Document ID: EPA-HQ-OPP-2012-0591-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-08-22T04:00Z

Petition for an exemption from the requirement of a tolerance for
residues of products containing the active ingredient “2-Phenethyl
Propionate” and its degradates “Phenethyl Alcohol” and
“Propionic Acid” in and on all food commodities

Submitted for:	EcoSMART Technologies, Inc.

20 Mansell Court, Suite 375

Roswell, GA 30076

Submitted by:	Technology Sciences Group Inc.

			712 Fifth Street, Suite A

			Davis, CA 95616

			

SECTION A  		Product name and proposed use practice

Product Name:	2-PEP Technical (TGAI)

				EcoPCO® ACU (EP); EPA Reg. No. 67425-14

Proposed Use Practice:	EcoSMART Technologies, Inc. uses 2-PEP as a
minimum risk pesticide active ingredient in a variety of exempt 25(b)
products and as a broad spectrum contact insecticide/miticide for
application in commercial, industrial and residential areas.  With the
establishment of an exemption from the requirement of a tolerance for
residues of this active ingredient, EcoSMART Technologies, Inc. proposes
to expand the use of its products to include crack and crevice
treatments in food and feed handling and processing facilities for the
control of insect pests.  This is an indoor use pattern that does not
involve direct application to food crops.

SECTION B		Product identity/chemistry

		

Active Ingredient:	2-Phenethyl Propionate (CAS No. 122-70-3).

	

	Information regarding the name, identity and chemical composition has
been submitted to EPA and can be found in MRID No. 487536-02.

	2-Phenethyl Propionate (2-PEP) degrades after twenty-four (24) hours
into Phenethyl Alcohol (PEA) (CAS No. 60-12-8) and Propionic Acid (CAS
No. 79-09-4).  It also degrades rapidly in water and soil.  2-PEP also
hydrolyzes in the gut to PEA. (MRID Nos. 487536-05 and 487536-06).
Therefore, this tolerance exemption covers 2-PEP and its degradates.

	2-PEP is classified as a minimum risk pesticide per 40 CFR 152.25(f)
and is exempt from federal registration requirements under section 25(b)
of the Federal Insecticide Fungicide Rodenticide Act (FIFRA).  It is
also found in registered products, as a biochemical active ingredient,
when combined with other non-exempt active ingredients or with inert
ingredients that do not meet the criteria of 40 CFR 152.25(f). 
Historically, 2-PEP has been used to attract Japanese Beetles to traps
and as an insecticide/miticide on a wide variety of insects, mites,
ticks, spiders, etc.  (EPA, Floral Attractants, Repellents and
Insecticides Fact Sheet, 11/04).  

	2-PEP is a naturally occurring plant volatile ingredient derived from
peanut oil.   In addition to its use as a pesticide active ingredient,
it is listed as GRAS and approved as a direct food additive by the FDA
(21 CFR 172.515) as a flavoring agent.  2-PEP is widely used as an
additive in the food and flavor industry, and occurs naturally in the
human diet.  It is an ester formed from PEA and Propionic Acid, and is
often in natural sources with those two compounds.

	PEA is a degradate of 2-PEP.  PEA has been identified as a volatile
component in various raw and processed foods.  PEA is commonly used as a
flavoring agent in food and as a fragrance in cosmetics, household and
laundry cleaning products and air fresheners.  PEA is cleared by the FDA
for use as a synthetic flavoring substance in food per 21 CFR 172.515. 
EPA has conducted an extensive review of the toxicity and fate of PEA
(MRID No. 487536-06).

	Propionic Acid is a degradate of 2-PEP.  Propionic Acid is used widely
as a preservative and flavoring agent in packaged foods such as baked
goods and cheese.  Propionic Acid occurs naturally in dairy products and
is a normal component of human metabolism.  Propionic Acid is exempt
from the requirement of a tolerance for residues when used as an active
or an inert ingredient on all food crops per 40 CFR 180.1023(c). 
Propionic Acid is affirmed GRAS as a direct human food ingredient per 21
CFR 184.1081.

Mode of Action:	When used as an insecticide/miticide, 2-PEP has a unique
mode of action that targets and blocks a key neurotransmitter receptor
site called octopamine, which is found in all invertebrates, but not
mammals.  Octopamine regulates an insect’s heart rate, movement and
metabolism.  Interrupting the function of octopamine results in a total
breakdown of the insect’s nervous system.  2-PEP degrades after 24
hours into PEA and Propionic Acid. 2-PEP and its degradates dissipate
rapidly leaving low concentrations for short periods of time, likely due
to their ready volatility (MRID No. 487536-05).

Magnitude of residues and

method to determine:	An analytical method for residues is not
applicable.  It is expected that, when used as proposed, 2-PEP, and its
degradates PEA and Propionic Acid, would not result in residues that are
of toxicological concern.	

 SECTION C	Toxicological Profile

Toxicity of 2-PEP: 

1)	Acute Toxicity of 2-PEP.  2-Phenethyl Propionate is of low acute oral
and dermal toxicity, with two oral LD50s in rats reported at 4,000 mg/kg
and 3980 mg/kg (Toxicity Category III), and a dermal LD50 in rabbits
reported at greater than 5,000 mg/kg (Toxicity Category IV).  Low acute
inhalation toxicity was demonstrated in a study on the active ingredient
on rats that resulted in an LC50 of greater than 2.06 mg/L (Toxicity
Category IV).  2-Phenethyl Propionate is a moderate irritant in an eye
irritation study (Toxicity Category III) and a slight irritant in skin
irritation study (Toxicity Category IV).  Finally, 2-PEP was shown to
not be a dermal sensitizer.

2)	Subchronic Toxicity, Teratogenicity and Genotoxicity of 2-PEP. 
EcoSMART Technologies, Inc. has requested that existing data be
considered to satisfy these data requirements based on the results of
toxicity testing available in published literature, studies on
persistence and dissipation of 2-PEP in the environment, the results of
toxicity testing on appropriate degradates available in published
literature, the ingredient’s status as GRAS and as a direct food
additive with the FDA, and the ingredient’s status as a minimum risk
active ingredient with the EPA (MRID No. 487536-07).

	Studies performed on structurally similar degradates are of low
toxicity in subchronic and teratogenicity studies and had negative
results in genotoxicity studies, and that 2-Phenethyl Propionate is a
common ingredient in the diet as a result of its natural occurrence in
food and as a food additive.  Further, 2-Phenethyl Propionate is
classified by EPA as a minimum risk active ingredient and is known to be
non-hazardous to humans and animals.  2-Phenethyl Propionate meets the
criteria for minimum risk in that it is 1) listed GRAS by the FDA, 2)
has a non-toxic mode of action and is generally considered non-toxic, 3)
has negligible human or environmental exposure, and 4) is nonpersistent.
 Moreover, 2-Phenethyl Propionate has been shown to rapidly degrade in
water and soil and in the gut.  Its primary degradates are well studied,
are rapidly metabolized and excreted, and pose no significant risk.  

Toxicity of Degradates PEA and Propionic Acid:

2-PEP rapidly degrades to PEA and Propionic Acid which are the principal
residues following use of 2-PEP.  Both compounds are approved for use in
food by FDA.  The toxicology of PEA has been extensively documented in
the literature, and the Agency has conducted robust reviews of that
information (MRID No. 487536-06).  Moreover, Propionic Acid is a normal
metabolite in mammalian systems and would be expected to undergo the
same metabolic process as endogenous Propionic Acid.

The results of toxicity testing on 2-PEP, information on toxicity of the
major degradates, the direct food additive status of 2-PEP, and its
status as a minimum risk active ingredient show there is no risk to
human health from 2-Phenethyl Propionate.  Both dietary and non-dietary
exposures would not be expected to pose any quantifiable risk due to a
lack of residues of toxicological concern.  

SECTION D	Aggregate Exposure

1)	Dietary Exposure:

	  SEQ CHAPTER \h \r 1 Dietary exposure from use of 2-PEP, as proposed,
is minimal.  The intended use of 2-PEP is as a crack and crevice
treatment in food and feed handling and processing facilities for the
control of insect pests.  2-PEP is a plant volatile that rapidly
degrades into PEA and Propionic Acid in the environment.  It is a
naturally occurring ingredient and is not considered persistent based on
its characteristics, properties or known degradation pathways. 

	The results of toxicity testing, information on toxicity testing of
degradates, and the ingredient’s status as GRAS, as a direct food
additive, and as a minimum risk active ingredient show there is no risk
to human health from 2-PEP.  There are no reports of ecological or human
health hazards caused by 2-PEP. Dietary exposures would not be expected
to pose any quantifiable risk, due to a lack of residues of
toxicological concern.  

2)	Drinking Water Exposure:

Similarly, exposure to humans from residues of 2-PEP or it’s
degradates in consumed drinking water would be unlikely.  Potential
exposure to surface water would be unlikely and exposure to drinking
water (well or ground water) would be impossible to measure. The
intended use of 2-PEP is as a crack and crevice treatment in food and
feed handling and processing facilities for the control of insect pests.
 The ingredient is not applied directly to water.

	The results of toxicity testing, information on toxicity testing of
degradates, and the ingredient’s status as GRAS, as a direct food
additive, and as a minimum risk active ingredient show there is no risk
to human health from 2-PEP.  There are no reports of ecological or human
health hazards caused by 2-PEP.  Drinking water exposures would not be
expected to pose any quantifiable risk due to a lack of residues of
toxicological concern.  

3)	Non-Dietary Exposure:

	The potential for non-dietary exposure to the general population,
including infants and children, is unlikely as the proposed use sites
are commercial food handling and processing facilities.  The intended
use of 2-PEP is as a crack and crevice treatment in food and feed
handling and processing facilities for the control of insect pests. 
2-PEP is a plant volatile that rapidly degrades into PEA and Propionic
Acid in the environment.  It is a naturally occurring ingredient and is
not considered persistent based on its characteristics, properties or
known degradation pathways. 

	The results of toxicity testing, information on toxicity testing of
degradates, and the ingredient’s status as GRAS, as a direct food
additive, and as a minimum risk active ingredient show there is no risk
to human health from 2-PEP.  There are no reports of ecological or human
health hazards caused by 2-PEP. Non-dietary exposures would not be
expected to pose any quantifiable risk due to a lack of residues of
toxicological concern.  

SECTION E	Cumulative Effects

  SEQ CHAPTER \h \r 1 It is not expected that, when used as proposed,
2-PEP would result in residues that are of toxicological concern. The
intended use of 2-PEP is as a crack and crevice treatment in food and
feed handling and processing facilities for the control of insect pests.
 2-PEP is a plant volatile that rapidly degrades into PEA and Propionic
Acid in the environment.  It is a naturally occurring ingredient and is
not considered persistent based on its characteristics, properties or
known degradation pathways. The results of toxicity testing, information
on toxicity testing of surrogates, and the ingredient’s status as
GRAS, as a direct food additive, and as a minimum risk active ingredient
show there is no risk to human health from 2-PEP.  There are no reports
of ecological or human health hazards caused by 2-PEP. 

SECTION F	Safety Determination

1)	General US Population:

	

	The results of toxicity testing, information on toxicity testing of
degradates, and the ingredient’s status as GRAS, as a direct food
additive, and as a minimum risk active ingredient show there is no risk
to human health from 2-PEP. The intended use of 2-PEP is as a crack and
crevice treatment in food and feed handling and processing facilities
for the control of insect pests. It is not expected that, when used as
proposed, 2-PEP would result in residues that are of toxicological
concern.  2-PEP is a plant volatile that rapidly degrades into PEA and
Propionic Acid in the environment.  It is a naturally occurring
ingredient and is not considered persistent based on its
characteristics, properties or known degradation pathways. There are no
reports of ecological or human health hazards caused by 2-PEP.  There is
a reasonable certainty of no harm to the general US population from
exposure to this active ingredient.

2)	Infants and Children:

As mentioned above, it is not expected that, when used as proposed,
2-PEP would result in residues that are of toxicological concern. There
is a reasonable certainty of no harm for infants and children from
exposure to 2-PEP from the proposed uses.  

SECTION G – Effects on Immune and Endocrine Systems

To date there is no evidence to suggest that 2-PEP or its degradates PEA
or Propionic Acid function in a manner similar to any known hormone, or
that they acts as an endocrine disrupter. 

SECTION H – Existing Tolerances

There is no US EPA tolerance or tolerance exemption for 2-PEP.  

There is an existing exemption from the requirement of a tolerance for
residues of the degradate Propionic Acid, when used as an active or an
inert ingredient, on all foods at 40 CFR 180.1023.

SECTION I – International Tolerances

A Codex Alimentarium Commission Maximum Residue Level (MRL) is not
established for 2-PEP or it’s degradates PEA and Propionic Acid.

 

2-Phenethyl Propionate Petition to Establish a Tolerance Exemption –
March 1, 2012

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