[Federal Register: May 6, 2004 (Volume 69, Number 88)]
[Notices]
[Page 25384-25390]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06my04-51]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2004-0122; FRL-7356-8]
DCPA; 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 ID number OPP-2004-0122, must be
received on or before June 7, 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@epamail.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)
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. 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
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. EPA Docket. EPA has established an official public docket for
this action under docket ID number OPP-2004-0122. 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, 1921 Jefferson Davis Hwy.,
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 on 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
[[Page 25385]]
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-2004-0122. 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-2004-0122. 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-2004-0122.
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, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket
ID number OPP-2004-0122. 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 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 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.
[[Page 25386]]
List of Subjects
Environmental protection, Agricultural commodities, Feed
additives, Food additives, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: April 26, 2004.
Betty Shackleford,
Acting Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner's summary of the pesticide petition is printed
below as required by FFDCA section 408(d)(3). The summary of the
petition was prepared by Interregional Research Project Number 4 (IR-
4), 681 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 (IR-4)
PP 2E6442
EPA has received a pesticide petition 2E6442 from 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 part 180 by establishing
a tolerance for residues of DCPA, or chlorthal dimethyl (dimethyl
tetrachloroterephthalate) in or on the raw agricultural commodities
Oriental radish, basil, coriander, dill, marjoram, chives, ginseng,
celeriac, chicory, mradicchio, parsley (fresh) and parsley (dried) at
2.0, 5.0, 5.0, 5.0, 5.0, 5.0, 2.0, 2.0, 5.0, 2.0, 5.0 and 15 parts per
million (ppm), respectively. EPA has determined that the petition
contains data or information regarding the elements set forth in
section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated
the sufficiency of the submitted data at this time or whether the data
support granting of the petition. Additional data may be needed before
EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. The qualitative nature of the residue in
plants is adequately understood based on acceptable studies on onions,
turnips, and tobacco. The residues of concern in plants are DCPA, and
its metabolites monomethyl tetrachloroterephthalic acid (MTP) and
tetrachloroterephthalic acid (TPA) which are the parent and metabolites
that are currently regulated. The proposed metabolism of DCPA in plants
is via ester hydrolysis. Studies conducted with onion and turnip
indicate that the impurity hexachlorobenzene (HCB) is not metabolized
appreciably in these plants.
2. Analytical method. Three tolerance enforcement methods for plant
commodities are published in the Pesticide Analytical Manual (PAM),
Vol. II (Section 180.185), as Methods A, B, and C. Residue data
submitted in response to the 6/88 Guidance Document were collected
using gas chromatography/electron capture (GC/EC) methods similar to
the PAM, Vol. II methods. The Agency has found these methods to be
adequate for collection of DCPA, HCB, MTP, and TPA residue data from
potatoes (including processed commodities), sweet potatoes, broccoli,
celery, cucumbers, green and bulb onions, strawberries, sweet and bell
peppers, cantaloupes, tomatoes (including processed commodities),
summer squash, and processed commodities of beans and cottonseed. The
limits of detection (LOD) are 0.01 ppm each for DCPA, MTP, and TPA, and
0.0005 ppm for HCB. These methods are suitable candidates for
validation procedures as enforcement methods for plant commodities.
Another GC/EC method, similar to those submitted for plants, is
available for determining DCPA, MTP, and TPA in milk and beef fat.
Recoveries of each compound using 12 samples each of milk and beef fat
fortified at 0.01-5 ppm were acceptable. The LOD is 0.01 ppm. The
Agency has deemed this method is suitable for its validation and
inclusion in PAM, Vol. II pending successful independent laboratory
validation. DCPA per se is completely recovered using PAM, Vol. I
Multiresidue Protocols D and E (PESTDATA, PAM, Vol. I, Appendix, 8/93).
Data submitted by the previous registrant indicate that TPA is not
recovered by Protocols B and C. The Agency has indicated that
multiresidue testing data on MTP are still required.
3. Magnitude of residues--i. Oriental radish. IR-4 has received a
request from California for the use of DCPA on oriental radish. IR-4
supports the requested tolerance of 2 ppm on oriental radish based on
other existing tolerances.
ii. Basil. IR-4 has received a request from California for the use
of DCPA on basil. IR-4 supports the requested tolerance of 5 ppm on
basil based on other existing tolerances.
iii. Coriander. IR-4 has received a request from California for the
use of DCPA on coriander. IR-4 supports the requested tolerance of 5
ppm on coriander based on other existing tolerances.
iv. Dill. IR-4 has received a request from California for the use
of DCPA on fresh dill. IR-4 supports the requested tolerance of 5 ppm
on fresh dill based on other existing tolerances.
v. Marjoram. IR-4 has received a request from California for the
use of DCPA on marjoram. IR-4 supports the requested tolerance of 5 ppm
on marjoram based on other existing tolerances.
vi. Chives. IR-4 has received a request from California for the use
of DCPA on chives. IR-4 supports the requested tolerance of 5 ppm on
chives based on other existing tolerances.
vii. Ginseng. IR-4 has received requests from Wisconsin and North
Carolina for the use of DCPA on ginseng. IR-4 supports the requested
tolerance of 2 ppm on ginseng based on other existing tolerances.
viii. Celeriac. IR-4 has received a request from California for the
use of DCPA on celeriac. IR-4 supports the requested tolerance of 2 ppm
on celeriac based on other existing tolerances. Chicory: IR-4 has
received a request from California for the use of DCPA on chicory. IR-4
supports the requested tolerance of 5 ppm on chicory based on other
existing tolerances.
ix. Radicchio. IR-4 has received a request from California for the
use of DCPA on radicchio. IR-4 supports the requested tolerance of 2
ppm on radicchio based on other existing tolerances.
B. Toxicological Profile
DCPA technical is classified under Toxicity Category IV
(practically non-toxic) for acute-oral toxicity and dermal irritation
and Toxicity Category III (slightly toxic) for dermal lethal dose
(LD)50, inhalation lethal concentration (LC)50,
and eye irritation. DCPA is not a dermal sensitizer. DCPA has been
classified as a Group C, possible human carcinogen, based on increased
incidence of thyroid tumors in both sexes of the rat (although, only at
an excessive dose in the female), and liver tumors in female rats and
mice, at doses which were not excessive.
1. Acute toxicity. The acute oral LD50 values for DCPA
in the rat was >5,000 milligrams/kilogram (mg/kg). The acute dermal
LD50 was >2,000 mg/kg in the rabbit. The 4-hour rat
inhalation LC50 was >4.48 milligrams/per Liter (mg/L). DCPA
was a mild irritant to rabbit skin and eyes. DCPA (performed with a 90%
material) did not cause skin sensitization in guinea pigs.
2. Genotoxicity. Mutagenicity studies as shown below have
demonstrated that
[[Page 25387]]
DCPA is non-mutagenic both in vivo and in vitro. DCPA did not induce a
mutagenic response in two independently performed mouse lymphoma
forward mutation assays. The nonactivated concentration range was 7.5
to 100 milligrams/milliliter (mg/mL) and the S9-activated range was 15
to 200 mg/mL (MRID 41054822). In an in vitro cytogenetic assay, Chinese
hamster ovary cells were exposed to DCPA at dose levels of 0, 30, 100,
300, or 1,000 mg/mL for 4 hours both with and without S-9 activation.
Cells were harvested at 12 and 18 hours. There were no indications of a
clastogenic response as a result of exposure to test material at any
dose level (MRID 41054823). DCPA was not genotoxic in two independently
performed unscheduled DNA synthesis (UDS) assays in which the
concentration ranged from 3 to 1,000 mg/mL (MRID 41054824). An in vitro
assay for sister chromatid exchange (SCE) in Chinese hamster ovary
cells was performed at dose levels of 0, 38, 75, 150, or 300 mg/mL both
with and without S9-activation. There was no indication of a positive
response; therefore, under the conditions of this assay the test
material is negative (MRID 41054825).
3. Reproductive and developmental toxicity. A developmental
toxicity study with Sprague Dawley rats used doses of 0, 500, 1,000, or
2,000 mg/kg/day given by gavage on gestation days 6-15. No adverse
effects on the maternal rats or their offspring were observed.
Therefore, the maternal and developmental toxicity no observed effect
levels (NOELs) were set at 2,000 mg/kg/day, highest dose tested (MRID
00160685).
Two studies were conducted with New Zealand white rabbits. In the
first study, DCPA doses of 0, 500, 1,000, or 1,500 mg/kg/day were given
by gavage on gestation days 6-19. There were maternal deaths and
adverse clinical signs at all dose levels. In the second study, DCPA
doses of 0, 125, 250, or 500 mg/kg/day were given by gavage on
gestation days 7-19. None of these levels produced any maternal or
developmental toxicity. The second study tested dose levels that
overlapped those in the first study. Therefore, when considered
together, the no observed adverse effect level (NOAEL) for maternal
toxicity can be set at 250 mg/kg and the lowest observed adverse effect
level (LOAEL) can be set at 500 mg/kg based on maternal deaths. The
developmental toxicity NOAEL can be set at 500 mg/kg. Although, no
developmental effects were observed at any of the higher dose levels, a
higher NOAEL cannot be set based on the limited number of litters at
the higher dose levels.
In a 2-generation reproduction study, female Sprague Dawley rats
were fed DCPA at doses of 0, 63, 319, or 1,273 mg/kg/day while males
received doses of 45, 233, or 952 mg/kg/day DCPA. These doses were
equivalent to 0, 1,000, 5,000, and 20,000 ppm food residue values,
which the Agency used in mammalian environmental risk. No effects on
reproductive performance in 2 generations with 2 litters per generation
were seen. The maternal NOAEL was 63 mg/kg/day. The maternal LOAEL was
319 mg/kg/day, based on decreased body weight/body weight gain. The
reproductive NOAEL was 63 mg/kg/day. The LOAEL was 319 mg/kg/day, based
on decreased pup body weight. The paternal NOAEL was set at 233 mg/kg/
day, and the LOAEL was set at 952 mg/kg/day due to decreased body
weight gain. On day 0 of the F2b litters, the diets for the low and
mid-dose groups were changed to 18 and 47 mg/kg/day respectively to be
able to set a NOAEL for pup body weight. The offspring NOAEL was set at
18 mg/kg/day (200 ppm), and the LOAEL was 47 mg/kg/day (500 ppm) based
on decreased body weight. (MRIDs 41750103, 41905201).
4. Subchronic toxicity. In a 21-day dermal toxicity study, Charles
River CD rats were dermally exposed to DCPA doses of 0, 100, 300, or
1,000 mg/kg/day. No dermal irritation at the site of application was
observed. No adverse effects were found; therefore, the NOEL was equal
to or greater than 1,000 mg/kg/day, the highest dose tested (MRID
41231803).
CD VAF/Plus Sprague Dawley rats were given 0, 10, 50, 100, 150, or
1,000 mg/kg/day of DCPA in the diet for 90 days. The NOAEL was 10 mg/
kg/day. The LOAEL was 50 mg/kg/day, based on increased liver weight and
microscopic effects. The treatment-related effects were: Increased
weight and centrilobular hypertrophy in the liver; increased
accumulation of foamy macrophages in the lung; increased weight,
epithelial hyperplasia, and tubular hypertrophy of the kidney; and
follicular hypertrophy of the thyroid. There were slight decreases in
body weight and food consumption in high dose females only (MRID
41767901).
Male CD-1 mice were given doses of 0, 100, 199, 406, or 1,235 mg/
kg/day DCPA and females were given 0, 223, 517, 1049, or 2,198 mg/kg/
day DCPA in the diet for 90 days. There were no effects other than
minimal histopathological effects on the liver. The NOAEL was 406 mg/
kg/day for males and 517 mg/kg/day for females. The LOAEL for males was
1235 mg/kg/day and for females was 1,049 mg/kg/day, based on the liver
effects (MRID 41064801).
5. Chronic toxicity. Beagle dogs were given 0, 2.5, 25, or 250 mg/
kg/day DCPA in the feed for 2 years. Adverse effects were not found.
Therefore, the NOAEL was equal to or greater than 250 mg/kg/day (MRID
00083584).
A chronic toxicity and carcinogenicity study was conducted with
Sprague Dawley CD rats. The doses of DCPA given in the diet for 2 years
were 0, 1, 10, 50, 500 or 1,000 mg/kg/day. The NOAEL was 1 mg/kg/day.
The LOAEL was 10 mg/kg/day, with effects observed in the lungs, liver,
and thyroid; decreases in thyroid hormone levels in both sexes; and
effects in eyes in females. The specific effects were: (1) Increased
mortality in males at 1,000 mg/kg/day HDT during the second year; (2)
either decreased body weights or decreased body weight gains in both
sexes at 1,000 mg/kg/day, and in females at 500 mg/kg/day; (3) changes
in hematology and clinical chemistry parameters indicative of liver and
kidney toxicity at both 500 and 1,000 mg/kg/day in both sexes; (4)
treatment-related increases in thyroid, liver, and kidney weights in
both sexes; (5) a dose-related increase in white foci in the lungs,
which correlated with an increased incidence of foaming macrophages in
both sexes at doses of 10 mg/kg/day and higher; (6) treatment-related
exacerbation of chronic nephropathy in both sexes at 50 mg/kg/day and
higher; (7) a dose-related increase in centrilobular hepatocytic
swelling in both sexes at doses of 10 mg/kg/day and higher; (8) a dose-
related increase in liver neoplasms in females; (9) an increase in
follicular cell hyperplasia/hypertrophy at 10 mg/kg/day in males and at
doses of 50 mg/kg/day and higher in both sexes; (10) decreased T4
(thyroid hormone/thyroxine) values at 10 mg/kg/day in males, and at 50
mg/kg/day and higher in both sexes; and (11) a treatment-related
increase in thyroid follicular cell neoplasms in both sexes (MRID
42731001).
In another combined chronic toxicity and carcinogenicity study,
CD-1 mice were given DCPA in the diet for 2 years. The doses were 0,
12, 123, 435, or 930 mg/kg/day DCPA in the diet for males and 0, 15,
150, 510, or 1,141 mg/kg/day for females. The NOAEL for systemic
effects was 435 mg/kg/day in males; 510 mg/kg/day in females. The
systemic lowest observed effect level (LOEL) was 930 mg/kg/day in
males; 1,141 mg/kg/day in females, based on liver effects. There were
increased liver weights,
[[Page 25388]]
increased SDH (sorbital dehydrogenase) and GPT (glutamic-pyruvic
transaminase) activities, and increased incidence of hepatocyte
enlargement or vacuolation in both sexes at the high dose levels; 930
and 1,141 mg/kg/day for males and females, respectively. There was a
significant increase in hepatocellular neoplasms in females at the high
dose level of 1,141 mg/kg/day. Corneal opacity was observed in this
study (MRID 40958701).
Additionally, a supplementary rat chronic ophthalmology study was
conducted to investigate the corneal opacity observed in the mouse
study. There was no evidence of ocular toxicity observed in rats fed
DCPA in the diet at levels up to 1,000 mg/kg/day for 2 years (MRID
41750102).
6. Animal metabolism. In one study, a single oral dose of
14C -DCPA at either 1 or 1,000 mg/kg was given to Sprague-
Dawley rats (5 rats/sex/dose level). The major metabolite of DCPA in
the urine of both sexes at both dose levels was 4-carbomethoxy-2,3,5,6-
tetrachlorobenzoic acid. No radiolabel was excreted in the urine as the
parent compound, DCPA (MRID 42155501).
There was a second study in which a single oral dose of
14C -DCPA at either 1 or 1,000 mg/kg was given to Sprague-
Dawley rats. Bile was found to be a negligible excretory route for
radiolabeled DCPA. At the low dose, 61% of the administered
radiolabeled DCPA was excreted in the urine. The percent absorption
(urine, blood, bile, cage rinse, and carcass) was 79% of the
administered dose. At the high dose, 55% of the administered radiolabel
was excreted in the feces or was found in the GIT (gastro-intestinal
tract). The percent absorption was 8% of the administered dose (MRID
42155503).
There was a third study in which a single oral dose of
14C -DCPA at either 1 or 1,000 mg/kg was given to Sprague-
Dawley rats (3 rats/sex/dose level) to determine the major route of
excretion. Urine was the major route at the low dose, and feces was the
major route at the high dose. Negligible amounts of radiolabel were
found in the tissues examined at 48 hours following dosing. There were
no significant differences observed between the sexes at either dose
level (MRID 42155502).
In a different study, nonradiolabeled DCPA was administered in
single, daily oral doses to Crl:CD BR VAF/Plus rats (15 rats/sex/dose
level) for 14 consecutive days at either the 1 or 1,000 mg/kg/day dose
level. Twenty-four hours after the 14th dose, a single oral
dose of 14C-DCPA (1 or 1,000 mg/kg) was administered to each
rat. At the high dose level (both sexes), the majority of the
administered 14C-DCPA was unabsorbed and was eliminated in
the feces, while at the low dose level (both sexes) the majority of the
administered 14C-DCPA was absorbed and excreted in the
urine. Radiolabel was found in all tissues examined, and the radiolabel
concentration was higher in the high-dose rat tissue than in the same
tissue at the low dose level. At 168 hours, radiolabel was still
detectable in nearly all tissues at both dose levels and in both sexes.
The elimination half-life of radiolabel was calculated to be 22-23
hours at the high dose and approximately 18-hours at the low dose.
(MRID 42723201, 42723202).
In another study, Sprague-Dawley rats (5 rats/sex/dose level) were
given single or multiple 14-days oral doses of 14C-DCPA (1
or 1,000 mg/kg). The major metabolite of DCPA in the urine of both
sexes at both dose levels following both single and multiple dosing was
4-carbomethoxy-2,3,5,6-tetrachlorobenzoic acid. A minor metabolite was
tetrachloroterephthalic acid. No radiolabel was excreted in the urine
as the parent compound, DCPA (MRID 42723203). Together these studies
fulfill GLN 870.7485 (old GLN 85-1) (MRID 43052201).
7. Metabolite toxicology--i. Hexachlorobeneze (HCB) as a DCPA
impurity. HCB is a recognized impurity in DCPA. The Agency has
classified HCB as a B2 (probable human) carcinogen, based on data sets
which showed significant increases of tumor incidence in 2 species:
Hamsters and rats. In a 130-week feeding study in rats, the NOAEL was
0.08 mg/kg/day. (Effects observed were hepatic centrilobular basophilic
chromogenesis.) The dermal absorption factor of HCB is 26.46% (MRID
42651501). At this time no other toxicological endpoints of concern
have been identified for HCB.
The Agency risk assessment of HCB was based on levels in the
original DCPA source material. Since then, the Agency has acknowledged
in RED correspondence that the new registrant committed to reducing HCB
concentrations in its source material. Subsequently, the Agency in fact
confirmed a new technical registration (granted to AMVAC Chemical
Corporation) with HCB concentrations almost two orders lower in
magnitude than before. As a result, the potential HCB exposures to
humans is concomitantly reduced to a fraction of the potential exposure
considered by EPA in its original RED risk assessment.
ii. Polyhalogenated dibenzo-p-dioxins/dibenzofurans as DCPA
Impurities. Polyhalogenated dibenzo-p-dioxins/dibenzofurans (dioxin/
furans) are recognized impurities of DCPA. Of the dioxin/furans, only
the 2,3,7,8-tetrachloro-dibenzo-para-dioxin (2,3,7,8-TCDD) congener has
been assigned a quantified estimate of its carcinogenic potential. The
Agency has classified 2,3,7,8-TCDD as a B2 (probable human) carcinogen
based on data sets which showed significant increases of tumor
incidence in 2 species: Sprague-Dawley rats and B6C3F1 mice.
Enough data exist, however, regarding the potency of the other
congeners to estimate their relative potency in comparison to the
2,3,7,8-TCDD. Therefore, in evaluating the toxicological significance
of the dioxin/furan contamination, the Agency converts all of the
congener detection values into one value which represents the
equivalent 2,3,7,8-TCDD potency. For example, if a product contained 10
parts per billion (ppb) of a dioxin congener other than the 2,3,7,8-
TCDD, and if that congener is considered to be only 1/10th
as potent as 2,3,7,8-TCDD, the Agency would use the equivalent of 1 ppb
of 2,3,7,8-TCDD in its risk assessment. DCPA's prior registrant
submitted dioxin/furan detection values to the Agency from seven batch
samples, as required in the 1987 DCI. During the first sampling, one of
the dioxin/furan congeners was detected above the Agency specified
level of quantitation (LOQ). The manufacturing process was subsequently
altered in an effort to reduce this contamination. (MRID 41241801).
Subsequent to this change, none of the dioxin/furan congeners were
detected above Agency specified LOQs in the remaining six batch
samples. The 2,3,7,8-TCDD equivalency of the dioxin/furans reported to
the Agency is approximately 0.1 ppb, which would equal 0.00000001% of
the DCPA formulations. The Agency used this contamination value
(0.00000001%) to determine exposure values used in the risk assessments
for DCPA's reregistration eligibility evaluation. The Agency required
registrants to propose certified upper limits for all dioxin/furan
congeners for which detection values were reported to the Agency.
The reference dose (RfD) for 2,3,7,8-TCDD is 0.000001 [mu]g/kg/
day) based on a LOAEL of 0.001 [mu]g/kg/day from a three-generation
feeding study in rats. (Effects at the lowest dose tested included
dilated renal pelvises, decreased fetal weight, and changes in the
gestational index). An uncertainty factor of 100 was used to account
for the interspecies extrapolation and intraspecies variability. An
additional uncertainty factor of 10 was used to
[[Page 25389]]
account for the lack of a NOAEL. At this time, no other toxicological
endpoints of concern have been identified for 2,3,7,8-TCDD.
iii. Tetrachloroterephthalic acid (TPA) as a DCPA metabolite.
tetrachloro-terephthalic acid (TPA) is one of two DCPA animal
metabolites. DCPA fed to lactating goats was metabolized into both TPA
and monomethyl tetrachloroterephthalic acid (MTP). It is the TPA
metabolite, however, that is found most frequently in the environment
after DCPA use. Soil metabolism converts DCPA into TPA, which is known
to leach through soil and pollute ground water. Therefore, the prior
registrant submitted the following additional studies to specifically
assess the toxicity of TPA.
8. Subchronic toxicity of TPA. Disodium 2,3,5,6-
tetrachloroterephthalic acid was given to Charles River CD rats in the
diet for 13-weeks. There were 15 rats/sex/dose group using dose levels
of 0, 2.5, 25, 50, or 500 mg/kg/day. There were no adverse effects in
either sex at any dose level. The NOAEL is greater than or equal to 500
mg/kg/day, the highest dose tested. The LOAEL cannot be determined
(MRID 00100773).
CD Sprague-Dawley rats (10/sex/dose group) were given 2,3,5,6-
tetrachloroterephthalic acid via gavage for 30 days at dose levels of
0, 100, 500, or 2,000 mg/kg/day. There were no apparent adverse effects
observed at any dose level. The NOAEL is greater than or equal to 2,000
mg/kg/day, the highest dose tested. The LOAEL cannot be determined.
(MRID 00158011).
9. Developmental toxicity of TPA. In a developmental toxicity
study, 25 pregnant Charles River rats/dose group were dosed via gavage
on gestation days 6-15 with TPA at dose levels of 0, 625, 1,250, or
2,500 mg/kg/day. The maternal toxicity NOEL was 1,250 mg/kg/day. The
maternal LOAEL was set at 2,500 mg/kg/day based on decreased body-
weight gain and food consumption. There were no signs of developmental
toxicity, therefore, the developmental NOAEL was set at 2,500 mg/kg/
day, the highest dose tested. A LOAEL was not determined (MRID 262303).
10. Mutagenicity of TPA. TPA did not induce a mutagenic response in
the Ames assay or the HGPRT assay with or without metabolic activation
(MRID 262302). In the Sister Chromatid Exchange (SCE) assay, TPA did
not induce a significant increase in the SCE frequency of Chinese
hamster ovary cells, both with and without metabolic activation. TPA
did not induce an increase in unscheduled DNA synthesis. In an in vivo
mouse micronucleus assay, TPA was negative for clastogenicity in
females and at best equivocal in males. Based on the overall weight of
evidence of no mutagenic response of this compound in other studies, as
well as the lack of mutagenicity of the parent DCPA, further testing
for mutagenicity is not warranted at this time.
11. Endocrine disruption. The toxicology data base for DCPA is
current and complete. Studies in this data base include evaluation of
the potential effects on reproduction and development, and an
evaluation of the pathology of the endocrine organs following short-
term or long-term exposure. These studies revealed no primary endocrine
effects due to DCPA.
C. Aggregate Exposure
1. Dietary exposure--i. Food. Tolerances for residues of DCPA in or
on raw agricultural commodities are currently expressed as the combined
residues of DCPA and its metabolites monomethyl
tetrachloroterephthalate (MTP) and tetrachloroterephthalic acid (TPA)
calculated as DCPA. At present, no tolerances exist for residues of
DCPA in animal commodities. Although, all the data requirements of the
Reregistration Guidance had not been met when the Agency issued the
RED, the outstanding data were considered to be confirmatory to the
reregistration eligibility decision. The Agency determined that
sufficient data are available to conduct reasonable anticipated residue
assessments.
People may be exposed to residues of DCPA through the diet.
Tolerances or maximum residue limits have been established for residues
of DCPA in many food and feed crops (see 40 CFR 180.185). EPA has
reassessed the DCPA tolerances and found that some are acceptable,
others must be revoked because refinements in crop groups must be
replaced with new tolerances for the new crop groupings. Acute dietary
risk assessments were not necessary since there were no acute
toxicological endpoints of concern for DCPA or its impurities. Chronic
and carcinogenic dietary risks were assessed, however, due to exposure
to DCPA, HCB, and dioxin/furans.
Chronic risk estimates for the U.S. population and all subgroups
were well below 100% of the RfD for DCPA, HCB, and dioxin/furans. Based
on these estimates, the Agency concluded that DCPA use does not pose a
significant chronic dietary risk. Carcinogenic risk estimate for
exposure to DCPA, HCB, and dioxin/furans through food were 3.5 x
10-7, and 7 x 10-8, respectively. All of these
risk estimates are within the range (zero to 1 x 10-6)
generally considered to be negligible by the Agency. Thus, the Agency
concluded that DCPA use does not pose a significant excess lifetime
cancer risk.
ii. Drinking water. The Agency assessed both chronic (non-cancer)
and carcinogenic risk due to exposure to DCPA and its metabolites
through contaminated ground water and surface water. The Agency used
annual contamination averages from five geographic regions as potential
drinking water exposure values. The highest annual average was 50 ppb
in New York from a turf study. Although, this represents approximately
71% of the health advisories (HA), it only corresponds to 11% of RfD.
Even if part of this population were to the maximum 3% of the RfD from
other dietary sources, the chronic dietary risk would still be
considered minimal.
Individual excess lifetime cancer risk from the New York turf site
was 1.7 x 10-6. The next highest risk estimate is based on
data from Suffolk County, New York. The risk estimate from that site is
9.7 x 10-7. DCPA's previous registrant voluntarily withdrew
from selling the product in Suffolk, New York. Exposure values from all
other sites resulted in risks below the Agency's cancer benchmark of 1
x 10-6. Based on these estimates, the Agency concluded that
DCPA and its metabolites do not currently pose a significant cancer or
chronic non-cancer risk from non-turf uses to the overall U.S.
population from exposure through contaminated drinking water.
2. Non-dietary exposure. DCPA is currently registered for
commercial and residential use. Risk assessments were performed to
assess the individual excess lifetime cancer risk from DCPA and HCB
resulting from occupational and residential exposure to DCPA. The
Agency will not generally allow non-dietary risks to exceed
10-4, except in cases where EPA has determined that benefits
exceed the risks.
i. Occupational exposure. Risk was estimated for occupational
exposures to both DCPA and HCB. The highest risk for both commercial
applicators and private applicators is associated with the use of the
wettable powder formulation. For the commercial applicator, the highest
risk for DCPA was estimated to be 7.5 x 10-5 and for HCB (in
DCPA) to be 1.9 x 10-4. The Agency is requiring mixer/
loader/applicators using DCPA wettable powders to wear a dust-mist
respirator fitted with a TC-21 filter to mitigate this risk. Wearing a
dust-mist respirator reduces the risks to 4.0 x 10-5 and 1.3
x 10-4 for DCPA and HCB respectively.
[[Page 25390]]
For the private applicator, the highest risk for DCPA was
estimated to be 1.6 x 10-6 and for HCB (in DCPA) to be 4.6 x
10-6.
ii. Turfgrass. Risks to children playing on a treated lawn were
assessed for exposure to DCPA and HCB. The risks from DCPA and HCB to
children playing on an irrigated lawn are 5.6 x 10-7 and 3.9
x 10-7, respectively. The risks from DCPA and HCB to
children playing on non-irrigated lawns are 2.0 x 10-6 and
2.7 x 10-6, respectively. The Agency is conducting a risk/
benefit assessment to determine whether the turf use is eligible for
reregistration. However, in the interim, the Agency is requiring that
residential lawns be watered after DCPA product use and that reentry
not occur until sprays have dried, in an effort to mitigate risks to
children.
iii. Re-entry. Risk from exposure to DCPA and HCB through worker
re-entry into a cucumber field was assessed. Harvesting cucumbers
immediately after application resulted in risk estimates of 1.8 x
10-4 for DCPA and 3.2 x 10-4 for HCB. Delayed re-
entry periods only minimally reduced risk estimates. However, the
Agency reported in the RED that it believes that the worker exposures
are overestimates. These scenarios were based solely on a foliar
dissipation study, not on dermal exposure studies. DCPA's current
registrant is a member of a task force which will address dermal
exposure for hand labor tasks required by various crops, such as
cucumber harvesting. The risk assessment will be refined when the task
force submits it dermal exposure data.
D. Cumulative Effects
DCPA is a pre-emergent herbicide used to control annual grasses
and broadleaf weeds. At this time, the EPA has not made a determination
that DCPA and other substances that may have a common mechanism of
toxicity would have cumulative effects. Therefore, for these tolerance
petitions, it is assumed that DCPA does not have a common mechanism of
toxicity with other substances and only the potential risks of DCPA in
its aggregate exposure are considered.
E. Safety Determination
DCPA and its metabolites generally are of low acute and chronic
toxicity. DCPA has been classified as a Group C, possible human
carcinogen. Many food crop uses are registered, however, dietary
exposure to DCPA residues in foods is at a low level, as is the cancer
risk posed to the general population.
Of greater concern is the risk posed to DCPA handlers,
particularly mixers/loaders/applicators, and field workers who come
into contact with treated areas following application of this
pesticide. Exposure and risk to workers will be mitigated by the use of
personal protective equipment required by the Worker Protection
Standard. Because the pesticide is a possible human carcinogen, the
Agency required mixer/loader/applicators using DCPA wettable powder to
wear a dust-mist respirator fitted with a TC-21 filter to mitigate this
risk.
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine,
after submission of relevant data concerning an active ingredient,
whether products containing the active ingredient are eligible for
reregistration. The Agency has previously identified and required the
submission of the generic (i.e., active ingredient specific) data
required to support reregistration of products containing DCPA. The
Agency completed its review of these generic data, and determined that
the data are sufficient to support reregistration of all products
containing DCPA under the conditions specified in the RED. The generic
data that the Agency reviewed as part of its determination of
reregistration eligibility of were sufficient to allow the Agency to
assess the registered uses of DCPA and to determine that DCPA can be
used without resulting in unreasonable adverse effects to humans and
the environment, if used according to the labels as amended by the RED.
The Agency, therefore, found that all products containing DCPA as the
active ingredient are eligible for reregistration under the conditions
specified in the RED.
F. International Tolerances
No maximum residue limits for DCPA have been established by Codex
for any agricultural commodity. Therefore, no compatibility questions
exist with respect to U.S. tolerances.
[FR Doc. 04-10288 Filed 5-5-04; 8:45 am]
BILLING CODE 6560-50-S