2- Phenethyl Propionate Petition to Establish a Tolerance Exemption – March 1, 2012 Page 1 of 1 0 

## Petition **for an exempt** **ion from the requirement of a tolerance for residues of products containing the activ** **e ingredient “ 2**  **- Phenethy** **l Propionate ”**  **and it s degradates**  **“ Phenethy** **l Al**  **cohol ”**  **and “**  **Propionic A cid**  **” in**  **and on all food**

**commodities**

**Submitted for**  **:** EcoSMART Technologies, Inc.

20 Mansell Court , Suite 375 Roswell , GA 300 76 **Submitted by :**  Technology Sciences Group Inc.

712 Fifth Street, Suite A Davis, CA 956162- Phenethyl Propionate Petition to Establish a Tolerance Exemption – March 1, 2012 Page 2 of 1 0 

## SECTION A **Product name and proposed use practice Product N**  **ame:** 2 - PEP Technical (TGAI) EcoPCO® ACU (EP); EPA Reg. No. 67425- 14 **Proposed Use Practice:** EcoSMART Technologies , Inc. uses 2 - P EP 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. W ith 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 i ts 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 /che**  **mistry Ac** **tive 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 ) . I t 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 - P EP 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 i s 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 - P EP has been used to attract Japan ese 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 - P EP is a naturally

occurring plant volatile ingredient derived from peanut oil . I n addition to its use as a pesticide active ingredient, it is2- Phenethyl Propionate Petition to Establish a Tolerance Exemption – March 1, 2012 Page 3 of 1 0 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 u sed as an additive in the food and flavor industry, an d occurs naturally i n the human diet. I t 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. P EA 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 lau n dry

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 h as conducted an extensive review of the toxicity and fate of PEA (MRID No. 487536-06). Propionic Acid is a degradate of 2 - PEP. P ropionic Acid is used widely as a preservative and flavoring agent in packaged foods such as baked goods and cheese. P ropion ic Acid occurs naturally i n 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 A ction:**  Wh en used as an insecticide/miticide , 2 - P EP has a unique mode of action that targets and blocks a key n eurotransmitter receptor site called octopamine, wh ich 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

d ue to their ready

volatility ( MRID No. 487536 - 05 ). **Magnitude of residues and method to determine:**  An analytical method fo r residues is not applicable. I t 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.2- Phenethyl Propionate Petition to Establish a Tolerance Exemption – March 1, 2012 Page 4 of 1 0 

## SECTION C **Toxicological Profile Toxicity**  **of 2 -** **PEP** : **1) Ac**  **ute T** **oxicity 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

I II) , 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

I V) . 2 - Phenethyl Propionate is a moderate irritant in an eye irritation study (Toxi city Category

I II) 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 appropri ate 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 s imilar 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. F urther, 2 - Phenethyl Propionate is classified by E PA 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 th e 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

d egradates are well studied, are rapidly m etabolized and excreted, and pose no significant risk . **Toxicity of Degradates**  **PEA and Propionic**  **Ac id**  **:** 2 - PEP rapidly degrades to PEA and Propionic Acid which are the principal residues following u se of 2 - PEP. Both compounds are approved for use in food by FDA. The toxicology

of PEA has been extensively

d ocumented in the literature, and the Agency h as 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 a nd non -dietary

exposures would not be expected to pose any quantifiable risk due to a lack of residues of toxicolog ical concern.2- Phenethyl Propionate Petition to Establish a Tolerance Exemption – March 1, 2012 Page 5 of 1 0 

## SECTION D **Ag gregate Exposure**  **1) Dietary Exposure:**  Dietary exposure from use of 2 - P EP , as proposed, is minimal. T he intended use of 2- P EP is as a crack and crevice treatment in food and feed handling and processi ng facilities for the control of insect pests . 2 - P EP is a plant volatile that rapidly d egrades into PEA and Propionic Acid in the environment. I t is a naturally occurring ingredient an d 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 - P EP . Drinking water exposures would not be expected to pose any q uantifiable 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 unli kely

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 vol atile that rapidly

d egrades into PEA and Propionic Acid in the environment. I t 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 -d ietary exposures would not be expected to pose any

quantifiable risk due to a lack of residues of toxicological concern.2- Phenethyl Propionate Petition to Establish a Tolerance Exemption – March 1, 2012 Page 6 of 1 0 

## SECTION E **Cumulativ e Effects**  It is not expected that, when used as proposed, 2 - PE P 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 d egrades into PEA and Propionic Acid in the environment. I t 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 .2- Phenethyl Propionate Petition to Establish a Tolerance Exemption – March 1, 2012 Page 7 of 1 0 

## SEC**TION 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 . I t is not expected that, when used as proposed, 2 - PEP would result in res idues that are of toxicological concern. 2 - PEP is a plant volatile that rapidly d egrades into PEA and Propionic Acid in the environment. I t 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.2- Phenethyl Propionate Petition to Establish a Tolerance Exemption – March 1, 2012 Page 8 of 1 0 

## SECTION G **– Ef** 

**fects on Immune and E ndocrine**  **S ys** **tems** 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.2- Phenethyl Propionate Petition to Establish a Tolerance Exemption – March 1, 2012 Page 9 of 1 0 

## SECTION H **– Existing Toleran**  **ces** 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 18 0.1023.2- Phenethyl Propionate Petition to Establish a Tolerance Exemption – March 1, 2012 Page 10 of 1 0 

## 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.