[Federal Register Volume 66, Number 148 (Wednesday, August 1, 2001)]
[Notices]
[Pages 39762-39767]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-19169]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-1032; FRL-6789-2]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
fora Certain Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket control number PF-1032, must be 
received on or before August 31, 2001.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-1032 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, 
Fungicide Branch, Registration Division (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 305-7740; 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 certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this

[[Page 39763]]

document, on the Home Page select ``Laws and Regulations,'' 
``Regulations and Proposed Rules,'' and then look up the entry for this 
document under the ``Federal Register--Environmental Documents.'' You 
can also go directly to the Federal 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 PF-1032. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, 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 Highway, 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.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-1032 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [email protected], or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-1032. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI 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. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under FOR FURTHER INFORMATION 
CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set forth in section 408(d)(2); however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data support granting of the petition. Additional data 
may be needed before EPA rules on the petition.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.


    Dated: July 13, 2001.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the view of the 
petitioners. EPA is publishing the petition summary verbatim without 
editing it in any way. The petition summary announces the availability 
of a description of the analytical methods available to EPA for the 
detection and measurement of the pesticide chemical residues or an 
explanation of why no such method is needed.

E.I. duPont de Nemours

PP7E4847

    EPA has received a pesticide petition (PP7E4847) from E.I. duPont 
de Nemours and Company (Dupont, P.O. Box 80038, Wilmington, DE 19880-
0038 proposing, pursuant to section 408(d) of the Federal Food, Drug, 
and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 
by establishing a tolerance for residues of famoxadone in or on the raw 
agricultural commodity grapes at 2.0 parts per million and raisins at 4 
parts per million (ppm). EPA has determined that the 4 ppm petition 
contains data or information regarding the elements set forth in 
section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated 
the sufficiency of the submitted data at this time or whether the data 
supports granting of

[[Page 39764]]

the petition. Additional data may be needed before EPA rules on the 
petition.

A. Residue Chemistry

    1. Plant metabolism. The plant metabolism of famoxadone is 
adequately understood in three distinct crops to support these 
tolerances: Tomatoes, potatoes and grapes. These studies showed no 
significant metabolites (all < 10%TRR) in the raw agricultural 
commodities (tubers,tomato fruit, grape berries). The only significant 
residue in any of the studies was the parent compound, famoxadone, 
occurring primarily as surface residues (grape berries and tomato 
fruit). No residues were detected in potato tubers. Thus, the proposed 
tolerance expression is for the parent compound, famoxadone (DPX-JE874) 
only.
    2. Analytical method. An analytical enforcement method is available 
for determining famoxadone plant residues in or on grapes, raisins, 
potatoes, cucurbit vegetables (cucumbers, melons and squash), fruiting 
vegetables (tomatoes, peppers), and head lettuce using gas-
liquidchromatography (GC) with nitrogen phosphorus detection (NPD). The 
method is applicable to high and medium moisture, oily and non-oily 
crops and related matrices. The limit of quantitation is 0.02 ppm. The 
limit of quantitation allows monitoring of crops with famoxadone 
residues at or above the levels proposed in these tolerances.
    3. Magnitude of residues -- grapes and raisins. Results from 
magnitude of residue and residue decline studies conducted on grapes in 
major European producing and exporting regions support the grape 
tolerance of 2.0 ppm. The mean residue value was 0.61 ppm +/- 0.38 ppm 
with a range of 0.07 to 2.14 ppm.
    No residues were detected in juice or wine fractions upon 
processing or fermentation of grapes treated with exaggerated rates of 
famoxadone. The limit of quantitation was 0.02 ppm. Residues did 
concentrate by a factor of 1.9X in raisins, thus supporting a tolerance 
of4.0 ppm.

B. Toxicological Profile

    1. Acute toxicity. A battery of acute toxicity tests with technical 
famoxadone places it in the following Toxicity Categories:

----------------------------------------------------------------------------------------------------------------
              Study Type                       Species                  Results             Toixcity Category
----------------------------------------------------------------------------------------------------------------
Oral LD50                              Rat                      > 5,000 mg/kg            Category IV
Dermal LD50                            Rabbit                   >2,000 mg/kg             Category III
Inhalation LC50                        Rat                       >5.3 mg/L               Category IV
Eye irritation                         Rabbit                   Transient redness;       Category III
                                                                 clear by 72 hours
Dermal irritation                      Rabbit                   Minimal irritation at    Category IV
                                                                 72 hours
Dermal sensitization                   Guinea pig               Not a sensitizer
----------------------------------------------------------------------------------------------------------------

    In an acute neurotoxicity test, famoxadone was not neurotoxic to 
rats. The NOAEL was 1,000 milligams/kilogram (mg/kg) in males, based on 
systemic toxicity at 2,000 mg/kg. The NOAEL in females was 2,000 mg/kg, 
the highest dose tested (HDT).
    2. Genotoxicity. Famoxadone was tested in a battery of assays to 
evaluate genotoxicity and chromosome aberrations with the following 
results. Based on the weight-of-evidence, famoxadone is not considered 
to be genotoxic or clastogenic.

 
------------------------------------------------------------------------
 
------------------------------------------------------------------------
Bacterial genemutation..........  Salmonella and E.   Negative
                                   Coli.
 Mammalian gene mutation in        CHO/HGPRT           Negative
 vitro
Mammalian chromosome aberrations  CHO                 Positive without
 in vitro                                              activation
                                                       Negative with
                                                       activation
 Mammalian chromosome              Mouse               Negative
 aberrations in vivo               micronucleus
Unscheduled DNA synthesis in      Primary rat         Negative
 vitro                             hepatocytes
Unscheduled DNA synthesis in      Primary rat         Negative
 vivo.                             hepatocytes.
------------------------------------------------------------------------

    3. Reproductive and developmental toxicity. The results of a series 
of studies indicated that there were no reproductive, developmental or 
teratogenic hazards associated with famoxadone.
    In a 2-generation rat reproduction study, the NOAEL for both adults 
and offspring was 200 ppm (11.3-17.5 mg/kg/day depending on gender and 
generation) based on clinical signs, decreased body weights, effects on 
nutritional parameters, and liver toxicity in adults and decreased 
weight of pups. Effects on pups occurred only at a maternal effect 
level and may have been due to altered growth and nutrition in the 
dams. There were no effects on reproduction (mating, fertility, and 
reproductive organs) up to and including the highest concentration 
tested, 800 ppm (44.7-71.8 mg/kg/day).
    In studies conducted to evaluate developmental toxicity potential, 
famoxadone was neither teratogenic nor uniquely toxic to the conceptus. 
In a rat developmental toxicity study, the maternal NOAEL was 250 mg/
kg/day based on decreased weight gain and food consumption at 500 mg/
kg/day. The fetal NOAEL was 1,000 mg/kg/day, the HDT. In rabbits, NOAEL 
for compound-related systemic toxicity was 1,000 mg/kg/day. There were 
no developmental effects at any dose level. Several rabbits had weight 
loss, decreased food consumption, clinical signs, fecal impactions and 
subsequent abortion at 1,000 mg/kg/day. These effects were considered 
due to the physical properties of the dosing solution rather than 
systemic toxicity. Often fecal impaction preceded abortions.
    4. Subchronic toxicity. Subchronic (90-day) feeding studies were 
conducted with rats, mice, and dogs. In addition, the following 
subchronic feeding studies were conducted: A 90-day in rats to evaluate 
neurotoxicity and 28-day feeding studies in rats and mice to evaluate 
immunotoxicity. A 28-day dermal study was conducted in rats.
    In a 90-day feeding study in rats, the NOAEL was considered to be 
200 ppm (13 and 17 mg/kg/day) based on mild hepatotoxicity and mild 
regenerative hemolytic anemia in both sexes and decreased body weight 
in females at 800 ppm (52 and 66 mg/kg/day, in males and females 
respectively) and higher. An effect on weight gain in female rats at 17 
mg/kg/day was considered spurious since it was not duplicated in any 
other rat studies including those of thesame or longer duration.
    In a subchronic neurotoxicity study in rats, there was no evidence 
of neurotoxicity up to and including the highest concentration tested, 
800 ppm (46.9 and 59.3 mg/kg/day for males and females, respectively). 
The NOAEL for systemic toxicity was 200 ppm (11.7 and 14.4 mg/kg/day in 
males and females, respectively) based on body weight and nutritional 
effectsat 800 ppm.

[[Page 39765]]

    In mice, the subchronic NOAEL was 350 ppm (62.4 and 79.4 mg/kg/day 
in males and females, respectively), based on hepatotoxicity and mild 
anemic effects at higher concentrations.
    In a 90-day feeding study in dogs, the NOAEL was 40 ppm (1.3 mg/kg/
day) in males. In females, 40 ppm (1.4 mg/kg/day) was a marginal effect 
level for lens lesions. At 300 ppm, lens lesions were observed in males 
and females upon ophthalmologic exam and confirmed by histopathology. 
These lesions were not considered relevant to human health and to acute 
risk assessment, since they did not occur in a 1-year primate study. 
Excluding lens lesions, the NOAEL was 300 ppm (10.0 and 10.1 mg/kg/day 
in males and females, respectively), based upon effects on body weight 
and food consumption, hemolytic anemia, and hyperkalemia with 
associated clinical signs at 1000/600 ppm (23.8/21.2 and 23.3/20.1 mg/
kg/day in males and females, respectively). The test concentration was 
lowered to 600 ppm after 5.3 weeks because of the signs related to 
hyperkalemia.
    Famoxadone was tested in 28-day feeding studies in rats and mice, 
designed to evaluate immunotoxicity. The NOAEL in rats was 200 ppm (14 
and 16 mg/kg/day in males and females, respectively) based on decreased 
body weight, body weight gain, food consumption, food efficiency, and 
increased spleen weights at 800 ppm (55 and 57 mg/kg/day for male and 
females, respectively). There was no effect in response to sheep red 
blood cell (SRBC) challenge at any concentration tested. In mice, the 
NOAEL was 2,000 ppm (327 and 417 mg/kg/day in males and females, 
respectively) based onincreased spleen weights and a minimal decrease 
in humoral response to SRBC. Famoxadone is not considered immunotoxic 
in rats and produced equivocal evidence of immunotoxicity in mice.
    In a 28-day repeated dose dermal study, the NOAEL for male rates 
was 250 mg/kg/day based on changes in liver enzymes at 500 mg/kg/day. 
The NOAEL for female rats was 1,000 mg/kg/day, the HDT.
    5. Chronic toxicity. Chronic studies with famoxadone were conducted 
on rats, mice, dogs and monkeys to determine oncogenic potential and/or 
chronic toxicity of the compound. Effects generally similar to those 
observed in the 90-day studies were seen in the chronic studies. 
Famoxadone was not oncogenic.
    Famoxadone was not oncogenic in rats. The chronic NOAEL was 200 ppm 
(8.4 and 10.7 mg/kg/day in males and females, respectively) based on 
hepatotoxicity and anemia in both sexes and decreased body weight, body 
weight gain, and food efficiency in females at 400 ppm (16.8 and 23.0 
mg/kg/day in males and females, respectively).
    In mice, the chronic NOAEL was 700 ppm (95.6 and 130 mg/kg/day for 
males and females, respectively) based on hepatotoxicity in males and 
females and amyloidosis in females at 2,000 ppm (274 and 392 mg/kg/day 
in males and females, respectively). Famoxadone was not oncogenic in 
mice.
    In a 1-year feeding study in dogs, the only effect observed was 
lens lesions at 300 ppm (8.8 and 9.3 mg/kg/day for males and females). 
The NOAEL for these lesions was 40 ppm (1.2 mg/kg/day in both sexes). 
Use of this NOAEL is considered very conservative since these lesions 
are not considered appropriate to human risk assessment based on the 
absence of this effect in a primate study.
    In a 1-year gavage study, the NOAEL in cynomolgus monkeys was 100 
mg/kg/day in both males and female based on slight hemolytic anemia in 
both sexes at the 1,000 mg/kg/day dose level. There were no other 
effects observed at any level.
    6. Animal metabolism. Famoxadone was rapidly eliminated in the rat, 
primarily by fecal excretion and to a lesser extent in the urine. 
Absorption and metabolism of famoxadone was limited. There was no 
accumulation in organs or tissues. Parent famoxadone was the major 
component recovered. Hydroxylated parent compound and sulfated cleavage 
products were also recovered to a much lesser extent.
    7. Metabolite toxicology. There are no metabolites of toxicological 
significance to mammals.
    8. Endocrine disruption. Chronic, lifespan, and multigenerational 
bioassays in mammals and acute andsubchronic studies on aquatic 
organisms and wildlife did not reveal endocrine effects. Any endocrine 
related effects would have been detected in this definitive array of 
required tests. The probability of any such effect due to agricultural 
uses of famoxadone is negligible.

C. Aggregate Exposure

    1. Dietary exposure. Famoxadone is a new fungicide with proposed 
uses on the commercial crops: Fruiting vegetables (tomatoes and 
peppers), cucurbit vegetables (cucumbers, melons and squash), head 
lettuce, potatoes and imported grapes. There are no residential uses 
for the famoxadone-containing fungicide.
    i. Food. The chronic RfD of 0.012 mg/kg/day is based on a NOAEL of 
1.2 mg/kg/day for lens lesions from a 1-year dog feeding study and an 
uncertainty factor of 100. This is considered highly conservative 
because these lesions were not produced in a chronic monkey study. The 
acute NOAEL of 10.0 mg/kg bw/day is based upon body weight effects 
occurring early in a 90-day dog study. Since body weight is not 
actually an acute effect, the acute NOAEL selected is highly 
conservative and it is likely that the actual acute NOAEL is much 
higher than 10.0 mg/kg/day.
    a. Chronic dietary exposure assessment. Chronic dietary exposure, 
resulting from all of the proposed uses of famoxadone, cucurbit 
vegetables, fruiting vegetables, head lettuce, potatoes, and imported 
grapes, is well within acceptable limits for all sectors of the 
population. The Chronic Module of the Dietary Exposure Evaluation Model 
(DEEM, Novigen Sciences, Inc., 1998 Version 6.4 (chronic) and 6.54 
(acute)) was used to conduct the assessment with the anticipated 
reference dose (RfD) of 0.012 mg/kg/day. The analysis employed overall-
mean field-trial values and conservatively assumed that 30% of the 
crops on the proposed label plus imported grapes would be treated with 
famoxadone.
    For the general U.S. population, the estimated chronic dietary 
exposure to famoxadone is 0.000335 mg/kg/day, and utilizes 2.8% of the 
chronic RfD. The exposure for the potentially most highly exposed 
subgroup in the population, children 1-6 years, is 0.000487 mg/kg/day 
or 4.1% of the chronic RfD. The table below lists the results of this 
analysis, which indicate large margins of exposure for each population 
subgroup and very low probability of effects resulting from chronic 
exposure to famoxadone. Since the RfDs are well below 100%, the chronic 
dietary safety of famoxadone clearly meets the FQPA standard of 
reasonable certainty of no harm.

              Results of Chronic Dietary Exposure Estimate
------------------------------------------------------------------------
                                    Maximum Dietary
        Population Group           Exposure (mg/kg/          % RfD
                                         day)
------------------------------------------------------------------------
U.S. Population                   0.000335            2.8
Non-Nursing Infants (<1 year)     0.000111            0.9
Children (1-6 years)              0.000487            4.1
 Children (7-12 years)            0.000391            3.3
Females (13+ years)               0.000430            3.6
------------------------------------------------------------------------


[[Page 39766]]

    b. Acute dietary exposure. The acute dietary exposure to famoxadone 
(99th percentile) is 0.001848 mg/kg/day, or 1.85% acute RfD for the 
overall U.S. population. The exposure (99th percentile) of the most 
highly exposed subgroup in the population, children 1-6 years, is 
0.002559 mg/kg/day or 2.56% aRfD. The results of this analysis are 
given in the table below. All of the results are extremely reassuring, 
because they are based on several very conservative assumptions. Foods 
that were considered in exposure estimates were cucurbit vegetables, 
fruiting vegetables, head lettuce, imported grapes, and potatoes. Since 
the% aRfDs are well below 100%, the acute dietary safety of famoxadone 
clearly meets the FQPA standard of reasonable certainty of no harm.

                                   Results of Acute Dietary Exposure Estimate
----------------------------------------------------------------------------------------------------------------
                                                                      99TH Percentile of    99.9TH Percentile of
                                                                           expsure                expsure
                         Population group                          ---------------------------------------------
                                                                      Exposure               Exposure
                                                                    (mg/kg/day)    % RfD   (mg/kg/day)    % RfD
----------------------------------------------------------------------------------------------------------------
U.S. Population                                                        0.001848      1.85     0.006128      6.13
Non-Nursing (<1 year)                                                  0.000949      0.95     0.003667      3.67
Children (1-6 years)                                                   0.002559      2.56     0.008944      8.94
Children (7-12 years)                                                  0.002002      2.00     0.007364      7.36
Females (13-50 years)                                                  0.001843      1.84     0.006072      6.07
----------------------------------------------------------------------------------------------------------------

    ii. Drinking water. Famoxadone is highly unlikely to contaminate 
groundwater resources due to its immobility in soil, low water 
solubility, high soil sorption, moderate soil half-life, and resulting 
low ground and surface water exposure. Both acute and chronic drinking 
water exposure analyses were calculated using EPA screening models 
(SCI-GROW for groundwater and GENEEC for surface water). Results 
indicate that a reasonable certainty exists that famoxadone residues 
will not contribute significantly to the aggregate acute and chronic 
human risk. The predicted concentration for famoxadone in groundwater 
under worst case conditions was 0.0097 parts per billion (ppb). The 
predicted peak concentration for famoxadone in surface water in a small 
non-flowing pond, directly adjacent to treated fields (aerial 
application at the maximum rate), was 2.49 ppb. The 56-day average 
concentration predicted for the same pond scenario was 0.05 ppb. The 
EPA uses drinking water levels of comparison (DWLOCS) as a surrogate 
measure to capture risk associated with exposure to pesticides in 
drinking water. The DWLOC is the concentration of a pesticide in 
drinking water that would be acceptable as an upper limit in light of 
total aggregate exposure to that pesticide from food, water and 
residential uses. A DWLOC will vary depending on the residue level in 
foods, the toxicity endpoint, drinking water consumption patterns, and 
body weights for specific subpopulations. The chronic DWLOCs are 0.41 
ppm for the U.S. population and 0.12 ppm for the most exposed 
population subgroup, children (1-6 years). The DWLOCs are substantially 
higher than the GENEEC 56-day estimated environmental concentration of 
0.05 ppb for famoxadone in surface water or the Sci-Grow estimate of 
0.0097 ppb famoxadone in ground water. Therefore, since the estimated 
famoxadone concentrations are well below the chronic DWLOCs, the 
chronic dietary safety of famoxadone residues from drinking water 
clearly meets the FQPA standard of reasonable certainty of no harm. 
Using the appropriate inputs, the acute DWLOCs are 3.3 parts per 
million (ppm) for the U.S. population, and 0.91 ppm for the most 
exposed population subgroup, children (1-6 years). The estimated 
maximum concentration of famoxadone in surface water (2.49 ppb, derived 
from GENEEC) or in groundwater (0.0097 ppb, derived from Sci-Grow) is 
much lower than the acute DWLOC. Since the estimated famoxadone 
concentrations in ground and surface water are well below acute DWLOCs, 
the acute dietary safety of famoxadone residues from drinking water 
clearly meets the FQPA standard of reasonable certainty of no harm.
    2. Non-dietary exposure. Famoxadone products are not labeled for 
residential non-food uses, thereby eliminating the potential for 
residential exposure. Non-occupational, non-dietary exposure for 
famoxadone has not been estimated because the proposed products are 
limited to commercial crop production. Therefore, the potential for 
non-occupational exposure is insignificant.

D. Cumulative Effects

    EPA's consideration of a common mechanism of toxicity is not 
necessary at this time because there is no indication that toxic 
effects of famoxadone should be cumulative with those of any other 
chemical. Famoxadone is a member of a new class of fungicides that acts 
by inhibition of mitochondrial respiration. Famoxadone's biochemical 
mode of action on fungi and toxicological profile in animals appear to 
be unique. Given the distinct chemical, biological and toxicological 
profile, famoxadone's low acute toxicity, absence of genotoxic, 
oncogenic, developmental or reproductive effects and low exposure 
potential, the expression of cumulative human health effects with any 
other natural or synthetic pesticide is not anticipated.

E. Safety Determination

    1. U.S. population. Dietary and occupational exposure will be the 
major routes of exposure to the U.S. population. Ample margins of 
safety have been demonstrated for both situations. For the U.S. 
population, the chronic dietary exposure to famoxadone from all 
proposed uses is 0.000335 mg/kg/day, which utilizes 2.8% of the RfD for 
the overall U.S. population, assuming 30% of the crops are treated. The 
acute dietary exposure to the U.S. population is 0.001848 mg/kg/day 
(99th percentile) or 1.85% of the aRFD (99th percentile). At the 99th 
percentile, the acute dietary exposure for the U.S. population is 
0.006128 mg/kg/day or 6.13% of the aRfD.
    Using only PHED data levels A and B (those with a high level of 
confidence), the margin of exposures (MOEs) for occupational exposure 
are 2,665 to 5,329 for mixer/loaders, 34,418 for aerial applicators, 
and 1,096 for ground applicators. For flaggers, the MOE is 13,500. 
Based on the completeness and reliability of the toxicity data and the 
conservative exposure assessments, there is a reasonable certainty that 
no harm will result from the aggregate exposure of residues of 
famoxadone including all anticipated dietary

[[Page 39767]]

exposure and all other non-occupational exposures.
    2. Infants and children. Chronic dietary exposure of the most 
highly exposed subgroup in the population, children 1-6, is 0.000487 
mg/kg/day or 4.1% of the RfD. The acute dietary exposure of the most 
exposed subgroup, children 1-6, is 2.56% of the aRfD (99th percentile). 
For non-nursing infants (< 1 year), the acute dietary exposure is 0.95% 
RfD (99th percentile).
    There are no residential uses of famoxadone and contamination of 
drinking water is extremely unlikely. Based on the completeness and 
reliability of the toxicity data, the lack of toxicological endpoints 
of special concern, the lack of any indication of greater sensitivity 
of children, and the conservative exposure assessment, there is a 
reasonable certainty that no harm will result to infants and children 
from the aggregate exposure to residues of famoxadone from all 
anticipated sources of dietary and non-occupational exposure. 
Accordingly, there is no need to apply an additional safety factor for 
infants and children.

F. International Tolerances

    To date, no Codex, Canadian, or Mexican tolerances exist for 
famoxadone.
[FR Doc.01-19169 File7-31-01;8:45 am]
BILLING CODE 6560-50-S