[Federal Register Volume 68, Number 136 (Wednesday, July 16, 2003)]
[Notices]
[Pages 42035-42040]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-17899]


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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: [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 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 [email protected], 
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