Alkyl Ether Amine Dicarboxyethyl Sodium Salts; Notice of Filing a Pesticide Petition to Establish a Tolerance Exemption for a Certain Pesticide Chemical in or on Food, 7103-7108 [05-2620]
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Federal Register / Vol. 70, No. 27 / Thursday, February 10, 2005 / Notices
(OCHP) activities and a presentation on
assessing cancer risks from early life
exposure. Other potential agenda items
include a panel discussion of the NAS
review of EPA’s Perchlorate Risk
Assessment, and a presentation on
PBDE.
Dated: February 2, 2005.
Elizabeth H. Blackburn,
Acting Designated Federal Official.
U.S. Environmental Protection Agency
Children’s Health Protection Advisory
Committee, Hotel Washington, 515 15th
Street, NW., Washington, DC 20004–
1099, February 22–24, 2005
Draft Agenda
Tuesday, February 22, 2005
Work Group Meetings
Wednesday, February 23, 2005
Plenary Session
9:00 Welcome, Introductions, Review
Meeting Agenda
9:15 Highlights of Recent OCHP
Activities
9:45 Presentation: Cancer Guidelines
Update
10:15 Break
10:30 Science and Regulatory
Workgroup Reports
12:00 Lunch (on your own)
1:30 Panel Discussion: NAS Review of
EPA’s Perchlorate Risk Assessment
3:00 Break
3:30 Presentation and Discussion:
OCHP Strategic Plan
5:15 Public Comment
Thursday, February 24, 2005
8:45 Discussion of Day One
9:00 Presentation: PBDE Update
10:15 Break
10:45 Presentation: Update on EPA’s
Response to CHPAC Mercury
Comment Letters
11:45 Wrap Up/Next Steps
[FR Doc. 05–2611 Filed 2–9–05; 8:45 am]
BILLING CODE 6560–50–P
ENVIRONMENTAL PROTECTION
AGENCY
[OPP–2005–0010; FRL–7695–9]
Alkyl Ether Amine Dicarboxyethyl
Sodium Salts; Notice of Filing a
Pesticide Petition to Establish a
Tolerance Exemption for a Certain
Pesticide Chemical in or on Food
Environmental Protection
Agency (EPA).
ACTION: Notice.
AGENCY:
SUMMARY: This notice announces the
initial filing of a pesticide petition
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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–2005–
0010, must be received on or before
March 14, 2005.
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.
Keri
Grinstead, Registration Division
(7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 308–8373; e-mail
address:grinstead.keri@epa.gov.
FOR FURTHER INFORMATION CONTACT:
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by
this action if you 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. Docket. EPA has established an
official public docket for this action
under docket ID number OPP–2005–
0010. 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
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whose disclosure is restricted by statute.
The official public docket is the
collection of materials that is available
for public viewing at the Public
Information and Records Integrity
Branch (PIRIB), Rm. 119, Crystal Mall
#2, 1801 S. Bell St., Arlington, VA. This
docket facility is open from 8:30 a.m. to
4 p.m., Monday through Friday,
excluding legal holidays. The docket
telephone number is (703) 305–5805.
2. Electronic access. You may access
this Federal Register document
electronically through the EPA Internet
under the ‘‘Federal Register’’ listings at
https://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 https://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
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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 email 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
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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 https://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–2005–0010. 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–
2005–0010. 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–2005–0010.
3. By hand delivery or courier. Deliver
your comments to: Public Information
and Records Integrity Branch (PIRIB),
Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm.
119, Crystal Mall #2, 1801 S. Bell St.,
Arlington, VA, Attention: Docket ID
number OPP–2005–0010. 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
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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);
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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: January 25, 2005.
Lois Rossi,
Director, Registration Division, Office of
Pesticide Programs.
Summary of Petition
The petitioner summary of the
pesticide petition is printed below as
required by FFDCA section 408(d)(3).
The summary of the petition was
prepared by Tomah3 Products, Inc. and
represents the view of the petitioner.
However, the summary may have been
edited by EPA if the terminology used
was unclear, the summary contained
extraneous material, or the summary
unintentionally made the reader
conclude that the findings reflected
EPA’s position and not the position 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.
Tomah3 Products, Inc.
PP 4E6861
Summary of Petitions
EPA has received a pesticide petition
4E6861 from Tomah3 Products, Inc., 337
Vincent Street (P.O. Box 388), Milton,
Wisconsin 53563–0388 proposing,
pursuant to section 408(d) of the Federal
Food, Drug, and Cosmetic Act (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 use of
any member of the class of amphoteric
surfactant inert ingredients described as
[beta-alanine, N-(2-carboxyethyl)- N-[3(polyoxaalkylalkoxy)propyl]-, (mono- or
disodium salt) and polyalkoxy, a-[3[bis(2-carboxyethyl)amino]propyl]-walkoxy, (mono- or disodium salt),
containing 0 to 20 repeating alkoxy/
polylalkoxy units (methoxy-, ethoxy-,
propoxy-, butoxy-) and 6 to 21 carbons
in an n-alkyloxy-, isoalkyloxy- or
branched alkyloxy- chain; also known
as alkyl ether amine dicarboxyethyl
sodium salts, in or on all raw
agricultural commodities and food. EPA
has determined that the petition
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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 supports granting of
the petition. Additional data may be
needed before EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. Any residues are
expected to be parent amphoteric
amines as described above.
2. Analytical method. Since this
petition is for an exemption from the
requirement of a tolerance, an analytical
method is not required.
3. Magnitude of residues. This
application is designed to follow EPA’s
new methodology for the evaluation of
low toxicity substances used in
pesticide products. To develop exposure
estimates, residue data for pesticide
active ingredients were used as
described below as surrogate data for
the class of inert ingredients. Several
complementary approaches were used.
Tier 1 Screening Level scenarios (i.e.,
bounding extreme worst-case) included
the following exposure assumptions.
Actual crop-specific residue data for
active ingredients, including secondary
residues were used as surrogates for the
surfactants without adjustment for the
percentage of inert in the formulation.
Data were used for all herbicides used
at >5 million pounds/year (lbs/yr) and
all fungicides and insecticides used at
>1 million lbs/yr, including all active
ingredients used in significant amount
on the top 25 crops consumed by
children; Both acute and chronic
exposure levels were determined; The
assessment assumed that 100% of all
crops are treated with pesticides
containing the surfactants.
More sophisticated Tier 2 worst-case
scenarios included the following
exposure assumptions. For chronic
exposure, actual crop-specific residue
data are used as surrogates for the
surfactants, with adjustment for
percentage of the inert in the
formulation using an upper-bound value
of 17.1%; frequency of detection of
pesticides was used as a method of
ranking all pesticides monitored in the
U.S. for residues. The top 30 pesticides
were found to account for 99.9% of the
total dietary intake of pesticide residues
and were selected as the surrogates to
use in estimating exposure. Exposure
levels were determined using actual
residue and frequency data for the 30
most frequently detected residues.
For acute exposures, EPA’s
Cumulative OP Acute Dietary Exposure
Distribution estimated for children 1–2
years in Florida (EPA, 2002) was used
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as a surrogate. No adjustment was made
to convert the active ingredient
exposure for actual percentage of inert
ingredient used in the formulation. The
methamidophos-equivalent exposure
estimates were used directly to
approximate the magnitude of potential
acute dietary exposures to the
amphoteric surfactants. Exposure
estimates were made for the 90th%,
95th% and 99.9th% consumption.
B. Toxicological Profile
1. Acute toxicity. Only a small amount
of primary data are available on the
acute toxicity of substances within the
proposed class of amphoteric
surfactants. These data have been
supplemented in the assessment
described below by using publicly
available data on the toxicology of alkyl
amines and related derivatives.
i. Acute dermal toxicity and eye
irritation. Virtually all of the amines
when administered directly or in
concentrated solution are primary skin
and eye irritants. Animals exposed to
concentrated vapors exhibit signs and
symptoms of mucous membrane and
respiratory tract irritation. Direct skin
contact with liquid amines can produce
severe burns and necrosis. Little toxicity
information is available on amines
containing eight or more carbons. But, it
is clear that these amines, either as the
neat liquid, or in concentrated solution,
would be strong local irritants for eyes,
skin, and mucous membranes. The
lowered vapor pressure for the higher
alkyl amines would tend to reduce the
hazard from vapor exposure.
ii. Acute oral toxicity. Estimated LD50
for amphoteric compounds 300 to 500
milligrams/Kilogram (mg/kg). The LD50s
for the shorter chain primary amines
(C2–C8) are in the 300 to 500 mg/kg
range. Secondary amines are slightly
more toxic than the corresponding
primary amines. As the chains increase
in length beyond C12 to C16 there is an
observable reduction in toxicity. For
example, the acute oral LD50 for
octadecylamine (C18H39N) in mice and
rats is approximately 2–3 gram/kilogram
(g/kg) compared to the 300 to 500 mg/
kg range for the shorter chain amines.
The addition of an alcohol group to the
molecule reduces the toxicity
significantly. The alkanolamines and
the alkylalkanolamines are typically 3–
5 times less toxic than their amine
congeners. For this reason it is expected
that the addition of propoxylate or
ethoxylate groups will not confer
additional toxicity beyond that of the
amine itself, and is likely to tower
toxicity substantially.
iii. Alkyl amines vs alkanolamines.
The acute toxicity of the alkylamines are
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reduced from 4 to 20–fold by the
introduction of hydroxyl groups into the
molecule. The toxicity of the alkyl
amines is reduced approximately 5–fold
as the molecular weight increases from
C2 - C16 and higher.
iv. Effect of carboxylic acid salts. This
trend of decreasing acute toxicity with
the addition of polar groups persists
when the added groups are acetate or
propionate carboxylic acid salts. These
are the groups found in the amphoteric
surfactants which are the subject of this
submission. The acute toxicity of the
C10–C12 alkyl amines is reduced from
2 to 15–fold when the alkyl groups on
the nitrogen atom are replaced by either
propionate or acetate salts.
2. Genotoxicity. There is no indication
that any alkyl amine is mutagenic.
Zeiger et al. (Ref. 1) reported on the
Salmonella Mutagenicity of 255
chemicals including 25 alkyl amines.
Twenty three of the alkyl amines tested
negative in the Ames test both with and
without activation and only two
substituted amines were weakly positive
(N-hydroxyethylethylenediamine and
monoisopropanolamine).
3. Reproductive and developmental
toxicity. Genamin TA (CAS # 61790–33–
8), a mixture consisting primarily of
C16–C18 primary amines was given to
both male and female rats 14 days prior
to mating continually for 54 days
thereafter (Ref. 2). The author noted that
the NOAEL for parental toxicity and for
effects on offspring was 12.5mg/kg. The
reported NOAEL for fertility was 50 mg/
kg.
4. Subchronic toxicity. N-methyl- Noctadecyl-1-octadecanamine was
administered to rats for 90–days at
doses of 1,500; 5,000; and 15,000 ppm
in the diet. Doses were reduced after
week 4 to 1,500; 4,000 and 10,000 ppm.
The presence of histiocytosis in all
groups precluded the establishment of a
NOEL in this dose range. The LOAEL
was 1,500 ppm or 75 mg/kg/day (Ref. 3).
Subchronic studies have also been
conducted on a few alkanolamines.
Ethomeen T/12 (CAS # 61791–44–4)
Ethanol,2,2-iminobis-, N-tallow alkyl
derivatives at doses of 15, 50, 150, and
450 mg/kg were fed to rats in their diet
for 90–days. Ethomeen T/12 is a mixture
of polyoxyethylene tallow amines. Gross
macroscopic effects were seen and body
weight gain was reduced only at the 450
mg/kg level. Microscopic findings were
seen in the intestine and regional
mesenteric nodes levels of 150 mg/kg
and greater. The no observed adverse
effect level (NOAEL) was 50 mg/kg and
the lowest observed adverse effect level
(LOAEL) was 150 mg/kg. A similar
study was conducted in dogs at doses of
13, 40, and 120 mg/kg. Vomiting
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occurred at doses of 40 mg and higher.
No gross pathologic variations or lesions
were observed in any dose group.
Histological evaluation revealed an
increase in the incidence of foamy
macrophages in the small intestine and
regional lymph nodes in the 40 mg/kg
and 120 mg/kg dose groups. The
NOAEL was 13 mg/kg/day and the
LOAEL 50 mg/kg/day (Ref. 4).
5. Chronic toxicity. Octadecylamine
[CH3(CH2)17 NH2] has been
administered to rats in a 2–year rat
feeding study (Ref. 5). The NOAEL was
500 parts per million (ppm) in the diet
and 3,000 ppm was a LOAEL. Rats fed
3,000 ppm showed some weight loss,
anorexia, and some histological changes
in the gastrointestinal tract, mesenteric
nodes, and liver. This NOAEL gives an
ADI of 0.25 mg/kg body weight/day
(bwt/day) using a 100–fold safety factor.
(500 ppm in old rats corresponds to 25
mg/kg bw/day). An earlier 1–year oral
study in dogs by Deichmann (Ref. 6),
reported a slight weight decrement at
the highest of three doses (0.6, 3.0, and
15 mg/kg bwt/day). The NOEL from this
study was 3.0 mg/kg bwt/day. A
corresponding ADI would be 0.03 mg/kg
bwt/day, or about 8–fold lower than the
study in rats.
Most of the amine repeat-dose
toxicology studies yield NOAELs in the
3 to 50 mg/kg bwt/day range. The lowest
repeated dose NOAEL in these reports is
3.0 mg/kg bwt/day (both rabbit
developmental study with olelyamine
and 1–year chronic dog study with
octadecyl amine). The application of
these data for amphoteric amines
depends on the toxicity of other
members of this surfactant family
having the same or lesser order of
toxicity as the long chain fatty amines.
The amphoterics in this submission
differ from the simpler alkyl amines in
two ways; first they are alkoxylated,
which introduces polar ether linkages,
second they additionally have two
charged carboxyl groups on the end of
the molecule. Both of these charges
make the molecule more polar, and can
decrease the systemic toxicity of the
substance. The increased polarity
canmake the substances easier to
eliminate in the urine. The increased
number of ether linkages can make the
substance harder to absorb. For these
reasons, we believe that the NOELS of
the ether amines establish an upper
bound to the toxicity of the amphoterics
at approximately 10 mg/kg bw/day; the
amphoterics themselves should be
considerably less toxic. Given that there
are norepeat-dose toxicity data in
animals available on the amphoterics,
we have endeavored, via a weight-ofevidence approach, to demonstrate that
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as the alkyl amine core of the molecule
is modified by the introduction of polar
constituents, the toxicity is decreased.
Thus the toxicity of the amphoterics
will be below that of the amines. In the
discussion below, we show how the
introduction of polar groups reduces the
toxicity of several related classes of
substances and how an average
numerical bound might be placed on
this effect.
With reference to the report of the
American Chemistry Council’s report of
the Fatty Nitrogen Derivatives Panel
Amines Task Group (Ref. 7), if alkyl
(C10 - C16) dimethyl amine oxide is
compared to the corresponding or
similar alkyl amine it is seen that the
toxicity drops by approximately 10-fold.
The NOEL for alkyl (C10 - C16)
dimethyl amine oxide in a chronic rat
study is 42.3 mg/kg bw/day. The NOEL
in a 90-day rat study was the same. The
urine was the primary pathway for
elimination and excretion was largely
complete in 24 hours (Ref. 8). In
contrast the maternal toxicity NOEL for
Cis- 9-octadecenylamine was 10 mg/kg
bw/day in rats and 3 mg/kg bw/day in
rabbits. The NOEL for octadecylamine
in a 1-year oral gavage study in rats was
3 mg/kg bw/day. It is seen that the
conversion of the amine to the amine
oxide tends to reduce the repeat-dose
toxicity by approximately 3 to 10-fold.
In a similar manner the acute toxicity of
the alkylamines are reduced from 4 to
20-fold by the introduction of hydroxyl
groups into the molecule, and the
toxicity of the alkyl amines is reduced
approximately 5-fold as the molecular
weight increases from C2 to C16 and
higher.
6. Animal metabolism. The aliphatic
amines are well absorbed from the gut
and respiratory tract. They are either
excreted intact or in the form of
metabolites, depending on the course of
metabolism, which depends on their
structure. Monamine oxidases are
mitichondrial enzymes that catalyze the
oxidation of many primary amines to
the corresponding aldehyde and
ammonia. The aldehydes are further
oxidized to the correspondingcarboxylic
acid and the ammonia to urea. In
addition microsomal enzymes can
metabolize amines not readily
transformed by monoamine oxidases,
through a variety of pathways. These
include: deamination, methylation, Ndealkylation, N-oxidation, Nacetylation, cyclization, Nhydroxylation, and nitrosation.
7. Metabolite toxicology. Secondary
amines are prone to react with nitrite,
depending on the pH of the media, to
form nitrosamines, some of which are
potent animal carcinogens. Some
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studies have suggested the possibility of
in vivo formation of carcinogenic
nitrosamines within the acidic
environment of the stomach following
ingestion of secondary amines. The
major human intake of nitrates (∼ 50
mg/day) comes from vegetables, water
supplies, or additives in the meat and
fish curing process (Ref. 9). Nitrates are
converted to nitrites in the upper part of
the gastrointestinal tract by
nitroreductase bacteria normally present
in the lower bowel.
Amines or amine precursors are
present in vegetables, wine, spirits, beer,
tea, fish, food flavoring agents, and
some drugs. As indicated above, at least
10 mg of amine nitrogen is excreted per
day; the intake of amines or their
precursors is therefore probably in the
100 mg/day range. Thus there exists the
required elements for the in vivo
formation of carcinogenic nitrosamines
from amine ingestion. Despite this
theoretical possibility, epidemiologic
studies have not provided evidence for
a causal association between nitrite
exposure and human cancer. Nor has a
causal link been shown between Nnitroso compounds preformed in the
diet or endogenously synthesized and
the incidence of human cancer (Ref. 10).
It has been demonstrated in animals that
nitrosation of diethylamine and
dimethyamine in vivo is a very slow
process. When these substances were
fed to rats together with nitrite for over
two years no tumors typical of treatment
of rats with nitrosodiethylamine were
observed (Ref. 11). In any event, the
addition to the diet of nanogram levels
of amines from the proposed used of
amine based surfactants is insignificant
compared to normal endogenous levels
and to those naturally occurring in food.
8. Endocrine disruption. There is no
evidence to suggest that the alkyl
amines have an effect on any endocrine
system. In developmental and twogeneration reproduction toxicity tests
systemic toxicity was noted but no
developmental or reproductive effects
were found.
C. Aggregate Exposure
1. Dietary exposure. Exposure through
both food and drinking water were
estimated using data and methods more
commonly applied to pesticide active
ingredients. The methods for estimating
dietary exposure are discussed above
under residues. Drinking water
exposures were estimated using EPA’s
combined Pesticide Root Zone Model/
Exposure Assessment Modeling System
(PRZM/EXAMS) and the 1 hectare pond
scenario.
i. Food. Both Tier 1 and Tier 2, acute
and chronic dietary assessments were
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constructed in several different ways
and in general MOEs >100 were found.
Tier 1 acute assessments did yield
MOEs <100, but the Tier 2 analysis gave
an MOE = 1,500 for the lowest Tier 1
scenario.
ii. Drinking water. Using the average
peak value fromPRZM/EXAMS
modeling for acute exposure, the
average 60-day concentration for
chronic exposure and the standard
estimates of water consumption, acute
and chronic margins of exposure for
drinking water all MOEs were greater
than 360. In using the model, maximum
application rates and number of
applications were assumed and the
amphoteric surfactants were assumed
not to degrade in water or the
environment. The modeling provides an
extreme worst-case estimate of exposure
in that the peak values simulated
accumulation (i.e., no degradation) of
the surfactants in water during a 30
years period of application.
2. Non-dietary exposure. For nondietary exposure and risk analysis
outdoor lawn care with broadcast
application via hose-end sprayer was
selected as the worst case. Dermal
absorption was assumed to be 10%.
Applicators were assumed to have
dermal and inhalation exposures, while
re-entry exposures were dermal and
oral, the oral via hand-to-mouth
activities by children. MOE’s >100 were
estimated by Tier 1 analyses, indicating
reasonable certainty of no harm for the
worst-case bounding scenario evaluated.
D. Cumulative Effects
Other amphoteric amine compounds
may be used in pesticide formulations.
However, the assessment of this class of
compounds assumes 100% of the
pesticide products applied to crops will
use one member of this class of
amphoteric amines. Therefore, the
cumulative risk for this class of
compound is covered by the
assessments in this submission.
E. Safety Determination
1. U.S. population. As a general rule
in any pesticide assessments, exposures
of children are the highest of any
subpopulation. This pattern was found
to hold true for the amphoteric
surfactants and lead to simplifications
in the assessment procedure. When
exposures to children were found to be
acceptable, e.g., acute and chronic Tier
2 estimated dietary exposures to
children yielded large MOEs, separate
estimates for other subpopulations were
not deemed necessary. In the risk
assessment we ultimately have adopted
the dietary exposures for children for all
subpopulations. Exposures for females
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7107
13 to 49 were calculated in certain
instances and found to be comparable to
each other and less than for children.
Hence, exposure estimates for the latter
were not formally completed. Rather the
exposure numbers for females were
assumed for the full U.S. population.
2. Infants and children. Except when
using acute Tier 1 dietary exposure
estimates and the most conservative
toxicity endpoint, 3 mg/kg-bw/day, all
MOEs were found to be comfortably
greater than 100. Given the worst-case
conservatism built into all the analyses,
the results support a conclusion that
Tomah3’s amphoteric surfactants may be
used safely in pesticide formulations
without concerns for dietary and nonoccupational exposures.
F. References
1. Zeiger, E., Anderson B., Haworth
S., Lawlor T., Mortelmans K., and
Speck, W. (1987) ‘‘Salmonella
Mutagenicity tests: III. Results from the
testing of 255 chemicals.’’
Environmental Mutagenesis, (1987) 3:
Suppl (9)1–110.)
2. Bussi R (2000). ‘‘Genamin TA100:
Reproduction/Development toxicity
Screening Test in rats by oral route.’’
APAG, Instituto di Recerche
Biomediche, ‘Santoine Marxer’ S.p.a.
3. Procter and Gamble, Ref. 3) EPA
submission, No. 88—9200007039,
microfiche No. 0T5537649.
4. Goater T.O., Griffiths D.,
McElliogott T.F., and AAB Swan, A.A.B,
(1970), ‘‘Summary of toxicology data acute oral toxicity and short-term
feeding studies on polyoxythylene
tallow amines in rats and dogs,’’ Food
and Cosmetics Toxicology 8:249—252.
5. Deichmann, W.B., Radomski, J.I.,
MacDonald, W.E., Kascht, R.L., and
Erdman, R.l., (1958), American Medical
Association Archives of Industrial
Health, 18:483.
6. Deichmann, W.B., et.al., (1957),
Archives Of Industrial Health, 18:483–
487.
7. Fatty Nitrogen Derivatives Panel
Amines Task Group, 2002, Fatty
Nitrogen Derived (FND) Amines
Category High Production Volume
(HPV) Chemicals Challenge, American
Chemistry Council, Washington, D.C.
8. U.S. EPA. 1999. The Use of
Structure-activity Relationships (SAR)
in the High Production Volume
Chemicals Challenge Program. https://
www.epa.gov/ch emrtk/sarfinl1.htm.
9. Ellen et al. 1990. Food Additives
Contaminants 7(2):207—221.
10. Gangilli., S.D., 1999, ‘‘Nitrate,
nitrite and N-nitroso compounds‘‘in
Ballintine, B., Marrs, T., and Turner, P.,
General and Applied Toxicology,
Stockton Press, New York, p 2111, 2143.
E:\FR\FM\10FEN1.SGM
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Federal Register / Vol. 70, No. 27 / Thursday, February 10, 2005 / Notices
11. Druckery et al, 1963 Cited by
Benya et al., Patty’s, 4th Ed. Vol II, Part
B, page 1097.
[FR Doc. 05–2620 Filed 2–9–05; 8:45 am]
BILLING CODE 6560–50–S
ENVIRONMENTAL PROTECTION
AGENCY
[FRL–7871–4]
Carolina Steel Drum Superfund Site;
Notice of Proposed Settlement
Environmental Protection
Agency (EPA).
ACTION: Notice of proposed settlement.
4, (WMD–SEIMB), 61 Forsyth Street,
SW., Atlanta, Georgia 30303, (404) 562–
8887, Batchelor.Paula@EPA.Gov.
Written comments may be submitted
to Ms. Batchelor within 30 calendar
days of the date of this publication.
Dated: January 26, 2005.
Rosalind H. Brown,
Chief, Superfund Enforcement & Information
Management Branch, Waste Management
Division.
[FR Doc. 05–2612 Filed 2–9–05; 8:45 am]
BILLING CODE 6560–50–M
AGENCY:
SUMMARY: The United States
Environmental Protection Agency is
proposing to enter into a settlement for
the partial reimbursement of past
response costs with fifty-four (54) de
minimis parties pursuant to section 122
of the Comprehensive Environmental
Response, Compensation, and Liability
Act (CERCLA), 42 U.S.C. 9622(h)(1)
concerning the Carolina Steel Drum
Superfund Site (Site) located in Rock
Hill, York County, South Carolina. EPA
will consider public comments on the
proposed settlement for March 14, 2005.
EPA may withdraw from or modify the
proposed settlement should such
comments disclose facts or
considerations which indicate the
proposed settlement is inappropriate,
improper or inadequate. Copies of the
proposed settlement are available from:
Ms. Paul V. Batchelor, U.S. EPA, Region
ENVIRONMENTAL PROTECTION
AGENCY
[FRL–7871–5]
Carolina Steel Drum Superfund Site;
Notice of Proposed Settlement
Environmental Protection
Agency (EPA).
ACTION: Notice of proposed settlement.
AGENCY:
SUMMARY: The United States
Environmental Protection Agency is
proposing to enter into a settlement for
the partial reimbursement of past
response costs with the de minimis
party Gresco Manufacturing, Inc.
pursuant to section 122 of the
Comprehensive Environmental
Response, Compensation, and Liability
Act (CERCLA), 42 U.S.C. 9622(h)(1)
concerning the Carolina Steel Drug
Superfund Site (Site) located in Rock
Hill, York County, South Carolina. EPA
will consider public comments on the
proposed settlement for March 14, 2005.
EPA may withdraw from or modify the
proposed settlement should such
comments disclose facts or
considerations which indicate the
proposed settlement is inappropriate,
improper or inadequate. Copies of the
proposed settlement are available from
Ms. Paula V. Batchelor, U.S. EPA,
Region 4, (WMD–SEIMB), 61 Forsyth
Street, SW., Atlanta, Georgia 30303,
(404) 562–8887,
Batchelor.Paula@EPA.gov.
Written comments may be submitted
to Ms. Batchelor within 30 calendar
days of the date of this publication.
Dated: January 26, 2005.
Rosalind H. Brown,
Chief, Superfund Enforcement & Information
Management Branch, Waste Management
Division.
[FR Doc. 05–2613 Filed 2–9–05; 8:45 am]
BILLING CODE 6560–5O–M
FEDERAL COMMUNICATIONS
COMMISSION
Sunshine Act Meeting; Open
Commission Meeting Thursday,
February 10, 2005
February 3, 2005.
The Federal Communications
Commission will hold an Open Meeting
on the subjects listed below on
Thursday, February 10, 2005, which is
scheduled to commence at 9:30 a.m. in
Room TW–C305, at 445 12th Street,
SW., Washington, DC.
Item No.
Bureau
Subject
1 ...............
Media ..........................................................
2 ...............
Media ..........................................................
3 ...............
Consumer & Governmental Affairs ............
4 ...............
Consumer & Governmental Affairs ............
Title: Carriage of Digital Television Broadcast Signals: Amendments to part 76 of the
Commission’s Rules (CS Docket No. 98–120).
Summary: The Commission will consider a Second Report and Order and First Order
on Reconsideration concerning the carriage obligations of cable operators with respect to digital broadcasters.
Title: WRGT Licensee, LLC for Assignment of License of WRGT–TV, Dayton, Ohio,
to WRGT Licensee, LLC (New Nevada, LLC); WVAH Licensee, LLC for Assignment of License of WVAH–TV, Charleston, West Virginia, to WVAH Licensee, LLC
(New Nevada, LLC); WTAT Licensee, LLC for Assignment of License of WTAT–TV,
Charleston, South Carolina, to WTAT Licensee, LLC (New Nevada, LLC);
Cunningham Broadcasting Corp. (Transferor) and Sinclair Acquisition XIII, Inc.
(Transferee) for consent to transfer of control of television station WTTE–TV, Columbus, Ohio; Cunningham Broadcasting Corp. (Transferor) and Sinclair Acquisition
XIII, Inc. (Transferee) For consent to transfer of control of television station WNUV–
TV, Baltimore, Maryland.
Summary: The Commission will consider a Memorandum Opinion and Order concerning an Application for Review filed by various licensee subsidiaries of Sinclair
Broadcast Group, Inc. seeking review of a decision by the Media Bureau dismissing applications through which Sinclair sought to acquire television stations
from the licensee subsidiaries of Cunningham Broadcasting Corporation.
Title: Rules and Regulations Implementing the Telephone Consumer Protection Act of
1991 (CG Docket No. 02–278).
Summary: The Commission will consider a Second Order on Reconsideration addressing petitions for reconsideration filed regarding the national do-not-call registry
and other TCPA rules.
Title: Rules and Regulations Implementing Minimum Customer Account Record Exchange Obligations on All Local and Interexchange Carriers (CG Docket No. 02–
386).
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16:20 Feb 09, 2005
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E:\FR\FM\10FEN1.SGM
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Agencies
[Federal Register Volume 70, Number 27 (Thursday, February 10, 2005)]
[Notices]
[Pages 7103-7108]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-2620]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
[OPP-2005-0010; FRL-7695-9]
Alkyl Ether Amine Dicarboxyethyl Sodium Salts; Notice of Filing a
Pesticide Petition to Establish a Tolerance Exemption for a Certain
Pesticide Chemical in or on Food
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
-----------------------------------------------------------------------
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-
2005-0010, must be received on or before March 14, 2005.
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: Keri Grinstead, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 308-8373; e-mail address:grinstead.keri@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you 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. Docket. EPA has established an official public docket for this
action under docket ID number OPP-2005-0010. The official public docket
consists of the documents specifically referenced in this action, any
public comments received, and other information related to this action.
Although, a part of the official docket, the public docket does not
include Confidential Business Information (CBI) or other information
whose disclosure is restricted by statute. The official public docket
is the collection of materials that is available for public viewing at
the Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall 2, 1801 S. Bell St., Arlington, VA. This docket
facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The docket telephone number is (703) 305-
5805.
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at https://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 https://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
[[Page 7104]]
without change, unless the comment contains copyrighted material, CBI,
or other information whose disclosure is restricted by statute. When
EPA identifies a comment containing copyrighted material, EPA will
provide a reference to that material in the version of the comment that
is placed in EPA's electronic public docket. The entire printed
comment, including the copyrighted material, will be available in the
public docket.
Public comments submitted on computer disks that are mailed or
delivered to the docket will be transferred to EPA's electronic public
docket. Public comments that are mailed or delivered to the docket will
be scanned and placed in EPA's electronic public docket. Where
practical, physical objects will be photographed, and the photograph
will be placed in EPA's electronic public docket along with a brief
description written by the docket staff.
C. How and to Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through hand
delivery/courier. To ensure proper receipt by EPA, identify the
appropriate docket ID number in the subject line on the first page of
your comment. Please ensure that your comments are submitted within the
specified comment period. Comments received after the close of the
comment period will be marked ``late.'' EPA is not required to consider
these late comments. If you wish to submit CBI or information that is
otherwise protected by statute, please follow the instructions in Unit
I.D. Do not use EPA Dockets or e-mail to submit CBI or information
protected by statute.
1. Electronically. If you submit an electronic comment as
prescribed in this unit, EPA recommends that you include your name,
mailing address, and an e-mail address or other contact information in
the body of your comment. Also, include this contact information on the
outside of any disk or CD ROM you submit, and in any cover letter
accompanying the disk or CD ROM. This ensures that you can be
identified as the submitter of the comment and allows EPA to contact
you in case EPA cannot read your comment due to technical difficulties
or needs further information on the substance of your comment. EPA's
policy is that EPA will not edit your comment, and any identifying or
contact information provided in the body of a comment will be included
as part of the comment that is placed in the official public docket,
and made available in EPA's electronic public docket. If EPA cannot
read your comment due to technical difficulties and cannot contact you
for clarification, EPA may not be able to consider your comment.
i. EPA Dockets. Your use of EPA's electronic public docket to
submit comments to EPA electronically is EPA's preferred method for
receiving comments. Go directly to EPA Dockets at https://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-2005-0010. 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-2005-0010. 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-2005-0010.
3. By hand delivery or courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Office of Pesticide
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall
2, 1801 S. Bell St., Arlington, VA, Attention: Docket ID
number OPP-2005-0010. 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);
[[Page 7105]]
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: January 25, 2005.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by FFDCA section 408(d)(3). The summary of the petition was
prepared by Tomah3 Products, Inc. and represents the view of
the petitioner. However, the summary may have been edited by EPA if the
terminology used was unclear, the summary contained extraneous
material, or the summary unintentionally made the reader conclude that
the findings reflected EPA's position and not the position 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.
Tomah3 Products, Inc.
PP 4E6861
Summary of Petitions
EPA has received a pesticide petition 4E6861 from
Tomah3 Products, Inc., 337 Vincent Street (P.O. Box 388),
Milton, Wisconsin 53563-0388 proposing, pursuant to section 408(d) of
the Federal Food, Drug, and Cosmetic Act (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 use of any member of the class of amphoteric
surfactant inert ingredients described as [beta-alanine, N-(2-
carboxyethyl)- N-[3-(polyoxaalkylalkoxy)propyl]-, (mono- or disodium
salt) and polyalkoxy, a-[3-[bis(2-carboxyethyl)amino]propyl]-w-alkoxy,
(mono- or disodium salt), containing 0 to 20 repeating alkoxy/
polylalkoxy units (methoxy-, ethoxy-, propoxy-, butoxy-) and 6 to 21
carbons in an n-alkyloxy-, isoalkyloxy- or branched alkyloxy- chain;
also known as alkyl ether amine dicarboxyethyl sodium salts, in or on
all raw agricultural commodities and food. 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
supports granting of the petition. Additional data may be needed before
EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. Any residues are expected to be parent
amphoteric amines as described above.
2. Analytical method. Since this petition is for an exemption from
the requirement of a tolerance, an analytical method is not required.
3. Magnitude of residues. This application is designed to follow
EPA's new methodology for the evaluation of low toxicity substances
used in pesticide products. To develop exposure estimates, residue data
for pesticide active ingredients were used as described below as
surrogate data for the class of inert ingredients. Several
complementary approaches were used.
Tier 1 Screening Level scenarios (i.e., bounding extreme worst-
case) included the following exposure assumptions. Actual crop-specific
residue data for active ingredients, including secondary residues were
used as surrogates for the surfactants without adjustment for the
percentage of inert in the formulation. Data were used for all
herbicides used at >5 million pounds/year (lbs/yr) and all fungicides
and insecticides used at >1 million lbs/yr, including all active
ingredients used in significant amount on the top 25 crops consumed by
children; Both acute and chronic exposure levels were determined; The
assessment assumed that 100% of all crops are treated with pesticides
containing the surfactants.
More sophisticated Tier 2 worst-case scenarios included the
following exposure assumptions. For chronic exposure, actual crop-
specific residue data are used as surrogates for the surfactants, with
adjustment for percentage of the inert in the formulation using an
upper-bound value of 17.1%; frequency of detection of pesticides was
used as a method of ranking all pesticides monitored in the U.S. for
residues. The top 30 pesticides were found to account for 99.9% of the
total dietary intake of pesticide residues and were selected as the
surrogates to use in estimating exposure. Exposure levels were
determined using actual residue and frequency data for the 30 most
frequently detected residues.
For acute exposures, EPA's Cumulative OP Acute Dietary Exposure
Distribution estimated for children 1-2 years in Florida (EPA, 2002)
was used as a surrogate. No adjustment was made to convert the active
ingredient exposure for actual percentage of inert ingredient used in
the formulation. The methamidophos-equivalent exposure estimates were
used directly to approximate the magnitude of potential acute dietary
exposures to the amphoteric surfactants. Exposure estimates were made
for the 90th%, 95th% and 99.9th%
consumption.
B. Toxicological Profile
1. Acute toxicity. Only a small amount of primary data are
available on the acute toxicity of substances within the proposed class
of amphoteric surfactants. These data have been supplemented in the
assessment described below by using publicly available data on the
toxicology of alkyl amines and related derivatives.
i. Acute dermal toxicity and eye irritation. Virtually all of the
amines when administered directly or in concentrated solution are
primary skin and eye irritants. Animals exposed to concentrated vapors
exhibit signs and symptoms of mucous membrane and respiratory tract
irritation. Direct skin contact with liquid amines can produce severe
burns and necrosis. Little toxicity information is available on amines
containing eight or more carbons. But, it is clear that these amines,
either as the neat liquid, or in concentrated solution, would be strong
local irritants for eyes, skin, and mucous membranes. The lowered vapor
pressure for the higher alkyl amines would tend to reduce the hazard
from vapor exposure.
ii. Acute oral toxicity. Estimated LD50 for amphoteric
compounds 300 to 500 milligrams/Kilogram (mg/kg). The LD50s
for the shorter chain primary amines (C2-C8) are in the 300 to 500 mg/
kg range. Secondary amines are slightly more toxic than the
corresponding primary amines. As the chains increase in length beyond
C12 to C16 there is an observable reduction in toxicity. For example,
the acute oral LD50 for octadecylamine (C18H39N) in mice and
rats is approximately 2-3 gram/kilogram (g/kg) compared to the 300 to
500 mg/kg range for the shorter chain amines. The addition of an
alcohol group to the molecule reduces the toxicity significantly. The
alkanolamines and the alkylalkanolamines are typically 3-5 times less
toxic than their amine congeners. For this reason it is expected that
the addition of propoxylate or ethoxylate groups will not confer
additional toxicity beyond that of the amine itself, and is likely to
tower toxicity substantially.
iii. Alkyl amines vs alkanolamines. The acute toxicity of the
alkylamines are
[[Page 7106]]
reduced from 4 to 20-fold by the introduction of hydroxyl groups into
the molecule. The toxicity of the alkyl amines is reduced approximately
5-fold as the molecular weight increases from C2 - C16 and higher.
iv. Effect of carboxylic acid salts. This trend of decreasing acute
toxicity with the addition of polar groups persists when the added
groups are acetate or propionate carboxylic acid salts. These are the
groups found in the amphoteric surfactants which are the subject of
this submission. The acute toxicity of the C10-C12 alkyl amines is
reduced from 2 to 15-fold when the alkyl groups on the nitrogen atom
are replaced by either propionate or acetate salts.
2. Genotoxicity. There is no indication that any alkyl amine is
mutagenic. Zeiger et al. (Ref. 1) reported on the Salmonella
Mutagenicity of 255 chemicals including 25 alkyl amines. Twenty three
of the alkyl amines tested negative in the Ames test both with and
without activation and only two substituted amines were weakly positive
( N-hydroxyethylethylenediamine and monoisopropanolamine).
3. Reproductive and developmental toxicity. Genamin TA (CAS
61790-33-8), a mixture consisting primarily of C16-C18
primary amines was given to both male and female rats 14 days prior to
mating continually for 54 days thereafter (Ref. 2). The author noted
that the NOAEL for parental toxicity and for effects on offspring was
12.5mg/kg. The reported NOAEL for fertility was 50 mg/kg.
4. Subchronic toxicity. N-methyl- N-octadecyl-1-octadecanamine was
administered to rats for 90-days at doses of 1,500; 5,000; and 15,000
ppm in the diet. Doses were reduced after week 4 to 1,500; 4,000 and
10,000 ppm. The presence of histiocytosis in all groups precluded the
establishment of a NOEL in this dose range. The LOAEL was 1,500 ppm or
75 mg/kg/day (Ref. 3). Subchronic studies have also been conducted on a
few alkanolamines. Ethomeen T/12 (CAS 61791-44-4)
Ethanol,2,2-iminobis-, N-tallow alkyl derivatives at doses of 15, 50,
150, and 450 mg/kg were fed to rats in their diet for 90-days. Ethomeen
T/12 is a mixture of polyoxyethylene tallow amines. Gross macroscopic
effects were seen and body weight gain was reduced only at the 450 mg/
kg level. Microscopic findings were seen in the intestine and regional
mesenteric nodes levels of 150 mg/kg and greater. The no observed
adverse effect level (NOAEL) was 50 mg/kg and the lowest observed
adverse effect level (LOAEL) was 150 mg/kg. A similar study was
conducted in dogs at doses of 13, 40, and 120 mg/kg. Vomiting occurred
at doses of 40 mg and higher. No gross pathologic variations or lesions
were observed in any dose group. Histological evaluation revealed an
increase in the incidence of foamy macrophages in the small intestine
and regional lymph nodes in the 40 mg/kg and 120 mg/kg dose groups. The
NOAEL was 13 mg/kg/day and the LOAEL 50 mg/kg/day (Ref. 4).
5. Chronic toxicity. Octadecylamine [CH3(CH2)17 NH2] has been
administered to rats in a 2-year rat feeding study (Ref. 5). The NOAEL
was 500 parts per million (ppm) in the diet and 3,000 ppm was a LOAEL.
Rats fed 3,000 ppm showed some weight loss, anorexia, and some
histological changes in the gastrointestinal tract, mesenteric nodes,
and liver. This NOAEL gives an ADI of 0.25 mg/kg body weight/day (bwt/
day) using a 100-fold safety factor. (500 ppm in old rats corresponds
to 25 mg/kg bw/day). An earlier 1-year oral study in dogs by Deichmann
(Ref. 6), reported a slight weight decrement at the highest of three
doses (0.6, 3.0, and 15 mg/kg bwt/day). The NOEL from this study was
3.0 mg/kg bwt/day. A corresponding ADI would be 0.03 mg/kg bwt/day, or
about 8-fold lower than the study in rats.
Most of the amine repeat-dose toxicology studies yield NOAELs in
the 3 to 50 mg/kg bwt/day range. The lowest repeated dose NOAEL in
these reports is 3.0 mg/kg bwt/day (both rabbit developmental study
with olelyamine and 1-year chronic dog study with octadecyl amine). The
application of these data for amphoteric amines depends on the toxicity
of other members of this surfactant family having the same or lesser
order of toxicity as the long chain fatty amines.
The amphoterics in this submission differ from the simpler alkyl
amines in two ways; first they are alkoxylated, which introduces polar
ether linkages, second they additionally have two charged carboxyl
groups on the end of the molecule. Both of these charges make the
molecule more polar, and can decrease the systemic toxicity of the
substance. The increased polarity canmake the substances easier to
eliminate in the urine. The increased number of ether linkages can make
the substance harder to absorb. For these reasons, we believe that the
NOELS of the ether amines establish an upper bound to the toxicity of
the amphoterics at approximately 10 mg/kg bw/day; the amphoterics
themselves should be considerably less toxic. Given that there are
norepeat-dose toxicity data in animals available on the amphoterics, we
have endeavored, via a weight-of-evidence approach, to demonstrate that
as the alkyl amine core of the molecule is modified by the introduction
of polar constituents, the toxicity is decreased. Thus the toxicity of
the amphoterics will be below that of the amines. In the discussion
below, we show how the introduction of polar groups reduces the
toxicity of several related classes of substances and how an average
numerical bound might be placed on this effect.
With reference to the report of the American Chemistry Council's
report of the Fatty Nitrogen Derivatives Panel Amines Task Group (Ref.
7), if alkyl (C10 - C16) dimethyl amine oxide is compared to the
corresponding or similar alkyl amine it is seen that the toxicity drops
by approximately 10-fold. The NOEL for alkyl (C10 - C16) dimethyl amine
oxide in a chronic rat study is 42.3 mg/kg bw/day. The NOEL in a 90-day
rat study was the same. The urine was the primary pathway for
elimination and excretion was largely complete in 24 hours (Ref. 8). In
contrast the maternal toxicity NOEL for Cis- 9-octadecenylamine was 10
mg/kg bw/day in rats and 3 mg/kg bw/day in rabbits. The NOEL for
octadecylamine in a 1-year oral gavage study in rats was 3 mg/kg bw/
day. It is seen that the conversion of the amine to the amine oxide
tends to reduce the repeat-dose toxicity by approximately 3 to 10-fold.
In a similar manner the acute toxicity of the alkylamines are reduced
from 4 to 20-fold by the introduction of hydroxyl groups into the
molecule, and the toxicity of the alkyl amines is reduced approximately
5-fold as the molecular weight increases from C2 to C16 and higher.
6. Animal metabolism. The aliphatic amines are well absorbed from
the gut and respiratory tract. They are either excreted intact or in
the form of metabolites, depending on the course of metabolism, which
depends on their structure. Monamine oxidases are mitichondrial enzymes
that catalyze the oxidation of many primary amines to the corresponding
aldehyde and ammonia. The aldehydes are further oxidized to the
correspondingcarboxylic acid and the ammonia to urea. In addition
microsomal enzymes can metabolize amines not readily transformed by
monoamine oxidases, through a variety of pathways. These include:
deamination, methylation, N-dealkylation, N-oxidation, N-acetylation,
cyclization, N-hydroxylation, and nitrosation.
7. Metabolite toxicology. Secondary amines are prone to react with
nitrite, depending on the pH of the media, to form nitrosamines, some
of which are potent animal carcinogens. Some
[[Page 7107]]
studies have suggested the possibility of in vivo formation of
carcinogenic nitrosamines within the acidic environment of the stomach
following ingestion of secondary amines. The major human intake of
nitrates ( 50 mg/day) comes from vegetables, water supplies, or
additives in the meat and fish curing process (Ref. 9). Nitrates are
converted to nitrites in the upper part of the gastrointestinal tract
by nitroreductase bacteria normally present in the lower bowel.
Amines or amine precursors are present in vegetables, wine,
spirits, beer, tea, fish, food flavoring agents, and some drugs. As
indicated above, at least 10 mg of amine nitrogen is excreted per day;
the intake of amines or their precursors is therefore probably in the
100 mg/day range. Thus there exists the required elements for the in
vivo formation of carcinogenic nitrosamines from amine ingestion.
Despite this theoretical possibility, epidemiologic studies have not
provided evidence for a causal association between nitrite exposure and
human cancer. Nor has a causal link been shown between N-nitroso
compounds preformed in the diet or endogenously synthesized and the
incidence of human cancer (Ref. 10). It has been demonstrated in
animals that nitrosation of diethylamine and dimethyamine in vivo is a
very slow process. When these substances were fed to rats together with
nitrite for over two years no tumors typical of treatment of rats with
nitrosodiethylamine were observed (Ref. 11). In any event, the addition
to the diet of nanogram levels of amines from the proposed used of
amine based surfactants is insignificant compared to normal endogenous
levels and to those naturally occurring in food.
8. Endocrine disruption. There is no evidence to suggest that the
alkyl amines have an effect on any endocrine system. In developmental
and two-generation reproduction toxicity tests systemic toxicity was
noted but no developmental or reproductive effects were found.
C. Aggregate Exposure
1. Dietary exposure. Exposure through both food and drinking water
were estimated using data and methods more commonly applied to
pesticide active ingredients. The methods for estimating dietary
exposure are discussed above under residues. Drinking water exposures
were estimated using EPA's combined Pesticide Root Zone Model/Exposure
Assessment Modeling System (PRZM/EXAMS) and the 1 hectare pond
scenario.
i. Food. Both Tier 1 and Tier 2, acute and chronic dietary
assessments were constructed in several different ways and in general
MOEs >100 were found. Tier 1 acute assessments did yield MOEs <100, but
the Tier 2 analysis gave an MOE = 1,500 for the lowest Tier 1 scenario.
ii. Drinking water. Using the average peak value fromPRZM/EXAMS
modeling for acute exposure, the average 60-day concentration for
chronic exposure and the standard estimates of water consumption, acute
and chronic margins of exposure for drinking water all MOEs were
greater than 360. In using the model, maximum application rates and
number of applications were assumed and the amphoteric surfactants were
assumed not to degrade in water or the environment. The modeling
provides an extreme worst-case estimate of exposure in that the peak
values simulated accumulation (i.e., no degradation) of the surfactants
in water during a 30 years period of application.
2. Non-dietary exposure. For non-dietary exposure and risk analysis
outdoor lawn care with broadcast application via hose-end sprayer was
selected as the worst case. Dermal absorption was assumed to be 10%.
Applicators were assumed to have dermal and inhalation exposures, while
re-entry exposures were dermal and oral, the oral via hand-to-mouth
activities by children. MOE's >100 were estimated by Tier 1 analyses,
indicating reasonable certainty of no harm for the worst-case bounding
scenario evaluated.
D. Cumulative Effects
Other amphoteric amine compounds may be used in pesticide
formulations. However, the assessment of this class of compounds
assumes 100% of the pesticide products applied to crops will use one
member of this class of amphoteric amines. Therefore, the cumulative
risk for this class of compound is covered by the assessments in this
submission.
E. Safety Determination
1. U.S. population. As a general rule in any pesticide assessments,
exposures of children are the highest of any subpopulation. This
pattern was found to hold true for the amphoteric surfactants and lead
to simplifications in the assessment procedure. When exposures to
children were found to be acceptable, e.g., acute and chronic Tier 2
estimated dietary exposures to children yielded large MOEs, separate
estimates for other subpopulations were not deemed necessary. In the
risk assessment we ultimately have adopted the dietary exposures for
children for all subpopulations. Exposures for females 13 to 49 were
calculated in certain instances and found to be comparable to each
other and less than for children. Hence, exposure estimates for the
latter were not formally completed. Rather the exposure numbers for
females were assumed for the full U.S. population.
2. Infants and children. Except when using acute Tier 1 dietary
exposure estimates and the most conservative toxicity endpoint, 3 mg/
kg-bw/day, all MOEs were found to be comfortably greater than 100.
Given the worst-case conservatism built into all the analyses, the
results support a conclusion that Tomah3's amphoteric
surfactants may be used safely in pesticide formulations without
concerns for dietary and non-occupational exposures.
F. References
1. Zeiger, E., Anderson B., Haworth S., Lawlor T., Mortelmans K.,
and Speck, W. (1987) ``Salmonella Mutagenicity tests: III. Results from
the testing of 255 chemicals.'' Environmental Mutagenesis, (1987) 3:
Suppl (9)1-110.)
2. Bussi R (2000). ``Genamin TA100: Reproduction/Development
toxicity Screening Test in rats by oral route.'' APAG, Instituto di
Recerche Biomediche, `Santoine Marxer' S.p.a.
3. Procter and Gamble, Ref. 3) EPA submission, No. 88--9200007039,
microfiche No. 0T5537649.
4. Goater T.O., Griffiths D., McElliogott T.F., and AAB Swan,
A.A.B, (1970), ``Summary of toxicology data - acute oral toxicity and
short-term feeding studies on polyoxythylene tallow amines in rats and
dogs,'' Food and Cosmetics Toxicology 8:249--252.
5. Deichmann, W.B., Radomski, J.I., MacDonald, W.E., Kascht, R.L.,
and Erdman, R.l., (1958), American Medical Association Archives of
Industrial Health, 18:483.
6. Deichmann, W.B., et.al., (1957), Archives Of Industrial Health,
18:483-487.
7. Fatty Nitrogen Derivatives Panel Amines Task Group, 2002, Fatty
Nitrogen Derived (FND) Amines Category High Production Volume (HPV)
Chemicals Challenge, American Chemistry Council, Washington, D.C.
8. U.S. EPA. 1999. The Use of Structure-activity Relationships
(SAR) in the High Production Volume Chemicals Challenge Program. http:/
/www.epa.gov/ch emrtk/sarfinl1.htm.
9. Ellen et al. 1990. Food Additives Contaminants 7(2):207--221.
10. Gangilli., S.D., 1999, ``Nitrate, nitrite and N-nitroso
compounds`` in Ballintine, B., Marrs, T., and Turner, P., General and
Applied Toxicology, Stockton Press, New York, p 2111, 2143.
[[Page 7108]]
11. Druckery et al, 1963 Cited by Benya et al., Patty's, 4th Ed.
Vol II, Part B, page 1097.
[FR Doc. 05-2620 Filed 2-9-05; 8:45 am]
BILLING CODE 6560-50-S