Federal Register/Vol. 66, No. 239/Wednesday, December 12
Federal Register / Vol. 66, No. 239 / Wednesday, December 12, 2001 / Notices 64251
process, please contact the person listed Arlington, VA, from 8:30 a.m. to 4 p.m., NAICS Examples of poten- under FOR FURTHER INFORMATION Categories Codes tially affected Monday through Friday, excluding legal CONTACT. entities holidays. The PIRIB telephone number is (703) 305–5805. List of Subjects Industry 111 Crop production 112 Animal production C. How and to Whom Do I Submit Environmental protection, Reporting 311 Food manufac- Comments? and recordkeeping requirements. turing 32532 Pesticide manufac- You may submit comments through Dated: December 3, 2001. turing the mail, in person, or electronically. To Stephen L. Johnson, ensure proper receipt by EPA, it is Assistant Administrator for Prevention, This listing is not intended to be imperative that you identify docket Pesticides and Toxic Substances. exhaustive, but rather provides a guide control number PF–1053 in the subject [FR Doc. 01–30597 Filed 12–11–01; 8:45 am] for readers regarding entities likely to be line on the first page of your response. affected by this action. Other types of 1. By mail. Submit your comments to: BILLING CODE 6560–50–S entities not listed in the table could also Public Information and Records be affected. The North American Integrity Branch (PIRIB), Information ENVIRONMENTAL PROTECTION Industrial Classification System Resources and Services Division AGENCY (NAICS) codes have been provided to (7502C), Office of Pesticide Programs assist you and others in determining (OPP), Environmental Protection whether or not this action might apply Agency, 1200 Pennsylvania Ave., NW., [PF–1053; FRL–6809–8] to certain entities. If you have questions Washington, DC 20460. 2. In person or by courier. Deliver Notice of Filing of a Pesticide Petition regarding the applicability of this action to a particular entity, consult the person your comments to: Public Information to Establish a Tolerance for a Certain and Records Integrity Branch (PIRIB), Pesticide Chemical in or on Food listed under FOR FURTHER INFORMATION CONTACT. Information Resources and Services AGENCY: Division (7502C), Office of Pesticide Environmental Protection B. How Can I Get Additional Agency (EPA). Programs (OPP), Environmental Information, Including Copies of this Protection Agency, Rm. 119, Crystal ACTION: Notice. Document and Other Related Mall #2, 1921 Jefferson Davis Highway, Documents? SUMMARY: This notice announces the Arlington, VA. The PIRIB is open from initial filing of a pesticide petition 1. Electronically. You may obtain 8:30 a.m. to 4 p.m., Monday through proposing the establishment of electronic copies of this document, and Friday, excluding legal holidays. The regulations for residues of a certain certain other related documents that PIRIB telephone number is (703) 305– pesticide chemical in or on various food might be available electronically, from 5805. commodities. the EPA Internet Home Page at http:// 3. Electronically. You may submit www.epa.gov/. To access this your comments electronically by e-mail DATES: Comments, identified by docket document, on the Home Page select to: [email protected], or you can control number PF–1053, must be ‘‘Laws and Regulations,’’ ‘‘Regulations submit a computer disk as described received on or before January 11, 2002. and Proposed Rules,’’ and then look up above. Do not submit any information ADDRESSES: Comments may be the entry for this document under the electronically that you consider to be submitted by mail, electronically, or in ‘‘Federal Register—Environmental CBI. Avoid the use of special characters person. Please follow the detailed Documents.’’ You can also go directly to and any form of encryption. Electronic instructions for each method as the Federal Register listings at http:// submissions will be accepted in provided in Unit I.C. of the www.epa.gov/fedrgstr/. Wordperfect 6.1/8.0 or ASCII file SUPPLEMENTARY INFORMATION. To ensure 2. In person. The Agency has format. All comments in electronic form proper receipt by EPA, it is imperative established an official record for this must be identified by docket control that you identify docket control number action under docket control number PF– number PF–1053. Electronic comments PF–1053 in the subject line on the first 1053. The official record consists of the may also be filed online at many Federal page of your response. documents specifically referenced in Depository Libraries. FOR FURTHER INFORMATION CONTACT: By this action, any public comments D. How Should I Handle CBI That I mail: Carol E. Frazer PhD., Biopesticides received during an applicable comment Want to Submit to the Agency? and Pollution Prevention Division, period, and other information related to (7511), Office of Pesticide Programs, this action, including any information Do not submit any information Environmental Protection Agency, 1200 claimed as confidential business electronically that you consider to be Pennsylvania Ave., NW., Washington, information (CBI). This official record CBI. You may claim information that DC 20460; telephone number: (703) includes the documents that are you submit to EPA in response to this 308–8810; e-mail address: physically located in the docket, as well document as CBI by marking any part or [email protected]. as the documents that are referenced in all of that information as CBI. those documents. The public version of Information so marked will not be SUPPLEMENTARY INFORMATION: the official record does not include any disclosed except in accordance with I. General Information information claimed as CBI. The public procedures set forth in 40 CFR part 2. version of the official record, which In addition to one complete version of A. Does this Action Apply to Me? includes printed, paper versions of any the comment that includes any You may be affected by this action if electronic comments submitted during information claimed as CBI, a copy of you are an agricultural producer, food an applicable comment period, is the comment that does not contain the manufacturer or pesticide manufacturer. available for inspection in the Public information claimed as CBI must be Potentially affected categories and Information and Records Integrity submitted for inclusion in the public entities may include, but are not limited Branch (PIRIB), Rm. 119, Crystal Mall version of the official record. to: #2, 1921 Jefferson Davis Highway, Information not marked confidential
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will be included in the public version required by section 408(d)(3) of the Abstract Services (CAS) index names for of the official record without prior FFDCA. The summary of the petition the six active ingredients are as follows: notice. If you have any questions about was prepared by the petitioner and • Octanoic acid, monoester with 1,2,3- CBI or the procedures for claiming CBI, represents the view of the petitioners. propanetriol, CAS Registry No. 26402– please consult the person identified EPA is publishing the petition summary 26–6; • under FOR FURTHER INFORMATION verbatim without editing it in any way. Decanoic acid, monoester with CONTACT. The petition summary announces the 1,2,3-propanetriol, CAS Registry No. availability of a description of the 26402–22–2; E. What Should I Consider as I Prepare analytical methods available to EPA for • Dodecanoic acid, monoester with My Comments for EPA? the detection and measurement of the 1,2,3-propanetriol, CAS Registry No. You may find the following pesticide chemical residues or an 27215–38–9; • suggestions helpful for preparing your explanation of why no such method is Octanoic acid, monoester with 1,2- comments: needed. propanediol, CAS Registry No. 68332– 1. Explain your views as clearly as EPA has received a pesticide petition 79–6; • possible. (PP) 1F6314 from 3M, St. Paul, Decanoic acid, monoester with 1,2- 2. Describe any assumptions that you Minnesota 55144–1000, proposing propanediol, CAS Registry No. 68795– used. 69–7; and pursuant to section 408(d) of the Federal • 3. Provide copies of any technical Food, Drug, and Cosmetic Act (FFDCA), Dodecanoic acid, monoester with information and/or data you used that 21 U.S.C. 346a(d), to amend 40 CFR part 1,2-propanediol, CAS Registry No. support your views. 180 to establish an exemption from the 27194–74–7. The residues expected in treated raw 4. If you estimate potential burden or requirement of a tolerance for the agricultural commodities and food are costs, explain how you arrived at the biochemical pesticides the C , C and 8 10 the parent compounds and/or their estimate that you provide. C saturated fatty acid monoesters of 12 hydrolysis products (metabolites). The 5. Provide specific examples to glycerol and propylene glycol in or on hydrolysis products are a mixture of the illustrate your concerns. all raw agricultural commodities and free fatty acid and glycerol or propylene 6. Make sure to submit your food. comments by the deadline in this Pursuant to section 408(d)(2)(A)(i) of glycol. The glycerol fatty acid notice. the FFDCA, as amended, 3M has monoesters are natural components in 7. To ensure proper receipt by EPA, submitted the following summary of dietary fats and natural breakdown be sure to identify the docket control information, data, and arguments in products from the metabolism of fat number assigned to this action in the support of their pesticide petition. This (triacylglycerol) in all living systems. subject line on the first page of your summary was prepared by 3M and EPA The propylene glycol monoesters are response. You may also provide the has not fully evaluated the merits of the metabolized by the same pathways and name, date, and Federal Register pesticide petition. The summary may with the same ease as glycerol. Both citation. have been edited by EPA if the types of active ingredient are metabolized by living matter as food. II. What Action is the Agency Taking? terminology used was unclear, the summary contained extraneous The first step in their metabolism is EPA has received a pesticide petition material, or the summary hydrolysis to free fatty acid and glycerol as follows proposing the establishment unintentionally made the reader or propylene glycol. and/or amendment of regulations for 2. Magnitude of residue at the time of conclude that the findings reflected residues of a certain pesticide chemical harvest and method used to determine EPA’s position and not the position of in or on various food commodities the residue. An unreasonable worst cast the petitioner. under section 408 of the Federal Food, physical model was constructed to Drug, and Cosmetic Act (FFDCA), 21 3M generate the residue data. A typical end- U.S.C. 346a. EPA has determined that PP 1F6314 use formulation was prepared this petition contains data or containing one of the active ingredients. information regarding the elements set A. Product Name and Proposed Use A typical diluted treatment solution forth in section 408(d)(2); however, EPA Practices (0.86% active ingredient by weight) was has not fully evaluated the sufficiency 3M’s VWX–42 Technology System is prepared by diluting the formulation of the submitted data at this time or comprised of six very closely related with water. Eighteen different raw whether the data support granting of the active ingredients that are used singly or agricultural commodities were obtained petition. Additional data may be needed in combination against Gram positive from local supermarkets in St. Paul, before EPA rules on the petition. and Gram negative bacteria, fungi, Minnesota and treated with the diluted List of Subjects yeasts and lipid coated viruses to formulation by soaking at room control spoilage of food and feed crops temperature for 15 minutes. Ten Environmental protection, after harvest. The choice of which active samples of each commodity were Agricultural commodities, Feed ingredient or mix of ingredients to use weighed to the nearest milligram before additives, Food additives, Pesticides is determined by the identity of the pest treatment and allowed to drain on a and pests, Reporting and recordkeeping organisms to be controlled and the wire grate for 1 minute before requirements. characteristics desired for the end-use reweighing. The difference between pre- Dated: November 27, 2001. formulation. The active ingredients are and post-soak weights was used as the Janet L. Andersen, generally applied at levels between measure of residue for each commodity Director, Biopesticides and Pollution 0.1% and 1% in the diluted formulation sample. Prevention Division, Office of Pesticide at a rate sufficient to wet thoroughly the The commodities obtained from Programs. commodity being treated. supermarket shelves, particularly beans, had inevitably lost moisture between Summary of Petition B. Product Identity/Chemistry the time of harvest and the time when The petitioner summary of the 1. Identity of the pesticide and they were treated to generate residue pesticide petition is printed below as corresponding residues. The Chemical data. The treatment solution, being
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aqueous, under the test conditions 1. Acute oral toxicity (rat) for glycerol abnormalities were observed for animals replaced moisture lost since harvest. In monolaurate: Non-toxic. A group of 6 killed at study termination on Day 15. some cases, the absorption of the fasted rats (3 male and 3 female) The acute lethal dermal dose to rats diluted aqueous pesticide formulation received a single oral gavage dose of of propylene glycol monocaprylate was by the commodity was substantially glycerol monolaurate, formulated in demonstrated to be greater than 5,000 greater than what would be expected if corn oil and administered at a dose level mg/kg bwt. it had been treated immediately after of 5,000 mg/kg bwt, in a limit test. No 5. Acute inhalation (rat) for glycerol harvest and treated by wetting its abnormalities were revealed in any of monolaurate: Harmless by inhalation. In surface rather than soaking. Although the animals at the macroscopic all instances, the aerosol generator was certain residue levels determined by our examination at study termination on blocked following the start of worst-case physical model were clearly Day 15. generation. The waxiness of glycerol excessive, all of the experimentally The acute lethal oral dose to rats was monolaurate made it impossible to determined values were included in the demonstrated to be greater than 5,000 generate aerosols. Because respirable dietary analysis in keeping with the mg/kg. particles cannot be produced from such intended worst-case nature of the 2. Acute oral toxicity (rat) for low melting waxy materials, the test assessment. The experimentally propylene glycol monocaprylate: Non- substance is considered harmless by the determined residue levels used in the toxic. A group of 6 fasted rats (3 males inhalation route of exposure under aggregate dietary risk assessment ranged and 3 females) received a single oral normal handling conditions. 6. Acute inhalation (rat) for propylene from 10 to 400 parts per million (ppm) gavage dose of the test substance glycol monocaprylate: Non-toxic. The (milligrams/kilograms (mg/kg) administered at a dosage of 5,000 mg/kg acute toxicity of propylene commodity) active ingredient residue. bwt. Clinical signs of reaction to monocaprylate was assessed by 3. A statement of why an analytical treatment were confined to piloerection exposing a group of rats (5 males and 5 method for detecting and measuring the (all rats) and increased salivation (one female), for a period of 4 hours, to a levels of the pesticide residue are not female only), both evident within a few droplet aerosol generated from the test needed. An exemption from tolerance is minutes of dosing with only sought because use of the VWX-42 substance at a target concentration of 5 piloerection persistent during the mg/L. Another group (5 male and 5 Technology System active ingredients remainder of Day 1. There were no signs will create only minuscule exposures (< female), acting as a control was exposed of reaction to treatment and piloerection to clean dry air only. The nominal 1 mg/kg-bodyweight (bwt)/day) when had resolved by Day 2 in female rats and compared to the natural levels of such concentration of propylene by Day 4 in male rats. No abnormalities monocaprylate was 5.6 mg/L. The mass compounds in living tissue and in foods were revealed in any of the animals at (∼50–100 grams per/day (g/day)), and median aerodynamic (MMAD) was 2.0 the macroscopic examination at study compared to the levels permitted in µm and was within the ideal range (1 termination on Day 15. food as direct additives (g/day). Hence, µm to 4 µm) for an acute inhalation The acute lethal oral dose to rats of there will be no need to monitor for study. Approximately 88% of the propylene glycol monocaprylate was pesticide residues and there is no need particles were considered of a respirable demonstrated in this study to be greater for an analytical method for detecting size (< 7 µm in aerodynamic diameter). than 5,000 mg/kg bwt. and measuring such residues in the The LC5O (4–hour inhalation) for commodities treated. 3. Acute dermal toxicity (rat) for propylene glycol monocaprylate, is in glycerol monolaurate: Non-toxic. A excess of 4.92 mg/L (4920 ppm) in air. C. Mammalian Toxicological Profile group of 10 rats (5 males and 5 females) EPA’s limit dose for this test is 2 mg/ A substantial body of primary received a single topical application of L. toxicology data were generated to glycerol monolaurate formulated in corn 7. Eye irritation (rabbit) for glycerol support EPA registration as biochemical oil and administered at a dosage of monolaurate: Slight irritant. Three pesticides. In all studies, EPA’s limit 5,000 mg/kg bwt. There were no clinical rabbits were each administered a single doses were used and the test signs of reaction to treatment observed ocular dose of 0.1 mL of the test compounds were found to be safe, but in any animal throughout the study. All substance (mean weight 60 mg) and all tests were not conducted on all 6 animals were killed as scheduled at observed for up to 7 days after active ingredients. Propylene glycol study termination (Day 15) and instillation. The instillation in one monocaprylate (the C8 ester) was subjected to a macroscopic examination. animal elicited a corneal lesion and selected as the test material to represent No macroscopic abnormalities were iritis (both Graded 1) 48 hours post all 6 active ingredients in subchronic observed for animals killed at study dose. All 3 rabbits exhibited transient testing (90–day rat oral toxicity study). termination on Day 15. conjunctival inflammation (up to Grade Because the metabolism and toxicity of The acute lethal dermal dose to rats 3). Resolution was complete in two the VWX-42 Technology System active of glycerol monolaurate was instances within approximately 72 ingredients have been well documented demonstrated to be greater than 5,000 hours of dosing and in one animal 7 in the scientific literature and all six mg/kg bwt. days after dosing. The test material is active ingredients are known to be 4. Acute dermal toxicity (rat) for considered a slight eye irritant. identical with respect to toxicity and propylene glycol monocaprylate: Non- 8. Eye irritation (rabbit) for propylene metabolism, a new 90–day study was toxic. A study was performed to assess glycol monocaprylate: Non-irritant. conducted on only 1 of the 6 active the acute dermal toxicity of propylene Three rabbits were each administered a ingredients. A full acute toxicity test glycol monocaprylate to the rat. A group single ocular dose of 0.1 mL of battery (6 studies) was generated on the of 10 rats (5 males and 5 females) propylene glycol monocaprylate test C8 propylene glycol monoester and on received a single topical application of substance and observed for three days the C12 glycerol ester, thereby bounding the test substance at a dosage of 5,000 after instillation. The single instillation the chemical structures of all 6 mg/kg bwt. All animals were killed as of propylene glycol monocaprylate ingredients. scheduled at study termination (Day 15) elicited in two of the three rabbits a The results of the individual studies and subjected to a macroscopic transient, slight to well-defined are summarized below. examination. No macroscopic conjunctival irritation only. The test
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substance is not considered an ocular of a preliminary study and in Waivers of genotoxicity, reproductive irritant. compliance with the regulatory and developmental toxicity studies were 9. Skin irritation (rabbit) for glycerol guidelines, the following dose levels also requested on the bases described monolaurate: Non-Irritant. Three rabbits were selected: below. were each administered a single dermal • Intradermal injection: 0.5% v/v in 15. Genotoxicity. Because the VWX– dose of 0.5 gm of the test substance sterile water 42 active ingredients themselves in glycerol monolaurate, under semi- • Topical application: as supplied vertebrate systems are immediately occlusive conditions for 4 hours and • Challenge application: 25 and 50% metabolized like any fats to polyols and observed for up to 11 days. The test v/v in sterile water free fatty acids, upon ingestion they material produced transient slight Ten test and five control guinea pigs become indistinguishable from the erythema only in one animal. The test were used in this study. In this study natural background of such compounds substance is not considered a dermal propylene glycol monocaprylate in living systems. Polyols and free fatty irritant. produced evidence of skin sensitization acids in living systems are not 10. Skin irritation (rabbit) for (delayed contact hypersensitivity) in all genotoxic. Hence, waivers were propylene glycol monocaprylate: Non- of the test animals. Propylene glycol requested for all genotoxicity testing irritant. Three rabbits were each monocaprylate is considered to have the requirements on the basis that administered a single dermal dose of 0.5 potential to cause skin sensitization. conducting such tests would not be of mL of the test substance propylene Propylene glycol itself is known to value to EPA in its evaluation of risks. glycol monocaprylate under semi- cause allergic reactions in patients The VWX–42 active ingredients are occlusive conditions for 4 hours and receiving medical treatments containing already known, from a metabolic observed for up to 11 days. Propylene this substance. standpoint, not to be genotoxic. glycol monocaprylate produced only The sensitivity of the guinea-pig 16. Reproductive and developmental slight erythema in all animals. The test strain used was checked periodically by toxicity. Also on the basis of their substance is not considered a dermal the laboratory with a weak to moderate metabolism, the VWX–42 active irritant. sensitizer - hexyl cinnamic aldehyde ingredients, and their natural 11. Skin sensitization (guinea-pig) for (HCA). In this study HCA produced breakdown products, are known not to glycerol monolaurate: Non-sensitizer. evidence of skin sensitization (delayed be reproductive or developmental Guinea pigs were dosed by intradermal contact hypersensitivity) in nine of the toxicants. Waivers were requested for all injection and topical application. Based ten animals, thus confirming the such testing requirements on the basis on the results of a preliminary study sensitivity and reliability of the that conducting such tests would not be and in compliance with regulatory experimental technique. of value to EPA in its evaluation of guidelines, the following dose levels 13. 28–Day oral (rat): for propylene risks. were selected: glycol monocaprylate: Non-toxic. The 17. Scientific literature on toxicity • Intradermal injection: 2.5% w/v in effects of propylene glycol and metabolism. Basic toxicity testing sterile water monocaprylate (T–7475.8) were on mono and diacylglycerols and • Topical application: 10% w/v in assessed in rats (groups of 5 males and saturated fatty acids was done in the sterile water 5 females) by oral gavage administration 1930–1960 period. The available data • Challenge applications: 0.5 and 1% once a day for 4 weeks, employing dose include extensive testing in w/v in sterile water levels of 0, 500, 750 or 1,000 mg/kg/day. intermediate and long-term studies. Less Ten test and five control guinea pigs Doses up to 1,000 mg/kg/day were well work has been published on propylene were used in this study. Following the tolerated with the only effects noted glycol saturated fatty acid esters, but the first challenge application, negative being higher protein and albumin values available data are adequate to responses were observed in six test and a higher lung and liver weight, all demonstrate an equivalence between animals, inconclusive responses were in females. In the absence of propylene glycol esters and seen in three animals and a positive histopathological examination, the acylglycerols. Comprehensive reviews response was observed in the remaining toxicological importance of these are available prepared by a number of test animal. A second challenge was findings is unclear. However, it was sources including the Food and Drug conducted to clarify these reactions. considered that 1,000 mg/kg/day was Administration (FDA) and the Food and Following the second challenge well tolerated and that it would be Agricultural Organization of the United application glycerol monolaurate did suitable for use as a high dose level in Nations (FAO) and the World Health not produce dermal reactions in any of the subsequent 13 week toxicity study. Organization (WHO) through the Joint the test or control animals. Glycerol 14. 13–Week oral (rat) for propylene FAO/WHO Expert Committee on Food monolaurate is not considered to have glycol monocaprylate: Non-toxic. The Additives (JECFA). the potential to cause skin sensitization. systemic toxicity of propylene glycol The NOAELs for mono acylglycerols, The sensitivity of the guinea-pig monocaprylate (T–7475.8) was assessed regardless of the saturated fatty acid, are strain used by the laboratory is checked in groups of rats (20 males and 20 similar. Rats can be fed from 10–15% in periodically with a weak/moderate females per group) by oral (gavage) the diet for a lifetime without ill effects, sensitizer - hexyl cinnamic aldehyde administration at 0, 100, 500, and 1,000 dose levels corresponding to 5 g/kg-bwt/ (HCA). In this study HCA produced mg/kg/day dose levels for 13 weeks. day. Rats fed propylene glycol evidence of skin sensitization (delayed There were no unscheduled deaths in monosuccinate and monostearate at contact hypersensitivity) in nine of the any of the groups and clinical levels up to 10% of the diet for six ten animals, thus confirming the observation, neurotoxicity, metabolic months showed no evidence of gross or sensitivity and reliability of the parameters and organ histopathology histological pathology attributable to experimental technique. indicated no changes of toxicological treatment. Dogs fed at the same levels 12. Skin sensitization (guinea-pig) for significance. It was concluded that a for six months showed no signs of propylene glycol monocaprylate: dosage of 1,000 mg/kg/day was toxicity. Potential sensitizer. The guinea pigs considered to be a no observable The particular fatty acid moiety in were dosed by intradermal injection and adverse effect level (NOAEL) for both mono acylglycerols does not matter topical application. Based on the results sexes. because vertebrate systems are capable
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of metabolizing each of the acids in the Food Intake by Individuals, 1994–1996 2. Non-dietary exposure. The only range of C8 to C18 with equal facility. (CSFII 1994–1996). non-dietary exposures from pesticidal Oxidation of fatty acids is a primary i. Food. Food residue estimates were uses of the VWX–42 active ingredients source of energy in vertebrate systems. generated for use in the DEPM analysis will be occupational, i.e., commercial Fatty acids are supplied in the diet in to simulate very broad use of the VWX– applicator/mixer loader exposures. the form of triacylglycerols (fats) which 42 active ingredients. Specifically, Occupational exposures are not are hydrolyzed by pancreatic lipase residues estimates were constructed for included under the FFDCA in the enzymes to form free fatty acids, all food commodities corresponding to assessment of aggregate exposures for glycerol and mono acylglycerols. The the 18 raw agricultural commodities the purpose of establishing tolerances VWX–42 gylcerol active ingredients are (RACs) for which residue data were and exemptions from tolerance. indistinguishable from the natural generated for the following major food E. Cumulative Exposure acylglycerols and fatty acids found in groups: the intestine following ingestion of fats. • Fruits; In assessing their cumulative effects, Specificity of the pancreatic lipase • Vegetables; the VWX–42 active ingredients are enzyme is independent of the nature of • Beverages; and members of a much larger class of the fatty acid. It is also not • Infant food. compounds that are toxicologically and stereospecific in its action and glycerol In keeping with the worst case nature metabolically equivalent. This class of esters and propylene glycol esters are of the analysis, residue data for a tested compounds are dealt with by all hydrolyzed by it with equal facility. commodity was used also for similar vertebrate systems as food rather than Studies with 14C-labeled propylene commodities not tested (e.g., spinach toxicants. Glycerol fatty acid monoesters glycol show that it is readily absorbed values were used for other delicate are natural components in dietary fats from the gastrointestinal tract and greens; kale values were used for other and natural breakdown products from rapidly converted in the liver to 14C- heavy greens such as collard; peach metabolism of fat (triacylglycerol) in all 14 glycogen or CO2. In a like manner, values were used for apricots). The living systems. Fatty acid esters of when 14C-glycerol is administered to the assumption was also made that residue propylene glycol also occur as direct rat, radiolabel appears in expired CO2, levels are not changed by cooking and food additives in the human diet in blood glucose, liver glycogen, liver fat that fruit and vegetable mixtures contain substantial quantities. Toxicologically and liver phosphatides within 15 50% of one or more RAC, unless the and metabolically the glycerol and minutes. Within 6 hours, 40% of the composition of the mixture is specified. propylene glycol esters are equivalent. label is contained in expired CO2 and Total dietary exposure estimates were The proposed use of VWX–42 active the remainder is distributed through the generated using the model for the U.S. ingredients as pesticides will contribute test animal. Very small amounts are population and 20 subpopulations, a negligible amount (total U.S. excreted. including non-nursing infants and population worst case estimate <0.2 mg/ FDA has looked at metabolism of children. The subpopulation groups kg/day) to the existing cumulative propylene glycol mono and distearate as were defined by age, gender, geographic exposure to the class of compounds a model compounds to represent location, ethnicity and income level. All when compared to natural levels of such propylene glycol fatty acids. In studies calculations represented residue levels compounds and their metabolites in on radiolabeled propylene glycol assuming treatment of 100% of every tissue and foods (50–100 g/day in distearate the rate limiting factor in the commodity consumed in the U.S. for humans for glycerol esters), and to the metabolism was found to be hydrolysis which residue estimates could be levels permitted in food as direct of the ester, which is complete in about generated, another severe worst-case additives (grams per day). assumption. The model produced data 3 hours. In 5 hours, 94% of the F. Safety Determination propylene glycol is absorbed and 94% tables containing the consumption of of the absorbed material is found in each food, its assumed residue level and 1. U.S. population. Generating a expired CO2 in 72 hours. The fatty acid the calculated exposure from that quantitative measure of safety, such as portion of the ester is absorbed and consumption in µg/kg-bwt/day for each a margin of exposure value (MOE), is metabolized more slowly than the of the subpopulations. difficult for the VWX–42 active propylene glycol. Only 51% of the For all subpopulation groups, the ingredients because they function as stearic acid label was expired as CO2 in commodity that contributed in the foods rather than toxicants in all test the same period. analysis the most to exposure was animal systems, giving no clear toxicity cooked green beans. This result reflects endpoints even when tested at levels D. Aggregate Exposure the fact that green beans absorbed an representing a substantial portion of the 1. Dietary exposure. Aggregate dietary unexpectedly large amount of treatment diet. Both acute and subchronic primary exposure estimates were generated solution in the experimental procedure data generated to support this petition using EPA’s Dietary Exposure Potential used to generate RAC residue estimates. show no observed adverse effects at the Model (DEPM) customarily used by the Based upon the worst-case data and limit doses established for such tests by agency in making such estimates. The assumptions described above, the model EPA. Subchronic and chronic exposure model is designed to generate dietary calculated the highest exposure of 0.5 studies reported in the literature run at exposure estimates by combining data mg/kg-bwt/day for non-nursing infants. much higher levels (e.g., 10% or more from established food consumption data Dietary exposure for the total U.S. of the total diet) also produced no bases with residue data. In this case, population was less than 0.2 mg/kg-bwt/ adverse effects. In its review of such food consumption data came from the day. compounds, the JECFA observed that 10th National Food Consumption ii. Drinking water. All anticipated or ‘‘dietary loads of a food additive in Survey conducted during the three year proposed use for the VWX–42 active excess of 10 percent are of little value period of 1994–1996 by the Agricultural ingredients will be indoors and the in assessment of safety-in-use...’’, and Research Service of the U.S. Department active ingredients are not soluble in the committee based its conclusion of of Agriculture. These data are also water. Hence, drinking water is not a safety upon the biochemical and known as the Continuing Survey of feasible route of exposure. metabolic evidence that the breakdown
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product of such additives are ‘‘normal this petition. These values represent the day that may be used to derive an MOE dietary constituents.’’ highest levels tested, not the highest estimate. The several MOE calculations MOE levels can be calculated for the level tolerated without adverse effects. presented in Table 1 demonstrate that U.S. population as shown below in JECFA has also established an allowable exposures, even when estimated using Table 1, using various NOAELs, daily intake value (ADI) for propylene severe worst-case assumptions, are well including the NOAEL for the 90–day glycol monostearate of 25 mg/kg-bwt/ below any level of concern. gavage study submitted in support of
TABLE 1. CALCULATED MARGINS OF EXPOSURE FOR VWX–42 ACTIVE INGREDIENTS
Basis for calculation Acceptable level Estimated exposure Margin of exposure
NOAEL, 90–day gavage study using NOAEL = 1,000 mg/kg-bwt/day U.S. Population = 0.13 mg/kg- U.S. population = 7,690 propylene glycol monocaprylate bwt/day Non-nursing infants = 0.44 mg/ kg-bwt/day
FDA NOAEL, 90–day dietary study with NOAEL = 7.52% of diet (= Same as above U.S. population = 24,770 propylene glycol monostearate* highest dose tested = 3.22 g/ kg-bwt/day)
JECFA ADI for propylene glycol ADI = 25 mg/kg-bwt/day includ- Same as above U.S. population = 19,230 monostearate* ing safety factor of 100 *Propylene glycol monostearate is widely accepted as a surrogate for all glycerol and propylene glycol monoesters.
2. Infants and children. MOE levels same toxicity endpoints as for the U.S. for infants and children can be population. calculated as shown in Table 2 using the
TABLE 2. CALCULATED MARGINS OF EXPOSURE FOR VWX–42 ACTIVE INGREDIENTS
Basis for calculation Acceptable level Estimated exposure Margin of exposure
NOAEL, 90–day garage study using pro- NOAEL = 1,000 mg/kg-bwt/day Non-nursing infants = 0.44 mg/ Non-nursing infants = 2,270 pylene glycol monocaprylate kg-bwt/day Children 1–6 = 3,570 Children 1–6 = 0.28 mg/kg-bwt/ Children 7–12 = 6,670 day Children 7–12 = 0.15 mg/kg- bwt/day
FDA NOAEL, 90–day dietary study with NOAEL = 7.52% of diet (= Same as above Non-nursing infants = 7,320 propylene glycol monostearate* highest dose tested = 3.22 g/ Children 1–6 = 11,500 kg-bwt/day) Children 7–12 = 21,470
JECFA ADI for propylene glycol ADI = 25 mg/kg-bwt/day, in- Same as above Non-nursing infants = 5,680 monostearate* cluding safety factor of 100 Children 1–6 = 8,930 Children 7–12 = 16,670 *Propylene glycol monostearate is widely accepted as a surrogate for all glycerol and propylene glycol monoesters.
G. Effects on the Immune and Endocrine ingredients. They may be used as inert 172.856 for general use in food; 21 CFR Systems ingredients in pesticide formulations 172.860 permits the corresponding fatty and many clearances exist under the acid metabolites in foods; and 21 CFR Because VWX–42 active ingredients FFDCA for their use as direct and 172.863 permits salts of fatty acids in in vertebrate systems are immediately indirect food additives. food. The monoesters are also permitted metabolized, like any fat, to polyols and free fatty acids, upon ingestion they Mono and diglycerides from fats or under 21 CFR 175.105 as ingredients in become indistinguishable from the oils or fat-forming acids are affirmed as adhesives used in food contact natural background of such compounds GRAS as direct food additives under 21 applications. Propylene glycol esters of in living systems. On the basis that they CFR 184.1505. Mono and diglycerides of fatty acids are also cleared by USDA as are natural components of vertebrate C8–C14 fatty acids are exempt from the emulsifiers in margarine or systems, the VWX–42 active requirement for tolerance under 40 CFR oleomargarine at 2% (48 FR 52696, Nov. ingredients, and their breakdown 180.1001(c) for use as surfactants and 22, 1983). products, are not expected to have any adjuvants in pesticide formulations. Glycerol, a hydrolysis product of effect on immune and endocrine Numerous fatty acids, the hydrolysis mono acylglycerols, is listed by FDA as systems. products of both the glycerol and a substance generally recognized as safe propylene glycol esters, are themselves (GRAS) as a multiple purpose food H. Existing Tolerances also affirmed as GRAS (21 CFR additive when used in accordance with No tolerances exist for any of the 184.1025). good manufacturing practice (21 CFR VWX–42 Technology System Propylene glycol mono and diesters of 182.1320) and as a GRAS substance compounds as pesticide active fatty acids are permitted under 21 CFR when migrating to food from paper and
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paperboard products (21 CFR 182.90). ENVIRONMENTAL PROTECTION assist you and others in determining An exemption from tolerance has been AGENCY whether or not this action might apply to certain entities. If you have questions established by FDA under 21 CFR [PF–1058; FRL–6812–7] 182.99 and by EPA under 40 CFR regarding the applicability of this action 180.1001(c) and (e) for its use as a Notice of Filing a Pesticide Petition to to a particular entity, consult the person solvent and co-solvent in pesticide Establish a Tolerance fora Certain listed under FOR FURTHER INFORMATION formulations and as an adjuvant when Pesticide Chemical in or on Food CONTACT. added to pesticide dilutions by growers B. How Can I Get Additional AGENCY: Environmental Protection or applicators prior to application. It is Information, Including Copies of this Agency (EPA). also deemed GRAS by the Expert Panel Document and Other Related of the Flavor and Extract ACTION: Notice. Documents? Manufacturers’Association of America. SUMMARY: This notice announces the 1. Electronically. You may obtain Propylene glycol, a hydrolysis initial filing of a pesticide petition electronic copies of this document, and product of the propylene glycol esters, proposing the establishment of certain other related documents that is affirmed as GRAS under 21 CFR regulations for residues of a certain might be available electronically, from 184.1666. It is used as an anticaking pesticide chemical in or on various food the EPA Internet Home Page at http:// agent, antioxidant, dough strengthener, commodities. www.epa.gov/. To access this emulsifier, flavor agent, formulation aid, DATES: Comments, identified by docket document, on the Home Page select humectant, processing aid, solvent and control number PF–1058, must be ‘‘Laws and Regulations,’’ ‘‘Regulations vehicle, stabilizer and thickener, received on or before January 11, 2002. and Proposed Rules,’’ and then look up the entry for this document under the surface-active agent, and tenderizer in ADDRESSES: Comments may be ‘‘Federal Register—Environmental foods at levels not to exceed current submitted by mail, electronically, or in person. Please follow the detailed Documents.’’ You can also go directly to good manufacturing practice. The the Federal Register listings at http:// approved uses result in maximum instructions for each method as provided in Unit I.C. of the www.epa.gov/fedrgstr/. levels, as served of 5% in alcoholic 2. In person. The Agency has beverages, 24% in confections and SUPPLEMENTARY INFORMATION. To ensure proper receipt by EPA, it is imperative established an official record for this frostings, 2.55% in frozen dairy action under docket control number PF– products, 97% in seasonings and that you identify docket control number PF–1058 in the subject line on the first 1058. The official record consists of the flavoring, 5% in nuts and nut products, page of your response. documents specifically referenced in and 2% in all other food categories. this action, any public comments FOR FURTHER INFORMATION CONTACT: Propylene glycol is also exempt from By received during an applicable comment mail: Hoyt Jamerson, Registration the requirement of tolerance by EPA period, and other information related to Division (7505C), Office of Pesticide under 40 CFR 180.1001(c) and (e), and this action, including any information Programs, Environmental Protection has been deemed GRAS by the Expert claimed as confidential business Agency, 1200 Pennsylvania Ave., NW., information (CBI). This official record Panel of the Flavor and Extract Washington, DC 20460; telephone Manufacturers’ Association of America. includes the documents that are number: (703) 308–9368; e-mail address: physically located in the docket, as well I. International Tolerances [email protected]. as the documents that are referenced in SUPPLEMENTARY INFORMATION: those documents. The public version of No international tolerances have been the official record does not include any established for the active ingredients in I. General Information information claimed as CBI. The public the VWX–42 Technology system. The A. Does this Action Apply to Me? version of the official record, which FAO and the WHO through the JECFA You may be affected by this action if includes printed, paper versions of any has reviewed mono and diacylglycerol you are an agricultural producer, food electronic comments submitted during and propylene glycol esters of fatty manufacturer or pesticide manufacturer. an applicable comment period, is acids and determined that they may be Potentially affected categories and available for inspection in the Public used safely in foods at levels of 1–3 entities may include, but are not limited Information and Records Integrity grams per day for an adult. It as to: Branch (PIRIB), Rm. 119, Crystal Mall observed that ‘‘alterations in the fatty #2, 1921 Jefferson Davis Highway, acid distribution or polyglycerol content NAICS Examples of poten- Arlington, VA, from 8:30 a.m. to 4 p.m., of individual members of a group of Categories tially affected enti- Monday through Friday, excluding legal codes ties diverse substances have no toxicological holidays. The PIRIB telephone number bearing and only affect the physical and Industry 111 Crop production is (703) 305–5805. emulsifying properties of each ester.’’ 112 Animal production C. How and to Whom Do I Submit The Committee concluded safety based 311 Food manufac- Comments? upon the biochemical and metabolic turing evidence that the breakdown products 32532 Pesticide manufac- You may submit comments through turing of such additives are normal dietary the mail, in person, or electronically. To ensure proper receipt by EPA, it is constituents. This listing is not intended to be imperative that you identify docket [FR Doc. 01–30371 Filed 12–11–01; 8:45 am] exhaustive, but rather provides a guide control number PF–1058 in the subject BILLING CODE 6560–50–S for readers regarding entities likely to be line on the first page of your response. affected by this action. Other types of 1. By mail. Submit your comments to: entities not listed in the table could also Public Information and Records be affected. The North American Integrity Branch (PIRIB), Information Industrial Classification System Resources and Services Division (NAICS) codes have been provided to (7502C), Office of Pesticide Programs
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