusted Dose (cPAD) and the chronic RfD are the same because the FQPA 
Safety Factor has been reduced to 1x for difenoconazole. A long-term 
dermal endpoint was not identified by the Agency because long-term 
dermal exposure is not expected based on a one-time application as a 
seed treatment.
    4. Carcinogenicity. In 1994, the Agency concluded that 
difenoconazole should be classed as a Group C carcinogen (possible 
human carcinogen) and recommended that, for the purpose of risk 
assessment, the MOE approach be used for the quantification of human 
risk. The decision to classify difenoconazole as a Group C carcinogen 
was based on statistically significant increases in liver adenomas, 
carcinomas, and combined adenomas and carcinomas in both sexes of CD-1 
mice, but only at doses that were considered to be excessively high for 
carcinogenicity testing. The MOE approach was recommended because there 
was only very weak (limited) evidence of carcinogenic potential at dose 
levels not considered to be excessive, with significant changes 
observed only at excessive doses. In addition, there was no evidence of 
genotoxicity. However, to date the Agency has not defined the level of 
concern for cancer risk using the MOE approach. Therefore, a 
quantitative risk analysis was conducted utilizing the Q1* 
approach. The Q1* was determined to be 0.157 (mg/kg/day)-
1. This value incorporates the scaling factor and is based 
on the male mouse liver adenomas and/or carcinomas combined.

C. Exposures and Risks

    1. From food and feed uses. Tolerances have previously been 
established (40 CFR 180.475) for the fungicide difenoconazole in or on 
the following raw agricultural commodities: Bananas, barley (grain 
only); eggs; the fat, meat, and meat byproducts of cattle, goats, hogs, 
horses, poultry, and sheep; milk; rye (grain only); sweet corn (fodder, 
forage, and grain) and wheat (forage, grain, and straw). The food risk 
analyses also included the pending residue tolerances for canola and 
sweet corn. The risk assessments conducted by EPA to assess food 
exposures were handled as follows. In the acute food risk analysis, 
present and proposed tolerance level residues and 100% crop treated 
(PCT) values were used in the calculation, producing a Theoretical 
Maximum Residue Contribution (TMRC). In the chronic and cancer food 
risk analyses, anticipated residues were used for most commodities, 
while reduced values for PCT were used for barley, sweet corn, and 
wheat. The PCT value used for barley is actually a percent crop 
imported value, because the barley residue tolerance is an import 
tolerance. Percent crop imported and PCT have equivalent effects on the 
calculations.
    Section 408(b)(2)(E) authorizes EPA to use available data and 
information on the anticipated residue levels of pesticide residues in 
food and the actual levels of pesticide chemicals that have been 
measured in food. If EPA relies on

[[Page 55914]]

such information, EPA must require that data be provided 5 years after 
the tolerance is established, modified, or left in effect, 
demonstrating that the levels in food are not above the levels 
anticipated. Following the initial data submission, EPA is authorized 
to require similar data on a time frame it deems appropriate. As 
required by section 408(b)(2)(E), EPA will issue a data call-in for 
information relating to anticipated residues to be submitted no later 
than 5 years from the date of issuance of this tolerance.
    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: Condition 1, 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; Condition 2, that the exposure estimate does not 
underestimate exposure for any significant subpopulation group; and 
Condition 3, 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. To 
provide for the periodic evaluation of the estimate of PCT as required 
by section 408(b)(2)(F), EPA may require registrants to submit data on 
PCT.
    The Agency used PCT information as follows and believes that the 
three conditions listed above have been met. With respect to Condition 
1, PCT estimates are derived from Federal and private market survey 
data, which are reliable and have a valid basis. EPA uses a weighted 
average PCT for chronic food exposure estimates. This weighted average 
PCT figure is derived by averaging State-level data for a period of up 
to 10 years, and weighting for the more robust and recent data. The 
percent imported data for barley were derived from statistics published 
by the National Agricultural Statistics Service and the Economic 
Research Service, both of which are units of the United States 
Department of Agriculture. A weighted average of the PCT reasonably 
represents a person's food exposure over a lifetime, and is unlikely to 
underestimate exposure to an individual because of the fact that 
pesticide use patterns (both regionally and nationally) tend to change 
continuously over time, such that an individual is unlikely to be 
exposed to more than the average PCT over a lifetime. For acute food 
exposure estimates, EPA uses estimated maximum PCTs (in this case 
100%). The exposure estimates resulting from this approach reasonably 
represent the highest levels to which an individual could be exposed, 
and are unlikely to underestimate an individual's acute dietary 
exposure. The Agency is reasonably certain that the percentage of the 
food treated is not likely to be underestimated. As to Conditions 2 and 
3, regional consumption information and consumption information for 
significant subpopulations is taken into account through EPA's 
computer-based model for evaluating the exposure of significant 
subpopulations including several regional groups. Use of this 
consumption information in EPA's risk assessment process ensures that 
EPA's exposure estimate does not understate exposure for any 
significant subpopulation group and allows the Agency to be reasonably 
certain that no regional population is exposed to residue levels higher 
than those estimated by the Agency. Other than the data available 
through national food consumption surveys, EPA does not have available 
information on the regional consumption of food to which difenoconazole 
may be applied in a particular area.
    A food exposure analysis using the Dietary Exposure Evaluation 
Model (DEEM) for the acute and both of the chronic (cancer and non-
cancer) analyses evaluated individual food consumption as reported by 
respondents during the USDA 1989-1992 Continuing Surveys of Food Intake 
by Individuals (CSFII) and accumulated exposure to the chemical from 
each commodity.
    i. Acute exposure and risk. Acute food 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. The endpoint used for all population 
subgroups that were analyzed in the acute food analyis was an aPAD of 
0.25 mg/kg that incorporated Uncertainty Factors of 10x for 
interspecies extrapolation, 10x for intraspecies variability, and 1x 
for the FQPA Safety Factor. The subgroups analyzed and the exposure 
values calculated at the 95th percentile were females 13+ years old, 
pregnant, and not nursing--0.000852 mg/kg; females 13+ years old, 
nursing--0.000889 mg/kg; females 13-29 years old, not pregnant, not 
nursing--0.000750 mg/kg; females 20+ years old, not pregnant, not 
nursing--0.000668 mg/kg; females 13-50 years old--0.000701 mg/kg. In 
each case the exposure value is less than 1% of the aPAD. The exposure 
values calculated at the 99th percentile were females 13+ years old, 
pregnant, and not nursing--0.001093 mg/kg; females 13+ years old, 
nursing--0.001086 mg/kg; females 13-29 years old, not pregnant, not 
nursing--0.001008 mg/kg; females 20+ years old, not pregnant, not 
nursing--0.000987 mg/kg; females 13-50 years old--0.001008 mg/kg. In 
each of these cases the exposure value is also less than 1% of the 
aPAD. The exposure values calculated at the 99.9th percentile were 
females 13+ years old, pregnant, and not nursing--0.001265 mg/kg; 
females 13+ years old, nursing--0.001115 mg/kg; females 13-29 years 
old, not pregnant, not nursing--0.001570 mg/kg; females 20+ years old, 
not pregnant, not nursing--0.001359 mg/kg; females 13-50 years old--
0.001436 mg/kg. Once again, in each of these cases the exposure value 
is less than 1% of the aPAD. The exposures were below the Agency's 
level of concern for all subgroups of females who were 13 to 50 years 
old. The Agency's level of concern is for exposures greater than 100% 
of the aPAD.
    ii. Chronic (non-cancer and cancer) exposure and risk. For the 
chronic (non-cancer) food analysis, a cPAD of 0.01 mg/kg/day was used. 
It incorporated Uncertainty Factors of 10x for interspecies 
extrapolation and 10x for intraspecies variability, and an FQPA Safety 
Factor of 1x. The chronic (both cancer and non-cancer) analyses for 
difenoconazole are both partially refined estimates (Tier 3 
assessments) because they use anticipated residues for all commodities 
and PCT information for some commodities.
    The exposure estimates produced by the chronic (non-cancer) dietary 
exposure analysis are the following: U.S. population (48 states)--
0.000005 mg/kg/day; all infants less than 1 year old--0.00016 mg/kg/
day; nursing infants less than 1 year old--0.000007; non-nursing 
infants less than 1 year old--0.000016 mg/kg/day; children 1-6 years 
old--0.000011 mg/kg/day; children 7-12 years old--0.000005 mg/kg/day; 
females 13-19 years old, not pregnant, not nursing--0.000003 mg/kg/day; 
females 20+, not pregnant, not nursing--0.000004 mg/kg/day; females 13-
50--0.000004 mg/kg/day; females 13+ years old, pregnant, nursing--
0.000004 mg/kg/day; females (13+ years old, nursing--0.000006 mg/kg/
day; non-Hispanic Whites--0.000006 mg/kg/day; non-Hispanic/non-White/
non-Black--0.000006 mg/kg/day. In each case the exposure estimate is 
less than 1% of the cPAD.
    The endpoint calculated for the chronic (cancer) analysis was a 
Q1* of 0.157 (mg/kg/day)-1. The result of the 
exposure analysis was that the exposure

[[Page 55915]]

for the U.S. population was estimated to be 0.000005 mg/kg/day. This 
exposure estimate produces a lifetime cancer risk estimate of 8.6 x 
10-7, below the Agency's 1 x 10-6 level of 
concern.
    2. From drinking water. The Agency does not have the monitoring 
data available that is needed to perform a quantitative drinking water 
risk assessment for difenconazole at this time. Ground and surface 
water concentration estimates, for the parent chemical only, were 
therefore calculated. These estimates may be used qualitatively.
    The Agency's Tier 1 models for estimating surface and ground water 
pesticide concentrations, GENEEC (Generic Estimated Environmental 
Concentration) and SCI-GROW (Screening Concentration in Ground Water), 
are not designed to estimate runoff or leaching values for seed 
treatment pesticides. Therefore, there are uncertainties in the 
predictive potential of the Tier 1 modeling. Additionally, it was 
necessary to use screened environmental fate data in the assessment 
because there was insufficient time to conduct a formal review of data 
that had previously been submitted by a predecessor company to Novartis 
Crop Protection, Inc. The uncertainties in the water assessment, 
however, are not expected to substantially decrease the 
conservativeness of the Tier 1 modeling results. The Tier 1 water 
modeling used in the instant analysis is the same as the analysis 
previously done for wheat. Because wheat is seeded at a much higher 
rate (by weight of seed) than canola, even more conservative estimates 
of resulting difenoconazole concentrations in ground and surface waters 
should result. Wheat is seeded at a rate of 60-120 pounds (lbs.) per 
acre, while canola is seeded at a rate of 5-10 lbs. per acre.
    Therefore, the application rate of difenconazole used in the 
analysis is based on a wheat seed treatment rate of 0.025 lb. active 
ingredient (a.i.) per 100 lbs. of seed and the maximum seeding rate 
(120 lbs./acre). This produces a maximum application rate of 0.03 lb. 
difenconazole per acre. Based on the preliminary screen of the 
environmental fate data submitted by the registrant, difenoconazole is 
expected to be relatively immobile but persistent in terrestrial 
environments. The adsorption coefficients for difenoconazole that were 
used in these calculations were 12.76 microliters per gram (L/
g; producing a Koc = 3,866) in an agricultural sand, 62.97 
L/g (Koc = 3,470) in sandy loam soil, 54.84 
L/g (Koc = 7,734) in silt loam soil, and 47.18 
L/g (Koc = 7,734) in a silty clay loam soil. The 
aerobic soil metabolism half-life for difenoconazole ranged from 175 to 
1,600 days. Difenoconazole had a first-order photodegradation half-life 
of 5.68 days in water.
    GENEEC deals with surface water and models the results of a single 
runoff event (but can handle multiple spray-drift events, though spray 
drift is not a consideration in the instant analysis of a seed 
treatment fungicide) and manditorily represents an outdoor system 
consisting of a 10 hectare (ha) field immediately adjacent to a 1 ha 
pond that is 2 meters (m) deep and has no outlet. GENEEC allows 
reduction of the amount of pesticide that runs off by accounting for 
degradative processes in the field and soil-binding. However, 
limitations of this approach are that surface-source drinking water 
usually comes from bodies of water that are much larger than a 1-ha 
pond, the entire drainage basin (the 10-ha field) of the pond is 
assumed to receive an application of the pesticide (quite unlikely for 
a drinking water source), and most surface drinking water sources will 
have at least some water turnover (outflow, etc.). Despite this, GENEEC 
still allows screening calculations and the provision of an upper bound 
estimate (probably often a substantial overestimate) of surface water 
concentrations of a pesticide. Where the level of concern for drinking 
water concentrations is exceeded, the Agency can use various methods to 
refine the estimate.
    SCI-GROW deals with ground water and is an empirical screening 
model based on actual ground water monitoring data collected from 
small-scale prospective ground water monitoring studies for the 
registration of a number of pesticides that serve as benchmarks for the 
model. The current version of SCI-GROW provides realistic estimates of 
pesticide concentrations in shallow, highly vulnerable (sandy soil and 
depth-to-ground-water of 10 to 20 feet) ground water, nearly a worst-
case scenario for ground water contamination. There may be exceptional 
circumstances under which concentrations of a pesticide may exceed the 
SCI-GROW estimates but such circumstances should be rare. The ground 
water concentrations generated by SCI-GROW are based on the largest 90-
day average concentration recorded during the sampling period. Because 
of the conservative nature of the monitoring data on which the model is 
based, SCI-GROW is considered to provide an upper bound estimate of 
pesticide residues in ground water. Since it is believed that pesticide 
concentrations in ground water do not fluctuate widely, SCI-GROW 
provides one estimate that is used both as a maximum and as an average 
concentration value in ground water.
    A Drinking Water Level of Comparison (DWLOC) is a theoretical upper 
limit on a pesticide's concentration in drinking water in light of 
total aggregate exposure to a pesticide in food, drinking water, and 
through residential uses. A DWLOC will vary depending on the toxic 
endpoint, with drinking water consumption, and with body weight 
variances. Different populations will have different DWLOCs. The Agency 
uses DWLOCs internally in the risk assessment process as a surrogate 
measure of potential exposure associated with pesticide exposure 
through drinking water. In the absence of monitoring data for 
pesticides, it is used as a point of comparison against conservative 
model estimates of a pesticide's concentration in water. DWLOC values 
are not regulatory standards for drinking water. They do have an 
indirect regulatory impact through aggregate exposure and risk 
assessments.
    The Agency's default bodyweights are 70 kg for males, 60 kg for 
females, and 10 kg for children. The Agency's default water consumption 
values are 2 liters (L) for males and females, and 1 L for children. 
The equation for the calculation is: DWLOC (micrograms/Liter) equals 
(water exposure (mg/kg/day) times body weight) divided by (consumption 
(Liters) times 10-3 milligrams/microgram).
    i. Acute exposure and risk. The GENEEC model (Tier 1) estimate of 
the acute or peak Estimated Environmental Concentration (EEC) for 
difenoconazole in surface water was 0.125 parts per billion (ppb). The 
SCI-GROW model estimate of the concentration of difenoconazole in 
ground water was 0.00084 ppb. The Agency calculated DWLOCs for acute 
exposure to difenoconazole in surface and ground water for females 13-
50 years old. To calculate the DWLOC for acute exposure relative to an 
acute toxicity endpoint, the acute dietary food exposure (from the DEEM 
analysis) was subtracted from the aPAD to obtain the acceptable acute 
exposure to difenoconazole in drinking water. DWLOCs were then 
calculated using the default body weights and drinking water 
consumption figures. The results were that the acute DWLOC for both the 
subgroup females (13+ years old, pregnant, and not nursing) and for the 
subgroup females (13+ years old, nursing), was 7,470 ppb. For the 
subgroup females (13-29 years old, not pregnant, and not nursing), the

[[Page 55916]]

subgroup females (20+ years old, not pregnant, non-nursing), and the 
subgroup females (13-50 years old) the DWLOC was 7,480 ppb.
    ii.Chronic (cancer and non-cancer) exposure and risk. The GENEEC 
model (Tier 1) estimate of the chronic 56-day EEC was 0.048 ppb. Agency 
drinking water guidance calls for this value to be divided by 3 to 
obtain the value to use in the chronic risk assessment. Therefore, the 
surface water value used in the chronic risk assessment of 
difenoconazole was 0.016 ppb. The SCI-GROW model estimate of the 
concentration of difenoconazole in ground water was 0.00084 ppb.
    The Agency calculated DWLOCs for chronic (non-cancer) exposure to 
difenoconazole in surface and ground water. To calculate the DWLOC for 
chronic exposure relative to a chronic toxicity endpoint, the chronic 
dietary food exposure (from the DEEM analysis) was subtracted from the 
cPAD to obtain the acceptable chronic (non-cancer) exposure to 
difenoconazole. DWLOCs were then calculated using the default body 
weights and drinking water consumption figures. For the group U.S. 
population (48 states), the subgroup non- Hispanic Whites, and the 
subgroup non-Hispanic/non-White/non-Black, the DWLOC was 350 ppb. For 
the subgroup all infants less than 1 year old, the subgroup nursing 
infants less than 1 year old, the subgroup non-nursing infants less 
than 1 year old, the subgroup children 1-6 years old, and the subgroup 
children 7-12 years old, the DWLOC was 100 ppb. For the subgroup 
females (13-19 years old/not pregnant, non-nursing), the subgroup 
females (20+ years old/not pregnant, non-nursing), the subgroup females 
(13-50 years old), the subgroup females (13+ years old/pregnant/non-
nursing), and the subgroup females (13+ years old/nursing), the DWLOC 
was 300 ppb. The population group U.S. population (48 states), all 
infant and children subgroups, all subgroups for females 13-50 years 
old, and any other population subgroup whose exposure exceeded that of 
the U.S. population group were included in this analysis.
    The Agency calculated DWLOCs for chronic (cancer) exposure to 
difenoconazole in surface and ground water for the U.S. population 
group. To calculate the DWLOC for chronic (cancer) exposure relative to 
a carcinogenic toxicity endpoint (Q1*), the chronic (cancer) 
dietary food exposure from the DEEM analysis was subtracted from the 
ratio of the negligible cancer risk (1 x 10-6) to the 
Q1* to obtain the acceptable chronic (cancer) exposure to 
difenoconazole in drinking water. DWLOCs were then calculated using the 
default body weights and drinking water consumption figures. The DWLOC 
cancer for the U.S. population group is 0.048 ppb.
    3. From non-dietary exposure. Difenococonazole has no residential 
uses so non-dietary exposure is not a factor in the difenoconazole 
exposure/risk analysis.
    4. Cumulative exposure to substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) requires that, when considering 
whether to establish, modify, or revoke a tolerance, the Agency 
consider ``available information'' concerning the cumulative effects of 
a particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.''
    EPA does not have, at this time, available data to determine 
whether difenococonazole has a common mechanism of toxicity with other 
substances or how to include this pesticide in a cumulative risk 
assessment. Unlike other pesticides for which EPA has followed a 
cumulative risk approach based on a common mechanism of toxicity, 
difenococonazole 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 difenococonazole has a common 
mechanism of toxicity with other substances. For information regarding 
EPA's efforts to determine which chemicals have a common mechanism of 
toxicity and to evaluate the cumulative effects of such chemicals, see 
the final rule for Bifenthrin Pesticide Tolerances (62 FR 62961, 
November 26, 1997).

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

    1. Acute risk. The acute aggregate exposure includes food and 
water. The acute risk scenario for difenoconazole for the 5 subgroups 
analyzed is as follows. For females (13+ years old/pregnant/non-
nursing) the aPAD was 0.25 mg/kg, the NOAEL was 25 mg/kg, the food 
exposure estimate from DEEM was 0.000852 mg/kg/day, the water exposure 
estimate was 0.249 mg/kg/day, the SCI-GROW ground water EEC estimate 
was 0.00084 ppb, the GENEEC surface water EEC estimate was 0.125 ppb, 
and the DWLOC was 7,470 ppb. For females (13+ years old/nursing) the 
aPAD was 0.25 mg/kg, the NOAEL was 25 mg/kg, the food exposure estimate 
from DEEM was 0.000889 mg/kg/day, the water exposure estimate was 0.249 
mg/kg/day, the SCI-GROW ground water EEC estimate was 0.00084 ppb, the 
GENEEC surface water EEC estimate was 0.125 ppb, and the DWLOC was 
7,470 ppb. For females (13-29 years old/not pregnant/non-nursing) the 
aPAD was 0.25 mg/kg, the NOAEL was 25 mg/kg, the food exposure estimate 
from DEEM was 0.000750 mg/kg/day, the water exposure estimate was 0.249 
mg/kg/day, the SCI-GROW ground water EEC estimate was 0.00084 ppb, the 
GENEEC surface water EEC estimate was 0.125 ppb, and the DWLOC was 
7,480 ppb. For females (20+ years old/not pregnant/non-nursing) the 
aPAD was 0.25 mg/kg, the NOAEL was 25 mg/kg, the food exposure estimate 
from DEEM was 0.000668 mg/kg/day, the water exposure estimate was 0.249 
mg/kg/day, the SCI-GROW ground water EEC estimate was 0.00084 ppb, the 
GENEEC surface water EEC estimate was 0.125 ppb, and the DWLOC was 
7,480 ppb. For females (13-20 years old) the aPAD was 0.25 mg/kg, the 
NOAEL was 25 mg/kg, the food exposure estimate from DEEM was 0.000701 
mg/kg/day, the water exposure estimate was 0.249 mg/kg/day, the SCI-
GROW ground water EEC estimate was 0.00084 ppb, the GENEEC surface 
water EEC estimate was 0.125 ppb, and the DWLOC was 7,480 ppb.
    From the acute dietary (food only) risk assessments, high-end 
exposure estimates were calculated for the female 13-50 subgroups only. 
The percent aPADs were below the Agency's level of concern at the 95th 
percentile for all female 13-50 year old sugroups with all estimated 
acute dietary exposures <1% of the aPAD. The maximum estimated 
concentrations of difenoconazole in surface and ground water are less 
than the Agency's acute DWLOCs for difenoconazole as a contribution to 
acute aggregate exposure. Therefore, taking into account the uses 
proposed in this action, the Agency concludes with reasonable certainty 
that residues of difenoconazole in drinking water (when considered 
along with other sources of exposure for which the Agency has reliable 
data) would not result in unacceptable levels of acute aggregate human 
health risk at this time.
    2. Chronic (non-cancer) risk. There are no registered or proposed 
residential uses of difenoconazole. Therefore, chronic (non-cancer) 
aggregate exposure will include risk from food and water only. The 
chronic (non-cancer) scenario for difenoconazole is as follows. For the 
U.S. population group the food exposure estimate (from the DEEM 
assessment) is 0.000005 mg/kg/day, the water exposure estimate (the 
cPAD minus the DEEM dietary exposure estimate) is 0.00995 mg/kg/day, 
the cPAD is 0.01 mg/kg/day, the ground

[[Page 55917]]

water concentration estimate (from SCI-GROW modeling) is 0.00084 ppb, 
the surface water concentration estimate (from GENEEC modeling) is 
0.016 ppb, and the DWLOC is 350 ppb. For the subgroup females (13+ 
years old, nursing) the food exposure estimate is 0.000007 mg/kg/day, 
the water exposure estimate is 0.01 mg/kg/day, the cPAD is 0.01 mg/kg/
day, the ground water concentration estimate is 0.00084 ppb, the 
surface water concentration estimate is 0.016 ppb, and the DWLOC is 300 
ppb. For the subgroup non-nursing infants (< 1 year old) the food 
exposure estimate is 0.000019 mg/kg/day, the water exposure estimate is 
0.00999 mg/kg/day, the cPAD is 0.01 mg/kg/day, the ground water 
concentration estimate is 0.00084 ppb, the surface water concentration 
estimate is 0.016 ppb, and the DWLOC is 100 ppb. Using the ARC exposure 
assumptions described in this unit, EPA has concluded that aggregate 
exposure to difenoconazole from food will utilize < 1% of the cPAD for 
the U.S. population. The major identifiable subgroup with the highest 
aggregate exposure is discussed below. From the chronic (non-cancer) 
dietary (food only) risk assessments, the percent cPADs were below the 
Agency's level of concern for the U.S. population and all population 
subgroups. The estimated chronic dietary risk associated with the use 
of difenoconazole is below the Agency's level of concern. The estimated 
average concentrations of difenoconazole in surface and ground water 
are less than the Agency's chronic (non-cancer) DWLOCs for 
difenoconazole in drinking water as a contribution to chronic aggregate 
exposure. Aggregate chronic (non-cancer) risk estimates due to exposure 
to difenoconazole in both food and water are also below the Agency's 
level of concern. EPA therefore concludes that there is a reasonable 
certainty that no harm will result from aggregate exposure to 
difenoconazole residues.
    3. Aggregate cancer risk for U.S. population. There are no 
registered or proposed residential uses for difenoconazole, so chronic 
(cancer) aggregate exposure/risk estimates are derived from food and 
water exposure only. The chronic (cancer) scenario is as follows. For 
the U.S. population group the food exposure estimate (from DEEM) is 
0.000005 mg/kg/day, the water exposure estimate (negligible risk (1 x 
10-6) divided by the Q1* is 0.00000137 mg/kg/day, 
the Q1* is 0.157 (mg/kg/day)-1, the ground water 
concentration estimate (from SCI-GROW modeling) is 0.00084 ppb, the 
surface water estimate (from GENEEC modeling) is 0.016 ppb, and the 
DWLOC is 0.048 ppb. From the chronic (cancer) dietary (food only) risk 
assessments, the estimated lifetime risk for the U.S. population was 
8.6 x 10-7, which is below the Agency's level of concern 
(generally 1 x 10-6). The estimated average concentrations 
of difenoconazole in surface and ground water are less than the 
Agency's DWLOC cancer for difenoconazole in drinking water 
as a contribution to chronic (cancer) aggregate exposure. EPA therefore 
concludes that there is a reasonable certainty that no harm will result 
from aggregate chronic (cancer) exposure to difenoconazole residues.
    4. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
from aggregate exposure to 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 difenoconazole, EPA considered data from 
developmental toxicity studies in the rat and rabbit and a 2-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 prenatal and postnatal toxicity and 
the completeness of the data base 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 interspecies and 
intraspecies 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. Difenoconazole was administered 
to pregnant rats at dose levels of 0, 2, 20, 100, and 200 mg/kg/day 
from day 6 to day 15 of gestation. Statistically significant decreases 
in maternal body weight gain and feed consumption were observed during 
the dosing period at dose levels of 100 and 200 mg/kg/day. At 200 mg/
kg/day the incidence of bifid or unilateral ossification of the 
thoracic vertebrae was significantly increased on a fetal basis. There 
were also significant increases in the average number of ossified hyoid 
and decreases in the numbers of sternal centers of ossification (per 
fetus per litter). The average number of ribs was significantly 
increased, with accompanying increases in the number of thoracic 
vertebrae and decreases in the number of lumbar vertebrae in this 
group. These findings at the highest dose tested (200 mg/kg/day) appear 
to be the result of maternal toxicity. The NOAEL for maternal toxicity 
was 20 mg/kg/day and the LOAEL for maternal toxicity was determined to 
be 100 mg/kg/day based on decreased body weight gains and decreased 
food consumption at 100 mg/kg/day and higher. The NOAEL for 
developmental toxicity was 100 mg/kg/day and the LOAEL was 200 mg/kg/
day based on the incidence of bifid or unilateral ossification of the 
thoracic vertebrae, which was significantly increased on a fetal basis, 
and the significant increases in the average number of ossified hyoid 
and decreases in the number of sternal centers of ossification (per 
fetus per litter). The average number of ribs was also significantly 
increased, with accompanying increases in the number of thoracic 
vertebrae and decreases in the number of lumber vertebrae in this 
group.
    In a developmental toxicity study in rabbits, impregnated females 
(16 per dose) were orally administered difenoconazole at 0, 1, 25, and 
75 mg/kg/day during days 7 through 19 of gestation. At 75 mg/kg/day, 
maternal toxicity was manifested as decreased body weight gain and food 
consumption; no maternal toxicity was observed at lower doses. 
Developmental toxicity, observed only at 75 mg/kg/day, was a slight 
nonsignificant increase in post-implantation loss and resorption per 
dose and a significant decrease in fetal weight. For maternal toxicity, 
the LOAEL of 75 mg/kg/day is based on decreases in body weight gain and 
food consumption; the NOAEL is 25 mg/kg/day. For developmental 
toxicity, the LOAEL of 75 mg/kg/day is based on increases in post-
implantation loss and

[[Page 55918]]

resorption and decreases in fetal body weight; the NOAEL is 25 mg/kg/
day. The increases in post-implantation loss and resorption are 
presumed to occur after a single exposure.
    iii. Reproductive toxicity study. In a 2-generation reproduction 
study, difenoconazole was administered in the diet to male and female 
rats at 0, 25, 250, and 2,500 ppm (0, 1.25, 12.5, and 125 mg/kg/day, 
respectively). Statistically significant reductions in bodyweight gains 
of F0 and F1 males were observed at 2,500 ppm 
during days 70-77 and during the course of the study (terminal 
bodyweight minus day 0 bodyweight). Significant reductions in 
bodyweight gains of F0 and F1 females were seen 
during the pre-mating, gestation, and lactation periods. A dose-
related, but non-statistically significant decrease in bodyweight gain 
was seen in F0 at 250 ppm during days 70-77 prior to mating, 
days 0-7 of gestation, and days 7-14 of lactation. At 2,500 ppm, 
significant reductions in pup bodyweight were detected on days 0, 4 
(pre- and post-culling), 7, 14, and 21 for males and females of both 
generations. There was a significant reduction in the bodyweight of 
F1 male pups on day 21 in the 250 ppm group. The percentage 
of male pups in the F1 generation surviving days 0-4 was 
significantly reduced in the 2,500 ppm group. For parental toxicity, 
the LOAEL of 250 ppm (12.5 mg/kg/day) is based on the decreased 
maternal bodyweight gain; the NOAEL is 25 ppm (1.25 mg/kg/day). For 
reproductive toxicity, the LOAEL of 250 ppm (12.5 mg/kg/day) is based 
on decreased pup weight at day 21; the NOAEL is 25 ppm (1.25 mg/kg/
day).
    iv. Prenatal and postnatal sensitivity. The data provided no 
indication of increased susceptibility of rats or rabbits to in utero 
and/or postnatal exposure to difenoconazole. In the prenatal 
developmental toxicity study in rats, no evidence of developmental 
toxicity was seen even in the presence of maternal toxicity. In the 
developmental toxicity study in rabbits, developmental toxicity was 
seen in the presence of maternal toxicity at the highest dose tested. 
In the 2-generation reproduction study in rats, effects in the 
offspring were observed only at or above treatment levels which 
resulted in evidence of parental toxicity.
    v. Conclusion. A complete toxicology data base exists for 
difenoconazole, and exposure data are complete or are estimated based 
on data that reasonably account for potential exposures. Taking into 
account the completeness of the data and the absence of any evidence of 
increased sensitivity, EPA determined that the additional tenfold 
safety factor for the protection of infants and children was not 
necessary.
    2. Acute risk. An acute dose and endpoint were not chosen for the 
general population including infants and children because there were no 
effects observed in oral toxicology studies including maternal toxicity 
in the developmental toxicity studies in rats and rabbits that are 
attributable to a single exposure (dose). Acute exposure/risk analyses 
were performed only for subgroups of females 13-50 years old.
    3. Chronic risk. Using the exposure assumptions described in this 
unit, EPA has concluded that aggregate exposure to difenoconazole from 
food will utilize < 1% of the cPAD for infants and children. EPA 
generally has no concern for exposures below 100% of the cPAD because 
the cPAD 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 difenoconazole in 
drinking water, EPA does not expect the aggregate exposure to exceed 
100% of the cPAD.
    4. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to infants and children from aggregate exposure to residues.

IV. Other Considerations

A. Metabolism in Plants and Animals

    The nature of the residue in plants is understood. Plant metabolism 
studies were conducted on wheat, tomatoes, grapes, potatoes, and canola 
and found to be acceptable. The canola metabolism study was performed 
using a foliar treatment of difenoconazole on canola. The proposed use 
is a seed treatment. The results in these studies are consistent with 
foliar metabolism studies submitted and reviewed for wheat, tomatoes, 
and potatoes. The metabolic pathway in canola appears to proceed by 
hydrolysis of the ketal to the ketone followed by reduction of the 
ketone to the alkanol. The alkanol can be conjugated with sugars or the 
bridge linking the phenyl and triazole moities is cleaved, forming free 
triazole. The free triazole can be conjugated with serine to yield an 
intermediate which can be oxidatively deaminated to the lactic acid 
analogue and then degraded further. There was no evidence for a minor 
metabolic pathway via hydroxylation of the phenyl ring moiety.
    Metabolism studies for a wheat seed treatment have been submitted 
and reviewed. The seed treatment metabolism studies had similar results 
to the foliar studies. Therefore, the Agency has translated the foliar 
canola studies to seed treatment and considers the nature of the 
residue in canola understood.
    The nature of the difenoconazole residue in animals was considered 
understood for wheat and barley (PP 2F4107) only. It was concluded that 
for any future petition in which there is a greater potential for 
transfer of residues to meat and milk, additional animal metabolism 
studies would be required. Since the proposed use on canola is a seed 
treatment and canola is not a major feed item, there is not a greater 
potential for transfer of residues to meat and milk. Therefore, 
additional animal metabolism studies were not required for this action 
and the nature of the residue in animals is considered understood for 
this action.

B. Analytical Enforcement Methodology

    For plants, the petitioner has submitted a copy of method AG-676, 
which is similar to the enforcement method for wheat (method 575). 
Therefore, an Independent Laboratory Validation (ILV) was not required. 
Acceptable recoveries were obtained for all matrices. Samples are 
homogenized and centrifuged in an ACN/hexane mixture. The resulting 
solution is then decanted and extracted repeatedly, then partially 
evaporated, and, finally, eluted and brought to volume. The sample is 
analyzed by gas chromatography with mass spectral detection (GC/MSD). 
The reported limit of quantitation (LOQ) is 0.01 ppm.
    A Petition Method Validation (PMV) has been successfully completed 
for petitioner proposed residue method 676, so adequate enforcement 
methodology is available to enforce the tolerance expression. When this 
method is formally completed, it will be forwarded to the Food and Drug 
Administration (FDA) to be included in Pesticide Analytical Manual II 
(PAM II).
    The petitioner proposed Method AG-544A, ``Difenoconazole (CGA-
169374) Analytical Method for the Determination of CGA-169374 Residues 
in Dairy and Poultry Tissue, Eggs and Milk by Gas Chromatography,'' as 
the analytical enforcement method. The sample is extracted by 
homogenization with acetonitrile and concentrated ammonium hydroxide 
for 1 minute, the extract is filtered, the filtrate is diluted with 
water and saturated sodium chloride, partitioned twice, then cleaned 
up. The final sample is then analyzed by packed column gas 
chromatography (GC) using alkali flame ionization detection. The 
reported LOQ

[[Page 55919]]

for livestock tissue is 0.05 ppm and for milk is 0.01 ppm. The Agency 
concluded that Method AG-544A is adequate for the purpose of enforcing 
difenoconazole tolerances in animal commodities. A satisfactory ILV of 
the method was submitted and a satisfactory PMV was completed by the 
Agency's residue analysis laboratory. This method was forwarded to FDA 
to be included in PAM II.
    These methods may be requested from: Calvin Furlow, PIRIB, IRSD 
(7502C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: 
(703) 305-5229; e-mail address: [email protected].

C. Magnitude of Residues

    A total of six field trials were submitted and reviewed. The 
residue levels of difenoconazole in canola seed were all less than the 
LOQ of 0.01 ppm. The submitted data indicate that the appropriate 
tolerance level for residues of difenoconazole in canola seed is 0.01 
ppm.
    No processing study is required for this tolerance petition. The 
maximum theoretical concentration factor for processing of canola seed 
to canola oil is 3x. Difenoconazole was applied to canola at an 
exaggerated rate of 3.6x (0.09 pounds of active ingredient per 100 
pounds of seed) as a seed treatment at two locations. Residue levels 
for each location were below the LOQ of 0.01 ppm.
    The petitioner had requested (in support of wheat use, PP 2F4107) a 
waiver for animal feeding studies based on the low potential for 
residues in feed items and the exaggerated rates used in the animal 
feeding studies. Based on a diet composed of 100% wheat raw 
agricultural commodities (RACs) and residues at the levels of the 
proposed tolerances, the maximum dietary burden for dairy cattle is 
estimated to be 0.30 ppm. Two metabolism studies were performed on 
ruminants (lactating goats) in a 10-day study with a dose rate of 4.17 
ppm (14 x the 0.30 ppm estimated dietary burden) and a 3-day study with 
a dose rate of 100 ppm (333 x the 0.30 ppm estimated dietary burden). 
The total radioactive residue (TRR) in the goat tissues was used to 
estimate the expected residues in a feeding study with a dose rate of 
0.30 ppm. The maximum residue observed was in liver, estimated to be at 
a level of 0.02 ppm from both metabolism studies. This value is 2.5 x 
below the LOQ of the proposed analytical enforcement method (0.05 ppm). 
The estimated residue in milk would be 0.5 ppb, 200 x below the method 
LOQ of 0.1 ppm. The Agency accepted the petitioner's proposal to allow 
the animal metabolism studies to also serve as feeding studies. Feeding 
studies in cattle and poultry, as appropriate, will be needed for any 
future tolerance request which could result in higher residues of 
concern in meat, milk, poultry, and eggs.
    The proposed use in/on canola in this action does not appear to 
result in higher residues of concern in meat, milk, poultry, and eggs. 
The proposed use pattern (seed treatment) and low animal dietary feed 
consumption (canola meal only commodity consumed, 15% of diet) support 
the assumption of no increase in residues. Therefore, animal feeding 
studies are not required for this action with the same caveat that if, 
in the future, uses are proposed that result in higher residues in 
animal commodities, feeding studies will be required.

D. International Residue Limits

    There is neither a Codex proposal, nor Canadian or Mexican maximum 
residue limits for residues of difenoconazole in canola. Therefore, a 
compatibility issue is not relevant to the proposed tolerance.

E. Rotational Crop Restrictions

    The nature of the residue is understood. The data indicate that the 
phenyl/triazole bridge of difenoconazole is cleaved in the soil and 
that triazole-specific metabolites are preferentially taken up by the 
rotational crops. The maximum TRR observed with phenyl-labeled 
difenoconazole was 0.009 ppm (wheat stalks) and with triazole-labeled 
difenoconazole was 0.314 ppm in wheat grain. The registrant has 
submitted the results of two confined rotational studies using phenyl-
labeled difenoconazole. In the RACs of all rotational crops planted 30-
33 days after application of difenoconazole, the TRR was < 0.01 ppm. 
These results support the proposed 30-day plant-back restrictions for 
all rotational crops. A 30-day plantback restriction for all crops is 
appropriate.

V. Conclusion

    Therefore, a tolerance is established for residues of 
difenoconazole in or on canola, seed at 0.01 ppm.

VI. Objections and Hearing Requests

    Under section 408(g) of the FFDCA, as amended by the FQPA, any 
person may file an objection to any aspect of this regulation and may 
also request a hearing on those objections. The EPA procedural 
regulations which govern the submission of objections and requests for 
hearings appear in 40 CFR part 178. Although the procedures in those 
regulations require some modification to reflect the amendments made to 
the FFDCA by the FQPA of 1996, EPA will continue to use those 
procedures, with appropriate adjustments, until the necessary 
modifications can be made. The new section 408(g) provides essentially 
the same process for persons to ``object'' to a regulation for an 
exemption from the requirement of a tolerance issued by EPA under new 
section 408(d), as was provided in the old FFDCA sections 408 and 409. 
However, the period for filing objections is now 60 days, rather than 
30 days.

A. What Do I Need to Do To File an Objection or Request a Hearing?

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket control number OPP-301005 in the subject line on the 
first page of your submission. All requests must be in writing, and 
must be mailed or delivered to the Hearing Clerk on or before November 
14, 2000.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
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.
    Mail your written request to: Office of the Hearing Clerk (1900), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460. You may also deliver your request to the Office 
of the Hearing Clerk in Rm. M3708, Waterside Mall, 401 M St., SW., 
Washington, DC 20460. The Office of the Hearing Clerk is open from 8 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
telephone number for the Office of the Hearing Clerk is (202) 260-4865.

[[Page 55920]]

    2. Tolerance fee payment. If you file an objection or request a 
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or 
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must 
mail the fee to: EPA Headquarters Accounting Operations Branch, Office 
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please 
identify the fee submission by labeling it ``Tolerance Petition Fees.''
    EPA is authorized to waive any fee requirement ``when in the 
judgement of the Administrator such a waiver or refund is equitable and 
not contrary to the purpose of this subsection.'' For additional 
information regarding the waiver of these fees, you may contact James 
Tompkins by phone at (703) 305-5697, by e-mail at [email protected], 
or by mailing a request for information to Mr. Tompkins at Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    If you would like to request a waiver of the tolerance objection 
fees, you must mail your request for such a waiver to: James Hollins, 
Information Resources and Services Division (7502C), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460.
    3. Copies for the Docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit VI.A., you 
should also send a copy of your request to the PIRIB for its inclusion 
in the official record that is described in Unit I.B.2. Mail your 
copies, identified by docket control number OPP-301005, to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. 
In person or by courier, bring a copy to the location of the PIRIB 
described in Unit I.B.2. You may also send an electronic copy of your 
request via e-mail to: [email protected]. Please use an ASCII file 
format and avoid the use of special characters and any form of 
encryption. Copies of electronic objections and hearing requests will 
also be accepted on disks in WordPerfect 6.1/8.0 file format or ASCII 
file format. Do not include any CBI in your electronic copy. You may 
also submit an electronic copy of your request at many Federal 
Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

    A request for a hearing will be granted if the Administrator 
determines that the material submitted shows the following: There is a 
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(s) in the manner sought 
by the requestor would be adequate to justify the action requested (40 
CFR 178.32).

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) (Public Law 104-4). Nor 
does it require any prior consultation as specified by Executive Order 
13084, entitled Consultation and Coordination with Indian Tribal 
Governments (63 FR 27655, May 19, 1998); 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 or 
any Agency action under Executive Order 13045, entitled Protection of 
Children from Environmental Health Risks and Safety Risks (62 FR 19885, 
April 23, 1997). This action does not involve any technical standards 
that would require Agency consideration of voluntary consensus 
standards pursuant to section 12(d) of the National Technology Transfer 
and Advancement Act of 1995 (NTTAA), Public Law 104-113, section 12(d) 
(15 U.S.C. 272 note). Since tolerances and exemptions that are 
established on the basis of a petition under FFDCA section 408(d), such 
as the tolerance in this final rule, do not require the issuance of a 
proposed rule, the requirements of the Regulatory Flexibility Act (RFA) 
(5 U.S.C. 601 et seq.) do not apply. In addition, the Agency has 
determined that this action will not have a substantial direct effect 
on States, on the relationship between the national government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government, as specified in Executive Order 13132, 
entitled Federalism (64 FR 43255, August 10, 1999). Executive Order 
13132 requires EPA to develop an accountable process to ensure 
``meaningful and timely input by State and local officials in the 
development of regulatory policies that have federalism implications.'' 
``Policies that have federalism implications'' is defined in the 
Executive Order to include regulations that have ``substantial direct 
effects on the States, on the relationship between the national 
government and the States, or on the distribution of power and 
responsibilities among the various levels of government.'' This final 
rule directly regulates growers, food processors, food handlers and 
food retailers, not States. This action does not alter the 
relationships or distribution of power and responsibilities established 
by Congress in the preemption provisions of FFDCA section 408(n)(4).

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 this final rule in the Federal Register. This final 
rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

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

    Dated: September 7, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
    Therefore, 40 CFR chapter I is amended as follows:

PART 180-[AMENDED]

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

    Authority:  21 U.S.C. 321(q), (346a) and 371.
    2. Section 180.475 is amended by revising the introductory text of

[[Page 55921]]

paragraph (a) and alphabetically adding canola, seed to the table in 
paragraph (a) to read as follows:


Sec. 180.475  Difenoconazole; tolerances for residues.

    (a)General. Tolerances are established for residues of the 
fungicide difenoconazole [(2S,4R)/(2R/4S)]/[(2R/4R)/(2S,4S) 1-(2-[4-(4-
chlorophenoxy)-2-chlorophenyl]-4-methyl-1,3-dioxolan-2-yl-methyl)-1H-
1,2,4-triazole in or on the following raw agricultural commodities.

 
------------------------------------------------------------------------
                 Commodity                        Parts per million
------------------------------------------------------------------------
 
                  *        *        *        *        *
Canola, seed..............................  0.01
 
                  *        *        *        *        *
------------------------------------------------------------------------

    *    *    *    *    *
[FR Doc. 00-23773 Filed 9-14-00; 8:45 am]
BILLING CODE 6560-50-F