[Federal Register: February 10, 2005 (Volume 70, Number 27)]
[Notices]
[Page 7103-7108]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10fe05-71]
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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.
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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-
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 http://www.epa.gov/fedrgstr/.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although, not all docket materials may be
available electronically, you may still access any of the publicly
available docket materials through the docket facility identified in
Unit I.B.1. Once in the system, select ``search,'' then key in the
appropriate docket ID number.
Certain types of information will not be placed in the EPA
Dockets. Information claimed as CBI and other information whose
disclosure is restricted by statute, which is not included in the
official public docket, will not be available for public viewing in
EPA's electronic public docket. EPA's policy is that copyrighted
material will not be placed in EPA's electronic public docket but will
be available only in printed, paper form in the official public docket.
To the extent feasible, publicly available docket materials will be
made available in EPA's electronic public docket. When a document is
selected from the index list in EPA Dockets, the system will identify
whether the document is available for viewing in EPA's electronic
public docket. Although, not all docket materials may be available
electronically, you may still access any of the publicly available
docket materials through the docket facility identified in Unit I.B.
EPA intends to work towards providing electronic access to all of the
publicly available docket materials through EPA's electronic public
docket.
For public commenters, it is important to note that EPA's policy
is that public comments, whether submitted electronically or on paper,
will be made available for public viewing in EPA's electronic public
docket as EPA receives them and
[[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 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-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
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and Speck, W. (1987) ``Salmonella Mutagenicity tests: III. Results from
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Nitrogen Derived (FND) Amines Category High Production Volume (HPV)
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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
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[[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