BIOPESTICIDES REGISTRATION ACTION DOCUMENT

Lysophosphatidylethanolamine (LPE)

(PC Code 105120)

U.S. Environmental Protection Agency

Office of Pesticide Programs

Biopesticides and Pollution Prevention Division

Lysophosphatidylethanolamine (LPE)

(PC Code 105120)

Updated November 2011
Lysophosphatidylethanolamine (LPE)

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Table of Contents

I. Executive Summary

A. IDENTITY

B. USE/USAGE

C. RISK ASSESSMENT

D. DATA GAPS / LABELING RESTRICTIONS

II. Overview

A. ACTIVE INGREDIENT OVERVIEW

B. USE PROFILE

C. DATA REQUIREMENTS

D. REGULATORY HISTORY

E. CLASSIFICATION

F. FOOD CLEARANCES/TOLERANCES

III.Science Assessment

A. PHYSICAL/CHEMICAL PROPERTIES ASSESSMENT 

1. Product Identity and Mode of Action

2. Physical and Chemical Properties Assessment

B. HUMAN HEALTH ASSESSMENT

1. Toxicology Assessment

 a. Acute Toxicology

b. Genotoxicity, Immune Response, Mutagenicity, Developmental, 

Oncogenicity, Subchronic and Chronic Toxicity

 c. Effects on the Endocrine System

2. Dose Response Assessment

3. Dietary Exposure and Risk Characterization

4. Occupational, Residential, School and Day care Exposure and Risk Characterization

 a. Occupational Exposure and Risk Characterization

 b. Residential, School and Day Care Exposure and Risk Characterization

5. Drinking Water Exposure and Risk Characterization

6. Acute and Chronic Dietary Risks for Sensitive Subpopulations Particularly Infants and 

Children

7. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation

8. Cumulative Effects

9. Risk Characterization 

C. ENVIRONMENTAL ASSESSMENT

1. Ecological Effects Hazard Assessment

2. Environmental Fate and Ground Water Data

3. Ecological Exposure and Risk Characterization

D. EFFICACY DATA 
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IV.Risk Management Decision

A. DETERMINATION OF ELIGIBILITY FOR REGISTRATION

B. REGULATORY POSITION

1. Conditional/Unconditional Registration

2. CODEX Harmonization

3. Nonfood Re/Registrations

4. Risk Mitigation

5. Endangered Species Statement

C. LABELING RATIONALE

1. Human Health Hazard

 a. Worker Protection Standard

 b. Non-Worker Protection Standard

 c. Precautionary Labeling

2. Environmental Hazards Labeling

 a. End-Use Product Environmental Hazards Labeling

3. Application Rate

D. LABELING

V. Actions Required by Registrants

VI.Approved Use Sites

VII. References
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BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

Office of Pesticide Programs:

Biopesticides and Pollution Prevention Division

Biochemical Pesticides Branch 

Sheryl K. Reilly, Ph.D. Biologist, Branch Chief

Freshteh Toghrol, Ph.D. Chemist, Senior Scientist 

Linda Hollis Microbiologist, Team Leader

Russell S. Jones, Ph.D. Biologist, Health Effects/Nontarget Organisms

Carol E. Frazer, Ph.D. Toxicologist, Regulatory Action Leader

Chris Pfeifer Regulatory Action Leader
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I. Executive Summary

A. IDENTITY

The technical grade active ingredient (TGAI) consists of 94% lysophosphatidylethanolamine 

(LPE), a natural constituent of all living cell membranes, created when phosphatidylethanolamine 

is broken down by a phospholipase. Fifty percent of the membrane is phospholipid and the LPE is 

one to ten percent of the lipid content of the cell, depending on cell type. The end-use product, 

LPE-94 10% Aqueous Growth Regulator, contains 10% LPE.

B. USE/USAGE

LPE-94 10% Aqueous Growth Regulator is a pre-harvest spray for use on various fruit and 

vegetable crops to enhance ripening mechanisms. The product may also be used in a post-harvest 

bath application to increase the shelf life of fruits, vegetables and cut flowers. The use is classified 

as a food crop application.

C. RISK ASSESSMENT

No unreasonable adverse effects on humans or the environment are anticipated from aggregate 

exposure to LPE-94 10% Aqueous Growth Regulator. This includes all anticipated exposures for 

which there is reliable information.

On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunity for 

the public to participate in major registration decisions before they occur. According to this policy, 

EPA intends to provide a public comment period prior to making a registration decision for, at 

minimum, the following types of applications: new active ingredients; first food uses; first outdoor 

uses; first residential uses; or any other registration actions for which EPA believes there may be 

significant public interest.

 

Consistent with the policy of making registration actions more transparent, the proposed pesticide 

products containing LPE, a new active ingredient, are subject to a 30-day comment period. In 

addition to containing a new active ingredient, the registration of these products would result in the 

first outdoor use and first food use for LPE. The docket identification number associated with 

these registration actions, EPA-HQ-OPP-2011-0899, can be accessed through 

http://www.regulations.gov/. The following documents are available for comment in the docket: 

(1) LPE Biopesticides Registration Action Document; (2) a draft label for the manufacturing-use 

product, LPE E94T (EPA File Symbol 73652-R); and (3) a draft label for the end-use product, 

Signa-Fresh 10EC (EPA File Symbol 73652-E). While a final decision on registration is 

contingent upon review and consideration of public comments, EPA presently believes that, based 

upon the risk assessment and information submitted in support of LPE, it is in the best interest of 

the public and the environment to issue these registrations. The basis for this preliminary decision 

can be found in the risk assessment for LPE, which is presented in this document. 
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1. Human Health Risk Assessment

a. Toxicological Endpoints

No toxicological endpoints were identified. Mammalian toxicology data requirements were 

submitted and adequately satisfy data requirements to support the registration. Submitted data for 

the TGAI and the end-use product indicate Toxicity Category IV for acute oral and acute 

inhalation toxicity. Acute dermal toxicity data is represented by a Toxicity Category III as the limit

dose tested, only 2,000 mg/kg, had no toxic effects. The data reported for primary eye irritation 

studies showed that the test substance was minimally irritating, and is thus a Toxicity Category III 

when the TGAI is used and Toxicity Category IV when the end use product is used as the test 

material. Exposure to either the TGAI or the end-use product produced no skin irritation in animal 

tests; as a result, a Toxicity Category IV is given for dermal irritation. Both the technical grade and 

end-use product are dermal sensitizers.

b. Human Exposure

Exposure to the general population would be low but worker exposure is expected. Appropriate 

protective wear and precautionary label language will mitigate handler risk. 

c. Risk Assessment

The Biopesticides and Pollution Prevention Division (BPPD) has not identified, and is not aware 

of, any subchronic, chronic, immune, dietary or nondietary toxicity associated with exposure of 

children or the general U.S. population to LPE. Dermal sensitization risk to applicators is 

mitigated provided that label directions are followed. No toxicological endpoints have been 

identified, and there is limited exposure of the general public to this product when used according 

to the label instructions. The Agency has considered LPE in light of relevant safety factors in the 

under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and determined there are

no unreasonable adverse effects from the use of this product.

2. Ecological Risk Assessment

a. Ecological Toxicity Endpoints

The data requirements for ecological testing were waived because no toxic endpoints were 

identified from the submitted mammalian data or literature review.

b. Ecological Exposure
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The active ingredient is a natural constituent found in biological organisms. Sprayed LPE residues 

are low, and are reduced further by catabolism through the lipid metabolic system found in most 

organisms.

c. Risk Assessment

Risk to non-target organisms is expected to be minimal due to the low degree of exposure. 

Moreover, the active ingredient is a metabolic degradation product of most biological entities. 

BPPD concludes that when LPE is used according to label directions, it will not result in 

significant adverse effects to wildlife or other organisms.

D. DATA GAPS / LABELING RESTRICTIONS

There are no data gaps or special labeling restrictions. 

II. Overview

A. ACTIVE INGREDIENT OVERVIEW

Common Name: LPE

Chemical Name: Lysophosphatidylethanolamine

CAS Number: 95046-40-5

Trade and Other Names: LPE E94T; LPE-94 10% Aqueous; phospholipid; lyso-PE

OPP Chemical Code: 105120

 

B. USE PROFILE

Proposed uses and application methods for LPE include the following: 

Type of Pesticide: Plant Growth Regulator

Use Sites: LPE is approved for field use on any type of agricultural commodity, for storage 

of harvested crops and on cut flowers.

Formulation Types: Liquid 

Method and Rates of Application: Conventional spray application equipment should be 

used in the field. The maximum concentration is 1 gallon (0.1 gallon of the active 

ingredient) per 100 gallons of spray solution (400 ppm LPE).
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When used for post-harvest treatment, raw agricultural commodities are dipped into or 

sprayed with a solution and air dried prior to storage. 

Use Practice Limitations: Do not allow workers into treated areas for four hours 

following application.

Timing: Application in the field should start at 20 to 30 days before first harvest, 

depending on crop. Repeat at 7 to 10 day intervals.

C. DATA REQUIREMENTS

BPPD reviewed data requirements for granting this registration under Section 3(c)(5) of FIFRA. 

Mammalian toxicology and ecological effects data requirements for LPE were fulfilled. Product 

analysis data requirements are adequately satisfied. 

D. REGULATORY HISTORY

On July 18, 1997, EPA received an application from JP BioRegulators, Inc. for an Experimental 

Use Permit (EUP) covering the use of lysophosphatidylethanolamine to enhance ripening and 

extend storage time. On September 25, 1998, the Agency granted the EUP (63 FR 51352) to use 72 

kilograms/year of the biochemical phospholipid: Lyso-PE (lysophosphatidylethanolamine) on 570 

acres of apples, citrus, cranberries, grapes, nectarines, peaches, pears, strawberries, and tomatoes 

in nine states at a concentration of 100-500 ppm active ingredient. This was to evaluate ripening 

and storage shelf life. On June 2, 2001, three additional crops, blueberries, cherries and peppers, 

were added to the exemption from the requirement for a tolerance. The EUP was extended to 

include 2,475 acres in 10 states for two years at a rate of 12-500 ppm active ingredient (66 FR 

39648). 

On November 21, 2000, the Agency received an application for two new products with the new 

active ingredient, lysophosphatidylethanolamine. A notice of receipt of the application for 

registration of lysophosphatidylethanolamine was published in the Federal Register on 19 

September 2001 (66 FR 48256) with a 30-day comment period. No comments were received 

following this publication. On January 3, 2001, EPA published a Notice of Filing Petition to 

Establish an Exemption from the Requirement of a Tolerance (67 FR 323) with a 30-day comment 

period. No comments were received. On April 11, 2002, an Exemption from the Requirement of a 

Tolerance was established for the residues of LPE on all food commodities (40 CFR 180.1199); 

and on June 12, 2002 a Notice of Issuance (67 FR 113) was published in the Federal Register 

announcing the first registrations containing LPE.

In 2008, the registrant, Nutra-Park, Inc., went out of business. Their registered products containing 

LPE (EPA Reg. Nos. 70515-2 and 70515-3) were cancelled for non-payment of maintenance fees.

Upon dissolution of Nutra-Park, Doosan Corporation, a partner in manufacturing Nutra-Park 
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Inc.’s products, was granted all rights to the original registrations (including rights to data). On 

September 20, 2010 Doosan Corpooration submitted an application to register anew the former 

LPE registrations (EPA Reg Nos. 73652-R and 73652-E). No new data evaluations were 

developed because no new data were required, and the exemption from the requirement of a 

tolerance was still active. This LPE BRAD with its updated ‘Regulatory History’ is considered to 

be the current risk assessment for LPE. As part of the Agency’s Public Participation Process, 

EPA will open a 30-day comment period on November 30, 2011 to provide the public an 

opportunity to comment on the Agency’s draft risk assessment and its intention to re-register this 

pesticide product. 

E. CLASSIFICATION

In 1995, the Biochemical Classification Committee determined that LPE is a biochemical 

pesticide, a plant growth regulator, because it is naturally occurring with a non-toxic, indirect 

mode of action.

F. FOOD CLEARANCES/TOLERANCES

On June 12, 1998 (63 FR 32134), Phospholipid: Lyso-PE (lysophosphatidylethanolamine) was 

exempted from tolerance, on a temporary basis, until June 1, 200l. On August 1, 2001 (66 FR 

39648), the temporary exemption was extended to June 1, 2003. On January 3, 2001, EPA 

published a Notice of Filing Petition to Establish an Exemption from the Requirement of a 

Tolerance (67 FR 323) with a 30-day comment period. No comments were received. A Final Rule 

establishing an Exemption from the Requirement of a Tolerance (67 FR 70) was published on 

April 11, 2002. There are no Codex tolerances for lysophosphatidylethanolamine. 

III. Science Assessment

A. PHYSICAL/CHEMICAL PROPERTIES ASSESSMENT 

All product chemistry data requirements for the technical grade and the end-use product are met.

1. Product Identity and Mode of Action

a. Product Identity:

The technical grade active ingredient, LPE E94T consists of 94% LPE and the end-use product, 

LPE-94 10% Aqueous Growth Regulator, 10% LPE. 

 

b. Mode of Action:

The precise mode of action is unknown, but LPE has been shown to enhance ripening and extend 

the shelf life of certain fruits by increasing ethylene production without increasing respiration. It 
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has also been shown to inhibit senescence of ornamental flowers by inhibiting ethylene production 

and the activity of certain phospholipase enzymes. 

2. Physical and Chemical Properties Assessment

The physical and chemical characteristics of the TGAI and the end-use product were submitted to 

support the registration. They are summarized in Table 1. 

Table 1. Product chemistry data requirements:

Product Chemistry TGAI/MP (MRID 454357-02) EP (MRID 452736-06)

151B-10 (880.1100): Product 

identity

LPE E94T, the technical product, 

consists of 94% 

lysophosphatidylethanolamine and 

6% impurities

LPE-94 10% Aqueous, the end-use 

product, contains 10% 

lysophosphatidylethanolamine

151B-11 (880.1620): Formulation 

process 

An acceptable description of the 

manufacturing process was 

submitted. 

The product is formulated via a 

simple mixing process without any 

chemical reactions. 

151B-12 (880.1400): Discussion 

of formulation of unintentional 

impurities 

Acceptable nominal concentrations 

and certified limits were reported for 

the manufacturing impurities. 

No impurities of toxicological

concern are formed during the 

formulation process. 

151B-13 (880.1700): Preliminary 

analysis

Data obtained from the five-batch 

analysis demonstrate that the 

analytical method is precise and 

accurate. (MRID 452740-06)

No five-batch preliminary analysis 

data were submitted, but none are 

required since the end-use product 

is not manufactured via an 

integrated system, and because the 

TGAI/MP will be registered 

simultaneously with the EP.

880.1750: Certified limits The certified limits for the active 

ingredient and other impurities are 

acceptable. 

Acceptable nominal concentrations 

and certified limits were reported 

for the other (inert) ingredient in 

the formulation. 

880.1800: Enforcement analytical 

method

The analytical method is HPLC with 

an evaporative light scattering 

detector (ELSD). 

An acceptable HPLC/ELSD 

analytical method was submitted. 

Physical/Chemical Properties TGAI/MP (MRID 454357-02) EP (MRID 454361-03)

880.6302: Color Off white to yellow Off white to faint yellow

880.6303: Physical State Fine powder (solid) Suspension

880.6304: Odor Faint lipid (vegetable oil) aroma Faint characteristic odor of lipid 

(vegetable oil)
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Product Chemistry TGAI/MP (MRID 454357-02) EP (MRID 452736-06)

880.7200: Melting Point Melts over a range of temperatures 

(MRID 4444534-01)

N/A, not a solid

880.7220: Boiling Point N/A, not a liquid Not required under 40 CFR 

§158.190

880.7300: Density, Bulk Density, 

or Specific Gravity

Approximately 1 g/cc ~1.2 g/cc3

(MRID 443399-02)

880.7840: Solubility Forms micelles in water Not reported, but required for 

TGAI under 40 CFR §158.190

880.7050: Vapor Pressure < 2.1 x 10-4

Pa at 25C (MRID 

452740-07)

Not required for EP

880.7370: Dissociation constant N/A, does not dissociate N/A, does not dissociate

880.7550: Octanol/water partition 

coefficient

log Pow > 6.2 (MRID 452740-07) Not required for EP

880.7000: pH 6-8 6.5-7.0

Stability Over an extended period of time the 

unsaturated acyl chains will slowly 

oxidize (MRID 4444534-01)

Not reported, but required for 

TGAI under 40 CFR §158.190

880.6314: Oxidizing or Reduction 

Action

N/A, does not contain an oxidizing or 

reducing agent

N/A, does not contain an oxidizing 

or reducing agent.

880.6315: Flammability/Flame 

Extension

N/A, is not a combustible liquid. N/A, is not a combustible liquid.

880.6316: Explodability N/A, is not a potential explosive. N/A, does not contain explosive 

material.

880.6317: Storage Stability Stable at -20C for 6 months Interim reports show the end-use 

formulation is stable for more than 

30 days under normal storage 

conditions.

880.7100: Viscosity N/A, is not a liquid. 7.3 cps (at 60 rpm) at 20C

6.2 cps (at 60 rpm) at 40C

880.6319: Miscibility N/A, is not an emulsifiable liquid. N/A, is not to be diluted with 

petroleum solvents.

880.6320: Corrosion 

Characteristics

Non-corrosive Non-corrosive

880.6321: Dielectric Breakdown N/A, is not a liquid used around N/A, is not to be used around 
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Product Chemistry TGAI/MP (MRID 454357-02) EP (MRID 452736-06)

Voltage electrical equipment electrical equipment

B. HUMAN HEALTH ASSESSMENT

Information submitted to support the registration application of the technical grade active 

ingredient LPE E94T and the end-use product LPE-94 10% Aqueous adequately satisfies the food 

and non-food use requirements set forth in 40 CFR 158.690 (c) for biochemical pesticides. The 

overall toxicological risk from human exposure to LPE is negligible.

1. Toxicology Assessment

Adequate mammalian toxicology data are available and support registration of the product 

containing the active ingredient LPE.

a. Acute Toxicity

The registrant submitted acceptable acute toxicity studies. Based on a lack of mortality observed in 

albino rats, the oral LD50 of both the technical grade LPE E94T and the liquid end-use product 

LPE-94 10% Aqueous were >5,000 mg/kg, placing them in Toxicity Category IV. Based on a lack 

of mortality observed in albino rabbits dermally dosed with 2,000 mg/kg of both the technical and 

the end-use liquid product, the LD50 was >2,000 mg/kg, placing them in Toxicity Category III. 

All animals lived and gained weight after inhaling the product for 4 hours. The LC50 for LPE E94T 

is >2.50, while for the end-use product it is >4.63 mg/L; placing them in Toxicity Category IV. 

With a dose of 0.1 ml of liquid LPE-94 10% Aqueous only, one rabbit demonstrated conjunctivitis 

at the first reading which cleared by 24 hours. This classifies LPE-94 10% Aqueous as practically 

non-irritating with a Toxicity Category IV. However, when the TGAI was used as a test material, 

all rabbits had iritis and conjunctivitis one hour after instillation of LPE; all symptoms cleared by 

48-hours post-instillation. Based on the data, LPE Technical was considered a minimal irritant and 

classified as Toxicity Category III. Dermal application of 0.5 g of liquid product did not cause any 

dermal irritation symptoms up to 72 hours postdosing, placing it in Toxicity Category IV. Based 

on the data submitted for dermal sensitization, both the technical and the end-use product are 

definite contact sensitizers in guinea pigs by the Maximization method. Agency reviews are 

available in the docket (Refs. 1 and 2)

b. Genotoxicity, Immune Response, Mutagenicity, Developmental, Oncogenicity, 

Subchronic and Chronic Toxicity 

These studies are required, or conditionally required, for all food use biochemical pesticides, 

however, the registrant submitted published information to justify waivers for these studies (Refs. 

3 and 4), based on its presence in all cellular organisms. LPE is present in all cells in all organisms 
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as part of the cell membrane metabolites, from 1-10% depending on cell type. It is also present in 

high quantities in food products containing egg yolk and meat as well as in human breast milk 

(Ref. 5). Because of the ubiquitous nature of LPE and non-toxicity of the acute studies, further 

studies are waived (Refs. 1 and 6).

Data Waivers (Ref. 3) were requested for the following studies:

Studies to detect genotoxicity (OPPTS 870.5300)

Immune Response (OPPTS 880.3800

Mammalian mutagenicity test (OPPTS 870.5195

90-Day feeding (1 species) (OPPTS 870.3100)

90-Day dermal (1 species) (OPPTS 870.3250)

90-Day inhalation (1 species) (OPPTS 870.3465)

Teratogenicity (1 species) (OPPTS 870.3700)

Chronic exposure (OPPTS 870.4100) (Tier III)

Oncogencity (OPPTS 870.4200) (Tier III)

Much of these data regarding LPE and related phospholipids were submitted in support of similar 

waivers for additional acute toxicity testing, subchronic toxicity testing, and chronic toxicity

testing in conjunction with a temporary tolerance exemption (see 40 CFR §180.1199)(Ref. 4) for 

the use of this active ingredient under an Experimental Use Permit (EPA Reg. No. 70515-EUP-1). 

The registrant’s rationale to support the waivers is that LPE is ubiquitous in nature, and this and 

related phospholipids are synthesized by microorganisms, plants, and animals. These compounds 

are also ubiquitous in the human diet. Also, phospholipids have specific roles in cellular 

functions and in maintaining the integrity of cell membranes. See also memo from Russell Jones, 

Ph.D. to Sheila Moats, Ph.D., 8 Oct. 1997 (Ref. 6). The aforementioned data may be bridged to 

support the current waiver requests. In addition, there is a long history of consumption by humans 

of lipids in food and the Agency known of no instance where lipids have been associated with any 

toxic effects related to the consumption of food. Due to this knowledge of LPE’s presence and 

function in the human system (Ref. 5) and the recent acute testing, EPA believes LPE is unlikely to 

be carcinogenic or have other long-term toxic effects.

Mammalian toxicity data for LPE are summarized in Table 2. 

Table 2. Toxicity data requirements

GUIDELINE NO. STUDY RESULTS MRID NO.

152-10, 870.1100

Acute oral toxicity in rats Both TGAI and EU:

LD50 is > 5000 mg/kg Toxicity 

Category IV

452740-01

452736-01
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GUIDELINE NO. STUDY RESULTS MRID NO.

152-11, 870.1200 Acute dermal toxicity in 

rabbits

Both TGAI and EU:

LC50 is >2000 mg/Kg Toxicity 

Category III

452740-02

454361-01

152-12, 870.1300 Acute inhalation toxicity 

in rats

TGAI LC50 is >2.50 mg/L, EU LC50

is >4.63;

Both TGAI and EU: Toxicity 

Category IV

452740-05

452736-04

152-13, 870.2400 Primary eye irritation in 

rabbits

TGAI: Toxicity Category III

EU: Toxicity Category IV

452740-04

452736-03

152-14, 870.2500 Primary dermal irritation 

in rabbits

Both TGAI and EU:

Toxicity Category IV

452740-03

452736-02

152-15, 870.2600 Dermal sensitization in 

guinea pigs

Both TGAI and EU are considered 

to be contact sensitizers in guinea 

pigs by the Maximization method. 

454357-01

452736-05

152-17, 870.5300 Studies to detect 

genotoxicity 

Waived N/A

152-18, 870.8700 Cellular immune 

response

Waived N/A

152-19, 870.5195 Mammalian mutagenicity 

test

Waived

N/A

152-20, 870.3100 90-day feeding study Waived N/A

152-21, 870.3200 90-day dermal study Waived N/A

152-22, 870.3250 90-day inhalation study Waived N/A

152-23, 870.3700 Developmental toxicity Waived N/A

83-1, 870.4100 Chronic exposure Waived N/A

83-2, 870.4200 Oncogenicity Waived N/A
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c. Effects on the Endocrine Systems

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor Screening 

Program (EDSP) to determine whether certain substances (including pesticide active and other 

ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally 

occurring estrogen, or other such endocrine effects as the Administrator may designate.” The 

EDSP employs a two-tiered approach to making the statutorily required determinations. Tier 1 

consists of a battery of 11 screening assays to identify the potential of a chemical substance to 

interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go 

through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal 

systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the 

Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any

adverse endocrine related effects caused by the substance, and establish a dose-response 

relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA is issuing test orders/data call-ins for the first 

group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. This 

list of chemicals was selected based on the potential for human exposure through pathways such as 

food and water, residential activity, and certain post-application agricultural scenarios. This list 

should not be construed as a list of known or likely endocrine disruptors.

LPE is not among the group of 58 pesticide active ingredients on the initial list to be screened 

under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. 

Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all pesticide active 

ingredients. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/.

While no data are presently being required for LPE, the Agency reserves the right to require new 

information, should the program require it. Presently, based on the lack of exposure and the 

negligible toxicity profile of the extract, no adverse effects to the endocrine or immune systems are 

known or expected. The Agency intends to issue a complete EDSP assessment in the Registration 

Review process or as might be required earlier.

2. Dose Response Assessment

No toxicological endpoints are identified. 

 

3. Aggregate Exposure and Risk Characterization

a. Dietary
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ii. Food

In the absence of any toxicological endpoints, risk from the consumption of residues is not 

expected for the general population including infants and children. Sprayed LPE on food crops is 

relatively low (examples from 0.06-0.18% over native content [Ref. 7]) and are reduced further by

catabolism through the lipid metabolic system found in most organisms (Ref.5). Further, 

commercial phospholipid products containing LPE are in use already and approved by FDA for 

food use, animal feed and for dietetics (Ref. 5).

iii. Drinking Water

Treatment of crops in the fields may include run-off to surface and ground water, but the 

compound is a natural metabolite further metabolized by microbial organisms (Ref. 5). Significant 

exposure to LPE in drinking water is not expected. 

b. Other Non-occupational Exposure

LPE is a naturally occurring lipid metabolite and exposure is expected to be universal. In addition, 

FDA has approved LPE-containing substances for use for many other purposes (Ref. 5).

4. Occupational, Residential, School and Day Care Exposure and Risk 

Characterization

Significant additional human exposure to LPE is not expected in residential, school and day care 

areas. Commercial phospholipid products containing LPE have been approved by FDA for 

pharmaceuticals and cosmetic uses (Ref. 5).

a. Occupational Exposure

Agricultural use of LPE is subject to the Worker Protection Standards (WPS), requiring Personal 

Protective Equipment (PPE), a long-sleeved shirt, long pants, socks, shoes and gloves, plus a 4 

hour Restricted Entry Interval (REI). 

b. Residential, School and Day Care Exposure and Risk Characterization

In the absence of any toxicological endpoints, risk from the consumption of residues is not 

expected for populations in residential, school and day care facilities. 
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5. Acute and Chronic Dietary Risks for Sensitive Subpopulations Particularly Infants and 

Children

FFDCA section 408 provides that EPA shall apply an additional tenfold margin of exposure 

(safety) for infants and children in the case of threshold effects to account for pre- and post-natal 

toxicity and the completeness of the database unless EPA determines that a different margin of 

exposure (safety) will be safe for infants and children. Margins of exposure (safety) are often 

referred to as uncertainty (safety) factors. In this instance, based on all the available information, 

the Agency concludes that LPE is practically non-toxic to mammals, including infants and 

children. Thus, there are no threshold effects of concern and, as a result the provision requiring an 

additional margin of safety does not apply. Further, the provisions of consumption patterns, 

special susceptibility, and cumulative effects do not apply. LPE is found naturally in many foods 

already consumed by infants and children - human breast milk, eggs, and fruits and vegetables. 

No toxic endpoints have been identified for LPE. As a result, EPA has not used a margin of 

exposure (safety) approach to assess the safety of LPE.

 

6. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation

Aggregate exposure to LPE by field workers and applicators may occur via oral, dermal and 

inhalation routes. These risks are measured via the acute toxicity studies submitted to support 

registration. The oral toxicity studies for LPE showed no toxicity (Toxicity Category IV), the 

risks anticipated from oral exposure are considered minimal. Because the inhalation toxicity

studies for LPE showed no toxicity (Toxicity Category IV), the risks anticipated for this route of 

exposure are also considered minimal. 

Results of the acute dermal toxicity study indicated no toxicity at the maximum dose tested (2,000 

mg) (Toxicity Category III) and no significant dermal irritation (Toxicity Category IV). Based on 

these results, the anticipated risks from dermal exposure are also considered minimal. Therefore, 

the risks from aggregate exposure via oral, dermal and inhalation exposure are a compilation of 

three low risk exposure scenarios and are negligible. 

Dermal sensitization may occur, as the products are sensitizers. However, this risk is mitigated as 

long as the product is used according to label directions, which requires the use of protective 

equipment (a long-sleeved shirt and long pants, socks, shoes and gloves) by users and a 4-hour 

restricted re-entry interval into treated areas. Aggregate exposure to LPE by the consumer would 

include other sources in addition to the limited amount on the agricultural products. Commercial 

phospholipid products containing LPE are used in the technical industry, and have been approved 

by FDA for food use, pharmaceuticals, cosmetics and dietetics and animal feed (Ref. 5). 

7. Cumulative Effects

LPE is not toxic and it is not anticipated that there would be cumulative effects from a common 

mechanism of toxicity.
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8. Risk Characterization

The Agency has considered LPE in light of the relevant safety factors in FQPA and FIFRA. A 

determination has been made that no unreasonable adverse effects to the U. S. population in 

general, and to infants and children in particular, will result from the use of LPE-94 10% Aqueous 

when label instructions are followed.

C. ENVIRONMENTAL ASSESSMENT

1. Ecological Effects Hazard Assessment

The end use product LPE-94 10% Aqueous is intended for agricultural and horticultural use. When 

applied according to the proposed label directions, no direct exposure of birds or aquatic 

organisms to LPE-94 10% Aqueous is expected to occur. Moreover, the active ingredient is a 

natural metabolite of a common biological lipid. Many published studies were supplied to the 

Agency (Ref. 8), which indicate that the potential environmental/ecological effects LPE-94 10% 

Aqueous are likely to be negligible. As a result, nontarget organism/ecological effects studies were 

waived for these particular uses of LPE-94 10% Aqueous. However, standard precautionary label 

statements under “Environmental Hazards” are presented on the label.

2. Environmental Fate and Ground Water Data 

The need for environmental fate and groundwater data (Tier II, (40 CFR Section 158.690(d)(2)(vii 

through xv)) was not triggered because the Tier I studies were waived. Risk is minimal due to the 

lack of exposure, low toxicity, use pattern, and application methods.

3. Ecological Exposure and Risk Characterization

Sprayed LPE residues are low (examples are from 0.06-0.18% over native content [Ref. 7]), and 

are reduced further by catabolism through the lipid metabolic system found in most organisms 

(Ref. 5). Minimal potential for exposure exists to insects, fish and other nontarget wildlife as a 

result of LPE-94 10% Aqueous use.

D. EFFICACY DATA

No efficacy data are required, because no public health uses are involved.

IV. Risk Management Decision
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A. DETERMINATION OF ELIGIBILITY FOR REGISTRATION

Section 3(c)(5) of FIFRA provides for the registration of new active ingredients if it is determined 

that (A) its composition is such as to warrant the proposed claims for it; (B) its labeling and other 

materials required to be submitted comply with the requirements of FIFRA; (c) it will perform its 

intended function without unreasonable adverse effects on the environment and (D) when used in 

accordance with widespread and commonly recognized practice it will not generally cause 

unreasonable adverse effects on the environment.

To satisfy criteria “A” above, LPE is not expected to cause unreasonable adverse effects when 

used according to label instructions. Criteria “B” is satisfied by the current label and by the data 

presented in this document. It is believed that this new pesticidal active ingredient will not cause 

any unreasonable adverse effects, will enhance fruit, hasten ripening and increase shelf life, 

satisfying Criteria “C”. Criteria “D” is satisfied by the data submitted and the low exposure to the 

product when used according to the label's directions.

Therefore, LPE is eligible for registration. The uses are listed in Table 4, Appendix A. 

B. REGULATORY POSITION

1. Unconditional Registration

All data requirements have been fulfilled and/or waived by the Agency and the Biopesticides and 

Pollution Prevention Division supports unconditional registration of products which contain LPE 

as their sole active ingredient.

2. Tolerances for food uses and/or exemptions

40 CFR 180.1199 establishes an exemption from the requirement of a tolerance for the residues of 

LPE in or on all food commodities. 

2. CODEX Harmonization

There are no CODEX values for LPE.

3. Nonfood Re/Registrations
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There are no non-food issues at this time. The non-food uses are listed in Appendix A, Table 4.

4. Risk Mitigation

There are no significant risk issues. Risks to workers are mitigated by protective clothing 

requirements and a 4-hour re-entry interval restriction.

5. Endangered Species Statement

Given LPE’s non-toxic mode of action, its negligible potential for exposure to non-target 

organisms, and its lack of toxicological endpoints, the Agency has determined that the pesticidal 

use of LPE will have “no effect” on currently listed endangered and threatened species.

C. LABELING RATIONALE

It is the Agency’s position that the labeling of LPE-94 10% Aqueous and the technical grade active 

ingredient LPE E94T containing, respectively, 10% and 94% LPE complies with current pesticide 

labeling requirements.

1. Human Health Hazard

a. Worker Protection Standard

This product comes under the provisions of the Worker Protection Standards (WPS). 

PPE (long-sleeved shirt and long pants, socks, shoes, and gloves) and REI (4-hour) required.

b. Non-Worker Protection Standard

There are no non-WPS human health hazard issues.

c. Precautionary Labeling

The Agency has examined the toxicological data base for LPE E94T and LPE-94 10% Aqueous 

product and concluded proposed precautionary labeling (i.e. Signal Word, Statement of Practical 

Treatment and other label statements) adequately mitigates any risks associated with the proposed 

uses. 

Technical Product Precautionary Labeling: “Caution”
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Hazards to Humans and Domestic Animals:

Harmful if absorbed through skin. Causes moderate eye irritation. Avoid contact with skin, eyes or 

clothing. Wear protective eyewear. Wash thoroughly with soap and water after handling and 

before eating, drinking, chewing gum, or using tobacco. Wear long-sleeved shirt and long pants, 

socks, shoes, and gloves. Remove and wash contaminated clothing before reuse. 

Prolonged or frequently repeated skin contact may cause allergic reactions in some individuals.

First Aid:

If on skin:

-Take off contaminated clothing.

-Rinse skin immediately with plenty of water for 15-20 minutes.

-Call a poison control center or doctor for treatment advice.

If in eyes:

-Hold eye open and rinse slowly and gently with water for 15-20 minutes.

-Remove contact lenses, if present, after the first 5 minutes, then continue rinsing.

-Call a poison control center or doctor for treatment advice.

End-Use Product Precautionary Labeling: “CAUTION.” 

Hazards to Humans and Domestic Animals:

Harmful if absorbed through skin. Avoid contact with skin, eyes or clothing. Wash thoroughly 

with soap and water after handling and before eating, drinking, chewing gum, or using tobacco. 

Remove and wash contaminated clothing before reuse. Wear: long-sleeved shirt and long pants, 

socks, shoes, and gloves.

Prolonged or frequently repeated skin contact may cause allergic reactions in some individuals.

First Aid:

If on skin:

-Take off contaminated clothing.

-Rinse skin immediately with plenty of water for 15-20 minutes.

-Call a poison control center or doctor for treatment advice.

Have the product container or label with you when calling a poison control center or doctor or 

going for treatment. 

2. Environmental Hazards Labeling
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End-Use Product Environmental Hazards Labeling: Although LPE is considered to be 

non-toxic, the environmental hazard statement is nevertheless required on the end-use product’s 

label.

3. Application Rate

Labeling for the pesticide product containing LPE complies with current pesticide labeling 

requirements. The Agency has not stipulated a maximum number of applications for the active 

ingredient. Pre-harvest applications should use conventional spray or foliar application 

equipment at a rate of 100-400 ppm depending on crop. Begin applications at 30 to 20 days before 

harvest and continue at 7 to 10 day intervals. Post-harvest dips or sprays are applied immediately

after harvest, before storage, at a rate of 25-100 ppm LPE, while use as a solution for maintenance 

of cut flowers is at the same rate.

D. LABELING 

(1) Product name: LPE E94T

Active Ingredient:

Lysophosphatidylethanolamine (LPE). . . . . . . . . . . . . . . . ........94.0%

Other Ingredients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..........6.0%

 ______________________________________________________

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100.00%

(2) Product name: LPE-94 10% Aqueous

Active Ingredient:

Lysophosphatidylethanolamine . . . . . . . . . . . . . . . . . . . . . . . .10.0%

Other Ingredients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .....90.0%

 ______________________________________________________

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100.00%

The Signal Word is "CAUTION". Dermal toxicity and hypersensitivity warning is appropriate.

The product shall contain the following information:

 - Product Name

 - Ingredient Statement

 - Registration Number

 - Signal Word (CAUTION)

V. Actions Required by Registrants
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There are no data requirements, label changes or other responses necessary for the reregistration of 

the end-use product since the product is being registered after November 1984 and is, therefore, 

not subject to reregistration. There are also no existing stocks provisions at this time.

VI. Approved Use Sites

Agency Recognized Use Sites for LPE: Field Crops, Storage Facilities, Horticultural Facilities

VII. References

1. USEPA; Science Review in Support of Registration of LPE E94T Technical and 

LPE 94 20% Aqueous Growth Regulator, memo from Jones, Russell S., Ph.D., to 

Carol E. Frazer, Ph.D., 13 Sep. 2001.

2. USEPA; Data Evaluation Record: Skin Sensitization (MRID 454357-01), memo 

from Reilly, Sheryl K., Ph.D., to Carol E. Frazer, Ph.D., 21 Jan. 2002.

3. JP BioRegulators, Inc.: Waiver Request from Biochemical Pesticides Toxicology

Data Requirements, 2000.

4. Palta, Jiwan, Dr. and Hartman, Christina L., Dr.: Phospholipid Safety Data in 

Support of a Petition Proposing a Temporary Exemption from the Requirement of a 

Tolerance for Phospholipid for Use in Grapes, Tomatoes, Apples, Pear, Peaches, 

Nectarines, Citrus, Cranberries and Strawberries, 1997 (MRID 443399-05).

5. JP BioRegulators, Inc.: A Review on Lysophosphatidylethanolamine and Related 

Phospholipids, 2000.

6. USEPA. An Experimental Use Permit (EUP) and Petition for a Temporary 

Tolerance Exemption for Phospholipid; memo from Jones, Russell S., Ph.D., to 

Sheila Moats, Ph.D., 8 October 1997.

7. Nutra-Park, Inc., 2002: Effect of LPE Applications; Memo to Carol E. Frazer, 

Ph.D.

8. Palta, Jiwan, Dr. and Hartman, Christina L., Dr.: Phospholipid – Safety Data for 

Environmental Effects, 1997 (MRID 443399-06).