[Federal Register Volume 66, Number 53 (Monday, March 19, 2001)]
[Notices]
[Pages 15443-15459]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-6721]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-997; FRL-6766-7]


Notice of Filing Pesticide Petitions to Establish Tolerances for 
Certain Pesticide Chemicals in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

DATES: Comments, identified by docket control number PF-000, must be 
received on or before April 18, 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-000 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: Joseph Tavano, Registration 
Support Branch, Registration Division (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 305-6411; 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'' 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

[[Page 15444]]

action under docket control number PF-000. 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-000 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-000. 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: February 26, 2001.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petitions

    Petitioner summaries of the pesticide petitions are printed below 
as required by section 408(d)(3) of the Federal Food, Drug, and 
Cosmetic Act (FFDCA). The summaries of the petitions were prepared by 
the petitioner and represent the view of the petitioner. EPA is 
publishing the petition summaries verbatim without editing them 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.

1. Rohm and Haas Company

PP 0F6176

    EPA has received a pesticide petition (0F6176) from Rohm and Haas 
Company, 100 Independence Mall West, Philadelphia, PA 19106-02399 
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 
tebufenozide benzoic acid, 3,5-dimethyl-,1-(1,1-dimethylethyl)-2-(4-4-
ethylbenzoyl) hydrazide in or on the raw agricultural commodity citrus 
crop group (Crop Group 10) at 0.8 parts per million (ppm) and in or on 
citrus oil at 15 parts per million (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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Nature of the residue--Plants. The qualitative nature of the 
residue in plants is adequately understood based

[[Page 15445]]

upon acceptable apple, sugar beet, and rice metabolism studies. The 
Agency has concluded that the residue of regulatory concern is 
tebufenozide per se.
    2.  Nature of the residue--Animal. The results of the ruminant and 
poultry metabolism studies have been reviewed by the Agency and the 
determination was made that the tebufenozide residues of regulatory 
concern in animals are the parent tebufenozide and the four metabolites 
designated: RH-2703 [benzoic acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-
2-((4-carboxymethyl)benzoyl)hydrazide], RH-9886 [benzoic acid, 3-
hydroxymethyl,5-methyl-1-(1,1-dimethylethyl)-2-(4-
ethylbenzoyl)hydrazide], the stearic acid conjugate of RH-9886, and RH-
0282 [benzoic acid, 3-hydroxymethyl-5-methyl-1-(1,1-dimethylethyl)-2-
(4-(1-hydroxyethyl) benzoyl)hydrazide].
    3. Analytical method-- i. Plant tissues. Rohm and Haas method TR 
34-96-184, with minor modifications, was used to determine tebufenozide 
residue levels in/on lemons, grapefruit and oranges. This method was 
independently validated. The method involves extraction by blending 
with solvents, purification of the extracts by liquid-liquid partitions 
and final purification of the residues using solid phase extraction 
column chromatography. The limit of quantitation (LOQ) of the method 
for all matrices is 0.02 ppm for tebufenozide and the limit of 
detection (LOD) is 0.006 ppm.
    ii. Animal tissues. A submitted high performance liquid 
chromotography (HPLC/UV) Method, Rohm and Haas Method TR 34-96-109, has 
been determined to be adequate for collecting data on residues of 
tebufenozide in animal tissues. The validated LOQ for tebufenozide in 
animal tissue is 0.02 ppm. The LOQ for each of the metabolites studied 
are as follows: RH-2703 in liver, 0.02 ppm; RH-9886 and RH-0282 in 
meat, 0.02 ppm; RH-9526 in fat, 0.02 ppm. The LODs for the analytes are 
0.006 ppm in tissues.
    iii. Multi-residue methods. Rohm and Haas has previously submitted 
data involving multi-residue method testing.
    a. Magnitude of residues. Field residue trials were conducted in 
the representative citrus fruit crops lemons, grapefruit and oranges 
and residues of tebufenozide were measured in whole fruit, peel and 
fresh pulp. The highest average field trial residue observed was in 
oranges at 047 ppm. Results of analyses showed that residues of 
tebufenozide will not exceed 0.8 ppm in whole fruit. Residues were 
found to be mainly associated in the peel and not in the fresh pulp.
    b. Processed food/feed. Grapefruit and orange processing studies 
were conducted. Residues of tebufenozide did not concentrate in dry 
pulp or juice. Residues of tebufenozide concentrated in citrus oil. The 
average concentration factor for citrus oil was determined to be 26. 
The Highest Average Field Trial residue was in oranges at 0.47 ppm. 
Residues of tebufenozide in citrus oil should not exceed 15 ppm 
(rounded up from 0.47 ppm X 26).

B. Toxicological Profile

    1. Acute toxicity. Acute toxicity studies with technical grade: 
Oral LD50 in the rat is > 5 grams for males and females - 
Toxicity Category IV; dermal LD50 in the rat is = 5,000 
milligram/kilogram (mg/kg) for males and females - Toxicity Category 
III; inhalation LD50 in the rat is > 4.5 mg/l - Toxicity 
Category III; primary eye irritation study in the rabbit is a non-
irritant; primary skin irritation in the rabbit > 5 mg - Toxicity 
Category IV. Tebufenozide is not a sensitizer.
    In a 21-day dermal toxicity study, Crl: CD rats (6/sex/dose) 
received repeated dermal administration of either the technical 96.1% 
product RH-75,992 at 1,000 mg/kg/day Limit-Dose or the formulation 
23.1% a.i. product RH-755,992 2F at 0, 62.5, 250, or 1,000 mg/kg/day, 6 
hours/day, 5 days/week for 21 days. Under conditions of this study, RH-
75,992 Technical or RH-75,992 2F demonstrated no systemic toxicity or 
dermal irritation at the highest dose tested 1,000 mg/kg/ during the 
21-day study. Based on these results, the NOAEL for systemic toxicity 
and dermal irritation in both sexes is 1,000 mg/kg/day highest dose 
tested (HDT). A lowest-observable-effect level (LOAEL) for systemic 
toxicity and dermal irritation was not established.
    2. Genotoxicity. Several mutagenicity tests which were all 
negative. These include an Ames assay with and without metabolic 
activation, an in vivo cytogenetic assay in rat bone marrow cells, and 
in vitro chromosome aberration assay in CHO cells, a CHO/HGPRT assay, a 
reverse mutation assay with E. Coli, and an unscheduled DNA synthesis 
assay (UDS) in rat hepatocytes.
    3. Reproductive and developmental toxicity. In a prenatal 
developmental toxicity study in Sprague-Dawley rats 25/group 
Tebufenozide was administered on gestation days 6-15 by gavage in 
aqueous methyl cellulose at dose levels of 50, 250, or 1,000 mg/kg/day 
and a dose volume of 10 ml/kg. There was no evidence of maternal or 
developmental toxicity; the maternal and developmental toxicity NOAEL 
was 1,000 mg/kg/day.
    In a prenatal developmental toxicity study conducted in New Zealand 
white rabbits 20/group Tebufenozide was administered in 5 ml/kg of 
aqueous methyl cellulose at gavage doses of 50, 250, or 1,000 mg/kg/day 
on gestation days 7-19. No evidence of maternal or developmental 
toxicity was observed; the maternal and developmental toxicity NOAEL 
was 1,000 mg/kg/day.
    In a 1993 two-generation reproduction study in Sprague-Dawley rats 
tebufenozide was administered at dietary concentrations of 0, 10, 150, 
or 1,000 ppm (0, 0.8, 11.5, or 154.8 mg/kg/day for males and 0, 0.9, 
12.8, or 171.1 mg/kg/day for females). The parental systemic NOAEL was 
10 ppm (0.8/0.9 mg/kg/day for males and females, respectively) and the 
LOAEL was 150 ppm (11.5/12.8 mg/kg/day for males and females, 
respectively) based on decreased body weight, body weight gain, and 
food consumption in males, and increased incidence and/or severity of 
splenic pigmentation. In addition, there was an increased incidence and 
severity of extra-medullary hematopoiesis at 2,000 ppm. The 
reproductive NOAEL was 150 ppm. (11.5/12.8 mg/kg/day for males and 
females, respectively) and the LOAEL was 2,000 ppm (154.8/171.1 mg/kg/
day for males and females, respectively) based on an increase in the 
number of pregnant females with increased gestation duration and 
dystocia. Effects in the offspring consisted of decreased number of 
pups per litter on postnatal days 0 and/or 4 at 2,000 ppm (154.8/171.1 
mg/kg/day for males and females, respectively) with a NOAEL of 150 ppm 
(11.5/12.8 mg/kg/day for males and females, respectively).
    In a 1995 two-generation reproduction study in rats tebufenozide 
was administered at dietary concentrations of 0, 25, 200, or 2,000 ppm 
(0, 1.6, 12.6, or 126.0 mg/kg/day for males and 0, 1.8, 14.6, or 143.2 
mg/kg/day for females). For parental systemic toxicity, the NOAEL was 
25 ppm (1.6/1.8 mg/kg/day in males and females, respectively), and the 
LOAEL was 200 ppm (12.6/14.6 mg/kg/day in males and females), based on 
histopathological findings (congestion and extra-medullary 
hematopoiesis) in the spleen. Additionally, at 2,000 ppm (126.0/143.2 
mg/kg/day in M/F), treatment-related findings included reduced parental 
body weight gain and increased incidence of hemosiderin-laden cells in 
the spleen. Columnar changes in the vaginal squamous epithelium and 
reduced uterine and ovarian weights were also observed at

[[Page 15446]]

2,000 ppm, but the toxicological significance was unknown. For 
offspring, the systemic NOAEL was 200 ppm. (12.6/14.6 mg/kg/day in 
males and females), and the LOAEL was 2,000 ppm (126.0/143.2 mg/kg/day 
in M/F) based on decreased body weight on postnatal days 14 and 21.
    4. Subchronic toxicity. A 1-year dog feeding study with a (LOAEL) 
of 250 ppm, 9 mg/kg/day for male and female dogs based on decreases in 
RBC, HCT, and HGB, increases in Heinz bodies, methemoglobin, MCV, MCH, 
reticulocytes, platelets, plasma total bilirubin, spleen weight, and 
spleen/body weight ratio, and liver/body weight ratio. Hematopoiesis 
and sinusoidal engorgement occurred in the spleen, and hyperplasia 
occurred in the marrow of the femur and sternum. The liver showed an 
increased pigment in the Kupffer cells. The no-observed effect level 
(NOAEL) for systemic toxicity in both sexes is 50 ppm (1.9 mg/kg/day).
    5. Chronic toxicity. An 18-month mouse carcinogenicity study with 
no carcinogenicity observed at dosage levels up to and including 1,000 
ppm.
    A 2-year rat carcinogenicity with no carcinogenicity observed at 
dosage levels up to and including 2,000 ppm (97 mg/kg/day and 125 mg/
kg/day for males and females, respectively).
    6. Animal metabolism. The pharmacokinetics and metabolism of 
tebufenozide were studied in female Sprague-Dawley rats (3-6/sex/group) 
receiving a single oral dose of 3 or 250 mg/kg of RH-5992 
14C labeled in one of three positions (A-ring, B-ring or N-
butyl carbon). The extent of absorption was not established. The 
majority of the radio labeled material was eliminated or excreted in 
the feces within 48 hours within 48 hours; small amounts (1 to 7% of 
the administered dose) were excreted in the urine and only traces were 
excreted in expired air or remained in the tissues. There was no 
tendency for bioaccumulation. Absorption and excretion were rapid. A 
total of 11 metabolites, in addition to the parent compound, were 
identified in the feces; the parent compound accounted for 96 to 99% of 
the administered radioactivity in the high dose group and 35 to 43% in 
the low dose group. No parent compound was found in the urine; urinary 
metabolites were not characterized. The identity of several fecal 
metabolites was confirmed by mass spectral analysis and other fecal 
metabolites were tentatively identified by cochromatography with 
synthetic standards. A pathway of metabolism was proposed based on 
these data. Metabolism proceeded primarily by oxidation of the three 
benzyl carbons, two methyl groups on the B-ring and an ethyl group on 
the A-ring to alcohols, aldehydes or acids. The type of metabolite 
produced varies depending on the position oxidized and extent of 
oxidation. The butyl group on the quaternary nitrogen also can be 
cleaved (minor), but there was no fragmentation of the molecule between 
the benzyl rings. No qualitative differences in metabolism were 
observed between sexes, when high or low dose groups were compared or 
when different labeled versions of the molecule were compared.
    The absorption and metabolism of tebufenozide were studied in a 
group of male and female bile-duct cannulated rats. Over a 72 hour 
period, biliary excretion accounted for 30%[M] to 34%[F] of the 
administered dose while urinary excretion accounted for about 5% of the 
administered dose and the carcass accounted for <0.5% of the 
administered dose for both males and females. Thus systemic absorption 
(percent of dose recovered in the bile, urine and carcass) was 35%[M] 
to 39%[F]. The majority of the radioactivity in the bile (20%[M] to 
24%[F] of the administered dose) was excreted within the first 6 hours 
post-dosing indicating rapid absorption. Furthermore, urinary excretion 
of the metabolites was essentially complete within 24 hours post-
dosing. A large amount [67%[F] to 70%[M)] of the administered dose was 
unabsorbed and excreted in the feces by 72 hours. Total recovery of 
radioactivity was 105% of the administered dose.
    7. Metabolite toxicology. A total of 13 metabolites were identified 
in the bile; the parent compound was not identified, i.e. unabsorbed 
compound, nor were the primary oxidation products seen in the feces in 
the pharmacokinetics study. The proposed metabolic pathway proceeded 
primarily by oxidation of the benzylic carbons to alcohols, aldehydes 
or acids. Bile contained most of the other highly oxidized products 
found in the feces. The most significant individual bile metabolites 
accounted for 5% to 18% of the total radioactivity (F and/or M). Bile 
also contained the previously undetected (in the pharmacokinetics 
study) ``A'' Ring ketone and the ``B'' Ring diol. The other major 
components were characterized as high molecular weight conjugates. No 
individual bile metabolite accounted for 5% of the total administered 
dose. Total bile radioactivity accounted for about 17% of the total 
administered dose.
    No major qualitative differences in biliary metabolites were 
observed between sexes. The metabolic profile in the bile was similar 
to the metabolic profile in the feces and urine.
    8. Short- and intermediate-term toxicity. No dermal or systemic 
toxicity was seen in rats receiving 15 repeated dermal applications of 
the technical (97.2%) product at 1,000 mg/kg/day (Limit- Dose) as well 
as a formulated (23% a.i) product at 0, 62.5, 250, or 1,000 mg/kg/day 
over a 21-day period. In spite of the hematological effects seen in the 
dog study, similar effects were not seen in the rats receiving the 
compound via the dermal route indicating poor dermal absorption. Also, 
no developmental endpoints of concern were evident due to the lack of 
developmental toxicity in either rat or rabbit studies. This risk is 
considered to be negligible.

C. Aggregate Exposure

    1. Dietary exposure--i. Food-- From food and feed uses. Tolerances 
have been established (40 CFR 180.482) for the residues of 
tebufenozide, in or on a variety of raw agricultural commodities. The 
current petition requests establishment of tolerances in or on the crop 
group Citrus Fruit at 0.8 ppm and in citrus oil at 15 ppm. Risk 
assessments were conducted by Rohm and Haas to assess dietary exposures 
and risks from tebufenozide, benzoic acid, 3,5-dimethyl-1-(1,1-
dimethylethyl)-2-(4-ethylbenzoyl) hydrazide as follows:
    a. Acute exposure and risk. Acute dietary risk assessments are 
performed for a food-use pesticide if a toxicological study has 
indicated the possibility of an effect of concern occurring as a result 
of a one day or single exposure. Neither neurotoxicity nor systemic 
toxicity was observed in rats given a single oral administration of 
tebufenozide at 0, 500, 1,000 or 2,000 mg/kg. No maternal or 
developmental toxicity was observed following oral administration of 
tebufenozide at 1,000 mg/kg/day (Limit-Dose) during gestation to 
pregnant rabbits. This risk is considered to be negligible.
    b. Chronic exposure and risk. The RfD used for the chronic dietary 
analysis is 0.018 mg/kg/day. In conducting the DEEM (Dietary Exposure 
Evaluation Model) analysis for chronic exposure to and risk from 
tebufenozide residues in food, Rohm and Haas used tolerance level 
residues for all crops and other commodities with established or 
pending tebufenozide tolerances; and percent crop-treated (PCT) 
information for some of these crops. The following tolerances were 
used: Citrus fruit at 0.8 ppm, citrus oil at 15 ppm, tree nut crop 
group at 0.1 ppm, pome fruit at 1.5 ppm, cotton at 1.5 ppm, leafy and 
cole crop groups ranging from 2.0 to 10.0 ppm,

[[Page 15447]]

turnip tops at 9.0 ppm, turnip roots at 0.25 ppm, canola seed at 1.75 
ppm, canola oil at 3.75 ppm, mint at 10.0 ppm, fruiting vegetables at 
1.0 ppm, sugarcane at 1.0 ppm, molasses at 0.6 ppm, cranberries at 1.0 
ppm, berry crops at 3.0 ppm, imported kiwifruit at 1.0 ppm and imported 
wine grapes at 0.5 ppm, and the livestock commodities milk, meat and 
meat by-products ranging from 0.05 to 0.25 ppm. The % CT information 
utilized is found in Table 1 below:

Table 1.--Maximum Percent Crop Treated Values for Various Crops Utilized
                  in Chronic Dietary Exposure Analyses
------------------------------------------------------------------------
                   Crop                         Maximum PCT (Percent)
------------------------------------------------------------------------
Cranberries                                 100
Kiwifruit                                   100
Canola                                      100
Mint                                        100
Grapes                                      100
Citrus                                      100
Meat, Meat By-Products, Milk                100
Sugarcane                                   82
Turnips                                     75
Pecans                                      40
Walnuts                                     30
Berry Crops                                 25
Cotton                                      19
Cole Crop Vegetables                        18
Almonds                                     16
Leafy Vegetables                            14
Pome Fruit                                  10
Fruiting Vegetables                         10
------------------------------------------------------------------------

    The Novigen DEEM system (version 7.075) was used for this chronic 
dietary exposure analysis. The analysis evaluates individual food 
consumption as reported by respondents in the USDA Continuing Surveys 
of Food Intake by Individuals conducted in 1989 through 1992. Summaries 
of the exposures and their representations as percentages of the cPAD 
for the general population and subgroups of interest are presented in 
Table 2 below. The subgroups listed below are (1) the U.S. Population 
(48 states); (2) those for infants and children; and (3) the other 
subgroups (adult) for which the percentage of the RfD occupied is 
greater than that occupied by the subgroup U.S. Population (48 states). 
cPAD% is defined as Exposure X 100% divided by the cPAD. The results 
are summarized below in Table 2:

 Table 2.--Chronic Exposure Analysis by the DEEM System for Tebufenozide
------------------------------------------------------------------------
                                   Exposure (mg/kg/
           Population                    day )          cPAD  (Percent)
------------------------------------------------------------------------
U.S. Population                   0.0038              21.1
All Infants (< 1 year )           0.0041              23.0
Nursing Infants (< 1 year)        0.0023              12.9
Non-Nursing Infants (< 1 year)    0.0049              27.3
Children (1-6 years old)          0.0092              51.0
Children (7-12 years old)         0.0057              31.8
Females (13+ years, nursing)      0.0043              23.9
U.S. Population Autumn            0.0038              21.4
U.S. Population Winter            0.0039              21.9
Hispanics                         0.0042              23.1
Non-Hispanic Blacks               0.0043              23.6
Non-Hispanic Other than Black or  0.0049              27.5
 White
Northeast Region                  0.0042              23.1
Western Region                    0.0042              23.5
Pacific Region                    0.0043              24.1
------------------------------------------------------------------------

    This chronic dietary (food only) risk assessment should be viewed 
as conservative. Further refinement using anticipated residue values 
and additional PCT information would result in a lower estimate of 
chronic dietary exposure from food.
    ii. Drinking water-- a. Acute exposure and risk. Because no acute 
dietary endpoint was determined, Rohm and Haas concludes that there is 
a reasonable certainty of no harm from acute exposure from drinking 
water.
    b. Chronic exposure and risk. The Agency calculated the Tier I 
Estimated Environmental Concentrations (EECs) for tebufenozide using 
generic expected environmental concentration (GENEEC) (surface water) 
and screening concentration in ground water (SCI- GROW) (ground water) 
models for use in the human health risk assessment. For chronic 
exposure, the worst case EECs for surface water and ground water were 
16.5 parts per billion (ppb) and 1.04 ppb, respectively. These values 
represent upper-bound estimates of the concentrations that might be 
found in surface and ground water. These modeling data were compared to 
the chronic drinking water levels of comparison (DWLOC) for 
tebufenozide in ground and surface water.
    For purposes of chronic risk assessment, the estimated maximum 
concentration for tebufenozide in surface and ground waters (16.5 ppb) 
was compared to the back-calculated human health DWLOCs for the chronic 
(non-cancer) endpoint. These DWLOCs for various population categories 
are summarized below in Table 3:

                                  Table 3.--Drinking Water Levels of Comparison for Chronic Exposure to Tebufenozide\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                     EEC\7\ calc. max.
       Population Category\2\          Chronic RfD (mg/kg/    Food exposure (mg/kg/   exposure Max. water     DWLOC (g/     (g/L) (in
                                              day)                    day)               (mg/kg/day)\3\           L)\4,5,6\               percent)
--------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. Population (48 contiguous       0.018                   0.0038                  0.0142                 497                    16.5
 states)
Females (13+ years)                  0.018                   0.0043                  0.0137                 411                    16.5
Children (1-6 years)                 0.018                   0.0092                  0.0088                 88                     16.5
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Values are expressed to 2 significant figures.
\2\ Within each of these categories, the subgroup with the highest food exposure was selected.
\3\ Maximum water exposure (chronic) (mg/kg/day) = Chronic PAD (mg/kg/day).
\4\ DWLOC (g/L) = Max. water exposure (mg/kg/day) x body wt (kg) divided by 10-\3\ mg/g) x water consumed daily (L/day).
\5\ HED Default body weights are: General U.S. population, 70 kg; females (13+ years old), 60 kg; other adult populations, 70 kg; and, all infants/
  children, 10 kg.
\6\ HED Default daily drinking rates are 2 L/day for adults and 1 L/day for children.
\7\ EEC: Estimated Environmental Concentration. (Chronic 56-day value).


[[Page 15448]]

    2. Non-dietary exposure. There is a potential for occupational 
exposure to tebufenozide during mixing, loading, and application 
activities. However, the Agency did not identify dermal or inhalation 
endpoints for tebufenozide and determined that risks from these routes 
of exposure are negligible.

D. Cumulative Effects

    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 tebufenozide 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, tebufenozide does not appear to produce a toxic metabolite 
produced by other substances. For the purposes of this tolerance 
petition, Rohm and Haas has not assumed that tebufenozide has a common 
mechanism of toxicity with other substances.

E. Safety Determination

    1. U.S. population-- aggregate risks and determination of safety 
for U.S. population--i. Acute risk. The Agency did not identify an 
acute dietary toxicological endpoint, therefore, the risk from this 
route of exposure is negligible.
    ii. Chronic risk. Using the exposure assumptions described above, 
and taking into account the completeness and reliability of the 
toxicity data, Rohm and Haas has concluded that dietary (food only) 
exposure to tebufenozide will utilize 21% of the cPAD for the U.S. 
population, and 51% of the cPAD for the most highly exposed population 
subgroup (children 1-6 years old). EPA generally has no concern for 
exposures below 100% of the cPAD. Submitted environmental fate studies 
suggest that tebufenozide is moderately persistent to persistent and 
mobile; thus, tebufenozide could potentially leach to ground water and 
runoff to surface water under certain environmental conditions. The 
modeling data for tebufenozide indicate levels less than the Agency's 
DWLOCs. There are no chronic non- occupational/residential exposures 
expected for tebufenozide. Therefore, the Rohm and Haas concludes that 
there is a reasonable certainty that no harm will result to adults, 
infants and children from chronic aggregate exposure to tebufenozide 
residues.
    iii. Short- and intermediate-term risk. There are potential non-
occupational/residential short-term post application exposures 
(incidental non-dietary ingestion) to toddlers from the use of 
tebufenozide on ornamentals. However, since the Agency did not identify 
acute dietary endpoint, the short-term post application exposure risk 
assessment is expected to be negligible. Intermediate-term incidental 
non-dietary exposures are not expected.
    iv. Determination of safety. Based on these risk assessments, Rohm 
and Haas concludes that there is a reasonable certainty that no harm 
will result from aggregate exposure to tebufenozide residues.
    2. Infants and children--aggregate risk and determination of safety 
for infants and children-- i. Safety factor for infants and children. 
In assessing the potential for additional sensitivity of infants and 
children to residues of tebufenozide, EPA considered data from 
developmental toxicity studies in the rat and rabbit and a two-
generation reproduction study in the rat. The developmental toxicity 
studies are designed to evaluate adverse effects on the developing 
organism resulting from maternal pesticide exposure gestation. 
Reproduction studies provide information relating to effects from 
exposure to the pesticide on the reproductive capability of mating 
animals and data on systemic toxicity.
    FFDCA section 408 provides that EPA shall apply an additional 
tenfold margin of safety for infants and children in the case of 
threshold effects to account for pre- and post-natal toxicity and the 
completeness of the database unless EPA determines that a different 
margin of safety will be safe for infants and children. Margins of 
safety are incorporated into EPA risk assessments either directly 
through use of a MOE analysis or through using uncertainty (safety) 
factors in calculating a dose level that poses no appreciable risk to 
humans. EPA believes that reliable data support using the standard 
uncertainty factor (usually 100 for combined inter- and intra-species 
variability) and not the additional tenfold MOE/uncertainty factor when 
EPA has a complete data base under existing guidelines and when the 
severity of the effect in infants or children or the potency or unusual 
toxic properties of a compound do not raise concerns regarding the 
adequacy of the standard MOE/safety factor.
    ii. Conclusion. There is a complete toxicity data base for 
tebufenozide and exposure data are complete or are estimated based on 
data that reasonably accounts for potential exposures. For the reasons 
summarized above, Rohm and Haas concludes that an additional safety 
factor is not needed to protect the safety of infants and children.
    iii. Acute risk. Since no acute toxicological endpoints were 
established, it is unlikely that acute aggregate risk exists.
    iv. Chronic risk. Using the exposure assumptions described above, 
and taking into account the completeness and reliability of the 
toxicity data, the Agency has concluded that dietary (food only) 
exposure to tebufenozide will utilize 21% of the cPAD for the U.S. 
population, and 51% of the cPAD for the most highly exposed population 
subgroup (children 1-6 years old). EPA generally has no concern for 
exposures below 100% of the cPAD. Despite the potential for exposure to 
tebufenozide in drinking water and from non-dietary, non- occupational 
exposure, Rohm and Haas does not expect the aggregate exposure to 
exceed 100% of the RfD.
    v. Short- or intermediate-term risk. Short- and intermediate-term 
risks are judged to be negligible due to the lack of significant 
toxicological effects observed.
    vi. Determination of safety. Based on these risk assessments, Rohm 
and Haas concludes that there is a reasonable certainty that no harm 
will result to infants and children from aggregate exposure to 
tebufenozide residues.

F. International Tolerances

    Codex MRLs have been established for residues of tebufenozide in/on 
pome fruit (1.0 ppm), husked rice (0.1 ppm) and walnuts (0.05 ppm). 
Tebufenozide is registered in Canada, and a tolerance for residues in/
on apples is established at 1.0 ppm. EPA has set the pome fruit 
tolerance at 1.5 ppm based on U.S. field residue trials.

2. Rohm and Haas Company

PP 0F6201

    EPA has received a pesticide petition (0F6201) from Rohm and Haas 
Company, 100 Independence Mall West, Philadelphia, PA, 19106-2399 
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 time-limited tolerances for indirect or inadvertent 
residues of methoxyfenozide [benzoic acid, 3-methoxy-2-methyl-, 2-(3,5-
dimethylbenzoyl)-2-(1,1-dimethylethyl) hydrazide] and its metabolites 
RH-117,236 (free phenol of methoxyfenozide; 3,5-dimethylbenzoic

[[Page 15449]]

acid N-tert-butyl-N'-(3-hydroxy- 2-methylbenzoyl) hydrazide), RH-
151,055 (the glucose conjugate of RH-117,236; 3,5-dimethylbenzoic acid 
N-tert- butyl-N-[3( -D-glucopyranosyloxy)-2-methylbenzoyl]-hydrazide) 
and RH-152,072 (the malonylglycosyl conjugate of RH-117,236) in or on 
the raw agricultural commodities root and tuber vegetables at 0.05 
parts per million (ppm); leaves of root and tuber vegetables at 0.1 
ppm; bulb vegetables at 0.1 ppm; leafy vegetables (except Brassica) at 
0.2 ppm; Brassica vegetables at 0.2 ppm; legume vegetables at 0.05 ppm; 
foliage of legume vegetables at 8 ppm; forage, fodder, hay and straw of 
cereal grains at 7 ppm; grass forage, fodder and hay at 7 ppm; forage, 
fodder, straw and hay of non-grass animal feeds at 8 ppm; and herbs and 
spices at 8 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 supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.

A. Residue Chemistry

    1. Plant metabolism. The qualitative nature of methoxyfenozide 
residues in plants is adequately understood based upon acceptable 
cotton, apple and grape metabolism studies. EPA has determined that the 
residue of concern for dietary exposure and tolerance setting purposes 
in primary crops and water is the parent compound, methoxyfenozide. The 
qualitative nature of methoxyfenozide residues in rotation crop plants 
is adequately understood based upon 14C confined rotation 
crop studies. The residue of concern for dietary exposure and tolerance 
setting purposes in rotation crops is the parent compound, 
methoxyfenozide and its metabolites RH-117,236 (free phenol of 
methoxyfenozide; 3,5-dimethylbenzoic acid N-tert-butyl-N'-(3-hydroxy-2-
methylbenzoyl) hydrazide), RH-151,055 (the glucose conjugate of RH-
117,236; 3,5-dimethylbenzoic acid N-tert-butyl-N-[3(-D-
glucopyranosyloxy)-2- methylbenzoyl]-hydrazide) and RH-152,072 (the 
malonylglycosyl conjugate of RH-117,236).
    The qualitative nature of the residue in animals is adequately 
understood based on acceptable studies conducted on goats and laying 
hens. EPA has determined that the residue of concern in milk and 
ruminant tissues (other than liver and kidney) is the parent compound, 
methoxyfenozide. The residue of concern in ruminant liver and kidney is 
the parent compound, methoxyfenozide, and its glucuronide metabolite 
designated as RH-141,518 (also referred to as RH-1518).
    2.  Analytical method. An HPLC/UV Method TR 34-00-41 for the 
enforcement of tolerances in rotation crops has been developed. 
Confirmatory method validation, radiovalidation, and independent method 
validation data have been submitted for this method. The validated 
limit of quantitation (LOQ) of the analytical method was 0.02 ppm in 
all matrices for methoxyfenozide and RH-117,236 and 0.05 ppm for RH-
151,055.
    3. Magnitude of residues. Magnitude of the residue in rotation 
crops. Two geographically representative field trials were submitted to 
support the proposed time-limited tolerances on rotation crops. 
Turnips, onions, mustard greens, tomatoes, cucumbers, soybeans and 
wheat were planted back 7 days after the last application to growing 
lettuce crops of methoxyfenozide 80WP formulation according to the 
maximum proposed use patterns. The rotated crops were harvested at 
maturity. Residues of methoxyfenozide in turnip roots, turnip tops, 
onions, mustard greens, tomatoes and cucumbers ranged from no-
detectable residues to 0.07 ppm.
    The results of the field trials indicate that residues of 
methoxyfenozide will not exceed the proposed tolerances of 0.05 ppm in 
root and tuber vegetables, 0.1 ppm in the leaves of root and tuber 
vegetables, 0.1 ppm in bulb vegetables, 0.2 ppm in leafy and cole crop 
vegetables. No residues were found in fruiting vegetables or cucurbit 
vegetables. Residues of methoxyfenozide and its metabolites RH-117236, 
RH-151055 and RH-152072 in soybean seeds did not exceed 0.033 ppm and 
no residues were detected in wheat grain. Residues of methoxyfenozide 
and its metabolites concentrated in the dry matrices soybean hay and 
wheat straw at 7.1 ppm and 6.4 ppm, respectively. The results of the 
field trials indicate that residues of methoxyfenozide and its 
metabolites will not exceed the proposed tolerances of 7 ppm in forage, 
fodder and straw of cereal grains and grass forage, fodder and hay. 
Residues of methoxyfenozide and its metabolites will not exceed the 
proposed tolerances of 8 ppm in foliage of legume vegetables, forage, 
fodder, straw and hay of non-animal feeds, or in herbs and spices. 
Additional rotation crop trials are in progress to support these time-
limited tolerances.
    Residues in meat, milk, poultry, and eggs. The maximum theoretical 
dietary burden of methoxyfenozide for dairy or beef cattle associated 
with this petition is estimated to be less than 20 ppm. The established 
tolerances of 0.02 ppm in the milk and meat of cattle, goats, hogs, 
horses, and sheep, 0.1 ppm in the fat of cattle, goats, hogs, horses, 
and sheep, 0.1 ppm in liver and 0.02 ppm in meat byproduct (except 
liver) of cattle, goat, hogs, horses, and sheep were established based 
on a dairy cow feeding level of 45 ppm. These tolerances are adequate 
for the proposed rotation crop tolerances.
    The maximum theoretical dietary burden of methoxyfenozide for 
poultry animals associated with this petition (from cotton meal and 
soybean seed) would contribute a maximum theoretical dietary burden for 
methoxyfenozide at 0.41 ppm. A poultry metabolism study was conducted 
at feeding levels of 58 ppm, 60 ppm, and 68 ppm which are equivalent to 
145x, 150x, and 170x, respectively, the maximum theoretical dietary 
burden for poultry. Assuming a linear relationship between dose and 
residues, the expected residues in eggs and poultry tissues would be 
below the LOD for methods used to measure residues in poultry products. 
Rohm and Haas concludes that there is no reasonable expectation of 
finite residues in eggs and poultry tissues and that a poultry feeding 
study is not required at this time.

B. Toxicological Profile

    1. Acute toxicity. Acute toxicity studies with technical grade: 
Oral LD50 in the rat is 5,000 milligrams/kilograms (mg/kg) 
for males and females- Toxicity Category IV; Oral LD50 in 
the mouse is 5,000 mg/kg for males and females-Toxicity Category IV; 
Dermal LD50 in the rat is > 2,000 mg/kg-Toxicity Category 
III; Inhalation LC50 in the rat is > 4.3 milligram/liter 
(mg/L)-Toxicity Category IV; Primary Eye Irritation in the rabbit-very 
mild irritant-Toxicity Category IV; Primary skin irritation in the 
rabbit-not a skin irritant-Toxicity Category IV. Methoxyfenozide is not 
a skin sensitizer.
    In an acute neurotoxicity study in rats, statistically significant 
decreased hind limb grip strength was observed in male rats at 3 hours 
(approximate time of peak effect) following a single oral dose of 2,000 
mg/kg (limit dose) of methoxyfenozide. Decreased hindlimb grip strength 
was also observed in the male rats at 7 and 14 days, but was not 
statistically significant. No other systemic or neurotoxic effects were 
observed in the male rats or in the female rats at any time in this 
study. Since this marginal effect occurred only in one sex, was 
statistically significant at only one time, was observed only at the 
high dose (limit dose) and no other

[[Page 15450]]

signs of toxicity were observed in the rats in this study, this 
possible effect is not considered to be biologically significant. In 
addition, neither decreased hindlimb grip strength nor any other signs 
of neurotoxicity were observed in any of the animals at any time in a 
90-day subchronic neurotoxicity study in rats.
    2. Genotoxicity. In a battery of four mutagenicity studies (with 
and without metabolic activation, as appropriate for the specific 
study), technical grade methoxyfenozide was negative for genotoxicity 
in all four studies. The four studies satisfy the new revised 
mutagenicity guideline requirements for a new chemical (published in 
1991). An additional mutagenicity study, performed on RH-117,236 
(Metabolite M-B), a metabolite of methoxyfenozide, was also negative 
for genotoxicity.
    3. Reproductive and developmental toxicity. In a developmental 
toxicity study in rats, no signs of maternal toxicity in dams or of 
developmental toxicity in fetuses were observed at the limit dose of 
1,000 mg/kg/day. The No Observed Adverse Effect Level (NOAEL) in this 
study for both maternal toxicity and developmental toxicity was 1,000 
mg/kg/day. The Lowest Observed Adverse Effect Level (LOAEL) > 1,000 mg/
kg/day. Similarly, in a developmental toxicity study in rabbits, no 
signs of maternal toxicity or of developmental toxicity were observed 
at the limit dose of 1,000 mg/kg/day. The NOAEL in this study for both 
maternal toxicity and developmental toxicity was 1,000 mg/kg/day. The 
LOAEL was > 1,000 mg/kg/day.
    In neither the developmental toxicity study in rats nor in the 
developmental toxicity study in rabbits was there any evidence for 
increased susceptibility of fetuses to in utero exposure to 
methoxyfenozide. In these studies, methoxyfenozide was determined not 
to be a developmental toxicant.
     In a 2-generation (1 litter/generation) reproduction study in 
rats, treatment-related parental toxicity was observed only at 20,000 
ppm, the highest dose tested (HDT). At this dose, increased liver 
weights were observed in males and females of both generations and 
midzonal to periportal hepatocellular hypertrophy was observed in the 
livers of all males and females of both generations. The LOAEL for 
parental toxicity was 20,000 ppm (1,552/1,821 mg/kg/day for males/
females,respectively) and the NOAEL was 2,000 ppm (153/181 mg/kg/day 
for males/females, respectively). There were no treatment-related 
effects on reproductive parameters for adult (parent) animals. The 
NOAEL for reproductive toxicity was 20,000 ppm. Since no treatment-
related effects were observed in the pups, the NOAEL for neonatal 
toxicity was also, 20,000 ppm. The NOAEL for parental toxicity in this 
reproduction study is higher than the NOAEL for the 2-year combined 
chronic feeding/carcinogenicity study in rats because many of the toxic 
effects observed in the 2-year study at the LOAEL (hematological 
changes, liver toxicity, histopathological changes in the thyroid gland 
and increased adrenal weights) were not examined in the reproduction 
study.
    4. Subchronic toxicity. In a 2-week range-finding dietary study in 
rats, treatment-related effects were observed at > 5,000 ppm in the 
liver (increased liver weights and hepatocellular hypertrophy in males 
and females), in the thyroid gland (hypertrophy/hyperplasia of 
follicular cells in males and females), and in the adrenal gland 
(increased adrenal weights and/or hypertrophy of the zona fasciculata 
in females). Hypertrophy/hyperplasia of thyroid follicular cells was 
also observed in males and females at 1,000 ppm, the lowest observed 
adverse effect level (LOAEL) in this study. The no observed adverse 
effect level (NOAEL) was 250 ppm. Treatment-related hematological 
changes were not observed in the rats in this study.
    In a 3-month feeding study in rats, the predominant treatment-
related effects were increased liver weights in males and females and 
periportal hepatocellular hypertrophy in all males and females at 
20,000 ppm highest dose tested (HDT) and at 5,000 ppm. In addition, at 
20,000 ppm, a slightly decreased (7-8%) RBC count and slightly 
decreased (7-8%) hemoglobin concentration, compared to control rats, 
were observed in the females. The LOAEL in this study was 5,000 ppm 
(353/379 mg/kg/day in males/females, respectively). The NOAEL was 1,000 
ppm (69/72 mg/kg/day in males/females, respectively). Although observed 
in the 2-week dietary study and in the 2-year chronic feeding/
carcinogenicity study in rats, treatment-related effects in the thyroid 
and adrenal glands were not observed in the rats in this 3-month study. 
There is no available biological explanation for this difference in 
findings in the studies.
    In a 2-week range-finding study in dogs, treatment-related 
hematological changes were observed in both males and females at 3,500 
ppm, 7,000 ppm, 15,000 ppm, and 30,000 ppm (HDT). These changes 
included decreased RBC counts, decreased hemoglobin concentrations, 
decreased hematocrits, decreased MCHC, increased MCV, increased MCH, 
increased Heinz bodies, methemoglobinemia, changes in RBC morphology 
such as Howell-Jolly bodies and polychromasia, increased reticulocyte 
counts, increased nucleated RBC and increased platelet counts. At the 
same dose levels (> 3,500 ppm), increased spleen weights and/or 
enlarged spleens were also observed. At 7,000 ppm, plasma total 
bilirubin was increased. The LOAEL in this study was 3,500 ppm (90-184 
mg/kg/day in males and females). The NOAEL was 300 ppm (11-16 mg/kg/day 
in males and females).
    In a 3-month feeding study in dogs, no treatment-related effects 
other than a suggestion of decreased body weight gains in males and 
females were observed in either males or females at the HDT viz. 5,000 
ppm (198/209 mg/kg/day in males/females, respectively). Although 
hematological effects were noted in dogs in the 2-week range-finding 
study > 3,500 ppm (90-184 mg/kg/day) and in the 1-year chronic feeding 
study at > 3,000 ppm (106/111 mg/kg/day), hematological changes were 
not observed in this 3-month study at 5,000 ppm (198/209 mg/kg/day). 
There is no available biological explanation for this difference in 
findings in the studies.
    As part of the 3-month study in dogs, some male and female dogs 
were given 15 ppm (0.6 mg/kg/day) of methoxyfenozide in the diet for 15 
weeks followed by an increase in the dietary dose to 15,000 ppm (422/
460 mg/kg/day in males/females, respectively) for an additional 6 
weeks. After about 2 weeks and 6 weeks at 15,000 ppm, hematological 
examinations were conducted. No hematological changes in these dogs 
were observed. Apparently, pretreatment of the dogs at 15 ppm for 15 
weeks prevented the occurrence of hematological changes which would 
have been expected to occur based on results in the 2-week and 1-year 
feeding studies. One possible explanation is that the liver microsomal 
enzyme system may have been stimulated so much during pretreatment at 
15 ppm that the metabolic (detoxification) rate of methoxyfenozide was 
increased to the point where blood levels of methoxyfenozide may have 
remained below critical effect levels at 15,000 ppm. Another possible 
explanation is that compensatory mechanisms for replacing damaged RBC 
in pretreated dogs may have been so efficient that hematological 
changes were not observed in these dogs even at 15,000 ppm. Other 
explanations for this finding are also possible.
    5. Chronic toxicity. In a 2-year combined chronic feeding/

[[Page 15451]]

carcinogenicity study in rats, the following treatment-related effects 
were observed at 20,000 ppm (highest dose tested): decreased survival 
in males, decreased body weight and food efficiency in females during 
the last year of the study, hematological changes (decreased RBC 
counts, hemoglobin concentrations, and/or hematocrits; 
methemoglobinemia; and increased platelet counts) in males and females, 
increased liver weights and periportal hepatocellular hypertrophy in 
males and females, thyroid follicular cell hypertrophy in males, 
altered thyroid colloid in males and females, and increased adrenal 
weights in males and females. At 8,000 ppm, the following treatment-
related effects were observed: hematological changes (decreased RBC 
counts, hemoglobin concentrations, and/or hematocrits in males and 
females), liver toxicity (increased liver weights in males and 
periportal hepatocellular hypertrophy in males and females), 
histopathological changes in the thyroid (increased follicular cell 
hypertrophy in males and altered colloid in males) and possible adrenal 
toxicity (increased adrenal weights in males and females). The LOAEL in 
this study was 8,000 ppm (411/491 mg/kg/day in males/females, 
respectively), based on the effects described above. The NOAEL was 200 
ppm (10.2/11.9 mg/kg/day in males/females, respectively). This NOAEL 
was used to establish the reference dose (RfD) for methoxyfenozide. 
Utilizing an uncertainty factor of 100 to account for both interspecies 
extrapolation (10x) and intraspecies variability (10x), the chronic RfD 
for methoxyfenozide was calculated to be 0.10 mg/kg/day. No evidence of 
carcinogenicity was observed in this study. Dosing was considered 
adequate because of the decreased survival in males and the decreased 
body weights and food efficiency in females at 20,000 ppm. In addition, 
the HDT for both males and females, 20,000 ppm (1,045/1,248 mg/kg/day 
in males/females, respectively), is higher than the limit dose of 1,000 
mg/kg/day.
    In a 1-year chronic feeding study in dogs, the predominant toxic 
effects were anemia and signs of an associated compensatory response. 
At 30,000 ppm, the HDT, the following treatment-related effects were 
observed in both males and females: decreased RBC counts, decreased 
hemoglobin concentrations, decreased hematocrits, methemoglobinemia, 
nucleated RBC, increased platelets, increased serum total bilirubin, 
bilirubinurea, increased hemosiderin in macrophages in liver and 
spleen, and increased hyperplasia in bone marrow of rib and sternum. 
Increased liver weights in males and females and increased thyroid 
weights in males were also observed at 30,000 ppm. Signs of anemia were 
also noted at 3,000 ppm and included decreased RBC counts, decreased 
hemoglobin concentrations, decreased hematocrits, methemoglobinemia, 
increased platelets, and increased serum total bilirubin and 
bilirubinurea. The LOAEL in this study was 3,000 ppm (106/111 mg/kg/day 
in males/females, respectively). The NOAEL was 300 ppm (9.8/12.6 mg/kg/
day in males/females, respectively).
    6. Animal metabolism. In a metabolism study in rats, 
14C-methoxyfenozide was rapidly absorbed, distributed, 
metabolized and almost completely excreted within 48 hours. The major 
route of excretion was feces (86-97%) with lesser amounts in the urine 
(5-13%). An enterohepatic circulation was observed. The test material 
was metabolized principally by O-demethylation of the A-ring methoxy 
group and oxidative hydroxylation of the B-ring methyl groups followed 
by conjugation with glucuronic acid. No significant sex-related or 
dose-dependent differences in metabolic disposition were noted. Seven 
metabolites and the parent accounted for 74-90% of the administered 
dose in all groups. The glucuronide conjugates are considered to be 
less toxic than the parent compound because glucuronide conjugation is 
well known to be a commonly occurring ``detoxification'' mechanism in 
mammalian species since it results in the formation of more polar, more 
water-soluble metabolites which are readily and easily excreted from 
the body (in this case, in the bile and urine). Further, based on 
similarities of chemical structure, the non-conjugated metabolites 
would be expected to be no more toxic than the parent compound. In a 
dermal absorption study in rats using an 80% wettable powder 
formulation as the test material, the cumulative dermal absorption of 
test material after a 10- or 24-hour dermal exposure was determined to 
be 2%. In a 28-day dermal toxicity study in rats, no treatment-related 
systemic or skin effects were observed at the limit dose of 1,000 mg/
kg/day (HDT). Regarding effects on endocrine organs, methoxyfenozide 
affected the thyroid gland and adrenal gland in the 2-week and 2-year 
feeding studies in rats. In the thyroid gland, hypertrophy/hyperplasia 
of follicular cells and altered colloid were observed in males and 
females at or near the LOAEL in both of these studies. In the adrenal 
gland, increased adrenal weights and hypertrophy of the zona 
fasciculata were also observed in males and females at or near the 
LOAEL. In addition, in the 1-year chronic feeding study in dogs, 
increased thyroid weight in males was observed, but only at the very 
high dose of 30,000 ppm. Since the definition and regulatory 
significance of the term ``endocrine disruptor chemical'' has not yet 
been established by the Agency, it is not clear whether 
methoxyfenozide, on the basis of these effects on the thyroid gland and 
adrenal gland, should be considered to be an ``endocrine disruptor 
chemical.'' Other than the morphological changes described above, there 
were no signs of thyroid or adrenal dysfunction in these or in any 
other studies on methoxyfenozide.
    7. Endocrine disruption. Regarding effects on endocrine organs, 
methoxyfenozide affected the thyroid gland and adrenal gland in the 2-
week and 2-year feeding studies in rats. In the thyroid gland, 
hypertrophy/hyperplasia of follicular cells and altered colloid were 
observed in males and females at or near the LOAEL in both of these 
studies. In the adrenal gland, increased adrenal weights and 
hypertrophy of the zona fasciculata were also observed in males and 
females at or near the LOAEL. In addition, in the 1-year chronic 
feeding study in dogs, increased thyroid weight in males was observed, 
but only at the very high dose of 30,000 ppm. Since the definition and 
regulatory significance of the term ``endocrine disruptor chemical'' 
has not yet been established by the Agency, it is not clear whether 
methoxyfenozide, on the basis of these effects on the thyroid gland and 
adrenal gland, should be considered to be an ``endocrine disruptor 
chemical.'' Other than the morphological changes described above, there 
were no signs of thyroid or adrenal dysfunction in these or in any 
other studies on methoxyfenozide.

C. Aggregate Exposure

    1. Dietary exposure--i. Food.-- From food and feed uses. Tolerances 
have been established (40 CFR 180.544) for residues of methoxyfenozide 
on cotton, undelinted seed; cotton gin byproducts; pome fruit; apple 
pomace, wet; milk; meat of cattle, goats, hogs, horses and sheep and 
fat of cattle, goats, hogs, horses and sheep at 2.0, 35.0, 1.5, 7.0, 
0.02, 0.02, 0.1 ppm and tolerances for the combined residues of 
methoxyfenozide and its glucuronide metabolite in liver of cattle, 
goats, hogs, horses and sheep and meat byproducts (except liver) of 
cattle, goats, hogs, horses and sheep at 0.1 and 0.02 ppm

[[Page 15452]]

respectively. Other petitions pending request tolerances for grapes at 
1.0 ppm, raisins at 1.5 ppm, fruiting vegetables at 2.0 ppm, Leafy 
Vegetables (4A) at 25 ppm, Leaf Petioles (4B) at 10.0 ppm, Head and 
Stem Brassica (5A) at 6.5 ppm and Leafy Brassica Greens (5B) at 20.0 
ppm. The current petition requests establishment of tolerances due to 
indirect or inadvertent residues of methoxyfenozide [benzoic acid, 3-
methoxy-2-methyl-, 2-(3,5-dimethylbenzoyl)-2-(1,1-dimethylethyl) 
hydrazide] in or on root and tuber vegetables at 0.05 parts per million 
(ppm); leaves of root and tuber vegetables at 0.1 ppm; bulb vegetables 
at 0.1 ppm; leafy vegetables (except Brassica) at 0.2 ppm; Brassica 
vegetables at 0.2 ppm; and for indirect or inadvertent combined 
residues of methoxyfenozide and its metabolites RH-117,236 (free phenol 
of methoxyfenozide; 3,5-dimethylbenzoic acid N-tert-butyl-N'-(3-
hydroxy-2-methylbenzoyl) hydrazide), RH-151,055 (the glucose conjugate 
of RH-117,236; 3,5-dimethylbenzoic acid N-tert-butyl-N-[3( -D-
glucopyranosyloxy)-2-methylbenzoyl]-hydrazide) and RH-152,072 (the 
malonylglycosyl conjugate of RH-117,236) in or on legume vegetables at 
0.05 ppm; foliage of legume vegetables at 8 ppm; forage, fodder, hay 
and straw of cereal grains at 7 ppm; grass forage, fodder and hay at 7 
ppm; forage, fodder, straw and hay of non-grass animal feeds at 8 ppm; 
and herbs and spices at 8 ppm.
    Risk assessments were conducted by Rohm and Haas to assess dietary 
exposures and risks from methoxyfenozide as follows:
    a. Acute exposure and risk. Acute dietary risk assessments are 
performed for a food-use pesticide if a toxicological study has 
indicated the possibility of an effect of concern occurring as a result 
of a 1-day or single exposure. No appropriate toxicological endpoint 
attributable to a single exposure was identified in the available 
toxicology studies on methoxyfenozide including the acute neurotoxicity 
study in rats, the developmental toxicity study in rats and the 
developmental toxicity study in rabbits. This risk is considered to be 
negligible.
    b. Chronic exposure and risk. Rohm and Haas used the Dietary 
Exposure Evaluation Model (DEEM ) software for conducting a chronic 
dietary (food) risk analysis. DEEM is a dietary exposure analysis 
system that is used to estimate exposure to a pesticide chemical in 
foods comprising the diets of the U.S. population, including population 
subgroups. DEEM contains food consumption data as reported by 
respondents in the USDA Continuing Surveys of Food Intake by 
Individuals conducted in 1989-1992. Rohm and Haas assumed 100% of crops 
would be treated and contain methoxyfenozide residues at the tolerance 
level. The following tolerance levels were used in the analysis:

 
------------------------------------------------------------------------
                                             Tolerance Level (parts per
                 Commodity                         million) (ppm)
------------------------------------------------------------------------
Cotton, undelinted seed                     2.0
Pome fruits                                 1.5 ppm
Grapes                                      1.0 ppm
Raisins                                     1.5 ppm
Leafy Vegetables (4A)                       25 ppm
Leaf Petioles (4B)                          10.0 ppm
Head and Stem Brassica (5A)                 6.5 ppm
Leafy Brassica Greens (5B)                  20.0 ppm
Fruiting vegetables                         2.0 ppm
Root and tuber vegetables                   0.05 ppm
Leaves of root and tuber vegetables         0.1 ppm
Bulb vegetables                             0.1 ppm
Leafy vegetables (except Brassica)          0.2 ppm
Brassica vegetables                         0.2ppm
Legume vegetables                           0.05 ppm
Herbs and spices                            8 ppm
Milk                                        0.02 ppm
Meat*                                       0.02 ppm
Meat byproducts* (except liver)             0.02 ppm
Fat*                                        0.1 ppm
Liver                                       0.1 ppm
------------------------------------------------------------------------
* of cattle, goats, hogs, horses and sheep.

    Processing factors were also applied to grape juice (1.2x), grape 
juice concentrate (3.6x), apple juice/cider (1.3x), apple juice 
concentrate (3.9x), dried apples (8x), dried beef (1.92x), dried pears 
(6.25x), tomato juice (1.5x), tomato puree (3.3x), tomato paste (5.4x), 
tomato catsup (2.5x), dried tomatoes (14.3x), dehydrated onions (9x), 
white dry potatoes (6.5x), and dried veal (1.92x). The processing 
factors are default values from DEEM.
    As shown in the following table, the resulting dietary food 
exposures occupy up to 28.3% of the Chronic PAD for the most highly 
exposed population subgroup, children 1-6 years old. These results 
should be viewed as conservative (health protective) risk estimates. 
Refinements such as use of percent crop-treated information and/or 
anticipated residue values would yield even lower estimates of chronic 
dietary exposure.

       Summary: Chronic Dietary Exposure Analysis by DEEM (Tier 1)
------------------------------------------------------------------------
                                   Exposure (mg/kg/   Percent of Chronic
     Population Subgroup\1\              day)               PAD\2\
------------------------------------------------------------------------
U.S. Population - 48 States       0.0149............  14.9
All infants (<1 year)             0.0144              14.4
Nursing Infants<1 year old        0.0084              8.4
Non-Nursing Infants < 1 year old  0.0169              6.9
Children 1-6 years old             0.0283             28.3
Children 7-12 years old           0.0193              19.3
Females 13 + (nursing)            0.0172              17.2
U.S. population (autumn season)   0.0150              15.0
U.S. population (winter season)   0.0151              15.1
U.S. population (spring season)   0.0152              15.2
Northeast region                  0.0161              16.1
Western region                    0.0161              16.1
Non-Hispanic whites               0.0150              15.0
Non-Hispanic/non-white/non-black  0.0171              17.1
Pacific region                    0.0162              16.2
------------------------------------------------------------------------
\1\The subgroups listed are: (1) The U.S. population (total); (2) Those
  for infants and children; (3) The other subgroup(s), if any, for which
  the percentage of the Chronic PAD occupied is greater than that
  occupied by the subgroup U.S.population (total); and, (4) The most
  highly exposed of the females subgroups (in this case, females, (13+
  years, nursing).
\2\Percent chronic PAD = (Exposure divided by Chronic PAD) x 100%.

    ii. Drinking water-- From drinking water. The are no water-related 
exposure data from monitoring to complete a quantitative drinking water 
exposure analysis and risk assessment for methoxyfenozide. GENEEC and/
or PRZM/EXAMS (both produce estimates of pesticide concentration in a 
farm pond) are used to generate EECs for surface water and SCI-GROW (an 
empirical model based upon actual monitoring data collected for a 
number of pesticides that serve as benchmarks) predicts EECs in ground 
water. These models take into account the use patterns and the 
environmental profile of a pesticide, but do not include consideration 
of the impact that processing raw water for distribution as drinking 
water would likely have on the removal of pesticides from the source 
water. The primary use of these models at this stage is to provide a 
coarse screen for assessing whether a pesticide is likely to be present 
in drinking water at concentrations which would exceed human health 
levels of concern.

[[Page 15453]]

    A drinking water level of comparison (DWLOC) is the concentration 
of a pesticide in drinking water that would be acceptable as a 
theoretical upper limit in light of total aggregate exposure to that 
pesticide from food, water, and residential uses. HED 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 a pesticide, the DWLOC is 
used as a point of comparison against the conservative EECs provided by 
computer modeling (SCI-GROW, GENEEC, PRZM/EXAMS).
    a. Acute exposure and risk. Because no acute dietary endpoint was 
determined, Rohm and Haas concludes that there is a reasonable 
certainty of no harm from acute exposure from drinking water.
    b. Chronic exposure and risk. Tier II screening-level assessments 
can be conducted using the simulation models SCI-GROW and PRZM/EXAMS to 
generate EECs for ground and surface water, respectively. The modeling 
was conducted based on the environmental profile and the maximum 
seasonal application rate proposed for methoxyfenozide (1.0 lb ai/acre/
season). PRZM/EXAMS was used to generate the surface water EECs, 
because it can factor the persistent nature of the chemical into the 
estimates.
    The EECs for assessing chronic aggregate dietary risk used by HED 
are 6 parts per billion (ppb) (in ground water, based on SCI-GROW) and 
98.5 ppb (in surface water, based on the PRZM/EXAMS, long-term mean). 
The back-calculated DWLOCs for assessing chronic aggregate dietary risk 
range from 720 ppb for the most highly exposed population subgroup 
(children 1-6 years old) to 2,979 ppb for the U.S. population (48 
contiguous States--all seasons).
    The SCI-GROW and PRZM/EXAMS chronic EECs are less than the Agency's 
level of comparison (the DWLOC value for each population subgroup) for 
methoxyfenozide residues in drinking water as a contribution to chronic 
aggregate exposure. Rohm and Haas thus concludes with reasonable 
certainty that residues of methoxyfenozide in drinking water will not 
contribute significantly to the aggregate chronic human health risk and 
that the chronic aggregate exposure from methoxyfenozide residues in 
food and drinking water will not exceed the Agency's level of concern 
(100% of the cPAD) for chronic dietary aggregate exposure by any 
population subgroup. EPA generally has no concern for exposures below 
100% of the cPAD, because it is a level at or below which daily 
aggregate dietary exposure over a lifetime will not pose appreciable 
risks to the health and safety of any population subgroup. This risk 
assessment is considered high confidence, conservative, and very 
protective of human health.

                                       Drinking Water Levels of Comparison for Chronic Exposure to Methoxyfenozide
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                              Max. Water                             GENEEC 56-Day
       Population Subgroup        Chronic PAD (mg/kg/  Food Exposure (m/   Exposure (mg/kg/    SCI-GROW (/
                                          d)                 kg/d)               d)\1\              m>g/L)              m>g/L)                L)%
--------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. Population -48 States        0.10                0.0149              0.0851              6                   98.5                2,979
Females 13+ (nursing)             0.10                0.0171              0.0829              6                   98.5                2,487
Non-Nursing>1 year old            0.10                0.0169              0.083               6                   98.5                830
Children 1-6 years old            0.10                0.0283              0.0720              6                   98.5                720
Children 7-12 years old           0.10                0.0193              0.0807              6                   98.5                807
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\Maximum Water Exposure (mg/kg/d) = Chronic PAD (mg/kg/day) - Chronic Food Exposure DWLOC (/L) = [Maximum water Exposure (mg/kg/d) x body
  weight (kg)] divided by [1/1000 mg/ x water consumed daily (L/day)].

    2. Non-dietary exposure. From non-dietary exposure. Methoxyfenozide 
is not currently registered for use on any residential non-food sites. 
Therefore, there is no non-dietary acute, chronic, short- or 
intermediate-term exposure.

D. Cumulative Effects

    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.''
    PA does not have, at this time, available data to determine whether 
methoxyfenozide 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, 
methoxyfenozide does not appear to produce a toxic metabolite produced 
by other substances. For the purposes of this tolerance action, 
therefore, it is assumed that methoxyfenozide does not have a common 
mechanism of toxicity with other substances.

E. Safety Determination

    1. U.S. population -- i. Acute risk. Since no acute toxicological 
endpoints were established, Rohm and Haas considers acute aggregate 
risk to be negligible.
    ii. Chronic risk. Using the DEEM exposure assumptions described in 
this unit, Rohm and Haas has concluded that aggregate exposure to 
methoxyfenozide from food will utilize 14.9% of the cPAD for the U.S. 
population. The major identifiable subgroup with the highest aggregate 
exposure is children 1-6 years old at 28.3% of the cPAD and is 
discussed below. 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 methoxyfenozide in drinking water, the aggregate exposure is not 
expected to exceed 100% of the cPAD. Rohm and Haas concludes that there 
is a reasonable certainty that no harm will result from aggregate 
exposure to methoxyfenozide residues.
    iii. Short- and intermediate-term risk. Short- and intermediate-
term aggregate exposure takes into account chronic dietary food and 
water (considered to be a background exposure level) plus indoor and 
outdoor residential exposure.
    Since there are currently no registered indoor or outdoor 
residential non-dietary uses of methoxyfenozide and no short or 
intermediate term toxic endpoints, Rohm and Haas considers short or 
intermediate term aggregate risks to be negligible.
    iv. Aggregate cancer risk for U.S. population. Methoxyfenozide is 
classified as a ``not likely'' human carcinogen. Therefore this risk 
does is negligible.

[[Page 15454]]

    v. Determination of safety. Based on these risk assessments, Rohm 
and Haas concludes that there is a reasonable certainty that no harm 
will result from aggregate exposure to methoxyfenozide residues.
    2. Safety factor for infants and children-- i. In general. In 
assessing the potential for additional sensitivity of infants and 
children to residues of methoxyfenozide, 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 ten-
fold 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 margin of exposure (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/UF 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. Prenatal and postnatal sensitivity. The toxicology data base 
for methoxyfenozide included acceptable developmental toxicity studies 
in both rats and rabbits as well as a 2-generation reproductive 
toxicity study in rats. The data provided no indication of increased 
sensitivity of rats or rabbits to in utero and/or postnatal exposure to 
methoxyfenozide.
    iii. Conclusion. There is a complete toxicity data base for 
methoxyfenozide and exposure data are complete or are estimated based 
on data that reasonably accounts for potential exposures. Based on the 
completeness of the data base and the lack of prenatal and postnatal 
toxicity, EPA determined that an additional safety factor was not 
needed for the protection of infants and children.
    iv. Acute risk. Since no acute toxicological endpoints were 
established, acute aggregate risk is considered to be negligible.
    v. Chronic risk. Using the exposure assumptions described in this 
unit, Rohm and Haas has concluded that aggregate exposure to 
methoxyfenozide from food will utilize 28.3% 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 
methoxyfenozide in drinking water, Rohm and Haas does not expect the 
aggregate exposure to exceed 100% of the cPAD.
    vi. Short- or intermediate-term risk. Short and intermediate term 
risks are judged to be negligible due to the lack of significant 
toxicological effects observed.
    vii. Determination of safety. Based on these risk assessments, Rohm 
and Haas concludes that there is a reasonable certainty that no harm 
will result to infants and children from aggregate exposure to 
methoxyfenozide residues.

F. International Tolerances

    There are no established or proposed Codex, Canadian or Mexican 
limits for residues of methoxyfenozide in/on plant or animal 
commodities. Therefore, no compatibility issues exist with regard to 
the proposed U.S. tolerances discussed in this petition review.

3. Rohm and Haas Company

PP OF6213

    EPA has received a pesticide petition (0F6213) from Rohm and Haas 
Company, 100 Independence Mall West, Philadelphia, PA, 19106-2399 
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 tolerances for residues of methoxyfenozide [benzoic acid, 
3-methoxy-2-methyl-, 2-(3,5-dimethylbenzoyl)-2-(1,1- dimethylethyl) 
hydrazide] in or on the raw agricultural commodities field corn grain 
at 0.05 parts per million (ppm), sweet corn (K +CWHR) at 0.05 ppm, 
field corn forage at 15 ppm, field corn stover (fodder) at 105 ppm, 
corn oil at 0.2 ppm, aspirated grain factions at 1.0 ppm, corn silage 
at 5.0 ppm, sweet corn forage at 30 ppm, and sweet corn stover (fodder) 
at 60 ppm. In addition, this petition requests an increase in the 
established tolerance for residues of methoxyfenozide to 0.1 ppm in 
milk and an increase in the established tolerances for residues of 
methoxyfenozide and its glucuronide metabolite to 0.5 ppm in fat, to 
0.4 ppm in liver and to 0.1 ppm in meat by products (except liver) of 
cattle, goats, horses, hogs and sheep. 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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The qualitative nature of methoxyfenozide 
residues in plants and animals is adequately understood and was 
previously published in the Federal Register of July 5, 2000 (65 FR 
41355)(FRL-6496-5). The qualitative nature of methoxyfenozide residues 
in rotation crop plants is adequately understood based upon 
14C confined rotation crop studies. The residue of concern 
for dietary exposure and tolerance setting purposes in rotation crops 
is the parent compound, methoxyfenozide and its metabolites RH--117,236 
(free phenol of methoxyfenozide; 3,5-dimethylbenzoic acid N-tert-butyl-
N'-(3-hydroxy-2-methylbenzoyl) hydrazide), RH-151,055 (the glucose 
conjugate of RH-117,236; 3,5-dimethylbenzoic acid N-tert-butyl-N-[3( -
D-glucopyranosyloxy)-2-methylbenzoyl]-hydrazide) and RH-152,072 (the 
malonylglycosyl conjugate of RH-117,236).
    2. Analytical method. An high performance liquid chromatography 
using ultra violet Method TR 34-00-38 for the enforcement of tolerances 
in field and sweet corn matrices has been developed. Confirmatory 
method validation, radiovalidation, and independent method validation 
data have been submitted for this method. The validated limit of 
quantitation (LOQ) of the analytical method was 0.02 ppm in all 
matrices for methoxyfenozide.
    3. Magnitude of residues-- i. Magnitude of the residue. 
Geographically representative field trials with methoxyfenozide 80WP 
and 2F formulations were conducted to support the proposed tolerances 
on field and sweet corn. The results of the field trials indicate that 
residues of methoxyfenozide will not exceed the proposed tolerances of 
0.05 ppm in field grain and sweet corn (K+CWHR), 15 ppm in field corn 
forage, 105 ppm in

[[Page 15455]]

field corn stover (fodder), 1.0 ppm in aspirated grain factions, 5.0 
ppm in corn silage, 30 ppm in sweet corn forage and 60 ppm in sweet 
corn stover (fodder). A processing study was conducted and showed that 
residues concentrated in oil and a tolerance of 0.2 ppm is proposed.
    ii. Residues in meat, milk, poultry, and eggs. The maximum 
theoretical dietary burden of methoxyfenozide for dairy or beef cattle 
associated with this petition and previous petition is estimated to be 
less than 75 ppm. Based on a feeding study with methoxyfenozide at 150 
ppm, tolerances should be increased to 0.1 ppm in milk, to 0.5 ppm in 
fat, to 0.4 ppm in liver and to 0.1 ppm in meat by-products (except 
liver). The maximum theoretical dietary burden of methoxyfenozide for 
poultry animals associated with this petition (from cotton meal, corn 
meal and grain) was calculated to be 0.03 ppm.
    A poultry feeding study was conducted at levels of 2 ppm, 6 ppm, 
and 20 ppm which are equivalent to 67x, 200x, and 1,500x, respectively, 
the maximum theoretical dietary burden for poultry. No detectable 
residues of methoxyfenozide were found in any of the muscle, fat or 
liver samples from any dose level. In eggs, no quantifiable residues 
(i.e., greater than the limit of quantitation of 0.01 ppm) of either 
methoxyfenozide or its glucuronide metabolite were found in any of the 
samples. Average residues of RH-1518 in liver from hens dosed at 6 ppm 
were 0.016 ppm while those in the liver of hens dosed at 20 ppm were 
0.031 ppm. After a 7-day depuration period, no detectable residues of 
RH-1518 were found in the liver of hens dosed at 20 ppm. Assuming a 
linear relationship between dose and residues, the expected residues in 
eggs and poultry tissues would be below the LOD of 0.01 ppm for methods 
used to measure residues in poultry products. Rohm and Haas concludes 
that there is no reasonable expectation of finding finite residues in 
eggs and poultry tissues.

B. Toxicological Profile

    1. Acute toxicity. Acute toxicity studies with technical grade: 
Oral LD50 in the rat is > 5,000 milligrams/kilograms (mg/kg) 
for males and females- Toxicity Category IV; Oral LD50 in 
the mouse is > 5,000 mg/kg for males and females-Toxicity Category IV; 
Dermal LD50 in the rat is > 2,000 mg/kg-Toxicity Category 
III; Inhalation LD50 in the rat is > 4.3 milligram/liter 
(mg/L)-Toxicity Category IV; Primary Eye Irritation in the rabbit -very 
mild irritant-Toxicity Category IV; Primary skin irritation in the 
rabbit-not a skin irritant-Toxicity Category IV. Methoxyfenozide is not 
a skin sensitizer.
    In an acute neurotoxicity study in rats, statistically significant 
decreased hind limb grip strength was observed in male rats at 3 hours 
(approximate time of peak effect) following a single oral dose of 2,000 
mg/kg (limit dose) of methoxyfenozide. Decreased hindlimb grip strength 
was also observed in the male rats at 7 and 14 days, but was not 
statistically significant. No other systemic or neurotoxic effects were 
observed in the male rats or in the female rats at any time in this 
study. Since this marginal effect occurred only in one sex, was 
statistically significant at only one time, was observed only at the 
high dose (limit dose) and no other signs of toxicity were observed in 
the rats in this study, this possible effect is not considered to be 
biologically significant. In addition, neither decreased hindlimb grip 
strength nor any other signs of neurotoxicity were observed in any of 
the animals at any time in a 90-day subchronic neurotoxicity study in 
rats.
    2. Genotoxicity. In a battery of four mutagenicity studies (with 
and without metabolic activation, as appropriate for the specific 
study), technical grade methoxyfenozide was negative for genotoxicity 
in all four studies. The four studies satisfy the new revised 
mutagenicity guideline requirements for a new chemical (published in 
1991). An additional mutagenicity study, performed on RH-117,236 
(Metabolite M-B), a metabolite of methoxyfenozide, was also negative 
for genotoxicity.
    3. Reproductive and developmental toxicity. In a developmental 
toxicity study in rats, no signs of maternal toxicity in dams or of 
developmental toxicity in fetuses were observed at the limit dose of 
1,000 mg/kg/day. The No Observed Adverse Effect Level (NOAEL) in this 
study for both maternal toxicity and developmental toxicity was 1,000 
mg/kg/day. The Lowest Observed Adverse Effect Level (LOAEL) 1,000 mg/
kg/day. Similarly, in a developmental toxicity study in rabbits, no 
signs of maternal toxicity or of developmental toxicity were observed 
at the limit dose of 1,000 mg/kg/day. The NOAEL in this study for both 
maternal toxicity and developmental toxicity was 1,000 mg/kg/day. The 
LOAEL was > 1,000 mg/kg/day.
    In neither the developmental toxicity study in rats nor in the 
developmental toxicity study in rabbits was there any evidence for 
increased susceptibility of fetuses to in utero exposure to 
methoxyfenozide. In these studies, methoxyfenozide was determined not 
to be a developmental toxicant.
    In a 2-generation (1 litter/generation) reproduction study in rats, 
treatment-related parental toxicity was observed only at 20,000 ppm, 
the HDT. At this dose, increased liver weights were observed in males 
and females of both generations and midzonal to periportal 
hepatocellular hypertrophy was observed in the livers of all males and 
females of both generations. The LOAEL for parental toxicity was 20,000 
ppm (1,552/1,821 mg/kg/day for males/females, respectively) and the 
NOAEL was 2,000 ppm (153/181 mg/kg/day for males/females, 
respectively). There were no treatment-related effects on reproductive 
parameters for adult (parent) animals. The NOAEL for reproductive 
toxicity was 20,000 ppm. Since no treatment-related effects were 
observed in the pups, the NOAEL for neonatal toxicity was also, 20,000 
ppm. The NOAEL for parental toxicity in this reproduction study is 
higher than the NOAEL for the 2-year combined chronic feeding/
carcinogenicity study in rats because many of the toxic effects 
observed in the 2-year study at the LOAEL (hematological changes, liver 
toxicity, histopathological changes in the thyroid gland and increased 
adrenal weights) were not examined in the reproduction study.
    4. Subchronic toxicity. In a developmental toxicity study in rats, 
no signs of maternal toxicity in dams or of developmental toxicity in 
fetuses were observed at the limit dose of 1,000 mg/kg/day. The NOAEL 
in this study for both maternal toxicity and developmental toxicity was 
1,000 mg/kg/day. The LOAEL > 1,000 mg/kg/day. Similarly, in a 
developmental toxicity study in rabbits, no signs of maternal toxicity 
or of developmental toxicity were observed at the limit dose of 1,000 
mg/kg/day. The NOAEL in this study for both maternal toxicity and 
developmental toxicity was 1,000 mg/kg/day. The LOAEL was > 1,000 mg/
kg/day.
    In neither the developmental toxicity study in rats nor in the 
developmental toxicity study in rabbits was there any evidence for 
increased susceptibility of fetuses to in utero exposure to 
methoxyfenozide. In these studies, methoxyfenozide was determined not 
to be a developmental toxicant.
    In a 2-generation (1 litter/generation) reproduction study in rats, 
treatment-related parental toxicity was observed only at 20,000 ppm, 
the HDT. At this dose, increased liver weights were observed in males 
and females of both generations and midzonal to periportal 
hepatocellular hypertrophy was observed in the livers of all males and 
females of both generations. The LOAEL

[[Page 15456]]

for parental toxicity was 20,000 ppm (1,552/1,821 mg/kg/day for males/
females, respectively) and the NOAEL was 2,000 ppm (153/181 mg/kg/day 
for males/females, respectively). There were no treatment-related 
effects on reproductive parameters for adult (parent) animals. The 
NOAEL for reproductive toxicity was 20,000 ppm. Since no treatment-
related effects were observed in the pups, the NOAEL for neonatal 
toxicity was also, 20,000 ppm. The NOAEL for parental toxicity in this 
reproduction study is higher than the NOAEL for the 2-year combined 
chronic feeding/carcinogenicity study in rats because many of the toxic 
effects observed in the 2-year study at the LOAEL (hematological 
changes, liver toxicity, histopathological changes in the thyroid gland 
and increased adrenal weights) were not examined in the reproduction 
study.
    5. Chronic toxicity. In a 2-year combined chronic feeding/
carcinogenicity study in rats, the following treatment-related effects 
were observed at 20,000 ppm (highest dose tested): decreased survival 
in males, decreased body weight and food efficiency in females during 
the last year of the study, hematological changes (decreased RBC 
counts, hemoglobin concentrations, and/or hematocrits; 
methemoglobinemia; and increased platelet counts) in males and females, 
increased liver weights and periportal hepatocellular hypertrophy in 
males and females, thyroid follicular cell hypertrophy in males, 
altered thyroid colloid in males and females, and increased adrenal 
weights in males and females. At 8,000 ppm, the following treatment-
related effects were observed: hematological changes (decreased RBC 
counts, hemoglobin concentrations, and/or hematocrits in males and 
females), liver toxicity (increased liver weights in males and 
periportal hepatocellular hypertrophy in males and females), 
histopathological changes in the thyroid (increased follicular cell 
hypertrophy in males and altered colloid in males) and possible adrenal 
toxicity (increased adrenal weights in males and females). The LOAEL in 
this study was 8,000 ppm (411/491 mg/kg/day in males/females, 
respectively), based on the effects described above. The NOAEL was 200 
ppm (10.2/11.9 mg/kg/day in males/females, respectively). This NOAEL 
was used to establish the reference dose (RfD) for methoxyfenozide. 
Utilizing an uncertainty factor of 100 to account for both interspecies 
extrapolation (10x) and intraspecies variability (10x), the chronic RfD 
for methoxyfenozide was calculated to be 0.10 mg/kg/day. No evidence of 
carcinogenicity was observed in this study. Dosing was considered 
adequate because of the decreased survival in males and the decreased 
body weights and food efficiency in females at 20,000 ppm. In addition, 
the HDT for both males and females, 20,000 ppm (1,045/1,248 mg/kg/day 
in males/females, respectively), is higher than the limit dose of 1,000 
mg/kg/day.
    In a 1-year chronic feeding study in dogs, the predominant toxic 
effects were anemia and signs of an associated compensatory response. 
At 30,000 ppm, the HDT, the following treatment-related effects were 
observed in both males and females: decreased RBC counts, decreased 
hemoglobin concentrations, decreased hematocrits, methemoglobinemia, 
nucleated RBC, increased platelets, increased serum total bilirubin, 
bilirubinurea, increased hemosiderin in macrophages in liver and 
spleen, and increased hyperplasia in bone marrow of rib and sternum. 
Increased liver weights in males and females and increased thyroid 
weights in males were also observed at 30,000 ppm. Signs of anemia were 
also noted at 3,000 ppm and included decreased RBC counts, decreased 
hemoglobin concentrations, decreased hematocrits, methemoglobinemia, 
increased platelets, and increased serum total bilirubin and 
bilirubinurea. The LOAEL in this study was 3,000 ppm (106/111 mg/kg/day 
in males/females, respectively). The NOAEL was 300 ppm (9.8/12.6 mg/kg/
day in males/females, respectively).
    6. Animal metabolism. In a metabolism study in rats, 14C-
methoxyfenozide was rapidly absorbed, distributed, metabolized and 
almost completely excreted within 48 hours. The major route of 
excretion was feces (86-97%) with lesser amounts in the urine (5-13%). 
An enterohepatic circulation was observed. The test material was 
metabolized principally by O-demethylation of the A-ring methoxy group 
and oxidative hydroxylation of the B-ring methyl groups followed by 
conjugation with glucuronic acid. No significant sex-related or dose-
dependent differences in metabolic disposition were noted. Seven 
metabolites and the parent accounted for 74-90% of the administered 
dose in all groups. The glucuronide conjugates are considered to be 
less toxic than the parent compound because glucuronide conjugation is 
well known to be a commonly occurring ``detoxification'' mechanism in 
mammalian species since it results in the formation of more polar, more 
water-soluble metabolites which are readily and easily excreted from 
the body (in this case, in the bile and urine). Further, based on 
similarities of chemical structure, the non-conjugated metabolites 
would be expected to be no more toxic than the parent compound. In a 
dermal absorption study in rats using an 80% wettable powder 
formulation as the test material, the cumulative dermal absorption of 
test material after a 10- or 24-hour dermal exposure was determined to 
be 2%. In a 28-day dermal toxicity study in rats, no treatment-related 
systemic or skin effects were observed at the limit dose of 1,000 mg/
kg/day (HDT). Regarding effects on endocrine organs, methoxyfenozide 
affected the thyroid gland and adrenal gland in the 2-week and 2-year 
feeding studies in rats. In the thyroid gland, hypertrophy/hyperplasia 
of follicular cells and altered colloid were observed in males and 
females at or near the LOAEL in both of these studies. In the adrenal 
gland, increased adrenal weights and hypertrophy of the zona 
fasciculata were also observed in males and females at or near the 
LOAEL. In addition, in the 1-year chronic feeding study in dogs, 
increased thyroid weight in males was observed, but only at the very 
high dose of 30,000 ppm. Since the definition and regulatory 
significance of the term ``endocrine disruptor chemical'' has not yet 
been established by the Agency, it is not clear whether 
methoxyfenozide, on the basis of these effects on the thyroid gland and 
adrenal gland, should be considered to be an ``endocrine disruptor 
chemical.'' Other than the morphological changes described above, there 
were no signs of thyroid or adrenal dysfunction in these or in any 
other studies on methoxyfenozide.
    7. Endocrine disruption. Regarding effects on endocrine organs, 
methoxyfenozide affected the thyroid gland and adrenal gland in the 2-
week and 2-year feeding studies in rats. In the thyroid gland, 
hypertrophy/hyperplasia of follicular cells and altered colloid were 
observed in males and females at or near the LOAEL in both of these 
studies. In the adrenal gland, increased adrenal weights and 
hypertrophy of the zona fasciculata were also observed in males and 
females at or near the LOAEL. In addition, in the 1-year chronic 
feeding study in dogs, increased thyroid weight in males was observed, 
but only at the very high dose of 30,000 ppm. Since the definition and 
regulatory significance of the term ``endocrine disruptor chemical'' 
has not yet been established by the Agency, it is not clear whether 
methoxyfenozide, on the basis of these effects on the thyroid

[[Page 15457]]

gland and adrenal gland, should be considered to be an ``endocrine 
disruptor chemical.'' Other than the morphological changes described 
above, there were no signs of thyroid or adrenal dysfunction in these 
or in any other studies on methoxyfenozide.

C. Aggregate Exposure

    1. Dietary exposure-- i. Food.-- From food and feed uses. 
Tolerances have been established (40 CFR 180.544) for residues of 
methoxyfenozide on cotton, undelinted seed; cotton gin byproducts; pome 
fruit; apple pomace, wet; milk; meat and fat of cattle, goats, hogs, 
horses and sheep and for the combined residues of methoxyfenozide and 
its glucuronide metabolite in liver and meat byproducts (except liver) 
of cattle, goats, hogs, horses and sheep. The established tolerances 
are listed in the table below. Other petitions pending request 
tolerances for grapes, raisins, fruiting vegetables, Leafy Vegetables 
(4A), Leaf Petioles (4B), Head and Stem Brassica (5A) and Leafy 
Brassica Greens (5B), and tolerances due to indirect or inadvertent 
residues of methoxyfenozide [benzoic acid, 3-methoxy-2-methyl-, 2-(3,5-
dimethylbenzoyl)-2-(1,1-dimethylethyl) hydrazide] in or on root and 
tuber vegetables; leaves of root and tuber vegetables; bulb vegetables; 
leafy vegetables (except Brassica); Brassica vegetables; and for 
indirect or inadvertent combined residues of methoxyfenozide and its 
metabolites RH-117,236 (free phenol of methoxyfenozide; 3,5-
dimethylbenzoic acid N-tert-butyl-N'-(3-hydroxy-2-methylbenzoyl) 
hydrazide), RH-151,055 (the glucose conjugate of RH-117,236; 3,5-
dimethylbenzoic acid N-tert-butyl-N-[3( -D-glucopyranosyloxy)-2-
methylbenzoyl]-hydrazide) and RH-152,072 (the malonylglycosyl conjugate 
of RH-117,236) in or on legume vegetables; foliage of legume 
vegetables; forage, fodder, hay and straw of cereal grains; grass 
forage, fodder and hay; forage, fodder, straw and hay of non-grass 
animal feeds; and herbs and spices. The proposed tolerances are listed 
in the table below. The current petition requests establishment of 
tolerances in field corn grain at 0.05 ppm, sweet corn (K+CWHR) at 0.05 
ppm, field corn forage at 15 ppm, field corn stover (fodder) at 105 
ppm, corn oil at 0.2 ppm, aspirated grain factions at 1.0 ppm, corn 
silage at 5.0 ppm, sweet corn forage at 30 ppm, and sweet corn stover 
(fodder) at 60 ppm. In addition, this petition requests an increase in 
the established tolerance for residues of methoxyfenozide to 0.1 ppm in 
milk and an increase in the established tolerances for residues of 
methoxyfenozide and its glucuronide metabolite to 0.5 ppm in fat, to 
0.4 ppm in liver and to 0.1 ppm in meat by products (except liver) of 
cattle, goats, horses, hogs and sheep.
     Risk assessments were conducted by Rohm and Haas to assess dietary 
exposures and risks from methoxyfenozide as follows:
    a. Acute exposure and risk. Acute dietary risk assessments are 
performed for a food-use pesticide if a toxicological study has 
indicated the possibility of an effect of concern occurring as a result 
of a 1-day or single exposure. No appropriate toxicological endpoint 
attributable to a single exposure was identified in the available 
toxicology studies on methoxyfenozide including the acute neurotoxicity 
study in rats, the developmental toxicity study in rats and the 
developmental toxicity study in rabbits. Since no acute toxicological 
endpoints were established, Rohm and Haas considers acute aggregate 
risk to be negligible.
    b. Chronic exposure and risk. Rohm and Haas used the Dietary 
Exposure Evaluation Model (DEEM ) software for conducting a chronic 
dietary (food) risk analysis. DEEM is a dietary exposure analysis 
system that is used to estimate exposure to a pesticide chemical in 
foods comprising the diets of the U.S. population, including population 
subgroups. DEEM contains food consumption data as reported by 
respondents in the USDA Continuing Surveys of Food Intake by 
Individuals conducted in 1994-1996. Rohm and Haas assumed 100 percent 
of crops would be treated and contain methoxyfenozide residues at the 
tolerance level. The following table shows the tolerance levels which 
were used in the analysis:

 
------------------------------------------------------------------------
                                             Tolerance Level (parts per)
                 Commodity                          million (ppm)
------------------------------------------------------------------------
Cotton, undelinted seed                     2.0
Pome fruit                                  1.5
Grapes                                      1.0
Raisins                                     1.5
Leafy Vegetables (4A)                       25
Leaf Petioles (4B)                          10.0
Head and Stem Brassica (5A)                 6.5
Leafy Brassica Greens (5B)                  20.0
Fruiting vegetables                         2.0
Root and tuber vegetables                   0.05
Leaves of root and tuber vegetables         0.1
Bulb vegetables                             0.1
Legume vegetables                           0.05
Herbs and spices                            8
Corn, field, grain                          0.05
Corn, field, forage                         15
Corn, field, stover (fodder)                105
Corn, oil                                   0.2
Corn, aspirated grain fractions             1.0
Corn, silage                                5.0
Corn, sweet (K+CWHR)                        0.05
Corn, sweet, forage                         30
Corn, sweet, stover (fodder)                60
Milk                                        0.1
Meat\1\                                     0.02
Meat byproducts\1\ (except liver)           0.1
Fat\1\                                      0.5
Liver                                       0.4
------------------------------------------------------------------------
\1\of cattle, goats, hogs, horses and sheep.

    Processing factors were also applied to grape juice (1.2x), grape 
juice concentrate (3.6x), apple juice/cider (1.3x), apple juice 
concentrate (3.9x), dried apples (8x), dried pears (6.25x), tomato 
juice (1.5x), tomato puree (3.3x), tomato paste (5.4x), tomato catsup 
(2.5x), dried tomatoes (14.3x), dehydrated onions (9x), white dry 
potatoes (6.5x), sprouted soybean seeds (0.33x), corn grain sugar (high 
fructose corn syrup; 1.5x), dried beef (1.92x), and dried veal (1.92x). 
The processing factors are default values from DEEM.
    As shown in the following table the resulting dietary food 
exposures occupy up to 34.5% of the Chronic PAD for the most highly 
exposed population subgroup, children 1-6 years old. These results 
should be viewed as conservative (health protective) risk estimates. 
Refinements such as use of percent crop-treated information and/or 
anticipated residue values would yield even lower estimates of chronic 
dietary exposure.

       Summary: Chronic Dietary Exposure Analysis by DEEM (Tier 1)
------------------------------------------------------------------------
                                   Exposure (mg/kg/
       Population Subgroup               day)          % of Chronic PAD*
------------------------------------------------------------------------
U.S. Population -- 48 States      0.0176              17.6
All infants (< 1 year)            0.226               22.6
Nursing Infants < 1 year old      0.00678             6.8
Non-Nursing Infants < 1 year old  0.0273              27.3
Children 1-6 years old            0.0345              34.5

[[Page 15458]]

 
Children 7-12 years old           0.0200              20.0
Females 13+ (nursing)             0.0177              17.7
U.S. population (autumn season)   0.0181              18.1
U.S. population (winter season)   0.0178              17.8
U.S. population (spring season)   0.0178              17.8
Northeast region                  0.0193              19.3
Western region                    0.0195              19.5
Hispanics                         0.0177              17.7
Non-Hispanic/non-white/non-black  0.0237              23.7
------------------------------------------------------------------------
*Percent chronic PAD = (Exposure divided by Chronic PAD) x 100%

    The subgroups listed are: (1) The U.S. population (total); (2) 
those for infants and children; (3) the other subgroup(s), if any, for 
which the percentage of the Chronic PAD occupied is greater than that 
occupied by the subgroup U.S. population (total); and, (4) the most 
highly exposed of the females subgroups (in this case, females, (13+ 
years, nursing).
    ii. Drinking water-- From drinking water. The are no water-related 
exposure data from monitoring to complete a quantitative drinking water 
exposure analysis and risk assessment for methoxyfenozide. GENEEC and/
or PRZM/EXAMS (both produce estimates of pesticide concentration in a 
farm pond) are used to generate EECs for surface water and SCI-GROW (an 
empirical model based upon actual monitoring data collected for a 
number of pesticides that serve as benchmarks) predicts EECs in ground 
water. These models take into account the use patterns and the 
environmental profile of a pesticide, but do not include consideration 
of the impact that processing raw water for distribution as drinking 
water would likely have on the removal of pesticides from the source 
water. The primary use of these models at this stage is to provide a 
coarse screen for assessing whether a pesticide is likely to be present 
in drinking water at concentrations which would exceed human health 
levels of concern.
    A drinking water level of comparison (DWLOC) is the concentration 
of a pesticide in drinking water that would be acceptable as a 
theoretical upper limit in light of total aggregate exposure to that 
pesticide from food, water, and residential uses. HED 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 a pesticide, the DWLOC is 
used as a point of comparison against the conservative EECs provided by 
computer modeling (SCI-GROW, GENEEC, PRZM/EXAMS).
    a. Acute exposure and risk. Because no acute dietary endpoint was 
determined, Rohm and Haas concludes that there is a reasonable 
certainty of no harm from acute exposure from drinking water.
    b. Chronic exposure and risk. Tier II screening-level assessments 
can be conducted using the simulation models SCI-GROW and PRZM/EXAMS to 
generate EECs for ground and surface water, respectively. The modeling 
was conducted based on the environmental profile and the maximum 
seasonal application rate proposed for methoxyfenozide (1.0 lb ai/acre/
season). PRZM/EXAMS was used to generate the surface water EECs, 
because it can factor the persistent nature of the chemical into the 
estimates.
    The EECs for assessing chronic aggregate dietary risk used by HED 
are 6 parts per billion (ppb) (in ground water, based on SCI-GROW) and 
98.5 ppb (in surface water, based on the PRZM/EXAMS, long-term mean). 
The back-calculated DWLOCs for assessing chronic aggregate dietary risk 
range from 655 ppb for the most highly exposed population subgroup 
(children 1-6 years old) to 2,884 ppb for the U.S. population (48 
contiguous States--all seasons).
    The SCI-GROW and PRZM/EXAMS chronic EECs are less than the Agency's 
level of comparison (the DWLOC value for each population subgroup) for 
methoxyfenozide residues in drinking water as a contribution to chronic 
aggregate exposure. Rohm and Haas thus concludes with reasonable 
certainty that residues of methoxyfenozide in drinking water will not 
contribute significantly to the aggregate chronic human health risk and 
that the chronic aggregate exposure from methoxyfenozide residues in 
food and drinking water will not exceed the Agency's level of concern 
(100% of the cPAD) for chronic dietary aggregate exposure by any 
population subgroup. EPA generally has no concern for exposures below 
100% of the cPAD, because it is a level at or below which daily 
aggregate dietary exposure over a lifetime will not pose appreciable 
risks to the health and safety of any population subgroup. This risk 
assessment is considered high confidence, conservative, and very 
protective of human health. The following table shows the drinking 
water level of comparison for chronic exposure to methoxyfenozine:

                                       Drinking Water Levels of Comparison for Chronic Exposure to Methoxyfenozide
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                     GENEEC 56-Day
       Population Subgroup        Chronic PAD (mg/kg/  Food Exposure (m/      Max. Water       SCI-GROW (g/
                                          d)                 kg/d)        Exposure (mg/kg/d)        m>g/L)              m>g/L)               L) %
--------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. Population - 48 States       0.10                0.0176              0.0824              6                   98.5                2,884
Females 13+ (nursing)             0.10                .0177               0.0823              6                   98.5                2,469
Non-Nursing Infants < 1 year old  0.10                0.0273              0.0727              6                   98.5                727
Children 1-6 years old            0.10                0.0345              0.0655              6                   98.5                655
Children 7-12 years old           0.10                0.0200              0.080               6                   98.5                800
--------------------------------------------------------------------------------------------------------------------------------------------------------
Maximum Water Exposure (mg/kg/d) = Chronic PAD (mg/kg/day) - Chronic Food Exposure DWLOC (g/L) = [Maximum water Exposure (mg/kg/d) x body
  weight (kg)] divided by [1/1,000 mg/g x water consumed daily (L/day)]. Body weights (kg) for adults is 70, for females 13+ is 60 kg and for
  all children is 10 kg. Drinking water consumption is 2 liters per day for adults and 1 liter per day for children.

    2. Non-dietary exposure. Methoxyfenozide is not currently 
registered for use on any residential non-food sites. Therefore, there 
is no non-dietary acute, chronic, short- or intermediate-term exposure.

D. Cumulative Effects

    Cumulative exposure to substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) requires that,

[[Page 15459]]

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 methoxyfenozide 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, 
methoxyfenozide does not appear to produce a toxic metabolite produced 
by other substances. For the purposes of this tolerance action, 
therefore, it is assumed that methoxyfenozide does not have a common 
mechanism of toxicity with other substances.

E. Safety Determination

    1. U.S. population. Using the DEEM exposure assumptions described 
in this unit, Rohm and Haas has concluded that aggregate exposure to 
methoxyfenozide from food will utilize 17.6% of the cPAD for the U.S. 
population. The major identifiable subgroup with the highest aggregate 
exposure is children 1-6 years old at 34.5% of the cPAD and is 
discussed below. 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 methoxyfenozide in drinking water, the aggregate exposure is not 
expected to exceed 100% of the cPAD. Rohm and Haas concludes that there 
is a reasonable certainty that no harm will result from aggregate 
exposure to methoxyfenozide residues.
    2. Safety factor for infants and children--i. In general. In 
assessing the potential for additional sensitivity of infant and 
children to residues of methoxyfenozide, 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 margin of exposure (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/UF 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. Prenatal and postnatal sensitivity. The toxicology data base 
for methoxyfenozide included acceptable developmental toxicity studies 
in both rats and rabbits as well as a 2-generation reproductive 
toxicity study in rats. The data provided no indication of increased 
sensitivity of rats or rabbits to in utero and/or postnatal exposure to 
methoxyfenozide.
    iii. Conclusion. There is a complete toxicity data base for 
methoxyfenozide and exposure data are complete or are estimated based 
on data that reasonably accounts for potential exposures. Based on the 
completeness of the data base and the lack of prenatal and postnatal 
toxicity, EPA determined that an additional safety factor was not 
needed for the protection of infants and children.
    iv. Acute risk. Since no acute toxicological endpoints were 
established, acute aggregate risk is considered to be negligible.
    v. Chronic risk. Using the exposure assumptions described in this 
unit, Rohm and Haas has concluded that aggregate exposure to 
methoxyfenozide from food will utilize 34.5% 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 
methoxyfenozide in drinking water, Rohm and Haas does not expect the 
aggregate exposure to exceed 100% of the cPAD.
    vi. Short- or intermediate-term risk. Short and intermediate term 
risks are judged to be negligible due to the lack of significant 
toxicological effects observed.
    vii. Determination of safety. Based on these risk assessments, Rohm 
and Haas concludes that there is a reasonable certainty that no harm 
will result to infants and children from aggregate exposure to 
methoxyfenozide residues.

F. International Tolerances

    There are no established or proposed Codex, Canadian or Mexican 
limits for residues of methoxyfenozide in/on plant or animal 
commodities. Therefore, no compatibility issues exist with regard to 
the proposed U.S. tolerances discussed in this petition review.

[FR Doc. 01-6721 Filed 3-16-01; 8:45 am]
BILLING CODE 6560-50-S