[Federal Register Volume 66, Number 239 (Wednesday, December 12, 2001)]
[Notices]
[Pages 64251-64257]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-30371]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-1053; FRL-6809-8]


Notice of Filing of 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 control number PF-1053, must be 
received on or before January 11, 2002.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-1053 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: Carol E. Frazer PhD., 
Biopesticides and Pollution Prevention Division, (7511), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460; telephone number: (703) 308-8810; e-
mail address: [email protected].

SUPPLEMENTARY INFORMATION:   

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS Codes         potentially
                                                      affected  entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    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 the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
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 Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-1053. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-1053 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [email protected], or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-1053. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
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 version of the 
official record. Information not marked confidential

[[Page 64252]]

will be included in the public version of the official record without 
prior notice. If you have any questions about CBI or the procedures for 
claiming CBI, please consult the person identified 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 
control 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 section 408(d)(2); however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data support granting of the petition. Additional data 
may be needed before EPA rules on the petition.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: November 27, 2001.
Janet L. Andersen,
Director, Biopesticides and Pollution Prevention Division, Office of 
Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the view of the 
petitioners. EPA is publishing the petition summary verbatim without 
editing it in any way. The petition summary announces the availability 
of a description of the analytical methods available to EPA for the 
detection and measurement of the pesticide chemical residues or an 
explanation of why no such method is needed.
    EPA has received a pesticide petition (PP) 1F6314 from 3M, St. 
Paul, Minnesota 55144-1000, proposing pursuant to section 408(d) of the 
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to 
amend 40 CFR part 180 to establish an exemption from the requirement of 
a tolerance for the biochemical pesticides the C8, 
C10 and C12 saturated fatty acid monoesters of 
glycerol and propylene glycol in or on all raw agricultural commodities 
and food.
    Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended, 3M 
has submitted the following summary of information, data, and arguments 
in support of their pesticide petition. This summary was prepared by 3M 
and EPA has not fully evaluated the merits of the pesticide petition. 
The summary may have been edited by EPA if the terminology used was 
unclear, the summary contained extraneous material, or the summary 
unintentionally made the reader conclude that the findings reflected 
EPA's position and not the position of the petitioner.

3M

PP 1F6314

A. Product Name and Proposed Use Practices

    3M's VWX-42 Technology System is comprised of six very closely 
related active ingredients that are used singly or in combination 
against Gram positive and Gram negative bacteria, fungi, yeasts and 
lipid coated viruses to control spoilage of food and feed crops after 
harvest. The choice of which active ingredient or mix of ingredients to 
use is determined by the identity of the pest organisms to be 
controlled and the characteristics desired for the end-use formulation. 
The active ingredients are generally applied at levels between 0.1% and 
1% in the diluted formulation at a rate sufficient to wet thoroughly 
the commodity being treated.

B. Product Identity/Chemistry

    1. Identity of the pesticide and corresponding residues. The 
Chemical Abstract Services (CAS) index names for the six active 
ingredients are as follows:
     Octanoic acid, monoester with 1,2,3-propanetriol, CAS 
Registry No. 26402-26-6;
     Decanoic acid, monoester with 1,2,3-propanetriol, CAS 
Registry No. 26402-22-2;
     Dodecanoic acid, monoester with 1,2,3-propanetriol, CAS 
Registry No. 27215-38-9;
     Octanoic acid, monoester with 1,2-propanediol, CAS 
Registry No. 68332-79-6;
     Decanoic acid, monoester with 1,2-propanediol, CAS 
Registry No. 68795-69-7; and
     Dodecanoic acid, monoester with 1,2-propanediol, CAS 
Registry No. 27194-74-7.
    The residues expected in treated raw agricultural commodities and 
food are the parent compounds and/or their hydrolysis products 
(metabolites). The hydrolysis products are a mixture of the free fatty 
acid and glycerol or propylene glycol. The glycerol fatty acid 
monoesters are natural components in dietary fats and natural breakdown 
products from the metabolism of fat (triacylglycerol) in all living 
systems. The propylene glycol monoesters are metabolized by the same 
pathways and with the same ease as glycerol. Both types of active 
ingredient are metabolized by living matter as food. The first step in 
their metabolism is hydrolysis to free fatty acid and glycerol or 
propylene glycol.
    2. Magnitude of residue at the time of harvest and method used to 
determine the residue. An unreasonable worst cast physical model was 
constructed to generate the residue data. A typical end-use formulation 
was prepared containing one of the active ingredients. A typical 
diluted treatment solution (0.86% active ingredient by weight) was 
prepared by diluting the formulation with water. Eighteen different raw 
agricultural commodities were obtained from local supermarkets in St. 
Paul, Minnesota and treated with the diluted formulation by soaking at 
room temperature for 15 minutes. Ten samples of each commodity were 
weighed to the nearest milligram before treatment and allowed to drain 
on a wire grate for 1 minute before reweighing. The difference between 
pre- and post-soak weights was used as the measure of residue for each 
commodity sample.
    The commodities obtained from supermarket shelves, particularly 
beans, had inevitably lost moisture between the time of harvest and the 
time when they were treated to generate residue data. The treatment 
solution, being

[[Page 64253]]

aqueous, under the test conditions replaced moisture lost since 
harvest. In some cases, the absorption of the diluted aqueous pesticide 
formulation by the commodity was substantially greater than what would 
be expected if it had been treated immediately after harvest and 
treated by wetting its surface rather than soaking. Although certain 
residue levels determined by our worst-case physical model were clearly 
excessive, all of the experimentally determined values were included in 
the dietary analysis in keeping with the intended worst-case nature of 
the assessment. The experimentally determined residue levels used in 
the aggregate dietary risk assessment ranged from 10 to 400 parts per 
million (ppm) (milligrams/kilograms (mg/kg) commodity) active 
ingredient residue.
    3. A statement of why an analytical method for detecting and 
measuring the levels of the pesticide residue are not needed. An 
exemption from tolerance is sought because use of the VWX-42 Technology 
System active ingredients will create only minuscule exposures (< 1 mg/
kg-bodyweight (bwt)/day) when compared to the natural levels of such 
compounds in living tissue and in foods (~50-100 grams per/day (g/
day)), and compared to the levels permitted in food as direct additives 
(g/day). Hence, there will be no need to monitor for pesticide residues 
and there is no need for an analytical method for detecting and 
measuring such residues in the commodities treated.

C. Mammalian Toxicological Profile

    A substantial body of primary toxicology data were generated to 
support EPA registration as biochemical pesticides. In all studies, 
EPA's limit doses were used and the test compounds were found to be 
safe, but all tests were not conducted on all 6 active ingredients. 
Propylene glycol monocaprylate (the C8 ester) was selected 
as the test material to represent all 6 active ingredients in 
subchronic testing (90-day rat oral toxicity study). Because the 
metabolism and toxicity of the VWX-42 Technology System active 
ingredients have been well documented in the scientific literature and 
all six active ingredients are known to be identical with respect to 
toxicity and metabolism, a new 90-day study was conducted on only 1 of 
the 6 active ingredients. A full acute toxicity test battery (6 
studies) was generated on the C8 propylene glycol monoester 
and on the C12 glycerol ester, thereby bounding the chemical 
structures of all 6 ingredients.
    The results of the individual studies are summarized below.
    1. Acute oral toxicity (rat) for glycerol monolaurate: Non-toxic. A 
group of 6 fasted rats (3 male and 3 female) received a single oral 
gavage dose of glycerol monolaurate, formulated in corn oil and 
administered at a dose level of 5,000 mg/kg bwt, in a limit test. No 
abnormalities were revealed in any of the animals at the macroscopic 
examination at study termination on Day 15.
    The acute lethal oral dose to rats was demonstrated to be greater 
than 5,000 mg/kg.
    2. Acute oral toxicity (rat) for propylene glycol monocaprylate: 
Non-toxic. A group of 6 fasted rats (3 males and 3 females) received a 
single oral gavage dose of the test substance administered at a dosage 
of 5,000 mg/kg bwt. Clinical signs of reaction to treatment were 
confined to piloerection (all rats) and increased salivation (one 
female only), both evident within a few minutes of dosing with only 
piloerection persistent during the remainder of Day 1. There were no 
signs of reaction to treatment and piloerection had resolved by Day 2 
in female rats and by Day 4 in male rats. No abnormalities were 
revealed in any of the animals at the macroscopic examination at study 
termination on Day 15.
    The acute lethal oral dose to rats of propylene glycol 
monocaprylate was demonstrated in this study to be greater than 5,000 
mg/kg bwt.
    3. Acute dermal toxicity (rat) for glycerol monolaurate: Non-toxic. 
A group of 10 rats (5 males and 5 females) received a single topical 
application of glycerol monolaurate formulated in corn oil and 
administered at a dosage of 5,000 mg/kg bwt. There were no clinical 
signs of reaction to treatment observed in any animal throughout the 
study. All animals were killed as scheduled at study termination (Day 
15) and subjected to a macroscopic examination. No macroscopic 
abnormalities were observed for animals killed at study termination on 
Day 15.
    The acute lethal dermal dose to rats of glycerol monolaurate was 
demonstrated to be greater than 5,000 mg/kg bwt.
    4. Acute dermal toxicity (rat) for propylene glycol monocaprylate: 
Non-toxic. A study was performed to assess the acute dermal toxicity of 
propylene glycol monocaprylate to the rat. A group of 10 rats (5 males 
and 5 females) received a single topical application of the test 
substance at a dosage of 5,000 mg/kg bwt. All animals were killed as 
scheduled at study termination (Day 15) and subjected to a macroscopic 
examination. No macroscopic abnormalities were observed for animals 
killed at study termination on Day 15.
    The acute lethal dermal dose to rats of propylene glycol 
monocaprylate was demonstrated to be greater than 5,000 mg/kg bwt.
    5. Acute inhalation (rat) for glycerol monolaurate: Harmless by 
inhalation. In all instances, the aerosol generator was blocked 
following the start of generation. The waxiness of glycerol monolaurate 
made it impossible to generate aerosols. Because respirable particles 
cannot be produced from such low melting waxy materials, the test 
substance is considered harmless by the inhalation route of exposure 
under normal handling conditions.
    6. Acute inhalation (rat) for propylene glycol monocaprylate: Non-
toxic. The acute toxicity of propylene monocaprylate was assessed by 
exposing a group of rats (5 males and 5 female), for a period of 4 
hours, to a droplet aerosol generated from the test substance at a 
target concentration of 5 mg/L. Another group (5 male and 5 female), 
acting as a control was exposed to clean dry air only. The nominal 
concentration of propylene monocaprylate was 5.6 mg/L. The mass median 
aerodynamic (MMAD) was 2.0 m and was within the ideal range (1 
m to 4 m) for an acute inhalation study. 
Approximately 88% of the particles were considered of a respirable size 
(< 7 m in aerodynamic diameter). The LC5O (4-hour 
inhalation) for propylene glycol monocaprylate, is in excess of 4.92 
mg/L (4920 ppm) in air. EPA's limit dose for this test is 2 mg/L.
    7. Eye irritation (rabbit) for glycerol monolaurate: Slight 
irritant. Three rabbits were each administered a single ocular dose of 
0.1 mL of the test substance (mean weight 60 mg) and observed for up to 
7 days after instillation. The instillation in one animal elicited a 
corneal lesion and iritis (both Graded 1) 48 hours post dose. All 3 
rabbits exhibited transient conjunctival inflammation (up to Grade 3). 
Resolution was complete in two instances within approximately 72 hours 
of dosing and in one animal 7 days after dosing. The test material is 
considered a slight eye irritant.
    8. Eye irritation (rabbit) for propylene glycol monocaprylate: Non-
irritant. Three rabbits were each administered a single ocular dose of 
0.1 mL of propylene glycol monocaprylate test substance and observed 
for three days after instillation. The single instillation of propylene 
glycol monocaprylate elicited in two of the three rabbits a transient, 
slight to well-defined conjunctival irritation only. The test

[[Page 64254]]

substance is not considered an ocular irritant.
    9. Skin irritation (rabbit) for glycerol monolaurate: Non-Irritant. 
Three rabbits were each administered a single dermal dose of 0.5 gm of 
the test substance glycerol monolaurate, under semi-occlusive 
conditions for 4 hours and observed for up to 11 days. The test 
material produced transient slight erythema only in one animal. The 
test substance is not considered a dermal irritant.
    10. Skin irritation (rabbit) for propylene glycol monocaprylate: 
Non-irritant. Three rabbits were each administered a single dermal dose 
of 0.5 mL of the test substance propylene glycol monocaprylate under 
semi-occlusive conditions for 4 hours and observed for up to 11 days. 
Propylene glycol monocaprylate produced only slight erythema in all 
animals. The test substance is not considered a dermal irritant.
    11. Skin sensitization (guinea-pig) for glycerol monolaurate: Non-
sensitizer. Guinea pigs were dosed by intradermal injection and topical 
application. Based on the results of a preliminary study and in 
compliance with regulatory guidelines, the following dose levels were 
selected:
     Intradermal injection: 2.5% w/v in sterile water
     Topical application: 10% w/v in sterile water
     Challenge applications: 0.5 and 1% w/v in sterile water
    Ten test and five control guinea pigs were used in this study. 
Following the first challenge application, negative responses were 
observed in six test animals, inconclusive responses were seen in three 
animals and a positive response was observed in the remaining test 
animal. A second challenge was conducted to clarify these reactions. 
Following the second challenge application glycerol monolaurate did not 
produce dermal reactions in any of the test or control animals. 
Glycerol monolaurate is not considered to have the potential to cause 
skin sensitization.
    The sensitivity of the guinea-pig strain used by the laboratory is 
checked periodically with a weak/moderate sensitizer - hexyl cinnamic 
aldehyde (HCA). In this study HCA produced evidence of skin 
sensitization (delayed contact hypersensitivity) in nine of the ten 
animals, thus confirming the sensitivity and reliability of the 
experimental technique.
    12. Skin sensitization (guinea-pig) for propylene glycol 
monocaprylate: Potential sensitizer. The guinea pigs were dosed by 
intradermal injection and topical application. Based on the results of 
a preliminary study and in compliance with the regulatory guidelines, 
the following dose levels were selected:
     Intradermal injection: 0.5% v/v in sterile water
     Topical application: as supplied
     Challenge application: 25 and 50% v/v in sterile water
    Ten test and five control guinea pigs were used in this study. In 
this study propylene glycol monocaprylate produced evidence of skin 
sensitization (delayed contact hypersensitivity) in all of the test 
animals. Propylene glycol monocaprylate is considered to have the 
potential to cause skin sensitization. Propylene glycol itself is known 
to cause allergic reactions in patients receiving medical treatments 
containing this substance.
    The sensitivity of the guinea-pig strain used was checked 
periodically by the laboratory with a weak to moderate sensitizer - 
hexyl cinnamic aldehyde (HCA). In this study HCA produced evidence of 
skin sensitization (delayed contact hypersensitivity) in nine of the 
ten animals, thus confirming the sensitivity and reliability of the 
experimental technique.
    13. 28-Day oral (rat): for propylene glycol monocaprylate: Non-
toxic. The effects of propylene glycol monocaprylate (T-7475.8) were 
assessed in rats (groups of 5 males and 5 females) by oral gavage 
administration once a day for 4 weeks, employing dose levels of 0, 500, 
750 or 1,000 mg/kg/day. Doses up to 1,000 mg/kg/day were well tolerated 
with the only effects noted being higher protein and albumin values and 
a higher lung and liver weight, all in females. In the absence of 
histopathological examination, the toxicological importance of these 
findings is unclear. However, it was considered that 1,000 mg/kg/day 
was well tolerated and that it would be suitable for use as a high dose 
level in the subsequent 13 week toxicity study.
    14. 13-Week oral (rat) for propylene glycol monocaprylate: Non-
toxic. The systemic toxicity of propylene glycol monocaprylate (T-
7475.8) was assessed in groups of rats (20 males and 20 females per 
group) by oral (gavage) administration at 0, 100, 500, and 1,000 mg/kg/
day dose levels for 13 weeks. There were no unscheduled deaths in any 
of the groups and clinical observation, neurotoxicity, metabolic 
parameters and organ histopathology indicated no changes of 
toxicological significance. It was concluded that a dosage of 1,000 mg/
kg/day was considered to be a no observable adverse effect level 
(NOAEL) for both sexes.
    Waivers of genotoxicity, reproductive and developmental toxicity 
studies were also requested on the bases described below.
    15. Genotoxicity. Because the VWX-42 active ingredients themselves 
in vertebrate systems are immediately metabolized like any fats to 
polyols and free fatty acids, upon ingestion they become 
indistinguishable from the natural background of such compounds in 
living systems. Polyols and free fatty acids in living systems are not 
genotoxic. Hence, waivers were requested for all genotoxicity testing 
requirements on the basis that conducting such tests would not be of 
value to EPA in its evaluation of risks. The VWX-42 active ingredients 
are already known, from a metabolic standpoint, not to be genotoxic.
    16. Reproductive and developmental toxicity. Also on the basis of 
their metabolism, the VWX-42 active ingredients, and their natural 
breakdown products, are known not to be reproductive or developmental 
toxicants. Waivers were requested for all such testing requirements on 
the basis that conducting such tests would not be of value to EPA in 
its evaluation of risks.
    17. Scientific literature on toxicity and metabolism. Basic 
toxicity testing on mono and diacylglycerols and saturated fatty acids 
was done in the 1930-1960 period. The available data include extensive 
testing in intermediate and long-term studies. Less work has been 
published on propylene glycol saturated fatty acid esters, but the 
available data are adequate to demonstrate an equivalence between 
propylene glycol esters and acylglycerols. Comprehensive reviews are 
available prepared by a number of sources including the Food and Drug 
Administration (FDA) and the Food and Agricultural Organization of the 
United Nations (FAO) and the World Health Organization (WHO) through 
the Joint FAO/WHO Expert Committee on Food Additives (JECFA).
    The NOAELs for mono acylglycerols, regardless of the saturated 
fatty acid, are similar. Rats can be fed from 10-15% in the diet for a 
lifetime without ill effects, dose levels corresponding to 5 g/kg-bwt/
day. Rats fed propylene glycol monosuccinate and monostearate at levels 
up to 10% of the diet for six months showed no evidence of gross or 
histological pathology attributable to treatment. Dogs fed at the same 
levels for six months showed no signs of toxicity.
    The particular fatty acid moiety in mono acylglycerols does not 
matter because vertebrate systems are capable

[[Page 64255]]

of metabolizing each of the acids in the range of C8 to 
C18 with equal facility. Oxidation of fatty acids is a 
primary source of energy in vertebrate systems. Fatty acids are 
supplied in the diet in the form of triacylglycerols (fats) which are 
hydrolyzed by pancreatic lipase enzymes to form free fatty acids, 
glycerol and mono acylglycerols. The VWX-42 gylcerol active ingredients 
are indistinguishable from the natural acylglycerols and fatty acids 
found in the intestine following ingestion of fats.
    Specificity of the pancreatic lipase enzyme is independent of the 
nature of the fatty acid. It is also not stereospecific in its action 
and glycerol esters and propylene glycol esters are hydrolyzed by it 
with equal facility.
    Studies with 14C-labeled propylene glycol show that it 
is readily absorbed from the gastrointestinal tract and rapidly 
converted in the liver to 14C-glycogen or 
14CO2. In a like manner, when 14C-
glycerol is administered to the rat, radiolabel appears in expired 
CO2, blood glucose, liver glycogen, liver fat and liver 
phosphatides within 15 minutes. Within 6 hours, 40% of the label is 
contained in expired CO2 and the remainder is distributed 
through the test animal. Very small amounts are excreted.
    FDA has looked at metabolism of propylene glycol mono and 
distearate as a model compounds to represent propylene glycol fatty 
acids. In studies on radiolabeled propylene glycol distearate the rate 
limiting factor in the metabolism was found to be hydrolysis of the 
ester, which is complete in about 3 hours. In 5 hours, 94% of the 
propylene glycol is absorbed and 94% of the absorbed material is found 
in expired CO2 in 72 hours. The fatty acid portion of the 
ester is absorbed and metabolized more slowly than the propylene 
glycol. Only 51% of the stearic acid label was expired as 
CO2 in the same period.

D. Aggregate Exposure

    1. Dietary exposure. Aggregate dietary exposure estimates were 
generated using EPA's Dietary Exposure Potential Model (DEPM) 
customarily used by the agency in making such estimates. The model is 
designed to generate dietary exposure estimates by combining data from 
established food consumption data bases with residue data. In this 
case, food consumption data came from the 10th National Food 
Consumption Survey conducted during the three year period of 1994-1996 
by the Agricultural Research Service of the U.S. Department of 
Agriculture. These data are also known as the Continuing Survey of Food 
Intake by Individuals, 1994-1996 (CSFII 1994-1996).
    i. Food. Food residue estimates were generated for use in the DEPM 
analysis to simulate very broad use of the VWX-42 active ingredients. 
Specifically, residues estimates were constructed for all food 
commodities corresponding to the 18 raw agricultural commodities (RACs) 
for which residue data were generated for the following major food 
groups:
     Fruits;
     Vegetables;
     Beverages; and
     Infant food.
    In keeping with the worst case nature of the analysis, residue data 
for a tested commodity was used also for similar commodities not tested 
(e.g., spinach values were used for other delicate greens; kale values 
were used for other heavy greens such as collard; peach values were 
used for apricots). The assumption was also made that residue levels 
are not changed by cooking and that fruit and vegetable mixtures 
contain 50% of one or more RAC, unless the composition of the mixture 
is specified.
    Total dietary exposure estimates were generated using the model for 
the U.S. population and 20 subpopulations, including non-nursing 
infants and children. The subpopulation groups were defined by age, 
gender, geographic location, ethnicity and income level. All 
calculations represented residue levels assuming treatment of 100% of 
every commodity consumed in the U.S. for which residue estimates could 
be generated, another severe worst-case assumption. The model produced 
data tables containing the consumption of each food, its assumed 
residue level and the calculated exposure from that consumption in 
g/kg-bwt/day for each of the subpopulations.
    For all subpopulation groups, the commodity that contributed in the 
analysis the most to exposure was cooked green beans. This result 
reflects the fact that green beans absorbed an unexpectedly large 
amount of treatment solution in the experimental procedure used to 
generate RAC residue estimates. Based upon the worst-case data and 
assumptions described above, the model calculated the highest exposure 
of 0.5 mg/kg-bwt/day for non-nursing infants. Dietary exposure for the 
total U.S. population was less than 0.2 mg/kg-bwt/day.
    ii. Drinking water. All anticipated or proposed use for the VWX-42 
active ingredients will be indoors and the active ingredients are not 
soluble in water. Hence, drinking water is not a feasible route of 
exposure.
    2. Non-dietary exposure. The only non-dietary exposures from 
pesticidal uses of the VWX-42 active ingredients will be occupational, 
i.e., commercial applicator/mixer loader exposures. Occupational 
exposures are not included under the FFDCA in the assessment of 
aggregate exposures for the purpose of establishing tolerances and 
exemptions from tolerance.

E. Cumulative Exposure

    In assessing their cumulative effects, the VWX-42 active 
ingredients are members of a much larger class of compounds that are 
toxicologically and metabolically equivalent. This class of compounds 
are dealt with by all vertebrate systems as food rather than toxicants. 
Glycerol fatty acid monoesters are natural components in dietary fats 
and natural breakdown products from metabolism of fat (triacylglycerol) 
in all living systems. Fatty acid esters of propylene glycol also occur 
as direct food additives in the human diet in substantial quantities. 
Toxicologically and metabolically the glycerol and propylene glycol 
esters are equivalent.
    The proposed use of VWX-42 active ingredients as pesticides will 
contribute a negligible amount (total U.S. population worst case 
estimate <0.2 mg/kg/day) to the existing cumulative exposure to the 
class of compounds when compared to natural levels of such compounds 
and their metabolites in tissue and foods (50-100 g/day in humans for 
glycerol esters), and to the levels permitted in food as direct 
additives (grams per day).

F. Safety Determination

    1. U.S. population. Generating a quantitative measure of safety, 
such as a margin of exposure value (MOE), is difficult for the VWX-42 
active ingredients because they function as foods rather than toxicants 
in all test animal systems, giving no clear toxicity endpoints even 
when tested at levels representing a substantial portion of the diet. 
Both acute and subchronic primary data generated to support this 
petition show no observed adverse effects at the limit doses 
established for such tests by EPA. Subchronic and chronic exposure 
studies reported in the literature run at much higher levels (e.g., 10% 
or more of the total diet) also produced no adverse effects. In its 
review of such compounds, the JECFA observed that ``dietary loads of a 
food additive in excess of 10 percent are of little value in assessment 
of safety-in-use...'', and the committee based its conclusion of safety 
upon the biochemical and metabolic evidence that the breakdown

[[Page 64256]]

product of such additives are ``normal dietary constituents.''
    MOE levels can be calculated for the U.S. population as shown below 
in Table 1, using various NOAELs, including the NOAEL for the 90-day 
gavage study submitted in support of this petition. These values 
represent the highest levels tested, not the highest level tolerated 
without adverse effects. JECFA has also established an allowable daily 
intake value (ADI) for propylene glycol monostearate of 25 mg/kg-bwt/
day that may be used to derive an MOE estimate. The several MOE 
calculations presented in Table 1 demonstrate that exposures, even when 
estimated using severe worst-case assumptions, are well below any level 
of concern.

                      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/ U.S. Population = 0.13   U.S. population = 7,690
 propylene glycol monocaprylate         day                      mg/kg-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 =
 propylene glycol monostearate*         (= highest dose tested                            24,770
                                        = 3.22 g/kg-bwt/day)
----------------------------------------------------------------------------------------------------------------
JECFA ADI for propylene glycol         ADI = 25 mg/kg-bwt/day   Same as above            U.S. population =
 monostearate*                          including safety                                  19,230
                                        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 for infants and children can be 
calculated as shown in Table 2 using the same toxicity endpoints as for 
the U.S. population.

                      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       NOAEL = 1,000 mg/kg-bwt/ Non-nursing infants =    Non-nursing infants =
 propylene glycol monocaprylate         day                      0.44 mg/kg-bwt/day       2,270
                                                                Children 1-6 = 0.28 mg/  Children 1-6 = 3,570
                                                                 kg-bwt/day.             Children 7-12 = 6,670
                                                                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 =
 propylene glycol monostearate*         (= highest dose tested                            7,320
                                        = 3.22 g/kg-bwt/day)                             Children 1-6 = 11,500
                                                                                         Children 7-12 = 21,470
----------------------------------------------------------------------------------------------------------------
JECFA ADI for propylene glycol         ADI = 25 mg/kg-bwt/day,  Same as above            Non-nursing infants =
 monostearate*                          including safety                                  5,680
                                        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 Systems

    Because VWX-42 active ingredients in vertebrate systems are 
immediately metabolized, like any fat, to polyols and free fatty acids, 
upon ingestion they become indistinguishable from the natural 
background of such compounds in living systems. On the basis that they 
are natural components of vertebrate systems, the VWX-42 active 
ingredients, and their breakdown products, are not expected to have any 
effect on immune and endocrine systems.

H. Existing Tolerances

    No tolerances exist for any of the VWX-42 Technology System 
compounds as pesticide active ingredients. They may be used as inert 
ingredients in pesticide formulations and many clearances exist under 
the FFDCA for their use as direct and indirect food additives.
    Mono and diglycerides from fats or oils or fat-forming acids are 
affirmed as GRAS as direct food additives under 21 CFR 184.1505. Mono 
and diglycerides of C8-C14 fatty acids are exempt 
from the requirement for tolerance under 40 CFR 180.1001(c) for use as 
surfactants and adjuvants in pesticide formulations. Numerous fatty 
acids, the hydrolysis products of both the glycerol and propylene 
glycol esters, are themselves also affirmed as GRAS (21 CFR 184.1025).
    Propylene glycol mono and diesters of fatty acids are permitted 
under 21 CFR 172.856 for general use in food; 21 CFR 172.860 permits 
the corresponding fatty acid metabolites in foods; and 21 CFR 172.863 
permits salts of fatty acids in food. The monoesters are also permitted 
under 21 CFR 175.105 as ingredients in adhesives used in food contact 
applications. Propylene glycol esters of fatty acids are also cleared 
by USDA as emulsifiers in margarine or oleomargarine at 2% (48 FR 
52696, Nov. 22, 1983).
    Glycerol, a hydrolysis product of mono acylglycerols, is listed by 
FDA as a substance generally recognized as safe (GRAS) as a multiple 
purpose food additive when used in accordance with good manufacturing 
practice (21 CFR 182.1320) and as a GRAS substance when migrating to 
food from paper and

[[Page 64257]]

paperboard products (21 CFR 182.90). An exemption from tolerance has 
been established by FDA under 21 CFR 182.99 and by EPA under 40 CFR 
180.1001(c) and (e) for its use as a solvent and co-solvent in 
pesticide formulations and as an adjuvant when added to pesticide 
dilutions by growers or applicators prior to application. It is also 
deemed GRAS by the Expert Panel of the Flavor and Extract 
Manufacturers'Association of America.
    Propylene glycol, a hydrolysis product of the propylene glycol 
esters, is affirmed as GRAS under 21 CFR 184.1666. It is used as an 
anticaking agent, antioxidant, dough strengthener, emulsifier, flavor 
agent, formulation aid, humectant, processing aid, solvent and vehicle, 
stabilizer and thickener, surface-active agent, and tenderizer in foods 
at levels not to exceed current good manufacturing practice. The 
approved uses result in maximum levels, as served of 5% in alcoholic 
beverages, 24% in confections and frostings, 2.55% in frozen dairy 
products, 97% in seasonings and flavoring, 5% in nuts and nut products, 
and 2% in all other food categories. Propylene glycol is also exempt 
from the requirement of tolerance by EPA under 40 CFR 180.1001(c) and 
(e), and has been deemed GRAS by the Expert Panel of the Flavor and 
Extract Manufacturers' Association of America.

I. International Tolerances

    No international tolerances have been established for the active 
ingredients in the VWX-42 Technology system. The FAO and the WHO 
through the JECFA has reviewed mono and diacylglycerol and propylene 
glycol esters of fatty acids and determined that they may be used 
safely in foods at levels of 1-3 grams per day for an adult. It as 
observed that ``alterations in the fatty acid distribution or 
polyglycerol content of individual members of a group of diverse 
substances have no toxicological bearing and only affect the physical 
and emulsifying properties of each ester.'' The Committee concluded 
safety based upon the biochemical and metabolic evidence that the 
breakdown products of such additives are normal dietary constituents.
[FR Doc. 01-30371 Filed 12-11-01; 8:45 am]
BILLING CODE 6560-50-S