[Federal Register Volume 66, Number 7 (Wednesday, January 10, 2001)]
[Notices]
[Pages 1981-1986]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-576]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-988; FRL-6760-8]


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

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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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-988, must be 
received on or before February 9, 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-988 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Cynthia L. Giles-Parker, 
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 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-988. 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-988 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-988. 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

[[Page 1982]]

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: December 26, 2000.
  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 
petitioner. 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 and Company (DuPont)

PP 0F6070

    EPA has received a pesticide petition (PP 0F6070) from E. I. DuPont 
de Nemours and Company (DuPont), DuPont Agricultural Products, Barley 
Mill Plaza, Wilmington, DE 19880-0038 proposing, pursuant to section 
408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by 
establishing a tolerance for residues of the fungicide famoxadone in or 
on the raw agricultural commodities(RACs) potatoes at 0.05 parts per 
million (ppm), cucurbit vegetable crop group (cucumbers, melons, and 
squash) at 0.7 ppm, fruiting vegetable crop group (tomatoes and 
peppers) at 1.0 ppm, and head lettuce at 15 ppm. EPA has determined 
that the 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 support granting of 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 3 distinct crops to support these tolerances: 
tomatoes, potatoes, and grapes. These studies showed no significant 
metabolites all (< 10% total radioactive residue (TRR)) in the RACs 
(tubers, tomato fruit, and 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 potatoes, cucurbit 
vegetables (cucumbers, melons, and squash), fruiting vegetables 
(tomatoes, peppers), and head lettuce using gas-liquid chromatography 
(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 (LOQ) is 0.02 ppm.
    The analytical enforcement for use on tomato processed fractions 
and also the RAC, tomato, utilizes column switching liquid 
chromatography with ultraviolet (UV) detection. The LOQ is 0.02 ppm.
    The LOQ in each method allows monitoring of crops with famoxadone 
residues at or above the levels proposed in these tolerances.
    3. Magnitude of residues--i. Cucurbit vegetables. The magnitude and 
decline of residues of famoxadone were determined on cucumber, 
cantaloupe, and summer squash, the representative commodities for the 
cucurbit vegetable crop group. Seventeen field trials were conducted in 
1997 and 1998.
    DPX-KP481 50DF, containing 25% cymoxanil and 25% famoxadone, was 
applied as 7 broadcast applications, each at the maximum rate of 3 oz 
famoxadone/Acre, for a maximum seasonal use rate of 21 oz famoxadone/
Acre. Applications were made approximately 5 days apart.
    The target pre-harvest interval (PHI) was 3 days.
     Residues of famoxadone in cucumbers from 6 test sites 
ranged from <0.02 to 0.19 ppm.
     Residues of famoxadone in cantaloupe from 6 test sites 
ranged from 0.11 to 0.46 ppm.
     Residues of famoxadone in summer squash from 5 test sites 
ranges from <0.02 to 0.37 ppm.
    ii. Fruiting vegetables. The magnitude and decline of famoxadone 
residues were determined on tomatoes, and peppers (bell and non-bell), 
the representative commodities for the fruiting vegetable crop group. 
Twenty-one residue trials were conducted in 1996 and 1997.
    DPX-KP481 50DF, containing 25% cymoxanil and 25% famoxadone, was 
applied as nine broadcast applications at a maximum seasonal use rate 
of 18 oz famoxadone/Acre. Applications were made approximately 5 days 
apart. The target PHI was 3 days. Residues of famoxadone on peppers 
(bell and non-bell) from 9 test sites ranged from 0.10-

[[Page 1983]]

0.70 ppm. Residues of famoxadone on tomatoes from 12 test sites ranged 
from 0.06-0.48 ppm.
    DPX-KP481 50DF, containing 25% cymoxanil and 25% famoxadone, was 
applied to 1 site in California to determine the magnitude of residue 
in tomato and the extent of potential residue concentration in tomato 
processed fractions. DPX-KP481 50DF was applied in 9 broadcast 
applications at 2 oz famoxadone/Acre (1X) and 10 oz famoxadone/Acre 
(5X). Applications were made approximately 5 days apart. The target PHI 
was 3 days. When applied at 5X the maximum seasonal use rate, 
famoxadone residues decreased with washing and did not concentrate in 
puree, with respect to the unwashed raw agricultural commodity (RAC). 
Famoxadone residues concentrated in tomato paste derived from tomato, 
treated at the 5X rate by a factor of 1.3. The 1.3 concentration factor 
does not warrant a special tolerance for paste. At the 1X rate, the 
proposed tomato tolerance for the RAC, 0.7 ppm, is adequate to cover 
this level of concentration in the paste. A separate tolerance for 
paste does not need to be established.
    iii. Head lettuce. Residue trials for head lettuce were conducted 
at 8 sites in 1997 and 1998. DPX-KP481 50DF, containing 25% cymoxanil 
and 25% famoxadone, was applied as 7 broadcast applications, each at 
the maximum rate of 3 oz famoxadone /Acre, for a maximum seasonal use 
rate of 21 oz famoxadone /Acre. Applications were made approximately 5 
days apart. The target PHI was 3 days. Residues of famoxadone on head 
lettuce ranged from 0.64 to 14 ppm (with wrapper leaves) and 0.024 to 
3.1 ppm (wrapper leaves removed).
    iv. Potato. Residue trials for famoxadone were conducted at 16 
sites in 1997. DPX-KP481 50DF, containing 25% cymoxanil and 25% 
famoxadone, was applied as 6 broadcast applications, each at 3 oz 
famoxadone/Acre, for a maximum seasonal use rate of 18 oz famoxadone/
Acre. Applications were made approximately 5 days apart. The target PHI 
was 14 days. No quantifiable residues of famoxadone were seen in any 
potato sample above the LOQ (0.02 ppm).
    DPX-KP481 50DF, containing 25% cymoxanil and 25% famoxadone, was 
applied to 1 test site in Washington to determine the magnitude of 
residue in potato and the extent of potential residue concentration in 
potato processed fractions. DPX-KP481 50DF was applied 6 times as a 
broadcast spray, each at 15 oz famoxadone/Acre, for a total seasonal 
application rate of 90 oz ai/Acre (5X). When applied under these 
conditions, no quantifiable famoxadone residues were detected in 
unwashed or washed potatoes/culls, chips, or granule fractions. Thus no 
concentration occurred in these fractions. At the 5X rate, quantifiable 
residues were detected in wet potato peels at 0.033 0.035 ppm. The 
concentration factor was 1.12 (based on LOQ of 0.02 ppm). When 
adjusting the residues in wet peels from the seasonal 5X to the 1X rate 
(18 oz famoxadone/Acre), residues in peels are less than the LOQ. 
Therefore, the negligible residues in the peels (less than 2X the LOQ) 
are covered by the proposed tolerance for the RAC, 0.05 ppm, and no 
separate tolerance for potato peels need be established.

B. Toxicological Profile

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

                                               Toxicity Categories
----------------------------------------------------------------------------------------------------------------
           Acute toxicities                  Test animals              Tolerances               Categories
----------------------------------------------------------------------------------------------------------------
Oral LD50                              Rat                      >5,000 milligrams/       Category IV
                                                                 kilograms (mg/kg)
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 no observed adverse effect level (NOAEL) was 1,000 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 gene mutation       Salmonella and E.     Negative
                               Coli
Mammalian gene mutation in    CHO/HGPRT             Negative
 vitro
Mammalian chromosome          chinese hampter       Positive without
 aberrations in vitro          ovary (CHO)           activation negative
                                                     with
                                                    activation
Mammalian chromosome          Mouse micronucleus    Negative
 aberrations in vivo
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 (bwt), 
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

[[Page 1984]]

reproduction (mating, fertility, 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 bwt 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 the same 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 bwt and nutritional effects 
at 800 ppm.
    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 foodconsumption, hemolytic anemia, and hyperkalemia with associated 
clinical signs at 1,000/600 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 
bwt, bwt gain, food consumption, food efficiency, and increased spleen 
weights at 800 ppm (55 and 57 mg/kg/day for males and females, 
respectively). There was no effect in response to anti-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 on increased 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 bwt, bwt 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 multi-generational 
bioassays in mammals and acute and subchronic 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

    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, and potatoes. There are 
no residential uses for the famoxadone-containing fungicide.
    1. Dietary exposure. The chronic reference dose (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 bwt/day is 
based upon bwt effects occurring early in a 90-day dog study. Since bwt 
is not actually an acute effect, the acute NOAEL selected is highly 
conservative and it is likely that the

[[Page 1985]]

actual acute NOAEL is much higher than 10.0 mg/kg/day.
    i. Food--a. Chronic dietary exposure assessment. Chronic dietary 
exposure, resulting from the proposed use of famoxadone on 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 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 food quality protection 
act (FQPA) standard of reasonable certainty of no harm.

                                  Results of Chronic Dietary Exposure Estimate
----------------------------------------------------------------------------------------------------------------
                                                       Maximum Dietary Exposure (mg/
                   Population Group                               kg/day)                        %RfD
----------------------------------------------------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------

    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% RfD. 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 percent RfDs 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 Exposure            99.9th Percentile of Exposure
                                 -------------------------------------------------------------------------------
        Population Group           Exposure (mg/kg/                        Exposure (mg/kg/
                                         day)                % RfD               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 
ground water 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 
concentration in ground water ((SCI-GROW) for ground water and generic 
expected environmental concentration (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 ground water 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 concern (DWLOC) 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

[[Page 1986]]

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 ground water (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 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 RFD (99th percentile). At the 
99.9th percentile, the acute dietary exposure for the U.S. 
population is 0.006128 mg/kg/day or 6.13% of the RfD.
    Using only pesticide handlers exposure data base (PHED) data levels 
A and B (those with a high level of confidence), the margin of exposure 
(MOE) 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 
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 RfD (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. 01-576 Filed 1-9-01; 8:45 am]
BILLING CODE 6560-50-S