BIOPESTICIDES REGISTRATION ACTION DOCUMENT

Cold Pressed Neem Oil

PC Code 025006

U.S. Environmental Protection Agency

Office of Pesticide Programs

Biopesticides and Pollution Prevention Division

(Last updated March 22, 2012)

This document is for informational purposes only and is representative of the Agency’s justification in registering 

products containing this active ingredient. This is not a legal document. 
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TA BLE OF CONTENTS

I. EXECUTIVE SUMMARY .................................................................................................. 5

II. ACTIVE INGREDIENT OVERVIEW............................................................................... 6

III. REGULATORY BACKGROUND...................................................................................... 6

A. Classification .....................................................................................................................................................7

B. Food Clearances/Tolerances ............................................................................................................................7

IV. RISK ASSESSMENT ........................................................................................................... 7

A. Active Ingredient Characterization.................................................................................................................7

B. Human Health Assessment...............................................................................................................................8

1. Toxicology..........................................................................................................................................................8

a. Acute Toxicity.................................................................................................................................................8

b. Sub-chronic Toxicity.......................................................................................................................................8

c. Developmental Toxicity and Mutagenicity......................................................................................................9

d. Effects on the Endocrine System.....................................................................................................................9

2. Dose Response Assessment.............................................................................................................................10

3. Food Quality Protection Act (FQPA) Consideration...................................................................................10

a. Dietary Exposure and Risk Characterization.................................................................................................10

b. Drinking Water Exposure and Risk Characterization....................................................................................10

c. Acute and Chronic Dietary Risks for Sensitive Subpopulations Particularly Infants and Children...............11

4. Occupational, Residential, School and Day Care Exposure and Risk Characterization..........................11

a. Occupational Exposure and Risk Characterization........................................................................................11

b. Residential, School and Day Care Exposure and Risk Characterization .......................................................11

5. Cumulative Effects..........................................................................................................................................12

6. Risk Characterization.....................................................................................................................................12

C. Environmental Assessment.............................................................................................................................12

1. Ecological Hazards .........................................................................................................................................12

2. Environmental Fate and Ground Water Data..............................................................................................12

3. Ecological Exposure and Risk Characterization..........................................................................................13

4. Endangered Species Assessment....................................................................................................................13

D. Product Performance (Efficacy)....................................................................................................................13

V. RISK MANAGEMENT DECISION................................................................................. 14

A. Determination of Eligibility for Registration................................................................................................14
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B. Regulatory Decision........................................................................................................................................14

C. Environmental Justice ....................................................................................................................................14

VI. ACTIONS REQUIRED BY REGISTRANTS ................................................................. 15

A. Reporting of Adverse Effects.........................................................................................................................15

B. Reporting of Hypersensitivity Incidents .......................................................................................................15

VII. APPENDIX A...................................................................................................................... 16

VIII. APPENDIX B..................................................................................................................... 19

IX. APPENDIX C...................................................................................................................... 20
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BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

Office of Pesticide Programs:

Biopesticides and Pollution Prevention Division

Biochemical Pesticides Branch (BPB)

Driss Benmhend Regulatory Action Leader

Gina Burnett, M.S. Regulatory Action Leader

Linda Hollis, M.S. Branch Chief

Jacob Moore Chemist

Manying Xue, M.S Chemist

Clara Fuentes, Ph.D. Entemologist

Russell Jones, Ph.D. Senior Biologist
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I. EXECUTIVE SUMMARY

The active ingredient Cold Pressed Neem Oil is pressed directly from seeds of the Neem tree 

(Azadirachta indica), which is a tropical evergreen tree native to India and also found in other 

Southeast Asian and African countries. Cold Pressed Neem Oil has a brown color, a bitter taste 

and a garlic/sulfur smell. Cold pressed Neem Oil has demonstrated properties as an insect

repellent, insect growth regulator, and insecticide. 

In October 2009, the Biopesticides and Pollution Prevention Division (BPPD) reviewed data 

required to support the registration of this biochemical active ingredient, under Section 3(c)(5) of 

the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), for use on outdoor and 

greenhouse agricultural food and ornamental crops. At that time, product chemistry data 

requirements were satisfied by acceptable guideline studies. Adequate mammalian toxicology

data/information was submitted to support registration of Cold Pressed Neem Oil for outdoor 

uses on crops and ornamentals. Specifically, acceptable acute toxicity guideline studies were 

submitted, and data waivers were granted by the Agency for the remaining toxicity requirements 

based on the lack of toxicity of the active ingredient. Ecological effects data requirements for 

Cold Pressed Neem Oil were fulfilled by acceptable guideline studies and additional 

data/information from the scientific literature sufficient to support the remaining Tier I and Tier 

II requirements.

In March 2012, BPPD reviewed data required to support the addition of a “new use” to the Cold 

Pressed Neem Oil registration. The “new use” is indoor use for the control of bed bugs. In 

support of this use, additional mammalian toxicology data/information was submitted to fulfill 

the biochemical pesticide data requirements of 90-day dermal toxicity and 90-day inhalation 

toxicity. 

Based on the data available to the Agency, it has been determined that no unreasonable adverse 

effects to the U.S. population and the environment will result from the use of the active 

ingredient when label instructions are followed and good agricultural practices are employed. 

Laboratory studies indicate that the active ingredient is not toxic following oral, inhalation or 

dermal exposure. Cold Pressed Neem Oil and neem extracts are widely used in cosmetics (soap, 

hair products, hand creams, etc.), traditional folk medicine (acne, fevers, rheumatism, diuretics, 

inflammations, etc.), as an insect repellent, insecticide, nematicide, fungicide, and as a fertilizer.

There are no reports of adverse effects following human exposure to this biochemical. Moreover, 

the pesticidal usage of Cold Pressed Neem Oil will not have any harmful environmental effects. 

Studies indicate that Cold Pressed Neem Oil will not cause adverse effects to mammals, birds, 

fish and aquatic invertebrates, other non-target insects, or plants. 

Due to the negligible risk concerns when used as an insect repellent, insect growth regulator, and 

insecticide, Cold Pressed Neem Oil meets the criteria as specified in §3(c)(5) of the Federal 

Insecticide, Fungicide and Rodenticide Act (FIFRA), as amended, and is thus eligible for 

unconditional registration. It was determined that the data/information submitted adequately

satisfy applicable data requirements at 40 C.F.R. Subpart U §158.2000.
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II. ACTIVE INGREDIENT OVERVIEW

Common Name: Neem Oil

Chemical Names: Cold Pressed Neem Oil

Trade & Other Names: Cold Pressed Neem Oil

CAS Registry Number: 8002-65-1

OPP Chemical Code: 025006

Type of Pesticide: Insect repellent, insect growth regulator (anti-feedant), insecticide. 

Application rates and methods vary depending on the product. For specific information 

regarding the product(s) refer to Appendix B.

III. REGULATORY BACKGROUND

On August 02, 2007, Plasma Power of India, submitted an application for the registration of the 

end use product (EP) Plasma NeemTM Oil (azadirachtin 3000 ppm) Insecticide (84185-U), and 

Plasma NeemTM Oil Manufacturing Use Product (84185-G). Both products contain 100% Cold 

Pressed Neem Oil. A notice of receipt of the application for registration of Cold Pressed Neem 

Oil as a new active ingredient was published in the Federal Register on October 24, 2007 (72 FR 

60365), with a 30-day comment period. No comments were received following this publication.

Consistent with the Agency’s new policy for making pesticide registration actions more 

transparent, EPA provided a 30-day public comment period on the decision to register Cold 

Pressed Neem Oil. No comments were received during the 30 day public comment period

On September 19, 2011, Terramera, Inc., submitted an application for the registration of end-use 

products(EPs) TER-RTU1 (88760-R), containing 5.5% Cold Pressed Neem Oil, and TER-CX1 

(88760-E), containing 22.0% Cold Pressed Neem Oil. These EPs indicate a “new use” for this 

active ingredient (indoor use for the control of bed bugs). A notice of receipt of the application 

for registration of Cold Pressed Neem Oil for indoor use was published in the Federal Register 

on November 9, 2011 (76 FR 69730), with a 30-day comment period. No comments were 

received following this publication.

Consistent with the Agency’s policy of making registration actions more transparent, the 

registration of the TER-RTU1 and TER-CX1 EPs is subject to a 30-day comment period as a 

“first indoor use.” While a final decision on registration of these EPs is contingent upon review 

and consideration of public comments, EPA presently believes that, based on the preliminary risk 

assessment and information submitted in support of the registration of Cold Pressed Neem Oil 

for indoor use, that 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 Cold 

Pressed Neem Oil, which is characterized in this BRAD. 
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A. Classification

The Biochemical Classification Committee determined that Cold Pressed Neem Oil is a

biochemical pesticide due to its apparent non-toxic mode of action and natural occurrence in the 

environment.

B. Food Clearances/Tolerances 

Plasma Power of India filed a petition (PP 7F7249) proposing to establish an exemption from the 

requirement of a tolerance for residues of Cold Pressed Neem Oil in or on all food commodities. 

A notice of filing was published on November 2, 2007 (72 FR 62237). On October 13, 2009, 

EPA promulgated a final rule exempting residues of the biochemical pesticide Cold Pressed 

Neem Oil, from the requirement for tolerance in or on all food commodities.

IV. RISK ASSESSMENT

A. Active Ingredient Characterization

Cold Pressed Neem Oil is pressed directly from seeds of the Neem tree (Azadirachta indica), 

which is a tropical evergreen tree native to India and also found in other Southeast Asian and 

African countries. Cold Pressed Neem Oil has a brown color, a bitter taste and a garlic/sulfur 

smell. A single seed may contain up to 50 percent oil by weight. Cold Pressed Neem Oil contains 

various compounds that have insecticidal and medicinal properties. It is used in making 

shampoos, toothpaste, soaps, cosmetics, mosquito repellents, creams and lotions, and pet 

products such as pet shampoo. It also contains vitamin E, other essential amino acids and fatty

acids. Cold Pressed Neem Oil is used for treating many skin diseases, including eczema, 

psoriasis, and skin allergies. 

Cold Pressed Neem Oil is a mixture of several C26 terpenoids that are naturally occurring organic 

compounds composed of a five-carbon skeleton (simple terpenoids) or complex terpenoids with 

structures that possess between 20 and 40 carbon atoms. Azadirachtin, the most common 

terpenoid in Cold Pressed Neem Oil and the most thoroughly characterized, is a federally

registered active ingredient pesticide. Cold Pressed Neem Oil also contains steroids, fatty acids, 

and a number of essential oils. 

Descriptions of the technical grade active ingredient (TGAI) product formulation and production 

process, as well as the formation of impurities, were examined by the Agency and found to meet 

current standards. A preliminary analysis was conducted to determine Cold Pressed Neem Oil

content in five batches of the product, and the results were determined to be acceptable by the 

Agency. The analytical method used to determine the content of the active ingredient is also 

acceptable. Physical and chemical properties were submitted for the TGAI and are adequate. 

Refer to Table 1 in Appendix A for a summary of product chemistry data requirements. Refer to 

Table 2 in Appendix A for the summary of physical and chemical characteristics. All product 

chemistry data requirements for registration of Cold Pressed Neem Oil have been satisfied.
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B. Human Health Assessment

1. Toxicology 

Toxicity categories are assigned based on the hazard(s) identified from studies and/or 

information on file with the Agency. An active ingredient is classified into Toxicity Category I, 

II, III or IV, in which Toxicity Category I indicates the highest toxicity and Toxicity Category IV

indicates the lowest toxicity. 

Adequate mammalian toxicology data/information is available to support registration of Cold 

Pressed Neem Oil. All toxicology data requirements for Cold Pressed Neem Oil have been 

satisfied.

a. Acute Toxicity

Acute toxicity testing is required to 1) determine systemic toxicity from acute exposure via the 

dermal, inhalation and oral routes, 2) determine irritant effects from exposure to the eyes and 3) 

determine the potential for skin sensitization (allergic contact dermatitis). 

Tier I toxicity data submitted and reviewed showed that Cold Pressed Neem Oil is a toxicity

category IV (low toxicity) compound via acute oral and acute inhalation routes of exposure. 

Cold Pressed Neem Oil is in Toxicity Category III (slightly toxic) for acute dermal irritation. 

Cold Pressed Neem Oil is not an eye or skin irritant, and it is not a dermal sensitizer. No 

additional toxicity data are required to support usage of this biochemical. 

For more information regarding the acute toxicity data requirements, refer to Table 3 in 

Appendix A.

b. Sub-chronic Toxicity

Subchronic data is required to determine a no-observed-effect-level (NOEL) and toxic effects (if 

any) associated with repeated or continuous exposure to a test substance for a period of 90 days. 

To address the 90-day oral toxicity the data requirement as appropriate for an agricultural 

registration, the applicant submitted data obtained from the technical public literature in lieu of a 

guideline study. The study showed that test animals did not exhibit any clinical signs of toxicity

that were statistically different from untreated controls. There were no significant changes in 

body weight, serum liver damage indicators, direct bilirubin and total bilirubin, or other blood 

parameters during the 90-day study period. The 90-day oral feeding LD50 is higher than 5000 mg 

crude Cold Pressed Neem Oil/kg body weight. Based on the review of this data, the Agency

concluded that no subchronic oral toxicity is expected to occur when this compound is used in 

accordance with good agricultural practices.

The 90-day dermal and 90-day inhalation toxicity data requirements were waived for the initial 

agricultural use of Cold Pressed Neem Oil. For the addition of a “first indoor use,” these data 

requirements have been fulfilled using rationale supported by published scientific literature.

Specifically, dermal metabolism of the product is not expected to differ from its oral metabolism

(EPA, 2009). In the acute guideline studies, the product was demonstrated to have no acute 
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dermal toxicity (LD50 >4000 mg/kg), was not a dermal irritant, and was not a dermal sensitizer. 

Similarly, there is a lack of inhalation toxicity (Toxicity Category IV) demonstrated in the 

submitted acute inhalation toxicity study (LC50 >2.11 mg/L). In addition, repeated inhalation 

exposure is mitigated by indoor use label language requiring a four hour re-entry period after 

application of the product. Alongside the low toxicity present in the acute and subchronic studies, 

the Agency concludes that no subchronic dermal or inhalation toxicity is expected to occur when 

used in accordance with good agricultural practice and when used indoors in accordance with 

label instructions. 

Furthermore, humans are regularly exposed to this substance in medicinal and cosmetic products, 

via the oral, inhalation and dermal routes, and at comparatively high levels (Schmutterer, 1995). 

These uses are also expected to result in exposures that are significantly greater than that which 

would be expected from pesticidal uses, including both agricultural and indoor uses.

For more information regarding the subchronic data requirements, refer to Table 3 in Appendix 

A.

c. Developmental Toxicity and Mutagenicity 

Studies from technical public literature were submitted to address the data requirements for 

developmental toxicity and mutagenicity (OPPTS 870.3700). 

Based on In vitro and in vivo studies, and subcutaneous and intravaginal applications of Cold 

Pressed Neem Oil, it seems that developmental toxicity may occur in test animals when exposed

to Cold Pressed Neem Oil by intravaginal, intrauterine, subcutaneous injection, or by direct 

exposure to mammalian sperm and eggs in in vitro laboratory studies. The three generation study

in rats fed Cold Pressed Neem Oil in the diet, however, demonstrates that chronic oral ingestion 

of food commodities containing Cold Pressed Neem Oil residues does not result in any

mammalian developmental toxicity. Taken together, these data demonstrate that no 

developmental toxicity is expected to occur from the use of Cold Pressed Neem Oil as a 

pesticide.

Furthermore, Cold Pressed Neem Oil and its components are not structurally related to known 

mutagens, nor do they belong to any chemical class of compounds containing known mutagens. 

Humans are regularly exposed to this substance via oral exposure (as a traditional folk medicinal 

product) and dermal exposure (when used on skin and hair) at levels that are significantly greater 

than that which would be expected from the product as a pesticide under conditions of use. In 

addition, an extensive literature search of several scientific databases (i.e. ChemIDPlus, HSDB, 

Toxline, CCCRIS, DART, GENETOX, IRIS, ITER, LactMed, Multi-Database, TRI, HazMap, 

Household Products, TOXMAP and TOXNET) for the period 1980 to 2008 failed to locate any

other data / information regarding mutagenicity or genotoxicity of Cold Pressed Neem Oil. As a 

result, EPA concludes that Cold Pressed Neem Oil is not mutagenic or genotoxic. 

d. Effects on the Endocrine System

EPA is required under the Federal Food, Drug, and Cosmetics Act (FFDCA) to develop a 

screening program to determine whether certain substances (including all pesticide active and 

other ingredients) “may have an effect in humans that is similar to an effect produced by a 
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naturally-occurring estrogen, or other such endocrine effects as the Administrator may

designate.” Following the recommendations of its Endocrine Disruptor Screening and Testing 

Advisory Committee (EDSTAC), EPA determined that there was scientific basis for including, 

as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen 

hormone system. EPA also adopted EDSTAC’s recommendation that the program include 

evaluations of potential effects in wildlife. When the appropriate screening and/or testing 

protocols being considered under the Agency’s Endocrine Disrupter Screening Program (EDSP) 

have been developed and vetted, Cold Pressed Neem Oil may be subjected to additional 

screening and/or testing to better characterize effects related to endocrine disruption.

2. Dose Response Assessment

No meaningful toxicological endpoints were identified on Cold Pressed Neem Oil when used as 

a pesticide; therefore, a dose response assessment was not required. 

3. Food Quality Protection Act (FQPA) Consideration

a. Dietary Exposure and Risk Characterization

The most likely human exposure to Cold Pressed Neem Oil will occur via dietary exposure 

(consumption) to treated fruits, seeds, or leafy vegetables. EPA modeling (using the Terrestrial 

Exposure model (T-REX; EPA, 2005) of potential residues of Cold Pressed Neem Oil following 

terrestrial treatments indicated that following 12 consecutive applications of 100% Cold Pressed 

Neem Oil at 7-day intervals, the maximum dietary residues present would be approximately 881 

ppm on broadleaf plant foliage; and approximately 98 ppm on fruits, pods, and seeds. The 

modeling indicated that residues would decline rapidly between foliar applications 

(approximately 245-440 ppm on broadleaf foliage; and 27-49 ppm on fruits, pods, and seeds) and 

following the final application (see Table 4 in appendix A). As stated in section B (a) of this 

document, Cold Pressed Neem Oil is a toxicity category IV for oral exposure (LD50 = >5000 

mg/kg). The estimated maximum theoretical residues likely to be present on edible commodities 

are 882 ppm. This residue level is approximately 5-fold less than the highest doses used in acute 

and subchronic laboratory testing (5000 mg/kg) and approximately 20-fold less than chronic 

laboratory testing (10% in the diet) at which no mortalities or other signs of clinical toxicity were 

observed. Therefore, based on a lack of acute, subchronic, or chronic toxicity in laboratory

testing, estimated maximum residues that are well below the doses used in laboratory testing, and 

the rapid degradation of Neem Oil in the environment, it is highly unlikely that that there will be 

any adverse effects to humans resulting from dietary exposure to Neem Oil residue.

Moreover, humans are regularly exposed to this compound via consumption of Cold Pressed 

Neem Oil medicinal products, and at levels that are significantly greater than what would be 

expected from pesticide applications. EPA has determined that dietary exposure is not a concern 

because of the low toxicity of this active ingredient and the history of its use without any reports 

of adverse effects.

b. Drinking Water Exposure and Risk Characterization

No significant drinking water exposure or residues are expected to result from the pesticidal 

usage of Cold Pressed Neem Oil. The outdoor use of this active ingredient is intended as a foliar 
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application on food commodities and not to be applied directly to water. If used in accordance 

with EPA-approved labeling, is not likely to accumulate in drinking water. In the unlikely event 

that exposure via drinking water did occur from accidental spraying, the health risk would be 

expected to be minimal, based on the low acute oral toxicity and the long history of human 

exposure to Cold Pressed Neem Oil without adverse effects.

As a result, dietary and drinking water exposure to residue of Cold Pressed Neem Oil are 

expected to be minimal.

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

and Children

FFDCA section 408 provides that the Agency 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 the Agency 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 has concluded that there is reasonable certainty that no harm to 

infants and children or adults will result from the use of Cold Pressed Neem Oil when label 

instructions are followed. 

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

Characterization

a. Occupational Exposure and Risk Characterization

The potential for dermal, eye, and inhalation exposure to Cold Pressed Neem Oil for handlers 

and applicators is mitigated as long as products are used according to label directions. The 

Agency will require labels to include the appropriate signal word, re-entry interval and 

precautionary statements, including the requirement for personal protective equipment, to 

mitigate any risk of exposure.

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

As stated above, 90-day oral data show very low toxicity, indicating no concern for oral 

exposure, such as hand-to-mouth, that may occur during indoor residential use. Furthermore, 

humans are regularly exposed to this substance in medicinal and cosmetic products, via the oral, 

inhalation and dermal routes, and at comparatively high levels (Schmutterer, 1995). These uses 

are also expected to result in exposures that are significantly greater than that which would be 

expected from pesticidal uses, including hand-to-mouth exposure. 

Section 408(b)(2)(D)(v) of the FFDCA requires that, when considering whether to establish an 

exemption from a tolerance, the Agency consider “available information concerning the 

cumulative effects of [a particular pesticide's] residues and other substances that have a common 

mechanism of toxicity.'' These considerations include the possible cumulative effects of such 

residues on infants and children.
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5. Cumulative Effects

EPA has considered the potential for cumulative effects of Cold Pressed Neem Oil and other 

substances in relation to a common mechanism of toxicity. However, because of its low toxicity

to mammalian systems, the Agency does not expect any cumulative or incremental effects from 

exposure to residues of Cold Pressed Neem Oil when applied/used as directed on the label and in 

accordance with good agricultural practices.

6. Risk Characterization

The Agency considered human exposure to Cold Pressed Neem Oil 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 Cold Pressed Neem Oil when label instructions are followed. 

C. Environmental Assessment

1. Ecological Hazards

Adequate non-target toxicology data/information are available to support registration of Cold 

Pressed Neem Oil. All non-target toxicology data requirements for Cold Pressed Neem Oil have 

been satisfied.

There are no concerns for any non-target organisms when 100% Cold Pressed Neem oil is 

applied in accordance with EPA-approved label use directions. No toxic endpoints have been 

identified for non-target birds, non-target plants, and non-target soil organism such as 

earthworms. Although Cold Pressed Neem Oil is slightly toxic to aquatic organisms in laboratory

testing, as a result of the rapid biodegradation of Neem Oil under approved conditions of use, 

calculated Risk Quotients (RQs) for fish and aquatic invertebrates are well below any Levels of 

Concern (LOCs) for threatened and endangered species. There are no concerns for non-target 

insects. Only insects that feed directly on treated plant foliage or roots will be directly exposed to 

Cold Pressed Neem Oil at levels that will be pesticidal. Honey bees and other pollinators that 

feed on nectar, and predators of insect pests are unlikely to consume sufficient quantities of Cold 

Pressed Neem Oil to cause adverse effects. Bees have been reported to avoid foods that contain 

>100 ppm Cold Pressed Neem Oil. 

For more information regarding the non-target toxicity data requirements, refer to Table 4 in 

Appendix A.

2. Environmental Fate and Ground Water Data 

Since Cold Pressed Neem Oil is a multicomponent mixture, azadirachtin A was used as a 

surrogate when evaluating environmental fate for all of the insecticidally active liminoid 

components in 100% Cold Pressed Neem Oil.

A number of studies have addressed the degradation of Cold Pressed Neem Oil components in 

the environment. In forest environments, azadirachtin A persisted 3 to 6 days in terrestrial 

matrices and 8 to 13 days in water (Sundaram et al., 1999). In laboratory studies, azadirachtin A 
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was shown to have temperature dependent degradation rates in sandy loam soils with half-lives 

of 43.9 and 19.8 days at 15 oC and 25 oC, respectively (Stark and Walter, 1995). When the soil 

was autoclaved, half-lives increased to 91.2 (15 oC) and 31.5 days (25 oC), demonstrating the 

significant influence of microbial activity in the degradation of Cold Pressed Neem Oil. Half 

lives for azadirachtin B in sandy loam soil were comparable to that of azadirachtin A. 

Azadirachtin is extremely labile in light with photolysis half lives of 48 min to 3.98 days in thin 

films under UV light, and 2.47 days on leaf surfaces (Johnson et al., 2003). In field trials with 

olives, azadiractin residues had a half-life of 0.8 days (Caboni et al., 2002). 

Based on the submitted data, Cold Pressed Neem Oil is readily biodegradable in soil, water and 

on foliar surfaces. As a result, Cold Pressed Neem Oil and its components are not likely to persist 

in the environment. 

3. Ecological Exposure and Risk Characterization

The potential for exposure to non-target wildlife is minimal. Based on the results/information 

presented in the Environmental Fate and Groundwater Data section above, it is highly unlikely

that non-target organisms, particularly aquatic organisms, would be exposed to potentially toxic 

levels of Cold Pressed Neem Oil via runoff and/or movement through the soil. Cold Pressed 

Neem Oil undergoes rapid biodegradation in soil and water, and no unreasonable adverse effects 

to the environment are expected from the use of Cold Pressed Neem Oil when label instructions 

are followed.

4. Endangered Species Assessment

A nontarget organism hazard assessment and an Endangered Species Assessment has been 

conducted to support registration of Plasma Neem Oil Manufacturing Use Product and Plasma 

Neem Oil Biological Insecticide (an end-use product, EP) (the MP and the EP are identical 

formulations). There are no concerns for non-target mammals and birds, including threatened and 

endangered species. No toxic endpoints were identified for non-target terrestrial mammals (acute 

oral and dietary toxicity LD50s >5000 mg/kg and 5000 ppm, respectively) and birds (acute oral 

and dietary toxicity LD50s >1000 mg/kg and 12000 ppm, respectively. Moreover, based on 

submitted laboratory studies, no concerns were identified for non-target aquatic organisms, 

including threatened and endangered species. Calculated Risk Quotients (RQs) fish and aquatic 

invertebrates are well below any Levels of Concerns (LOCs) for threatened and endangered 

species.

Based on the fact that Cold Pressed Neem Oil is not toxic to non-target organisms and on its use 

pattern and use instructions, EPA has determined it will have "No Effect" on any currently listed 

threatened or endangered species or any designated critical habitat.

D. Product Performance (Efficacy)

Submission of product performance data (OPPTS 810.3000) is listed as a requirement for all 

pesticide products. Customarily, the Agency requires efficacy data to be submitted for review

only in connection with the registration of products directly pertaining to the mitigation of 

disease bearing human health organisms and certain designated quarantine pests, i.e., ticks, 

mosquitoes, fleas, Mediterranean fruit flies, gypsy moths, Japanese beetles, etc. For a list of 
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organisms considered by the Agency as “public health pests”, please refer to Pesticide

Registration Notice 2002-1 (http://www.epa.gov/PR_Notices/pr2002-1.pdf). 

V. Risk Management Decision

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. 

The four criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied by

the science assessments supporting products containing Cold Pressed Neem Oil. Such products 

are not expected to cause unreasonable adverse effects, and are likely to provide protection as 

claimed when used according to label instructions. Therefore, Cold Pressed Neem Oil is eligible 

for registration for the labeled uses. 

B. Regulatory Decision

EPA has determined that Cold Pressed Neem Oil, in either agricultural or indoor use practices,

presents no issues of toxicological, ecological, or environmental concern. As discussed above, 

acute toxicity data for Cold Pressed Neem Oil demonstrate that it is either toxicity category IV or 

III. Cold Pressed Neem Oil does not demonstrate subchronic or developmental toxicity, and it is 

not mutagenic or genotixic. EPA has no concerns for any non-target organisms exposed to Cold 

Pressed Neem Oil in accordance with approved label directions. EPA has not identified any toxic 

endpoints for non-target mammals, birds, plants, aquatic, or soil organisms. Nor are there 

concerns for any threatened and endangered species. Thus, given that Cold Pressed Neem Oil has 

very low toxicity and presents little if any risk to non-target organisms, EPA concludes that it is 

in the best interests of the public and the environment to both issue the registration for Cold 

Pressed Neem Oil and to approve its use indoors. Consistent with the Agency’s policy for 

making these registration actions more transparent, EPA has provided a 30-day public comment 

period on the decision to register Cold Pressed Neem Oil. No comments were received during 

the 30 day public comment period. Currently, EPA is providing a 30-day public comment period 

on the decision to approve the “first indoor use” of Cold Pressed Neem Oil.

The data submitted fulfill the requirements of registration of Cold Pressed Neem Oil for use in on

all outdoor and greenhouse ornamental and food crops to control insects using ground equipment 

and indoors for the control of bed bugs. Refer to Appendix B for product-specific information. 

C. Environmental Justice 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 
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population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to Cold pressed Neem Oil, compared to the general population. 

Please comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population.

VI. ACTIONS REQUIRED BY REGISTRANTS

The Agency evaluated all of the data submitted in connection with the initial registration of Cold 

Pressed Neem Oil and determined that these data are sufficient to satisfy current registration data 

requirements. No additional data are required to be submitted to the Agency at this time. For 

new uses and/or changes to existing uses, additional data may be required. 

Not withstanding the information stated in the previous paragraph, it should be clearly

understood that certain, specific, data are required to be reported to the Agency as a requirement 

for maintaining the Federal registration for a pesticide product. A brief summary of these types of 

data are listed below. 

A. Reporting of Adverse Effects

Reports of all incidents of adverse effects to the environment must be submitted to the Agency

under the provisions stated in FIFRA, Section 6(a)(2).

B. Reporting of Hypersensitivity Incidents

Additionally, all incidents of hypersensitivity (including both suspected and confirmed incidents) 

must be reported to the Agency under the provisions of 40 CFR Part 158.2050(d).
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VII. Appendix A 

TABLE 1. Product Chemistry Data Requirements for Cold Pressed Neem Oil (40 CFR § 158.2030)

Biochemical Data Requirement by 

OCSPP Guideline Number MRID(s) Description of Result

880.1100 Product identity;

880.1200 Manufacturing process;

880.1400 Discussion of formation of 

 unintentional ingredients

47538701 Submitted data satisfy the requirements for 

product identity, manufacturing process, and 

discussion of formation of impurities. 

830.1700 Analysis of samples 47538701 Submitted data satisfy the requirements for 

analysis of samples.

830.1750 Certified limits 47538701 Not required for TGAIs.

830.1800 Enforcement analytical 

 method

47538701 Not required for TGAIs.

a Data submitted via self certification per Pesticide Registration Notice (PRN) 98-1.

TABLE 2. Physical and Chemical Properties of Cold Pressed Neem Oil (40 CFR § 158.2030) 

Biochemical Data Requirement by 

OCSPP Guideline Number MRID(s) Description of Result

830.6302 Color

a Yellowish brown

830.6303 Physical State

a Liquid at 20°C

830.6304 Odor

a

Strong, garlic-like

830.6313 Stability 47476701 10% degradation at 11months under unregulated 

storage conditions/shipment

830.7000 pH

a

5.3 at 21°C (70°F)

830.7050 UV/Visible Absorption

a

215 nm

830.7200 Melting Range

a Not applicable; product is a liquid 

830.7220 Boiling Range

a BP > 200oC (392o

F)

830.7300 Density/Relative 

Density/Bulk Density

a

0.922 g/mL (8.27 lb/gal) at 22°C (72°F)

830.7370 Dissociation Constant in 

Water

a Not applicable; the product does not substantially 

dissociate in water

830.7550 Partition Coefficient

a Log Kow = 6.26

830.7840 Water Solubility

a

52.3 mg/L

830.7950 Vapor Pressure

a

2.5 x 10-7 mm Hg at 25oC
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Table 3. Human Toxicology Data Requirements for Cold Pressed Neem Oil (40 CFR § 158.2050)

Biochemical Data 

Requirement by OCSPP 

Guideline Number

MRID(s) Description of Result Toxicity 

Category

870.1100 Acute oral [rat] 

 toxicity

 470880021 

 472088012

LD50 = >5000 mg/kg for female IV

870.1200 Acute dermal 

 [rabbits] toxicity

 470880031

 472088022

LD50 = >2000 mg/kg for males, 

females, and combined

III

870.1300 Acute inhalation 

 [rat] toxicity

 470880051

 472088032

The inhalation LC50 for males, females, 

and combined was > 2.53 mg/L & > 

2.11 mg/L, respectively, at 

concentrations of azadirachtin of 

0.30% & 0.15% 

IV

870.2400 Acute eye

 irritation [rabbit]

 470880061

 472088042

No irritation was noted on any rabbit 

throughout the study. Plasma NeemTM 

Oil was non-irritating.

IV

870.2500 Acute dermal 

 irritation [rabbit]

 470880071 No irritation was noted on any rabbits 

throughout the study. The primary 

irritation index was 0.0. Plasma 

NeemTM Oil was non-irritating.

IV

870.2600 Skin sensitization 

 [guinea pig]

 470880041 After three consecutive weekly 

inductions, the test and control animals 

showed no signs of reactivity at 24 and 

48 hours after challenge.

Not a dermal 

sensitizer

870.3100 90-Day Oral 

 feeding [mouse]

Awad (2003) LD50 = >5000 mg/kg No subchronic 

oral toxicity

870.3250 90-Day Dermal 47195705

48606014

48751001

The product is not intended for 

purposeful application to human skin. 

Neem oil is not known nor expected to 

be metabolized differently by the 

dermal route of exposure than by the 

oral route of exposure. No literature 

reports of subchronic dermal toxicity.

No subchronic 

dermal toxicity

870.5100 90-Day Inhalation 47195705

48606014

48751001

The use patterns will not result in 

significant levels of repeated inhalation 

exposure to the pesticide as a gas, 

vapor, or aerosol. Indoor use label 

language includes 4hr re-entry interval 

following application. No literature 

reports of subchronic inhalation 

toxicity.

No subchronic 

inhalation 

toxicity

870.3500 Developmental 

 Toxicity 

 [Teratogenicity]

47195706

(see refs 

within this 

MRID)

No reproductive/developmental effects 

in a 3-gen rat study with 10% Neem Oil 

in diet. Reproductive/developmental 

effects occur only in in vitro studies on 

sperm or eggs, subcutaneous exposure; 

contraceptive effects with 

intrauterine/intravaginal exposure 

Not a 

developmental 

toxicant when 

used in 

accordance with 

approved 

labeling.

870.5100 Mutagenicity 

 Testing [Ames 

 Assay]

47088008 &

Polasa & 

Rukmini 

(1987)

No evidence of mutagenicity with or 

without S-9 activation in S. typhimurim

Not a mutagen

1 The test material contains 0.30% azadirachtin.

2 The test material contains 0.15% azadirachtin. 
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Table 4: Estimated Cold Pressed Neem Oil residues on terrestrial matrices using the Terrestrial Exposure 

model (T-Rex; 

 EPA, 2005)

Terrestrial matrix Dietary-based Estimated Environmental Concentrations (ppm)

0 days after last app 86 days after last app 106 days after last app

Edible broadleaf plant foliage 881.20 0.04 0.00

Fruits. pods, and seeds 97.91 0.00 0.00

TABLE 1 Tier I Non-Target Organism Profile 

Guideline 

No. Study Type References and/or MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 

toxicity

470880021

472088012

LD50 = >5000 mg/kg for female IV

870.3100 90-Day Oral 

Feeding

(mouse)

Awad (2003)

(476335-01) LD50 = >5000 mg/kg

No 

subchronic 

oral toxicity

850.2100 Avian Acute Oral 

Toxicity 

(redwingedblackbird)

Schafer & Jacobsen. 

(1983); (47633502)

LD50 >1000 mg/kg 

(highest acute dose tested)

No effects at 

highest dose 

tested

850.2100 Avian Dietary 

Toxicity 

(redwingedblackbird)

Schafer & Jacobsen. 

(1983); (47633502)

LD50 > 10000 ppm (1.0%) Practically 

non-toxic

Avian Dietary 

Toxicity (Leghorn 

hen)

Verma et al. (1998)

(474787-05)

12-week LD50 > 12000 ppm (6.0% 

neem oil in neem cake feed)

Practically

non-toxic

850.1075 Fish Toxicity Awad (2003)

(476335-01)

96-hr LC50s= 70.6 – 84.3 ppm Slightly Toxic

850.1300 Aquatic 

Invertebrates

Awad (2003)

(476335-01)

48-hr LC50s= 57.5 - 63.9 ppm Slightly Toxic

850.4150 Non-target Plants

(vegetative vigor)

476335-04 & -05 No toxicity observed in plants 

treated with up to 11000 ppm (1.1%) 

Neem Oil 3

Practically 

non-toxic

850.3020 Honey bees Melathoupoulos et al. 

(2000)

Contact LD50 > 45 ug/bee (adult) Practically 

non-toxic

Canadian Honey 

Council (2005)

-

1 The test material contains 0.30% azadirachtin.

2 The test material contains 0.15% azadirachtin. 

TABLE 5. Non-Target Organism Toxicity Requirements for Cold Pressed Neem Oil (40 CFR § 158.2060)
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VIII. Appendix B

For product specific information, please refer to: http://oaspub.epa.gov/pestlabl/ppls.home 
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IX. Appendix C

REFERENCES

Abudulai, M., B. Merle Shepard, and Paula Levin Mitchell. 2004. Effects of neem (Azadirachta 

indica A. Juss.) on predators of Nezara viridula (L.) (Hemiptera: Heteroptera: Pentatomidae). 

Journal of Agricultural Urban Entomology. 21(1): 9–13. 

Canadian Honey Council (CHC). 2005. Essential oils and their toxicity to honeybees. 

November-December. http://www.honeycouncil.ca/users/folder.asp?FolderID=5220

Da Silva, F. A. C. and S. S. Maritnez. 2004. Effect of neem seed oil aqueous solutions on 

survival and development of the predator Cycloneda sanguinea (L) (Coleoptera: Coccinellidae). 

Extension Toxicology Network (EXTOXNET). 1995. Pesticide Information Profile: 

Azadirachtin. Cornell University Cooperative Extension. 

http://pmep.cce.cornell.edu/profiles/extoxnet/24d-captan/azadirachtin-ext.html

Food and Agriculture Organization of the United Nations (FAO). 2003. Azadirachtin. FAO 

Specifications and Evaluations for Agricultural Pesticides. http://www.fao.org/ag/agpp/pesticid/)

Lowery, D. T. and M. B. Isman. 1995. Toxicity of neem to natural enemies of aphids. 

Phytoparasitica 23(4): 297-306. 

Methathopoulos, A. P., M. L. Winston, R. Whittington, T. Smith, C. Lindberg, A. Mukai, M. 

Moore. 2000. Comparative laboratory toxicity of neem pesticides to honey bees (Hymenoptera: 

Apidae), their mite parasites Varroa jacobsoni (Acari: Varroidae) and Acarapis woodi (Acari: 

Tarsonemidae), and brood pathogens Paenibacillus larvae and Ascophaera apis. Entomological 

Society of America 93(2):199-209. 

Mordue, J. A. and A. Blackwell. 1993. Azadirachtin: An update. Journal of Insect Physiology

39: 903-924.

National Research Council. 1992. Neem: A tree for solving global problems. National Academy

Press, Washington, DC. 

Naumann, K. and M. B. Isman. 1996. Toxicity of a neem (Azadirachta indica A. Juss) 

insecticide to larval honeybees. American Bee Journal. 7: 518-520.

Rembold, H., G. K. Sharma, C. Czoppelt, and H. Schmutterer. Evidence of growth disruption in 

insects without feeding inhibition by neem azadirachta-indica seed fraction. Journal of Plant 

Diseases and Protection 87:290-297. 

Schmutterer, H. 1995. Chapter 6: Medicinal Uses in Asia. The Neem Tree and Other Meliaceous 

Plants. New York: VCH Publishers, 1995. p. 518-525.

Stark, J. D. and J. F. Walter. 1995. Persistence of azadirachtin A and B in soil: Effects of 

temperature and microbial activity. Journal of Environmental Science and Health: Part B. 

Pesticides, food contaminants, and agricultural wastes. 30: 685-698. 
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Sundaram, K. M. S., A. Sundarum, J. Curry, and L. Sloane. 1999. Formulation selection, and 

investigation of azadirachtin-A persistence in some terrestrial and aquatic components of a forest 

environment. Pest Management Science 51(1):74-90. 

EPA. 2001. Generic Environmental Estimated Concentration (GENEEC) Version 2.0. Tier One 

Screening Model for Pesticide Aquatic Ecological Exposure Assessment. Environmental Fate 

and Effects Division/Office of Pesticide Programs. August 1, 2001. 

EPA. 2005. T-REX, Version 1.2.3. Terrestrial Biology and Exposure Teams, Environmental 

Fate and Effects Division/Office of Pesticide Programs. August 8, 2005. 

EPA. 2009. Memo from R. Jones to D. Benmhend. Tolerance Exemption Petition Review 

Plasma Neem Oil Manufacturing Use Product and Plasma Neem Oil Biological Insecticide. Each 

Product is Identical and Contains 100% Neem Oil (w/0.3% Azadirachtin) As Its Active 

Ingredient. March 9, 2009.