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Cis-3-hexen-1-ol; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food

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AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice.

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.

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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.

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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:

  • Crop production (NAICS code 111)
  • Animal production (NASICS 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-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 Start Printed Page 42036other 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 Start Printed Page 42037this time or whether the data support granting of the petition. Additional data may be needed before EPA rules on the petition.

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List of Subjects

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Dated: July 2, 2003.

Debra Edwards,

Director, Registration Division, Office of Pesticide Programs.

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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 Start Printed Page 42038typhimurium 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 â-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 â-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 Start Printed Page 42039the 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 Start Printed Page 42040States, cis-3-hexen-1-ol is cleared for use in non-food pesticide applications.

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[FR Doc. 03-17899 Filed 7-15-03; 8:45 am]

BILLING CODE 6560-50-S