[Federal Register Volume 69, Number 52 (Wednesday, March 17, 2004)]
[Notices]
[Pages 12670-12676]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E4-553]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2004-0011; FRL-7343-5]
Ammonium Nonanoate; Notice of Filing a Pesticide Petition to
Establish a Tolerance for a Certain Pesticide Chemical in or on Food
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of the
pesticide chemical ammonium nonanoate in or on various food
commodities.
DATES: Comments, identified by docket ID number OPP-2004-0011, must be
received on or before April 16, 2004.
ADDRESSES: Comments may be submitted electronically, by mail, or
through hand delivery/courier. Follow the detailed instructions as
provided in Unit I. of the SUPPLEMENTARY INFORMATION.
FOR FURTHER INFORMATION CONTACT: Bipin Gandhi, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 308-8380; e-mail address: [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural, food manufacturer, or pesticide manufacturer. Potentially
affected entities may include, but are not limited to:
Crop production (NAICS code 111)
Animal production (NAICS code 112)
Food manufacturing (NAICS code 311)
Pesticide manufacturing (NAICS code 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 identification (ID) number OPP-2004-0011. The
official public docket consists of the documents specifically
referenced in this action, any public comments received, and other
information related to this action. Although a part of the official
docket, the public docket does not include Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute. The official public docket is the collection of materials
that is available for public viewing at the Public Information and
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2,
1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The docket telephone number is (703) 305-5805.
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although not all docket materials may be
available electronically, you may still access any of the publicly
available docket materials through the docket facility identified in
Unit I.B.1. Once in the system, select ``search,'' then key in the
appropriate docket ID number.
Certain types of information will not be placed in 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.
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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 in paper,
will be made available for public viewing in EPA's electronic public
docket as EPA receives them and without change, unless the comment
contains copyrighted material, CBI, or other information whose
disclosure is restricted by statute. When EPA identifies a comment
containing copyrighted material, EPA will provide a reference to that
material in the version of the comment that is placed in EPA's
electronic public docket. The entire printed comment, including the
copyrighted material, will be available in the public docket.
Public comments submitted on computer disks that are mailed or
delivered to the docket will be transferred to EPA's electronic public
docket. Public comments that are mailed or delivered to the docket will
be scanned and placed in EPA's electronic public docket. Where
practical, physical objects will be photographed, and the photograph
will be placed in EPA's electronic public docket along with a brief
description written by the docket staff.
C. How and to Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through hand
delivery/courier. To ensure proper receipt by EPA, identify the
appropriate docket ID number in the subject line on the first page of
your comment. Please ensure that your comments are submitted within the
specified comment period. Comments received after the close of the
comment period will be marked ``late.'' EPA is not required to consider
these late comments. If you wish to submit CBI or information that is
otherwise protected by statute, please follow the instructions in Unit
I.D. Do not use EPA Dockets or e-mail to submit CBI or information
protected by statute.
1. Electronically. If you submit an electronic comment as
prescribed in this unit, EPA recommends that you include your name,
mailing address, and an e-mail address or other contact information in
the body of your comment. Also include this contact information on the
outside of any disk 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-2004-0011. 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-2004-0011. 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-2004-0011.
3. By hand delivery or courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Office of Pesticide
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall
2, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket
ID Number OPP-2004-0011. 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
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assigned to this action in the subject line on the first page of your
response. You may also provide the name, date, and Federal Register
citation.
II. What Action is the Agency Taking?
EPA has received a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical in or on various food commodities under section 408
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that this petition contains data or information
regarding the elements set forth in FFDCA section 408(d)(2); however,
EPA has not fully evaluated the sufficiency of the submitted data at
this time or whether the data support granting of the petition.
Additional data may be needed before EPA rules on the petition.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: March 4, 2004.
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 the petitioner and represents the view of the petitioner.
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.
Falcon Lab LCC
PP 3E6789
EPA has received a pesticide petition (PP 3E6789) from Falcon Lab
LLC, 1103 Norbee Drive, Wilmington, DE 19803 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 ammonium nonanoate in or on all raw
agricultural commodity. 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
support granting of the petition. Additional data may be needed before
EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. In solution, ammonium nonanoate (CAS No. 112-
05-0) is ionized and occurs as the straight chain C-9 nonanoic acid and
the ammonium ion. Nonanoic acid is metabolized by beta-oxidation and by
respiration through the citric acid cycle, converted to carbon dioxide
and water. Suryanarayanan and McConnell (Ref. 1) showed the tracer in
nonanoic acid-1-C14 was 98% assimilated into metabolites by beta-
oxidation to acetyl CoA and utilized via the glyoxylate cycle in wheat
stem rust uredospores.
2. Analytical method. In the Federal Register of February 19, 2003
(68 FR 7931) (FRL-7278-7), it is indicated that the analytical method
for nonanoic acid is being made available to anyone interested in
pesticide enforcement when requested, from Norm Cook, Antimicrobials
Division (7510C), Office of Pesticide Programs, U.S. Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001. Office location and telephone number: 1921 Jefferson Davis
Highway, 3rd Floor, Arlington, VA 22202, (703) 308-8253.
3. Magnitude of residues. Nonanoic acid is a naturally occurring
component of fatty acids in plants (68 FR 7931). Lowfat chedder cheese
contained small amounts of nonanoic acid (Ref. 2). Nonanoic acid is
naturally present at levels up to 224 parts per billion (ppb) in
apples, 385 parts per million (ppm) in the skin of grapes, and 143 ppm
in grape pulp. It is present in a number of other foods as well. An
average serving of grapes containing 385 ppm of nonanoic acid in the
grape skins would result in exposure to nonanoic acid to an average
consumer of 164 [mu]g/kg/day (68 FR 7931).
Nonanoic acid may be safely used as synthetic food flavoring
substances and adjuvants in food in the minimum quantity required to
reproduce the intended effect (21 CFR 172.515). Nonanoic acid may be
used in an aliphatic acid mixture for washing or to assist in the
peeling of fruits and vegetables. The aliphatic acid mixture may be
used at a level not to exceed 1% in the lye peeling solution (21 CFR
173.315), (68 FR 7931).
B. Toxicological Profile
1. Acute toxicity. Undiluted nonanoic acid administered orally to
rats at a dose of 3,200 milligrams/kilogram (mg/kg) did not cause death
which indicated a lethal dose LD50 3,200 mg/kg; however,
deaths did occur at this dose level when the chemical was administered
intraperitoneally (IP) for an IP LDL0 = 3,200 mg/kg. More recently,
nonanoic acid of unspecified source administered orally to rats and
mice had an LD50 5,000 mg/kg for both rat and mouse. For
male rats, the oral LD50 >9,000 mg/kg.
Nonanoic acid, as undiluted material, administered to mice by the
intravenous route (IV) had an IV LD50 = 224 mg/kg. A 10%
solution of nonanoic acid in corn oil failed to kill mice at a dose of
3,200 mg/kg when given orally (mouse oral LDL50 3,200 mg/
kg), but caused death at a dose of 1,600 mg/kg by the intraperitoneal
route (mouse IP LDL0 = 1,600 mg/kg). Symptoms in mice included labored
respiration and roughing of the coat and death was observed as soon as
4 days after treatment.
The dermal LD50 for undiluted nonanoic acid in rabbits
has been reported to be LD50 5,000 mg/kg. Nonanoic acid from
an unspecified source caused a dermal LD50 2,000 mg/kg on
rats.
Application of nonanoic acid to intact and abraded skin of rabbits
had an LD50 9,000 mg/kg, and caused moderate to severe
irritation.
These data indicate nonanoic acid has low acute toxicity by
intraperitoneal, oral or dermal routes. Intravenous exposure to
ammonium nonanoate (nonanoic acid) is irrelevant to its use as an inert
ingredient pesticide products. Intraperitoneal nonanoic acid may occur
via skin wounds, but the relatively low acute toxicity would be of low
risk. Oral and dermal exposure to nonanoic acid are of very low risk.
Nonanoic acid was delivered at 0.46 mg/liter (mg/L) as an aerosol
for 4 hours (h) to 10 rats without any mortality; however, at 3.8 mg/L,
80% mortality occurred. Relatively low degree of toxicity occurred
following inhalation of the aerosol. Respiratory irritation was
observed at both dose levels.
Acute toxicity to other environmental species has been determined
for a fatty acid similar to nonanoic acid. Fatty acid sodium salts were
found to be less toxic than the parent acids, and toxicities of both
increased with chain length (between 6 and 12 carbons). For capric acid
(decanoic acid) C-10 in fresh water, the 48 hr lethal concentration
(LC)50 for red killifish (Oryzias latipes) and
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gammarus (Hyale plumulosa) were 20 and 41 mg/L, respectively. Sodium
caprate was less toxic than the acid to killifish (54 mg/L). Based on
these data, nonanoic acid in the ammonium salt form (ammonium
nonanoate) would be expected to be no more than slightly toxic to
aquatic fauna.
Toxicity to algae may be estimated by comparison with data for
soaps in general. For example, an LC50 range of 180-320 mg/L
has been reported for Chlorella vulgaris. Therefore, nonanoic acid as
the potassium or sodium salt would not be expected to be significantly
toxic to algae at these low concentrations of approximately 0.032% w/w
(320 ppm).
Toxicity to fish, fathead minnow (Pimephales promelas), for 96 hr
exposure was reported to be LC50 = 104 ppm.
Fatty acids are toxic to aquatic invertebrates, but only slightly
toxic to cold and warm water fish species (RED: Soap Salts; EPA-738-R-
92-015). However, fatty acids are rapidly destroyed by microbial action
and sorption or formation of insoluble salts of calcium or magnesium in
soil and water. The proposed uses for nonanoic acid (ammonium
nonanoate) as an inert would not be applied near water or on drainage
ditches or onto marsh, ponds, lakes, streams or rivers.
Nonanoic acids are relatively non-toxic to waterfowl and upland
game birds (RED: Soap Salts; EPA-738-R-92-015).
As a result of a number of acute toxicity studies, technical
nonanoic acid is placed in the following Toxicity Categories: Primary
eye irritation (Toxicity Category II); acute dermal and inhalation
toxicity (Toxicity Category III); acute oral toxicity (Toxicity
Category IV). Sensitization test results showed that nonanoic acid
cannot be considered a dermal sensitizer (68 FR 7931).
2. Genotoxicity. It was reported that the Ames Test (Salmonella/
reverse mutation assay) showed nonanoic acid to be non-mutgenic.
Similarly, an in vivo cytogenetics study using micronucleus assay gave
a negative result. In a mouse lymphoma forward mutation study, nonanoic
acid appears to induce a weak mutagenic response at or higher than 50
milligrams/milliliter (mg/mL) level. This was observed in the presence
of increasing toxicity, and may be an indication of gross chromosomal
changes or damage and not actual mutational changes within the
thymidine kinese gene locus (68 FR 7931).
A dermal carcinogenicity study was performed on the shaved skin
area of 50 mice and treated twice-weekly with 50 mg doses of undiluted
nonanoic acid for 80 weeks. No evidence of severe dermal irritation or
systemic toxicity was seen. Histopathology revealed no tumors of the
skin or the internal organs (68 FR 7931).
3. Reproductive and developmental toxicity. Development toxicity
was conducted on a group of 22 pregnant Crl: COBS CD(SD)BR rats. These
rats were treated with nonanoic acid in corn oil at a dose of 1,500 mg/
kg on gestation days 6 through 15 (both days inclusive). Maternal body
weight was not significantly affected during the treatment. Only 1 out
of 22 animals showed signs of clinical toxicity. No significant
histopathology signs were observed in the maternal animals. Nonanoic
acid treatment did not have any significant effect on cesarean section
observations. Four fetuses in one litter showed a higher incidence of
cleft palate compared to the control mean. For maternal toxicity, EPA
determined the no observed adverse effect level (NOAEL) to be greater
than 1,500 mg/kg/day. Because fetal effects were observed at 1,500 mg/
kg/day, the NOAEL for developmental toxicity was not determined. EPA
has determined that this dose is in excess of the Agency's limit dose
for toxic effects. The type and level of exposure expected from the
active ingredient use of this chemical is much lower than the dose
level shown in the study (68 FR 7931).
Nonanoic acid was weakly positive for inducing mutations in mouse
lymphoma cells. Mutations were induced with nonanoic acid at greater
than or equal to 50 [mu]g/mL. Since the mutations were observed with
severe cytotoxicity and small colony development, the observed
mutations may have been an aberration caused by cell damage and not
actual mutational changes (61 FR 5716) (February 14, 1996) (FRL-5348-
9).
Nonanoic acid as single oral doses of 1,250, 2,500 and 5,000 mg/kg
to ICR mice followed by bone marrow harvest at 24, 48 and 72 hr after
treatment, did not significantly increase micronucleated polychromatic
erythrocytes which indicated a negative micronucleus assay test (61 FR
5716).
4. Subchronic toxicity.In an oral toxicity study (conducted for 14
days), no systemic toxicity was observed with either sex (animal
species unspecified) even at the highest nonanoic acid dose tested,
20,000 ppm (1,834 mg/kg/day). In addition, nonanoic acid showed no
adverse effects on survival, clinical signs, body weight gain, food
consumption, hematology, clinical chemistry or gross pathology. For
each dose, three animals per sex were tested. However, the study did
not report organ weights and histopathology. This was considered a
deficiency in this study. Nevertheless, the Agency determined that
because no toxic effects were observed at a very high level dose
approaching 2,000 mg/kg, a 90-day oral study was not necessary (68 FR
7931).
Nonanoic acid at 80, 40, 20 and 10% applied as a 15 micro-liter
aliquot to patches placed on the lower back of 152 women for 47 hr and
evaluated at 48 and 96 hr indicated erythema (redness) decreased with
time for all concentrations, but the higher concentrations increased
surface changes with time (Ref. 3). Reiche et al. suggested nonanoic
acid was an irritant rather than an allergen regardless of the increase
in skin reaction over patch test exposure time. The skin reaction to
10% nonanoic acid for 47 hr was considered to be mild by the National
Institute of Occupational Safety and Health (NIOSH).
Solutions of nonanoic acid at 0.5 M or 1.0 M in propanol
(approximately 10 to 20% w/w) caused skin irritation when applied under
occlusive patches in 25 human volunteers. A 20% nonanoic acid solution
in propanol and applied as a patch test produced skin reactions in 94%
of 116 healthy male volunteers. The lesions consisted of mainly
erythema (redness) at 48 hr and pigmentation at 96 hr (Ref. 4).
Forty two nonatopic healthy male subjects of 18 to 47 years of age
had 3 to 10 patch tests on the volar area of the forearm applied with 8
mm Finn Chambers which were assessed by two independent readers at 48
hr post application. A six point grading scale from no visible reaction
to intense erythema with bulbous formation indicated chemical
concentrations which produced patch test reactions of less than or
equal to 2+ in at least 75% of the subjects as follows: 0.5%
Benzalkonium-chloride, 5% sodium lauryl sulfate, 0.8% croton-oil, 0.02
dithranol, 80% nonanoic acid (propanol solution), 100% propylene glycol
and 2% sodium hydroxide (Ref. 5).
One hundred hospitalized patients with different types of skin
disease were patch tested with nonanoic acid with a 48 hr contact
period followed by evaluation at 1 and 72 hr after patch removal. The
nonanoic acid concentration to produce a discernible irritation
reaction in 50% of the population (ID50) was calculated by conventional
probit analysis. The calculated ID50 for males and females was 5.3 and
6.4%, respectively, nonanoic acid concentration. Three of 100 patients
reacted to 1% nonanoic
[[Page 12674]]
acid and all reacted to 20 to 39.3% nonanoic acid (Ref. 6). NIOSH
reported an 80 and 20% nonanoic acid solution with 48 and 24 hr human
skin contact, respectively, caused moderate skin irritation.
Sensitization reactions were not observed in 25 human volunteers
after patch testing with 12% nonanoic acid solution in petroleum ether.
Nonanoic acid is a non-sensitizing irritant which means it does not
cause allergic reactions in most humans. Nonanoic acid is lipophilic
and non-sensitizing.
Nonanoic acid at a dose of 500 mg/kg in contact with rabbit skin
for 24 hr was a moderate irritant. Nonanoic acid in an undiluted form
produced severe skin irritation in guinea pigs when applied to the
skin.
A 28-day dermal toxicity study conducted on rabbits was submitted
to EPA under TSCA section 8(e). Five male and five female New Zealand
white rabbits were dermally treated with nonanoic acid present in
mineral oil. In all, 10 applications were made (5 per week) at a dose
level of 500 mg/kg/day (25% w/w). A 2-week recovery period was allowed
for selected rabbits. During the first and second week of treatment
slight body weight loss and decreased food consumption were observed.
One female rabbit showed ocular discharge and hypoactivity during the
second week of treatment. All rabbits dermally treated with nonanoic
acid by day 14 showed signs of severe erythema and moderate edema.
Dermal reactions consisting of moderate desquamation, moderate
fissuring, eschar, exfoliation and necrosis were also observed at day
14. By day 29, all dermal reactions had reversed. It was evident that
at the treatment level of 500 mg/kg/day of nonanoic acid, significant
dermal signs of toxicity were observed but no significant systemic
reaction (68 FR 7931). There is additional information on the previous
study with 10 New Zealand rabbits which showed that mortality did not
occur and microscopic effects on kidneys, liver, lungs, heart and
brains were not observed. Slight to severe skin irritation occurred in
the first week and progressed to necrosis in the second week. Skin
irritation on four rabbits subsided during 2 weeks of recovery after
treatments ended. NIOSH characterized the effect on rabbit skin, in the
previous study, as moderate.
Severe irritation was produced by the application of 91 mg of
nonanoic acid to the rabbit eye. This same study was reported for
nonanoic acid as severely irritating to rabbit eyes and aerosols are
also an eye irritant. NIOSH reported two eye irritation studies which
showed 91 mg of nonanoic acid caused severe rabbit eye injury as
reported above and published in 1964, but another study, published in
1999, with a 100 uL (0.1 mL = approx one drop) dose or droplet to the
rabbit eye caused only mild injury. Since the source of nonanoic acid
is unknown in the 1999 study, it is impossible to compare the actual
dose; however, since nonanoic acid has a density less than water, the
doses used in these studies would appear similar. Therefore, these
results would appear inconclusive for eye irritation or indicate a
rather large range of experimental error.
Rats exposed to atmospheric concentrations of 840 mg/cubic-meter
(125 ppm) nonanoic acid for a period of 6 hr showed no symptoms of
toxicity. However, in another study, test animals (species not
specified) subjected to an atmospheric concentration of 3.75 mg/L
(1,150 ppm) nonanoic acid for a period of 6 hr developed clinical signs
of nasal discharge, blinking, and labored breathing. Inhalation
exposure indicated nonanoic acid was a respiratory irritant.
5. Chronic toxicity. Oral exposure of 8 male rats to nonanoic acid
at 4.17% in the diet (approximately 2,100 g/kg/day) for 4 weeks had no
effect on survival. A slight 4% decrease in mean growth was observed,
but not statistically significant.
A study on chronic toxicity/carcinogenicity in mice was conducted
for 80 weeks. A dose of 50 mg of nonanoic acid was dermally applied to
each shaved mouse twice/day for 80 weeks. Histopathology showed no non-
neoplastic or neoplastic lesions on skins and internal organs of mice.
The Agency concluded that this study although not exactly conducted
according to guideline, adequately assesses the chronic toxicity and
the carcinogenic potential of nonanoic acid via the dermal route (68 FR
7931).
6. Animal metabolism. Mammals, birds and invertebrates consume
fatty acids as a normal constituent of their daily diet (RED: Soap
Salts; EPA-738-R-92-015) and would metabolize nonanoic acid via normal
respiration, the same as plants.
7. Metabolite toxicology. Nonanoic acid, as a straight chain carbon
molecule, would be metabolized by beta-oxidation to form acetate
molecules which enter the citric acid cycle and are metabolized to
carbon dioxide, water and energy. None of the metabolites would be
considered to have any toxicological risk.
8. Endocrine disruption. Straight chain carbon molecules, as in the
C9 carbon chain of nonanoic acid would be unlikely to cause a risk of
endocrine disruption. Nonanoic acid occurs naturally in plants and
animals.
C. Aggregate Exposure
1. Dietary exposure. The Food and Drug Administration has cleared
nonanoic acid as a synthetic food flavoring agent (21 CFR 172.515), as
an adjuvant, production aid and sanitizer to be used in contact with
food (21 CFR 178.1010(b)) and in washing or to assist in lye peeling of
fruits and vegetables (up to 1%) (21 CFR 173.315). Nonanoic acid is
also exempt from the requirement of a tolerance when used in or on all
food commodities, as a plant regulator on plants, seeds, or cuttings
after harvest in accordance with Good Agricultural Practices (GAP). It
is also exempt from a tolerance when used as a herbicide on all plant
food commodity provided that allocations are not made directly to the
food commodity except when used as a harvest aid or desiccant to any
root or tuber vegetable, bulb, or cotton (40 CFR 180.1159), (68 FR
7931). Applications of ammonium nonanoate (dissociated into nonanoic
acid), as an inert ingredient additive, would potentially contact all
plant parts of food crops.
A calculation of the dietary exposure is complicated by the
exemption from tolerance for nonanoic acid and particularly for the 21
CFR 172.515 rule which allows direct addition of nonanoic acid into
food at the minimum quantity required to produce the desired effect.
However, in the aggregate, the daily consumption of nonanoic acid is
probably less than 1 mg/kg/day. The worst case scenarios presented
indicate nonanoic acid exposure as tens of [mu]g/kg/day. Based on cited
public data in this document, the no effect level for mice and rats for
ingested nonanoic acid is 3,000 mg/kg/day and the estimated maximum
human dietary exposure is 0.030 mg/kg/day; therefore, a 10,000 fold
safety factor or greater is estimated for nonanoic acid in food.
However, since nonanoic acid is rapidly metabolized in the human
digestive system, the estimated safety factor is a temporal and minimal
estimate. The petitioner believes that the surfactant properties of
ammonium nonanoate (nonanoic acid) should enhance the efficacy of
pesticides with a concomitant reduction of pesticide rates and reduce
dietary exposure to pesticides.
i. Food. For nonanoic acid as a sanitizer use, a worst case dietary
exposure estimate has been calculated, assuming that all food consumed
by an adult or child has contacted a sanitized surface using pelargonic
acid (nonanoic acid), that a 1 mg square centimeter (sq
[[Page 12675]]
cm) sanitizer residue remains on the surface, and that 100% of the
residue (170 ppm) is transferred to the food from the surface. Using
these assumptions, in which all food contacts 4,000 sq cm of sanitized
non-porous food-contact surfaces a worst case dietary exposure of 680
[mu]g/day is calculated. For a 70 kg adult this becomes 9.7 [mu]g/kg/
day and for a 15 kg child, exposure is calculated as 45 [mu]g/kg/day
(68 FR 7931).
For a typical use as an inert ingredient, nonanoic acid as ammonium
nonanoate at a concentration of 0.5% w/w in the dilute spray solution
applied in 20 gal/acre spray volume would apply approximately 8.7 mg/sq
ft of ammonium nonanoate of which 7.8 mg is nonanoic acid. If we assume
8 cucumbers of 4.0 lb total weight completely covered the 1 sq ft area,
the consumption of one-half of one cucumber (0.25 lb raw cucumber)
would result in an exposure to 0.5 mg nonanoic acid. Therefore, the
calculated exposure to a typical 70 kg adult would be 7 [mu]g/kg/day;
and for a child of 15 kg, the exposure would be 33 [mu]g/kg/day
nonanoic acid. The calculated human exposure would be the same for one
cucumber or more per sq ft because the application is uniformly applied
to the soil surface area or crop laying on the soil surface. The actual
exposure in the cucumber example should be less than calculated because
the consumption was assumed to occur on the day of application without
cucumber washing or preparation and without consideration of normal
interception of some of the spray application by plant foliage.
Some pesticide applications are directed sprays which would reduce
potential contact with the edible plant parts. Translocation of
nonanoic acid is unlikely to occur since its mode of action is a
physical reaction with cell membranes as a lipophilic chemical. The
petitioner believes that ammonium nonanoate would be a more acceptable
adjuvant alternative to many surfactants in use today.
ii. Drinking water. Nonanoic acid, as an inert ingredient in
pesticide formulations should not be applied near or on potable water.
The rapid dissipation of nonanoic acid in soil, with an estimated soil
half-life of 1-day for fatty acids, should mitigate any potential for
water contamination by run-off from treated fields. Drainage ditches
and lakes, ponds, streams and rivers will be prohibited from nonanoic
acid application. KX-6116 as a sanitizer contained nonanoic acid as its
active component and low concentrations of nonanoic acid could be
expected to be introduced into drinking water. However, EPA concluded
exposure through drinking water was expected to be low and not of
significance (68 FR 7931). The petitioner believes that ammonium
nonanoate (nonanoic acid) as an inert ingredient is not expected to be
applied near drinking water sources. Rapid metabolism of nonanoic acid
in 1 to 9 days in soil should prevent potential contamination of
surface water or ground water (68 FR 7931). The soil half-life of fatty
acids was estimated to be less than 1-day (RED: Soap Salts; EPA-738-R-
92-015).
The nonanoic acid log octanol/water partition coefficient is 3.42
which indicated the hydrophobic molecule, nonanoic acid, would have a
very strong affinity to the organic matter in soil and would not leach
into ground water. Microbial degradation in soil, which proceeds at a
half-life rate of 1-day for fatty acids, would probably rapidly
eliminate the strongly adsorbed nonanoic acid from soil. These factors
would probably assure nonanoic acid would not occur in ground water.
The salts of nonanoic acid would dissociate into the ionic forms of
nonanoic acid and the free salt in soil and although ammonium nonanoate
is water soluble, it would be bound to soil organic matter in the
dissociated form. Soils contain abundant magnesium and calcium ions
which would form insoluble salts of nonanoic acid and contribute to
protection of ground water.
2. Non-dietary exposure. Applicator exposure to nonanoic acid as an
inert ingredient is not expected to exceed the currently approved uses.
The use of ammonium nonanoate (nonanoic acid) with herbicides should
increase the rate of plant tissue necrosis and should reduce the
potential risk to adults or children who contact sprayed plant parts,
because the rapidly desiccated plant cells should retain nonanoic acid,
as an inert ingredient, and the herbicide active ingredient bound to
collapsed cell tissues. Off-target movement of the inert ingredient
additive, nonanoic acid, as ammonium nonanoate, should not be expected
to exceed the potential off-target movement of the pesticide active
ingredient.
Fatty acids and their salts are a potential risk for eye injury;
therefore, eye protection would be recommended when handling ammonium
nonanoate. The solid form of 100% ammonium nonanoate crystals could
have a reduced risk to eyes compared to the 40% liquid concentrate
because accidental facial exposure by splashing would be eliminated.
Also 100% crystalline ammonium nonanoate would have less eye exposure
risk compared to other typical liquid surfactants.
Nonanoic acid is slightly volatile and is a component of the odor
of milk, cheese, fats and soap. However, the estimated half-life in the
atmosphere for nonanoic acid is 1.6 days. Therefore, inhalation
exposure would be minimal for most occupations. Workers in the
aforementioned industries of cheese and soap, etc. have not been
seriously afflicted by long-term exposure to environments with nonanoic
acid in the work environment.
D. Cumulative Effects
EPA concluded that pelargonic acid (nonanoic acid) is sufficiently
non-toxic that EPA can determine that it does not share a common
mechanism of toxicity with other substances (68 FR 7931). The rapid
dissipation of nonanoic acid in the environment, i.e. soil half-life of
1-day and atmospheric half-life of 1.6 days, and normal metabolism of
nonanoic acid by humans would probably prevent an accumulation of
residual levels in the environment to trigger any cumulative effects.
The mechanism of action of nonanoic acid and some other fatty acids on
plants is a physical effect on plant cell walls which affects cell wall
integrity and would be less likely to have a cumulative effect as
compared to compounds with a mode of action that affects metabolic or
regulatory functions in organisms.
E. Safety Determination
1. U.S. population. Ammonium nonanoate forms nonanoic acid in
solution and nonanoic acid occurs naturally in laundry and hygienic
soaps as sodium or potassium nonanoate. Therefore, the toxicological
properties of the ionized form, nonanoic acid are reviewed for the
toxicological profile. Nonanoic acid is used as a antimicrobial agent
or sanitizer for food contact surfaces. It is also used in lithographic
plate developer solutions. The three uses described above involve
disposal via public sewer systems, which indicates the low risk concern
associated with nonanoic acid in the environment. Nonanoic acid is also
used as a herbicide with directed and shielded applications on all food
crops and is exempt from tolerance. However, the directed and shielded
application would be expected to prevent contact with the edible plant
parts. Nonanoic acid is exempt from a tolerance when applied to root or
tuber vegetable, bulb or cotton as a desiccant or harvest aid.
The proposed use, in this notice of filing for ammonium nonanoate
(nonanoic acid) as an inert ingredient,
[[Page 12676]]
would be for applications to agricultural commodities at rates less
than those used as an herbicide or crop desiccant.
Based on the following five considerations, EPA concluded that
nonanoic acid is unlikely to pose a risk under all reasonable exposure
scenarios:
i. Fatty acids such as nonanoic acid are processed by known
metabolic pathways within the body and contribute to normal
physiological function.
ii. Nonanoic acid is naturally present at levels up to 224 ppb in
apples, 385 ppm in the skin of grapes, and 143 ppm in grape pulp. It is
present in a number of other foods as well. An average serving of
grapes containing 385 ppm of nonanoic acid in the grape skins would
result in exposure to nonanoic acid to an average consumer of 164
[mu]g/kg/day. In comparison, a worst case estimate of dietary exposure
to nonanoic acid as a result of its use as sanitizer is 9.7 [mu]g/kg/
day for a 70 kg adult and 45 [mu]g/kg/day for a 15 kg child.
iii. The Food and Drug Administration has cleared nonanoic acid as
a synthetic food flavoring agent and adjuvant (21 CFR 172.515), as an
adjuvant, production aid and sanitizer to be used in contact with food
(21 CFR 178.1010(b)) and in washing or to assist in lye peeling of
fruits and vegetables (up to 1% nonanoic acid) (21 CFR 173.315).
Nonanoic acid is also exempt from the requirement of a tolerance when
used in or on all food commodities, as a plant regulator on plants,
seeds, or cuttings after harvest in accordance with GAP. It is also
exempt from a tolerance when used as a herbicide on all plant food
commodities provided that allocations are not made directly to the food
commodity except when used as a harvest aid or desiccant to any root or
tuber vegetable, bulb, or cotton (40 CFR 180.1159).
iv. Dietary toxicity testing evidenced adverse reactions only at
doses that were at or above limit doses. Dermal toxicity testing showed
no significant systemic reaction.
v. The estimated exposures to nonanoic acid and other fatty acids
from direct or indirect addition to food as well as sanitizer uses are
well below the doses administered in animal studies that are required
to elicit an adverse effect. Accordingly, EPA concludes that there is a
reasonable certainty of no harm to the general population, including
infants and children, from aggregate exposure to nonanoic acid (68 FR
7931).
Nonanoic acid has an estimated 1-day half-life in soil (RED: Soap
Salts; EPA-738-R-92-015) and the estimated half-life in the atmosphere
is about 1.6 days. Volatilization half-life of nonanoic acid from a
river was estimated to be 29 days from a model river and 210 days from
a model lake. Nonanoic acid is also inactivated in water by the
formation of calcium and magnesium salts which are insoluble
precipitates and non-reactive. In summary, nonanoic acid is highly
unlikely to accumulate in the environment due to rapid metabolism in
soils and neutralization as insoluble salts.
2. Infants and children. As previously discussed the dietary safety
factor for nonanoic acid is approximately 10,000 fold; therefore, risk
to children and infants, with primary exposure thru ingestion, would be
of minimal concern.
Section 408 of the FFDCA provides that EPA shall apply an
additional tenfold margin of safety for infants and children in the
case of threshold effects to account for prenatal and postnatal
toxicity and the completeness of the data base on toxicity and exposure
unless EPA determines that a different margin of safety will be safe
for infants and children. Margins of safety are incorporated into EPA
risk assessments either directly through use of a MOE analysis or
through using uncertainty (safety) factors in calculating a dose level
that poses no appreciable risk to humans. Based on the numerous
considerations, EPA concluded that pelargonic acid was sufficiently
non-toxic that a margin of safety analysis was not appropriate. For the
same reasons, EPA has not applied an additional margin of safety for
the protection of infants and children (68 FR 7931).
F. International Tolerances
Codex maximum residue levels have not been established for nonanoic
acid (68 FR 7931).
G. References
1. Suryanarayanan, S. and W. B. McConnell. 1964. The metabolism of
pelargonate-1-C14 by wheat stem rust uredospores. Report: NRC8214.
National Research Council of Canada, Saskatoon (Saskatchewan) Prairie
Regional Lab., May 8, 1964 (Abstract).
2. Haque, Z. U. and K. J. Aryana. 2002. Volatiles in lowfat chedder
cheese containing commercial fat replacers. Food Sci. Tech. Res. 8(2):
188-190 (Abstract).
3. Reiche, L., C. Willis, J. Wilkison, S. Shaw and O. de
Lacharriere. 1998. Clinical morphology of sodium lauryl sulfate and
nonanoic acid irritant patch test reactions at 48h and 96h in 152
subjects. Contact Dermatitis 39(5): 240-243 (Abstract).
4. Wahlberg, J. E. and H. I. Maibach. 1980. Nonanoic acid
irritation - A positive control at routing patch testing? Contact
Dermatitis 6(2): 128-130 (Abstract).
5. Willlis, C. M., C. J. M. Stephens and J. D. Wilkinson. 1988.
Experimentally-induced irritant contact dermatitis. Determination of
optimum irritant concentrations. Contact Dermatitis 18(1): 20-24
(Abstract).
6. Wahlberg, J. E., K. Wrangsjo and A. Hietasalo. 1985. Skin
irritancy from nonanoic acid. Contact Dermatitis 13(4): 266-269
(Abstract).
[FR Doc. E4-553 Filed 3-16-04; 8:45 am]
BILLING CODE 6560-50-S