[Federal Register Volume 70, Number 27 (Thursday, February 10, 2005)]
[Notices]
[Pages 7103-7108]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-2620]


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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:[email protected].

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 [email protected], 
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.
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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