[Federal Register: July 16, 2003 (Volume 68, Number 136)]
[Notices]
[Page 42035-42040]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr16jy03-83]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2003-0233; FRL-7316-2]
Cis-3-hexen-1-ol; Notice of Filing a Pesticide Petition to
Establish a Tolerance for a Certain Pesticide Chemical in or on Food
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by docket ID number OPP-2003-0233, must be
received on or before August 15, 2003.
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: Kathryn Boyle, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-6304; e-mail address: boyle.kathryn@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
[sbull] Crop production (NAICS code 111)
[sbull] Animal production (NASICS code 112)
[sbull] Food manufacturing (NAICS code 311)
[sbull] 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-2003-0233. 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.
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
[[Page 42036]]
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-2003-0233. 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-2003-0233. In contrast to EPA's
electronic public docket, EPA's e-mail system is not an ``anonymous
access'' system. If you send an e-mail comment directly to the docket
without going through EPA's electronic public docket, EPA's e-mail
system automatically captures your e-mail address. E-mail addresses
that are automatically captured by EPA's e-mail system are included as
part of the comment that is placed in the official public docket, and
made available in EPA's electronic public docket.
iii. Disk or CD ROM. You may submit comments on a disk or CD ROM
that you mail to the mailing address identified in Unit I.C.2. These
electronic submissions will be accepted in WordPerfect or ASCII file
format. Avoid the use of special characters and any form of encryption.
2. By mail. Send your comments to: Public Information and Records
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001, Attention: Docket ID Number OPP-2003-0233.
3. By hand delivery or courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Office of Pesticide
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall
2, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket
ID Number OPP-2003-0233. Such deliveries are only accepted during the
docket's normal hours of operation as identified in Unit I.B.1.
D. How Should I Submit CBI To the Agency?
Do not submit information that you consider to be CBI
electronically through EPA's electronic public docket or by e-mail. You
may claim information that you submit to EPA as CBI by marking any part
or all of that information as CBI (if you submit CBI on disk or CD ROM,
mark the outside of the disk or CD ROM as CBI and then identify
electronically within the disk or CD ROM the specific information that
is CBI). Information so marked will not be disclosed except in
accordance with procedures set forth in 40 CFR part 2.
In addition to one complete version of the comment that includes
any information claimed as CBI, a copy of the comment that does not
contain the information claimed as CBI must be submitted for inclusion
in the public docket and EPA's electronic public docket. If you submit
the copy that does not contain CBI on disk or CD ROM, mark the outside
of the disk or CD ROM clearly that it does not contain CBI. Information
not marked as CBI will be included in the public docket and EPA's
electronic public docket without prior notice. If you have any
questions about CBI or the procedures for claiming CBI, please consult
the person listed under FOR FURTHER INFORMATION CONTACT.
E. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing your
comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide copies of any technical information and/or data you used
that support your views.
4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
5. Provide specific examples to illustrate your concerns.
6. Make sure to submit your comments by the deadline in this
notice.
7. To ensure proper receipt by EPA, be sure to identify the docket
ID number assigned to this action in the subject line on the first page
of your response. You may also provide the name, date, and Federal
Register citation.
II. What Action is the Agency Taking?
EPA has received a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical in or on various food commodities under section 408
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that this petition contains data or information
regarding the elements set forth in FFDCA section 408(d)(2); however,
EPA has not fully evaluated the sufficiency of the submitted data at
[[Page 42037]]
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: July 2, 2003.
Debra Edwards,
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner's summary of the pesticide petition is printed below
as required by FFDCA section 408(d)(3). The summary of the petition was
prepared by the petitioner and represents the view of the petitioner.
EPA may have edited the summary 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
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.
Syngenta Crop Protection
PP 3E6569
EPA has received a pesticide petition (PP 3E6569) from Syngenta
Crop Protection, Inc., P.O. Box 18300, Greensboro, NC 27419 proposing,
pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40
CFR part 180 to establish an exemption from the requirement of a
tolerance for cis-3-hexen-1-ol when used as an inert ingredient in
pesticide formulations containing the active ingredient paraquat
dichloride. 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. The plant metabolism of cis-3-hexen-1-ol has
not been investigated. However, cis-3-hexen-1-ol has been commonly
detected as a volatile organic emission from a number of plant species.
Cis-3-Hexen-1-ol is also a naturally occurring aromatic substance in a
number of food products. Cis-3-Hexen-1-ol, is a terminal metabolite of
the fatty acid/lipoxygenase pathway catalyzing the normal oxidative
breakdown of plant membrane lipids.
2. Analytical method. No specific analytical method is provided
since the petition is for an exemption from the requirement of
establishing a tolerance for cis-3-hexen-1-ol. However, cis-3-hexen-1-
ol has been routinely detected in both raw agricultural commodities and
in processed foods by gas chromatography, mass spectroscopy, or a
combination of both. These methods could be readily developed and
adapted to detect cis-3-hexen-1-ol in food products to which paraquat
dichloride may be applied.
3. Magnitude of residues. Potential residues of cis-3-hexen-1-ol in
raw and or processed agricultural commodities are expected to be
minimal. Cis-3-hexen-1-ol would be present at a concentration of up to
4 grams/L only in pesticide formulations containing paraquat
dichloride. The maximum concentration of cis-3-hexen-1-ol (4 grams/L)
in paraquat dichloride formulations is much lower than the
concentration of the co-formulated active ingredient (paraquat
dichloride). Based on data presented in the re-registration eligibility
document on paraquat dichloride, and on the expected relative
concentrations of paraquat and cis-3-hexenol in end use formulations,
residues of cis-3-hexen-1-ol on agricultural commodities would be at
least 50-fold lower than paraquat dichloride. Under field conditions,
the residues of cis-3-hexen-1-ol are expected to be even lower since
cis-3-hexen-1-ol is a volatile organic compound with a substantially
higher vapor pressure than paraquat dichloride.
B. Toxicological Profile
1. Acute toxicity. The acute oral toxicity of cis-3-hexen-1-ol has
been evaluated in both rats and mice. The oral lethal dose
(LD)50 for cis-3-hexen-1-ol in rats was reported to be 4,700
milligrams/kilograms (mg/kg) body weight, with a 95% confidence
interval of 3,820 to 5,580 mg/kg body weight. In this study, most
deaths occurred within 3 hours of dosing, with all deaths occurring
within the first 24 hours post-dosing. Clinical signs observed prior to
death included ataxia followed by decreased spontaneous movement and
development of a comatose state. Necropsy evaluations revealed no
specific abnormalities in any of the rats, including decedents. Oral
lethal dose (LD)50 values of between 7,000 and 10,000 mg/kg
body weight have also been reported for both rats and mice. Rats and
mice were considerably more sensitive to the intraperitoneal
administration of cis-3-hexen-1-ol, with reported i.p. LD50
values of 600 and 400 to 500 mg/kg body weight, respectively.
Cis-3-Hexen-1-ol was essentially non-toxic by the dermal route,
with a dermal LD50 value of greater than 5,000 mg/kg body
weight (the highest dose tested) in rabbits. Similarly, the application
of neat solutions of cis-3-hexen-1-ol, held under an occlusive dressing
for 24 hours, to both the intact and abraded skin of rabbits was found
to be non-irritating. In human subjects, no dermal irritation was
reported following application of a 4% cis-3-hexen-1-ol preparation in
petrolatum held under an occlusive patch for 48 hours. In addition, the
cis-3-hexen-1-ol preparation produced no evidence of sensitization in a
maximization test conducted with 25 human volunteers.
The acute toxicity data available for cis-3-hexen-1-ol are
consistent with the data on related linear and branched chain aliphatic
unsaturated/unconjugated alcohols, aldehydes, and esters, showing this
class of substances to be of low toxicity when administered orally.
2. Genotoxicty. The genotoxicity of cis-3-hexen-1-ol has not been
formally investigated. However, cis-3-hexen-1-ol contains no structural
alerts for genotoxic potential. Cis-3-Hexen-1-ol is expected to be
oxidized to the corresponding aldehyde and carboxylic acid by high
capacity carbohydrate metabolic pathways (i.e., NAD+/NADH-dependent
metabolism to cis-3-hexenal followed by aldehyde dehydrogenase-mediated
conversion to cis-3-hexenoic acid). Products of these metabolic
pathways are not anticipated to show genotoxic activity. Information
available on substances structurally related to cis-3-hexen-1-ol
provides no evidence of mutagenic or chromosome-damaging potential. For
example, in various reverse mutation assays conducted in bacterial
cultures, oleic acid, methyl linoleate, and 2,6-dimethyl-5-heptenal
were reported to show no evidence of mutagenic activity. Similarly,
2,6-dimethyl-5-heptenal was reported to show no genotoxic activity in
an in vitro unscheduled DNA synthesis test or in an in vivo mouse
micronucleus test. Also, the longer chain saturated aliphatic alcohols
octadecan-1-ol and tetradecan-1-ol have been reported to be non-
mutagenic in the Ames test conducted with Salmonella
[[Page 42038]]
typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538.
3. Reproductive and developmental toxicity. No reproductive or
developmental toxicity studies on cis-3-hexen-1-ol were identified in
the scientific literature. Given the metabolism of cis-3-hexen-1-ol to
endogenous substrates of fatty acid oxidation pathways, or to readily
excreted carboxylic acids, it is not expected to be a reproductive
toxicant. A teratogenicity study has been conducted on 4-pentenoic
acid, a substance similar to the potential carboxylic acid metabolites
of cis-3-hexen-1-ol. In this study, 2 groups of 15 female NMRI mice
were mated with males for a period of 2 hours, and, on day 8 of
gestation, were administered, by subcutaneous injection, the sodium
salt of 4-pentenoic acid as a single 600 mg/kg body weight dose.
Implantation sites were counted and each live fetus was weighed and
examined for neural tube defects and any other visceral or skeletal
abnormalities. The study authors concluded that 4-pentenoic acid had no
effect on embryo survival, the number of live fetuses, fetal weight, or
on the incidence of neural tube defects. There were no reports of
effects of 4-pentenoic acid on the incidence rates of other visceral or
skeletal abnormalities.
Summaries of two reproductive toxicity studies on higher chain
length saturated primary alcohols also demonstrated lack of toxicity.
In these 1-generation reproductive toxicity studies, dodecan-1-ol or
octadecan-1-ol was administered in the diet to groups of male and
female rats for 14-days prior to mating and to pregnant females for an
additional 3 weeks. The maximum dietary dose tested for both compounds
was 2,000 mg/kg body weight/day. There were no reported effects of
treatment with either alcohol on the reproductive and developmental
parameters measured.
4. Subchronic toxicity. Cis-3-Hexen-1-ol has been evaluated for
subchronic toxicity in a 98-day drinking water study in rats. In this
study, groups of 15 male and 15 female weanling SPF-derived CFE rats,
housed 5 to a cage, were allowed to consume ad libitum drinking water
containing either 0, 310, 1,250, or 5,000 ppm cis-3-hexen-1-ol. Due to
volatilization loss, fresh solutions were prepared every 2 days. Body
weights, and food and water consumption were measured weekly. During
the sixth week of study, blood was collected from the tail vein of
eight rats of each sex from the control, 1,250, and 5,000 ppm dose
groups. At study termination, blood was collected from the aorta of all
animals. Hematological parameters measured included: hemoglobin
concentration, hematocrit value, erythrocyte and reticulocyte counts,
and total and differential leukocyte counts. At study termination,
serum was analyzed for the concentration of urea and for the activities
of glutamic-oxalacetic and glutamic-pyruvic transaminases. Urine was
collected from eight rats of each sex from each dose group during the
sixth week of study. Urine samples were also collected from 12 rats of
each group during the last week of study. Urine was analyzed for pH,
presence of microscopic constituents, and for bile, blood, and glucose
content. Kidney function was further evaluated through measurement of
the volume and specific gravity of urine produced during: (i) A 6-hour
period of water deprivation, (ii) the first 2 hours after loading with
a water dose of 25 milliliter (ml)/kg body weight, and (iii) a 4-hour
period starting 16 hours after water loading. Following termination
with barbiturate, all rats were necropsied, and all major tissues
grossly observed.
The brain, pituitary gland, thyroid gland, heart, liver, spleen,
kidneys, adrenals, and gonads were weighed. Tissues from the high-dose
and control rats were subject to histopathological examination.
Treatment with cis-3-hexen-1-ol had no effect on mortality,
clinical signs, body weight gains, or on food consumption. In males
treated at 5,000 ppm there was tendency to decreased water consumption,
likely as a result of the reduced palatability of the solution. In
addition, in the high-dose males, relative kidney weights were
increased and the urine collected during the first 2 hours following
water loading more concentrated (i.e., had a higher specific gravity)
in comparison to the controls. In high-dose females, transitory anemia
was observed with reduced hemoglobin concentration during week 6 of the
study. The no observed adverse effect level (NOAEL) was considered by
the study authors to be 1,250 ppm in the drinking water. This
concentration was stated to equate to a cis-3-hexen-1-ol intake of
approximately 120 to 150 mg/kg body weight/day.
5. Chronic toxicity. Cis-3-Hexen-1-ol has not been tested in a
chronic toxicity or in an oncogenicity study in rodents. Based on a
lack of structural alerts for genotoxicity, and given its
biotransformation to endogenous substrates that participate in fatty
acid metabolism in conjunction with the lack of target organ toxicity
or of effects potentially considered preneoplastic (e.g., hyperplasia)
in the 98-day drinking water study, cis-3-hexen-1-ol is not expected to
possess carcinogenic properties. In addition, cis-3-hexen-1-ol is a
linear unsaturated alcohol unrelated to the branched chain saturated
alcohol, 2-ethylhexanol, for which there exists some evidence of
hepatotoxic and neoplastic potential in rodents as a result of the
cascade of events associated with the induction of peroxisome
proliferation.
6. Animal metabolism. The metabolism of cis-3-hexen-1-ol in
mammalian systems has not been specifically investigated. One study on
the saturated homologue of cis-3-hexen-1-ol, n-hexanol, demonstrated
that following an oral dose of 8 millimol (mmol)/kg body weight (816
mg/kg body weight) to rabbits, the main metabolites (90%) were those
associated with oxidation to the corresponding aldehyde and acid, with
further [acirc]-oxidation to carbon dioxide and water. Direct
conjugation of n-hexanol with glucuronide was reportedly a minor (10%)
metabolic pathway.
Primary aliphatic alcohols attached to either linear, branched, or
unsaturated alky chains (i.e., as is the case with cis-3-hexen-1-ol)
are efficiently oxidized to the corresponding aldehyde by NAD+/NADH-
dependent alcohol dehydrogenase and then to the carboxylic acid by
aldehyde dehydrogenase. As a result, cis-3-hexen-1-ol would be expected
to be efficiently oxidized to the corresponding aldehyde and acid. The
unsaturated carboxylic acids that result from the oxidative metabolism
of linear unsaturated primary alcohols (e.g., cis-3-hexen-1-ol) are
known to participate in normal fatty acid metabolism.
7. Metabolite toxicology. The metabolism of cis-3-hexen-1-ol has
not been studied in mammalian species. Potential metabolites include 3-
hexanal, hexenoic acid, hexanoic acid and lower homologues produced
through [acirc]-oxidation. The Joint Expert Committee on Food Additives
has determined that at expected per capita intakes in the Unites
States, that cis-3-hexenal and cis-3-hexenoic acid pose no safety
concern. Dietary intakes were based on the use of the substances as
flavoring agents.
8. Endocrine disruption. In the 98-day drinking water study on cis-
3-hexen-1-ol in rats, there were no effects on endocrine or
reproductive tissues. There was no evidence of any toxic effect that
could be interpreted to indicated hormone-disrupting activity.
C. Aggregate Exposure
1. Dietary exposure. Chronic dietary exposure to cis-3-hexen-1-ol
has occurred for centuries due its natural presence in many foodstuffs
and due to
[[Page 42039]]
the use of this substance as a flavoring agent. With respect to the
natural presence of cis-3-hexen-1-ol in food, common sources include:
All green leafy plants, cruciferous plants, many fruits and vegetable,
particularly tomatoes, and many essential oils. More than 10,000 kg of
cis-3-hexen-1-ol may be consumed in the United Sates from its natural
presence in tomatoes alone.
Cis-3-Hexen-1-ol is consumed primarily through its use as a
flavoring agent. Based on measured concentrations in foods and the use
of consumption estimates of various food categories, per capita
consumption cis-3-hexen-1-ol is estimated at about 1 mg/kg body weight/
day. About 0.018 mg/kg body weight per day may be consumed as a result
of the use of cis-3-hexen-1-ol as a flavoring agent.
The residues of cis-3-hexen-1-ol on raw agricultural commodities,
due to application in paraquat formulations only, are expected to be
negligible, particularly in contrast to the human exposures to cis-3-
hexen-1-ol from its natural presence foods and from its use as a
flavoring agent.
Based on the expected relative concentrations of cis-3-hexen-1-ol
in paraquat formulations and on the chronic dietary intake of paraquat
calculated in the RED document (U.S. EPA, 1997) for paraquat
dichloride, chronic exposures to residues of cis-3-hexen-1-ol of
0.0000076 and 0.000024 mg/kg body weight/day, respectively, were
calculated for the U.S. population and for non-nursing infants less
than 1-year old. These calculated chronic exposures to cis-3-hexen-1-ol
residues on food are more than 40,000-fold lower than exposures
occurring from the natural presence of cis-3-hexen-1-ol in foods (i.e.,
1 mg/kg body weight/day from natural occurrence in food / 0.000024 mg/
kg body weight/day from possible residues on paraquat-treated food
products).
i. Food. Chronic dietary exposure to cis-3-hexen-1-ol has occurred
for centuries due its natural presence in many foodstuffs and due to
the use of this substance as a flavoring agent. With respect to the
natural presence of cis-3-hexen-1-ol in food, common sources include:
all green leafy plants, cruciferous plants, many fruits and vegetable,
particularly tomatoes, and many essential oils. More than 10,000 kg of
cis-3-hexen-1-ol may be consumed in the United Sates from its natural
presence in tomatoes alone.
Cis-3-Hexen-1-ol is consumed primarily through its use as a
flavoring agent. Based on measured concentrations in foods and the use
of consumption estimates of various food categories, per capita
consumption cis-3-hexen-1-ol is estimated at about 1 mg/kg body weight/
day. About 0.018 mg/kg body weight per day may be consumed as a result
of the use of cis-3-hexen-1-ol as a flavoring agent.
The residues of cis-3-hexen-1-ol on raw agricultural commodities,
due to application in paraquat formulations, are expected to be
negligible, particularly in contrast to the human exposures to cis-3-
hexen-1-ol from its natural presence foods and from its use as a
flavoring agent.
ii. Drinking water. Exposures to cis-3-hexen-1-ol from drinking
water are expected to be negligible. Given the volatile nature of cis-
3-hexen-1-ol, any trace concentrations of cis-3-hexen-1-ol that may
enter drinking water supplies would be readily off-gassed. In any case,
given its toxicological profile, cis-3-hexen-1-ol could not be present
in drinking water at concentrations of concern for human health.
2. Non-dietary exposure. Cis-3-Hexen-1-ol, and a number of related
alcohols and aldehydes, is a common constituent of the leafy portions
of many plant species, hence the name ``leaf alcohol ''. A number of
studies have reported the presence of cis-3-hexen-1-ol and other
compounds in the off-gas emissions from agricultural and non-
agricultural (forest) plant species. While emissions from these sources
appear considerable, it is not possible to determine the extent of
inhalation exposure to cis-3-hexen-1-ol from these sources.
D. Cumulative Effects
Cis-3-Hexen-1-ol has been shown in a 98-day toxicity study not to
produce overt organ toxicity. In addition, biochemical and metabolic
considerations indicate that cis-3-hexen-1-ol would be metabolized to
the corresponding aldehydes and acids, which, in turn, would be normal
substrates for enzymes involved in fatty acid catabolism. Based on
these data, there would appear to be no evidence for a ``common
mechanism '' of toxicity with other substances. Simple metabolism along
a common metabolic pathway does not constitute a ``common mechanism of
toxicity''. As a result, there is no expectation that the use of cis-3-
hexen-1-ol as an inert ingredient in paraquat dichloride pesticide
formulations (at up to 4 grams/L) would contribute to any cumulative
toxicity arising from exposure to other substances having a common
mechanism of toxicity.
E. Safety Determination
1. U.S. population. The results of the acute toxicity studies,
irritation and sensitization studies, and the 98-day subchronic
toxicity study demonstrate that cis-3-hexen-1-ol is of a low order of
toxicity, with no overt organ toxicity, even at high dosages. Cis-3-
Hexen-1-ol is not anticipated to be genotoxic, a conclusion consistent
with the results reported for similar compounds. Similarly, metabolic
considerations provide no evidence of severe toxicity since cis-3-
hexen-1-ol is likely biotransformed to the corresponding unsaturated
carboxylic acid, a compound that would participate in normal fatty acid
metabolism.
Use of cis-3-hexen-1-ol at up to 4 grams/L in paraquat dichloride
pesticide formulations is not expected to produce significant residues
in raw agricultural commodities. Based on tolerances established for
paraquat and on the anticipated relative concentrations of paraquat and
cis-3-hexen-1-ol in end use formulations, maximum residues of cis-3-
hexen-1-ol were estimated to be in the range of 0.0009 ppm. Under field
conditions, the residues of cis-3-hexen-1-ol are expected to be even
lower since cis-3-hexen-1-ol is highly volatile with a much higher
vapor pressure than paraquat dichloride. At these maximum residue
levels, the maximum chronic exposures to cis-3-hexen-1-ol were
estimated to be 0.0000076 and 0.000024 mg/kg body weight/day,
respectively, for the U.S. population and for non-nursing infants less
than 1-year old. These calculated chronic exposures to cis-3-hexen-1-ol
residues on food are more than 40,000-fold lower than exposures
occurring from the natural presence of cis-3-hexen-1-ol in foods.
Based on the preceding analysis, Syngenta Crop Protection, Inc.,
believes that there is a reasonable certainty that no harm will result
to the general population, including subgroups such as infants and
children, from aggregate exposures to cis-3-hexen-1-ol.
2. Infants and children. Based on the data presented in the
preceding sections and on the safety analysis presented above, Syngenta
Crop Protection, Inc., believes that there is a reasonable certainty
that no harm will result to infants and children from aggregate
exposures to cis-3-hexen-1-ol.
F. International Tolerances
No tolerances, or exemptions for tolerance, for cis-3-hexenol have
been previously requested by Syngenta Crop Protection, Inc. A maximum
residue level (MRL) for cis-3-hexen-1-ol has not been established by
the Codex Alimentarus Commission. In the United
[[Page 42040]]
States, cis-3-hexen-1-ol is cleared for use in non-food pesticide
applications.
[FR Doc. 03-17899 Filed 7-15-03; 8:45 am]
BILLING CODE 6560-50-S