[Federal Register Volume 62, Number 114 (Friday, June 13, 1997)]
[Notices]
[Pages 32331-32336]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-15369]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-738; FRL-5721-6]


Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various agricultural commodities.

DATES: Comments, identified by the docket control number PF-738, must 
be received on or before July 14, 1997.

ADDRESSES: By mail submit written comments to: Public Response and 
Program Resources Branch, Field Operations Divison (7505C), Office of 
Pesticides Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. In person bring comments to: Rm. 1132, CM #2, 
1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following 
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential 
business information should be submitted through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). CBI should not be 
submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2. A copy of the comment that does not contain CBI must be submitted 
for inclusion in the public record. Information not marked confidential 
may be disclosed publicly by EPA without prior notice. All written 
comments will be available for public inspection in Rm. 1132 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: The Product Manager (PM 90), 
Biopesticides and Pollution Prevention Division, (7501W), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460, listed in the table below:

                                                                                                                
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                 Name                          Location                Phone No.              E-mail address    
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Linda Hollis.........................  5th Floor 5-J, CS#1,     703-308-8733...........  [email protected]
                                        2800 Crystal Drive,                               a.gov                 
                                        Arlington, VA..                                                         
Sheryl Reilly........................  5th Floor 5-W31, do....  703-308-8265...........  [email protected]
pa.gov                
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemicals in or on various raw 
agricultural commodities under section 408 of the Federal Food, Drug, 
and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these 
petitions contain 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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.
    The official record for this notice, as well as the public version, 
has been established for this notice of filing under docket control 
number PF-738 (including comments and data submitted electronically as 
described below). A public version of this record, including printed, 
paper versions of electronic comments, which does not include any 
information claimed as CBI, is available for inspection from 8:30 a.m. 
to 4 p.m., Monday through Friday, excluding legal holidays. The 
official record is located at the address in ``ADDRESSES''.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in Wordperfect 5.1 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by the docket control number PF-738 and appropriate petition 
number. Electronic comments on this notice may be filed online at many 
Federal Depository Libraries.
    Authority: 21 U.S.C. 346a.

List of Subjects

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

    Dated: May 29, 1997.

Janet L. Andersen,
Director, Biopesticides and Pollution Prevention Division, Office of 
Pesticide Programs.

Summaries of Petitions

    Below summaries of the pesticide petitions are printed. The 
summaries of the petitions were prepared by the petitioners. 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.

1. W. Neudorff GmbH KG Petition Summary:

PP 7F4804

    EPA has received a pesticide petition (PP 7F4804) from W. Neudorff 
GmbH KG (``Neudorff''), c/o Walter G. Talarek, 1008 Riva Ridge Drive, 
Great Falls, VA 22066, proposing pursuant to section 408(d) of the 
Federal Food, Drug and Cosmetic Act, 21 U.S.C. section 346a(d), to 
amend 40 CFR Part 180 by establishing an exemption from the requirement 
for a tolerance for residues of the mollusicide iron phosphate when 
used in accordance with good agricultural practice as an active 
ingredient in pesticide formulations applied to growing crops.

A. Proposed Use Practices

    1. Recommended amount, frequency, method and time of application of 
pesticide chemical. The amount, frequency, method and time of 
application of the pesticide are described in detail on the label of 
``NEU 1165M Slug and Snail Bait''. This label was submitted to EPA as 
part of Neudorff's application for registration, EPA File Symbol 67702-
G. However, in

[[Page 32332]]

summary, the bait should be scattered by hand or with a granular 
spreader at the rate of 1 pound (lb.) per 1,000 square feet to the 
surface of damp soil. The bait can be applied either prior to or after 
infestation by slugs or snails. Evening is the best time to apply the 
bait. The bait should be reapplied as it is consumed or at least every 
two weeks.

B. Product Identity/Chemistry

    1. Identity of the pesticide and corresponding residues. The active 
ingredient is iron phosphate, also known as ferric orthophosphate; 
ferric phosphate; Fe(+3) phosphate; iron (III) phosphate; and 
phosphoric acid, and iron (3+) salt (1:1), which has a CAS #10045-86-0. 
Iron phosphate is practically insoluble in water and would only degrade 
through the metabolism of microorganisms in the soil and via the 
chemistry of plant root exudates which would utilize the degradates for 
plant growth. In certain soil types, iron phosphate may produce iron 
oxides and hydroxides that are no different from those normally found 
in soils, and which give soils their brown and red colors. Although 
some bacteria can reduce Iron (III) to the more mobile Iron (II), 
reoxidation and reprecipitation to Fe (III) oxides and hydroxides will 
rapidly immobilize any free Fe (II) that may form.
    2.  Magnitude of the residue anticipated at the time of harvest and 
method used to determine the residue. A waiver has been requested for 
these data requirements based on iron phosphate's (1) known low 
toxicity and risks, (2) natural occurrence and abundance in the 
environment, (3) widespread use as human nutrient and dietary 
supplements and in infant formula, (4) FDA generally recognized as safe 
(``GRAS'') status, (5) unique, non-toxic mode of action, (6) data 
available in the open literature, and (7) the fact that any degradates 
or metabolites of iron phosphate would be identical to those formed in 
nature, thus indicating that they should pose no unreasonable risks.
    There are other factors which indicate that residues of iron 
phosphate are unlikely to occur, or if they do occur they are unlikely 
to be at levels of concern to human health. Iron phosphate from the 
Slug and Snail Bait most likely would not occur in plants, because it 
needs to be biodegraded via microbial action or plant root exudates 
before plants can utilize it. Furthermore, the use pattern for the Slug 
and Snail bait, where the product is not applied directly to plants but 
around them, and the facts that iron phosphate is insoluble in water 
and readily adsorbs to soils, would limit the availability of the 
chemical to plants. Last, even if residues of the chemical were to 
occur on plants, this chemical contains substances which are essential 
animal and plant nutrients, and there are chemical and physical factors 
which limit their availability in humans and growing plants.
    3. Statement of why an analytical method for detecting and 
measuring the levels of the pesticide residue are not needed. Neudorff 
has not proposed an analytical method, because iron residue levels 
harmful to plants and animals are highly unlikely to occur when its 
Slug and Snail Bait product is applied according to label directions. 
Iron phosphate is an FDA-approved GRAS direct and indirect food 
additive which is not expected to present any significant adverse 
health effects to humans. Moreover, this chemical contains certain 
substances which are essential animal and plant nutrients, and there 
are chemical and physical factors which limit their availability in 
humans and growing plants. Furthermore, toxic levels of iron in plants 
induce an imbalance with other metals which causes plant dwarfing, 
stunted roots and decreased growth and yields, which effects appear 
before significant iron buildup occurs, and consequently acts as a 
warning which prevents excess application of iron compounds to plants. 
In addition, given the use pattern for the Slug and Snail Bait, where 
the product is not applied directly to plants but around them, and the 
fact that iron phosphate is insoluble in water and readily adsorbs to 
soils, there is unlikely to be significant amounts of residue in or on 
treated crops. Last, iron phosphate from the bait most likely would not 
occur in plants because it needs to be biodegraded via microbial action 
or plant root exudates before plants can utilize it.

C. Mammalian Toxicological Profile

    1. Acute toxicity. The iron salts are of low acute toxicity through 
oral, dermal and inhalation routes of exposure. Results of studies 
conducted on the end-use product for which Neudorff has applied for 
registration confirm that this chemical has low acute toxicities. Iron 
phosphate is insoluble in water. Because of this, it is not as 
bioavailable as other iron salts, and it is not readily absorbed from 
the gastrointestinal tract into the systemic circulation. Consequently, 
it may be concluded that iron phosphate will have lower acute 
toxicities than the water-soluble iron salts.
    2. Genotoxicity, reproductive and developmental toxicity, 
subchronic toxicity, and chronic toxicity. There is adequate 
information available from literature sources to characterize the 
toxicity of the iron salts (iron phosphate is an iron salt). Literature 
sources show that the iron salts have known low toxicities and risks 
and occur naturally and abundantly in the environment. Iron is 
recognized as an essential mineral nutrient for humans and all other 
vertebrate animals. It is a component of hemoglobin and myoglobin 
molecules, being the central atom in the heme portion of the molecule. 
The hemoglobin in red blood cells transports oxygen from the lungs to 
body cells and returns waste carbon dioxide from the cells to the 
lungs. The myoblobin in red muscle tissue transports oxygen into the 
tissues for energy storage. Iron also is a component of certain 
metabolic enzymes. Iron in the body that is not in use in these 
molecules is stored in the spleen, bone marrow and liver. Increased 
requirements for iron occur during the growth period and pregnacy and 
with excessive menses and other instances of blood loss. The average 
diet contains 10 to 15 mg a day, adequate for most people. Lack of 
sufficient iron causes fatigue and paleness and eventually leads to 
some form of anemia. With increases in iron beyond the physiologic 
limits, most of it is excreted in the feces, but small amounts may 
accumulate. Some iron may be excreted via the bile. In cases of 
overload, iron is excreted in the urine, and the presence of high 
urinary iron concentrations is indicative of excessive iron. Normally, 
significant quantities of iron are excreted by loss of epithelial cells 
of the gastrointestinal tract.
    The ``R.E.D. Facts on Iron Salts'', EPA-738-F-93-002 (February 
1993), state that ``[i]ron salts are normally present in the 
environment. Iron is the fourth most abundant element and the second 
most abundant metal in the earth's crystal rocks. Iron occurs in a wide 
variety of minerals, and is present in foods naturally and through 
added ingredients. ``The iron salts are of low acute toxicity through 
oral, dermal and inhalation routes of exposure. They have been placed 
in Toxicity Category III for these effects. ... Other toxicity studies 
normally required for registration were not necessary to evaluate the 
risks of the iron salts. ``Further, the iron salts are generally 
recognized as safe (GRAS) by the Food and Drug Administration for use 
as a flavoring agent and nutrient supplement in foods (please see 40 
CFR 180.2(a)).''
    It should be noted that FDA has promulgated GRAS direct and 
indirect food additive regulations for ferric

[[Page 32333]]

phosphate, at 21 CFR sections 184.1301 and 182.5301, respectively. As a 
direct food additive, ferric phosphate may be used as a nutrient 
supplement and in infant formula in accordance with good manufacturing 
practice. As an indirect food additive, it may be used as a dietary 
supplement in accordance with good manufacturing practice. The 
Reregistration Eligibility Document (``RED'') on Iron Salts, EPA-738-S-
93-001 (February 1993), indicates that the current toxicological 
database within the Agency and in the literature is adequate to support 
the reregistration eligibility of all iron sulfates.
    Further, this document states that there are some unusual factors 
which indicate that specific studies to fulfill the usual data 
requirements are not necessary to regulate these substances as 
pesticides. The document goes on to list these factors as: (1) iron 
salts are normally present in the environment; (2) they may be present 
in foods naturally and as added ingredients; and (3) there is no reason 
to expect that usage in accordance with the label will present any 
hazard beyond that from ordinary exposure. By inference, this rationale 
for not requiring additional toxicological data for iron sulfates 
should be equally applicable to any other iron salt, such as iron 
phosphate.

D. Aggregate Exposure

    1. Dietary exposure. (a) Food - There is no evidence of adverse 
health effects resulting from dietary exposure to insoluble iron salts, 
except in the case of massive intake disrupting the natural homeostatic 
mechanism controlling body level of iron. The risk from exposure to 
food containing iron phosphate is negligible due to its low toxicities, 
status as a food flavoring agent and a food nutrient supplement, and 
inherent function in the metabolic pathways of humans and animals.
    (b) Drinking water. Iron phosphate is insoluble in water. As such, 
its biologic availability is limited. EPA has not established a maximum 
contaminant level or a maximum contaminant level goal for iron under 
the Safe Drinking Water Act. However, a secondary maximum contaminant 
level of 0.3 mg/L has been established. This level represents a level 
protective of aesthetic values, such as odor or appearance.
    2. Non-Dietary exposure. Neudorff also is registering its Slug and 
Snail Bait for use on outdoor ornamentals and lawns. Therefore, 
applicators who apply this product to crops, ornamentals and lawns 
could be exposed. However, protective measures prescribed by the 
product's label are expected to be adequate to minimize exposure and 
protect applicators of this chemical. It also should be noted that the 
Iron Salts RED states that mixer/loader/applicator exposure to the iron 
sulfates is considered inconsequential, whether these substances are 
applied by spreaders, sprinkler cans or by hand and whether the product 
is granular or a soluble concentrate, because there is little concern 
from a toxicity perspective. Moreover, the document states that the 
risks from dietary and occupational exposures are considered to be 
negligible due to their low toxicities, status as food flavoring agents 
and food nutrient supplements, and inherent function in the metabolic 
pathways of humans and animals.

E. Cumulative Effects

    Since Neudorff's Slug and Snail Bait is the first pesticide product 
containing iron phosphate being registered with EPA, there will not be 
exposures to this chemical through other pesticides. Although not 
widely used as a fertilizer, due to its insolubility in water, iron 
phosphate can be used as a fertilizer in acidic soils. Therefore, there 
is the possibility that in certain limited circumstances, there could 
be cumulative exposures to this chemical.

F. Safety Determination

    1. U.S. population. The metabolism of iron in man and growing 
plants is well understood and documented in the available literature. 
The use of iron phosphate as an active ingredient in slug and snail 
baits applied around and not on growing crops would not contribute 
significantly to the level of iron found naturally in the environment 
and to which man is exposed. Further, there is adequate information to 
show that there is no toxicological concern raised by the contribution 
of iron to growing crops, which is likely to result from the use of 
slug and snail baits containing iron, and consequently no tolerance 
should be required for the use of iron phosphate.
    2. Infants and children. Increased requirements for iron occur 
during the growth period and pregnacy and with excessive menses and 
other instances of blood loss. The menstruating female requires about 
21 ug/kg per day (about 1.4 mg). In the last two trimesters of 
pregnancy, requirements increase to about 80 g/kg per day (5 
to 6 mg), and there are similar requirements for the infant due to its 
rapid growth (Finch, 1976). During these periods, absorption of iron is 
greatly increased (Casarett and Doull's, 1991). Iron has been shown to 
cross the placenta and concentrate in the fetus. The concentration of 
iron in the fetus may serve a valuable physiologic purpose, inasmuch as 
it prevents anemia caused by rapid growth in the absence of sufficient 
supplies of iron in the mother's milk (Casarett and Doull's, 1980).

G. Existing Tolerances

    1. Existing tolerances or tolerance exemptions. EPA has not 
established a tolerance or an exemption from the requirement for a 
tolerance for iron phosphate. However, EPA has established tolerance 
exemptions for other iron salts, i. e., iron sulfate and ferric 
chloride. See 40 CFR sections 180.1001(c) and (d).
    2. International tolerances. No maximum residue level has been 
established for this substance by the Codex Alimentarius Commission.   
(Sheryl Reilly)

2. Plant Health Technologies Petition Summary:

PP 7G4817

    EPA has received a pesticide petition (PP 7G4817) from Plant Health 
Technologies, P.O. Box 198, Lathrop, California 95330, proposing 
pursuant to section 408 (d) of the Federal Food, Drug and Cosmetic Act, 
21 U.S.C. section 346a (d), to amend 40 CFR part 180 by establishing an 
exemption from the requirement of a tolerance for the residues of the 
biochemical pesticide, Pantoea agglomerans Strain C9-1, when applied in 
accordance with good agricultural practices in or on all raw 
agricultural commodities.

A. Proposed Use Practices

    Pantoea agglomerans strain C9-1 is proposed for use to control Fire 
Blight (Erwinia amylovora) in apples and pears. Three to 6 applications 
will be made starting at 20 percent bloom through petal fall.

B. Product Identity/Chemistry

    1. Product name. The product trade name is BlightBan C9-1. The 
active ingredient is the naturally occurring bacterium, P. agglomerans 
strain C9-1. Formulated product will contain 71 percent active 
ingredient and 29 percent inert ingredients.
    2. Magnitude of residue. Plant Health Technologies believes that no 
residues are expected on the crop at the time of harvest. P. 
agglomerans colonizes the blossom and stigma and requires specific 
moisture and temperature conditions to grow. Strain C9-1 is not 
expected to colonize the fruit. This species occurs naturally in the 
environment and populations of indigenous P. agglomerans isolates may 
also be present in a variety of habitats.

[[Page 32334]]

    3. Plant Health Technologies states that an analytical method is 
not needed because residues are not expected on crops at harvest.

C. Mammalian Toxicological Profile

    Plant Health Technologies has submitted data in support of the 
exemption from tolerance for P. agglomerans Strain C9-1 to include: an 
acute oral toxicity in rats, an acute dermal toxicity/irritation study 
in rabbits; a primary eye irritation study in rabbits, an acute 
intratracheal toxicity/pathogenicity study in rats, and an acute 
intravenous toxicity/pathogenicity study in rats.
    The results of these studies indicate that P. agglomerans Strain 
C9-1 has an acute oral toxicity greater than 5 grams/kilograms (g/kg) 
body weight in rats, an acute dermal toxicity greater than 2 g/kg body 
weight in rabbits, and causes slight to mild skin and eye irritation in 
rabbits. There was no evidence of toxicity or pathogenicity related to 
P. agglomerans Strain C9-1 in rats administered 1.63  x  108, 9.83  x  
107, and 2.1  x  107 CFU by oral, intratracheal, or intravenous routes, 
respectively. Total clearance of the organism occurred rapidly in all 
cases.

D. Aggregate Exposure

    Dietary and non-dietary exposure: For the purpose of assessing the 
potential dietary exposure under this tolerance exemption, it was 
considered that P. agglomerans strain C9-1 would not be present in raw 
agricultural commodities. Strain C9-1 is applied at blossom, before 
fruit development, and several months before harvest. C9-1 does not 
readily colonize the fruit. Plant Health Technolgies states that 
because strain C9-1 is a plant colonizing microorganism and will not be 
used in residential, home garden, or lawn care situations, other 
potential sources of dietary and non-dietary exposure to the general 
population such as drinking water and non-occupational exposures are 
not expected to be significant.

E. Cumulative Effects

    The potential for cumulative effects of P. agglomerans strain C9-1 
was also considered. C9-1 inhibits pest microorganisms from becoming 
established by out-competing the pests for space and nutrients, and 
through the production of herbicolin antibiotics. Applying strain C9-1 
in relatively high doses to developing (uncolonized) apple and pear 
blossoms, confers a competitive advantage to strain C9-1, enabling the 
isolate to colonize specific plant surfaces before the pest 
microorganism has an opportunity to become established. While many 
microorganisms thrive in specific habitats due to competitive 
displacement, Plant Health Technologies believes that there is no 
reasonable basis to expect that P. agglomerans strain C9-1 exhibits a 
particular mechanism of toxicity in common with other pesticides and 
chemical substances. Moreover, aggregate exposure of humans to strain 
C9-1 is negligible. Therefore, PHT concludes that any effects 
attributable to P. agglomerans strain C9-1 would not be cumulative with 
those of any other substances. Thus, PHT believes it is appropriate to 
consider only the potential risks of P. agglomerans in the aggregate 
exposure assessment.

F. Safety Determination

    1. Population in general. As a species, Pantoea agglomerans is 
ubiquitous, having been isolated from plants, animals, soil and water. 
Scientists have worked with biocontrol isolates belonging to the 
Pantoea agglomerans complex for over 50 years with no reported adverse 
effects. There is no evidence of toxicity or pathogenicity related to 
P. agglomerans Strain C9-1 by oral, intratracheal or intravenous 
routes. Based on this, and the lack of exposure to humans, Plant Health 
Technologies believes that the aggregate exposure to P. agglomerans 
strain C9-1 over a lifetime will not pose appreciable risks to human 
health. Thus, PHT concludes that there is a reasonable certainty that 
no harm will result from aggregate exposure to Pantoea agglomerans 
strain C9-1 residues and that exempting P. agglomerans strain C9-1 from 
the requirement of a tolerance is safe.
    2. Infants and children. The toxicity, pathogenicity, and exposure 
data are sufficiently complete to adequately address the potential for 
additional sensitivity of infants and children to residues of P. 
agglomerans. Due to the lack of adverse effects and negligible 
exposure, Plant Health Technologies concludes with reasonable 
certainty, that no harm will result to infants and children from 
aggregate exposure to P. agglomerans.

G. Existing Tolerances

    No tolerances or exemptions for tolerance have been issued in the 
United States or internationally for this microorganism.   (Linda 
Hollis)

3. Tenneco Packaging Petition Summary:

PP 7F4818

A. Proposed Use Practices

    Tenneco Packaging, 1603 Orrington Ave., Evanston, IL., 60201, has 
requested EPA to exempt methyl salicylate from the requirement of a 
tolerance in or on agricultural commodities under section 408 of the 
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a, when used 
as a insect repellent in food packaging and animal feed packaging 
materials alone or in conjunction with inert components which conform 
to the requirements of regulations issued by the Food and Drug 
Administration under section 409 of the Federal Food, Drug, and 
Comestic Act (FFDCA).

B. Product Identity/Chemistry

    Methyl salicylate (CAS Registry Number 119-36-8) is the primary 
chemical component of a naturally occurring fragrant oil, oil of 
wintergreen. Petitioner has stated that, if present at all, residues of 
methyl salicylate that may be found in foods in contact with treated 
packaging materials will be minimal and considerably below the levels 
expected in existing GRAS uses of the active ingredient as a direct 
food flavoring ingredient.

C. Toxicological Profile

    The toxicity of methyl salicylate has been extensively studied in 
animal bioassays of acute, subchronic, and chronic duration. Studies 
include assessments of the mutagenicity, teratogenicity, and 
reproductive effects of methyl salicylate.
    1. Acute toxicity. The acute oral LD50 for methyl 
salicylate in the rat ranges from 887-1,250 mg/kg. Acute dermal 
toxicity (LD50 dermal) has been reported to be 0.70 ml/kg 
(approx. 700 mg/kg) in guinea pigs, and > 5 g/kg in the rabbit.
    2. Skin and eye irritation. Methyl salicylate has been reported to 
be a severe eye irritant. Methyl salicylate has been reported to 
produce mild dermal irritation in rabbits at a concentration of 1 
percent. Moderate to severe irritation is produced in rabbits and 
guinea pigs at concentrations above 1 percent. Applied full strength to 
intact or abraded rabbit skin for 24 hours under occlusion, methyl 
salicylate was moderately irritating. However, tested at 8 percent in 
petrolatum, it produced no irritation after a 48 hour closed-patch test 
on human subjects.
    3. Mutagenicity. No evidence for genotoxicity was observed in two 
studies with prokaryotic test systems;

[[Page 32335]]

no data on genotoxicity in mammalian test systems are available.
    4. Subchronic toxicity. Studies of subchronic duration with 
administration by the oral route have been conducted in both rats and 
dogs. In rats, no adverse effects were seen at a dose of 0.1 percent in 
the diet. In dogs, doses 250 mg/kg/day did not result in any 
adverse effects, however, the liver appeared to be the target organ of 
toxicity at doses above this level. No toxicity was observed when rats 
were exposed to methyl salicylate via inhalation of saturated air 
(approx. 700 mg/m3) after twenty 7-hour exposures.
    5. Teratogenicity. Methyl salicylate has been tested for 
teratogenic potential in hamsters, rats and mice by several different 
routes of administration. In hamsters, at dose levels of methyl 
salicylate which produced maternal toxicity, an increased incidence of 
neural tube defects was also observed. The no observed adverse effects 
level (NOAEL) for developmental effects in rats given methyl salicylate 
by the dermal route (assuming 100 percent absorption) was 180 mg/kg/day 
(the highest dose tested). In mice, the NOAEL for developmental effects 
in a continuous breeding study using oral administration was 100 mg/kg/
day based on decreases in numbers of live pups per litter, percentage 
of live pups, and pup weight.
    6. Chronic Toxicity. Toxicity resulting from chronic exposure has 
been evaluated in studies of two-years' duration as well as studies 
initially intended to evaluate multi-generational reproductive and 
developmental effects. In mice, the NOAEL for reproductive parameters 
and the other toxic endpoints examined has been reported as 250 mg/kg/
day. When rats were exposed to methyl salicylate in the diet for two 
years, no adverse effects were noted at levels of 0.1 percent (approx. 
50 mg/kg/day); pituitary lesions were increased in animals exposed to 
0.5 percent (approx. 250 mg/kg/day). In dogs orally exposed to methyl 
salicylate for two years, no adverse effects were observed at 50 mg/kg/
day; the LOAEL (liver effects) was reported as 150 mg/kg/day.
    7.  Carcinogenicity. No studies have been performed with the 
primary purpose of determining the oncogenicity of methyl salicylate; 
however, chronic exposure studies with two-year exposure durations that 
included extensive pathology did not indicate any increases in 
incidences of benign or malignant tumors.
    8. GRAS Assessment. The Flavoring Extract Manufacturer's 
Association ( FEMA) has determined GRAS levels of methyl salicylate and 
oil of wintergreen in foods and beverages as indicated in the table 
below.


                     FEMA GRAS Levels in Food (ppm)                     
------------------------------------------------------------------------
              Food                 Methyl Salicylate  Oil of Wintergreen
------------------------------------------------------------------------
Beverages                         59                  56                
Ice cream                         27                  44                
Candy                             840                 260               
Baked goods                       54                  1,500             
Chewing gum                       8,400               3,900             
Syrups                            200                                   
------------------------------------------------------------------------


    GRAS food levels in the Table are above both the maximum food 
residue concentration (approx. 16 ppm) and the maximum dietary exposure 
concentration (approx. 4.7 ppm) estimated by the Petitioner for the 
proposed use pattern for methyl salicylate. These estimates used highly 
conservative assumptions for migration of methyl salicylate from 
packaging and food consumption. Petitioner has shown that even under 
worst-case exposure conditions (i.e., assuming 30 percent of all food 
consumed is in contact with packaging containing methyl salicylate, and 
100 percent of the methyl salicylate migrates to food) exposure to 
methyl salicylate from use in packaging materials would be less than 
that received by chewing one stick of chewing gum at the GRAS-approved 
level. Based on this comparison, use of methyl salicylate in food 
packaging materials should also be considered GRAS.

D. Aggregate Exposure

    There is no established Maximum Contaminant Level (MCL) for 
residues of methyl salicylate in drinking water under the Safe Drinking 
Water Act.
    The Petitioner is aware of five currently registered products 
containing methyl salicylate as an active ingredient. These products 
include two categories: (1) impregnated materials and pellets to be 
used as vertebrate repellents, and (2) disinfectants/germicides 
registered for use in household, institutional, hospital, and eating 
establishment premises. Although these registered uses could 
potentially result in exposures to methyl salicylate, EPA did not 
require establishment of a tolerance (or an exemption from the 
requirement of a tolerance) for methyl salicylate as a condition for 
granting registrations for these products. Petitioner believes that 
anticipated dietary exposures from these registered products would be 
indirect (i.e., resulting from food contact with a treated surface) and 
therefore very low.
    In addition to the anticipated dietary exposure to methyl 
salicylate from Petitioner's proposed use (i.e., food packaging 
materials) estimated in Section A.8., above, drinking water is the only 
reasonably anticipated additional exposure resulting from pesticidal 
uses of methyl salicylate. Based on its rapid environmental 
degradation, Petitioner does not anticipate the occurrence of 
pesticidal residues of methyl salicylate in drinking water and is not 
aware of any existing residues.
    Therefore, the potential for non-occupational, non-dietary exposure 
to the general population as a result of pesticidal use of methyl 
salicylate in food packaging materials is not expected to be 
significant.

E. Cumulative Effects

    The Petitioner has also considered the potential for cumulative 
toxicity effects of pesticidal uses of methyl salicylate and other 
pesticidal substances that may have a common mechanism of toxicity. 
Petitioner has concluded that consideration of a common mechanism of 
toxicity is not appropriate because there is no information available 
from the publicly available literature indicating that there are other 
pesticidal substances that operate via a mechanism of action common 
with methyl salicylate. Thus, Petitioner recommends that only the 
potential risks of methyl salicylate be considered in this request for 
an exemption from the requirement of a tolerance.

F. Safety

    1. U.S. population. Methyl salicylate is the major component of a 
naturally occurring fragrant oil. The Flavor and Extract Manufacturer's 
Association (FEMA) has listed methyl salicylate on its GRAS list for 
use as a flavoring ingredient in foods and beverages. An FDA Advisory 
Review Panel has concluded that methyl salicylate is safe for use up to 
a concentration of 0.4 percent in the form of a rinse or mouthwash. The 
compound is extensively used in foods, beverages, pharmaceuticals, 
lotions and perfumes and has wide distribution in commerce with no 
reports of adverse outcomes associated with intended uses. The toxicity 
of the active ingredient (i.e., methyl salicylate) has been adequately 
and reliably characterized; it is summarized in this submission.
    Based on this information, the Petitioner recommends that EPA 
conclude that there is reasonable certainty of no harm from aggregate 
exposures to pesticidal uses of methyl salicylate over a lifetime, and 
that no

[[Page 32336]]

significant human health risks will result from such exposures. 
Accordingly, Petitioner recommends that EPA determine that exempting 
methyl salicylate from the requirement of a tolerance is safe.
    2. Infants and children. Petitioner believes that EPA has 
sufficient data to address the issue of the potential additional 
sensitivity of infants and children to pesticidal methyl salicylate 
residues. Petitioner points to the long history of use of this 
substance as a flavoring in foods, its GRAS status, and the data 
submitted to the Agency in support of this petition. Reproductive and 
developmental effects have been found in toxicology studies for methyl 
salicylate; however, these adverse effects occurred at exposure levels 
that were also maternally toxic or at exposure levels higher than those 
producing other adverse effects following chronic exposure. Petitioner 
believes that infants and children are not differentially sensitive to 
methyl salicylate either by virtue of increased toxicological 
susceptibility or increased potential exposures. Therefore, Petitioner 
requests that EPA conclude that there is a reasonable certainty that no 
harm will result to infants and children from aggregate exposures to 
pesticidal chemical residues of methyl salicylate.
    3. Endocrine effects. Methyl salicylate has been studied in several 
tests of reproductive and developmental effects, including 
multigenerational studies. In addition, the pathology of endocrine-
sensitive tissues and organs has been evaluated following repeated 
(i.e., subchronic) and long-term (i.e., chronic) exposures. These 
studies are sufficient to detect endocrine effects. No such effects 
were reported in any of these studies. Therefore, Petitioner concludes 
that pesticidal uses of methyl salicylate are unlikely to have an 
effect in humans that is similar to an effect produced by a naturally 
occurring estrogen or other endocrine effects.

G. Analytical Method

    Petitioner proposes that EPA establish this exemption from the 
requirement of a tolerance without any numerical limitation; therefore, 
analytical methods for residues of methyl salicylate would not be 
required for enforcement purposes. Petitioner is confident that, if 
present at all, residues of methyl salicylate that may be found in 
foods in contact with treated packaging materials will be minimal and 
considerably below the levels expected in existing GRAS uses of the 
active ingredient as a direct food flavoring ingredient. The Petitioner 
believes that an analytical method for the detection and measurement of 
methyl salicylate residues is not necessary to protect the public 
health or the environment. The natural occurrence of methyl salicylate 
in the environment (as oil of wintergreen), and its widespread use as a 
flavoring agent in the food supply preclude the need to quantify 
pesticidal methyl salicylate residues. Therefore, Petitioner has 
requested that EPA waive the requirement for an analytical method.

H. Existing Tolerances or Tolerance Exemptions

    There are no known existing tolerances or tolerance exemptions for 
methyl salicylate; however, oil of wintergreen is exempt from the 
requirement of a tolerance when used in accordance with good 
agricultural practice as an inert (or occasionally active) ingredient 
in pesticide formulations applied to growing crops or to raw 
agricultural commodities (40 CFR 180.1001(c)).

I. Codex Maximum Residue Level

    No known maximum residue limits (MRLs) have been established for 
methyl salicylate by the Codex Alimentarius Commission.   (Sheryl 
Reilly)

[FR Doc. 97-15369 Filed 6-12-97; 8:45 am]
BILLING CODE 6560-50-F