[Federal Register Volume 69, Number 166 (Friday, August 27, 2004)]
[Notices]
[Pages 52688-52693]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-19616]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2004-0288; FRL-7676-3]


Clofentezine; Notice of Filing a Pesticide Petition to Establish 
a Tolerance for a Certain Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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

DATES: Comments, identified by docket identification (ID)number OPP-
2004-0288, must be received on or before September 27, 2004.

ADDRESSES:  Comments may be submitted electronically, by mail, or 
through hand delivery/courier. Follow the detailed instructions as 
provided in Unit I. of the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: Sidney Jackson, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 305-7610; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS 111)
     Animal production (NAICS 112)
     Food manufacturing (NAICS 311)
     Pesticide manufacturing (NAICS 32532)
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. Other types of 
entities not listed in this unit could also be affected. If you have 
any 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 Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket ID number OPP-2004-0288. The official public docket 
consists of the documents specifically referenced in this action, any 
public comments received, and other information related to this action. 
Although a part of the official docket, the public docket does not 
include Confidential Business Information (CBI) or other information 
whose disclosure is restricted by statute. The official public docket 
is the collection of materials that is available for public viewing at 
the Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall 2, 1801 S. Bell St., Arlington, VA. This docket 
facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The docket telephone number is (703) 305-
5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Although not all docket materials may be 
available electronically, you may still access any of the publicly 
available docket materials through the docket

[[Page 52689]]

facility identified in Unit I.B.1. Once in the system, select 
``search,'' then key in the appropriate docket ID number.
    Certain types of information will not be placed in the EPA Dockets. 
Information claimed as CBI and other information whose disclosure is 
restricted by statute, which is not included in the official public 
docket, will not be available for public viewing in EPA's electronic 
public docket. EPA's policy is that copyrighted material will not be 
placed in EPA's electronic public docket but will be available only in 
printed, paper form in the official public docket. To the extent 
feasible, publicly available docket materials will be made available in 
EPA's electronic public docket. When a document is selected from the 
index list in EPA Dockets, the system will identify whether the 
document is available for viewing in EPA's electronic public docket. 
Although not all docket materials may be available electronically, you 
may still access any of the publicly available docket materials through 
the docket facility identified in Unit I.B. EPA intends to work towards 
providing electronic access to all of the publicly available docket 
materials through EPA's electronic public docket.
    For public commenters, it is important to note that EPA's policy is 
that public comments, whether submitted electronically or in paper, 
will be made available for public viewing in EPA's electronic public 
docket as EPA receives them and without change, unless the comment 
contains copyrighted material, CBI, or other information whose 
disclosure is restricted by statute. When EPA identifies a comment 
containing copyrighted material, EPA will provide a reference to that 
material in the version of the comment that is placed in EPA's 
electronic public docket. The entire printed comment, including the 
copyrighted material, will be available in the public docket.
    Public comments submitted on computer disks that are mailed or 
delivered to the docket will be transferred to EPA's electronic public 
docket. Public comments that are mailed or delivered to the docket will 
be scanned and placed in EPA's electronic public docket. Where 
practical, physical objects will be photographed, and the photograph 
will be placed in EPA's electronic public docket along with a brief 
description written by the docket staff.

C. How and To Whom Do I Submit Comments?

    You may submit comments electronically, by mail, or through hand 
delivery/courier. To ensure proper receipt by EPA, identify the 
appropriate docket ID number in the subject line on the first page of 
your comment. Please ensure that your comments are submitted within the 
specified comment period. Comments received after the close of the 
comment period will be marked ``late.'' EPA is not required to consider 
these late comments. If you wish to submit CBI or information that is 
otherwise protected by statute, please follow the instructions in Unit 
I.D. Do not use EPA Dockets or e-mail to submit CBI or information 
protected by statute.
    1. Electronically. If you submit an electronic comment as 
prescribed in this unit, EPA recommends that you include your name, 
mailing address, and an e-mail address or other contact information in 
the body of your comment. Also include this contact information on the 
outside of any disk or CD ROM you submit, and in any cover letter 
accompanying the disk or CD ROM. This ensures that you can be 
identified as the submitter of the comment and allows EPA to contact 
you in case EPA cannot read your comment due to technical difficulties 
or needs further information on the substance of your comment. EPA's 
policy is that EPA will not edit your comment, and any identifying or 
contact information provided in the body of a comment will be included 
as part of the comment that is placed in the official public docket, 
and made available in EPA's electronic public docket. If EPA cannot 
read your comment due to technical difficulties and cannot contact you 
for clarification, EPA may not be able to consider your comment.
    i. EPA Dockets. Your use of EPA's electronic public docket to 
submit comments to EPA electronically is EPA's preferred method for 
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket/, and follow the online instructions for submitting comments. 
Once in the system, select ``search,'' and then key in docket ID number 
OPP-2004-0288. The system is an ``anonymous access'' system, which 
means EPA will not know your identity, e-mail address, or other contact 
information unless you provide it in the body of your comment.
    ii. E-mail. Comments may be sent by e-mail to [email protected], 
Attention: Docket ID Number OPP-2004-0288. In contrast to EPA's 
electronic public docket, EPA's e-mail system is not an ``anonymous 
access'' system. If you send an e-mail comment directly to the docket 
without going through EPA's electronic public docket, EPA's e-mail 
system automatically captures your e-mail address. E-mail addresses 
that are automatically captured by EPA's e-mail system are included as 
part of the comment that is placed in the official public docket, and 
made available in EPA's electronic public docket.
    iii. Disk or CD ROM. You may submit comments on a disk or CD ROM 
that you mail to the mailing address identified in Unit I.C.2. These 
electronic submissions will be accepted in WordPerfect or ASCII file 
format. Avoid the use of special characters and any form of encryption.
    2. By mail. Send your comments to: Public Information and Records 
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001, Attention: Docket ID Number OPP-2004-0288.
    3. By hand delivery or courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Office of Pesticide 
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall 
2, 1801 S. Bell St., Arlington, VA, Attention: Docket ID 
Number OPP-2004-0288. Such deliveries are only accepted during the 
docket's normal hours of operation as identified in Unit I.B.1.

 D. How Should I Submit CBI to the Agency?

    Do not submit information that you consider to be CBI 
electronically through EPA's electronic public docket or by e-mail. You 
may claim information that you submit to EPA as CBI by marking any part 
or all of that information as CBI (if you submit CBI on disk or CD ROM, 
mark the outside of the disk or CD ROM as CBI and then identify 
electronically within the disk or CD ROM the specific information that 
is 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 docket and EPA's electronic public docket. If you submit 
the copy that does not contain CBI on disk or CD ROM, mark the outside 
of the disk or CD ROM clearly that it does not contain CBI. Information 
not marked as CBI will be included in the public docket and EPA's 
electronic public docket without prior notice. If you have any 
questions about CBI or the procedures for claiming CBI, please consult 
the person listed under FOR FURTHER INFORMATION CONTACT.

[[Page 52690]]

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 
ID 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 Cosmetic 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) of the FFDCA; 
however, EPA has not fully evaluated the sufficiency of the submitted 
data at this time or whether the data support granting of the petition. 
Additional data may be needed before EPA rules on the petition.

List of Subjects

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


    Dated: August 20, 2004.
Betty Shackleford
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the view of the 
petitioner. 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.

Interregional Research Project Number 4

PP 4E6824

    EPA has received a pesticide petition (PP 4E6824) from the 
Interregional Research Project Number 4 (IR-4), 681 U.S. Highway 1 
South, North Brunswick, NJ 08902-3390, proposing pursuant to section 
408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR 180.446 by 
establishing a tolerance for residues of the miticide, clofentezine, 
(3,6-bis (2-chlorophenyl)-1,2,4,5-tetrazine) in or on the raw 
agricultural commodity persimmon at 0.05 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 support granting of the petition. The 
registrant, Makhteshim-Agan of North America, Inc., New York, NY 10176 
has prepared this summary in support of the pesticide petition. This 
summary does not necessarily reflect the findings of EPA. Additional 
data may be needed before EPA rules on the petition.
    Clofentezine is marketed in the U.S. under tradenames including 
APOLLO SC. APOLLO[reg]SC Ovicide/Miticide (42% active 
ingredient (a.i.)) is registered for use on apples, pears, almonds, 
walnuts, apricots, cherries, nectarines, and peaches to control 
European red mites and several spider mite species (tolerance for 
grapes is pending, petition 0F6119). APOLLO SC is an environmentally 
friendly, IPM-compatible product used at low dose rates, and only once 
per season. The product has been shown to be relatively non-toxic in 
studies conducted on mammals, fish, birds, aquatic invertebrates, 
predacious and other beneficial mites, bees, algae, and plants.

A. Residue Chemistry

    1. Plant metabolism. The qualitative nature of clofentezine 
residues in plants is adequately understood. The metabolism of 
clofentezine has been studied in three crops representative of the use 
pattern for APOLLO SC: Apples (pome fruit), peaches (stone fruit), and 
grapes (vines/small fruit). In each case, unchanged clofentezine was 
the major extractable residue present. Non-extractable residues (fiber-
bound) were negligible. Minor amounts of 2-chlorobenzonitrile, the 
major photo-degradation product, were detected, predominantly on the 
fruit surface. Dissipation of this component may be a significant route 
in the degradation of clofentezine on the surface of these crops. The 
nature of the residue in grapes, and in all the other registered crops, 
is therefore adequately understood. The residue of concern is the 
parent, clofentezine.
    2. Analytical method. An adequate method for purposes of 
enforcement of the proposed clofentezine tolerance is available. An 
independent method validation was successfully completed, and the 
method was found acceptable. An extensive database of method validation 
data using this method on various crop commodities is available. The 
Limit of Quantitation (LOQ) and Minimum Detection Limit (MDL) were 
determined to be 0.01 ppm and 0.003 ppm, respectively. The method was 
forwarded to FDA for inclusion in PAM-II.
    3. Magnitude of residues. Residue data covering the major growing 
area for persimmon has been submitted in support of the requested 
tolerance. The magnitude of residues for the proposed tolerance is 
adequately understood. The results demonstrate that the maximum residue 
of clofentezine in or on persimmon was 0.0305 ppm, measured 133 to 140 
days after application (0.25 pounds active ingredient (lb a.i.)/acre).

B. Toxicological Profile

    The toxicology of clofentezine has been thoroughly evaluated by EPA 
as part of previous regulatory actions. The studies are considered to 
be valid, reliable and adequate for the purposes of evaluating 
potential health risks and for establishing tolerances. The primary 
studies submitted in support of the registration of clofentezine are 
summarized below.
    1. Acute toxicity. Clofentezine has a relatively low degree of 
acute toxicity and irritation potential. It is classified as toxicity 
category III for oral, dermal and inhalation toxicity, and toxicity 
category IV for eye and skin irritation. The acute oral lethal dose 
(LD50) of clofentezine was determined to be >5,200 
milligrams/kilograms (mg/kg) in rats and mice, >3,200 mg/kg in 
hamsters, and >2,000 mg/kg in beagle dogs. The acute rat dermal 
LD50 was >2,100 mg/kg. Clofentezine is considered to be 
practically non-irritating to eyes and skin but is considered to be a 
week skin sensitizer in the guinea pig maximization assay.
    APOLLO SC is classified as toxicity category IV for oral toxicity 
and skin irritation, and as toxicity category III for dermal toxicity 
and eye irritation. The

[[Page 52691]]

acute oral LD50 of APOLLO SC was determined to be >5,000 mg/
kg in rats; the acute dermal LD50 in rats was >2,400 mg/kg. 
APOLLO SC is considered slightly irritating to eyes and skin.
    2. Genotoxicity. No evidence of genotoxicity was noted in a battery 
of in vitro and in vivo studies. Studies submitted included Ames 
Salmonella and mouse lymphoma gene mutation assay, a mouse micronucleus 
assay, a rat dominant lethal assay, and a gene conversion and mitotic 
recombination assay in yeast. Therefore, the registrant concludes that 
clofentezine has no potential to induce genotoxicity.
    3. Reproductive and developmental toxicity. A multigeneration rate 
reproduction study was conducted at dietary concentrations of 0, 4, 40, 
and 400 ppm. The parental no observed adverse effect level (NOAEL) was 
40 ppm based on slightly reduced body weights, increased liver weights 
and hepatocellular hypertrophy at 400 ppm. No treatment-related 
reproductive effects were noted at any dose level.
    In a rat developmental toxicity study, clofentezine was 
administered by gavage at dose levels of 0, 320, 1, 280 and 3,200 mg/
kg/day during gestation days 6 to 20. Evidence of maternal toxicity was 
noted at 3,200 mg/kg/day and consisted of decreased weight gain, 
increased liver weights and centrilobular hepatocellular enlargement. 
No developmental effects were observed at any dose level.
    In a rabbit developmental toxicity study, clofentezine was 
administered by gavage at dose levels of 0, 250, 1,000 and 3,000 mg/kg/
day during gestation days 7 to 28. Slight maternal toxicity (decreased 
maternal food consumption and weight gain) and a slight decrease in 
fetal weight were noted at 3,000 mg/kg/day. Thus, the NOAEL was 
considered to be 1,000 mg/kg/day for both maternal and developmental 
effects.
    4. Subchronic toxicity. In a preliminary 90-day feeding study 
designed to select a suitable high dose level for a subsequent chronic 
rate study, clofentezine was administered to rats at dietary 
concentrations of 0, 3,000, 9,000 and 27,000 ppm. A significant 
reduction in weight gain was noted at 9,000 and 27,000 ppm. In 
addition, a marked, dose-related hepatomegaly and centrilobular 
hepatocyte enlargement was noted in all treatment groups.
    In a subsequent 90-day feeding study, clofentezine was administered 
to rats at dietary concentrations of 0, 40, 400, and 4,000 ppm. 
Slightly reduced weight gain, alterations in several clinical pathology 
parameters, increased liver, kidney and spleen weights, and 
centrilobular hepatocyte enlargement were noted at 400 and/or 4,000 
ppm. Thus, 40 ppm (2.8 mg/kg/day) was considered to be the NOAEL for 
this study.
    Clofentezine was administered to beagle dogs for 90 days at dietary 
concentrations of 0, 3,200, 8,000 and 20,000 ppm. Increased liver 
weights were noted at all dose levels but no histopathological changes 
nor any other treatment-related effects were observed.
    5. Chronic toxicity. In a 12-month feeding study, clofentezine was 
administered to beagle dogs at dietary concentrations of 0, 50, 1,000, 
and 20,000 ppm. An increase in adrenal and thyroid weights, as well as 
moderate hepatotoxicity consisting of minimal periportal hepatocyte 
enlargement with cytoplasmic eosinophilia, hepatomegaly and increased 
plasma cholesterol, triglycerides and alkaline phosphatase levels, were 
noted at 20,000 ppm. Evidence of slight hepatotoxicity was also noted 
at 1,000 ppm. Thus, the NOAEL for this study was considered to be 50 
ppm (1.25 mg/kg/day).
    In a 27-month feeding study, clofentezine was administered to rats 
at dietary concentrations of 0, 10, 40, and 400 ppm. Effects noted at 
400 ppm were limited to the liver and thyroid, primarily of males, and 
consisted of increased liver weights, a variety of microscopic liver 
lesions (centrilobular hepatocyte hypertrophy and vacuolation, focal 
cystic hepatocellular degeneration and diffuse distribution of fat 
deposits), increased serum thyroxine levels, and a slight but 
statistically significant increase in the incidence of thyroid 
follicular cell tumors. The NOAEL was considered to be 40 ppm (2 mg/kg/
day).
    Clofentezine was not oncogenic to mice when administered for 2 
years at dietary concentrations of 0, 50, 500, and 5,000 ppm. Decreased 
weight gain, increased liver weights, and increased mortality were 
noted at 5,000 ppm. An increased incidence of eosinophilic or 
basophilic hepatocytes was noted at 5,000 ppm, and possibly 500 ppm.
    Numerous studies were conducted to investigate the mechanism for 
the increased incidence of male thyroid follicular tumors that was 
observed in the chronic rat study. These studies suggest that the 
tumors may have been caused by increased thyroid stimulating hormone 
(TSH) levels, which, in turn, resulted from clofentezine's liver 
toxicity, and were not attributable to a genotoxic mode of action.
    6. Animal metabolism. The metabolism, tissue distribution and 
excretion of clofentezine have been evaluated in a number of species. 
In all species, almost all of the administered dose was recovered 
within 24 to 48 hours after treatment, primarily via the feces. The 
major route of metabolism was found to be ring hydroxylation, sometimes 
preceded by the replacement of a chlorine atom with a methyl-thio 
group. Blood and tissue levels in the fetuses of pregnant rats that had 
been treated with clofentezine were much lower than the levels found in 
the mother, indicating that clofentezine does not readily pass across 
the placenta. In addition, less than 1% of the administered dose was 
absorbed through the skin of rats following a 10-hour exposure to the 
end use formulation of clofentezine, APOLLO SC.
    Following oral dosing of a cow and three goats with 14C-labeled 
clofentezine, the residue in milk was identified as a single 
metabolite, 4-hydroxyclofentezine. Similarly, 4-hydroxyclofentezine has 
been shown to be the only metabolite present in fat, liver, and kidney. 
No unchanged clofentezine or other metabolites were found. Therefore, 
the nature of the residue in animals is adequately understood. The 
residues of concern in ruminant commodities and milk are the combined 
residues of the parent, clofentezine, and the 4-hydroxyclofentezine 
metabolite.
    7. Metabolite toxicology. There are no metabolites of toxicological 
concern and therefore, no metabolites need to be included in the 
tolerance expression and require regulation.
    8. Endocrine disruption. Except for the thyroid mechanistic studies 
mentioned above, no special studies have been conducted to investigate 
the potential of clofentezine to induce estrogenic or other endocrine 
effects. However, the standard battery of required toxicity studies has 
been completed. These studies include an evaluation of the potential 
effects on reproduction and development, and an evaluation of the 
pathology of the endocrine organs following repeated or long-term 
exposure. Repeated dose studies are generally considered to be of 
substantial value as a means for detection of any endocrine effects. 
However, with the exception of a slightly increased incidence of 
thyroid tumors in male rats, no such effects were noted in any of the 
repeated dose toxicity studies with clofentezine. The male rat is known 
to be much more susceptible than humans to the carcinogenic effects 
resulting from thyroid hormone imbalance and/or increased levels of 
TSH. Therefore, the alterations in thyroid hormone and subsequent 
thyroid pathological

[[Page 52692]]

changes, which have been noted following administration of high doses 
of clofentezine, are considered to be of minimal relevance to human 
risk assessment, particularly considering the low levels of 
clofentezine to which humans are likely to be exposed.

C. Aggregate Exposure

    1. Dietary exposure. Current tolerances (40 CFR 180.446) have been 
established for almonds (hulls, nutmeat), apples (fruit, pomace), 
apricots, cherries, nectarines, peaches, pears, walnuts, ruminant 
commodities, and milk. There is also a proposed tolerance for grapes 
pending (PP OF6119). A notice of filing for grapes was published in the 
Federal Register of July 12, 2000 (65 FR 43004; FRL-6591-8). In 
addition to the registered and pending uses, this notice of filing 
includes exposure assessments for potential residues of clofentezine in 
or on persimmon. Presently and in the future, clofentezine is not 
considered for residential uses. Thus, potential sources of non-
occupational exposure to clofentezine would consist only of any 
potential residues in food and drinking water. No acute dietary 
assessments were conducted since no appropriate toxicological endpoint 
attributable to a single exposure was identified in the available 
toxicology studies. Therefore, only chronic exposure calculations were 
compared against the chronic RfD of 0.0125 mg/kg/day.
    i. Food. A conservative dietary exposure assessment was performed 
for clofentezine using Exponent's Dietary Exposure Evaluation Model 
(DEEM) software, and consumption data derived from the 1994-1996 USDA 
Continuing Surveys of Food Intake by Individuals (CSFII). This 
assessment used all existing and proposed tolerances, residue levels at 
current and proposed tolerance levels, and percent crop treated (PCT) 
data based on the following assumptions: 24% apples, 0% apricots, 6% 
cherries, 30% nectarines, 12.2% peaches, 16% pears, 1.4% plums and 
prunes, 9.2% almonds, 7.4% walnuts, and 25% for grapes and 25% 
persimmon. The PCT data for current uses are in agreement with USEPA 
earlier assessment for clofentezine (April 19, 1999, 64 FR 19042; FRL-
6075-6).
    Based on these assumptions, the chronic dietary exposure estimates 
(DEEM) from the existing and proposed tolerances are well below the 
chronic RfD, ranging from 2.7% to 10.3% of the cRfD for the U.S. and 
its subpopulations.
    ii. Drinking water. Sufficient ground or surface water monitoring 
data are not available to perform a quantitative risk assessment for 
clofentezine at this time. However, in the final rule published in the 
Federal Register on April 19, 1999 (see cite above), EPA previously 
determined estimated drinking water environmental concentrations 
(DWECs) for clofentezine in ground and surface water using available 
environmental fate data and the screening model for ground water (SCI-
GROW) and the generic expected environmental concentration (GENEEC) 
model for surface water. The DWEC of clofentezine in groundwater was 
estimated to be 0.04 parts per billion (ppb) using SCI-GROW, and the 
chronic DWEC for surface water was estimated to be 0.3 ppb using 
GENEEC. EPA's policy allows the 90/56-day GENEEC value to be divided by 
3 to obtain a value for chronic risk assessment calculations. 
Therefore, a surface water estimate of 0.1 ppb was used in the chronic 
risk assessment.
    2. Non-dietary exposure. Not applicable.
    3. Chronic exposure (diet plus water). EPA uses the Drinking Water 
Level Of Comparison (DWLOC) as a theoretical upper limit on a 
pesticide's concentration in drinking water when considering total 
aggregate exposure to a pesticide in food, drinking water, and 
residential uses (not applicable for this assessment). DWLOCs are not 
regulatory standards for drinking water. However, EPA uses these values 
in the risk assessment process as a point of comparison against 
conservative model estimates of a pesticide's concentration in water. 
To calculate the DWLOC for chronic exposure relative to a chronic 
toxicity endpoint, the chronic dietary exposure analysis (DEEM) was 
subtracted from the RfD to obtain the acceptable chronic exposure to 
clofentezine in drinking water. DWLOCs were then calculated using 
default body weights and drinking water consumption factors. If the 
DWLOC exceeds the DWEC value then there is reasonable certainty that no 
harm will result from the aggregate exposure.
    The estimated average concentration of clofentezine in surface 
drinking water (0.1 ppb) is far below the range of calculated DWLOCs: 
442 ppb (U.S. population), 233 ppb (children 1-6 years) and 117 ppb 
(All infants < 1 year, and Non-nursing infants). Therefore, Makhteshim-
Agan believes there is reasonable certainty that no harm will result 
from aggregate exposure to residues arising from all current and 
proposed clofentezine uses.

D. Cumulative Effects

    To our knowledge there are currently no available data or other 
reliable information indicating that any toxic effects produced by 
clofentezine would be cumulative with those of other chemical 
compounds; thus only the potential risks of clofentezine have been 
considered in this assessment of its aggregate exposure.

E. Safety Determination

    1. U.S. population. The toxicity and residue databases for 
clofentezine are considered to be valid, reliable, and essentially 
complete. No acute dietary assessment was conducted because there is no 
toxicological endpoint attributable to a single exposure. Although 
clofentezine has been classified by EPA as category C for oncogenicity 
(April 3, 1990), quantitative oncogenic risk assessment was considered 
inappropriate given the weight of the evidence presently supported by 
the Agency's position that human health risk associated with long-term 
exposure to clofentezine is most appropriately evaluated by a chronic 
RfD value derived from the 1-year dog feeding study (NOAEL of 1.25 mg/
kg/day), and using a 100-fold uncertainty factor. No effect on the 
thyroid, including the induction of thyroid follicular cell tumors 
would be expected at exposure levels that did not affect the liver. 
Furthermore, male rats are believed to be much more susceptible than 
humans to this type of effect. Therefore, the registrant concludes that 
quantification of carcinogenic risk based on thyroid follicular cell 
tumors in male rats is not appropriate.
    Using worst-case assumptions of 100% percent crop treated, and that 
all crops and animal commodities contain residues of clofentezine at 
the current tolerance levels data maximum percent crop treated data, 
the aggregate exposure of the general population to clofentezine from 
the established and proposed tolerances utilizes about 8.7% of the 
chronic RfD or 2.7% if more realistic estimates of percent crop treated 
data have been used. The theoretical maximum residue contribution 
(TMRC) for the proposed use on persimmon is negligible. There is 
generally no concern for exposures, which utilize less than 100% of the 
RfD because the RfD represents the level at or below which daily 
aggregate exposure over a lifetime would not pose significant risks to 
human health. Therefore, Makhteshim-Agan concludes that there is a 
reasonable certainty that no harm will result to the general population 
from aggregate exposure to clofentezine residues.
    2. Infants and children. The toxicology database for clofentezine 
regarding potential prenatal and

[[Page 52693]]

postnatal effects in children is complete according to existing Agency 
data requirements and does not indicate any developmental or 
reproductive concerns.
    No indication of increased sensitivity to infants and children was 
noted in any of the studies with clofentezine. No developmental effects 
were noted in rats, even at a dose level (3,200 mg/kg/day) that 
exceeded the 1,000 mg/kg/day limit dose and produced maternal toxicity. 
In addition, no evidence of reproductive toxicity was noted in the rat 
multigeneration reproduction study. Slight developmental toxicity 
(decreased fetal weights) was noted in rabbits, but only at a dose 
level (3,000 mg/kg/day) that exceeded the EPA limit dose and also 
produced maternaltoxicity.
    FFDCA section 408 provides that EPA may apply an additional safety 
factor for infants and children to account for prenatal and postnatal 
toxicity and the completeness of the database. The toxicology database 
for clofentezine regarding potential prenatal and postnatal effects in 
children is complete according to existing Agency data requirements and 
does not indicate any developmental or reproductive concerns. 
Furthermore, the existing RfD is based on a NOAEL of 1.25 mg/kg/day 
(from the 1-year dog study), which is already more than 800-fold lower 
than the NOAEL in the rabbit developmental toxicity study. Thus, the 
registrant believes that the existing RfD of 0.0125 mg/kg/day is 
considered to be appropriate for assessing potential risks to infants 
and children and an additional uncertainty factor is not warranted.
    Using the conservative exposure assumptions described above 
(proposed and current tolerances, 100% crop treated, and no adjustments 
for percent contribution from livestock diet), aggregate exposure to 
residues of clofentezine are expected to utilize about 48% of the RfD 
in non-nursing infants, 20% of the RfD in nursing infants, and 36% of 
the RfD in children aged 1 to 6 years old. Using more realistic 
estimates of percent crop treated, the percent of RfD utilized is less 
than or equal to 10% for these population subgroups. These numbers 
would be lowered further if anticipated residues and/or an adjustment 
for percent contribution from livestock diet were utilized rather than 
tolerance values. The residue contribution for the proposed use on 
persimmon is negligible. Therefore, Makhteshim-Agan concludes that 
there is reasonable certainty that no harm will result to infants or 
children from aggregate exposure to clofentezine residues.

F. International Tolerances

    There are no international maximum residue levels (MRL) established 
for clofentezine in or on the raw agricultural commodity, persimmon.

[FR Doc. 04-19616 Filed 8-26-04; 8:45 am]
BILLING CODE 6560-50-S