[Federal Register: December 17, 2003 (Volume 68, Number 242)]
[Notices]
[Page 70251-70255]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr17de03-68]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2003-0352; FRL-7336-4]
Cis-Isomer of 1-(3-Chloroallyl)-3,5,7-Triaza-1-Azoniaadamantane
Chloride; 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-
2003-0352, must be received on or before January 16, 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: James Parker, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 308-0371; e-mail address: parker.james@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:
[sbull] Crop production (NAICS 111)
[sbull] Animal production (NAICS 112)
[sbull] Food manufacturing (NAICS 311)
[sbull] 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. Docket. EPA has established an official public docket for this
action under docket ID number OPP-2003-0352. 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 EPA's 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.1. 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
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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-2003-0352. 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-2003-0352. 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-2003-0352.
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-2003-0352. 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.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: Decembern 4, 2003.
Peter Caulkins,
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 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.
Dow Chemical Company
PP 3E6656
EPA has received a pesticide petition (3E6656) from Dow Chemical
Company, Building 1803, Midland, Michigan 48674, proposing pursuant to
section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part
180 to establish an exemption from the requirement of a tolerance for
the cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride (CAS Reg. No. 51229-78-8), when used as an inert ingredient, a
preservative in pesticide formulations applied to growing crops. EPA
has determined that the petition contains data or information regarding
the elements set forth in section
[[Page 70253]]
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. Residue chemistry data are not generally
required by EPA regarding tolerance exemption petitions. Consequently,
no plant metabolism data have been generated.
2. Analytical method. Since this petition is for an exemption from
the requirement of a tolerance, an enforcement analytical method for
cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride is not needed.
3. Magnitude of residues. Based on the negligible amount of cis-
isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride to
be used in final product formulations (0.14% by weight (wt) or less),
the recommended frequency and rates of application to growing crops,
and the hydrolysis characteristics of cis-isomer of 1-(3-chloroallyl)-
3,5,7-triaza-1-azoniaadamantane chloride with the rapid degradation
action of formaldehyde, the Dow Chemical Company believes that residues
are expected to be essentially undetectable and not toxicologically
significant.
B. Toxicological Profile
In the Dowicil CTAC Reregistration Eligibility Document (RED),
dated April 1995, EPA completed it's assessment of the potential human
health and environmental risks associated with the active ingredient
non-food uses of the cis and trans isomer mixture of 1-(3-chlorallyl)-
3,5,7-triaza-1-azoniaadamantane chloride and the cis-isomer of 1-(3-
chlorallyl)-3,5,7-triaza-1-azoniaadamantane chloride. Due to the
similarities of the two active ingredients the Agency accepted
toxicology studies conducted using either the cis and trans isomer
mixture or the cis isomer only. Thus, the existing data base includes
toxicity studies that were performed with the cis-isomer and the
toxicity studies that were performed with a mixture of the cis and
trans isomers.
1. Acute toxicity--i. Acute oral. Cis-isomer of 1-(3-chloroallyl)-
3,5,7-triaza-1-azoniaadamantane chloride was administered by single-
dose gavage to 6 groups of 6 rats/sex/dose at dosages of 200, 400, 800,
1,600, 3,200, and 6,300 milligrams/kilogram (mg/kg). Clinical signs of
lethargy, diarrhea, and lacrimation, were observed at the 800, 1,600,
and 3,200 mg/kg dose groups. Body tremors and exudate staining of the
nares were also seen in the 3,200 mg/kg group. Animals were observed
for 7 days including the day of treatment. There were no mortalities in
the 200, 400, 800, and 1,600 mg/kg dose groups. Five of six mortalities
occurred in the 3,200 mg/kg dose group within 4 days of treatment, and
6/6 mortalities in the 6,300 mg/kg dose group on day-1 of treatment.
All animals which survived gained weight during the observation period.
There were no treatment-related changes on gross necropsy. The oral
lethal dose (LD)50 (95% confidence interval) was 2,664 mg/kg
for males and females combined.
ii. Acute dermal. Cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane chloride was administered to four rabbits per dose
level. Each dose group was topically treated for 24 hours with 160,
320, 630, 1,300, 2,500, or 5,000 mg/kg of undiluted test material
(moistened with 5 meters/Liter (m/L) of distilled water) and with 250,
500, 1,000, and 2,000 mg/kg of the material as a 50% aqueous solution.
In the undiluted test group, mortality rates were as follows: 160 mg/kg
(0/4); 320 mg/kg (1/4); 630 mg/kg (1/4); 1,300 mg/kg (4/4); 2,500 mg/kg
(2/4); 5,000 mg/kg (3/4).
The acute dermal LD50 (95% confidence interval) was 923
mg/kg for males and females combined with undiluted test material.
Lethargy and anorexia were reported in the surviving animals. Topical
reactions ranging from slight erythema to marked swelling and necrosis
were observed. Treatment-related necropsy lesions (decreased abdominal
adipose tissue, serous atrophy of the remaining adipose tissue and
thymic atrophy) were observed at the two highest dose levels. The
lesions were judged to be the result of stress and decreased appetite.
The number of mortalities observed in the 50% aqueous preparation
was as follows: 250 mg/kg (1/4); 500 (3/4); 1,000 (1/4); 2,000 (4/4).
The acute dermal LD50 (95% confidence interval) was 605
mg/kg for males and females combined. Lethargy and anorexia were
observed in the three lowest dose groups; lethergy and rapid, shallow
breathing were seen in the highest dose group. Topical reactions
ranging from slight edema to marked necrosis were reported. There were
no lesions on necropsy attributable to treatment.
iii. Acute inhalation. In an acute inhalation study 10 rats (5
males/5 females) were exposed to 1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane cloride and cis-1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane chloride. There were no mortalities during the
exposure period nor during the post-exposure observation period. There
was generalized soiling and test material stains on fur. All animals
exhibited a significant weight loss (9-11%) in the first few days post-
exposure. Weight gain resumed 4 days post-exposure to end of study.
Normal activity throughout the test period continued to the end of the
study. One animal had unilateral corneal opacity. All other tissues and
organs examined were normal. The acute inhalation toxicity lethal dose
(LC)50 to 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride and cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride was greater than 4.7 milligrams/Liter (mg/L).
iv. Primary eye irritation. In a primary eye irritation study, nine
New Zealand white rabbits had a 1 gram dose of cis-isomer of 1-(3-
chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride instilled into
the conjunctival sac of the right eye of each of six rabbits (Groups
A). The same procedure was followed with three other rabbits (Group B),
however these eyes were washed with tap water after a 30-second
exposure period. The left eye served as an untreated control in all of
the animals. Twenty four hours prior to treatment, the eyes of all nine
rabbits were examined using 5% fluoresein stain and found to be normal.
The eyes were examined 1, 2, 3, 4, and 7 days after the instillation
and scored for evidence of damage to the conjunctival (redness,
chemosis, and discharge), cornea (degree of opacity and area of cornea
involved), and iris (area involved). In Group A rabbits, there was
slight (3/6) or moderate (1/6) conjunctival redness and slight (1/6)
conjunctival discharge. In Group B rabbits, there was slight (2/3)
conjunctival redness. No corneal opacity was observed with either
group. Signs of irritation were absent 72 and 48 hours in Groups A and
B, respectively. The test material was determined to be a slight
primary eye irritant.
v. Primary dermal irritation. In a primary dermal irritation study,
0.5 grams of undiluted cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane chloride was applied to the backs of six rabbits to an
intact and an abraded site on each animal. The areas were covered with
gauze patch and then a piece of heavy-gauge Saran[reg] film.
Elizabethan collars were placed on the rabbits to prevent ingestion.
After 24 hours of exposure, the bandages were removed and each site was
scored on a scale of 0 (normal) to 4 (severe) for dermal irritation
(erythema and edema) then, and again at 72 hours from the
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initial exposure. There was no evidence of erythema in the intact skin
at either time point. The abraded skin on one animal showed a slight
erythematous reaction at 24 hours; at 72 hours, two abraded areas were
graded very slight and one moderate. The intact skin of one animal
showed very slight edematous reaction at 24 hours. The abraded areas
had either a very slight or slight edematous reaction at both time
points. Cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride was considered to be only a slight irritant.
vi. Dermal sensitization. The dermal sensitization potential of
cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride was tested using the modified Maguire method. Ten male Hartley
Albino guinea pigs received four induction doses of 0.1 milliliter (mL)
of 10% solution of the cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane chloride in 8 days. Freund's Adjuvant was injected
intradermally adjacent to the site at the time of the third
application. On challenge 2 weeks after the last induction application,
the test material produced a positive response in one animal. The
positive control, a 10% solution of DER 331 epoxy resin, confirmed that
the test system was operating appropriately. The study demonstrated
that a 0.1 mL dose of a 10% solution of cis-isomer of 1-(3-
chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride is not a dermal
sensitizer in guinea pigs.
2. Genotoxicity. Cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane chloride was mutagenic in the in vitro Chinese hamster
ovary (CHO) cell hypoxanthine guanine phophoribosyl transferase (HGPRT)
forward mutation assay with activation but nonmutagenic without
activation. Cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane chloride was negative in the rat hepatocyte
unscheduled deoxyribonucleic acid (DNA) synthesis assay. It was
negative also in the mouse micronucleus test.
3. Reproductive and developmental toxicity. A dermal developmental
toxicity study was conducted with Fischer 344 rats. Doses of 0, 250, or
500 mg/kg/day of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride as a 50% aqueous solution were applied to the dorsal skin
daily on gestation days 6 through 15. No significant adverse effects
from treatment with the test compound were found but the study was
considered adequate because the doses were sufficiently high.
4. Subchronic toxicity--i. Dermal subchronic study. In a 13-week
dermal subchronic study, New Zealand white rabbits were given dermal
applications of cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane chloride for 13 weeks. The doses were 0, 50, 200, or
1,000 mg/kg/day. The only treatment related effect was a dose-dependent
increase in ulcerative dermatitis, at the treatment site, that was
correlated with the abrasions from clipping. The NOAEL for systemic
toxicity was 1,000 mg/kg/day.
ii. A 90-day oral subchronic study. One study was conducted to
determine the level of cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane chloride in the diet which would result in complete
acceptance of the diet by rats. Ten rats/sex/group were administered
the chemical in the diet at dosages of 0, 1, 2, or 4 mg/kg/day for 90
days. The only parameters evaluated were body weight, food consumption,
and organ weight (absolute and relative). Male rats in the 4 mg/kg/day
group had a significant decrease in body weight at approximately 36% of
the weighing periods. This group also had a significant decrease in
food consumption throughout the study. The absolute weight of the heart
in the 4 mg/kg/day group males was significantly decreased. The
relative weight of the brain and liver were increased in the 4 mg/kg/
day group of females.
iii. A 90-day oral subchronic study. In another study, cis-isomer
of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride was
administered in the diet to groups of 10 rats/sex/group at dosages of
0, 7.5, 15, 30, and 60 mg/kg/day for 90 days. Mean body weight was
significantly decreased in all the treated males and females throughout
the study. Overall mean body weight gain was decreased in all the
treated groups. Mean food consumption was significantly decreased in
the treated males, especially at the beginning of the study. Although
all of the treated female groups had significantly reduced intake at
some time during the study, females were not as frequently affected as
males. Calculation of feed efficiency values for the overall study and
for the latter half of the study showed that the major effect of
decreased food intake on body weight occurred at the beginning of the
study. However, the decrease in food efficiency does indicate that the
chemical had a toxic effect on body weight that cannot be accounted for
solely by decreased food consumption. The only other possible effect of
treatment was an increase in the incidence of minimal hepatocellular
swelling in the 60 mg/kg/day group males (0/5 in the control vs. 3/5 in
the 60 mg/kg/day group).
iv. A 90-day oral subchronic study. In a dog study, cis-isomer of
1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride was
administered in gelatin capsules to four Beagle dogs/sex/group at
dosages of 0, 7.5, 15, or 30 mg/kg/day for 90 days. One female in the
30 mg/kg/day was sacrificed due to general deterioration on the 84th
day of the study; necropsy revealed ascites with evidence of liver
toxicity. The only other toxicologically significant findings during
the study included a significant decrease in the hematocrit (HCT),
hemoglobin (Hgb), and white blood count (WBC) measurements in the 30
mg/kg/day group males and histopathological changes, especially in the
liver, in the 30 mg/kg/day group males and females. The incidence and/
or severity of several findings in the liver were increased in the 30
mg/kg/day group males and females during the following:
[sbull] Obliterative vasculitis and perivasculitis of the hepatic
blood vessels.
[sbull] Perivascular and pericholangiolar infiltration of
mononuclear cells.
[sbull] Hyperplasia of the reticuloendothelial cells lining the
hepatic sinusoid.
5. Endocrine disruption. No specific tests have been conducted with
cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride to determine whether the chemical may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen
or other endocrine effects. However, there are no significant findings
in other relevant toxicity tests, i.e., developmental toxicity, which
would suggest cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane chloride produces effects characteristic of the
disruption of endocrine function.
C. Aggregate Exposure
Dietary exposure. The proposed use of cis-isomer of 1-(3-
chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride as a preservative
in end-use product formulations applied to growing crops is not
expected to result in significant additional dietary exposure, due to
the low concentration of cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-
1-azoniaadamantane chloride employed in the formulation and the
extremely low probability of contact by the general public following
treatment.
Cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride,
[[Page 70255]]
when used according to good manufacturing practices, meets the
requirements of food additive regulations in 21 CFR 175.105 for use as
a preservative in adhesives; 21 CFR 176.1680 for preservation of
polyurethane resins in contact with dry bulk foods; 21 CFR 176.170 for
preservation of components of paper and paperboard intended for use in
contact with aqueous and fatty foods; and 21 CFR 176.180 for
preservation of components of paper and paperboard intended for use in
contact with dry foods. These uses are not expected to result in
quantifiable residues in the diet when used as a preservative, at low
levels, in end-use agriculture pesticide formulations applied to
growing crops.
D. Cumulative Effects
There is no reliable information that would indicate or suggest
that cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane
chloride has any toxic effects on mammals that would be cumulative with
those of any other chemical.
E. Safety Determination
1. U.S. population. The Dow Chemical Company believes that based on
the following information it is not expected that a tolerance for cis-
isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride is
required because:
[sbull] The cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-
azoniaadamantane chloride is practically nontoxic to slightly toxic to
humans.
[sbull] It will not pose a significant risk to humans.
[sbull] The parent compound as well as formaldehyde formation
dissipate fairly rapidly under hydrolysis.
[sbull] The level of cis-isomer of 1-(3-chloroallyl)-3,5,7-triaza-
1-azoniaadamantane chloride to be included as a preservative in
pesticide formulations applied to growing crops will be at low levels
(0.14% by weight or less).
Therefore, it is not anticipated that a tolerance for the cis-
isomer of 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride
would be necessary to protect the public health.
2. Infants and children. An exemption from a tolerance as proposed
is expected to be negligible and not place infants and children at
increased health risks.
F. International Tolerances
There are no known international tolerances for cis-isomer of 1-(3-
chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride.
[FR Doc. E3-00560 Filed 12-16-03; 8:45 am]
BILLING CODE 6560-50-S