BIOPESTICIDES REGISTRATION ACTION DOCUMENT

Isopropyl Myristate Tetradecanoic acid, 1

–methylethyl ester

PC Code : 000207

U.S. Environmental Protection Agency Office of Pesticide Programs Biopesticides and Pollution Prevention Division

Ju ly 20 , 2011Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 2 of 34

TABLE OF CONTENTS

I. EXECUTIVE SUMMARY ......... ...... .......................................... ... ..........5 II. ACTIVE INGREDIENT OVERVIEW ................................................... .. .7 III. REGULATORY BACKGROUND ...................................................... .. ...8 A. Classification ... ..................................................................... ... ............8 B. Food Clearances and Tolerances ......... .... ..................................................8 IV. RISK ASSESSMENT ..................... ... ...... .. ...............................................8 A. Active Ingredient Characterization ...... . ...... . .............................................8 B. Human Health Assessment ....................................... .. .............................9 1. Toxicology .................................................................... . ...... . ........9 2. Dose Response Assessment .......................................... ......... ... . .......1 3 Drinking Water Exposure and Risk Characterization..................... .. . . ....13 3. Occupational, Residential, School and Day Care Exposure and Risk Characterization...... ... ......................................................... . ... . ....13 4. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation ......................................................... . ........................13 5. Cumulative Effects ......................................................................14 6. Risk Characterization ........................ ..........................................14 C. Environmental Assessment ...................................................................14 1. Ecological Hazards .......................................................................14 2. Environmental Fate and Ground Water Data .............................. ... ....16 3. Ecological Exposure and Risk Characterization ..................................16 4. Endangered Species Assessment ....................................... ............ ...16 D. Product Performance/ Efficacy Data .................................................. . ....16Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 3 of 34

V. RISK MANAGEMENT DECISION ...................................................... .... 16 A. Determination of Eligibility for Registration .......................................... . .....16 B. Regulatory Decision ................................................... ... .........................17 C. Environmental Justice .................................................................. ... .......17 VI. ACTIONS REQUIRED BY REGISTRANTS .................................... ... ...... .....17 A. Reporting of Adverse Effects ............................................................ .. ......17 VII. APPENDIX A. Data Requirements (40 CFR Part 158) ......... ... ............... .. . ......19 VIII. APPENDIX B . Product Specific Information ..............................................26 IX. APPENDIX C. References .............................................................. . ......26 X. GLOSSARY OF ACRONYMS AND ABBREVIATIONS ............................ 32Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 4 of 34

BIOPESTICIDES REGISTRATION ACTION DOCUMENT (BRAD) TEAM

Office of Pesticide Programs Biopesticides and Pollution Prevention Division Biochemical Pesticides Branch (BPB)

Branch Chief Li nda A. Hollis, M.S.
Health Effects Angela Gonzales, Biologist
Product Performance Clara Fuentes, Entomologist
Environmental Effects Miachel Rexrode, Ph.D., Senior Biologist
Product Chemistry Jacob Moore, Chemist Regulatory Action Leader Cheryl GreeneIsopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 5 of 34

I. EXECUTIVE SUMMARY :
I. BACKGROUND
RISK ASSESSMENT AND STUDY SUMMARIES FOR ISOPROPYL MYRISTATE
I. Introduction
Is opropyl my

ristate is a pesticidal active ingredient intend ed fo r formulation in to end
- use insecticidal products that are intended to kill ticks on cats and dogs. Is opropyl my ristate is a clear, odorless liquid produced from the reaction of my ristic acid esters and isopropyl al cohol
. My ristic acid is a naturally occurring fatty

acid found in plant s, plant oils and animal fats including the nutmeg tree, palm oil, coconut oil , butter fat and sperm whale oil
. Is opropyl alcohol , commonly known as rubbing alcohol, is a secondary alcohol produced and used since the 192 0’s in chemical experimentation and since 1957 in cosmetic, pharmaceutical and household products. Is opropyl my

ristate is commercially

sy nthesized for use as a f

lavoring agent in a wide range of foods including bake goods and desserts. I t is used in over 900 cosmetic and personal care products at concentrations ranging from 0.00008
- 78%
. Such products include face powders, liquid makeup, beauty creams, body

spray s, aftershave, deodorant s , lotions, and hand sanitizer’s. I sopropy l my ristate is also used as a carrier or solvent in a variety of pharmaceutical, therapies that require good precutaneous absorption is needed. Such products include hair rinses for killing and controlling head lice and transdermal patches for delivery of pain management drugs and antibiotics
. The Agency ’s assessment of risks, hazards and benefits associated with isopropyl my ristate is based on data submitted on the unregistered technical active ingredient formulated into the single end
- use product containing isopropyl my ristate as an active ingredient. The Biopesticides and Pollution Prevention Division (BPPD) has determined that the data submitted for Product Chemistry , Tier IAcute Toxicity , Ecologica l Effects and Environmental Fate for isopropy l my

ristate satisfy

current guideline requirements. T he Agency notes , however , that if the intended end
- use applications result in different exposures to humans than is anticipated, then the registrant may

be required to address additional data requirements in future submissions
. Based on this information, the Agency has determined that use of isopropyl my ristate as an active ingredient in end
- use pesticide produ cts to kill ticks on cats and dogs will have No Effect on threatened and/or endangered species. The mode of action of the active ingredient is desiccation; the chemical dissolves the wax on the cuticle or exoskeleton of the insect which causes the insect t o dry out or desiccate.
Based on the a cute t oxicity data submitted for isopropy l my ristate , the Agency

classifies the activeIsopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 6 of 34

ingred ient as a toxicity

category II out of four categories with category I being the most toxic and category I V being the least toxic. EPA has no concerns about non
- target organisms exposed to isopropy l my

ristate in accordance with approved label directions. There are no concerns for any threatened or endangered species. G iven that iso propy l my ristate has very

low toxicity

and the potential for exposure to the environment is insignificant or unlikely , EPA concludes , based on the proposed use pattern , that it is in the best interests of the public and the environment to issue the registr ation for isopropy l my ristate
. The Biopesticides and Pollution Prevention Division (BPPD) has reviewed the data and information in support of the requirements for granting registration under Section 3(c ) ( 5) of the Federal In secticide, Fungicide and Rodenticide Act (FI FRA). We have determined that the data/information submitted adequately

satisfy current guideline requirements ( see 40 CFR Subpart U § 158.2000). On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunity fo r the public to participate in major registratio n decisions
. According to this new policy , EPA intends to provide a public comment period prior to making a registration decision for, at minimum, the following ty

pes of applications: new active ingredient, f irst food use, first outdoor use, first residential use; and any

registration decisions for which the Agency believes there may

be substantial public interest. Consistent with the new policy of making registration actions more transparent, isopropy l my ri state is subject to a 30
- day

comment period as a “new active ingredient. The intent of the 30
- day comment period is to provide a more meaningful opportunity for the public to participate in major registration decisions before they

occur. The docket identif ication for this action is EPA
- HQ
- OPP
- 2010
- 0082. While a final decision on registration is contingent upon review and consideration of public comments, at this time the Agency believes that the risk assessment and information submitted support the regist ration of isopropy l my ristate and that it is in the best interest of the public and the environment to issue the reg istration for isopropy l my ristate
. The basis for this preliminary decision can be found in the risk assessment for isopropy l my ristate which is characterized in this BRAD.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 7 of 34

II. ACTIVE INGREDIENT OVERVIEW Common Name: Is opropyl My ristate Chemical Names: Tetradecanoic acid isopropyl ester My ristic acid isopropyl ester
Trade & Other Names: Tetradecanoic acid, 1

–methylethyl ester Chemical /Sy stemic name Is opropyl my

ristate Other Common name Starfol IS OPROPYLMYRI STATE Trade name Kessco Is opropyl my

ristate 95 Trade name Stepan D
- 50 Trade name RESUL TI XTM Trade n ame CAS Registry Number: 110
- 27
- 0 OPP Chemical Code: 000207 Type of Pesticide: Biochemical Pesticide / In secticide Chemical Structure

Molecular formula: C 17 H 34 O 2 Molecular Weight: 270.46 g/molIsopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 8 of 34

III. REGULATORY BACKGROUND
Is opropyl my

ristate was first registered by EPA on October 31 , 1986 , as an active ingredient for use in antimicrobial pesticide s . By the end of 1987 , all products containing isopropyl my ristate as an active ingredient were cancelled following a generic dat a call
- in. On December 3, 2009, EPA received an application f

iled by Piedmont Animal Health, ( 204 Muirs Chapel Road, Suite 200, Greensboro, NC 27410 ) to register an end
- use product (EP) containing isopropy l my ristate as an insecticide to kill ticks on cats and dogs
. RESUL TI XTM, the EP contains 50.0 % isopropy l my ristate as an active ingredient. A notice of receipt of this application, allowing for a 30
- day comment period, was published in the Federal Register o n March 10, 2010 (7 5 FR 28702 ) . No comments were received following this publication
. A. Classification Is opropyl my

ristate is classified as a sy nthetic substance, not naturally occurring
. Moreover, some may question whether its mode of action is actually non - toxic. Nonetheless, on March 27, 2009 , the Agency ’s Biochemical Classification Committee completed a review of isopropy l my ristate , which determined that , although the substance is not naturally occurring , it nonetheless is eligible for a reduced set of data requirements , based on a mode of pesticidal action similar to sucrose octanoate , which is a registered biochemical pesticide
. B. F ood Clearances/Tolerances Currently this active ingredient is not registered on food or feed commodities. IV. RISK ASSESSMENT A. A ctive Ingredient Characterization Is opropyl my

ristate is a pesticidal active ingredient intended for formulation into products to kill ticks on cats and dogs. I t is a clear, odorless liquid produced from the reaction of my ristic acid esters and isopropyl alcohol. My ristic acid is a naturally

occurring fatty

acid found in plant and plant oils and animal fats including the nutmeg tree, palm oil, coconut oil, butter fat and sperm whale oil. I sopropy l alcohol, commonly known as rubbing alcohol, is a secondary alcohol produced and used since the 1920’s in chemical experimentation, and since 1957 in cosmetic, pharmaceuti cal and household products. The proposed end
- use product (EP) is intended for use on cats and dogs to kill ticks. The mode of action of th is active ingredient is p hy sical in th a t isopropy l my

ristate de
- waxes the cuticle or outer skel e t on of the target pest (tick ). In sects such as ticks need waxed cuticles in part to maintain body fluids. Once cuticle wax is destroy ed or compromised the insect loses critical body fluids and simply dries up or undergoes desiccation
. All data requirements have been satisfied per 40 CFR 158.20 30 for registration of the end
- use product RESUL TI XTM The data presented in Table 1 of the appendix to this document are a summary of the produ ct chemistry data and information submitted to support the EP, RESUL TI XTM
.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 9 of 34

B. Human Health Assessment 1. Toxicology For acute toxicity

data requirements, toxicity categories are assigne d based o n the hazard (s) identified from studies and/or information on file with the Agency . The active ingredient is classified into Toxicity Category I , I I, I II or I V where Toxicity Category Iindicates the highest toxicity and Toxicity

Category I V indicates the lowest toxic ity
. Adequate mammalian toxicology data/information is available to support registration of i sopropy l m yr istate
. All toxicology data requirements for i sopropy l m yr istate have been satisfied. The Agency has classified isopropyl my ristate into T oxicity C a tegory II
. a. Acute Toxicity Acute toxicity

testing is required to 1) determine sy stemic toxicity from acute exposure via the dermal, inhalation and oral routes, 2) determine irritant effects from exposure to the ey es, and 3) determine the potential for skin sensitization (allergic co ntact dermatitis). All data cited by

the registrant to satisfy

the biochemical pesticide data requirements for the single registered product containing isopropyl my ristate were submitted from the open scientific literature. Additional data were obtained using the Hazardous Substances Database (HSDB) from the National L ibrary

of Medicine. I sopropy l my ristate has low acute oral, acute dermal and acute inhalation toxicity . An additional acute inhalation toxicity study from the HSDB (2011) indicate s no mortality

or significant adverse effects when rats were exposed to an aerosol formulation containing 4.7% isopropyl my ristate (9.7 mg/L ) for four 15
- minute periods. Several ey e irritation studies conducted on rabbits ind icate that the chemical is nonirritating to minimally irritating. Studies on the dermal irritation of isopropyl my ristate have yielded mixed results. The majority of these studies indicate that the chemical is minimally irritating when applied to rabbits. O ne study showed severe irritation in rabbits, moderate irritation in guinea pigs and mild irritation in rats. The Agency

has conservatively

classified isopropyl my

ristate into toxicity

category I I on a scale of I V for dermal irritation based on the resul ts of this study . T he results of the other studies demonstrate that the chemical is only mildly irritating and meets the Agency ’s classification of a toxicity category III active ingredient
. The active ingredient is not considered to be a skin sensitizer. For additional information regarding acute toxicity data requirements, refer to Table 2 in Appendix A of this document
.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 10 of 34

b. Subchronic Toxicity Subchronic data are required to determine a no
- observed
- effect
- level (NOEL) and any toxic effects associated with repeated or continuous exposure to a test substance for a period of ninety day s. 90
-Day Oral Ina 28
- day

non - guideline oral toxicity study , Wistar rats were exposed to isopropyl my ristate via gavage once per day

for five day s a week at 0, 100, 500 or 1000 mg/kg bw. No treatment
- related mortality or adverse effects were observed. Hy perplasia of the fore stomach mucosa was recorded in all the test groups, including the control group. The injury was reversible following the 14
- day recovery period. The NOAEL is ≥ 1000 mg/kg bw; the L OAEL could not be determined (no adverse effects at the highest dose t ested). (HSDB, 2011) Repeat human oral exposure is not expected based on the use pattern; the proposed use of isopropy l my

ristate is not food
- use and will be applied dermally to cats and dogs to kill ticks. 90
-Day Dermal Ina 28
- day

non - guideline dermal toxicity study , L andrace
- Duroc pigs were exposed to the proposed end
- use product ( RESUL TI XTM ) every three day s. The applied doses were equivalent to 0, 20.31
- 33.89, 59.62
- 94.43, or 196.3
- 321.3 mg/kg bw. No mortality or adve rse treatment related effects were observed. At the highest dose, there was a slight increase in male pituitary weights and there was an equivocal increase in female adrenal weights. These changes were not detected by the end of the 14
- day

recovery period . These observations may be treatment
- related, but are not considered toxicologically significant due to the lack of associated findings or changes in the evaluated toxicological parameters. The NOAEL is ≥ 196.3
- 321.3 mg/kg bw and the LOAEL could not be de termined as no adverse eff ects were identified at the highest dose tested
. Prolonged dermal exposure to the human skin is not expected as the proposed product is not intended to be purposely

applied directly

to the skin. 90
-Day Inhalation Ina 13
- week in halation study , guinea pigs were exposed for three one
- hour periods every day to an aerosol formulation containing 16
- 20% isopropyl my ristate at 0, 63.3, or 224 mg/m 3 . At four weeks, half of the animals were sacrificed. One female died during the course of the study from unknown causes. There was an increase in absolute and relative lung weights in the treated animals compared to the control animals. No other adverse treatment
- related effects were observed during gross necropsy and histology

in the animals that were sacrificed at four weeks and 13 weeks. Ina 13
- week inhalation study , cy nomolgus monkey s were exposed for three one
- hour periods every day to the same formulation used in the guinea pig study (above) at 0, 5.3, 8.4, 33.6, or 37.0 mg/m 3 . During the study , coughing and wheezing were observed and there was a bloody nasal discharge in two of the animals exposed to the 8.4 mg/m 3 dose. Accumulations of macrophages within the bronchiolar and alveolar walls were observed and were dose
- related in treate d monkey s. No other adverse treatment
- related effects were noted.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 11 of 34

Significant repeat inhalation exposure is unlikely based on the use pattern and low volatility of the active ingredient (<1 Torr at 20o C). For additional information regarding subchronic to xicity data requirements, refer to Table 2 in Appendix A of this document
. c. Developmental Toxicity Developmental toxicity

data on technical grade active ingredients are a standard requirement for the registration of pesticide active ingredients ; however, because end
- use products containing isopropy l my

ristate under widespread and commonly recognized practice are reasonably not expected to result in significant exposure to female humans (e.g., occupational exposure or repeated application of insec t repellents directly to the skin) the Agency

is not requiring these data at this time. The Agency

believes that under the proposed use pattern, o ral exposure to isopropy l my ristate is not expected and would be incidental . Further, based on the proposed us e pattern and the low volatility

of isopropy l my

ristate, significant inhalation exposure is not expected when labeling instructions are followed. W hile dermal exposure may occur during application of the product and while handling animals post
- application, the Agency does not expect significant exposure based on the proposed use pattern as a contact pesticide used to kill ticks. Additionally , female humans already are exposed to isopropy l in cosmetic, personal care and pharmaceutical products. d. Mutagenici ty Results were negative in an Ames mutagenicity assay with and without metabolic activation using Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 at concentrations of 4, 20, 100, 500 and 2500 μg/plate. In a similar Ames assay , result s were negative using the same S. typhimurium strains with and without metabolic activation at a concentration of 50 mg/mL. Isopropyl my

ristate was non
- mutagenic in these assay s. Data from an in vitro mammalian mutagenicity assay are unavailable. However, significant human exposure is unlikely ; isopropy l my ristate is not structurally

related to a known mutagen and does not belong to a chemical class of compounds containing a known mutagen. Ina life
- time dermal carcinogenicity study , 10%, 50% and 100% is opropyl my ristate diluted in acetone applied to the backs of female Swill mice resulted in no difference in skin tumor frequency when compared to controls. Negative and positive controls were employ ed. I n another dermal carcinogenicity

study conducted in S will albino mice, isopropy l my ristate was applied once per week for 19 months at a concentration of 1% in acetone (42.5
- 56.6 mg.kg/wk
- initially
dose decreased as mice grew). Negative and positive controls were employed. Of the 20 mice treated with isopropyl my ristate, five escaped during treatment and four died before the end of the exposure period. No tumors were observed on the remaining 11 surviving mice or the four mice that died before the end of the exposure period.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 12 of 34

e. Effects on the Endocrine System 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 eff ect produced by

a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employ s a two - tiered approach to making the statutorily required determinations. Tier 1 consists of a battery

of 11 screening ass ay s to identify the potential of a chemical substance to interact with the estrogen, androgen, or thy roid (E, A, or T) hormonal sy stems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal sy s tems 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 issued test orders/data call
- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and nine in ert ingredients. This list of chemicals was selected based on the potential for human exposure through pathway s such as food and water, residential activity , and certain post
- application agricultural scenarios. This list should not be construed as a list o f known or likely endocrine disruptors. Is opropyl my

ristate is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Under FFDCA section 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/
. 2 . Dose Response Assessment N o relevant toxicological endpoints were identified; therefore, a dose response assessment is not required for this pesticidal act ive ingredient. 3. Drinking Water Exposure and Risk Characterization Based on the proposed use pattern of isopropyl my ristate as a contact pesticide to kill ticks on dogs and cats, pesticide residues in drinking water are not expected when products containing isopropyl my ristate are used according to label instructions. Pesticide application to pets is generally considered by the Agency

to be an indoor use pattern; therefore, isopropyl my ristate residues in drinking water are highly unlikely
.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 13 of 34

4. Occupational, Residential, School and Day Care Exposure and Risk Characterization a. Occupational Exposure and Risk Characterization An occupational exposure assessment was not conducted for isopropyl my ristate. Based on the proposed use pattern and toxicity data available to the Agency , anticipated exposure is not likely to result in unreasonable risk to humans. No relevant toxicologic al endpoints were identified and significant exposure in an occupational setting is not expected. b. Residential, School and Day Care Exposure and Risk Characterization A residential, school and day care exposure assessment was not conducted for isoprop yl my ristate. Based on the use pattern, school and day care exposures are unlikely . Although the proposed product will be used in residential settings, based on the proposed use pattern and toxicity data available to the Agency , anticipated exposure is not likely to result in unreasonable risk to humans. No relevant toxicological endpoints were identified and significant exposure in a residential setting is not expected. 5 . Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation There is reasonable certainty that no harm to the U
. S
. population will result from aggregate exposure to isopropy l my

ristate. This includes all exposures for which there is reliable information. The Agency arri ved at this conclusion based on isopropy l my ristate highly

specific mode of action as a topical insecticide limited to use on cats and dogs, its lo w toxicity to mammalian sy stems and the intended non
- food use. The risk from aggregate exposure ( via oral, dermal and inhalation exposure s) is negligib le. T he Agency has conservatively

classified isopropyl my

ristate into toxicity

category I I for possible ey e irritation. The Agency will mitigate the potential for ey e irritation through product labeling language. 6 . Cumulative Effects EPA has considered the potential for cumulative effects of isopropy l my ristate and other substances in relation to a common mechanism of toxicity . However, because of its highly specific mode of action as a topical insecticide limited to use on cats and dogs, its low toxici ty to mammalian sy stems and the intended non
- food use , the Agency does not expect any

cumulative or incremental effects from exposure to residues of isopropy l my ristate. 7 . Risk Characterization The Agency

considered human exposure to isopropy l my ristate in light of the relevant safety factors in FQPA and FI FRA. 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 isopropy l my ri state when label instructions are followed. C. ENVIRONMENTAL ASSESSMENT 1. Ecological HazardsIsopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 14 of 34

The Agency

has evaluated the potential for toxicity of isopropyl my ristate and the proposed product s to aquatic and terrestrial ecosy stems and concludes that the potential for exposure to the environment is insignificant or unlikely
. Is opropyl my ristate will be formulated into products that will be applied to dog and cats as a topical spray treatment to kill tick s and is not expected to impact nontarget spec ies because of limited exposure due to its indoor use pattern . Therefore, Non Target Organisms and Environmental Fate Data Requirements were waived based on the rationales below
. T he Agency is requirin g that t he end
- use product label c arry environmental hazard information regarding potential toxicity to aquatic organisms and to prevent accidental release to aquatic environments and water bodies. Acute Toxicity Aquatic Invertebrates (Daphnids)

– TGAI & EP A search of available environmental fate and toxicity databases indicate no acute toxicity data for daphnids were available for isopropyl my ristate. The environmental fate data available indicate that isopropy l my

ristate would be readily

metabolized by aquatic organisms, although it is highly lipophilic and may

potentially

bioaccumulate. Is opropyl my ristate is also semi volatile and would not persist in aquatic environments
. Freshwater Fish Acute Toxicity - TGAI & EP A search of available environmental fate and toxicity databases indicate one acute 96
- hour L C 50 (100 mg/L; slightly

toxicity ) in fish was reported for isopropy l my ristate. The environmental fate data available show that isopropy l my ristate would be readily metabolized by aquatic organisms
. However, although isopropy l my ristate it is highly

lipophilic and may

potentially

bioaccumulate , it is also semi volatile and therefore we believe it w ill not persist in aquatic environments when used according to labelin g instructions. Avian Acute Oral and Dietary Toxicity Avian - TGAI & EP The proposed product is intended to be used indoors and applied as a topical spray to cats and dogs and therefore exposure to birds as a result of this indoor use pattern is unlikely . I n the event of label misuse, the potential routes of exposure to birds from the use of the proposed product are inhalation, dermal, and ora l. The route of exposure for these two studies is oral (gavage and dietary ); the other routes are not applicable. Because the EP is a colorless and practically odorless liquid product, it is unlikely that the EP would be gastronomically attractive for bird s to ingest. Usually toxicity to birds is from ingestion of pesticide products that resemble seeds (e.g., granular formulation) or from ingestion of pesticide residues on plant and other food items (insects). Additionally , t he proposed EP container is smal l (20 mL ) and spilla ge of the colorless fluid would result in minimal amounts present on soil or plant surfaces. Birds are also unlikely to mistake accidental spillage of the proposed end
- use product as water, particularly because of the small volume and r apid volatilization of the proposed product
. Terrestrial Plant Toxicity Seedling Emergence and Vegetative Vigor - TGAI & EP The target species for products containing isopropyl my ristate are ticks found on domestic dogs and cats. Therefore, d irect or indirect application of the end
- use product to terrestrial plants is not expected to occur if label instructions are followed.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 15 of 34

Nontarget Insect Testing - TGAI & EP Because isopropy l my

ristate is used to kill ticks by desiccation (solubilizing the cuticle), it is likely to have this affect on all insects and other arthropods. However, the use pattern and limited application (20 ml) precludes contact with nontarget insects, particularly honey bees. Enviro nmental Fate and Groundwater The need for environmental fate and groundwater data was not triggered because isopropy l my ristate acute toxicity

studies did not trigger any additional Tier I

studies. Ecological Exposure and Risk Characterization Based on the information submitted in the data waiver requests for nontarget plants and nontarget insects, exposure and risk from the proposed use of isopropy l my ristate is not expected to occur for other nontarget organisms. Endangered Species Assessment Based on the information discussed above, the Agency has determined that registered use of isopropy l my ristate as an active ingredient will have No Effects on threatened and/or endangered species
. When the product is used according to label use directions, the re are no concerns for any nontarget organisms
. D. PRODUCT PERFORMANCE DATA (EFFICACY) Product performance data must be developed for all pesticides to ensure that pesticide products will perform as intended and that unnecessary pesticide exposure to the environment will not occur as a result of the use of ineffective products. The Agency reserves the right to require , on a case - by
- case basis, submission of efficacy data for any

pesticide product s registered or proposed for registration that are intended to be used to control a pest of significan t public health importance an y public health pest defined in FI FRA section 28(d) and section 2(nn). For further guidance on product performance regulatory requirement s , refer to Pesticide Registration (PR) Notices 96
- 7 ( http://www.epa.gov/PR _Notices/pr1996
- 7.pdf

) , 2002
- 1 ( http://www.ea.gov/PR_Notices/pr2002
- 1.pdf ) and the Agency ’s “ Explanation of Statutory Framework for Risk
- Benefit Balancing for Public Health Pesticides ” ( http://www.epa.gov/pesticides/health/risk
- benefit.htm ). As required by

regulation (FI FRA section 28(d) and sec tion 2(nn) ) product performance data/information (MRI D 479253
- 17 and MRI D 479253
- 18) were submitted to support the efficacy of the end
- use product RESUL TI X TM
. T he Agency has determined that the submitted data/inf ormation submitted in support of the end
- use product RESUL TI XTM satisfies current testing requirements a s described at 40CFR 158.2070 for this active ingredient and the proposed end
- use product.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 16 of 34

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 warrant s proposed claims; (B) its labeling and other materials comply with the requirements of FI FRA; (C) it will perform its intended function with out 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 Determ ination for Pesticidal Active Ingredients are satisfied by the science assessments supporting products containing isopropy l my ristate . Such products are not expected to cau se unreasonable adverse effects and are likely to provide protection as claimed when used according to label instructions. Therefore , isopropy l my ristate is eligible for registration for the proposed labeled uses. B. Regulatory Decision The data submitted fulfill the registration requirements of isopropy l my ristate for use as a topical spray treatment for killing ticks on cats and dogs. Refer to Appendix B for product
- specific information. 1. Conditional/Unconditional Registration All data requirements are fulfilled , and EPA has determined that unconditional registration of isopropy l my

ristate is appropriate. 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

— with respect to 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 population who, as a result of their location, cultural practices, or other factors, may have aty pical or unusually

high exposure to isopropyl my ristate compared t the general population. Please comment if y ou are aware of any

sub
- populations that may have aty pical or unusually

high exposure as compared to the general population. For additional information regarding environmental justice issues, please visit EPA’s website at http://www.epa.gov/compliance/environmentaljustice/index.html
.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 17 of 34

V I . ACTIONS REQUIRED BY REGISTRANTS Notwithstanding the information stated in the previous paragraph, it should be clearly understood that certain specific data are required to be reported to EPA as a requirement for maintaining the Federal registration for a pesticide product. A brief summary of these ty

pes of data are listed below. A. R eporting of Adverse Effects Pursuant to FI FRA section 6(a ) ( 2), reports of all incidents of adverse effects to the environment must be submitted to EPA. B. Reporting of Hypersensitivity Incidents Additionally , all incidents of hy persensitivity

(including both suspected and confirmed incidents) must be reported to the Agency under the provisions of 40 CFR Part 158.2050(d).Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 18 of 34

VI I . Appendix A. Data Requirements (40 CFR Pa rt 158 - Subpart U ) *NOTE: Master Record I dentification ( MRI D ) numbers listed in the following tables are representative of supporting data for the original registration of the product containing this active ingredient. Subsequent to this registration, there may be additional MRI Ds that support registration of other products containing this active ingredient.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 19 of 34

TABLE 1. Physical and Chemical Properties for RESULTIXTM and isopropyl myristate TGAI a Guideline Reference No./Property Description of Result Methods 830.6302 Color TGAI: colorless EP: colorless Visual inspection
830.6303 Phy sical State TGAI: liquid EP: liquid Visual inspection
830.6304 Odor TGAI: odorless EP: odorless Olfactory inspection
830.6313 Stability TGAI: stable EP: stable Storage stability studies b,c
830.6315 Flammability TGAI: flash point 164.4°C closed cup EP: flash point 85.0°C closed cup; 95.0°C

open cup FDA, 16 CFR 1500.3 (c)(6) and 43 (a) e
830.6317 Storage Stability TGAI: No loss of isopropy l my ristate and no container leachate components identified. TGAI: Stored in 100 mL carbon steel containers at 25° and 40°C / 60% relative humidity for 48 months. b EP: No loss of isopropy l my ristate and no container leachate components identified. EP: Stored in 1 oz. and 2 oz. HDPE bottles at 25° and 40°C / 60% relative humidity

for 48 months. c 830.6319 Miscibility TGAI: not required EP: Not applicable, the product is not intended for dilution with petroleum

solvents. 830.6320 Corrosion

Characteristics TGAI: Not required EP: Not expected to be corrosive. Storage stability studies b,c 830.7000 pH TGAI: not applicable EP: not applicable Both the TGAI and EP are not soluble or dispersible in water.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 20 of 34

830.7100 Viscosity TGAI: not required EP: 3.5

– 3.7 cP Storage stability studies c

TABLE 1. (Cont.) Physical and Chemical Properties for RESULTIXTM and isopropyl myristate TGAI a Guideline Reference No./Property Description of Result Methods 830.7200 Melting Range TGAI : Not applicable, the product is a liquid. EP: not required 830.7220 Boiling Range TGAI : 192.6°C EP: not required CI R (1982) f
830.7300 Density

/Relative Density /Bulk Density TGAI : 0.85 to 0.86 g/mL EP: 0.85 to 0.86 g/mL CI R (1982) f
830.7370 Dissociation

Constant in Water TGAI : Not applicable, the product is not

pure active ingredient and is insoluble in

water. EP: not required CI R (1982) f

830.7550 Partition

Coefficient TGAI : 7.17

– 7.43 EP: not required CI R (1982) f
830.7840 Water Solubility TGAI : insoluble in water EP: not required CI R (1982) f
830.7950 Vapor Pressure TGAI : <1 Torr EP: not required CI R (1982) gIsopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 21 of 34

All toxicology

data requirements have been satisfied per 40 CFR 158.2050
. The data presented in Table 1 below are a summary of the toxicity

data and selected endpoints for isopropyl my ristate. Table 2 . Mammalian Toxicology Data and Selected Endpoints for isopropyl myristate (40 CFR § 158.2050) Study/OCSPP Guideline

No. Results 1 Toxicity Category/Description MRID Acute oral toxicity

(rat) (870.1100) LD 50 > 13.6 g/kg IV 47925309 48348202 Acute dermal toxicity (rabbit) (870.1200) LD 50 = 5000 mg/kg III 47925309 48348202 HSDB, 2011 Acute inhalation toxicity (rat) (870.1300) LC 50 > 33
- 41 mg/L 2 IV 47925309 48348202 HSDB, 2011 Primary ey e irritation (rabbit) (870.2400) Minimally irritating III 47925309 48348202 HSDB, 2011 Primary d ermal irritation (rabbit, guinea pig, rat) (870.2500) Minimally
- severely irritating 3 II 47925309 48348202 HSDB, 2011 Dermal sensitization (guinea pig) (870.2600) Not a sensitizer N/A 47925309 48348202 HSDB, 2011Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 22 of 34

All toxicology

data requirements have been satisfied per 40 CFR 158.2050
. The data presented in Table 1 below are a summary of the toxicity

data and selected endpoints for isopropyl my ristate. Table 2 . Mammalian Toxicology Data and Selected Endpoints for isopropyl myristate (40 CFR § 158.2050) Study/OCSPP Guideline

No. Results 1 Toxicity Category/Description MRID Hy persensitivity

incidents (885.3400) Must be reported N/A N/A

90
- Day oral toxicity (870.3100) Repeat human oral exposure is not expected based on the use pattern.

A 28
- day non - guideline oral toxicity study was submitted on the EP but is classified as unacceptable due to deficiencies in the study
. A 28
- day oral toxicity

study conducted in rats at 0, 100, 500 or 1000 mg/kg bw
- day

resulted in a NOAEL of ≥ 1000 mg/kg bw. The LOAEL could not be determined (no adverse effects at the highest dose tested)
. 3 47925315

HSDB, 2011Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 23 of 34

All toxicology

data requirements have been satisfied per 40 CFR 158.2050
. The data presented in Table 1 below are a summary of the toxicity

data and selected endpoints for isopropyl my ristate. Table 2 . Mammalian Toxicology Data and Selected Endpoints for isopropyl myristate (40 CFR § 158.2050) Study/OCSPP Guideline

No. Results 1 Toxicity Category/Description MRID

90
- Day dermal toxicity

(pig) (870.3250) No purposeful application to the human skin based on use pattern. Prolonged dermal exposure is not expected.
A 28
- day non - guideline dermal toxicity study in pigs was submitted on the EP. The dermal LOAEL could not be determined (no adverse effects at the highest dose tested) and the NOAEL ≥ 196.3
- 321.3 mg/kg bw. 3 48348201

47925316Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 24 of 34

All toxicology

data requirements have been satisfied per 40 CFR 158.2050
. The data presented in Table 1 below are a summary of the toxicity

data and selected endpoints for isopropyl my ristate. Table 2 . Mammalian Toxicology Data and Selected Endpoints for isopropyl myristate (40 CFR § 158.2050) Study/OCSPP Guideline

No. Results 1 Toxicity Category/Description MRID

90
- Day inhalation toxicity (870.3465) No likelihood of significant repeat inhalation exposure based on use pattern and low volatility of the active ingredient.
A 13
- week inhalation study conducted in guinea pigs with an aerosol formulation containing 16
- 20% isopropyl my

ristate at 0, 63.3, or 224 mg/m 3 resulted in increased absolute and relative lu ng weights. No other treatment - related effects were observed. A 13
- week inhalation study conducted in cy

nomolgus monkey s with the same formulation at 0, 5.3, 8.4, 33.6, or 37.0 mg/ m 3 resulted in accumulations of macrophages within the bronchiolar and alveolar walls that were dose
related in treated monkey s. No other treatment
- related effects were noted. 47925309
48348201 HSDB, 2011

Mutagenicity
- bacterial reverse mutation test (Ames) (870.5100) Negative at 4, 20, 100, 500, 2500 μg/plate with and without metabolic activation in Salmonella typhimurium
. HSDB, 2011Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 25 of 34

All toxicology

data requirements have been satisfied per 40 CFR 158.2050
. The data presented in Table 1 below are a summary of the toxicity

data and selected endpoints for isopropyl my ristate. Table 2 . Mammalian Toxicology Data and Selected Endpoints for isopropyl myristate (40 CFR § 158.2050) Study/OCSPP Guideline

No. Results 1 Toxicity Category/Description MRID

Mutagenicity
- in vitro mammalian cell assay (870.5300 and 870.5375) No data were submitted. However, significant human exposure is unlikely ; isopropy l my ristate is not structurally related to a known mutagen and does not belong to a chemical class of compounds containing a known mutagen.
A life
- time dermal carcinogenic ity

study conducted in mice at 10%, 50% and 100% isopropy l my

ristate diluted in acetone resulted in no difference in skin tumor frequency

when compared to controls. 48348201

47925309 HSDB, 2011

Developmental toxicity (870.3700) No data submitted. However, significant exposure to female humans is unlikely

based on use pattern and low volatility
. 47925309 48348201Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 26 of 34

Table 2. Mammalian Toxicology Data Requirements for RESUL TI XTM (40 CFR § 158.2050) Study/OCSPP Guideline

No. Results Toxicity Category/Description MRID Acute oral toxicity

(rat) (870.1100) No data were submitted for the EP. Based on reported LD 50 values for the active and inert ingredients, the estimated L D 50 >

4,800 mg/kg III 47925309
Acute dermal toxicity (rat and rabbit) (870.1200) LD 50 > 5,050 mg/kg (rabbit)
LD 50 > 5,050 mg/kg (rat) IV 47925310
47925311 Acute inhalation toxicity (rat) (870.1300) No data were submitted for the EP. Based on reported LD 50 values for the active and inert ingredients, the estimated L D 50 =

2.7 mg/L IV 47925309 Primary ey e irritation (rabbit) (870.2400) Minimally irritating IV 47925312 Primary d ermal irritation (rabbit) (870.2500) Nonirritating IV 47925313 Dermal sensitization (guinea pig) (870.2600) Not a sensitizer 47925314 Hy persensitivity

incidents (885.3400) Must be reportedIsopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 27 of 3 4

VII I . Appendix B. For product specific information, please refer to http://www.epa.gov/pesticides/pestlabels .

IX . Appendix C.
REFERENCES Environmental Canada (EC). 2008. Screening Assessment for the Challenge Decamethylcy clo
pentasiloxane (D5). Excerpt only
. http://www.ec.gc.ca/substances/ese/eng/challenge/batch2/batch2_541
- 02
- 6_en.pdf Office of Environmental Health Hazard Assessment for the State of California (OEHHA). 2007. Toxicity Data Review. Decamethylcy clopentasiloxane (D5). Excerpt only
. http://www.arb.ca.gov/toxics/dry clean/oehhad5review.pdf (FDA I nactive Ingredients Database, 2011). (Household Products Database, 2010)Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 28 of 34

X. Appendix DC.

BIBLIOGRAPHY MRID Citation Reference
78632 In stitut Francais de Recherches et Essais Biologiques (19??) A Study of the I rritant and Cough Provoking Potential of Ru 15 525 in the Guinea Pig and the Beagle: I. F.R.E.B.
- R 760363. (Unpublished study received on unknown date under unknown admin. no.; sub mitted by

McLaughlin, Gormley , King Co., Minneapolis, Minn.; CDL :238269
- L) 90603 Union Camp Corporation (19??) Material Safety Data Sheet: Unimate 605. (Unpublished study

received Feb 21, 1978 under 40195
- 1; submitted by Reaenge In sect Repellent Corp., S avannah, Ga.; CDL:232894
- C) 90604 Union Camp Corporation (1976) Unimate Fatty Esters for Use in Cosmetics. Way ne, N.J.: Union Camp. (Product specifications, Jun; also I n unpublished submission received Feb 21, 1978 under 40195
- 1; submitted by Reaenge Ins ect Repellent Corp., Savannah, Ga.; CDL :232894
- D) 90606 Bio
- Toxicology L aboratories, Incorporated (19??) Summary & Conclusions of Toxicity Data: Unimate 605 B 8126. Summary of studies 232895
- B through 232895
- D. (Unpublished study

received Feb 21, 1978 under 40195
- 1; submitted by Reaenge In sect Repel
- lent Corp., Savannah, Ga.; CDL :232895
- A) 90614 Bio
- Toxicology L aboratories, Incorporated (19??) Draize Ey e I rritation Study : Unimate 605 B 8126. (Unpublished study received Feb 21, 1978 under 40195
- 1; submitted by

Reaenge Insect Repel
- lent Corp., Savannah, Ga.; CDL :232895
- B) 90615 Bio
- Toxicology L aboratories, Incorporated (19??) Primary I rritation Study : Unimate 605 B 8126. (Unpublished study received Feb 21, 1978 under 40195
- 1; submitted by Reaenge I nsect Repel
- lent Corp., Savannah, Ga.; CDL :232895
- C) 90616 Bio
- Toxicology L aboratories, Incorporated (19??) Acute Oral Toxicity Study : Unimate 605 B 8126. (Unpublished study received Feb 21, 1978 under 40195
- 1; submitted by

Reaenge Insect Repellent Corp., Savannah, Ga.; CDL :232895
- D)Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 29 of 34

123292 Weil, C.; Scala, R. (1971) Study of intra
- and interlaboratory variability

in the results of rabbit ey e and skin irritation tests. Toxicology and Applied Pharmacology 19:276
- 360. (Also I n unpublished submission received Sep 16, 1982 under 3134
- 23; submitted by

Evsco Pharmaceutical Co., Bulna, NJ; CDL :248947
- A) 5000045 Stenbaeck, F. (1977) Local and sy stemic effects of commonly used cutaneous agents: Li fetime studies of 16 compounds in mice and rabbits. Acta Pharmacologica et Toxicologica 41(5):417
- 431. 5004319 Stenback, F.; Shubik, P. (1974) L ack of toxicity and carcinogenicity

of some commonly

used cutaneous agents. Toxicology an d Applied Pharmacology 30:7
- 13. 47811700 Piedmont Animal Health (2009) Submission of Product Chemistry and Toxicity

Data in Support of the Petition for Tolerance of (Inert I ngredient). Transmittal of 1 Study
. 47811701 Phillips, S. (2009) Chemistry and Toxicological Information for (I nert I ngredient). Unpublished study

prepared by

Piedmont Animal Health. 83 p. 47925300 Piedmont Animal Health (2009) Submission of Product Chemistry , Toxicity , and

Environmental Fate Data in Support of the Application for R egistration of RESUL TI XTM Transmittal of 20 Studies. 47925301 Phillips, S. (2009) Miscellaneous Chemistry I nformation: RESUL TI XTM
. Unpublished study

prepared by

Piedmont Animal Health. 77 p. 47925302 Ballard, T. (2009) Determination of the Percent Active Ingredient and I mpurities in

Five Batches of I sopropy l My ristate Technical Grade Active Material: ( RESUL TI XTM ). Project Number: 09/0033, PAH/09/0057. Unpublished study prepared by

En
- Cas Analy

tical L aboratories. 107 p. 47925303 Omoruan, P. (2005) The Forced Degradation Study for I sopropy l My

ristate Drug Substance and I sopropy l My ristate Solution (50% w/w) by GC: ( RESUL TI XTM ). Project Number: PED/AR/014/0105/R0. Unpublished Study Prepared by

Patheon, In c. 79 p. 47925304 Carr, G. (2009) Storage Stability of I s opropyl My

ristate Manufacturing
- Use Product at 25 degrees Celsius and 40 degrees Celsius in Carbon Steel Containers for up to 48 Months: RESUL TI XTM. Project Number: PED/SP/019/0706/R1. Unpublished study prepared by

Patheon. 41 p. 47925305 Kaminsky , M. (2007) Is opropyl my ristate Solution : Flammability /Flash Point: ( RESUL TI XTM)
. Project Number: 10633/07. Unpublished study prepared byIsopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 30 of 34 Stillmeadow, I nc. 9 p. 47925306 Serrano, S. (2007) Analy sis of Extractables and L eachables in HDPE Bottles and PP

Caps Used to Package the I sopropy l My ristate D5 Formulation (Feasibility Study ): ( RESUL TI XTM). Project Number: R061229B. Unpublished study prepared by Guidelines, I nc. 47 p. 47925307 Serrano, S. (2007) Photostability Protocol, Testing Schedule and Res ults for Is opropyl My

ristate Solution (50% w/w), ANDA: ( RESUL TI XTM ). Project Number: PED/SP/022/0107/R0. Unpublished Study Prepared by

Patheon, I nc. 10 p. 47925308 Carr, G. (2007) An Investigation of the UV/Visible Absorbance Properties of

Is opropyl My

ristate 50% Solution, I sopropy l My ristate and Cy clomethicone: ( RESUL TI XTM ). Project Number: PED/MI S/024/0307/R0. Unpublished Study Prepared by

Patheon, I nc. 14 p. 47925309 Phillips, S. (2009) Miscellaneous Toxicology I nformation: ( RESUL TI XTM ). Unpublished study

prepared by

Piedmont Animal Health. 315 p. 47925310 Kuhn, J. (2002) Piedmont Pediculicide 2: Final Report: Acute Dermal Toxicity

Study in Rabbits. Project Number: 7205/02. Unpublished study prepared by Stillmeadow, I nc. 31 p. 47925311 Kuhn, J. (2002) Piedmont Pediculocide 2: Final Report: Acute Dermal Toxicity

Study in Rats: Final Report. Project Number: 7204/02. Unpublished study prepared by Stillmeadow, I nc. 33 p. 47925312 Kuhn, J. (2002) Piedmont Pediculicide 1: Final Report: Acute Ey e I rrit ation Study in Rabbits. Project Number: 7089/02. Unpublished study prepared by

Stillmeadow, I nc. 16 p. 47925313 Kuhn, J. (2002) Piedmont Pediculocide 1: Final Report: Acute Dermal Irritation

Study in Rabbits. Project Number: 7090/02. Unpublished study pre pared by Stillmeadow, I nc. 11 p. 47925314 Kuhn, J. (2009) RESUL TI XTM Tick Spray : Final Report: Skin Sensitization Study in Guinea Pigs. Project Number: 13304/09. Unpublished study prepared by Stillmeadow, I nc. 16 p. 47925315 Goldenthal, E. (2003) 28
- Day O ral Toxicity

Study in Rats with a 14
- Day

Recovery : RESUL TI XTM . Project Number: 1016/001. Unpublished study prepared by

MPI Research, I nc. 603 p.Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 31 of 34

47925316 Goldenthal, E. (2003) 28
- Day Dermal Toxicity

Study in Pigs with a 14
- Day Recovery : RESUL TI XTM . Project Number: 1016/002. Unpublished study prepared by MPIResearch, Inc. 442 p. 47925317 Young, D. (2009) Pivotal Study to Determine Safety

and Efficacy

of I sopropy l My ristate ( IS OPROPYLMYRI STATE ) Tick Spray against Rhipicephalus sanguineus and Dermacentor var iabilis on Dogs. Project Number: PAH/09/0036. Unpublished study

prepared by

Young Veterinary

Research Services. 19 p. 47925318 Young, D. (2009) Pivotal Study to Determine Safety

and Efficacy

of I sopropy l My ristate ( IS OPROPYLMYRI STATE ) Tick Spray against Rhipicephalus sanuineus and Dermacentor variabilis on Cats. Project Number: PAH/09/0065. Unpublished study prepared by

Young Veterinary

Research Services. 18 p. 47925319 Garg, D. (2005) Pharmacokinetic, Safety and Tolerance Study

of RESUL TZ Pediculicide R inse in Pediatric Subjects with Pediculosis Capitis. Project Number: 04/123941/108. Unpublished study prepared by

Hill Top Research, Inc. 103 p. 47925320 Phillips, S. (2009) Environmental Fate Information: RESUL TI XTM . Unpublished

study prepared by

Piedmont Animal Health. 76 p. 48132300 Piedmont Animal Health L LC (2010) Submission of Product Chemistry Data in Support of the Application for Registration of RESUL TI XTM . Transmittal of 1 Study
. 48132301 Chastain, L . (2010) Stability Study of RESUL TI XTM 1 oz. and 2 oz. Bottles: I nterim Report (6 Month). Project Number: 9/066, 09/0066. Unpublished study prepared by Span Packaging Services, L LC . 14 p. 48348200 Piedmont Animal Health, L LC (2011) Submission of Toxicity Data in Support of the Application for Registrat ion of RESUL TI XTM End
- Use Product. Transmittal of 4 Studies. 48348201 Phillips, S.; Barer, G. (2011) Discussion of Submitted Information: ( RESUL TI XTM

End
- Use Product). Unpublished study prepared by

Piedmont Animal Health. 67 p. 48348202 Phillips, S.; Barer, G. (2011) Published Articles Concerning the Safety of My ristic Acid and its Derivatives, Including I sopropy l My ristate. Unpublished study prepared by Piedmont Animal Health. 123 p. 48348203 Young, D. (2011) Pivotal Study to Determine Safety

and Eff icacy of I sopropy l My ristate ( IS OPROPYLMYRI STATE ) Tick Spray against Rhipicephalus sanguineus and Dermacentor variabilis on Dogs: Amended Final Report. ProjectIsopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 32 of 34 Number: PAH/09/0036. Unpublished study prepared by

Young Veterinary

Research Services. 83 p. 4 8348204 Young, D. (2011) Pivotal Study to Determine Safety

and Efficacy

of I sopropy l My ristate ( IS OPROPYLMYRI STATE ) Tick Spray Against Rhipicephalus sanguineus and Dermacentor variabilis on Cats: Amended Final Report. Project Number: PAH/09/0065. Unpublis hed study prepared by

Young Veterinary

Research Services. 85 p. 48491400 Piedmont Animal Health L LC (2011) Submission of Product Chemistry Data in Support of the Registration of RESUL TI XTM . Transmittal of 1 Study
. 48491401 Chastain, L . (2010) Final Report (12 Month) Stability Study of RESUL TI XTM 1 oz and 2 oz Bottles. Project Number: PAH/09/0066. Unpublished study prepared by Span Packaging Services, LLC. 14 p.

===================================================================Isopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 33 of 34

X. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

a.i
. Active I ngredient BPPD Biopesticides and Pollution Prevention Division BRAD Biopesticide Registration Action Document CFR Code of Federal Regulations

cm 3 cubic centimeter CSF Confidential Statement of Formula °C degrees Celsius EDSP Endocrine Disruptor Screening Program EDSTAC Endocrine Disruptor Screening and Testing Advisory Committee EPA Environmental Protection Agency (the “Agency ”) FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal I nsecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FR Federal Register g gram kg kilogram L liter LD 50 median lethal dose. A statistically deri ved single dose that can be expected to cause death in 50% of the test animals when administered by the routeIsopropyl myristate PC Code 000207 Biopesticides Registration Action Docum ent Page 34 of 34 indicated (oral, dermal, or inhalation). I t is expressed as a weight of substance per unit weight of animal (e.g., mg/kg). MRI D No. Master R ecord I dentification Number mg milligram mL milliliter MP manufacturing
- use product MPCA microbial pest control agent NE “No Effect” NI OSH National I nstitute for Occupational Safety and Health OPP Office of Pesticide Programs OPPTS Office of Prevention, Pesticides, and Toxic Substances PCR poly

merase chain reaction PPE personal protective equ ipm ent TGAI technical grade of the active ingredient