[Federal Register Volume 68, Number 242 (Wednesday, December 17, 2003)]
[Notices]
[Pages 70251-70255]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E3-00560]



[[Page 70251]]

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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: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
    [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 [email protected], 
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

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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