Carfentrazone-ethyl and its metabolite carfentrazone-ethyl chloropropionic acid (FMC & IR4). July 28, 2004. Pesticide tolerance petition. Federal Register.

FLUORIDE ACTION NETWORK PESTICIDE PROJECT

Return to Carfentrazone-ethyl Index Page

Carfentrazone-ethyl and its metabolite, carfentrazone-ethyl chloropropionic acid.
(FMC Corporation and IR-4).
July 28, 2004. Pesticide tolerance petition. Federal Register.

http://www.epa.gov/fedrgstr/EPA-PEST/2004/July/Day-28/p16719.htm

[Federal Register: July 28, 2004 (Volume 69, Number 144)]
[Notices]
[Page 45042-45047]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28jy04-69]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2004-0177; FRL-7365-2]

Carfentrazone-ethyl; 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 pesticide
petitions 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-
2004-0177, must be received on or before August 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: Joanne I. Miller, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-6224; e-mail
address:miller.joanne@epa.gov.
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); and
• Pesticide manufacturing (NAICS).
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 this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
[[Page 45043]]
whether this action might apply to certain entities. 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-2004-0177. 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 Bell Street, 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 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-2004-0177. 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 opp-docket@epa.gov,
Attention: Docket ID Number OPP-2004-0177. 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),
[[Page 45044]]
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001, Attention: Docket ID Number OPP-2004-0177.
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 Bell St., Arlington, VA, Attention: Docket ID Number
OPP-2004-0177. 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.
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 assignedto this action in the subject line on the first page
of your response. You may also provide thename, 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 FFDCA section 408(d)(2); however,
EPA has not fully evaluated the sufficiency of the submitted data at
this time or whether the data support granting of the petition.
Additional data may be needed before EPA rules on the petition.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: July 9, 2004.
Betty Shackleford,
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition
The petitioner summary of the pesticide petitions are printed below
as required by FFDCA section 408(d)(3). The summary of the petitions
were 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.
FMC Corporation and IR-4
2F6468, 3E6746, 3E6554, 4E6814 and 3F6584
EPA has received pesticide petitions (2F6468, 3E6746, 3E6554,
4E6814 and 3F6584) from FMC Corporation and IR-4, 1735 Market Street,
Philadelphia, PA 19103 and Technology Center of New Jersey, 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 part 180 by establishing tolerances for residues of carfentrazone-
ethyl (ethyl-[alpha]-2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-
methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzene-propanoate) and the
metabolite carfentrazone-ethyl chloropropionic acid ([alpha], 2-
dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-
triazol-1-yl]-4-fluorobenzenepropanoic acid) in or on the raw
agricultural commodities: Acerola at 0.1 parts per million (ppm);
Almond hulls at 0.2 ppm and grass, forage, fodder and hay, group 17 at
12 ppm; Hops at 0.05 ppm; Avocado at 0.1 ppm; Atemoya at 0.1 ppm;
Banana at 0.1 ppm; Berry group 13 at 0.1 ppm; Birida at 0.1 ppm;
Borage, seed at 0.1 ppm; Cacao at 0.1 ppm; Cactus at 0.1 ppm; Canistel
at 0.1 ppm; Cherimoya at 0.1 ppm; Citrus, crop group 10 at 0.1 ppm;
Citrus cultivars and/or hybrids of grapefruit and pummelo, including
Uniq fruit at 0.1 ppm; Coconut at 0.1 ppm; Coffee at 0.1 ppm; Crambe,
seed at 0.1 ppm; Custard apple at 0.1 ppm; Date at 0.1 ppm; Feijoa at
0.1 ppm; Fig at 0.1 ppm; Fish at 0.2 ppm; Flax, seed at 0.1 ppm; Grape
at 0.1 ppm; Grapefruit at 0.1 ppm; Guava at 0.1 ppm; Guayule at 0.1
ppm; Herbs and spice group 19 at 0.1 ppm; Horseradish at 0.1 ppm; Ilama
at 0.1 ppm; Indian Mulberry at 0.1 ppm; Jabotica at 0.1 ppm; Juneberry
at 0.1 ppm; Kava at 0.1 ppm; Kiwi fruit at 0.1 ppm; Lingonberry at 0.1
ppm; Lychee at 0.1 ppm; Longan at 0.1 ppm; Mango at 0.1 ppm; Mustard
seed, Indian at 0.1 ppm; Mustard seed, Field at 0.1 ppm; Mustard seed,
Black at 0.1 ppm; Okra at 0.1 ppm; Olive at 0.1 ppm; Palm Heart, leaves
at 0.1 ppm; Passionfruit at 0.1 ppm; Papaya at 0.1 ppm; Pawpaw at 0.1
ppm; Peanut at 0.1 ppm; Persimmon at 0.1 ppm; Pistachio at 0.1 ppm;
Pome fruit, crop group 11 at 0.1 ppm; Pomegranate at 0.1 ppm; Pulasan
at 0.1 ppm; Pummelo at 0.1 ppm; Rambutan at 0.1 ppm; Rapeseed, Indian
at 0.1 ppm; Rapeseed, seed at 0.1 ppm; Safflower, seed at 0.1 ppm;
Salal at 0.1 ppm; Sapodilla at 0.1 ppm; Sapote, black at 0.1 ppm;
Sapote, mamey at 0.1 ppm; Shellfish at 0.2 ppm; Sorghum, sweet, stalks
at 0.1 ppm; Sorghum, sweet, syrup at 0.1 ppm; Soursop at 0.1 ppm;
Spanish lime at 0.1 ppm; Star apple at 0.1 ppm; Starfruit at 0.1 ppm;
Stone fruit, crop group 12 at 0.1 ppm; Strawberry at 0.1 ppm;
Strawberrypear at 0.1 ppm; Stevia at 0.1 ppm; Sugar apple at 0.1 ppm;
Sugarcane at 0.1 ppm; Sunflower, seed at 0.1 ppm; Ti, leaves at 0.1
ppm; Tea at 0.1 ppm; Tree nut, crop group 14 at 0.1 ppm; Tuberous and
corm vegetables, crop subgroup 1C at 0.1 ppm; Vanilla at 0.1 ppm;
Vegetable, brassica, leafy, group 5 at 0.1 ppm;
[[Page 45045]]
Vegetable, bulb, group 3 at 0.1 ppm; Vegetable, cucurbit group 9 at 0.1
ppm; Vegetable, foliage of legume, group 7 at 0.1 ppm; Vegetables,
Fruiting, Group, crop group 8 at 0.1 ppm; Vegetable, leaves of root and
tuber, group 2 at 0.1 ppm; Vegetable, leafy, except brassica, group 4
at 0.1 ppm; Vegetable, legume, group 6 at 0.1 ppm; Vegetable, root and
tuber, group 1 at 0.1 ppm; Wasabi, roots at 0.1 ppm; and Wax jambu at
0.1 ppm.
EPA has determined that the petitions contain 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
petitions. Additional data may be needed before EPA rules on the
petitions.

A. Residue Chemistry
1. Plant metabolism. The metabolism of carfentrazone-ethyl in
plants is adequately understood. Corn, wheat, radish and soybean
metabolism studies with carfentrazone-ethyl have shown uptake of
material into plant tissue with no significant movement into grain,
root or seeds. All four plants extensively metabolized carfentrazone-
ethyl and exhibited a similar metabolic pathway. The residues of
concern are the combined residues of carfentrazone-ethyl and
carfentrazone-ethyl- chloropropionic acid.

2. Analytical method. There is a practical analytical method for
detecting and measuring levels of carfentrazone-ethyl and its
metabolites in or on food with a limit of quantitation that allows
monitoring of food with residues at or above the levels set or proposed
in the tolerances. The analytical method for carfentrazone-ethyl
involves separate analyses for parent and its metabolites. The parent
is analyzed by gas chromatography/electron capture detection (GC/ECD).
The metabolites are derivatized with boron trifluoride and acetic
anhydride for analysis by gas chromatography mass spectrometry
detection (GC/MSD) using selective ion monitoring.

3. Magnitude of residues. Trials were conducted on several on
several crop groups listed above. Carfentrazone-ethyl (Aim EC, Aim EW
or Aim Herbicide) was applied as a broadcast application to soil at a
target rate of 0.032 pounds active ingredient per acre (lbs ai/A) 24-48
hours prior to planting. The second application was a post-emergent
banded application at a target rate of 0.064 lb ai/A within 12-24 hours
of harvest with a hooded sprayer to row middles with the hood riding
along the soil surface. Treated and untreated mature samples were
collected at crop maturity. Additional samples from one trial each of
several crops were collected to establish a residue decline pattern.
Additional samples from one trial each of several crops were collected
for processing studies for subsequent analysis of processed parts.
Residues of carfentrazone-ethyl and its metabolites in the crop group
samples were detected in low levels ranging from ND to 0.06 ppm with a
PHI of 1 day. Residues were not found in the exaggerated rate samples,
and therefore, processing was not conducted for most of the crops.
Residue values < 0.05 ppm are estimated values less than the limit of
quantitation (LOQ) and greater than the limit of detection (LOD) (0.01
- 0.02 ppm).
For berries, trials were conducted as follows: For blueberry, the
first application of carfentrazone-ethyl (Aim EC, Aim EW or Aim
Herbicide), was a dormant post-direct application to the base of tree
trunks at a targeted rate of 0.032 lb ai/A and the second application
was an indirect hooded sprayer application at a target banded rate of
0.064 lb ai/A 12-24 hours prior to harvest for a total of 0.096 lb ai/
A. For blackberry (Aim EC) and raspberry (Aim EW) carfentrazone-ethyl
was applied four times as a post-direct application each at a target
rate of 0.1 lb ai/A for a total of 0.4 lb ai/A with a PHI of 15 days.
Treated and untreated mature samples were collected at crop maturity.
Additional samples from one blueberry trial were collected to establish
a residue decline pattern. Residues were not detected (< 0.01 ppm) in
any of the samples.
For grape, tuberous and corm vegetables, citrus fruits, pome
fruits, stone fruits, tree nuts and grass, trials were conducted as
follows: Carfentrazone-ethyl (Aim EC, Aim EW or Aim Herbicide) was
applied three times as a broadcast foliar application at a target rate
of 0.031 lb ai/A for a total target rate of 0.093 lb ai/A. Additional
samples were collected from one trial each to establish a residue
decline pattern and for processing studies. For grass, forage samples
were collected on 0 day, hay was cut on 0 day and dried for 0 - 14 days
after the third application of the test substance. The maximum total
residue for carfentrazone-ethyl and its major metabolites in/on forage
and hay was 5.59 and 10.64 ppm, respectively. Low level residues were
found in the control samples in seven of the twelve trials ranging from
an estimated 0.02 ppm to 0.07 ppm. Residues of carfentrazone-ethyl and
its metabolites in the crop/group samples were detected in low levels
ranging from ND to < LOQ except for residues of almond hulls. Residue
values < 0.05 ppm are estimated values less than the LOQ and greater
than the LOD (0.01 - 0.04 ppm). RAC were harvested at the appropriate
time and subsequent analyses determined that the residues of
carfentrazone-ethyl and its metabolites would not exceed the proposed
tolerances.
No residues of carfentrazone-ethyl were found in any fish tissue
sample at any time. The maximum total residue of carfentrazone-ethyl
chloropropionic acid in the fish tissues were 0.17 ppm.

B. Toxicological Profile
1. Acute toxicity. Carfentrazone-ethyl demonstrates low oral,
dermal and inhalation toxicity. The acute oral LD50 value in
the rat was greater than 5,000 milligrams/kilogram (mg/kg), the acute
dermal LD50 value in the rat was greater than 4,000 mg/kg
and the acute inhalation LC50 value in the rat was greater
than 5.09 mg/Liter (L)/4h. Carfentrazone-ethyl is non-irritating to
rabbit skin and minimally irritating to rabbit eyes. It did not cause
skin sensitization in guinea pigs. An acute neurotoxicity study in the
rat had a systemic NOAEL of 500 mg/kg based on clinical signs and
decreased motor activity levels; the NOAEL for neurotoxicity was
greater than 2,000 mg/kg (highest dose tested) based on the lack of
neurotoxic clinical signs or effects on neuropathology.

2. Genotoxicty. Carfentrazone-ethyl did not cause mutations in the
Ames assay with or without metabolic activation. There was a positive
response in the Chromosome Aberration assay without activation but a
negative response with activation. The Mouse Micronucleus assay (an in
vivo test which also measures chromosome damage), the CHO/HGPRT forward
mutation assay and the Unscheduled DNA Synthesis assay were negative.
The overwhelming weight of the evidence supports the conclusion that
Carfentrazone-ethyl is not genotoxic.

3. Reproductive and developmental toxicity. Carfentrazone-ethyl is
not considered to be a reproductive or a developmental toxin. In the 2-
generation reproduction study, the NOAEL for reproductive toxicity was
greater than 4,000 ppm (greater than 323 to greater than 409 mg/kg/
day). In the developmental toxicity studies, the rat and rabbit
maternal NOAELs were 100 mg/kg/day and 150 mg/kg/day, respectively. The
developmental NOAEL for the rabbit was greater than 300 mg/kg/day,
which was the HDT and for the rat the NOAEL was 600 mg/kg/day based on
increased litter incidences of thickened and wavy ribs at 1,250 mg/
[[Page 45046]]
kg/day. These two findings (thickened and wavy ribs) are not considered
adverse effects of treatment but related delays in rib development
which are generally believed to be reversible.

4. Subchronic toxicity. Ninety-day feeding studies were conducted
in mice, rats and dogs with Carfentrazone-ethyl. The NOAEL for the
mouse study was 4,000 ppm (571 mg/kg/day), for the rat study was 1,000
ppm (57.9 mg/kg/day for males; 72.4 mg/kg/day for females) and for dogs
was 150 mg/kg/day. A 90-day subchronic neurotoxicity study in the rat
had a systemic NOAEL of 1,000 ppm (59.0 mg/kg/day for males; 70.7 mg/
kg/day for females) based on decreases in body weights, body weight
gains and food consumption at 10,000 ppm; the neurotoxicity NOAEL was
greater than 20,000 ppm (1178.3 mg/kg/day for males; 1433.5 mg/kg/day
for females) which was the highest dose tested.

5. Chronic toxicity. Carfentrazone-ethyl is not carcinogenic to
rats or mice. A 2-year Combined Chronic Toxicity/Oncogenicity study in
the rat was negative for carcinogenicity and had a chronic toxicity
NOAEL of 200 ppm (9 mg/kg/day) for males and 50 ppm (3 mg/kg/day) for
females based on red fluorescent granules consistent with porphyrin
deposits in the liver at the 500 and 200 ppm levels, respectively. An
18 Month Oncogenicity study in the mouse had a carcinogenic NOAEL that
was greater than 7,000 ppm (>1,090 mg/kg/day for males; >1296 mg/kg/day
for females) based on no evidence of carcinogenicity at the highest
dose tested. A 1-Year Oral Toxicity study in the dog had a NOAEL of 50
mg/kg/day based on isolated increases in urine porphyrins in the 150
mg/kg/day group (this finding was not considered adverse). Using the
Guidelines for Carcinogen Risk Assessment, carfentrazone-ethyl should
be classified as Group ``E'' for carcinogenicity -- no evidence of
carcinogenicity -- based on the results of carcinogenicity studies in
two species. There was no evidence of carcinogenicity in an 18-month
feeding study in mice and a 2-year feeding study in rats at the dosage
levels tested. The doses tested are adequate for identifying a cancer
risk. Thus, a cancer risk assessment is not necessary.

6. Animal metabolism. The metabolism of carfentrazone-ethyl in
animals is adequately understood. Carfentrazone-ethyl was extensively
metabolized and readily eliminated following oral administration to
rats, goats, and poultry via excreta. All three animals exhibited a
similar metabolic pathway. As in plants, the parent chemical was
metabolized by hydrolytic mechanisms to predominantly form
carfentrazone-ethyl-chloropropionic acid, which was readily excreted.

7. Endocrine disruption. An evaluation of the potential effects on
the endocrine systems of mammals has not been determined; however, no
evidence of such effects was reported in the chronic or reproductive
toxicology studies described above. There was no observed pathology of
the endocrine organs in these studies. There is no evidence at this
time that carfentrazone-ethyl causes endocrine effect.

C. Aggregate Exposure
1. Dietary exposure--i. acute dietary. Based on the available
toxicity data, the EPA has established an acute Reference Dose (aRfD)
for carfentrazone-ethyl of 5 mg/kg/day. The aRfD for carfentrazone-
ethyl is based on acute neurotoxicity study in rats with a threshold
NOAEL of 500 mg/kg/day and an uncertainty factor of 100.
ii. Chronic dietary. Based on the available toxicity data, the EPA
has established a RfD for carfentrazone-ethyl of 0.03 mg/kg/day. The
RfD for carfentrazone-ethyl is based on a 2-year chronic toxicity/
carcinogenicity study in rats with a threshold NOAEL of 3 mg/kg/day and
an uncertainty factor of 100. For purposes of assessing the potential
chronic dietary exposure, a Tier 1 dietary risk assessment was
conducted based on the Theoretical Maximum Residue Contribution (TMRC)
from the established and proposed tolerances for carfentrazone-ethyl.
The tolerances are as follows: 0.1 ppm in or on caneberry subgroup;
0.20 ppm in or on corn, field, forage; 0.20 ppm in or on corn, sweet,
forage;0.1 ppm corn, sweet, kernel plus cob with husk removed; 10 ppm
in or on cotton, gin by products; 0.20 ppm in or on cotton, undelinted
seed; 0.60 ppm in or on cotton, hulls; 0.35 ppm in or on cotton, meals;
1.0 ppm in or on cotton, refined oil; 1.0 ppm in or on grain, cereal,
forage (excluding corn and sorghum); 0.30 ppm in or on grain, cereal
hay; 0.10 ppm in or on grain, cereal, group; 0.30 ppm in or on grain,
cereal, stover; 0.1 ppm in or on grain, cereal, straw (excluding rice);
1.0 ppm in or on rice, straw; 0.20 ppm in or on sorghum, forage and0.1
ppm in or on soybean, seed. (The TMRC is a ``worse case'' estimate of
dietary exposure since it is assumed that 100 percent of all crops for
which tolerances are established are treated and that pesticide
residues are present at the tolerance levels.). In conducting this
exposure assessment, the following very conservative assumptions were
made - 100% of soybean, cotton, Caneberry and cereal grains will
contain carfentrazone-ethyl residues and those residues would be at the
level of the tolerance which result in an over estimate of human
exposure.

2. Food. Dietary exposure from the proposed uses would account for
1.0% or less of the aPAD in subpopulations (including infants and
children). Dietary exposure from the proposed uses would account for
15% or less of the cPAD in subpopulations (including infants and
children).

3. Drinking water. Acute DWLOC is estimated at 175,000 mg/kg/day,
surface water EEC at 21.4 parts per billion (ppb) and ground water EEC
at 13.4 ppb for U.S. subpopulations - all seasons. Chronic DWLOC is
estimated at 998 mg/kg/day, surface water EEC at 20.2 ppb and ground
water EEC at 13.4 ppb for U.S. subpopulations - all seasons.

4. Non-dietary exposure. No specific worker exposure tests have
been conducted with carfentrazone-ethyl. The potential for non-
occupational exposure to the general population has not been fully
assessed.

D. Cumulative Effects
EPA is also required to consider the potential for cumulative
effects of carfentrazone-ethyl and other substances that have a common
mechanism of toxicity. EPA consideration of a common mechanism of
toxicity is not appropriate at this time since EPA does not have
information to indicate that toxic effects produced by carfentrazone-
ethyl would be cumulative with those of any other chemical compounds;
thus only the potential risks of carfentrazone-ethyl are considered in
this exposure assessment.

E. Safety Determination
1. U.S. population. Using the conservative exposure assumptions
described and based on the completeness and reliability of the toxicity
data, the aggregate exposure to carfentrazone-ethyl will utilize less
than 1% of the aPAD and less than 15% of the cPAD for the US
subpopulations. EPA generally has no concern for exposures below 100
percent of the aPAD or cPAD. Therefore, based on the completeness and
reliability of the toxicity data and the conservative exposure
assessment, there is a reasonable certainty that no harm will result
from aggregate exposure to residues of carfentrazone-ethyl, including
all anticipated dietary exposure and all other non-occupational
exposures.

2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of carfentrazone-ethyl,
EPA considers data
[[Page 45047]]
from developmental toxicity studies in the rat and rabbit and the two-
generation reproduction study in the rat. The developmental toxicity
studies are designed to evaluate adverse effects on the developing
organism resulting from pesticide exposure during prenatal development.
Reproduction studies provide information relating to effects on the
reproductive capacity of males and females exposed to the pesticide.
Developmental toxicity was not observed in developmental toxicity
studies using rats and rabbits. In these studies, the rat and rabbit
maternal NOAELs were 100 mg/kg/day and 150 mg/kg/day, respectively. The
developmental NOAEL for the rabbit was greater than 300 mg/kg/day,
which was the highest dose, tested and for the rat was 600 mg/kg/day
based on increased litter incidences of thickened and wavy ribs. These
two findings are not considered adverse effects of treatment but
related delays in rib development, which are generally believed to be
reversible.
In a two-generation reproduction study in rats, no reproductive
toxicity was observed under the conditions of the study at 4,000 ppm,
which was the highest dose tested.
FFDCA section 408 provides that EPA may apply an additional safety
factor for infants and children in the case of threshold effects to
account for pre- and post-natal toxicity and the completeness of the
database. Based on the current toxicological data requirements, the
database relative to pre-natal and post-natal effects for children is
complete and an additional uncertainty factor is not warranted.
Therefore at this time, the RfD of 0.03 mg/kg/day is appropriate for
assessing aggregate risk to infants and children.

3. Population adjusted dose (aPAD and cPAD). Using the conservative
exposure assumptions described above, the percent of the aPAD that will
be utilized by aggregate exposure to residues of carfentrazone-ethyl
for non-nursing infants (< 1 year old) would be < 1% (aPAD) and < 10%
(cPAD); for children 1-6 years of age would be < 1% (aPAD) and < 15%
(cPAD), (the most highly exposed group). Based on the completeness and
reliability of the toxicity data and the conservative exposure
assessment, there is a reasonable certainty that no harm will result to
infants and children from aggregate exposure to the residues of
carfentrazone-ethyl including all anticipated dietary exposure.

F. International Tolerances
There are no Codex Alimentarius Commission (Codex) Maximum Residue
Levels (MRLs) for carfentrazone-ethyl on any crops at this time.
However, MRLs for small grains in Europe have been proposed which
consist of carfentrazone-ethyl and carfentrazone-ethyl-chloropropionic
acid.
[FR Doc. 04-16719 Filed 7-27-04; 8:45 am]
BILLING CODE 6560-50-S