[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