EPA Registration Jacket 2517‐133
1
2

EXponent 

June 15,2010 

Richard Gebken 

Product Manager 10 

Document Processing Desk 

Office of Pesticide Programs (7504P) 

U.S. Environmental Protection Agency 

Room S-4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202-4501 

Subject: Response to EPA Notice of Registration 

Dear Mr. Gebken: 

Exponent 

1150 Connecticut Avenue, NW 

Suite 1100 

Washington, DC 200)6 

telephone 202-772-4900 

facsimile 202-772-4979 

www.exponent.com 

On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158th Plaza, 

Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a 

response to EPA's Notice of Registration (dated April 30, 20 I 0) for the following product: 

• EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies (EPA File Symbol 2517-

133). 

The purpose ofthis letter is to address the requirement 13. a) Data to fulfill the OPPTS Guideline 

830.1800 -- Enforcement Analytical Method submitted within 45 days of the approvals. This 

study has been submitted under separate cover and an MRID has not yet been assigned. 

If you have any questions, please contact me at 202-772-4932. 

sifiCeJi ly Y7 ( , 

/--~j s B. Messina 

orized Representative of 

VSergeant's Pet Care Products, Inc. 

Enclosures 

cc: Kevin Sweeney, EPA 

Kelly Hoskins, Sergeant's 

;, ); 

. );' , 
3

Please read instructions on reverse before completing form Form Approved OMS No 2070-0060 Approval expires 05-31-98 

EPA United States 

Environmental Protection Agency 

Washington. DC 20460 

D_Registration 

DAmendment 

C2J Other 

OPP Identifier Number 

Application for Pesticide - Section I 

1. Company/Product Number 

2517-133 

4. Company/Product (Name) 

Sergeant's Pet Care Products, Inc./ EtofenproxINylar Spot-On Flea and 

Tick for Dogs and Puppies 

2. EPA Product Manager 

Richard Gebken 

PM#10 

3. Proposed Classification 

!:8JNone DRestricted 

5. Name and Address of Applicant (Include ZIP Code) 

Sergeant's Pet Care Products, Inc. 

6. Expedited Review. In accordance with FIFRA Section 3(c)(3)(b)(I). my 

product is similar or identical in composition and labeling to: 

2625 South 1581h Plaza 

Omaha, NE 68130 

D Check if this is a new address 

o Amendment - Explain below. 

!:8J Resubmission in response to Agency letter dated 4/30/2010 

o Notification - Explain below. 

EPA Reg. No. 

Product Name 

Section" 

o Final printed labels in response to Agency letter dated XX-XX-XX 

o "Me Too" Application 

o Other - Explain below. 

Explanation: Use additional page(s) if necessary. (For section I and Section II.) 

Response to EPA providing Enforcement Analytical Method. 

1. Material This Product Will Be Packaged In: 

Child-Resistant Packaging 

DYes" 

ONo 

'Certification must 

be submitted 

Unit Packaging 

DYes 

o No 

If "Yes" No. per 

Unit Packaging wgt. Container 

Section '" 

Water Soluble Packaging 

DYes 

o No 

It "Yes" 

Package wgt. 

I 

No. per 

Container 

3. Location of Net Contents Information 4. Size(s) Retail Container 

DLabel D Container 

6. Manner in Which Label is Affixed to Product DLithOgraph 

DPaper glued 

DStenciled 

DOther 

Section IV 

2. Type of Container 

o Metal 

DplaStic 

DGlass 

DPaper 

OOther (Specify) Plastic Bag 

5. Location of Label Directions 

DOn Can 

DOn Labeling accompanying product 

1. Contact Point (Complete items directly below for identification of individual to be contacted, if necessary, to process this application.) 

Name Title Telephone No. (Include Area Code) 

James Messina 

. 

Authorized Representative 202-772-4932 

~------------------------------------------L-------------------~----------------~---------,c~~~~----------~ Certification , J J ) ) .' ) /).) ba~ Application 

I certify that the statements I have made on this form and all attachments thereto are true, accurate and complet,e. I ~ ~eceived 

acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both [Stamped) 

under app.uCable law/I )}- ~ ) J. ~ ; J.) i) 

2. Signatt e Vi 3. Title ' 

BY' /....... Authorized Representative J J ) ) J 

. I·'j/~ ; 

I------H---I'---------+:~::___::_:__._::_=------"'- --I 

4. Typed Name: /J James Messina 5. Date: June 15, 2010 

:, ;) 

, 

.) J" 

,), , , , 
4
5

Sergeant's Pet Care Products, Inc. 

2625 South 158th Plaza • Omaha, NE 68130-1770 • Telephone 402.938.7000 • Fax 402.938.7099 • www.sergeants.com 

October 28, 2010 

Front Processing Desk 

Richard Gebken PM 10 

U.s. Environmental Protection Agency 

Office ofpesticide Program (7505 P) 

Room S-4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202-4501 

SUBJECT: Gold Seal Certificates 

Dear Mr. Gebken, 

Following is a list of products that Sergeant's would like to receive six Gold Seal Certificates for each 

product. I have enclosed two printed labels for each of the products listed. 

EPA No. 2517-129 Cyphenothrin+Pyriproxyfen Squeeze-On for Dogs (20%) 

Product labels: 

Sergeant's EVOLVE 21 Flea & Tick Squeeze-On for Dogs 

Sergeant's EVOLVE 40 Flea & Tick Squeeze-On for Dogs 

SENTRYPRO XFT 21 flea & tick squeeze-on for dogs 

SENTRYPRO XFT 40 flea & tick squeeze-on for dogs 

EPA No. 2517-130 

Product labels: 

Cyphenothrin+Pyriproxyfen Squeeze-On for Dogs (30%) 

Sergeant's EVOLVE 61 Flea & Tick Squeeze-On for Dogs 

SENTRYPRO XFT 61 flea & tick squeeze-on for dogs 

EPA No. 2517-133 EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies 

Product labels: 

Sergeant's EVOLVE II Flea & Tick Squeeze-On for Dogs 

SENTRYPRO XFT II flea & tick squeeze-on for dogs 

SENTRYPRO TOY & small breed flea & tick squeeze-on for dogs (4 to 10 Ibs) 

Sergeant's TOY BREED Flea & Tick Squeeze-On for Small Breed Dogs (4 to 10 Ibs.) 

Should you need further information, I can be reached at (402)938-7065 or my e-mail address is 

skane@sergeants.com. 

Thank you for your assistance in this matter. 

Susan Kane 

Regulatory Specialist 

Sergeant's Pet Care Products, Inc. 
6

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF PREVENTION, 

PESTICIDES AND 

TOXIC SUBSTANCES 

November 26, 2010 

I, Richard Gebken, Insecticide Branch, Registration Division, Office of Pesticide Programs, Office of 

Prevention, Pesticides and Toxic Substances, United States Environmental Protection Agency ("EPA"), 

certify that the pesticide product (s) listed below is, as of the date of this letter, a registered product under 

the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended, and that as such, the 

product(s) may be sold and marketed in the United States of America as authorized and limited by FIFRA. A 

true and correct copy of the product label approved by EPA is attached to accompany this letter. 

Registration of this product(s) with EPA also denotes that the registrant listed below is responsible for 

ensuring full compliance with all the laws of the United States of America, or governing jurisdiction, 

regarding the sale, storage and/or disposal of the product(s). Further, the recipient of this letter is on notice 

that the referenced registration and/or the accompanying label may change subsequent to the date of this 

letter. EPA assumes no responsibility to notify the recipient(s) of this letter of any change in the status of 

theregistration(s) and/or the product label for the product(s) listed below. 

EPA has issued registration numbers for the product(s) listed below to: 

Sergeant's Pet Care Products, Inc. 

2625 South 158Th Plaza 

Omaha, NE 681301703 

EPA Registration Number: 2517-133 

Name of Product: ETOFENPROXINYLAR SPOT-ON FLEA AND TICK FOR DO~ & PUPPIES 

~:.~.~ Jl'R'i~ken Risk Manager 13 

Insecticide Branch 

Registration Division (7505P) 
7

Material to be added to an e-Jacket/Jacket 

Reg. No. 2517-133 

Description: New Label 

1. Placement within the e-Jacket/jacket: 

X Default: (chronological, top = newest) 

D File Location: (PDF page number, i.e., "before page 

45") 

2. X Send to Data Extraction contractors this material: 

X Newly stamped accepted label 

D Notification 

X New CSF (3/6/10 are CSFs of record) 

X Other: Correspondence 

3. Attach this coversheet to the top of the material or jacket. It 

must be well organized and clipped together, NOT STAPLED. 

Then give the material with this coversheet to staff in the 

Information Services Center (Room S-4900). 

Reviewer's Name: Kevin Sweeney 

Phone: ----.:3::....:0::....:5:::.....-...=;5-=0-=6=3 ____ Division: -.:R:....:..D=-__ 

Date: 05/03/2010 

Created May 3, 2010 
8

U.S. ENVIRONMENTAL PROTECTION 

AGENCY 

Office of Pesticide Programs 

Registration Division (7505P) 

1200 Pennsylvania Ave., N.W. 

Washington, D.C. 20460 

NOTICE OF PESTICIDE: 

o Registration 

o Reregistration 

(under the Federal Insecticide, Fungicide, 

and Rodenticide Act, as amended) 

Name and Address of Registrant (include ZIP Code): 

Sergeant's Pet Care Products, Inc. 

2625 South 158'h Plaza 

Omaha, NE 68130 

EPA Registration No. Date of Issuance: 

2517-133 APR 30 2010 

Term of Issuance: 

Conditional Registration 

Expires April 30, 2012 

Name of Pesticide Product: 

EtofenproxlNylar Spot-on Flea and 

Tick for Dogs and Puppies 

On the basis of information furnished by the registrant, the above named pesticide is hereby registered under the 

Federal Insecticide, Fungicide and Rodenticide Act. 

Registration is in no way to be construed as an endorsement or recommendation of this product by the Agency. In 

order to protect health and the environment, the Administrator, on his motion, may at any time suspend or cancel the 

registration of a pesticide in accordance with the Act. The acceptance of any name in connection with tbe 

registration of a product under this Act is not to be construed as giving the registrant a right to exclusive use of the 

name or to its use if it has been covered by others. 

This product is conditionally registered in accordance witb FIFRA sec. 3(c)(7)(a) provided that: 

1. This registration is time-limited and expires two years from the date this product is first released 

for shipment. 

You must provide the Agency with a projected release for shipment date within 30 days of the date 

of this Notice of Registration. The Agency will calculate the expiration date based on the 

projected release for shipment date until an actual release for shipment date is provided in writing. 

2. Only one confidential statement offormula (basic) will be filed for this product; no alternate 

formulation or minor formulation statements may be submitted or approved for this product. 

3. Make the following changes to the label: 

a. All marketing statements and references to "mosquitoes" throughout the draft label must be 

deleted because the submitted efficacy study do not support these claims. West Nile virus and 

heartworm claims must also be removed 

b. On page one of the label, because all "mosquito" references are not permitted, you must 

correct the marketing statements that refer to "[Five] [5] Way Protection" to "[Four] [4] Way 

Protection ... " 
9

c. The claim "New [fonnulaJ" may appear on product produced for 6 months from the date of 

first distribution only. 

d. Revise the EPA Registration Number to read: "EPA Registration No. 2517-133. 

e. Remove the phrase "Before they can ... " made with reference to transmission of disease by 

ticks. There are no data to support this claim. 

f. Of the three statements proposed, you may use: "Some dogs may experience temporary startle 

effects when this product is applied." in the Precautionary Statements section of the label. 

g. Change the second weight class for dogs from 1 0-201bs to 11-20Ibs. 

4. All of the product chemistry data requirements for this product have been satisfied, except for 

OPPTS Guidelines 830.6317 and 830.6320, Storage Stability and Corrosion Characteristics 

studies, respectively. Within on-year of the date of this registration you must submit these data 

including interim reports made at 0, 3, 6, 9, and 12 month intervals. 

5. You must submit enhanced incident reports for this product on a quarterly basis beginning July I, 

2010. Please flag any Confidential Business Infonnation as such. Enhanced incident reporting 

should be submitted to the Product Manager. Quarterly sales information should be submitted to 

the Registration Division, Immediate Office (ATTN: Kimberly Nesci). 

The following is a list of infonnation needed by EPA to better characterize these incidents: 

EPA Registration Number 

Product name (brand name) 

Lot # 

Where purchased: internet, store, veterinarian 

Active Ingredient(s) 

Weight range for product 

Date on which incident occurred. (mmldd/yyyy) 

State in which the incident occurred. (standard 2 letter abbreviation) 

Registrant case # 

Species: dog, cat, other (specifY) 

Breed: (as reported by pet owner) 

Age: months or years 

Sex: M, F, or neutered 

Weight: pounds 

Primary Route of Exposure: dennal, oral, other animal, inhalation, other 

Body System: neurological, dermatological, GI, respiratory, ocular, other 

Major signs noted with separate column for each sign, using standard terminology 

Time to Onset: (hours, days) 

Treated by veterinarian: yes or no 

First time product used: yes or no 

Misuse: use on incorrect species, overdose, too frequent dosing, other (describe) 

Any known precondition 

EPA Severity Code: death, major, moderate, minor 
10

Outcome: died, recovered, still treated, unknown 

6. Along with the enhanced incident reporting, you must submit an analysis of the incidents seen, to 

include the following details: 

All incidents should be reported including all minor dermal and ocular irritation reports. 

Summary table for dogs showing number of incidents of each severity code for each route 

of exposure. Each incident should only be reported once. If one incident has several 

routes of exposure, the order should be ocular> oral> dermal. In other words, an incident 

with both oral and dermal exposure would be reported as oral exposure, and an incident 

with both ocular and oral exposure would be reported as ocular exposure. 

A similar summary table for cats (misuse or secondary exposure) showing number of 

incidents of each severity code for each route of exposure. 

Summary table for dogs and table for cats showing number of incidents that are believed 

due to secondary exposure (e.g., multi-pet households). 

A summary table for dogs showing number of incidents for each severity code for these 

age ranges: <3 months, 3-6 months, 6-9 months, 9-12 months, I yr, 2 yr, 3 yr, 4 yr, 5 yr, 6 

yr, 7yr,8yr,9yr, 10yr, II yr, 12yr, I3yr, 14yr, 15 yr, >15 yr. 

A summary table showing the number of dog incidents for each severity code for each pet 

weight range on the product label. 

A summary table for dog weight showing number of incidents for each product weight 

range. This table should show number of incidents in dogs weighing less than that product 

weight range, number of incidents in dogs in lower half of weight range, number of 

incidents in dogs in upper half of weight range, and dogs weighing more than the product 

weight range. 

Table showing number of incidents for each dog breed. 

Table showing number of incidents in dogs for each clinical sign. 

Table showing number of incidents in dogs for each organ system. 

Report aggregate incidents, but do not combine moderate and minor incidents. 

7. You must submit and/or cite all data required for registration of your product under FIFRA Section 

3(c)(5) when the Agency requires all registrants of similar products to submit such data, and 

submit acceptable responses required for reregistration of your product under FIFRA section 4. 

8. The basic Confidential Statement of Formula dated April 28, 2010 is acceptable, and is the basic 

CSF of record, superseding all previously submitted CSFs. As stated above, only one confidential 

statement of formula (basic) will be filed for this product; no alternate formulation or minor 

formulation statements may be submitted or approved for this product. 
11

9. The acute toxicity profile for this product is as follows: 

Route of Exposure 

Acute oral toxicity 

Acute dermal toxicity 

Acute inhalation toxicity 

Primary eye irritation 

Primary skin irritation 

Dermal sensitization 

Toxicity Category 

IV 

IV 

IV 

III 

IV 

Negative 

A stamped copy of the label and copies of the Data Evaluation Records (DERs) are included for 

your file. Two copies of the finished labeling must be submitted prior to releasing the product for shipment. 

Ifthese conditions are not complied with, the registration will be subject to cancellation in accordance with 

FIFRA sec. 6(e). Your release for shipment of the product constitutes acceptance of these conditions. 

If EPA determines that future mitigation measures are necessary for all pet spot-ons, the Agency 

will inform registrants. If mitigation measures are necessary, EPA may take regulatory action. If you have 

any questions concerning this registration, please contact Kevin Sweeney at (703) 305-5063. 

Si".,ra,hm'. Date: 

APR 3 0 2010 

EPA Fonn 8570-6 

Enclosure 
12

Sergeant's Pet Care Products, Inc. Master Label 

29 April 2010 EPA Reg. No. 2517-RGG 

Infonnation in I I is optional. Page I of 4 EPA SAL 

FRONT PANEL DOG SQUEEZE - ON 

Pyriproxyfen (NYLAR), Etofenprox 

Editors Note: [Optional proposed text appears in hmckcls -the final Jabd mu} blCh,de some or all of the optional text! 

ETOFENPROXJNYLAR SPOT-ON 

FLEA AND TICK FOR DOGS AND PUPPIES 

{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On} 

{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On for small breed dogs} 

{ABN: Sergeant's Toy Breed Flea and Tick Squceze-On for small and toy breed dogs] 

{ABN: Sergeant's Small Breed Flea and Tick Squeeze-On} 

fABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small breed dogs) 

{ABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} 

{ABN: Sentry Pro Toy and Small Breed Flea and Tick Squeeze-On} 

{ABN: Sentry Pro Toy and Small Breed Flea and Tick Squeeze-On for dogs} 

{ABN: Sentry Pro Toy and Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} 

{ABN: Sentry Pro Small Breed Flea and Tick Squeeze-On for Dogs} 

{ABN: Sentry Pro Small Breed Flea and Tick Squeeze-On for small breed dogs} 

{ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small and toy breed dogs) 

{ABN: Sergeant's® Evolve (4) Flea and Tick Squeeze-On for Dogs (and Puppies)} 

{ABN: Sergeant's® Evolve (10) Flea and Tick Squeeze-On for Dogs (and Puppies)} 

{ABN: SentryPro® XFTC (4) Flea and Tick Squeeze-On for Dogs (and Puppies)} 

{ABN: SentryPro® XFTC (10) Flea and Tick Squeeze-On for Dogs (and Puppies)} 

[One Application:(choose from the following)] 

• [with nylar®] 

• [(One) (Two) (Three) (Four) (XX) Applications] 

• [Bonus] 33% more [now includes 4 tubes] 

• [odorless] [unscented] [fragrance free] 

• [Dries quickly] [Quick drying formula] [Quick Drying] 

• [Squeeze-On] [stays on and doesn't rub oftl 

• [Spreads by using the dog's natural skin oils] 

• [Breaks the flea life cycle for up to (70 Days) (9 Weeks)] 

• [Controls reinfestation for up to (70 days) (9 weeks)] 

• [For toy breeds 4-10 Ibs.] 

• [For small breeds 10·20 Ibs.] 

• [For toy and small breeds [4-10][ 10-20]lbs.] 

• [Specially formulated for small breed[s] dogs] 

• [Specially formulated for toy breed[s] [dogs]] 

• [Specially formulated for [toy breed[s]] and [small breed[s]] dogs] 

• [Toy] [and] [small] breed formula] 

• [Gentle protection for [toy] [small] breed dogs] 

• [5 Way Protection] 

• [Controls fleas, ticks, flea eggs & larvae] 

ACCEP'l"El) 

with COMMENTS 

in~p~If~'~ Under the Fedem1 Insecticide, 

Fungtclde, and Rodenticide Act. as amended. for' the pesticfde 

regtst6D "",der EPA Reg. No, 

''S17 -13 3 

• [Kills Fleas, Ticks, Flea Eggs. Larvae] [and] [repels mosquitoes [for up to one month] [for up to 4 weeks]] 

• [Flea, tick, flea egg and larvae control] 

• [Kills fleas and ticks for up to [30 days] [4 weeks]] 

• [Kills ticks [for up to [30 days] [4 weeks]]] 

• [Kills Ticks] [Before they can] [that] [transmit Lyme Disease 

• [Kills [adult] fleas for up to [30 days) [4 weeks]] 

• [Kills Fleas and Ticks] [for up to [30 days][4 weeks]] 

• [Flea, Tick and Flea Egg Protection] 

• [Repels mosquitoes [for up to one month] [for up to 4 weeks]] 

• [Flea and Tick control] 

• [Kills fleas that may cause flea allergy dermatitis. and flea bite anemia] [for up to [30 days] [4 weeks)] 

• [Kills Flea Eggs and Larvae for up to (9 weeks) (70 days) (per application)] 
13

Sergeant's Pet Care Products, Inc. Master Label 

29 April 2010 EPA Reg. No. 2517-RGG 

Information in I I is optional. Page 2 of 4 EPA SAL 

• [Prevents flea eggs from developing mto biting adults for up to (9 weeks) (70 days) (per application)] 

• [Repels mosquitoes that may transmit [heartworm] [West Nile virus] [from feeding on dogs] [for up to [one 

month] [30 daysll4 weeks]] 

• [Repels Mosquitoes] [Prevents mosquitoes that transmit West Nile virus and heartworm] [from feeding on 

dogs] [for up to [one month] [30 daysl[ 4 weeks]) 

FRONT PANEL 

ACTIVE INGREDIENTS: 

DOG SQUEEZE - ON 

Pyriproxyfen (NYLAR), Etofenprox 

Etofenprox .................................................................................... 55.00% 

Pyriproxyfen .................................................................................. 2.20% 

OTHER INGREDIENTS: ....................................................................... 42.80% 

TOTAL 100.00% 

[Nylar' is a registered trademark of MCLaughlin Gormley King Company 1 

KEEP OUT OF REACH OF CHILDREN 

CAUTION 

See IBackllorllSidel Label Panells} for Additional Precautionary Statements 

NET CONTENTS: 

IOnellTwoliThreeliFourllFiveliSixl2.0 mL applicators. [for small dogs 4 to 10 IbsJ 

IOnellTwoliThreellFourllFiveliSixl4.0 mL applicators. [for small dogs 10 to 20 IbsJ 
14

Sergeant's Pet Care Products, Inc. Master Label 

29 April 2010 EPA Reg. No. 2517-RGG 

Infonnation in I I is optional. Page 3 of4 EPA SAL 

BACK PANEL DOG SQUEEZE - ON 

Pyriproxyfen (NYLAR), Etofenprox 

{Product Name} 

READ ENTIRE LABEL BEFORE EACH USE 

PRECAUTIONARY STATEMENTS 

HAZARDS TO HUMANS AND DOMESTIC ANIMALS 

CAUTION 

HAZARDS TO HUMANS: Causes moderate eye irritation. Avoid contact with eyes and clothing. Wash 

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

HAZARDS TO DOMESTIC ANIMALS: For External Use Only. Do not use on dogs under 13 weeks of age. 

Consult a veterinarian before using this product on debilitated. aged, medicated. pr'egnant. or nursing animals. 

Sensitivities may occur after using ANY pesticide product for pets. Ifsigns of sensitivity occur, bathe your pet with 

mild soap and rinse with large amounts of water. If signs continue. consult a veterinarian immediately. 

{Some dogs may startle when a room temperature squeeze-on is applied.][Some dogs may experience temporary 

startle effects when a squeeze-on is applied.J{Some dogs may experience temporary startle etTects when squcezeon's are applied.] 

FIRST AID 

IF IN EY ES: Hold eye open and rinse slowly and gently with water for 15-20 minutes. Remove contact lenses, if 

present, after the first 5 minutes. and then continue rinsing. Call a poison control center or doctor for treatment 

advice. Have the product container or label with you when calling a poison control Center or doctor or going for 

treatment. You may also contact 1-800-781-4738 for emergency medical treatment infomlation. 

PHYSICAL OR CHEMICAL HAZARDS: Combustible: Do not use or store near heat or open flame. 

DIRECTIONS FOR USE 

It is a violation of Federal Law to use this product in a manner inconsistent with its labeling. 

Do not get this product in your pet's eyes or mouth. Do not apply more often than {once a month] {once every 30 

days]. Use only on Dogs. FOR EXTERNAL USE ON DOGS ONLY. Do not use on puppies less than 13 weeks 

of age. Weigh your dog to be sure you are applying the right dose formulated for the weight of your pel. Do not 

treat your pet with more than one pesticide product at a time. Over dosing your animal can result in serious illness 

and even death. Best if used year round. Do not bathe pet with in the first 24 hours after squeeze-on has been 

applied. Households with more than one pet should not allow dogs or cats to groom each other until solution has 

dried. DO NOT USE ON CATS or animals other than dogs. Separate the treated dog from all other dogs and cats 

for 24 hours after treatment has been applied. Cats or dogs that actively groom or engage in close physical contact 

with treated dogs may be at risk of serious harmful effects. If your dog is exhibiting signs of and/or are being treated 

for skin dermatitis, talk to your vet before applying any topical flea and tick control product. Sensitiv tties may occur 

after using ANY pesticide product on pets, It is recommended to separate treated dogs from other household pets for 

24 hours after treatment has been applied, If signs of sensitivity occur, bathe your dog with mild soap and rinse with 

large amounts of water. 

FOR USE ON DOGS: 

Weighing 4 TO 10 LBS. - Apply contents of one (2.0 mL) tube [vial] of IProduct NameliSqueeze-on I as a spot 

high on the back of the dog's neck behind its head and apply as a stripe to a point midway between the neck and the 

tail. 

(INSERT DIAGRAM THAT DEPICTS APPLICATION OF PRODUCT ON THE DOG) 

FOR USE ON DOGS: 

Weighing 10 TO 20LBS. - Apply contents of one (4.0 mL) tube [vial] of )product NameliSqueeze-on I as a spot 

high on the back of the dog's neck behind its head and apply as a stripe to a point midway between the neck and the 

tail. 
15

Sergeant's Pet Care Products, Inc. Master Label 

29 Aprii2010 EPA Reg. No. 2517-RGG 

Information in I I is optional. Page 4 of 4 EPA SAL 

(INSERT DIAGRAM THAT DEPICTS APPLICATION OF PRODUCT ON THE DOG) 

HOW TO APPLY: 

Remove product tube [vial} from the package. Holding tube [viall with notched end pointing up and away from the 

face and body cut or tear off the narrow end at the notches. While holding the animal with one hand. use the other 

hand to apply the solution. Invert the tube b'iatj and use the narrow end to part the animal's hair while gently 

squeezing to app!y to the animal's skin. Hold the animal for a few seconds to give the solution time to be absorbed 

into the animal's coat. When finished. wrap the tube [vial] in paper and put into the trash. 
16

Sergeant's Pet Care Products, Inc. Master Label 

29 April 20 I 0 

Infonnation in I I is optional. 

BACK PANEL 

Page 5 of . t; 

EPA Reg. No. 25 I 7-RGG 

EPA SAL 

DOG SQUEEZE - ON 

Pyriproxyfen (NYLAR), Etofenprox 

STORAGE AND DISPOSAL 

Do not contaminate water, food or feed by storage or disposal. 

PESTICIDE STORAGE: Do not remove tube ITom the pack until ready to use. Store in a cool (below 25 G C) dry 

place out of reach of children. Do not re frigerate. Protect from direct sunlight. 

PESTICIDE DISPOSAL: Nonrefillable container. Do not reuse or refill this container. Offer for recycling or 

reconditioning, if available and appropriate. If empty: Do not reuse this container. Place in trash or offer for 

recycling if available. If partly filled: Call your local solid waste agency tor disposal instructions. Never place 

unused product down any indoor or outdoor drain. 

[WARRANTY 

Read the entire Directions for Use and Warranty before using this Product. By using this product, user or buyer 

accepts the following warranty. [[The directions for use of this product are believed to be adequate and must be 

follo\ ... 'cd carefully. However, it is impossible to eliminate all risks inherently associated with the use of this product. 

Unintended consequences may resu It because of such factors as weather conditions, presence or absence of other 

materials, or the manner of application, all of which are beyond the control ofScrgeanfs Pet Care Products, fnc .. ]) 

Sergeant's Pet Care Products, Jnc. is committed to providing high quality products. To the extent consistent with 

applicable law, Sergeant's Pet Care Products. Inc. makes no warranties. express or implied. of merchantability or of 

fitness for a particular purpose or otherwise, that extend beyond statements on this label. To the extent consistent 

with applicable law. Sergeant's Pet Care Products, Inc .. the manufacturer, or the Seller disclaims any liability 

whatsoever for special. incidental, or consequential damages resulting from the use of this product. To the extent 

consistent with the law, the exclusive remedy of the user or buyer shall not exceed the purchase price paid.) 

[Sergeant's Care Pet Products, Inc. is committed to providing high quality products. If you have questions or 

comments about this product. please write: Sergeant's Consumer Response. P.O. Box 5403Q9. Omaha. NE 68154-

0399.1 

In Case of Emergency, call: 1-800-781-4738 

Non-Emergency call: 1-800-224-PETS (7387) 

Distributed by: 

Sergeant's Pet Care Products, Inc. 

PO Box 540224 

Omaha. NE 68154 

{END - BACK I SIDE PANEL} 

TUBE / VIAL LABEL 

Front Label 

{product Name} 

Etofenprox .......... 55.0% W/W 

Pyriproxyfen ......... 2.2% W IW 

[For more information] [Visit us at] ~\\\'\\. .. 5'<;_I:g<';_~llJ_ts:com 

Made in USA 

EPA Reg. No. 2517-XX 

EPA Est. No. XXXXXXX 

{date & label code} 

Back Label 

KEEP OUT OF REACH OF CHILDREN I 

CA UTION: Read directions and precautions before 

using. 

[2.0][4.0j mL {label code} EPA REG. No. 2517-XX lIabel code} I 
17

ROUTING AND TRANSMITTAL SLIP Date 

April 30, 2010 

TO: (Name, office symbol, room number, building, Agency/Post) 

Vi'"' 

1. Marion Johnson (7505P) "- fJ . ;.t!3o'bo70 

2. I I 

3. 

xxx Action xxx File Note and Return 

xxx For Concurrence For Clearance Per Conversation 

xxx As ReQuested For Correction Prepare Reoly 

Circulate xxx For Your Information See Me 

Comment Investigate Signature 

Coordination Justify 

REMARKS 

2517-133 Registration for EtofenproxlNylar Spot-on for Dogs and 

Puppies 

DO NOT use this form as a RECORD of approvals, concurrences, disposals, 

clearances, and similar actions. 

FROM: (Name, org. symbol, Agency/Post) 

Kevin J. Sweeney 

Room No.- Bldg. 

8-7238 Potomac Yard 

Phone No. 

(703) 305-5063 
18

DOSE ADMINISTERED TO DOGS TREATED WITH 

ETOFENPRO~YLARPRODUCT 

Dose required for efficacious application to fleas and ticks = 250mglkg 

Product a.i. content: 55% etofenprox 

2.2% pyriproxyfen 

Etofenprox is the only a.i. of toxicological concern for humans and domestic 

animals. 

Product Density is 1.035g1ml, equivalent to 0.56925g etofenproxlml 

Conversions used 

1 kg = 2.205 lbs. 

1 kg = 1000g 

1 g = 1000mg 

Dog (lbs) / 2.2051bs = kg 

Etofenprox (mg) = 0.56925g1ml x #ml x 1000mg/kg 

Etofenprox Dose = etofenprox (mg)/(kg) dog 

Highest Dose in Companion Animal Study 

758 mglkg according to study. I calculated 766 mg/kg based on density 

reported in recent product chemistry data. 

Consultant says 689.7mglkg. 

EPA reviews do not express dose in mg/kg as a regulatory endpoint. Review 

states that 2.0 ml dose for 4-20 lbs weight class is acceptable. 

In original application the registrant proposed 4-20 lbs. dog weight class. 

Efficacy data from registrant clearly show that the minimum dose required 

for efficacy against fleas and ticks is 250 mglkg. Registrant revised label on 

April 29 and proposed two weight classes: 4-10 lbs. and 11-20Ibs. 
19

Weight Class I = 4-10 Ibs. 

Labeled 

Dog Dog Product Etofenprox 

Weight (Ibs.) Mass (kg) Dose (ml) Etofenprox (mg) Dose (mg/kg) 

4 1.81 2.0 1138.50 629.00 

5 2.27 2.0 1138.50 501.54 

6 2.72 2.0 1138.50 418.57 

7 3.17 2.0 1138.50 359.15 

8 3.63 2.0 1138.50 313.64 

9 4.08 2.0 1138.50 279.04 

10 4.54 2.0 1138.50 250.77 

Weight Class II = 11-20 Ibs 

Labeled 

Dog Dog Product Etofenprox 

Weight (Ibs.) Mass (kg) Dose (ml) Etofenprox (mg) Dose (mg/kg) 

11 4.99 4.0 2277.00 456.31 

12 5.44 4.0 2277.00 418.57 

13 5.90 4.0 2277.00 385.93 

14 6.35 4.0 2277.00 358.58 

15 6.80 4.0 2277.00 334.85 

16 7.26 4.0 2277.00 313.64 

17 7.71 4.0 2277.00 295.33 

18 8.16 4.0 2277.00 279.04 

19 8.62 4.0 2277.00 264.15 

20 9.07 4.0 2277.00 251.04 
20

April 29, 2010 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

Subject: Name of Pesticide Product: ETOFENPROXINYLAR SPOT-ON FLEA AND 

TICK FOR DOGS AND PUPPIES 

EPA Reg. No. IFile Symbol: 2517-RGG 

DP Barcode: DP 376746 

Decision No.: 420097 

Action Code: R310 

PC Codes: 

From: 

128965 (Etofenprox: 55%) 

129032 (Pyriproxyfen: 2.2%) 

Byron T. Backus, Ph.D., Toxicologist n ~ r-:---0 I , ~ l = 

Technical Review Branch <f ~ "L. i - L"'" O .. A.,. \ 

Registration Division (7505P) i U-~--~ 

To: Kevin SweeneylRichard Gebken, RM 13 

Insecticide Branch 

Registration Division (7505P) 

Registrant: SERGEANT'S PET CARE PRODUCTS, INC. 

FORMULATION FROM LABEL: 

Active IngredientCs): 

128965 Etofenprox 

129032 Pyriproxyfen 

Other IngredientCs): 

TOTAL 

ACTION REQUESTED: The Risk Manager requests: 

"TOX: Review response to companion animal safety review." 

Page I of7 

Bywt. 

55.00% 

2.20% 

42.80% 

100.00% 
21

BACKGROUND: 

The material received includes responses to comments in a previous TRB review (February 24, 

20 I 0) of a companion animal safety study (MRID 47849609). In addition, there is a label (dated 

10 September 2009) which indicates a dosage rate of2.0 mL for small dogs weighing from 4 to 

201bs. 

COMMENTS AND RECOMMENDATIONS: 

I. We can accept the registrant's arguments regarding the numbers of dogs (combining Groups 

A2 and B3) treated at a 5X dosage rate with Substance II (55.16% w/w etofenprox, 8.78% w/w 

s-methoprene, 2.31 % pyriproxyfen). 

2. While we would have preferred to have two separate studies (one with puppies, the other with 

adult dogs), the current 870.7200 Companion Animal Safety Guidelines state: "The age of 

animals in the study is dependant upon label claims. If only adults (6 months or older) are the 

targeted population of animals to receive treatment, adults only will suffice. However, if a 

product is registered for use on pediatric animals (i.e. puppies ... ), the label should state a 

minimum age for this group, for example, "Do not use on puppies .. .less than eight weeks of 

age". Consequently, the product should be tested in 8 week-old animals in the companion animal 

safety study." There is the additional stipulation: "At least six animals per sex should be used at 

each dosage level." 

3. From the original study report, Group Al puppies weighed from 4.66 to 12.23 lb (2.12 to 5.56 

kg) and were dosed once with from 3.1 to 7.5 mL [or from 1.5 to 3.75X the dosage rate of2.0 

mLl Substance II, while Group A2 puppies weighed from 5.94 to 16.11b (2.7 to 7.32 kg) and 

were dosed with cumulative amounts of 18.8 to 50 mL [or from 9.4 to 25X the dosage rate of2.0 

mLl Substance II. One Group B3 adult weighed 8.95 lbs (4.06 kg) and was treated with a 

cumulative amount of 12.5 mL (5 x 2.5 mL, or 7.5X the dosage rate of2,0 mL), while the 

remaining B3 dogs weighed from 15.4 to 20.llb (7.0 to 9.1 kg) and were each treated with a 

cumulative amount of22.5 mL (5 x 4.5 mL, or 11.25X the dosage rate of2.0 mL) Substance II. 

4. The registrant has presented statistics (Table 4) evaluating the % change body weight/day for 

the different puppy groups. These statistics show no significant differences between Groups AI, 

A2, and their controls (Cl) with respect to this parameter for the periods from day 1 to 7,7-14, 

and for 1-14. 

5. The registrant has presented statistics (Table 3) evaluating the % change body weight/day for 

Group B3 and C2 (a control group) adult dogs. These statistics show a significant difference (P 

< 0.05) between these groups (with Group B3 showing reduced gains) with respect to this 

parameter for the periods from day I to 7 and from day I to 14 (but no significance for the period 

from day 7-14). This has to be considered an effect of exposure. From the original study report 

(see p. 36 ofMRID 47849609) it is noted that individual daily food consumption was not 

reported in grams but by a scoring system (Fc 1 = 0-25%, Fc 2 >25-50%, Fc 3 >50-75%, and Fc 

4> 75-100%), and it is considered unlikely by this reviewer that the resulting data would be 

robust enough to show whether or not a moderate drop in food consumption actually occurred in 

the B3 (or any) group from day I to 7. 

Page 2 of7 
22

6. The material from the registrant includes (Table 5) a listing of the ages of the puppies. Group 

A2 ranged from 73 to 106 days (mean: 87.2), with only two puppies 84 days (12 weeks) of age 

or less. Group Al ranged from 79 to 99 days (mean: 91.5), with only one puppy 84 days (12 

weeks) of age or less. Group CI ranged from 91-106 days of age. It is recommended that the 

proposed label treatment age be raised from 12 to 13 weeks (or to 3 months). 

7. The registrant has provided a comment (letter dated II March 2010) from the investigator 

regarding the behavioral effect (response?) in some puppies immediately following topical 

application. According to this letter: "Two of six puppies in Al and four of six in group A2 did 

some running in circles immediately after application. It lasted one or two circles in the pen and 

then they calmed down. No scratching or attempts at licking. No vocalization... Our 

impression was that the puppies were stimulated by the application of a liquid. They got used to 

the effect of being wet and no similar signs were seen after the following applications ... " 

However, the response also includes the following: "The question that needs is answering is 

"why only the test item groups"? .. A subjective conclusion was that the test items may have 

been cold (or felt cold, maybe as a result of evaporation?). That could be the reason why the 

pups did not react after the next applications and also why no signs were seen on the skin and 

why no other changes were recorded ... " 

Since this effect was not seen in controls, it has to be considered an effect of the test substance. 

As there were no indications of scratching or licking at the application site, no vocalization, and 

the puppies calmed down within a short period of time, it can be considered a minor effect. 

However, it is recommended that there be a statement on the label noting this effect can occur 

but that the dog should quickly calm down. 

8. The revised executive summary (incorporating the above comments) is attached. The study is 

upgraded to Acceptable. 

9. TRB concludes that the companion animal safety study in MRID 47849609 will support the 

proposed dosage rate of 2.0 mL (of the formulation containing 55% Etofenprox and 2.2% 

Pyriproxyfen) on 4-20 lb dogs with retreatment at monthly (30-day) intervals. 

Page 3 of7 
23

EPA Reviewer: Byron T. Backns, Ph.D. 

Technical Review Branch, Registration Division (7505P) 

EPA Secondary Reviewer: Ayaad Assad, DVM, Ph.D. 

Toxicology and Epidemiology Branch, HED (7509P) 

Signature: Or ~ n-t-, 

Date: 0 "" - 'L-l - 1.. 0 \ 0 

Signature: An {£~ ~ Date: ~a?ilJ:~ 

I DATA EVALUATION RECORD I 

Note: This document contains only a revised Executive Summary 

STUDY TYPE: Companion animal safety study- dogs/puppies - OPPTS 870.7200 

PC CODE: 128965- Ethofenprox, 129032- Pyriproxyfen, DP BARCODE: 371676 

TEST MATERIAL (PURITy): Cyphenothrin (8.2% w/w), Fipronil (9.8% m/w), Etofenprox 

(55.16% w/w), S-Methoprene (8.78% w/w), Methoprene (8.90% w/w) and Pyriproxifen (2.31 % 

and 2.43% w/w) 

TRADE NAME: Not provided 

CITATION: De1port, P.C. (2009) Companion animal safety evaluation on dogs of spot-on 

products containing multiple toxicants and insect growth regulators. Clin Vet International (Pty) 

Ltd., Bloemfontein, Republic of South Africa. Study No. CV 08/551, August 6, 2009. MRID 

47849609. Unpublished. 

Miller, T. (2010) Response to February 24th, 2010, Decision 420097, 2517-RGG, Re: 

Etofenprox/Nylar Spot-On Flea & Tick for Dogs and Puppies. 

SPONSOR: Sergeant's Pet Care Products, Plano, Texas 

REVISED EXECUTIVE SUMMARY: In a companion animal safety study (MRID 

47849609), groups of random-source adult (> 6 months of age) and juvenile (10-15 weeks of 

age) dogs were topically administered 3 combinations of insecticides and insect growth 

regulators or one inert substance. Two groups of three male and three female juvenile dogs were 

administered test substance IA (8.2% w/w cyphenothrin and 9.8% m/w fipronil; Batch No. 

012003-09) and test substance II (55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31 % 

w/w pyriproxifen; Batch No. 011901-09) at either IX (recommended dose) or 5X (recommended 

dose hourly for 5 applications). The test substances were applied simultaneously as adjacent 

stripes along the dorswn of the dog from behind the ears caudally to the base of the tail. Two 

groups of three male and three female adult dogs weighing 9-20 kg were administered the test 

substance IA and test substance III (8.90% w/w methoprene and 2.43% w/w pyriproxifen; Batch 

No. 011902-09) at either IX (recommended dose) or 5X (recommended dose hourly for 5 

Page 40f7 
24

applications). The test substances were applied as previously described. A group of three male 

and three female adult dogs weighing less than 9 kg was administered test substance II at 5X 

(recommended dose hourly for 5 applications). A group of three male and three female juvenile 

dogs and another group of three male and three female adult dogs were administered control 

substance IV A (Batch No. 012004-09) containing inert ingredients (not otherwise stated) at 5X 

the recommended dose. The groups and test materials they received are shown in the table 

below: 

Group 

A Group Al (n-6) Puppies (10-15 weeks) Group A2 (n-6) Puppies (10-15 weeks) 

Single application of substance IA Five applications of substance IA 

Single application of substance II Five applications of substance II 

B Group Bl (n-6) Adults (9-20 kg) Group B2 (n-6) Adults (9-20 kg) 

Single application of substance IA Five applications of substance IA 

Single application of substance III Five applications of substance III 

C Group CI (n-6) Puppies (10-15 weekS) Group C2 (n-6) Adults (9-20 kg) 

Five applications control substance IVA Five applications control of substance IVA 

Substance IA containS 8.2% w/w cyphenothnn and 9.8% m/w fipronrL 

Substance II contains 55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.31 % w/w pyriproxifen. 

Substance III contains 8.90% rnethoprene, 2.43% w/w pyriproxifen. 

Control substance IVA contains inert control substances. 

Group B3 (n-6) Adults «9 kg) 

Five applications of substance II 

The animals were observed for clinical signs of toxicity and dermal irritation for four hours postapplication and then twice daily for the duration of the study (14 days post-application). Body 

weight, body weight gain, food consumption and clinical pathology parameters (hematology and 

clinical chemistry) were measured at the required intervals. 

All animals survived to the end of the study. Immediately after treatment, one adult dog in Group 

B I (IX applications of test substances IA and III) showed behavioral changes (running, circling). 

This behavioral change was not considered treatment-related in adults by the sponsor since it was 

not observed at 5X the recommended dose. Immediately after treatment, two puppies in Group 

Al (IX application of test substances IA and II) showed behavioral changes (running, circling). 

Four puppies in Group A2 (5X application of test substances IA and II) showed similar 

behavioral changes after the first application but not after subsequent applications. These 

behavioral changes are considered to be an adverse effect. White crystallization was observed on 

the hair tips of many adult and juvenile dogs in the treated and control groups. The application 

sites of all dogs in Group B3 (5X application of test substance II) had an oily or wet appearance. 

The sign disappeared from one dog on Day + 14 but was present on all others at the end of the 

study. 

All adult dogs and puppies gained weight from Day -1 to Day 14. However, mean weight gain in 

pups in the treated groups (AI and A2) was 15% lower than the control group pups, although 

statistics evaluating the % change body weight/day show no significant differences between 

Groups AI, A2, and their controls (CI) with respect to this parameter for the periods from day I 

to 7, 7 to 14, and for I to 14. The mean weight gain in the treated adult animals (Groups BI, B2 

and B3) was decreased (30-99% as compared to the control group). The difference relative to 

controls was largest in the smaller adult dogs in Group B3 (99% decrease as compared to the 

control group). Statistics evaluating the % change body weight/day for Groups B3 and their C2 

controls show a significant difference (P<0.05) between these groups (with Group B3 showing 

Page 5 of7 
25

reduced gains) with respect to this parameter from day 1 to 7 and from day 1 to 14 (but with no 

significance for the period from day 7 to 14). Individual food consumption was not reported in 

grams but by a scoring system (Fc 1 = 0-25%, Fc 2>25-50%, Fc 3 >50-75%, and Fc 75-100%) 

and it is considered unlikely by this reviewer that the resulting data would be robust enough to 

show whether a moderate drop in food consumption occurred actually occurred in the B3 (or 

any) group from day 1 to 7. No treatment-related hematology or clinical chemistry changes were 

observed. 

Seven animals (one adult, 6 puppies) showed behavioral changes (characterized as running and 

circling) immediately after the first application of the test substance. They were all exposed 

(applied "simultaneously") to test material IA (8.20% cyphenothrin, 9.8% fipronil, either in 

combination with material III, 8.90% methoprene and 2.43% pyriproxyfen, for the one adult, or 

in combination with material II, 55.16% etofenprox, 8.78% methoprene and 2.31 % pyriproxyfen 

for the puppies). The registrant has provided a comment (letter dated 11 March 2010) from the 

performing laboratory regarding this response: "Two of six puppies in Al and four of six in 

group A2 did some running in circles immediately after application. It lasted one or two circles 

in the pen and then they calmed down. No scratching or attempts at licking. No vocalization ... 

Our impression was that the puppies were stimulated by the application of a liquid. They got 

used to the effect of being wet and no similar signs were seen after the following applications ... " 

However, the response also includes the following: "The question that needs answering is "why 

only the test item groups"? ... A subjective conclusion was that the test items may have been cold 

(or felt cold, maybe as a result of evaporation?). That could be the reason why the pups did not 

react after the next applications and also why no signs were seen on the skin and why no other 

changes were recorded ... " 

Since this effect was not observed in controls, it has to be considered an effect of the test 

substance. As there were no indications of scratching or licking at the application site, no 

vocalization, and the puppies calmed down within a short period of time, it can be considered a 

minor effect. However, it is recommended that there be a statement on the label noting this 

effect can occur but the dog should quickly calm down. 

The response from the registrant includes a listing of the ages of the puppies. Group A2 ranged 

from 73 to 106 days (mean: 87.2), with only two puppies 84 days (12 weeks) of age or less. 

Group Al ranged from 79 to 99 days (mean: 91.5), with only one puppy 84 days (12 weeks) of 

age or less. Group C 1 ranged from 91 to 106 days of age. It is recommended that the proposed 

label treatment age be raised from 12 to 13 weeks (or to 3 months). 

It is concluded that although there were possible effects, which consisted of short-term 

running and circling in 2/6 IX and 4/6 5X puppies - not seen in their controls - following 

the first application of the test material and reduced weight gains in 5X adult dogs, these 

were minor. In particular, there were no indications that the puppies were in any pain or 

distress, and a similar response was not seen in those animals in which there was 

reapplication. It is recommended that there be a statement on the label noting that the 

puppy or dog may have a short-term response. 

Page 6 of7 
26

This companion anipJaI safety study in male and female random-source adult dogs and puppies is 

reclassified as Acceptable/Guideline and does satisfy the guideline requirement for a 

companion animal safety study (OPPTS 870.7200) on 4-20 Ib dogs for a formulation containing 

55% Etofenprox and 2.2% Pyriproxyfen with the proposed dosage rate of2.0 mL with 

retreatment at monthly (30-day) intervals. 

COMPLIANCE: Signed and dated GLP, Quality Assurance and Data Confidentiality 

statements were provided for Clin Vet International. Pathcare Veterinary Laboratory, which 

conducted the hematology and clinical chemistry analyses, is not GLP accredited but is ISO 

15189 certified. 

Page 7 of7 
27

DP BARCODE No.: 037674" File Symbol No.: 2517-RGG PRODUCT '-lAME: Etofenprox 

INylar Spot-On Flea and Tick for Dogs & Puppies COMPANY: Sergeant's Pet Care Products 

Incorporation 

DATE OUT: 291 APR 12010 

SUBJECT: 

FROM: 

TO: 

FEE.PRODUCT CHEMISTRY REVIEW OF MP [] EP [X] 

FOOD USE [] NON-FOOD USE [X] INTEGRATED FORMULATION [] 

PCC: 128965 & 129032 DECISION No. 420097 ACTION CODE: R310 

Shyam Mathur, 

Product Chemistry Team Leader 

Technical Review Branch/RD (7505P) 

Kevin Sweeney 1 Richard Gebken, PM 10 

Insecticide Branch 1 RD (7505P) 

INTRODUCTION: 

The product chemistry data cited for the proposed end use product was reviewed previously (see 

PCR dated February 1,2010. DP371682) by TRB and the cited data was found not acceptable. 

TRB also concluded that the proposed product is not identical to cited product with Reg. No. 

69332-3 from product chemistry point of view. The registrant was asked to provide product 

specific (group A & group B) chemistry data for the proposed end use product. 

After conversation with the Agency, the Registrant on April 28, 2010 submitted the revised 

product chemistry data with MRID Nos. 480584-01 & 480584-02 corresponding to group A & 

group B guidelines respectively. The registrant also submitted a revised basic CSF (dated April 

28, 2010). TRB has been asked to determine the acceptability of the product chemistry data 

submitted for the proposed end-use product and determine the acceptability of the proposed 

revised basic CSF dated April 28, 2010. 

SUMMARY OF FINDINGS 

1. The proposed end-use product contains , containing 

of etofenprox] and containing 

pyriproxyfen] as the active ingredients with label claim nominal concentrations of 55.0% and 

2.20% respectively. 

2. The proposed CSF for basic formulation (dated 04-28-10) is filled out completely and correctly. 

The nominal concentrations of the active ingredients concur with the product label claim nominal 

concentrations. The CSF is in compliance with PR Notice 91-2. All the inert ingredients present in 

the formulation have been approved by the Agency for the proposed uses (IIAB, 04-29-10). 

3. The standard certified limits have been proposed for the active ingredient and for the inert 

ingredients which are in compliance with the standard certified limit table set-forth in 

40CFR§158.350(b)(2). The data submitted corresponding to guidelines 830.1550 (product 

identity & composition) and 830.1750 (certified limits) satisfy the product chemistry data 

requirements of 40CFR §158.320 and §158.350 respectively [MRID No. 480584-01]. 

4. The data submitted corresponding to guidelines 830.1600 (description of material used to 

produce the product), 830.1650 (description of formulation process), 830.1670 (discussion on the 

formation of impurity) and 830.1750 (certified limits) satisfy the data requirements of 40CFR 

§158.325, §158.335, §158.340 and 158.350 respectively [MRID No. 480584-01]. 

1 

*Product ingredient source information may be entitled to confidential treatment*
28

DP BARCODE No.: D376745 File Symbol No.: 2517-RGG PRODUCT NAME: Etofenprox 

/Nylar Spot-On Flea and Tick for Dogs & Puppies COMPANY: Sergeant's Pet Care Products 

Incorporation 

5. The product chemistry data cited corresponding to guideline 830.1800 (enforcement analytical 

method) satisfy the data requirements of 40CFR§158.355. The GC-FID method was used for the 

determination of the active ingredients Etofenprox and Nylar in the formulated product using 

internal standard quantification technique. The method employed HP-1 Methyl Siloxane Capillary 

column, 25 m x 200 ~m x 0.11 ~m (particle size). Dibutyl phthalate was used as an internal 

standard [cited MRID No. 461613-01]. 

6. The product chemistry data submitted corresponding to the guidelines 830 series group B 

(physical-chemical properties) satisfy the data requirements of 40CFR §158.31 O(e), except for 

the guidelines 830.6317 & 830.6320. The registrant stated that the studies corresponding to the 

guidelines 830.6317 (one year storage stability) & 830.6320 (corrosion characteristics) will be 

submitted on completion [MRID No. 480584-02J. 

CONCLUSIONS: 

The TRB has reviewed the revised product chemistry data submitted for the proposed end-use 

product and has concluded that: 

1. The proposed CSF for basicformulation (dated 04-28-10) is acceptable and will supersede the 

basic CSF (dated 09-10-09). 

2. The data submitted corresponding to guidelines 830.1600 (description of materials used to 

produce the product), 830.1650 (description of formulation process), and 830.1670 (discussion on 

the formation of impurity), 830.1750 (certified limits) and cited 830.1800 (enforcement analytical 

method) are acceptable. 

3. The product chemistry data submitted corresponding to guidelines 830.6302 (color), 830.6303 

(physical state), 830.6304 (odor), 830.6314 (oxidation/reduction), 830.6315 (flammability), 

830.6316 (explodability), 830.7000 (pH), 830.7100 (viscosity) and 830.7300 (density) are 

acceptable. 

4. The registrant must submit the results of studies corresponding to guideline 830.6317 (1 year 

storage stability) and 830.6320 (corrosion characteristics) which are under progress. It is 

recommended that the observations should be made at 0, 3,6, 9, 12 months intervals. 

2 
29

DP BARCODE No.: 0376740 File Symbol No.: 2517-RGG PRODUCT NAME: Etofenprox 

lNylar Spot-On Flea and Tick for Dogs & Puppies COMPANY: Sergeant's Pet Care Products 

Incorporation 

Product Chemistry Data (Series 830 qroup A & qroup B) 

Subgroup A Data Reguired MRID No. 

Fulfilled 

830.1550. Chemical Identity (proposed basic CSF) A 04-28-10 

830.1600. Beginning Materials A 480584-01 

830.1650. Formulation Process A 480584-0t 

830.1670. Discussion of Impurities A 480584-01 

830.1700. Preliminary Analysis NA 

830. t750. Certified Limits (basic CSF) A 04-28-10 

830. tBOO. Enforcement Analytical Method A CITed 46t6t3-01 

Data Reguired Value or Qualitative MRID No. 

Subgroup B Fulfilled Descrigtion 

830.6302. Color A Light yellow 480584-02 

830.6303. Physical State A Liquid " " " 

830.6304. Odor A Sweet mild floral " " " 

fragrance 

830.63 t4. Oxidation/Reduction Action A None " " 

830.6315. FlammabilITY A t99.94'F (>93.3 'C) " " " 

830.6316. Explodability A Non-explosive " " 

830.6317. Storage stability I t year in progress " " " 

830.63t9. Miscibility NA 

830.6320. Corrosion Characteristics I t year in progress " " " 

830.632t. Dielectric Breakdown Voltage NA 

830.7000. pH A 9.35 @ 25'C " " " 

830.7 tOO. Viscosity A 39 cps @ 20'C " " 

830.7000. Density A 1.035 glee @ 20'C " " " 

830.7520. Particle size, fibre length, & diameter NA 

distribution 

Explanations: A = The Requirements Were Fulfilled; N = The Requirements Were Not Fulfilled; NA = Not Applicable; G = 

Data Gap; U - Requires Upgrading; I = Incomplete or In Progress; W = Waived. 

3 
30

Efficacy Review 

Date: April 23, 2010 

Efficacy Reviewer: Clayton Myers, Ph.D., Entomologist, RD-IB 

~~2-""'·IO 

Risk Manager Rev.: Kevin Sweeney 

Products: EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies 

EPA Reg. #: 2517-RGG 

A.I.'s: Etofenprox (55.0%), Pyriproxyfen (2.2%) 

Decision #: 420097 

DP#: 376747 

Submission: Rebuttal, correspondence 

MRIDs: None 

GLP: No 

Summary of Agency's previous product performance review(s): 

I. Various studies were submitted in support of a pet product with a retreatment interval of 

30 days, intended to protect small dogs from fleas and ticks. The data submitted did not 

support this claim, because at the appropriate dosages (which match the label dosages), 

efficacy was only demonstrated for 2-3 weeks for fleas and ticks, with some variability 

between studies. 

2. Ultimately, the underlying conclusion of the data is that a 250 mglkg dosage is required 

to provide adequate protection against fleas and ticks. For the most part, dosages under 

this threshold failed to offer adequate protection throughout the 30 day retreatment 

interval 

3. Claims against black legged ticks (deer ticks), Ixodes scapularis were only supported by 

data going out to 3 days after treatment. 

4. Claims against mosquitoes were not supported as the submitted study treated dogs at 

dosages exceeding those instructed on the product label. 

5. Claims against flea eggs/larvae were not supported by any submitted data for 

pyriproxyfen. 

Summary of Registrant submission/rebuttal: 
31

1. For flea and tick data all data from dog studies was pooled and re-analyzed. When dogs 

that received treatments above the proposed label dose (i.e., >2.0 mL per animal) were 

eliminated from the analysis, flea efficacy was demonstrated from 9-29 days, with a 

mean protection time of 20 days. Out of 18 dogs, 11 were adequately protected for 16 

days or less. For tick efficacy, the mean protection time was 26 days. Out of 18 dogs, 10 

were protected for 23 days or less. 

2. For mosquitoes, the registrant stated that only small dogs were used (hence, biasing the 

dosage toward dogs with a higher rate of ai/kg) because the available Gerberg type 

mosquito cages were not large enough to accommodate dogs ofiarger size. The 

registrant cites previous reviews where similar data was used to support a similar claim, 

including dogs over 60 lbs. Finally, while they concede that a controls or kills claim is 

not supported, they propose to retain a claim of repellency/prevention of blood feeding by 

female mosquitoes. 

3. For black legged ticks, the registrant cites a previous protocol that was used to support a 

30 day claim on another label, and proposes a retention of an open-ended controls claim 

for black legged ticks, since no explicit '30 day' claim is being proposed. 

4. For the pyriproxyfenlIGR claims (i.e., kills flea larvae, eggs, breaks flea life cycle), the 

registrant cites previously submitted data that supported a similar claim on a product 

containing a smaller nominal concentration of pyriproxyfen a.i. than the submitted 

product. 

Entomologist's ObservationslDiscussion: 

I. The registrant's ultimate conclusions after re-anaylsis do not substantially differ from the 

conclusion reached in the previous review. At a 2.0 mL dose, efficacy against fleas is 

supported for 2 weeks and ticks for 3 weeks. Because this product's use directions 

indicate retreatment on a 30 day interval, the implied duration for all control claims 

should be 30 days. In order to support a 30 day claim, the registrant would have to 

increase the dosage applied, based on the data submitted previously, which indicate that a 

dose of approximately 250mglkg is necessary to provide adequate 30 day control of both 

pests. 

2. The availability of mosquito cages is a consideration that should be taken when designing 

efficacy studies. A number of much larger mosquito cages are available for conducting 

these types of mosquito exposure studies, as the Agency has reviewed data where 

significantly larger dogs were used for similar studies. Prior acceptance by the Agency 

of inadequate data to support such claims is not an adequate justification to repeat the 

same mistake again in this instance. 

3. Open-ended controls claims are typically not allowed on any pesticide product with 

claims against pests of public health importance. Any claim of residual control must be 

qualified by an appropriate duration of control that is supported by the submitted/cited 

data. In the case of a pet spot on, the retreatment interval is considered an implicit 

duration of control claim. Consumers buying this product, and treating their pets on a 30 

day retreatment interval will expect the product to adequately protect their pets for that 

intervaloftime. Therefore, data demonstrating control of black legged ticks for 30 days 

would be required to support a controls claim on this pet product. Since the submitted 

study was terminated at 3 days after treatment, it does not support such a claim. 
32

Furthermore, as with point number 2, prior acceptance by the Agency of inadequate data 

to support such claims is not an adequate justification to repeat the same mistake again in 

this instance. 

4. The dose-titration study cited (MRlD 46346601) submitted in support of a similar IGR 

claims on another product and was found to be acceptable. This study supports IGR 

claims (i.e., kills/controls flea eggs and larvae, breaks the flea life cycle, etc.). 

Entomologist's Label Recommendations: 

1. Placement of2 or 3 week claims on the label (for fleas and ticks) would be contradictory 

to the reapplication directions for 30 days. For such pet products, a 30 day retreatment 

interval implies a time duration for control of listed pets. In this case, efficacy 

considerations may be in conflict with animal safety. This labeling decision is deferred 

to the Risk Manager Reviewer and the Product Manager. 

2. Claims against Mosquitoes are not supported for the application rate of 2.0 mL proposed 

on the current label. The dosage would have to be raised to support this claim, and the 

claim would only be for repellence/suppression of mosquito blood feeding. These claims 

must be removed from the product label. 

3. Claims against black legged ticks, deer ticks, Ixodes scapularis, or ticks that may 

carry/transmit Lyme Disease are not supported and must be removed from the label. 

4. While IGR claims are supported against flea eggs/larvae, the acceptance of this claim is 

contingent upon whether or not any general flea claims will be allowed at all, per point 

number 1. This labeling decision is deferred to the Risk Manager Reviewer and the 

Product Manager. 
33

April 29, 2010 

Richard Gebken 

Product Manager 10 

Document Processing Desk 

Office of Pesticide Programs (75041') 

U.S. Environmental Protection Agency 

Room S-4900, One Potomac Yard 

2777 South CJystal Drive 

Arlington, VA 22202-450 I 

Subject: Submission ofa Response to EPA Regarding Etlicacy and Labeling 

Etofenprox/Nylar Spot-On Flea and Tick I'or Dogs and Puppies (25 I 7-RGG) 

Dear Mr. Gebken: 

On behalf of our client, Sergeant's Pet Care Products. Inc. (Sergeant's), Exponent is providing 

additional information in response to a telephone call with Kevin Sweeney dated April 29, 2010 

regarding ellicacy data and proposed labeling telf Sergeant's Etofenprox/Nylar Spot-On Fica and 

Tick Products for Dogs and Puppies (EPA Filc Symbol 2517-RGGl. 

Based upon our discussions it is Sergeant's understanding that the available efficacy data Oil file 

with EPA for etofenprox support etlicHcy claims against fleas and ticks it)r four weeks when a 

dose of::::250 mg/kg is achieved. Therefore, Sergeant's proposes to change the current pending 

label that proposes a single 2.0ml dose for dogs weighing 4-20 pounds to two di ITerent proposed 

doses. The new proposed doses t(lr do gs are: 

4- I 0 pounds: 2.0 ml 

10-20 pounds: 4.0 ml 

Based on the above dose configurations, Sergeant's confirms that all dogs will receive :::250 

mg/kg of etofenprox, which will allow Sergeant's to claim t(lLir week efticacy on the product 

label. Please see Enclosure I tor a summary table that identities the calculated amount of active 

ingredient per pound of dog and a comparison of the dose versus the companion animal safety 

study (CASS) rates. The summary table confinns that 2.0 ml applied to 4-10 pound dogs applies 

636.6-254.6 mg/kg, respectively and that these rates are well within the I x C ASS rate of 689.7 

mg/kg. It also confirms that 4.0 ml applied tol 0-20 pound dogs applies 463.0-254.6 mgfkg, 

respectively and that these rates are wcll within the Ix CASS rate of689.7mg/kg. 

Based on this information we have updated the proposed product label to include the tollowing: 

• Two application sizes (2.0 and 4.0 ml) and corresponding label language; 

• Changed the age of puppies from 12 weeks to 13 weeks: 
34

• Added four alternate brand names: 

• Increased the efficacy claims for fleas and ticks to four weeks (30 days); and 

• Added proposed language warning of possible temporary effeels (see helow for proposed 

language ), 

Based on our discussion today with EPA. Sergeant's has added the following proposed label 

language: 

"[Some dogs may startle when a room temperature squeeze-on is applied.]fSome dogs may 

experience temporary startle effects when a squeeze-on is applied,][Somc dogs may experience 

temporary startle effects when squeeze-an's arc applied. r 

We believe the above language addresses EPA's concern related to the possihle effects noted in 

the CASS study. 

Please tind enclosed a copy of the new proposed label in track changes (Enclosure 2) and a copy 

with all comments accepted (Enclosure 3). 

Sergeant's requests that EPA review the new proposed label and supporting summary tahle and 

in support of the registration ofSergeanfs EtofenproxiNylar Spot-On Flea ,md Tick Products tc)r 

Dogs and Puppies. 

I r you have any questions or 'need additional injormation. please contact me at 202-772-4932 or 

30J-908-J J8J (cell). 

Sincerely. 

I 

! 

James Messina 

Authorized Representative of 

. Sergeant's Pet Care Products. Inc. 

Enclosures 

cc: Kevin Sweeney. EPA 

Kelly Hoskins. Sergeant" s 

Larry Nouvel. Sergeant" s 

Rick Tinsworth. Exponent 

--"""' 
35

Enclosure I 

Dosage Chart for Sergeant's Proposed Etofenprox-Containing 

Squeeze-On Lahel for Small Dogs 
36

TABLE 3 

Dosage Chart for Sergeant's Proposed Etofenprox-Containing Squeeze-On Label for Small Dog

Justification Extrapolation from CASS CV 08 55 

Dog weight Active Etofenprox CASS dose Pyriproxyfen CASS d

Label potency 55.0% rate factor 2.2% rate fac

@UCLofCSF 57.8% 1X 5X 2.3% 1X 

puppies 689.7 3796.3 ·28.9 

adults 1759.0 2.1 

Ib kg mL mg/kg 

4 1.8 2 636.6 25.5 

5 2.3 2 509.3 20A 

6 2.7 2 424A 17.0 

7 3.2 2 3638 14.6 

8 3.6 2 318.3 12.7 

9 4.1 2 282.9 0.16 11.3 

10 4.5 2 254.6 0.14 10.2 

11 5.0 4 463.0 0.26 18.5 

12 5A 4 424A 0.24 170 

13 5.9 4 391.7 0.22 15.7 

14 6A 4 363.8 0.21 14.6 

15 6.8 4 339.5 0.19 13.6 

16 7.3 4 318.3 0.18 12.7 

17 7.7 4 299.6 0.17 12.0 

18 8.2 4 282.9 0.16 11.3 

19 8.6 4 268.0 0.15 10.7 

20 9.1 4 254.6 0.14 10.2 

Potency is upper certified limit on Confidential Statements of Formulae 

all others based on adult CASS mean group dose rates 
37

Sergeant's Pet Care Products, Inc. Master Label 

i-.'! <:\PDL~~}Ji1 EPA Reg.. Nn, 2517~j{{_;_(_~ 

Information in I I is optional. Page I 01'4 EPA SAL 

FRONT PANEL DOG SQUEEZE - ON 

Pyriproxyfen (NVLARj, Etofenprox 

Edltor$ NOh:" {Optional proposed leXI appears In bra.::~cls the final label tna~ Include "ome Of atl of the optlonallcxl! 

ETOFENPROX/NYLAR SPOT-ON 

FLEA AND TICI( FOR DOGS AND PUPPIES 

{ABN: Sl."fgcanfs Toy Br.:cd Flea and Tick Squeeze-On I 

{ARN: Sergeant's Toy Breed Flea and Til:k Sqllceze·Qn lor small ore-cd dogs) 

{ABN: Sergeant's Toy Breed Flea and Tick Squce7C-0n for small and toy breed do!]..<;) 

{ABN: Sergeanrs Small Breed Fica and Tick Squcezc~)nJ 

r ABN: Sergeant's Small Breed Flea and Tick Squcezc·.()n for small breed dogs} 

{ABN: Sergeant's Small Breed Flea and Tick Squcezc-On for small and to), breed dlJgs} 

{ARN- SentryPro Toy and Small Breed Flea and TIck Squeeze-On} 

~ ABN: ScntryPro Toy and Small Breed Flea and Tick Squeezc-On ror dngs I 

\ARN: SClltryPro T(lY and Small Bn,"Cd fica ilnd Tick Squeeze-On filr small and toy breed dugs] 

{ABN' SentryPro Small Breed Flea and Tick Squcc7c-On for IAlgsj 

j AnN SemryPm Small Breed Fka altd Tick Squee:rc-On filr small brl!cd dogs 1 

tARN: SentryPro Smail Breed Flea and TIck Squee7~, .. On ror smail and OJy br\..-'Cd dogs) 

l \i{,\ \crgl',Ill(" Ii I \ ,d\:,,'_~-::i .[.1 l~"l All,J J ;,.:h \lilJ..:C/;:-I.)1l i(,r ! Id~"- L,~nd PIolPPk·\.!; 

: ·\il:,_ \<:rgl.':[Il{ ~J;. J_ \,'-'\.c U Ii!. I il',) ;llIJ Ixk \(!ii\.:Ch'-}}f! 1;'1_1 )llS-'- ('lll~ PIIPPI\."!; 

~ __ ll}_~_~~;:_LUr';.tr -'--~_~_ i.L.l L_di.Lki.l.;W!J.J_!!'_~ _2~l!i<;.l: ;:~« . 1)1 I, .. 'I .• 1), ~"o~. !.c@! L'!!l!1?J ~.~ i~ 

l.:\H~~. )S.llll lj)i.;.~._SULiJDJ1J!-!.;I.Ar\\lJ_!,,·k_. ':~lm·\.~~~:( __ I.1.1 J!.!£ .. P:'2.': L~! ~dJ )1'l'I'IC'~ .' 

lOne Applicatinn:{choose frnm the followillgJ! 

• [\~itb nylar)q 

HOnc) (Two) (Three) (Follr) (XX) Appileations] 

I BonU$] J.'i~';, mme lmlw incJtldes 4 tuhcs! 

lodorlessl Junsccnlcdj iIragranec freel 

lDries quickly] 1(>tJick drying formula I [QUIck Dryingl 

[Squeczco·Oullstays on and dnesn °t rub 0111 

ISpreads b)' tising the dog's natural skin oilsj 

• IBreaks thc flea life cycle fi)r up to (70 Days) (9 Wceks)j 

• lControls rcinfcstalion fhr up to (7f) da)'5) (9 wCl!ks)! 

[For Kly breeds 4-.LO Ibs.] 

I For small br\..'CdsJi'-20 Ibs,] 

• [For toy and sOlall hrct:dsI4-1(IHlii-20j Ibs.l 

• [Specially lonnulatcd fbr small hrecdlsl dogs I 

• [Spccmlly fonnulated for toy brccdls] [dogsl] 

ISpcclally fimnulatcd lor [tny breedls]I and l~mall breedlsll dogsl 

lToYllandj [SOlal!] hreed ronnula] 

rCcntle protection fiJr [toy] [small I breed dogs J 

• 15 Way Protectionl 

• lControls Ilea'>, ticks, flea eggs & larvael 

I Kills FI':llS, Ticks, !--lea Eggs, Larvae] [and II repels mosqllitoes j fi.lr up to olle month J [fi}r up to 4 ~t-eeks JJ 

• Wka, tick, nell. cgg and larvae controll 

• lKills Ilea'> aud ticks for up to L'fl days]l.:-i weeksll 

• f"-ills ticks [for up to ~,I) daysj 1.:-1 wceksl1] 

• JKiIls TicksJ [Berore they can} JthatJ [transmIt Lyme Disease 

[Kills laduJt] fleas for upto IJ!.; daysl!.:! wecksJ] 

• [Kills Flca~ and Ticks] Jfor up to k"iil daysl!;1 weeksl] 

• [Fica Tick and Flea Egg ProtectionJ 

• I Repels mosquitoes I ror up to one montJJ] ] lor up to 4 -'>-'.'Ccksl! 

I Fka and Tick ~'{)ntrol J 

• [Kills Ilea'> that may cause flea allergy dermatitis, and flea bite anemiltJ I fbr up to I,:~(I dayslll \\-eeks]] 

• ] Kills Flea Eggs and Larvae Ulr up to (9 weeks) ( 70 days) (per appilcatlOn)1 

I Detebed: 10 

Delel2d: S,"!I~"ll1~_~O,~,. 

Deleted: xx 

Defeted: "2 

Oefeted: 4 

Deleted: 21 

Deleted: :> 

Deieted: 11 

Deleted: 3 

Deleted: 2t 

Deleted: 3 

Deleted: 21 
38

Sergeant's Pet Care Products, Inc. Master Label 

"."-'J ~ WnL_~QEi EPA. Reg No. 2517~!~(_J(!. 

Ini(!rmatioll in I I is optional. Page 30(4 EPA SAL 

BACK PANEL DOG SQUEEZE-ON 

Pyriproxyfen (NYLAR), Elofenpro. 

{Product Name} 

REAl) E~TlRE LABEL BEFORE E,KIf [S~: 

PRECAVTIO:,\,,,RY STATElHE:\TS 

HAZARDS TO H[l'IA~S AND DOMESTIC ;\1\I\1..\I..S 

CAliTlON 

JIAZARDS TO II {;:MA~S: Causes moderate eve irritation. Avoid contact \vith eves and clutlrim.!_ W;l<;h 

thoroughly with soap and water after haJldlmg ~d ix=ij)rc eating, drinking, chc\.\illg gum, or using'i()hacco. 

HA7ARDS TO DO.'1ESTIC ANI\IALS: F,)r External Usc On!} Do no! usc on dogs under 1..-: weeks of age. 

(,onsult it veterinari:m bel()fC using this prnduc! Oil debilitated. aged. mcdicatcd. pregnant. Hr nursing anim:dj; 

SensitivitIes may (!CC{lf ailtr U~lng ANY pesticide product for pets, [fsigns orscllsitivit) occur, hathe your pet with 

mild soap and rinse with large anroullts of water If signs continue, conSilII a \-dcrillllrlan Immediately_ 

llW~ -,,;)flk \'iH.:n ;. ",;\'Ill \(liiI'CI ;i!li,C "'lHC~·/<:-'·H. I- "PP(lc-ci it'.,! '!11~' ), '.ie- :1!;I~, ..:\j1<.:r;':Il(C kllif','r;Jf:'. 

"""I"'JJ,,i'.""'"' L'''''''''':''':'J', ,'J'T' "" ,JL"!' 'Ie.'."'], !IF\~ "·'II~'J ~C.;.I":l· t_':!.i:'f':.'f:il). ,:1 ~lnk .. : 111'<\ ,:.\\!.~C.I.l. _,:q!!U;/~·.: 

"\1. '- .;()';_ ~!l~~\ I,~\t J 

FIRST AI[) 

IF I~ EYES: Hold eye open and rinse slowly and gently with Water filr 15~20 minutcs. Remove contact lenses, Ir 

pn "'SCnt. .. after the first 5 minutes. and thell continue rinsing. Call a POi$(lO cOnlTOI center or doctor for treatment 

advice Ilavc the- product container or labcl l\ith YOll when calling a poison cuntrul center {Ir dOl-1m or g\)ing for 

trea(ment. Ynu m:ly also contact 1-800 .. 781-4738 1(lr emergency medical treatment infiJrmation. 

PI-IYSICAL OR ClIEMICAL HA7ARf)S: Combustible; 1)(1 nil! use or St{lrc ncar heat or Opell namc. 

OIRECTIO~S FOR [Sf: 

It is a violation of Frderal Law to usc this product in a manner incon!iistcnt with its labeling. 

Do nHt get this product in your pet's eycs or mouth, Do Hot apply more otlcn thaJl lom.:c a month Iionee ev~ry 30 

daysl tlse only on Dogs. FOR EXTERNAL CSE ON DOGS ONLY Do not usc on puppiesle!is than l.' ',>,'1.:cks 

of age. Weigh your dog !H he sure Y(Hl are applying the right dose lormulated for thc weight Ill' yuur pct. Do nOl 

trC<lt your pet with more than one pesticIde pwduct at a rime. Over dosmg your wlimal can result in serious illucss 

ami even death. Best ifuscd ycar round. 00 not bnthe pct with In the ftrst 24 hours aticr squce7e-on ha<; been 

applied. f f(lUscholds \\ith more thmlllnc pet should no( allow dogs (Ir cats to groom each other until solution has 

dried. DO NOT USE ON CATS or ammals other than dogs. Separate the treated dog trum all other dogs and cats 

filr 24 hOllIS aftcr treatment has been applied. Cats or dogs that actively groom or engage in dose physical contact 

with treated dngs oray be:lt risk orsenous harmful elTccl<; I ryour dog is exhibiting signs o/'and/or arc being treated 

for skin dermatitis. talk to your vet before applying any topical flea and tick control product. Sensitivities ntayoccur 

after using ANY pesticide product on pets. It )s recommended to separate treated dogs from other household pets for 

24 hours after treatment ha~ hcen applied. Ifsigns of sensitivity occur. bathe YOllT d{'g v.r1th mild soap and nnse \\-ith 

large- amounts of\vater. 

FOR liSE 01\ DOGS: 

Wt'ighing 4 T0.t0 I,BS. - Apply contcnts of one (2,0 mL) tube Ina!} oflProduct i'ameIlSqueeu-tlnl as a spot 

high on the back of the dog's ncek behind it" head and apply as a stripe to a POlOt mid\\-ay between the neck and the 

tail 

! Deteted: 10 

I"_~: ~~!~::b:,!}{)0') 

\ Deleted: XX , 

Deleted: 1 

Deleted: 2 

I 
39

Sergeant's Pet Care Products, Inc. Master Label ,,:()~'\nrJL;UJn EPA Reg. No, 2517-F(,()~ 

In(bmlut}()}) in t J is optionaL Page 2 of 4 EPA SAL 

!'Prcvcnts flea eggs from developing into biting adults for up to (9 weeks) (70 days) (per application)] 

• lRcpcts mosquitoes that may tran<;mit rhc-artwoTm} [Wes\ Nile vlruS! [from fcedmg on dogs1 I for up to [one 

monthJ pO daysJ[ 4 weeksll 

• 

p<epels MO$quitoesJ I Prevent.:; mosquttoes that tJdnsmit West Nile viru..;; and heartWOmll1 from feeding on 

dogs] [t~)rlIP to lone momhl pO daysJf 4 weck~JJ 

FRONT PANEL DOG SQUEEZE-ON 

Pyriproxyfen (NYLAR). Etofenprox 

ACTIVE INGREDIENTS: 

Ewfenprox, 

Pyrirroxylcn .... 

OTHER INGREDIENTS:. 

55.Q()O/o 

2.201% 

1~Jli~Q 

TOTAL fOO.OO% 

INyJarK is a reg"!stered trademark of ,\kLaughlin Gonnky King Company! 

KEEP OUT OF REACII OF CHILDREN 

CAUTION 

See IBackl!orliSidel Label PanellsJ for Additional Precautionary Statements 

NET CO~TE:-';'rS: 

[Om'j jTwoljThreejjf'ourjjFivcj [Six I 2,0 mL. applicators. Uor small dogs 4 to.1.0 lh.\'! 

lii.llt'l ! 1 \\o!11Il1'{'{'I!I'1)}il'!!HH!f~i\! .t.n 1111 applit~\t()r' .... W,r \I1wll dOt:\ {fl Io J(j 11>\1 

Dcleted: 10 

0eJet:ed:. S~lembe12009 

Deleted: xx 
40

Sergeant's Pet Care Products, Inc. Master Label I 

,;>! /~N.!l.~_(lj(l EPA Reg. No. 2517'T{( J5_~ ! 

Inlomtation ill 1 f is optional. Page 4 of4 EPA ~~_" __ ~~ __ ~ 

(INSERT DIAGRA~1 THAT DEPlers APPLICATIO'i Of PROOFCf O~ l'UE DOG) 

H)H r:-.r 0\ 00(,:--: 

\\ (oj"hi!l(t Iii TO 2(1 I Jj.~~)h .~~:E.!:.~!..'{...:.:L~L!.!!LlJi!.!::~.L:_,:!..!:1 ,~Jlr.U!ili~r.!_~,!!!.fJlSi1~!_t:Y_£:,"~!lL!..':._;!_::i2~\' 

hl,\}<,r;.l1 Ih", b~!~-L ;," 1)1<.: )'-'.!s';. 11\.:.:), h,'\)\\1(3 I\'. l)"'.',t(j .1:1(: ;\1']'):' ,j, a ,t) T': 1 .\ pl>Jm. T!!id".;.1.; 11c'",:.::":1\ tho: w:"t. ;'1:" :!!~­

'<Iii 

LL'\SLRT DL\(, rt,\ \1 nl \.T nu' j( T'I \I'I'I.IC \T!O .... 01- PIH)lg.J...:L~L~lJ.J.L~~_Qiil 

HOW TO ;\ PPL Y: 

Relllove prodUL1 tube {VIal} frOnllhe packag.e. Holding lube /\'/0// ~",ilh ntJlchcd cnd pointing up and away from the 

face and body cut or Icar ofl'jhe naml\\' end at the nOlt.:'hes. While holding the animal with one hand. usc dIe OIher 

hand tn apply the solUlion. Invert the lObe {vlalj and (1St' the narrow end 10 part the anintal's hair whik~ gently 

:;qucczjng to apply to the animaf"s skin. Iiold the animal for a fcow seconds to give the solution time til be ahsoro.::d 

illw thc animal's coal. When finished. \\Tap the tube jVJaI! in paper and put into lhe tra"h. 

Deleted: 10 
41

Sergeant's Pet Care Products, Inc. Master Label 

':_::.:-'Dr)) __ J:PJ~1 EPA Reg. No. 2517-l<t,I(>, 

Illfomlation iul I is optional. Page 5 of4 EPA SAL 

BACK PANEL DOG SQUEEZE - ON 

Pyripro.yfen (NYLAR). Etofenpro. 

STOR",GE A~D I>ISPOSAL 

Du not cOlltaminalc waler. food or feed h~ s.hlragc llr uisposnl. 

PESTICIDE STORAGE: Do not remove tube from the pack until ready 10 USc, SWrc in a cool (bdtW, 25"C) dry 

place out ofrcach of children. 00 not refrigerate Protect from direct sunlight. 

PESTICIUE DISPOSA L; Nonrefillable container. Do not reuse or refill tillS container. OJfer for rec~cling or 

n."COnditioning, if available and appropriate. If empty: Do Hot reuse tbis container Place in trash or offer for 

rccycling ifavailahlc. If partly Oiled: Call your local solid wa<;IC agency f{lf dispos.!ll iostructions. Never place 

unused product do\\'n any indoor or oUldoor drain. 

IWARRANTY 

Rcad the entire Directions for Usc and Warranty before using this Product. By usiog this product. user or huyer 

accepts the following warranty. Ipne directions for usc of this produl.-1 arc believcd 10 be adequate and must be 

followed carefully. fIo'wever, it is impossible to eliminate all risks inherently associated with the use of this product 

Unintended consequences may result because of such facton; as weather conditions. presence or absence or other 

materials. {lr the manner ofapplication, all ofl\"hich are beyond the control of Sergeant's Pet Care Products. IneJJ 

Scrgeant's Pet Care Products, Inc. is ctlmmitted to providing higb quality products To the extent consistent with 

applicable 11'1\\'. Sergeant's Pct Care Products. Inc. makes no warranties. expt\'·ss or implied, ofmerchantabihty or of 

fitness fhr a parth .. l.llar purpose or othemisc. that extend beyond statements on this label. To thc extent consistent 

with applicable law. Sergeant's Pet Care Products. Inc., the manuf.'lCtut"er. or the Seller disclaims any liability 

whatsoever for special. incidental. or consequential damages resulting front the usc or this product. To the extent 

consistent with the 13\\. the cxcltL"I'ie rl!mcd~' of the user or buyer sha" npt exceed the purcha'>C price paid.! 

(Sergeant's Care Pet ProduelS, Inc. is committ<::d to providing hIgh quafit) produCl,\. I (you have queslions or 

IXlmlllcnts anout this product. please \\Tite; Sergeant's Consumer R!...""Sponsc. P.O. Box 540399, Olllaha. NF (18 I 54· 

03991 

In Ca~c ofF.ntergcncy. call: I-ROO-781-4738 

Non-Emergcncy call: 1-800-224-PETS (7387) 

Distnbuted by: 

Sergeant's Pet Care l>roducl". Inc. 

PO Box 540224 

Omaha. NE 681 54 

lEND - BACK I SlOE PANEL} 

TUBE I VIAL LABEL 

(For more inlormallonllVi~it Il~ tlt! \i. ,\ \\ ~c:rg~';lIlh ,', m 

Made in liSA 

EPA Reg. No. 2517-XX 

EPA Esi. No. >..'XXXXXX 

{date & lanel CQdcj 

Fr_on_t_L_._be_I_. _____________ -iB7ack Label 

{product Name} . . I KEEP 01 T OF Rl'~ACH OF CHlI.l)Rf~·--l 

Etofcnprox ..... , .. 55.0% W/W i CAUTION Read dlrectinns and pn:cautions beforc i 

Pyripm.xyfen ...... 2.2'-;'" W/W Ii LL"ine.. i 

2.01LL{U mL label code: EPA~ REG. No. 25J7-XX {label code} J 

Deleted: 10 

Deleted: 

Delemd:XX 
42

Enclosure 3 

Proposed Label with All Comments Accepted 
43

EXponent" 

April 28, 20 I 0 

Richard Gebken 

Product Manager 10 

Document Processing Desk 

Office of Pesticide Programs (7504P) 

U.S. Environmental Protection Agency 

Room S-4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202-4501 

Subject: Submission of a Response to EPA and Supporting Data 

Exponent 

1150 Connecticut Avenue, NW 

Suite 1100 

Washington, DC 20036 

telephone 202-772-4900 

facsimile 202-772-4979 

www.exponent.com 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies (2517-RGG) 

Dear Mr. Gebken: 

On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's), Exponent is providing a 

response to EPA's email dated April 26, 20 I 0 regarding product chemistry and acute toxicology 

data for Sergeant's EtofenproxlNylar Spot-On Flea and Tick Products for Dogs and Puppies 

(EPA File Symbol 2517-RGG). 

Product Chemistry 

Confidential Statement of Formula 

Sergeant's originally submitted a basic and alternate (#1) formulation for 2517-RGG in 

September 2009; however, based on recent EPA guidance, Sergeant's has limited the CSF for 

2517-RGG to a single formulation (basic CSF dated April 23, 2010, Enclosure I). Unfortunately 

the basic CSF dated April 23, 2010 has some errors on it. Sergeant's is now submitting a new 

basic CSF dated April 28, 2010 (Enclosure 2). The errors that were corrected are with regards to 

#7,8,9, II, and 12 to match the product specific product chemistry data submitted under MRID 

48058402 (please note the study title lists the formulation as "alternate" but this was before we 

switched to call the CSF the new "basic"). It is the preference of Sergeant's to obtain approvaJ ,., 

from EPA for the CSF located in Enclosure 2. • , : , )';" , . , .. The following is a comparison of the available product chemistry data: 

r-------===-------,-------~=-------_,--~~~~~----_,----~~-. }~ 

f-::-----;-~c:;C~SF";:_--_f----p!:?JH~---+__-...::F:...:I=:as~h:cP:;_o"'i:.::n"-t _---I~----;;.'. ~3'I'~ms~~ i-'B=a=s:o.:ic:..c9:.:..1,,-10:::,1.::.:09~-,-,-,-,,----+-__ ----,2=.,,-3 ___ + __ --,1:...:4.:,-9°:-F=--__ +-__ ~·~Hb,ilgal~~ 

Alternate #1 9110/09 2.3 149° F 8.9lbs/gal ~ 

Alternate#14/9110 9.35 >93.3° C (>199.94° F) 1.035 g/mL " .. I 

Basic 4/28110 9.35 >93.3° C (>199.94° F) 1.035 g/mL ~I 
44

Please note the data listed above for the two CSFs dated 911 0/09 were based on estimated data. 

The data listed for the CSFs dated 4/911 0 and 4/2811 0 are based on product-specific data 

submitted to EPA under MRID 48058402. 

Enforcement Analytical Method 

In response to EPA's question on what is the enforcement analytical method for 2517-RGG, 

Sergeant's is citing MRID 46161301. This is the enforcement analytical method submitted to 

EPA on SPI #8208-55D (EPA Registration Number 69332-3). Both products contain the same 

active ingredients at the same percentages; therefore, the analytical method is applicable to both 

products. Please see Enclosure 3 for a copy of the EPA review dated March II, 2004, in which 

EPA accepted this study. 

Acute Toxicology 

We have reviewed the available acute toxicology data submitted to EPA under EPA Registration 

Number 69332-3. The following table provides a surmnary ofthe acute toxicology study results 

and MRID numbers: 

Study ResultslEP A EPA Classification MRID 

Category 

Acute oral toxicity >5050 mg/kg (IV) Acceptable 46161303 

Acute dermal toxicity >5050 mg/kg (IV) Acceptable 46161304 

Acute inhalation >2.08 mglL (IV) Cited 45121105 

toxicity 

Primary eye irritation Mildly irritating (III) Acceptable 46161305 

Primary skin irritation Slightly irritating (IV) Acceptable 46161306 

Dermal sensitization Negative Acceptable 46161307 

Please refer to Enclosure 4 for a copy of the EPA DERs dated February 10, 2004. 

We then reviewed the basic formulation CSF for 69332-3 (CSF dated March 25,2004) and 

compared it versus the pending basic formulation CSF for 2517-RGG (CSF dated April 28, 

2010, Enclosure E). Please refer to Enclosure 5 for a copy of the basic CSF for 69332-3. The 

following is a comparison of the two formulations: 

Ingredient 69332-3 (Basic) 2517-RGG (Basic) ~J..-'-L 

Etofenprox 55.0% 55.0% ); >},) ),' ; 

CAS 80844-07-1 , , 

Pyriproxyfen 2.2% 2,.'{."19 .. , . . , 

CAS 95737-68-1 ' . " . ,}) J 

*Inert ingredient information may be entitled to confidential treatment*
45

Please see Enclosure 6 for 

a copy of the submission and EPA approval letter. This EPA approval was granted without the 

requirement for additional acute toxicology data on the new formulation. 

Further we reviewed available acute toxicology data on the two inert ingredients identified in the 

table above to determine if there was any concern related to each specific inert ingredient. The 

data were identified in publicly available MSDS. The following is a comparison ofthe available 

acute toxicology profile: 

Study/Species 

Acute oral toxicity-rat 

Acute oral toxicitymouse 

Acute dermal toxicityrabbit 

b Refer to MSDS Enclosure 7

2Refer to MSDS Enclosure 8 

Comparison 

Similar 

Similar 

Similar 

Based on the above-referenced comparison table, both inert ingredients have a similar acute 

toxicology profile; therefore, the available acute toxicology data on the basic formula of 69332-3 

is representative of both formulations. The results are not expected to be significantly different if 

new data were generated. 

If you have any questions or need additional information, please contact me at 202-772-4932 or 

jmessina@exponent.com. 

lru;erelY, ,,){)1v-:-/ 

! ! . 

(J¢nes Messma 

£;Authorized Representative of 

Sergeant's Pet Care Products, Inc. 

Enclosures 

cc: Kevin Sweeney, EPA 

Kelly Hoskins, Sergeant's 

Larry Nouvel, Sergeant's 

Rick Tinsworth, Exponent 

,') , 

*Inert ingredient information may be entitled to confidential treatment*
46

Enclosure 1 

2517-RGG Basic CSF Dated April 23, 2010 

i} , ';' , 

'))) , , 
Page 47 contains the product confidential statement of formula and is not 
48

Enclosure 2 

2517-RGG New Basic CSF Dated April 28, 2010 
Page 49 contains the product confidential statement of formula and is not 
50

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

April 15, 2010 

SERGEANT'S PET CARE PRODUCTS, INC. 

2625 SOUTH 158TH PLAZA 

OMAHA, NE 68130-1703 

Report of Analysis for Compliance with PR Notice 86-5 

OFFICE OF 

PREVENTION, PESTICIDES AND 

TOXIC SUBSTANCES 

Thank you for your submittal of 12-APR-I0. Our staff has completed a preliminary 

analysis of the material. The results are provided as follows: 

Your submittal was fouod to be in full compliance with the standards for submission of 

data contained in PR Notice 86-5. A copy of your bibliography is enclosed, annotated with 

Master Record !D's (MRIDs) assigned to each document submitted. Please use these numbers in 

all future references to these documents. Thank you for your cooperation. If you have any 

questionS concerning this data submission, please raise them with the cognizant Product Manager, 

to whom the data have been released. 
51

EXponent 

April 9, 2010 

Richard Gebken 

Product Manager 10 

Document Processing Desk 

Office of Pesticide Programs (7504P) 

U.S. Environmental Protection Agency 

Room S-4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202-4501 

Subject: Submission of a Response to EPA and Supporting Data 

480584·00 

Exponent 

1150 Connecticut Avenue, NW 

Suite 1100 

Washington, DC 20036 

telephone 202-772-4900 

facsimile 202-772-4979 

www.exponent.com 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies (2517-RGG) 

Dear Mr. Gebken: 

On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's), Exponent is providing a 

response to EPA's memorandum dated February 24, 2010 regarding efficacy and CASS Data 

Evaluation Records (DERs) for Sergeant's EtofenproxlNylar Spot-On Flea and Tick Products for 

Dogs and Puppies (EPA Reg. No. 2517-RGG). I will contact you in the near future to schedule a 

meeting with you and other Office of Pesticide Program's (OPP's) staff to discuss OPP's DERs 

and the Sergeant's response to the OPP reviews. Please find enclosed the following support 

documents: 

• Transmittal document; 

• EPA Form 8570-1; 

• Enclosure I. Sergeant's response to OPP's efficacy reviews for MRIDs 47849601, 

47849602,47849603,47849604,47849605,47849606, and 47849607. The response 

provides a narrative discussion and tables of data consistent with that discussion; 

• Enclosure 2. Revised Sergeant's Master Label for EPA Reg. No. 2517-RGG reflecting 

claims supported by the rebuttal discussion provided in Enclosure I; 

• Enclosure 3. Sergeant's response to OPP's CASS review for MRID 47849609. The 

response provides a narrative discussion and tables of data consistent with that 

discussion, and also includes a response from the testing laboratory relative to a particular 

comment made by OPP. Included is Enclosure 3 Attachment A; 

• Enclosure 4. Copy of EPA efficacy review; 

• Enclosure 5. Copy of EPA CASS review; and 

• Product -specific product chemistry data. 
52

If you have any questions or need additional information, please contact me at 202-772-4932 or 

jmessina@exponent.com. 

Sincerely! 

/ "'1' , ( ,J ['i \; 

'~'I-f (i~ [/ 

--" I 

Jmhes Messina 

,J(uthorized Representative of 

Sergeant's Pet Care Products, Inc. 

Enclosures 

cc: Kevin Sweeney, EPA 

Kelly Hoskins, Sergeant's 

Larry Nouvel, Sergeant's 

Rick Tinsworth, Exponent 
53

Data Transmittal Document: 

Product: Sergeant's EtofenproxfNylar Spot-On Flea and Tick for Dogs and Puppies 

2S17-RGG 

Submitter: Sergeant's Pet Care Products, Inc. (EPA Company Number 2S17) 

2637 South ISSth Plaza 

Suite 100 

Omaha, NE 68130-1703 

Return to: James Messina 

Exponent 

IISO Connecticut Ave., NW 

Suite 1100 

Washington, DC 20036 

Submittal Date: April 9, 2010 

Volume Study Title 

I Group A Product Chemistry for EtofenproxfNylar SpotOn Flea and Tick for Dogs and Puppies (Alternate) 

2 Group B Product Chemistry for EtofenproxfNylar SpotOn Flea and Tick for Dogs and Puppies (Alternate) 

MRlD 

48058401 

48058402 
54
55

EXponenr 

April 9, 2010 

Richard Gebken 

Product Manager 10 

Document Processing Desk 

Office of Pesticide Programs (7504P) 

U.S. Environmental Protection Agency 

Room S-4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202-4501 

Subject: Submission of a Response to EPA and Supporting Data 

Exponent 

1150 Connecticut Avenue, NW 

Suite 1100 

Washington, DC 20036 

telephone 202-772-4900 

facsimile 202-772-4979 

www.exponent.com 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies (2517-RGG) 

Dear Mr. Gebken: 

On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's), Exponent is providing a 

response to EPA's memorandum dated February 24, 2010 regarding efficacy and CASS Data 

Evaluation Records (DERs) for Sergeant's EtofenproxlNylar Spot-On Flea and Tick Products for 

Dogs and Puppies (EPA Reg. No. 2517 -RGG). I will contact you in the near future to schedule a 

meeting with you and other Office of Pesticide Program's (OPP's) staff to discuss OPP's DERs 

and the Sergeant's response to the OPP reviews. Please find enclosed the following support 

documents: 

• Transmittal document; 

• EPA Form 8570-1; 

• Enclosure 1. Sergeant's response to OPP's efficacy reviews for MRIDs 47849601, 

47849602,47849603,47849604,47849605,47849606, and 47849607. The response 

provides a narrative discussion and tables of data consistent with that discussion; 

• Enclosure 2. Revised Sergeant's Master Label for EPA Reg. No. 2517-RGG reflecting 

claims supported by the rebuttal discussion provided in Enclosure I; 

• Enclosure 3. Sergeant's response to OPP's CASS review for MRID 47849609. The 

response provides a narrative discussion and tables of data consistent with that 

discussion, and also includes a response from the testing laboratory relative to a particular 

comment made by OPP. Included is Enclosure 3 Attachment A; 

• Enclosure 4. Copy of EPA efficacy review; 

• Enclosure 5. Copy of EPA CASS review; and 

• Product-specific product chemistry data. 
56

If you have any questions or need additional information, please contact me at 202-772-4932 or 

jmessina@exponent.com. 

es Messina 

uthorized Representative of 

Sergeant's Pet Care Products, Inc. 

Enclosures 

cc: Kevin Sweeney, EPA 

Kelly Hoskins, Sergeant's 

Larry Nouvel, Sergeant's 

Rick Tinsworth, Exponent 
57

Data Transmittal Document: 

Product: Sergeant's EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies 

2517-RGG 

Submitter: Sergeant's Pet Care Products, Inc. (EPA Company Number 2517) 

2637 South 158th Plaza 

Suite 100 

Omaha, NE 68130-1703 

Return to: James Messina 

Exponent 

1150 Connecticut Ave., NW 

Suite 1100 

Washington, DC 20036 

Submittal Date: April 9, 2010 

Volume Study Title 

1 Group A Product Chemistry for EtofenproxINylar SpotOn Flea and Tick for Dogs and Puppies (Alternate) 

2 Group B Product Chemistry for EtofenproxINylar SpotOn Flea and Tick for Dogs and Puppies (Alternate) 

MRID 
58

Please read instructions on reverse before completing form Form Approved OMB No 2070 . 0060 Approval expi/es 05-3 t 98 . 

United States bJRegistration app Identitier Number 

EPA Environmental Protection Agency D_Amendment 

Washington, DC 20460 ~ Other 

Application for Pesticide - Section I 

t. Company/Product Number 2, EPA Product Manager 3. Proposed Classification 

2517·RGG R Gebken 

4. Company/Product (Name) PM# ~None DRestricted Etofenprox/Nylar Spot-On Flea and Tick for Dogs and Puppies to 

(30%) 

5, Name and Address of Applicant (/nclude ZIP Code) 6. Expedited Review. In accordance with FIFRA Section 3( c)(3)(b)(I), my 

Sergeant's Pet Care Products, Inc. product is similar or identical in composition and labeling to: 

2625 South 158'h Plaza 

Omaha, NE 68130 EPA Reg. No. 69332·3 

Product Name SPI #8208·55D 

D Check if this rs a new address 

Section II 

o Amendment ~ Explain below. D Final printed labels in response to Agency letter dated XX~XX~XX 

~ Resubmission in response to Agency letter dated 02~24~ 10 o "Me Toon Application 

D Notification - Explain below. D Other ~ Explain below, 

Explanation: Use additional page(s) if necessary, (For section I and Section II.) 

Submission of a rebuttal to EPA memorandum dated 2124/10 and product-specific product chemistry data 

Section III 

1, Material This Product Will Be Packaged In: 

Child~Resistant Packaging Unit Packaging Water Soluble Packaging 2. Type of Container 

OVes' [gives Oves o Metal 

ONo o No fZj No cg] Plastic 

If "Yes" No, per If~Yes" No, per DGlass 

'Certification must Unit Packaging wgt Container Packagewgt. Container 

DPaper be submitted 2.0mL I 1·6 I Dother (Specify) Plastic Bag 

3. Location ot Net Contents Information 4. Size(s) Retail Container 5. Location of Label Directions 

fZjLabel o Container 2.0mL Don Can 

Don Labeling accompanying product 

6. Manner in Which Label is Affixed to product DUthograph DOther 

DPaper glued 

DStenciled 

Section IV 

1. Contact Point (Comp/ele items directly below for idenfificalion of individual to be conlacled, if necessary, to process this appllcalion.) 

Name Title Telephone No. (include Area code) 

James Messina Authorized Representative (202) 772-4932 

Certification S. Date Application 

I certify that the statements I have made on this form and all attachments thereto are true, accurate and complete, I Received 

acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both (Stamped) 

under aPR' e w,,......-, 

2. Signatt 

il~ 3. Title 

BV: Authorized Representative 

4. Typed Nampl' 5, Date: 1-7-10 James Messina 
59

Enclosure 1 

Response to February 12th, 2010, Decision 420097, 2517-RGG, 

Re:~RlDs47849601,47849602,47849603,47849604,47849605,47849606,47849607 

EtofenproxlNylar Spot-on Flea & Tick for Dogs and Puppies 

By: Thomas A. ~iIIer, B.Sc. (Agric), B.V.~.S, D.V.~., Ph. D., ~.R.C.V.S, Consultant, 

VRRC Inc, Sequim, W A 98382 
60

Response to February 12th, 2010, Decision 420097, 2517-RGG, 

Re:~RIDs47849601,47849602,47849603,47849604,47849605,47849606,47849607 

EtofenproxlNylar Spot-on Flea & Tick for Dogs and Puppies 

By: Thomas A. ~iller, B.Sc. (Agric), B.V.~.S, D.V.~., Ph. D., ~.R.C.V.S, Consultant, 

VRRC Inc, Sequim, W A 98382 

Rather than responding to individual comments on each study, the following re-analyses of the 

entire project data were conducted, based on the dose rates (mg/kg) of etofenprox delivered to all 

treated dogs. The dog weights entered in these analyses were limited to the label range of 4 to 20 

Ib, thus excluding MRID 47849601, since its weights exceeded the label range. 

The label specifications (Table I) shows the dose rates, mglkg of etofenprox and pyriproxyfen 

applied in the 2.0 mL unit dose to dogs weighing from 4 to 20 Ib (1.8 to 9.1 kg). Since the 

claims in question are those related to the toxicant effect of etofenprox, the presence of the IGR, 

pyriproxyfen, will not be considered. 

The dose rates of etofenprox (from a 55% squeeze-on) range from a maximum of 606 mg/kg for 

the smallest dog weighing 4 Ib to the minimum dose rate of 121 mg/kg for the heaviest dog 

weighing 20 lb. The mean +/- s. d. dose rates for the range are 252 +/- 138 mglkg. 

The individual data for each treated dog in the efficacy study reports (MRIDs 47849603, 

47849604, 47849606 and 47849607, excluding 47849605 that addresses only the Black Leg 

Tick, Ixodes scapularis) were entered showing dog weight (lb and kg), unit dose volume (mL) 

and etofenprox dose rate (mg/kg). The efficacy result for each treated dog (against re-infestation 

with new fleas and ticks, at or exceeding 90%, comparing each dog's flea and tick counts with 

the respective mean group flea and tick counts on the control group in that study) were extracted 

from the data tables (Table 2). Individual etofenprox dose rates ranged from 122 to 411 mg/kg, 

with mean +/- s.d. dose rates for these forty (40) treated dogs of 266 +/- 82 mglkg. Statistical 

analysis (by Student's "t" test, two-tailed, assuming equal variances, Microsoft Office 2003), 

comparing the range of label dose rates of etofenprox (252 +/- 138) with the values for these 40 

treated dogs (266 +/- 82) showed that they were not significantly different (> 0.5), irrespective of 

the dose volumes applied to each treated dog. The post-treatment efficacy values against fleas 

and ticks ranged from 16 to 31 days with 3 outliers of 9 days (fleas only). The mean efficacy 

values (+/- s.d.) were 22 +/- 6.7 days for fleas and 25.4 +/- 4.7 days for ticks. Since the dose 

rates in the efficacy studies were not significantly different from the label dose rates at a 2.0 

mL unit dose, these findings support at least a 3-week residual efficacy label claim for both 

fleas and ticks. 

The data from Table 2 were copied into Table 3 and all results for treatments where the unit dose 

volumes exceeded the proposed label unit dose volume of 2.0 mL were removed. This provided 

data on 18 treated dogs that received the proposed label unit dose volume or less (6 received only 

1.5 mL). The mean +/- s.d. etofenprox dose rates for these 18 treated dogs were 214 +/- 89 

mg/kg. These values were also not significantly different from the dose rates applied by the 

proposed label (P> 0.3). The mean +/- s.d. residual day's efficacy values for these 18 treated 

dogs were 20 +/- 6 days for fleas and 26 +/- 4 days for ticks. Again these results support an 

approximately 3 week claim for fleas and at least a 3 week claim for ticks. 
61

The minimum label dose rates for the heaviest label dogs (17-20 Ib) are under 150 mglkg (Table 

I). Extracting the data from 176D/47849606, provides mean residual efficacy of 17 days for 

fleas and 25 days for ticks for these 6 treated dogs that were at the upper limit of the label weight 

range. These data support at least a 2 week claim for fleas and more than 3 weeks for ticks. 

The claims for efficacy against mosquitoes were partially rejected because the test dogs were 

limited by weight (163D 47849604) to small dogs. This is necessary because available Gerberg 

type mosquito cages are of limited sizes that necessitate the use of small dogs so that the 

anesthetized dogs can be totally contained in the cages and the free mosquitoes confined with the 

dog. This procedure and results reported in a previous efficacy study (MRID 47163701) have 

been accepted and label claims approved for registration numbers 2517-80,2517-85,2517-90. In 

the referenced report, mosquito tests were run on dogs under 201b. The data was considered 

adequate to enable registration of labels with no weight restriction, including dogs over 601b. 

The dogs were treated with 2.5 mL for a mean etofenprox dose rate of 364 mglkg approximating 

the middle of the range of label dose rates (121-606 mglkg). The "controls" mosquitoes claim is 

invalid and must be deleted but there is no "kills mosquitoes" claim on the proposed label. The 

mosquito data does however support a 30 day claim of repellency/preventing blood feeding 

by female mosquitoes 

The Ixodes scapularis Black Leg Tick nymph test (163-2D 47849605) was conducted to the 

same protocol that has been used previously and that secured registered labels with this claim 

((MRID 46166109 2517-80, 85, 90). These labels were accepted with a 30 day claim even 

though the tests were conducted at 14 and 22 days after treatment. In 47849605, since the tests 

were conducted only once, the proposed label does not associate any residual claim with this tick 

specie and the "long lasting" claim, has been removed. The suggestion that the test should have 

been run at 30 days becomes relevant only if a 30 day claim would be on the proposed label. 

The "quick acting" claim has been removed from the draft label since there were no flea or tick 

counts before 24 hours after treatment/re-infestation. 

The pyriproxyfen IGR claims are supported by the results of a dose-titration study on dogs 

(MRID 46346601). That report supported registration of 2517-80. The label of that registration 

specifies a unit dose volume (at 2.2% pyriproxyfen) for dogs 20 lb and less of 1.5 mL. Although 

the etofenprox-Nylar label specifies unit dose volume of 2.0 mL, increasing the dose rate of 

pyriproxyfen by approximately one third, the label for 2517-RGG maintains the same approved 

residual IGR claims 2517-80. 
62

TABLE 1 

Etofenprox-Containing Squeeze-On for Small Dogs 

Dosage and dose rates of active ingredients 

Dog weight Active Etofenprox Pyriproxyfen 

Label potency ~, 55.0% 2.2% 

Ib kg mL ~ mg/kg ~ mg/kg 

4 1.8 2 I 606 ~ 24 

5 2.3 2 485 I 19 

6 2.7 2 

m 

404 16 

7 3.2 2 346 14 

8 3.6 2 I 303 ~ 12 

9 4.1 2 269 11 

10 4.5 2 243 10 

11 5.0 2 220 9 

12 5.4 2 ~ 202 8 

13 5.9 2 I 187 7 

14 6.4 2 173 7 

15 6.8 2 I 162 6 

16 7.3 2 152 :. 6 

17 7.7 2 ltl 

~r 143 6 I 18 8.2 2 ~ 135 5 

19 8.6 2 Hi 128 , 5 

20 9.1 2 ~ 121 

~ 

5 

12 5 mean ~ 252 10 ~ b 

5 2 +/- s.d. 138 " 6 ~ ill 

Potency is label nominal 
63

Table 2 

Etofenprox-Containing Squeeze-On for Small Dogs 

Dosage and Residual Claim Support 

Dose rates mg/kg vs residual efficacy @ =/>90% 

All dogs weighing 4-20 Ib, irrespective of unit dose volumes applied 

Study no. MRID dog wt dose dose rate days @ =/>90% 

ka Ib mL mg/ka fleas ticks 

149D 47849601 4.2 9.2 1.5 199 16 31 

149D 47849601 5.5 12.2 1.5 150 16 23 

149D 47849601 4.5 10.0 1.5 183 23 31 

149D 47849601 4.8 10.6 1.5 173 16 31 

149D 47849601 3.0 6.7 1.5 273 16 31 

149D 47849601 2.0 4.5 1.5 407 16 22 

154D 47849602 3.2 7.0 2 349 29 22 

154D 47849602 4.4 9.8 2 249 29 22 

154D 47849602 3.3 7.2 2 339 15 22 

154D 47849602 4.4 9.8 2 249 29 29 

154D 47849602 4.5 9.9 2 246 29 22 

154D 47849602 4.0 8.8 2 277 15 29 

154D 47849602 8.5 18.8 4 260 29 29 

154D 47849602 9.1 20.0 4 244 29 29 

154D 47849602 9.0 19.9 4 245 29 22 

154D 47849602 7.1 15.6 4 313 29 29 

154D 47849602 8.3 18.3 4 267 29 29 

158D 47849603 3.8 8.3 2.5 367 23 23 

158D 47849603 4.4 9.8 2.5 311 30 30 

158D 47849603 4.5 9.9 2.5 307 30 30 

158D 47849603 4.5 9.9 2.5 307 9 23 

158D 47849603 3.7 8.2 2.5 371 16 30 

158D 47849603 4.2 9.2 2.5 331 9 16 

158D 47849603 9.4 20.8 4.7 274 23 23 

158D 47849603 8.7 19.2 4.3 274 30 23 

158D 47849603 9.4 20.8 4.7 274 30 30 

158D 47849603 8.8 19.4 4.4 274 30 30 

158D 47849603 8.7 19.1 4.3 274 23 30 

158D 47849603 9.2 20.2 4.5 274 30 30 

163D 47849604 3.6 8.0 2.5 380 23 16 

163D 47849604 4.4 9.6 2.5 317 23 23 

163D 47849604 4.5 9.9 2.5 307 23 16 

163D 47849604 3.7 8.1 2.5 376 23 23 

163D 47849604 4.5 10.0 2.5 304 23 16 

163D 47849604 3.4 7.4 2.5 411 23 23 

176D 47849606 8.3 18.3 2.0 133 9 23 

176D 47849606 8.4 18.6 2.0 131 15 23 

176D 47849606 8.6 19.0 2.0 128 23 30 

176D 47849606 8.9 19.6 2.0 124 16 30 

176D 47849606 9.0 19.9 2.0 122 23 23 

176D 47849606 9.1 20.0 2.0 122 16 23 

mean 6.0 13.2 2.7 266.2 22.4 25.4 

+/- s.d. 2.4 5.4 1.0 82.1 6.7 4.7 

PACE study excluded since all dogs were well over 20 Ib 

EX' 
64

Table 3 

Etofenprox-Containing Squeeze-On for Small Dogs 

=/< 2 mL dose to dogs 4-20 Ib 

Study no.lMRIO dogwt kg dose dose rate days @ =/>90% 

kfl Ib mL mfl/kfl fleas ticks 

1760 47849606 9.0 19.9 2.0 122 23 23 

1760 47849606 9.1 20.0 2.0 122 16 23 

1760 47849606 8.9 19.6 2.0 124 16 30 

1760 47849606 8.6 19.0 2.0 128 23 30 

1760 47849606 8.4 18.6 2.0 131 15 23 

1760 47849606 8.3 18.3 2.0 133 9 23 

1490 47849601 5.5 12.2 1.5 150 16 23 

1490 47849601 4.8 10.6 1.5 173 16 31 

1490 47849601 4.5 10.0 1.5 183 23 31 

1490 47849601 4.2 9.2 1.5 199 16 31 

1540 47849602 4.5 9.9 2.0 246 29 22 

1540 47849602 4.4 9.8 2.0 249 29 22 

1540 47849602 4.4 9.8 2.0 249 29 29 

1490 47849601 3.0 6.7 1.5 273 16 31 

1540 47849602 4.0 8.8 2.0 277 15 29 

1540 47849602 3.3 7.2 2.0 339 15 22 

1540 47849602 3.2 7.0 2.0 349 29 22 

1490 47849601 2.0 4.5 1.5 407 16 22 

mean 5.6 12.3 1.8 214 20 26 

+/- s.d. 2.4 5.3 0.2 89 6 4 
65

EncIosure2 

Revised Product Label 
66

Sergeant's Pet Care Products, Inc. Master Label 

10 September 2009 EPA Reg. No. 2517-XX 

Infonnation in [ ] is optional. Page I of 4 EPA SAL 

Editors Note: [Optional proposed text appears in brackets - the final label may 

ETOFENPROXINYLAR SPOT-ON 

FLEA AND TICK FOR DOGS AND PUPPIES 

{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On} 

{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On for small breed dogs} 

{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On for small and toy breed dogs} 

{ABN: Sergeant's Small Breed Flea and Tick Squeeze-On} 

{ABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small breed dogs} 

{ABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} 

{ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On} 

{ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On for dogs} 

{ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} 

{ABN: SentryPro Small Breed Flea and Tick Squeeze-On for Dogs} 

{ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small breed dogs} 

{ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} 

[One Application:(choose from the following)] 

• [with nylar®] 

• [(One) (Two) (Three) (Four) (XX) Applications] 

• [Bonus] 33% more [now includes 4 tubes] 

• [odorless] [unscented] [fragrance free] 

• [Dries quickly] [Quick drying fonnula] [Quick Drying] 

• [Squeeze-On] [stays on and doesn't rub off] 

• [Spreads by using the dog's natural skin oils] 

• [Breaks the flea life cycle for up to (70 Days) (9 Weeks)] 

• [Controls reinfestation for up to (70 days) (9 weeks)] 

• [For toy breeds 4-20 Ibs.] 

• [For small breeds 4-20 Ibs.] 

• [For toy and small breeds 4-20 Ibs.] 

• [Specially fonnulated for small breed[s] dogs] 

• [Specially fonnulated for toy breeq[s] [dogs]] 

• [Specially fonnulated for [toy breed[s]] and [small breed[s]] dogs] 

• [Toy] [and] [small] breed fonnula] 

• [Gentle protection for [toy] [small] breed dogs] 

• [5 Way Protection] 

• [Controls fleas, ticks, flea eggs & larvae] 

• [Kills Fleas, Ticks, Flea Eggs, Larvae] [and] [repels mosquitoes [for up to one month] [for up to 4 weeks]] 

• [Flea, tick, flea egg and larvae control] 

• [Kills fleas and ticks for up to [21 days] [3 weeks]] 

• [Kills ticks [for up to [21 days] [3 weeks]]] 

• [Kills Ticks] [Before they can] [that] [transmit Lyme Disease 

• [Kills [adult] fleas for up to [21 days] [3 weeks]] 

• [Kills Fleas and Ticks] [for up to [21 days][3 weeks]] 

• [Flea, Tick and Flea Egg Protection] 

• [Repels mosquitoes [for up to one month] [for up to 4 weeks]] 

• [Flea and Tick control] 

• [Kills fleas that may cause flea allergy dennatitis, and flea bite anemia] [for up to [21 days] [3 weeks]] 

• [Kills Flea Eggs and Larvae for up to (9 weeks) (70 days) (per application)] 

• [Prevents flea eggs from developing into biting adults for up to (9 weeks) (70 days) (per application)] 

• [Repels mosquitoes that may transmit [heartwonn] [West Nile virus] [from feeding on dogs] [for up to [one 

month] [30 days][ 4 weeks]] 
67

Sergeant's Pet Care Products, Inc. Master Label 

10 September 2009 EPA Reg. No. 2517-XX 

Information in [ jis optional. Page 2 of 4 EPA SAL 

• [Repels Mosquitoes] [Prevents mosquitoes that transmit West Nile virus and heartworm] [from feeding on 

dogs] [for up to [one month] [30 days] [ 4 weeks]] 

• :mB~~~~~~~~5'"""fi;'~' 

ACTIVE INGREDIENTS: 

Etofenprox ..................................................................................... 55.00% 

Pyriproxyfen................... ................. ........... ............................ ....... 2.20% 

OTHER INGREDIENTS: ....................................................................... 42.80% 

TOTAL 100.00% 

[Nylar® is a registered trademark of McLaughlin Gormley King Company] 

KEEP OUT OF REACH OF CHILDREN 

CAUTION 

See [Back][or][Side] Label Panel[s] for Additional Precautionary Statements 

NET CONTENTS: 

[One] [Two][Three][Four][Five][Six] 2.0 mL applicators.lfor small dogs 4 to 20 lbs/ 
68

Sergeant's Pet Care Products, Inc. Master Label 

10 September 2009 EPA Reg. No. 25 I 7-XX 

Information in [ J is optional. Page 3 of 4 EPA SAL 

{Product Name} 

READ ENTIRE LABEL BEFORE EACH USE 

PRECAUTIONARY STATEMENTS 

HAZARDS TO HUMANS AND DOMESTIC ANIMALS 

CAUTION 

HAZARDS TO HUMANS: Causes moderate eye irritation. Avoid contact with eyes and clothing. Wash 

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

HAZARDS TO DOMESTIC ANIMALS: For External Use Only. Do not use on dogs under 12 weeks of age. 

Consult a veterinarian before using this product on debilitated, aged, medicated, pregnant, or nursing animals. 

Sensitivities may occur after using ANY pesticide product for pets. If signs of sensitivity occur, bathe your pet with 

mild soap and rinse with large amounts of water. If signs continue, consult a veterinarian immediately. 

FmST AID 

IF IN EYES: Hold eye open and rinse slowly and gently with water for 15-20 minutes. Remove contact lenses, if 

present, after the fITst 5 minutes, and then continue rinsing. Call a poison control center or doctor for treatment 

advice. Have the product container or label with you when calling a poison control center or doctor or going for 

treatment. You may also contact 1-800-781-4738 for emergency medical treatment information. 

PHYSICAL OR CHEMICAL HAZARDS: Combustible: Do not use or store near heat or open flame. 

DIRECTIONS FOR USE 

It is a violation of Federal Law to use this product in a manner inconsistent with its labeling. 

Do not get this product in your pet's eyes or mouth. Do not apply more often than [once a month] [once evel)' 30 

days]. Use only on Dogs. FOR EXTERNAL USE ON DOGS ONLY. Do not use on puppies less than 12 weeks 

of age. Weigh your dog to be sure you are applying the right dose formulated for the weight of your pet. Do not 

treat your pet with more than one pesticide product at a time. Over dosing your animal can result in serious illness 

and even death. Best if used year round. Do not bathe pet with in the first 24 hours after squeeze-on has been 

applied. Households with more than one pet should not allow dogs or cats to groom each other until solution has 

dried. DO NOT USE ON CATS or animals other than dogs. Separate the treated dog from all other dogs and cats 

for 24 hours after treatment has been applied. Cats or dogs that actively groom or engage in close physical contact 

with treated dogs may be at risk of serious harmful effects. If your dog is exhibiting signs of and/or are being treated 

for skin dermatitis, talk to your vet before applying any topical flea and tick control product. Sensitivities may occur 

after using ANY pesticide product on pets. It is recommended to separate treated dogs from other household pets for 

24 hours after treatment has been applied. If signs of sensitivity occur, bathe your dog with mild soap and rinse with 

large amounts of water. 

FOR USE ON DOGS: 

Weighing 4 TO 20 LBS. - Apply contents of one (2.0 mL) tube [vial] of [Product Name][Squeeze-on] as a spot 

high on the back of the dog's neck behind its head and apply as a stripe to a point midway between the neck and the 

tail. 

(INSERT DIAGRAM THAT DEPICTS APPLICATION OF PRODUCT ON THE DOG) 

HOW TO APPLY: 

Remove product tube [vial] from the package. Holding tube [vial] with notched end pointing up and away from the 

face and body cut or tear off the narrow end at the notches. While holding the animal with one hand, use the other 

hand to apply the solution. Invert the tube [vial] and use the narrow end to part the animal's hair while gently 

squeezing to apply to the animal's skin. Hold the animal for a few seconds to give the solution time to be absorbed 

into the animal's coat. When fInished, wrap the tube [vial] in paper and put into the trash. 
69

Sergeant's Pet Care Products, Inc. Master Label 

10 September 2009 EPA Reg. No. 2517-XX 

Information in [ J is optional. Page 4 of 4 EPA SAL 

STORAGE AND DISPOSAL 

Do not contaminate water, food or feed by storage or disposal. 

PESTICIDE STORAGE: Do not remove tube from the pack until ready to use. Store in a cool (below 25'C) dry 

place out of reach of children. Do not refrigerate. Protect from direct sunlight. 

PESTICIDE DISPOSAL: Nonrefillable container. Do not reuse or refill this container. Offer for recycling or 

reconditioning, if available and appropriate. If empty: Do not reuse this container. Place in trash or offer for 

recycling if available. If partly filled: Call your local solid waste agency for disposal instructions. Never place 

unused product down any indoor or outdoor drain. 

[WARRANTY 

Read the entire Directions for Use and Warranty before using this Product. By using this product, user or buyer 

accepts the following warranty. [[The directions for use ofthis product are believed to be adequate and must be 

followed carefully. However, it is impossible to eliminate all risks inherently associated with the use of this product. 

Unintended consequences may result because of such factors as weather conditions, presence or absence of other 

materials, or the manner of application, all of which are beyond the control of Sergeant's Pet Care Products, Inc .. JJ 

Sergeant's Pet Care Products, Inc. is committed to providing high quality products. To the extent consistent with 

applicable law, Sergeant's Pet Care Products, Inc. makes no warranties, express or implied, of merchantability or of 

fitness for a particular purpose or otherwise, that extend beyond statements on this label. To the extent consistent 

with applicable Jaw, Sergeant's Pet Care Products, Inc., the manufacturer, or the Seller disclaims any liability 

whatsoever for special, incidental, or consequential damages resulting from the use of this product. To the extent 

consistent with the law, the exclusive remedy of the user or buyer shall not exceed the purchase price paid.J 

[Sergeant's Care Pet Products, Inc. is committed to providing high quality products. If you have questions or 

comments about this product, please write: Sergeant's Consumer Response, P.O. Box 540399, Omaha, NE 68154-

0399.J 

In Case of Emergency, call: 1-800-781-4738 

Non-Emergency call: 1-800-224-PETS (7387) 

Distributed by: 

Sergeant's Pet Care Products, Inc. 

PO Box 540224 

Omaha, NE 68154 

{END - BACK I SIDE PANEL) 

~~jAY~~lm 

Front Label 

{Product Name) 

Etofenprox .......... 55.0% WIW 

Pyriproxyfen ......... 2.2% WIW 

2.0mL {Jabel code} 

[For more information] [Visit us at:] www.sergeants.com 

Made in USA 

EPA Reg. No. 2517-XX 

EPA Est. No. XXXXXXX 

{date & label code) 

Back Label 

KEEP OUT OF REACH OF CHILDREN 

CAUTION: Read directions and precautions before 

using. 

EPA REG. No. 2517-XX {label code) 
70

Enclosnre 3 

Response to February 24'h, 2010, Decision 420097, 2517-RGG, 

Re: MRID 47849609 

EtofenproxINylar Spot-on Flea & Tick for Dogs and Puppies 

By: Thomas A. Miller, B.Sc. (Agric), B.V.M.S, D.V.M., Ph. D., M.R.C.V.S, Consultant, 

VRRC Inc, Sequim, W A 98382 
71

Response to February 24th, 2010, Decision 420097, 2517-RGG, 

Re: MRID 47849609 

EtofenproxlNylar Spot-on Flea & Tick for Dogs and Puppies 

By: Thomas A. Miller, B.Sc. (Agric), B.V.M.S, D.V.M., Ph. D., M.R.C.V.S, Consultant, 

VRRC Inc, Sequim, W A 98382 

1. Reviewer's comment: 

"Test groups consisted of 6 (3 male and 3 female) adult dogs or puppies". 

Response: 

The 5Xdosage rate test group consisted of 6 puppies (3 male and 3 female) and 6 adult dogs (3 

male and 3 female), total 12 animals (6 males and 6 females) in this dose rate test group. This 

conforms to the 870-7200 Guidelines. 

This protocol and dose grouping are essentially the same as the protocols and grouping in 

previous CASS reports (MRlDs, 46161309 & 46166108) that were accepted and supported 

several registrations including the following: 69332-3 & 2517-80. All were based on the 

referenced 1998 Guidelines which have not been amended since issue. 

That the IX test group consisted of only 6 adults (3 males and 3 females) becomes irrelevant if 

there are adequate safety-supporting data from the 5X group. The presence of a IX dose rate test 

group in the referenced CASS guidelines represents a fall-back "rescue" position should there be 

adverse effects at 5X. 

2. Reviewer's comments: 

"In addition, the adult dogs that were treated with the test substance II (containing ....... ) at 5X 

the dosage rate weighed ......... Since only one dog in this group weighed less than 9 Ib, the data 

could not be used to support .... " 

Response: 

The separation of the adult from the puppy 5X subgroups, rejected above, is artificial. The 

primary concern in CASS evaluation is that puppies are more likely to be susceptible to adverse 

effects of pesticides and that, depending on dose rate (mg a.i. per kg body weight), they should 

be more vulnerable, otherwise, there is no rationale for requiring separate testing of pups from 

adults. The IX and 5X puppy subgroups contained pups weights ranging from 4.71b up to 

16.11b, spanning most ofthe proposed label range of 4 to 20 lb. The 5X adult subgroup contained 

dogs weighing from 9 to 20 !lb. The entire label weight range for puppies and small dogs was 

therefore adequately covered. 

3. Reviewer's comments: 

"Cumulative dosage rates were ........ , which is also substantially above the proposed lower 

weight limit" 

Response: 

These statements do not accurately portray the dosages/dose rates of actives applied to the CASS 

test subjects. Table I calculates the dose rates (mg/kg) of each active ingredient that was applied 

to each test dog (with group mean dose rates +/- S.D.) in this study. Table 2 shows the label 
72

dose rates of etofenprox and pyriproxyfen (at upper certified limits of the CSF) administered to 

dogs and puppies from 4 to 20 lb. For the purpose of my response I will only address the 

etofenprox component since that would be the primary culprit in inducing any adverse effects. 

The other component of the product (pyriproxyfen insect growth regulator) is virtually 

mammalian-inert. The mean group CASS dose rates for the active at I X and 5 X, for dogs (5X 

CASS rate) and puppies (lX and 5X rate) are copied from Table I and entered at the top of the 

columns that calculate and display the ratio between CASS dose rates and label dose rates. The 

ratios never exceed and only approach a single dose value of I (i.e., 0.92) for the smallest (4Ib) 

dogs/puppies specified on the proposed label. The ratio, based on the 5X CASS puppy dose rate, 

is approximately 17% of the 5X CASS dose rate. At the upper weight limit of 20 Ib, the dogs 

receive approximately one third of the IX puppy dose rate, 14% of the IX CASS adult dose rate 

and only 7% of the 5X CASS puppy rate. 

The reviewer's calculations become irrelevant in comparison with these data. 

4. Reviewer's comments: 

"Also it was not possible to compare body weight changes between adult group B3 and the 

control (C2) group because initial ......... " 

Response: 

When considering weight changes after treatment, "adult dogs are adult dogs", irrespective of 

differences in body weights. Because of the need to address weight changes over the wide span 

of adult dogs' weights that represent the dog population and the label weight range, instead of 

analyzing weight changes based on individual weights before, after and gains therein, percent 

weight changes for each animal provide a more appropriate method. The individual weights on 

days 1,7 and 14, extracted from the [mal report, were transformed to provide (Table 3) changes 

over the test periods of 1-7, 7-14 and 1-14 days after treatment, then to change per day and 

[mally to % (of weight at start of each interval) per day. Student's "T" test was used to 

determine the significance of apparent differences in % change per day between groups pups B3 

and C2 (groups that received etofenprox only (over each of these three periods). There were 

statistically significant differences for days 1-7 and 1-14, in that the daily weight % 

changes/gains of the treated dogs were lower (P<0.05), but not between days 7 and 14. However, 

as noted the weight ranges of the treated dogs and the controls did not coincide. It is not clear 

whether the different ranges were responsible for the significant differences or whether it was 

application of the etofenprox test substance. However, the same data transformations and 

analyses, applied to the puppies that received, in addition to the etofenprox, cyphenothrin, 

fipronyl and two IGRs (Table 4) showed no evidence of treatment-mediated changes in % daily 

weight changes (gains) for treated compared with placebo-treated control puppies over any of the 

three test intervals. Since puppies are assumed to be more vulnerable to adverse effects of 

insecticide treatment compared with adult dogs and since these treated puppies also received two 

additional insecticide actives and an additional IGR, it is clear that the significant differences in 

the adult data were a function of the different and non-overlapping weight ranges and not an 

indication of toxicity. 
73

5. Reviewer's comments: 

"For the puppies, it is impossible to compare and interpret differences in body weight gains when 

there was such a range in ages (10-15 weeks with no information as to specific ages for 

individual animals), the dogs were mixed breed and .......... control group" 

Response: 

The records for puppy birth date, date of treatment and individual weights at treatment and days 

7 and 14 were obtained from the investigator. Age at treatment (days) were calculated (Table 5). 

Ages on day of treatment ranged from 73 days (10 weeks) to 106 days (15 weeks), with mean 

group ages of 12.5 weeks (group AI), 13.1 weeks (group A2) and 14.1 weeks (group CI). There 

were no significant differences between these groups' ages (P> 0.05). 

The group weights at time of treatment were analyzed (Table 5) and found not to be significantly 

different (P>0.05). Weigh gains over the duration of the study were shown not to be statistically 

different (paragraph 4 and Table 5). 

The proposed labels read "for dogs and puppies 12 weeks and older". While it may be argued 

that more uniform groups of pups might have been used with a tighter age and weight range, this 

is achievable only with purpose-bred pups, invariably Beagles, not with mixed breeds for which 

the product will be labeled. 

For many safety/toxicology studies, the exclusive dependence on closed colony Beagles has been 

questioned as not always providing results that can be uncritically applied to the general pet 

population. Availability of sufficient mixed breed pups with a tight age distribution at a specific 

start date necessitates a very large pool of simultaneously bred bitches, a requirement that is 

unrealistic (except for Beagles maintained under controlled, programmed climatic/seasonal light 

and temperature environments). 

6. Reviewer's comments: 

"In addition, it is concluded that the margin of safety in puppies administered ... substances IA 

and II. .. was less than the I X recommended dose ...... " 

Response: 

Table 2, discussed in paragraph 3 (above), clearly shows that for etofenprox and pyriproxyfen, 

administered at IX dosage to the safety study dogs and puppies, the ratio of label dose rate 

(mg/kg) to dose rates administered to the test dogs and puppies was less than I for dogs 

weighing 4 to 201b, as listed on the proposed label. Further this safety margin or ratio, based on 

the 5X dose rate test dogs and puppies, was from 0.06 to 0.17. 
74

7. Reviewer's comments: 

"In addition, it is concluded that the margin of safety in puppies ...... based on clinical signs of 

toxicity (behavioral change immediately post-application" and "showed running and circling 

....... after application ........ area had been numbed" 

Response: 

The investigator was asked to provide more information on these observations and questioned on 

whether he considered that the immediate post-application behavioral effect was a sign of local 

irritation from the topical application of the test substances. His response (attachment A), and I 

believe that of any veterinarian experienced in the often abnormal behavior of institutionalized 

experimental dogs, was that such behavior is common when one restrains and handles laboratory 

experimental dogs and applies any wet or cold substance to the back. They try to run away but 

since they are in a cage they can only move in a circular motion due to the physical constraints of 

the cage. This fleeing from the handler was very brief (one or two turns), was not accompanied 

by any vocalization, scratching of, or attempt to lick, the application area. The investigator (see 

appendix report from Clinvet) considers this behavior not to be evidence of toxicity or an 

adverse effect. The fact that the sequential 4 applications to the 5X dogs and puppies did not 

induce this "escape" behavior indicates that the dogs quickly accommodated to the application 

since they did not perceive the procedure of re-applying the test substances as irritating, itchy or 

painful and there was no evidence of subsequent dermal pathologic change. The proposal by the 

reviewer that the test substances had any analgesic or topical anesthetic properties that "numbed" 

the area is unsupported and presumptious conjecture. 

A previous CASS on dogs and puppies (MRID 46166208) for a test substance containing five 

times the present level of cyphenothrin (40% + lOR) caused some adverse effects, but only at 5X 

dosage level. Ocular discharge and some salivation were recorded but no neurologic effects. 

However this study was conducted by a different institution (in the US) and the "fugitive" 

behavior was not seen. Another CASS (MRID 45121109, conducted by the same US facility) of 

an etofenprox spot-on (55%+ lOR) applied to cats and kittens induced no adverse effects. 

Felines are recognized as being much more sensitive to pesticides and more likely to show 

adverse effects, especially of a neurological nature, than dogs. These previous CASS results 

support the registrant's contention that the very brief episodes of running and circling seen 

immediately after test substance application in the present CASS are not evidence of adverse 

effects but similar to the following observations. 

Veterinarians and their staff are well aware of the conditioned reflex shown by pets that have 

previously visited the clinic. Most pets will not enter the building without being leashed or 

caged. The "fugitive or flight" behavior of some of the test dogs after first test substance 

application is very likely a conditioned reflex learned from previous treatment and handling 

experiences. 

8. Reviewer's Comment: 

"The application sites of all dogs in Group B3 (5X application of test substance II) had an oily or 

wet appearance .... Persistence of test substance II on the hair of dogs for more than 14 days is of 

concern due to potential human exposure of owners to pets." 
75

Response: 

The oily or wet appearance involving a 5X application is not indicative of the appearance of the 

product as it is sold and used. EPA has conducted risk assessments and determined that the 

intended exposure for each of the active ingredients in test substance II is acceptable in currently 

registered products. 
76

TABLE 1 (page 1) 

Dosage Chart for Sergeanfs Proposed Fipronyl-Containing Squeeze-Ons Labels for D

Dosage rates delivered in the CASS 

Dog Test Dose Fi ron I IA C henothrin IA N lar II Metho rene II N lar III) Meth

10 Group No Weight sub mL 8.80 8', 2.31 8. 8 2.43 0 

lase doses Ib kS sinale mslks mslks mslkg mslkg mglkg 

8A81DA 81 I adutt 1 42.7 19.38 1A&11I 1.34 6.08 5.67 1.68 

985105 81 I adult 1 38.4 17.44 1A&1I1 1.34 6.76 6.30 1.87 

CD5308 81 I adult 1 34.9 15.82 1A& III 1.34 7.45 6.95 2.06 

4352FE 81 I adult 1 37.0 16.80 1A&1I1 1.34 7.02 6.54 1.94 436801 81 I adult 1 34.5 15.66 1A& III 1.34 7.53 7.02 2.08 

985000 81 I adult 1 24.9 11.30 1A& III 1.34 10.44 9:72 2.88 

Mean 35.4 16.1 7.5 7.0 2.1 

+/- S.D. 5.9 2.7 1.5 1.4 0.4 

CD3585 82 I adult 5 42.0 19.04 1A& III 1.34 30.97 28.86 8.55 

9AF 038 82 I adult 5 38.8 17.62 1A&11I 1.34 33.46 31.18 9.24 

89C D33 82 I adult 5 33.4 15.14 1A & III 1.34 38.94 36.29 10.75 

8A9086 82 I adult 5 35.4 16.04 1A& III 1.34 36.76 34.25 10.15 

963618 82 I adutt 5 35.3 16.02 1A& III 1.34 36.80 34.29 10.16 

CD4 EAE 82 I adult 5 20.9 9.50 1A&11I 1.34 62.06 57.83 17.14 

Mean 34.3 15.6 1.3 39.8 37.1 11.0 

+1- S.D. 7.2 3.3 0.0 11.2 10.5 3.1 

985772 83 I adult 5 19.4 8.78 II 4.50 225.00 

983860 83 I adult 5 17.6 7.98 II 4.50 247.56 

9598D6 83 I adult 5 15.4 7.00 II 4.50 282.21 

886138 83 I adun 5 20.1 9.10 II 4.50 217.09 

68F 157 83 I adult 5 19.7 8.94 II 4.50 220.97 8A9917 83 I adult 5 9.0 4.06 II 4.50 486.58 

Mean 16.9 7.6 279.9 

+1- S.D. 4.2 1.9 104.1 

6CC 3A1 C2 1 42.8 19.40 IVA 1.00 

95682D C2 1 37.2 16.88 IVA 1.00 

965249 C2 1 36.6 16.60 IVA 1.00 9AF 246 C2 1 37.9 17.18 IVA 1.00 984 C4D C2 1 29.2 13.26 IVA 1.00 

89D6C2 C2 1 28.7 13.00 IVA 1.00 

Mean 35.4 16.1 

+1- S.D. 5.5 2.5 

CV0855 

, 
77

TABLE 1 (page 2) 

Dosage rates delivered in the CASS 

Dog -Test Dose Fipronyl (IA) cyphenothrin (IA) N lar (II) Methoprene (II) N lar (III) Math

10 Group No Weight sub ml 8,8% 8 2,31% 8.78% 2.43c/c 

I age doses Ib ka single ma/ka rna/kg ma/ka mglkg ma/ka 

CD5 C9C All pup 12.1 5.48 IA 2,00 32.12 29.93 

12.1 5.48 II 7,50 31.61 120.16 

COB F23 Al I pup 1 11.4 5.16 IA 1.83 31.21 29,08 

1 11.4 5.16 II 6.90 30.89 117.41 

CC647B All pup 1 4.7 2,14 IA 0.83 34,13 31.80 

1 4.7 2.14 II 3.10 33.46 127,19 

CD6 lA8 Al I pup 1 12.3 5,56 IA 2,00 31.65 29,50 

1 12.3 5.56 II 7.50 31.16 118.44 

CD4 FE6 All pup 1 11.0 4.98 IA 1.83 32,34 30,13 

1 11.0 4.98 II 6.90 32,01 121.65 

CD6 2CO All pup 1 4,7 2,12 IA 0.83 34.45 32.10 

1 4.7 2.12 II 1,30 14.17 53.84 

Mean 9.3 4,2 32.7 30.4 28.9 109.8 

+1- S.D. 3.6 1.6 1,3 1.2 7.3 27,6 

CDC ECA A2 I pup 5 16,1 7.32 IA 2.66 159.89 148.99 

5 16,1 7,32 II 10.00 157.79 599.73 

CD4407 A21 pup 5 9.3 4.20 IA 1.50 157.14 146.43 

5 9.3 4,20 II 5.62 154.55 587,42 

CD6 56C A2 I pup 5 6.0 2.70 IA 1.00 162.96 151.85 

5 6.0 2.70 II 3.76 160,64 611.35 

CD6 OAE A2 I pup 5 15,3 6.96 IA 2,50 158,05 147.27 

5 15.3 6.96 II 9,38 155.66 591.64 

CD5 A8D A2 I pup 5 10.8 4,88 IA 1,84 165.90 154.59 

5 10,8 4,88 II 6,88 162.84 618.92 

CD5 OFB A21 pup 5 7.8 3.56 IA 1.34 165,62 154.33 

5 7.8 3.56 II 5.00 162.22 616.57 

Mean 10,9 4.9 161.6 160.6 159.0 604.3 

+1-5.0. 4.1 1.9 3,8 3.5 3.5 13.3 

CC7692 Cll pup 5 21.3 9.67 IVA 2.62 

CD3 lAE Cll pup 5 6.6 2.98 IVA 0.88 

CD44BC Cl I pup 5 6.3 2.88 IVA 0.74 CD47EC Cll pup 5 17.1 7,76 IVA 2.12 

CC6224 Cll pup 5 9,9 4.50 IVA 1.24 

CD4A2B Cl/pup 5 8.0 3.62 IVA 1.00 

Mean 11.5 5.2 

+1- 5,0, 6.2 2,8 

CV0855 

, 
78

, 

TABLE 2 

Dosage Chart for Sergeant's Proposed Etofenprox-Contalnlng Squeeze-On Label for Small D

Justification Extrapolation from CASS CV 08 55 

Dog weight Active Etofenprox CASS dose Pyriproxyfen CASS 

Label potency 55.0% rate factor 2.2% rate f

@UCLofCSF 57.8% 1X 5X 2.3% 1X 

puppies 689.7 3796.3 28.9 

adults 1759.0 2.1 

Ib kg mL mQlkg mQlkQ 

4 1.8 2 636.6 0.92 0.17 25.5 0.88 

5 2.3 2 509.3 0.74 0.13 1 20.4 0.71 6 2.7 2 424.4 0.62 0.11 17.0 0.59 

7 3.2 2 363.8 0.53 0.10 14.6 0.50 

8 3.6 2 318.3 0.46 0.08 12.7 0.44 

9 4.1 2 282.9 0.41 0.16 11.3 0.39 

10 4.5 4 509.3 0.74 0.29 20.4 0.71 

11 5.0 4 463.0 0.67 0.26 18.5 0.64 

12 5.4 4 424.4 0.62 0.24 17.0 0.59 

13 5.9 4 391.7 0.57 0.22 15.7 0.54 

14 6.4 4 363.8 0.53 0.21 14.6 0.50 

15 6.8 4 0", !!:J 339.5 0.49 0.19 •. 13.6 0.47 16 7.3 4 

J 

318.3 0.46 0.18 ! 12.7 0.44 

17 7.7 4 299.6 0.43 0.17 12.0 0.41 

18 8.2 4 282.9 0.41 0.16 11.3 0.39 19 8.6 4 268.0 0.39 0.15 10.7 0.37 

20 91 4 254.6 0.37 0.14 10.2 0.35 

- - -_. 

Potency is upper certified limit on Confidential Statements of Formulae 

Italicised CASS factor based on mean group dose rates to the smallest dogs tested (12-15 week old puppiesl, 

all others based on adult CASS mean group dose rates 
79

Table 3 

% daily weight changes after treatment date for adults receiving etofenprox and pyriproxyfen 

Body Weights. kg diange/dax % Changefday 

days 1 7 14 1-7 1-14 1-7 7-14 1-14 1-7 1-14 1·7 

1 7 14 1-7 7-14 1-14 1-7 7-14 1-14 1-7 7·14 1-14 83 

8.7 8.44 8.56 -0.26 0.12 ·0.14 -0.03714 0.017143 -0.01000 ·0.427% 0.203% -0.00115 P < 0.05 

8.1 8 8.3 -0.1 0.3 0.2 -0.01429 0.042857 0.01429 ·0.176% 0.536% 0.001764 C2 

6.78 7 6.94 0.22 -0.06 0.16 0.031429 -0.00857 0.01143 0.464% ·0.122% 0.001686 

9.08 9.14 9.02 0.06 -0.12 -0.06 0.008571 -0.01714 -0.00429 0.094% -0.188% -0.00047 

9.06 9.16 9.08 0.1 -0.08 0.02 0.014286 -0.01143 0.00143 0.158% -0.125% 0.000158 

83 3.98 3.96 3.98 -0.02 0.02 0 -0.00286 0.002857 0.00000 -0.072% 0.072% 0 

Mean 1.62 7.62 7.65 0.00 0.03 0.03 0.000 0.004 0.002 0.007% 0.063% 0.033% 

1 7 14 1-7 7-14 1·14 1-7 7·14 1-14 1-7 7-14 1-14 

19.4 19.66 19.62 0.26 ·0.04 0.22 0.037143 -0.00571 0.01571 0.191% -0.029% 0.00081 

17.06 17.42 17.28 0.36 -0.14 0.22 0.051429 -0.02 0.01571 0.301% -0.115% 0.000921 

16.76 17.7 17.94 0.94 0.24 1.18 0.134286 0.034286 0.08429 0.B01% 0.194% 0.005029 

17.46 18.26 17.7 0.8 -0.56 0.24 0.114286 -0.08 0.01714 0.655% -0.438% 0.000982 

13.72 14.5 14.32 0.78 -0.18 0.6 0.111429 -0.02571 0.04286 0.812% -0.177% 0.003124 

C2 13.4 14.02 14.16 0.62 0.14 0.76 0.088571 0.02 0.05429 0.661% 0.143% 0.004051 

Mean 16.30 16.93 16.84 0.63 -0.09 0.64 0.090 -0.013 0.038 0.570% ..0.070% 0.249% 

Conclusions: 

1 group 83 (etofenprox adults 5X) showed smaller daily percen1 weigh1 changes (gains). compared with the untreated controls 

2 there were no signlfican1 differences in weigh1 gains In treated adults between 1X and 5X dose rates (group 81 VS 82) 

t] 

, 
80

Table 4 

% daily weight changes after treatment date for puppies that received etofenprox, cyphenothrin, fipronyl and 1he IGRs 

Body Weights. kg change change/day 

day 1 7 14 1-7 7-14 1-14 1-7 7-14 1-14 1-7 7-14 1-14 

Al 5.36 5.9B 6.66 0.62 0.6B 1.30 0.09 0.10 0.Q9 1.65% 1.62% 1.73% 

4.92 5.72 6.5B O.B 0.B6 1.66 0.11 0.12 0.12 2.32% 2.15% 2.41% Al 

2 2.2 2.24 0.2 0.04 0.24 0.03 0.01 0.02 1.43% 0.26% 0.86% P 

5.9 6.54 7.46 0.64 0.92 1.56 0.09 0.13 0.11 1.55% 2.01% 1.89% C! 

5.54 5.B6 6.B 0.32 0.94 1.26 0.05 0.13 0.09 0.83% 2.29% 1.62% 

2.06 2.3B 2.BB 0.32 0.50 0.B2 0.05 0.07 0.06 2.22% 3.00% 2.84% 

mean 4.3 4.8 5.4 0.48 0.66 1.14 0.07 0.09 O.OB 1.7% 1.9% 1.9% 

A2 7.64 B.12 8.54 O.4B 0.42 0.90 0.07 0.06 0.06 0.90% 0.74% 0.84% A2 

4.2 4.74 5.52 0.54 0.7B 1.32 0.08 0.11 0.09 1.84% 2.35% 2.24% P 

2.7 3.02 3.34 0.32 0.32 0.64 0.05 0.05 0.05 1.69% 1.51% 1.69% Cl 

7.26 7.76 BAB 0.5 0.72 1.22 0.07 0.10 0.09 0.98% 1.33% 1.20% 

4.96 5.7 6.62 0.74 0.92 1.66 0.11 0.13 0.12 2.13% 2.31% 2.39% 

3.5B 3.92 4.4 0.34 0.48 0.82 0.05 0.07 0.06 1.36% 1.75% 1.64% 

Mean 5.1 5.5 6.2 0.49 0.61 1.09 0.07 0.09 0.08 1.5% 1.7% 1.7% 

Cl 10.46 11.42 11.86 0.96 0.44 lAO 0.14 0.06 0.10 1.31% 0.55% 0.96% Al 

3.14 3.54 4.24 0.4 0.70 1.10 0.06 0.10 0.08 1.82% 2.82% 2.50% P 

2.B6 3.1 3.54 0.24 0.44 0.68 0.03 0.06 0.05 1.20% 2.03% 1.70% A2 

7.74 7.78 8.88 0.04 1.10 1.14 0.01 0.16 O.OB 0.07% 2.02% 1.05% 

4.B6 5.44 6.1 0.58 0.66 1.24 O.OB 0.09 0.09 1.70% 1.73% 1.82% 

3.92 4.08 5.32 0.16 1.24 1.40 0.02 0.18 0.10 0.58% 4.34% 2.55% 

Mean 5.5 5.9 6.7 0.40 0.76 1.16 0.06 0.11 0.08 1.1% 2.2% 1.8% 

Conclusions: 

1 1here were no significant differences in daily percent weight gains between treated and control pups or between the 2 groups (1 X vs 5X) 

2 treatment. even at 5X had no adverse effect on the growth of these puppies 

, 
81

Table 5 

Analysis of puppy weights and ages at treatment 

group dosage ages weights @ treatment 

weeks difference "I' Test alles kll "r' Test weillht 

A2 5 91 A1 5.48 A1 A2 5 87 " 0.05 5.16 " 0.4 A2 5 79 C1 2.14 C1 A2 5 106 5.56 A2 5 73 4.98 A2 5 87 2.12 

mean 87.2 12.5 12.5 4.2 

+/- s.d. 11.3 1.6 1.6 1.6 

A1 1 94 A2 7.32 A2 A1 1 87 " 0.1 4.20 " 0.8 A1 1 79 C1 2.70 C1 

A1 1 99 6.96 

A1 1 99 4.88 A1 1 91 3.56 

mean 91.5 13.1 13.1 4.9 

+/- S.d. 7.7 1.1 1.1 1.9 

C1 control 106 A1 9.67 A1 

C1 control 91 "0.4 2.98 " 0.5 C1 control 91 A2 2.88 A2 

C1 control 106 7.76 

C1 control 99 4.50 C1 control 99 3.62 

mean 98.7 14.1 14.1 5.2 

+/- S.d. 6.7 1.0 1.0 2.8 

eV0855 

, 
82

Enclosure 3 Attachment A 

Letter from Clin Vet 
83

SANAS SANAS 

~c!P (.QUlltUNICllPR.\C/or./ IOOGG lAU~.IOn. 

~n~o!lCI 

II March 2010 

Sergeant's Pet Care products 

PO Box 261248, 

Plano, Texas, 75026 

United States of America 

Dear Dr Miller 

INTE:RNATIONAL IPTYj LTD 

For attention: Dr Thoma') Miller 

FINAL REPORT: STUDY CV 08 55l PERFORMIlD AT CLINVIlT 

I refer to your comments on the recorded signs in some ofthe dogs after topical application of the test item. 

Areas that were shaved 

The application sites were not shaved. We did clip/shave (using an electric clipper) the areas of blood 

collection over the jugular vein.' Some dogs are more sensitive than others and a rash sometimes OCCur 

011 such a clipped area. This skin condition was noted (and specifically mentioned to be present during 

application) to ensure that it was not considered a reaction to the test item during post application 

observations. 

2 Running in circles: 

Two of six puppies in group A I and four of six in group A2 did some running in circles immediately after 

application. It lasted one or twO circles in the pen and then they calmed down. No scratching or 

attempts at licking. No vocalisation. 

Our impr~ssion was that the puppies were stimulated by the application of a liquid. They got used 10 the 

effect of being wet and no similar signs were seen after the following applications. 1 doubt very much if 

any owner will regard this behaviour as abnonnal or irritating. . 

Note: We observe all kinds of changes in behaviour after topical application of test items in studies. The 

mere presence ofa wet compollnd is llsually enough to make the animal run away. Only in this case 

there were boundaries (pen walls) and it could only run in circles. The question that needs 

answering is "WllY only the test item groups"? and why the behaviour change and no other s'tgns of 

irritation on the skin. A subjective conclusion was that the test items may have been cold (or felt 

cold, maybe as result of evaporation?). That could be the reason why the pups did not react after the 

next appl icanons and also why no signs were seen on the skin and why no other changes were 

recorded. The important issue is that animals react differently to wet applications and in the one 

group the dose volume was 5 times higher than recommended. lfno clinical signs are observed 1 

behaviollral changes cannot necessarily be seen to be as reSllh of an irritant. 

Yours falthf~c: J/-

Dr P el port (BVSCZ: director 

ClinVet International (Pty) Ltd 

Dr PC Oe/port B V Sc 

SAVe reg no D 70 10903 

Veterinarian 

.,1" jj" ".". '.1,;·.. "; " 
84

Enclosure 4 

Copy of EPA Efficacy Review 
85

Efficacy Review 

Date: February 12, 2010 

Efficacy Reviewer: Clayton Myers, Ph.D., Entomologis 

tll'ers.ela'ton,a; 

703-347-8874 

Risk Manager Rev.: Kevin Sweeney 

Products: EtofenproxtNylar Spot-on Flea and Tick for Dogs 

EPAReg.#: 2517-RGG 

A.I.'s: Ethofenprox (55.0%), Pyriproxyfen (2.2%) 

Decision #s: 420097 

DPIIs: 371693 

Submission: R310, New Products, RD Science Review 

MRIDs: Submitted: 47849607,4789608 

GLP:. No. 

MRID 47849607: 

Title: AnalY$is of a Dose Titration to Determine the Relationship between Dose Rate of 

Etofenprox, When Applied as aSpot-On to Dogs, and the Duration of Residual Efficacy Against 

Flea lInel Tick Reinfestation. 

Guideline: OPPTS 810.3300 

Materials and Methods: 

12 dogs were allocated to 3 treatment groups (4 dogs each, with average size approximately 

equal, using 30-40 Ib dogs). One was an untreated contrOl group, and the other groups were both: 

treated with an, etofenprox squeeze on, applied at 2 different dosages (approximately 8g and 4g, 

respectively). Rates of a.i. applied to animals were approximately 38 I mglkg and 178 mglkg, 

re$Pectively. Infestations (andreinfestations over time) were conducted with 50 ticks (R. 

sanguineus) and 100 cat fleas (c. felis). Fleas were counted via a comb at both 24 hours and 72 

hours after each infestationlreinfestatioil. Ticks were counted by hand. Removal of both was 

done at 72 hours for mortality assessments. Weekly reinfestations were conducted until 

inadeqnate efficacy was shown. % Mortality was calculated in comparison to the control. 
86

Regression analysis was conducted to determine ifthere was a significant correlation between 

treatment dose and duration of efficacy. 

Study Summary of the Results; 

I. Average flea efficacy was >90% for dogs in the 381 mglkg treatment group through 

31 days. For the 178 mglkg treatment, average efficacy was 89% at day 23 and 84% 

at day 31. 

2. Average tick efficacy was 89% for dogs in the 381 mglkg treatment group through 31 

days. For the 178 mglkg treatment, average efficacy was only 77% at day 31, but 

was adequate through day 23 (96%). 

3. There was no significant correlation between dosage and efficacy duration for fleas 

and ticks, due to insufficient numbers of dogs. 

4. Dose rates in the range of 250-300 mglkg were associated with 90% or higher 

efficacy at 31 days after treatment (looking atreinfestations on the 28th day). This 

observation can be used to generate a hypothetical dosage schedule for the treatment 

of puppies and dogs 151bs or less, with dogs up to 15lbsreceiving 1.2 mL ofa 55% 

etofenprox product, supporting a claim for the product of "up to 28 days" efficacy 

against re-infestation with fleas and ticks. 

Entomologist's ObservationslDiscussion; 

I. Replication was inadequate for the study as typically a minimum of 6 dogs are required 

for each treatment group. TypiCally, the dogs should be of varying breeds and weights, 

including larger dogs, but this issue isn't as critical for this study, as the proposed product 

is intended only for small dogs less than 20 Ibs. 

2. Efficacy was demonstrated for the 381 mglkg treatment group, but not for the 178 mglkg 

group. 

3. Despite a statistically insignificant relationship between the dosage and the efficacy 

duration for this product, the authors propose a titration scheme that would support 

efficacy claims for a product applied at a minimum of 250 mglkg a.i. This appears to be 

supported by the efficacy data for this present study, as dogs treated with this rate and 

higher were adequately protected for 30 days (albeit an inadequately small sample size). 

However, according to the study's own titration table, which is a bit confusing, the 

proposed dose (1.6 mL) appears to be inadequate for dogs larger than 6lbs, because the 

ai dosage falls below the threshold of250 mglkg. 

MRID 47849608: 

Title: Analyses of Efficacy and Safety Data to Support Label Claims for Sergeant's Squeeze-On 

for Small Dogs Containing Etofenprox and Pyriproxyfen. 

This is a summary document of other studies cited/submitted in support of this product. 

Entomologist's ObservationslDiscussion: Summarized in other reviews. 
87

Efficacy Review 

Date: February 12,201 0 

Efficacy Reviewer: Clayton Myers, Ph.D., Entomolo ist, RD-IB 

In 'ers.clavton1lJe a.!Z.ov .\l"Av 

703-347-8874 11 

Risk Manager Rev.: Kevin Sweeney 

Products: 

EPA Reg.#: 

A.I.'s: 

Decision #s: 

DP#s: 

Submission: 

MRIDs: 

GLP: 

MRID 47849601: 

EtofenproxlNylar Spot-on Flea and Tick for Dogs 

2517-RGG 

Ethofenprox (55.0%), Pyriproxyfen (2.2%) 

420097 

371691 

R310, New Products, RD Science Review 

Subrrritted: 47849601,47849602,47849603,47849604,47849605, 

47849606 

No 

Title: Efficacy of a Water-Based Etofenprox Spot-on against Fleas and Ticks on Small Dogs 

Guideline: OPPTS 810.3300 

Materials and Methods: 2 experimental groups of dogs, 6 dogs in each group, with weights 

ranging from 4.5-12.2 lbs. One group was a treatment group and one was a control. Treated 

dogs were dosed with 1.5 mL of a 55% etofenprox spot-on. Infestations (and reinfestations over 

time) were conducted with 50 ticks (R. sanguineus) and 100 cat fleas (C.folis). Fleas were 

counted at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted 

by hand. Removal of both was done at 72 hours for mortality assessments. Weekly 

reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated 

in comparison to the control. . 

Study Summary of the Results: 
88

I. Due to varying dog weights, the effective dose applied ranged between ISO-407 

mglkg (mean of231 mglkg). Dogs ranged in weight from 4.S-12.2Ibs. 

2. Efficacy against fleas was only adequate through 16 days. 

3. Efficacy against ticks was adequate through 31 days (mean efficacy of 94%). 

4. The dose applied is less than proposed on the label (2.0 mL for dogs 4-20 lbs). 

Entomologist's ObservationslDiscussion: 

I. While the data support efficacy claims on dogs for ticks through 30 days, the study is 

limited by the lack of dogs at the upper margin of the weight class, which would be the 

most likely to have an inadequate level of coverage by a 2.0 mL application. 

2. Because the rate applied is less than what is proposed on the product label, an 

approximation can be made based on the titration. For example, if I.S mL is adequate for 

a 12 pound dog, then 2.0 mL would only be adequate for dogs up to 16lbs (for ticks 

only). 

3. Flea efficacy was not adequately supported by this study. 

MRID 47849602: 

Title: Efficacy, at Minimum Dose Rate, of an Etofenprox Spot-on against Fleas and Ticks on 

Small Dogs 

Guideline: OPPTS 810.3300 

Materials and Methods: 17 dogs were allocated to 3 treatment groups (S-6 dogs each). One 

was an untreated control group, and the other groups were both treated with an etofenprox 

squeeze on, applied at 2 different dosages (2 mL and 4 mL, respectively). Dogs were grouped by 

size so that all dogs received an approximate dosage of 250 mglkg of etofenprox, as a minimum. 

Group B dogs were all approximately 7-10 Ibs, while Group C dogs were approximately 18-20 

lbs. Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) and 

100 cat fleas (c. ftlis). Fleas were counted via a comb at both 24 hours and 72 hours after each 

infestationlreinfestation. Ticks were counted by hand. Removal of both was done at 72 hours 

for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was 

shown. % Mortality was calculated in comparison to the contro!' 

Study Summary of the Results: 

5. For Group B dogs receiving 2.0 mL of treatment, flea and tick efficacy is adequate 

through 22 days after treatment. For Group C dogs receiving 4.0 mL of treatment, 

efficacy is adequate through 29 days after treatment. 

Entomologist's ObservationslDiscussion: 

I. While the study was designed to assess a 'minimum' dosage (250 mg etofenproxlkg 

animal), this meant that animals at the upper range of the the weight classification (i.e., 
89

20 Ib dogs) received a treatment that is approximately double the dose instructed on the 

product label (2 mL product for dogs weighing 4-20 Ibs). 

2. Therefore, dogs in group C were treated with more material than what is on the proposed 

product label. The data from this study would only support efficacy claims for dogs 

under 10 Ibs, which received 2 mL per animal, and those claims would only be valid for 

22 days after treatment, not a full 30 days. 

MRID 47849603: 

Title: Efficacy, at Label Dose Volrune and at Minimum Dose Rate, of an Etofenprox Spot-on 

against Fleas and Ticks on Small Dogs 

Guideline: OPPTS 810.3300 

Materials and Methods: 18 dogs were allocated to 3 treatment groups (6 dogs each). One was 

an untreated control group, and the other groups were both treated with an etofenprox squeeze 

on, applied at 2 different dosages (2.5 mL and "4.5 mL, respectively). Dogs were grouped by 

size. Group B dogs were all approximately 8-9Ibs, while Group C dogs were approximately 18-

20 lbs. Group B dogs were treated with 2.5 mL of spot-on per animal. Group C dogs were 

dosed by weight, so that each dog received 247 mg ai/kg, with applications thus varying from 4.3 

mL to 4.7 mLper animal Infestations (and reinfestations over time) were conducted with 50 ticks 

(R. sanguine us) and 100 cat fleas (c. felis). Fleas were counted via a comb at both 24 hours and 

72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal of both was 

done at 72 hours for mortality assessments. Weekly reinfestations were conducted until 

inadequate efficacy was shown. % Mortality was calculated in comparison to the control. 

Study Summary of the Results: 

6. For Group B, flea efficacy was adequate through 16 days after treatment. 

7. For Group B, tick efficacy was 89% for 23 days after treatment and 85% for 30 days 

after treatment. 

8. For Group C, flea and tick efficacy was adequate through 30 days after treatment. 

Entomologist's ObservationslDiscussion: 

1. Both treatment groups were treated with dosages exceeding that proposed on the 

submitted label, and thus the data are not valid to support efficacy claims for that 

proposed dosage. 

2. For dosages applied as listed in the study, efficacy against fleas in Group B animals was 

only adequate through 16 days after treatment. Efficacy in Group C was maintained at 

89% through 30 days after treatment. 

3. For dosages applied as listed in the study, efficacy against ticks in Group B animals was 

demonstrated to be 89% at 23 days after treatment and 85% at 30 days after treatment. 

Efficacy in Group C was maintained through 30 days after treatment. 
90

MRID 47849604: 

Title: Evaluation of Sergeant's Etofenprox Squeeze-on Against Fleas, Ticks, and Mosquitoes on 

Dogs. 

Guideline: OPPTS 810.3300 

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was 

an untreated control group, and the other group was treated with an etofenprox squeeze on, 

applied at 2.5 mL per animal. Dogs in the treatment group were all 10 Ibs or less, while control 

dogs ranged in weight from 11-14.3 Ibs. Infestations (and reinfestations over time) were 

conducted with 50 each of 3 species of ticks (R. sanguineus, D. variabilis, and A. americana) at 

various infestation intervals, and 100 cat fleas (c. jelis). Fleas were counted via a comb at both 

24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. 

Removal of both was done at 72 hours for mortality assessments. Weekly reinfestations were 

conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to 

the control. In the 3rd and 4th weeks after treatment, all dogs were anesthetized and confined for 

1 hour with 25 unfed Aedes aegypti or (separately) with 25 Culex quinquejasciatus mosquitoes, 

inside a screen cage. Landings were counted for 5 minutes. Dogs were removed after 1 hour 

and mosquitoes were recovered to assess survival and blood feeding status. 

Study Summary of the Results: 

9. Actual dosages applied to dogs ranged from 304-411 mg ai/kg. 

10. Flea efficacy was adequate through 23 days after treatment. 

11. Tick efficacy was adequate through 16 days after treatment. 

12. Treatment was not lethal to either species of mosquitoes, but inhibited blood feeding 

>90% (compared to control) for 30 days for Aedes and 29 days for Culex. 

Entomologist's ObservationslDiscussion: 

1. Dogs were treated with dosages exceeding that proposed on the submitted label, and thus 

the data are not valid to support efficacy claims for that proposed dosage. 

2. For dosages applied as listed in the study (2.5 rnL), efficacy against fleas is only 

supported for 23 days after treatment for dogs under 10 Ibs. 

3. For dosages applied as listed in the study (2.5 mL), efficacy against ticks is only 

supported for 16 days after treatment for dogs under 10 Ibs. 

4. For the 2.5 mL doses, claims against mosquitoes for prevention of blood feeding are valid 

only for dogs less than 10 lbs., and no kills claims are supported for mosquitoes. 

MRID 47849605: 

Title: Efficacy of Sergeant's Etofenprox Squeeze-on against Ixodes scapularis Nymphs 
91

Guideline: OPPTS 810.3300 

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was 

an untreated control group, and the other group was treated with an etofenprox squeeze on, 

applied at 2.5 mL per animal. Dogs in the treatment group Were all 10 Ibs or less, while control 

dogs ranged in weight from 11-14.3 Ibs. 3 days after treatment, hair was clipped from each dog. 

Ten nymphal ticks placed in petri dishes with each hair sample and mortality was assessed at 24 

hand 48 h after placement. % Mortality was calculated in comparison to the control. 

Study Summary of the Results: 

13. Actual dosages applied to dogs ranged from 304-411 mg ai/kg. 

14. Efficacy was 100% for ticks exposed to hair taken 3 days after treatment (I 00% 

mortality was observed at both 24 h and 48 h after placement on hair). 

Entomologist's ObservationslDiscussion: 

1. Distribution of hair samples was not specified, and the randomization scheme was not 

defined (i.e., were multiple samples pooled for each dog, or were sub-replicates 

established for each dog?) 

2. Because hair was clipped 3 days after treatment, claims against Deer ticks would only be 

valid for 3 days after treatment. This data would not support the one-month claim 

proposed on the label. A study that exposed ticks to hair taken 30 days after treatment 

would be required to demonstrate efficacy against deer ticks. 

MRID 47849606: 

Title: Efficacy of a 2 mL Unit Dose of Sergeant's Etofenprox Squeeze-on, Applied at Minimum 

Dose Rates, against Fleas and Ticks on Small Dogs 

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was 

an untreated control group, and the other group was treated with an etofenprox squeeze on 

(55%), applied at 2.0 mL per animal (as proposed on new product label). Dogs in the treatment 

group Were all 18-20 Ibs., while control dogs ranged in weight from 20-30 Ibs. Infestations (and 

reinfestations over time) were conducted with 50 each of3 species ofticks(R. sanguineus, D. 

variabilis, andA. americana) at various Infestation intervals, and 100 cat fleas (C.felis). Fleas 

were counted via a comb at both 24 hours and 72 hours after each Infestationlreinfestation. 

Ticks were counted by hand. Removal of both was done at 72 hours for mortality assessments. 

Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was 

calculated in comparison to the control. 

Study Summary of the Results: 

15. Actual dosages applied to dogs ranged from 122·233 mg ai/kg (mean 127 mg/kg). 
92

16. Flea efficacy was adequate through 16 days after treatment and 85% through 23 days 

after treatment. 

17. Tick efficacy was adequate through 23 days after treatment and 80% through 30 days 

after treatment. 

Entomologist's ObservationslDiscussion: 

I. This is the only study where the dosage applied to animals exactly matches the dosage on 

the proposed label, and also used dogs at the upper margin of the 20 Ibs. weight class. 

2. Efficacy against fleas is only supported for 16 days after treatment and marginally for 23 

days after treatment 

3. Efficacy against ticks is only supported for 23 days after treatment. 

Overall Review of Label Claims and Directions: 

None of the studies were submitted under GLP standards, and protocols were vague on the exact 

specifications by which parasites were placed on animals (e.g., random anatomical distribution 

per 810.3300 guideline). 

Claims against Deer Ticks, Ixodes, are not supported and must be removed from the label. 

Claims against Mosquitoes are not supported for the application rate of 2:0 mL proposed on the 

current label. The dosage would have to be raised to support this claim, and the claim must only 

be for repellenceisuppression of mosquito blood feeding. Kills andlor control claims are not 

supported by the data. 

The preponderance of data indicates that a 2.0 mL application of the proposed 55% etofenprox 

product is not adequate to protect dogs on the upper end of the weight class for the 30 day 

retreatment interval from fleas and ticks. If animal safety data are adequate, the registrant shonld 

label the product for different application rates to different weight classes of dogs. Some 

variability is evident even when the dosage is raised to 2.5 mL for small dogs Under 10 lbs. For 

dogs between 10-20 Ibs, the dosage should be raised to 4.5-5.0 mL in order to support the label 

claims of control of fleas and ticks for 30 days. 

Claims against flea eggs and larvae are not supported by this data and must be removed from:jhe 

label. Also, claims regarding breakage of the flea life cycle and prevention offlea eggs from 

developing for up to 9 weeks (70 days) after application are not supported and also must be 

removed. 

Removal of unacceptable claims is deferred to the RM reviewer and PM, as some claims may 

possibly be acceptable under conditional registrations with later submission of acceptable 

efficacy data. 
93

Enclosure 5 

Copy of EPA CASS Review 
94

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF PREVENTION. PESTICIDES 

AND TOXIC SUBSTANCES 

February 24, 2010 

MEMORANDUM 

Subject: Name QfPesticide Product: ETOFENPROXINYLAR SPOT-ON FLEA AND 

TICR FOR DOGS AND PUPPIES 

EPA Reg. No. !File Symbol: 2517cRGG 

DP Barcode: DP 371676 

Decision No.: 42Q097 

Action Code: R310 

PC Codes: 128965 (Etofenprox: 55%) 

129032 (pyrlproxyfen: 2.2%) 

. From: l3yron T. Backus, Ph.D" Toxicologist (3 ~ (? - C • 

Technical Review Branch 01.- - 1-"t - 1-0 , Co 

To: 

Registration Division (7505P) . rf'V 

Kevin SweeneylRichard Gebken, RM 13 

Insecticide Branch 

Registration Division (7505P) 

Registrant: SERGEANT'S PET CARE PRODUCTS, INC. 

. FORMULATION FROM LABEL: 

Active Ingredient(s); 

128965 Etofenprox 

129032 Pyriproxyfim 

Other Ingredientfs): 

TOTAL 

ACTION REQVESTED: The Risk Manager requests: 

" ... Please review the attached study and documentation." 

Page I of16 

Bywt. 

55.00% 

2.20% 

42.80% 

100.00% 
95

BACKGROUND: 

The material received includes a companion animal safety study (in MRlD 47849609) titled: 

"Companion animal safety evaluation on dogs of spot-on products containing multiple toxicants 

and insect growth regulators" as well as a CSF apd a proposed label for the product which would 

be applied to small and/or toy breed dogs weighing 4-20 lbs. The label dosage rate is given as 

2.0 mLldog/application. 

COMMENTS AND RECOMMENDATIONS: 

1. An Agency contractor, Oak Ridge National Laboratory, conducted the primary review ofthe 

companion animal safety study. TRB perfonned the secondary review and made changes as 

nec·essary. 

2. The study is not acceptable to support the proposed use(s) on adult dogs and puppies and 

cannot be upgraded. Test groups consisted of 6 (3 male and 3 female) adult dogs or puppies. 

The 870.7200 Companion Animal Safety Guidelines specify that at least 6 animals per sex 

should be .used at each dosage level. In addition, the adult dogs that were treated with test 

substance II (containing 55..11;% w/wetofenprox, 8.78% wiwmethoprene, and 2.31 % w/w 

pyriproxyfen) at 5X theaosage rate weighed (on day -I) 4.06, 7.00, 7.98;8.78, 8.94 and 9.10 kg. 

Since .only one dog in this gtoup weighedless than 9 lbs ('tOo kg = 8.951bs» thedata.couldnot 

be. used to support thettse of this' formulation on adult dogs we:lg1:iing 4-9 lbs, particularly as the 

ratio .ofbody surface area to mass could be a motor in absotptionand toxicity. Cumulative 

dosage rates were 3.08, 3.21, 2.82, 2.56, 2.52 and 2.47 mLlkg (the 4.06 kg dog received a 

cumulative amount of 12.5 mL test material; the others each received 22.5 mL), with a mean of 

2.78 mLlkg; dividing this by 5 (for the 5X margin of exposlIte) gives 0.555 mLlkg; and dividing 

2.0 mL (the proposed dose) by 0.555 mLlkg giVes 3.60 kg (= 7.94lbs), which is also 

substantially above the proposed 4 lb lower weight limit For the puppies, it is impossible to 

compare and interpret differences in body weight gains between groups when tjJ.ere was such a 

range in ages (IQ-lSweeks, with no information as to specific ages for individual animals), the 

dogs were mixed breed and tjJ.e two heaviest puppies (CC7 692 andCD4 7Ee), which would be 

expected to showthe greatest weight gains, were both in the control group. 

3. TRB considers the behavioral changes (tunning and circling imi:nediately after application of 

the test substance) in 7 animals (one adult, 6 puppies) as an adverse effect. It is noted that the 

animals showing behavioral changes were all exposed to test materiallA (8.2(JO/o cypheaothrin, 

9,8% fipronil, either in combination with material III, 8.90%methoprene and 2.43% 

pyriproxyfen, for the one adult, orin combination with material II, 55.16% etofenprox, 8.78% 

methoprene and 2.31 % pyriproxyfen for the puppies). Although the four puppies in group A2 

(receiving 5 applications ofmateriallA and S of II) showed running and circling only after the 

first application of the test substance and not after the second, third, fourth or fifth application, 

this may simply be an indication that the application area had been numbed. 

4. Refer to the attached DER for additional comments. 

Page 2 of 18 
96

DATA EVALUATION RECORD 

CYPHENOTHRIN, FIPRONIL, ETOFENPROX, METHOPRENE, 

PYRIPROXIFEN 

COMPANION ANIMAL SAFETY STUDY- DOGSIPUPPIES - (OPPTS 870.7200) 

MRID 47849609 

Primary Reviewer: 

Prepared for 

Registration Division 

Office of Pesticide Programs 

U.S. Environmental Protection Agency 

One Potomac Yard 

2777 S. Crystal Drive 

Arlington, VA 22202 

Prepared by 

Toxicology and Hazard AssessmentGroup 

Environmental Sciences Division 

Oak Ridge National Laboratory 

OakRidge, TN 37831 

Virginia A. Dobow. V.M.D., M.P.H. Signature: 

Date: 

Secondary Reviewers: 

Dana F. GJass, D.V.M. Signature: 

Date: 

Robert H. Ross, M.S., Group Leader Signature: 

Date: 

Quality Assurance: 

Kimberly Slusher, M.S. Signature: 

Date: 

Disclaimer 

This review may have been altered subsequent to the contractor's signatures above. 

Oak Ridge National Laboratory managed and operated by UT_Battelle, LLC., for the U.S. Department of Energy 

under Contract No. DE_AC05_000R22725. 
97

EPA Reviewer: Byron T. Backus, Ph.D. 

Technical Review Branch, Registration Division (750SP) 

Signature: G ;r5'. (3 •. Q. ? 

Date: 0 -"1. t - 1-.<>\" 

Templ.te version 02/06 

I DATAEVALUATIONRECORD 

STUDY TYPE: Companion animal safety study- dogs/puppies - OPPTS 870.7200 

PC CODE: 128965- Ethofenprox, 129032- Pyriproxyfen, DP BARCODE: 371676 

TEST MATERIAL (PURITY): Cyphenothrin (8.2% w/w), Fipronil (9.8% rnlw), Etofenprox 

(55.16% w/w), S-Methoprene (8;78% w/w), Methoprene (8.90% w/w) and Pyriproxifen (2 .. 31% 

and 2.43% w/w) 

TRADE NAME: Not provided 

CITATION: Delpot:t, P.C. (2009) Companion animal safety evaluation on dogs of spot-on 

products containing multiple toJcicl;lllts and insect gI'9wth regulators. CliDVet International (pty) 

Ltd., Bloemfontein, Republic of South AfriCi!. Study No. CV 08/551, August 6, 2009. MRID 

47849609. Unpublished. 

SPONSOR: Sergeant's Pet Care Products, Plano, Texas 

EXECUTIVE SUMMARY: In a companion animal safety study (MRID 47849609), groups of 

tandom-source adult (> 6 monthsohge) and juvenile (10-15 weeks ofage) dogs were topically 

adn:iinistet!:d 3.combinations o.fiDsecticides and insect growth reguli!tofs or one 'inert substance. 

Two gi-oupsofthreemale and three.fumalejuveniLe dogs were administered test substance IA 

(8;2% wlw cyphenothrin and 9;8% nilwfiproniJ;' Batch No. 012003-09) and test substance n 

(55.16% w/wetofenpfox, 8.78% w/ws-methoprene and 2.31%w/wpyriproJcifen; Batch No. 

011901-09) at either IX (recommended dose) or 5X (recommended dose hourly ror 5 

applications). Thetestsubstances'were applied simultaneously as adjacent stripes along the 

dorsum of the dog fro1;l behind the ears caudally to the base of the tail. Two groups of three male 

and three female adult dogs 'Weighing 9-20 kg were administered the test substance IA and test 

substance III (8.90% w/w methoprene and 2.43% w/w pyriproxifen; Batcli No. 011902-09) at 

either IX (recommended dose) or 5X (recommended dose hourly for 5 applications). The test 

substances were applied as previously described. A group,ofthree male and three female adult 

dogs weighing less than 9 kg was administered test substance II at 5X (recommended dose 

houdy ror 5 appliClitions). A group of three IIlale and three female juvenile dogs and another 

group of three male and three female adult dogs were administered control substance IVA (Batch 

No. 012004-09) containing inert ingredients (not otherwise stated) at 5X the recommended dose. 

The groups and test materials they received are shown in the table below: 

Page 4 of 18 
98

Group 

A Group AI (n"'li) Puppies (10.15 weeks) Group A2 (.-6) Puppies (10· IS weeks) 

Single application of substance lA Fi'vc applications of substance IA 

Single application of substance II Five applications of substance II 

B Group B I (n"'li) Adults (9·20 kg) Group 82 (n-6) Adults (9·20 kg) Group B3 (n"'li) Adults (~ kg) 

Single application of substance lA Five appllcations of substance IA Fiv~ applications of substance II. 

Single aoolication of substance III Five· applications of substance; III 

C Group CI (n=6) Puppies (10-15 weeks) , Group C2 (n 6) Adults (9-20 kg) 

Five applications control subst,ance IVA Five applic.ations control of substance IVA , Substance IA contams 8.~% w/w cyphenothnn and 9.8 Va rrilw fiproml. 

Substance II contains 55.16% w/w etofenprox, 8.78% w/w s·methoprene, 2.3 1% w/w pyriproxifen. 

Substance III contains 8.90% methoprene, 2.43% w/w pyriproxifen. 

CO,Dtrol substance IVA contains inert control substances. 

The animals Were observed for clinical signs oftoxicity and dermal irritation for four hours postapplication and then twice daily for the dJJration of the study (14 days post-application). Body 

weight, body weight gain, food consumption and clinical pathology parameters (hematology Ilnd 

clinical chemistry) were measured at the required intervals. 

All animals survived to the end of the Stlldy. ,Immediately after treatment, one adult dog ,in Group 

BI (IX applications of test substances IA and III) showed behavioral changes (running,: circling). 

This behavioral chllnge was not considered treatment-related in adultS by the sponsor since it was 

not observed at 5X the recommended dose. Immediately aftet treatment, two puppies in Group 

AI OX application of test substances IA and II) showed behavioral changes (running,circl'ing). 

Four puppies in Group A2 (5X application of test substances IA and II) showed similar 

behavioral changes after the first application but not after subsequent applications. These 

behavioral changes are cOl1$idered to be art adverse effect. White crystallization was observed,on 

the hair'tips of many aduli: ,and juvenilc::,dogs in the treated and control groups. The application 

sites of all dogs in Group BS {5X application oftest'substance IT} had an oily or wet appearance. 

The ·sign disappeared from one dog on Day +14'but was present on all others at the, end of the 

study. 

All adult dogs and puppies' gained weight from Day -I to Day 14. However, mean weight gain in 

pups in !he treated, groups (AI and A:l) was 15% lower than the control group pups. The mean 

weight gain in the treated adult animals (Groups B 1, B2 and B3) was decreased (30-99% as 

compared to the control group). The difference, relative to controls was largest in the smaller 

adult dogs in Group B3 (99% decrease as compared to the control group). Food consumption 

was not affecte4 by treatiJ:!ent. No treatment-related hematology or clinical chemistzy changes 

were observed. 

It is noted that the 7 animals (one adult, 6 puppies) that showed behavioral changes {running and 

circling) immediately,after application of the test substance were all exposedto test material IA 

(8.20% cyphenothrin, 9.,8% fipronil, either in combination with material ill, 8.90%,methoprene 

and 2.43% pyriproxyfen, for the one adult, or in combination with material II, 55.16% 

etofenprox, 8,78% methoprene and 2.31 % pyriproxyfen for the puppies). Although the four 

puppies in group A2 (receiving 5 applications of material LA and 5 of II) showed running and 

,circling only after the first application of the test substance and not after the second, third, fourth 

or fifth application, this may simply be an indication that the application area had been numbed. 

Page 5 of\8 
99

Test groups consisted of 6 (3 male and 3 female) adult dogs or puppies. The 870.7200 

Companion Animal Safety Guidelines specify that at least 6 animals per sex should'be used 

at each dosage level. In addition, the adult dogs that were treated with test substance II 

(containing SS.16% w/w etofenprox, 8.78% wlw methoprene, and 2.31% wlw 

pyriproxyfen) at SX the dosage rate weighed (on day -1) 4.06, 7.00, 7.98, 8.78, 8.,94 and 9.10 

kg. Since only one dog in this group weighed less than 91bs (4.06 kg = 8.95 Ibs), the data 

could not be used to support the use of this product/formulation on adult dogs weighing 4-9 

Ibs, particularly' as the rlltio of body surface area to mass could be a factor in absorption 

and toxicity. Also, it was not possible to compare body weight changes between adult 

group B3 (which received the etofenprox-containing formulation) and the control (C2) 

group because initial mean body weights were so different. For the puppies, it is impossible 

to compare and interpret differences in body weight gains between groups when there was 

such a range in ages (10-15 weeks, with no information as to specific ages for individual 

animals), the dogs were mixed breed and the two heaviest ,puppies (CC7 692 and CD4 

7EC), whil:h would be expected to Show the greatest weight gains, were both in tbe control 

group. 

In addition, it is concluded that the margin of safety in puppies administered simultaneous 

topical application attest substances IA (8.2% wlw cyplienothrin and9;8% m1w fiproilil) 

and II (55:16% w/w etofenprox, 8.78% wlw s-methoprene and 2.;31% w/wpyriptoxit'en) 

was less than IX the recommended dose, based on clinical signs of toxicity (bebavioral 

changes immediately post-application). 

This companion animal safety study in male and female random-source adult dogs and puppies is, 

UnacceptablelGnidelineandd!les not satisfy the guideline requil:ement for a companionarumal 

safety study (OPPTS 870.7200) in the dog and canrtotbe upgraded for either adults or puppies. 

See Study Deficiencies section fotdetalls. Major deficiencies include too few' animals per group, 

failure to testthe end-use product and lack of some requil:edreporting, 

COMPLIANCE: Signed and dated' OLP, Quality Assurance and Data Confidentiality 

statements were provided for ClinVet International. Pathcare VetarinaryLaboratory, which 

conducted the hematology and clinical chemistry analyses, is not OLP accredited but is ISO 

15189 certified. 

Page 6 ofl8 
100

I. MATERIALS AND METHODS 

A. MATERIALS: 

1. Test materials: 

1a. Test substance 1 (code name IA) 

Description: 

Batch fl.: 

Purity: 

Storage: 

Not provided 

012003-09 

8.2% W/W cyPhenothrin and 9.8% m/w fipronil* 

At room temperature 

Compound Stability: Expiration date: January 20, 2011 

CASH: Not prov!ded 

• Batch 2008·Pip.D3. expiration date August 19, 2010, packed_in foil and stored at ambfent temperature, inside carton 

box. dry 

lb. Test substance 2 (code name II) 

Description: 

Batch #: 

Purity: 

Storage: 

CompouDdStability: 

CASH: 

Not provided 

01l901-09 

55.16% w/w etofenprox, 8.78% w/w s-mcthoprene,.2.31 % W/w pyriproxif~n 

At room temperature 

Expiration date: January 19,2011 

Not provided 

1c.·Test substance 3 (code naine III) 

Description: 

Batch #: 

Purity: 

Storage: 

Compound Stability: 

CAS#: 

Not provided 

011902-09 

8.90% w/w methoprene, 2.43% w!w"pyriproxifen 

At room t~~peratUrc 

Expiration date: Il!nuary 19. 2011 

Not l"avided 

1d. Cotttrolsubstance (code·name IVA) 

Description: 

Batcb#: 

Purity: 

S.orage: 

Compound Stability: 

CASH: 

Not provided 

012004-09 

Inert control substance (no purity provided) 

At room temperature 

Expiration date: II!nDOry 20, 2011 

Not provided 

2. Vehicle control: See control substance described in 1 d. above. 

Page 7 of 18 
101

3'. Test animals: 

Speeies; 

Strain: 

Age/weight 

Source: 

Housing: 

Diet: 

Water: 

Environmental conditions: 

Temperature: 

Humlalty: 

Air changes: 

Photoperiod: 

Acclimation period: 

B. STUDY DESIGN: 

Dog 

Described as "indifferent" 

Groups AI and A2: 10·15 weeks on day 0 (2.12 -7.32 kg or4.67-l6.14Ibs) 

Groups Bl and 82: ",6 mos on day 0 (> 9 kgS 20 kg or>19:84IbS 44.09Ibs) 

Group B3:;:: 6 mos on day 0 ($ 9 kg or:S 19.841b) 

Group CI: 10·15 weeks on day 0 (2_88 -9.67 kg or 6.35·21.32Ibs) 

Group C2:" 6 mos on day 0 (> 9 kg S 20 kg or >19.84Ib 544.09lbs) 

ClinVet International (Pty) Ltd. Colony 

individuaHy housed in pens 

Adults (>12 months) were fed a commercial dry dog food (example: ULTRADOG 

SUPERWOOF DOG FOOD); puppies « 12 months) were fed an "appropriate 

puppy food" (example: Eukanuba puppy and junior medium breed) 

Tap water, ad.libitum 

20" 4" c 

Not pro~rided 

12·15. air cbanges1hr 

12 hours Iight/12 hours dark 

Fourteen days 

1. In life dates: Start: March. 19, 2009; End: April 16, 2009 

2. Animal assignment: Forty.two animals were-assigned to the study, The genders were 

separated and the, dogs allocated to stody groups (Fable 1) Within the body weight 

requirements using randomization through. ~zation WiJh body weight as the only 

criterion. For medium sized adnlt dogs; Within each gender, animals were blocked into tlttee 

blocks oftbree dogs each. The three heaviest dOgs formed block 1; the next three heaviest 

dogs fonnedblock :2 and the next three formed block 3. Within blocks, dogs were allocated 

to one of three groups, I, 2 or 3. The first animal of block 1 was assigned to group I, the 

second to group 2 and the third to group 3. The first-animal ofblook2 was assigned to group 

3, the second to group 2 and the third to group I. The first animal of block 3 was assigned to 

group 1, the second to group 2 and the third to group 3. Groups 1, 2 and 3 wete then 

randomly assigned to the a'Ctuli1 groups B 1, B2 and C using Excel randbetween. Puppies 

were.similarly assigned to groups AI, A2 and Cl. The six dogs in group B3 were allocated; 

no randomization was possible. 

Page 8 ofl8 
102

Tablel: Stu4y 4esign 

Group 

A Group AI (n=6) Puppies (10-15 weeks) Group A2 (n=6) Puppies (IO-IS weeks) 

Single application of substance IA Five applications of substance IA 

Single application of substance rr Five applications of substance II 

B Group 8 I (n=6) Adults (9-20 kg) Group B2 (n=6) Adults (9-20 kg) Group 83 (n=6) Adults (<9 kg) 

Single application of substance lA Five applications of substance lA Five appli.cations of substance 11 

Single aooiication of substance I1I Five aoDlications of substance 111 

C Group CI (n~6) Puppies (IO-IS weeks) Group C2 (n=6) Adults (9-20 kg) 

Five R-qDlicatiQns COlllTol SUbS~CCi lVA 1:?ive applications'control ofsubS1attce IVA 0 .. Substance 0 fA contains g.2l-b w/w cyphenothnn and 9.8 j.b m/w fiproml. 

Substance II contains 55.16% Vi/w etofenproxt 8.78% w/w s~rneth6prene, 2.31 % w/w pyriproxif'en. 

SUbstance III contains 8,90% methoprene, 2.43% w/w pyripro.xifen. 

Control substance IVA contains inert control substances. 

3; nose selection rationale; The·dose rates for test substance IA are based on fipronil and 

methoprene on the Frontline Plus label and pyriproxyfen in Setgeant's Gold for Dogs. For 

t\lst substance II, the study report states that the maximum etofenprox smaIl dog dose rate is 

758 mg/kg. For test substance Ill, the dose ofpyriproxyfen and s-methoprene is based on 

Sergeant's Gold for Dogs and Frontline Plus label. However, none of the dose rates used is 

representative of the proposed label. 

4_ Preparation and treatment: Thetest and control substances were applied as measured 

doses from syringes (Without needles)toa furrow in the hair on the back, starting high ori the 

neck behind the ears and extending caudally towards the baseofl:he tall. The fur was not 

shaved or clipped. Technicians applying the substances were blinded to the test material. 

Test substances lA, II and III Were applied separately as "terminally adjacent stripes, 

applyiilg test substance IA anterior to test substance II or test substance IA anterior to test 

substance ill." The placebo control formulation IVA was applied separately. Substances lA, 

II and III Were not.mixed. 

Test substances.IA and II were applied as single doses,once only; to the pups in test group 

A1 and fi,vetimes conseqllently at hourly intervals, each time as a single dose, to the pups in 

test group A2. SubstancesIA and II were not mixed. 

Test substances IA and III were applied as single doses, once.onlY,to theadnlt dogs in group 

B 1, five times consequently at hourly intervals, each time as a single dose, to the adult dogs 

in group B2. Substances IA and III were not mixed_ Test substanee II was applied five times 

consequently at hourly intervals, each time as a single dose, to the adult dogs in group B3. 

The control substance IVA was applied five times consequently at hourly intervals, each time 

as a single dose, to pups and dogs ingroups CI and C2, respectively. 

The dose volumes of the test and control SUbstances were determined by the animal's weight 

on Day -I (fable 2). 

Page 9 ofiS 
103

Tab1.~l: Doses 

Groul> TesUllb,lan •• Total dos.admlnistered 

Al (puppies) IA 0.83 - 2.0 mL (lX) 

II 3.1 7.5 mL (ix) 

A2 (puppies) IA 5.0 -13.30mL (1.0 -2.66 mL x 5) 

- II 18.8 - 50.0 mLc3.16 -10.0 mL x5) 

Bl (adults) IA 1.34 mL (IX) 

III l.)4mLiIX) 

B2 (adults) IA 3.4 - 6.7 mL(0.58 - 1.34 mLx 5) 

III 3.4 - 6.7 mL (0.68 -1.34 mLx 5) 

B3 adults) II 12.5 - 22.5 mL (2.5 - 4.5 mL x 5) 

Cl( puppies) IVA l3.IOmL (2.62 mLx 5) 

C2 .d\ll~) IVA 5.0 mUl.O mL x 5) .. Substance lA contains 8.2% w/w cyphenothnn and 9.8%rilJw tipronlt. 

Substance U contains 55.16% w/w etofenprox. 8.78% w/w s.methoprencl 2.31% w/w pyriproxifcn. 

Substance In COriwns 8.90% metboprene, 2.43% w/w pyriproxifen. . 

Control substance IVA contains..incrt control substanc.cs. 

5. Statistics: The emphasis of the statistical analyses was the change from baseline of each of 

thehematololi,Yand clinical chemistry parameters. Individual hematology and clinical 

chemistry values on test days were tabulated separately for each varillble and each group, 

together with'the folloWing descriptive statistics: mean, standard deviation (SD), coefficient 

ofvl!fiatjol1 (~N %.), geQrnetricmean, geometric SD, minimum, maximum and the n\lltl.bet .of 

observations: fu the group. The fudividual changes and percentage changes from baseline (test 

day -3) for each of the post-treatrnent days were calcuhited.!!lld tabulated fot each variable 

and each group. The numbet of post-treatment values that fell outside the reference range 

was calculated. The post-treatment values were compared tothe baselfue values in an intratreatment comparison by means of an analysis of variance (ANOVA) with an animal and 

observation time as effects. Anintet-treatmentcomparison with respect to the changes from 

baseline was also performed. The post-treatment values of each the three test treatment 

groups (BI, B2 and B3) were compared to the col1trol group (C2) for adult dogs. The posttreatment values of each of th.e two test treatrPent groups (AI and A2) were COl11pared to the 

two controlgrollps (el) for puppies. An analysiS of covariance (CO'-AAOVA) wi\:h.a 

treatment effect and the baseline values as covariate was used. fur the analyseS. fu addition, 

the change from baselfue values of each of the three trea:trnemgroups (Bl, B2 and B3) Wete 

compared to those of the control group (02) ror dogs and the two test groups (AI and A2) 

were compared to those of the c6ntrol group (C1) for puppies by means of an ANOV A with 

a treatment effect. Groups AI and A2 were compared in a similar way. 

C. METHODS: 

1. Observations: 

a. Genel'a1.health observations: The anim:als were observed dally for genetai.health. 

Specific health observations were observed hoUrly on the day of application until four 

hours after application of the test material and twice daily, thereafter, for the duration of 

the study. Observations included, but were not limited to, changes in skin and fur, eyes 

and mucous membranes, nervous signs and behavior pattern as well as vomiting and 

diarrhea. Local tolerance observations were also included. 

Page 10 ofl8 
104

b. Veterinary examinations: Physioal examinations were conducted by a veterinarian on 

Days -14, -3, +1, +7 and +14. The examinations included but were not limited to body 

temperature. pulse rate, auscultation of the heart and lungs, mucous membranes and skin. 

j9ints, eyes, ears, mouth and genital organs .. 

2. Body weight: Animals were weighed on Days -14. -7. -1, +1, +7 and + 14. 

3. Food consumption: The amoUllt offood offered was measured and the food consumption 

was recorded daily and scored using the following scoring system. 

Fc 1- 0-25% 

Fc 2 - >25- 50% 

Fc 3 - >50-75% 

Fc 4 • >75·100% 

4. Hematology and clinical chemistry: Blood was collected from the jugular vein for 

hematology and clinical ohemistry·assessments on fasted animals on the following days: • 3. 

+ 1, +7 and +14. The tests were conducted byPathcare. Bloemfontein, South Africa, because 

ClinVet I11ternational did not have the expertise and apparatus to perfonn the analyses. The 

CHECKED (X) parameters were examined. 

a. Hematology 

x x 

X 

X . M'~n ";'rnJ~j~~:~.;). tiMC)' x '., v61ume (Mev)' 

X , count 

-x 

x 

!fur • haseiiOiiOWfS 

Page II of 18 
105

b. Clinicalchemistrv 

ELECTROLYTES OTHER 

X Calcium'" X Albumin* 

X Chloride" X Creatinine· 

Magnesium X Urea nitrogen" 

X PhospbQ~s .. Total Cholesterol. 

X Potassium· (K) X Globulins· 

X Sodi\lll1' (NA) X Glucose· 

ENZYMES (mor. than ~hepatie enzymes. eg .• ') X Total bilirubin .. 

X Alkolirte phosphatase (AP)' X Total protein" 

Cholinesterase (ChE) Triglycerides 

Creatine kinase AlbuminlGlobulin ratio 

Lactic aero dohy!1rogen ... (LDH) X Direct tlilirubin* 

X Alanine amirtotransferase (AL T/also SGPl)' I;1dircc:t bilirubin 

X Aspartaieamino1l"al!sferuc (AST/also SOOT)' BUN1Creatinine ratio 

GaInmiI. g1utamyl1;ansferoe (ool) TC02 Bicarbo,gate 

AnlY~· 

Sorbitol dehYdrogenase .. .. '" Recommended for a companIon annnal safety evaluation base<l on oPPrs 870.7200 

'5. Urinalysis: Urinalysis was J;lot conducted. 

6. Sacrifice and pathology: The study did not have a scheduled necropsy. 

II. RESULTS 

A. ACTUAL. DOSES ADMlNlSTERED: The mglkg doses of active ingredients were not 

calculated. Based oncalculauons· by the EPA reviewer, the IilL/kg doses to puppies were 

significantly higher than those to adults. For example, adults in Group B I weighing 11.3 to 

19.38 kg received 1.34 mL each of.test substances IA and III for a 0.12 to 0.07 mL/kg <lose 

of each substance'. Puppies in Group Al weighing 2.12 to 5.56 kg received 0.83 to 2.0 mr. Of 

test substance IA for a 0.36 to 0.39 mLIkg dose, apprOximately 5 times the·adult dose. 

Puppies in GroupIAreceived 3.1 to 7.5 mL oftest substance n fora 1.34 to 1.46 mLlkg 

dose, approximately 19 times the adult dog dose. 

B. OBSERVATIONS, 

1. Clinical sims or toxicity: Immediately after treatment, one adUlt dog in Group B I showed 

behavioral changes (running, circling). Ano.ther adult dog in Group 113 had skin irritation on 

the shaved area of the neck (asswned to be area shaved for blood collection). In· Group C2, 

one dog had loose feces three hours post-application, Qne dog had loose mucoid feces with 

blood on Day +2 and another dog had mucoid feces on Day +2. Minor clinical signs 

observed in adult dogs after treatment included the following: swollen marrunary gland 

(Group C2, Days +7 and +14); scab on scrotum (Group C2, Day +14); eczema on neck 

(Group B3, Day +7); hair loss on chin (Group B3, Days +7 and +14); and right eye 

lacrimation (Group B2, Day +7). A female in Group BI came into estrus on Day +1. 

Page 12 ofiB 
106

Immediately after treabnent, two puppies in Group AI showed behavioral changes (running, 

circling). Four puppies in Group A2 showed similar behavioral changes after the first 

application but not after subsequent applications. One pup in Group A I had loose feces on 

Day +1 with blood on Day +4. A pup in Group A2 had loose feces on Day +13. Minor· 

clinical signs in puppies after treabnent inCluded the followi;lg: thinning of hair in one pup in 

Group A2 On Day +7 which was diagnosed as demodicosis on Day +14; thinning of hair 

(Group A2, Day + 14); and scales (two pups in Group C 1, Day + 14). While the demodicosis 

(mange) was not life threatening, its occUrrence suggests that the overall health of the dogs 

and puppies may have been compromised. 

2. Application site examination: White crystallization was observed on the hair tips of adult . 

dogs in Groups Bl [four dogs at one hour post-application and one dog on Day +IJ, B2 

(three dogs at one hour post-application, one dog on Day + 1 and two dogs on day +2), B3 

(two dogs at one hour post-application, four dogs at three hours post-application and one dog 

at Day +2) and C2 (three dogs at two hours post-application, one dog at 3 hours postapplication, one dog at foUt hours post-application and one dog at Day +2). The application 

sites of all dagS in Group B3 had an oily or wet appearance. The sign disappeared from one 

dog on Day +14 but was present an all other dogs.at the end of the study. 

White crystals were. observed on the hair tips of pups in Groups Al (two pups atone hour 

post-application and one pup at three hours post-appli~tion), A2 (one pup each at one hour 

and two hours post-application) and CI (three pups at one hour post-application and one pup 

at two hours post-application). 

3. Mortality: All adult and juvenile dogs survived to the end of the study. 

B. BODY WEIGHT.AND WEIGHT GAIN: Body weight data1!I'e presented in Tabid. All 

adult and juvenile dogs gaiI),ed'weightfroinDay--l to Day 14. However, mean weight gain in 

pups in the treated groups CAl and A2) was 15% lower than the control group pups. The 

mean weight gain in the treated adult animals was decreased (30-99% as compared to the 

control group). The change was largest in the smaller adult-dogs in GrQUP B3 (99% dectease 

as compared to the contral group). 

Page 13 ofl8 
107

Tabl. 3: Mean bod. weighl and body wei.hl •• in' 

. Sody w.i.bt (kRl Sod. wei.ht •• in 1<2) 

GrQu~ Da.-1 D •• +1' Oay +7' .D •• +14 Da. -I to +1' Dov -I to +7" DaY -1 to +14 

Al ·up. 4.24 4.30 4.78 5.44 0.06 0.54 1.20115%)' 

A2 up, 4.94 5.06 5.S4 6.15 0.12 0.60 1.2[(15%)' 

CI nuos 5.24 5.50 5.89· 6.66 0.26 0.65 1.42 

.81 adults 16.07 16.41 16.63 16.62 0.34 0.56 0.55 30%)C 

B2 adulls 15.56 15.48 15.75 15.80 -0.08 0.19 0.24 70%)C 

B3 adults 7.64 7.62 7.62 7.65 -0.02 -0.02 0.01 99%)' 

C2 adults 16.05 16.30. 16.93 16.84 0.25 0.88 0.79 

• N "'" 6/group, exceptwhere noted. 

b Calculated by the reviewer from data on pages 4647, MRID 47849609 

t. Decrease com.pared to .control gro.up .. calculated by the reviewer" 

Group Al !)'ealechUXwith Substance IA (8.2% wlw cypfienothrin and 9.8% m!w fipronil) and Substance II (55.16% w/W 

etofenprox; 8.78% wlw s..mcthoprene, 2'.31 % w/w pyriproXifen) 

Group A2 treated al5X with Substance 1A(8.2% wlw cyphenothrin and 9.8% m!w fipronil) and Substance II (55.16% wlw 

elofonprox, 8.78% wlw s-methoprene, 203'I%wlw pyriproxifen) 

Groups CI and C2.treated· at 5X with Control stibstancc·1V A 

Group BI treated at IX with SubstancelA (8.2% wlw cyphenotlllin and 9.8% m/w fipronil) and Substance 1lI (8.90% 

mctboprene, 2.43~ w/w pyriproxifen) 

GroupB2 treated at 5X with Substance IA (8.2% wlw typhenothrin and 9.8% m!w fipronil) and Substance 111 (8.90% 

methoprene. 2.43% w/w pyriproxifen) 

C. FOOD CONSUMPTION: No treatment-related effects· were reported_ 

D .. 'CLINICAL PATHOLOGY ANALYSES: 

1_ Hematology: No treatment-related ch!mges were observed in adults or pups_ An increase 

(as compared to the control group) in monocyte counts in Group BI adult dogs on Day 

+1 was not. considered toxiccilogically significant. 

2. Clinical Chemistry: No treatment-related effects were reported in adults or pups. A 

decrease(as compared to the control group) in creatinine in Group B3 on Day +7 and a 

decrease in ASTin Group B3 on Day +14 were not considetedtoxicolagically 

Significant. The mean glucose valueinG1;oup A2 was increased from baseline (Day -3) to 

Days +1 and +14_ The mean chloride values in Groups Al and A2 were increased from 

baseline to Day +7_ These deviations are not considered toxicologically significant. 

m. DISCUSSION AND CONCLUSIONS 

A. INVESTIGATORS' CONCLUSIONS: The study author concluded that two test 

substances, blend IA containing 8.20% w/w cyphenothrin and 9.80% mlw fipronii and blend 

II containing 55.16% w/wetofenprox, 8_78% w/w s-methoprene and 2.31 % w/w 

pyriproxifen, were safe to use under the conditions of the study when applied simultaneously 

as a spot-on to puppies at the recommended dose as well as five times (5X) the recommended 

dose. 

Blend II containing 55.16% w/wetofenprox, 8,78% w/w s-methoprene and 2.31% w/w 

pyriproxifen, was safe to use under the conditions of the study when applied topically to 

adult dogs at five times the recommended dose. 

Page 140fI8 
108

Two test substances, blQnd IA containing 8.20% w/w cyphenothrin and 10.07% w/w fipromi 

and blend III contaiIDng 8.90% w/w methoprene and 2..43% w/w pyriproxifen, were safe to 

use under the conditions of the study when applied simultaneously as a spot-on to adult· dogs 

at the recqmmended dose as well as at five times the recommende.d dose. 

B. REVIEWER COMMENTS: All animals survived to the end of the study. Immediately after 

treatment, one adult dog in Group B 1 (IX applications of test substances IA and III) showed 

behavioral changes (running, circling). Immediately after treatment, tWo puppies in Group 

Ai (IX appliqation of test substanCes 1A and II) showed sirnilarbehavior. Four puppies in 

Group A2 (5X application of test substances IA and II) showed the same behavior after the 

first application but not after subsequent applications. The behavioral signs are considered 

treatment-related in puppies since they occurred in multiple ammals both at IX and 5X the 

recommended dose. The behavioral change in adult dogs is considered treatment-related 

since it also occurred in puppies. 

White crystallization was observed on the hair tips of many adult and puppies in the treate~ 

and control groups. The application Sites of all dogS in Group B3 (5X application oftest 

suhstancelI) had an olly or wet appear~ce. The sign disappeared from one dog on Day +14 

but was present on alI'other do gsattheend of the study, Since there was· no skin irritation, 

.theSigns are considered cosmetic. HllWever, the persistence ottest substance II on the hair of 

dogs for more thai114 days ls. of concern 4ue to potential human exposUre of owners to pets. 

All adult andjuvemle dogs gained weight from Day -I toDay 14. However, mean weight 

gain in pups in the treated groups (Aland A2) was -15% lower than the control group pups. 

The change is considered treatment-related. The mean weight gain in the treated adult 

aillmals (Groups Bl, B2 and B3)was decreased (30-99% as compared to the control group). 

The change was largest in the smaller adult dogs in Group B3 (99% decrease as compared to 

the control group). The anirna:ls were considered adults if \hey were >6 months of age. Adult 

. c:iogs usually are not expeeted to change weight in a '14-day period; however, dogs as young 

as 6 months may still be.gaining weighf. The birth. dates of the .an1ma:ls were not provided so 

their exact 'age is unknown. Since the decreases from the control gr-oup were large, the 

decreased body weigh/gain. is considered treatrnent-relatedin adults. FOod consumption was 

not affected by treatment. No treatment-related hematology or clinical chermstry changes 

were observed. 

It is concluded that the margin of safety in puppies administered simultaneous topical 

applications of test substances IA (8.2% wlw cyphenothrin and 9.8% mIw fipronil) and 

II (55.16% wlw etofenprox, 8.78% w/w s-methoprene and 2.31 % w/w pyriproxifen) was 

less than 1X the recommendell dose; based on clinical signs oftoxicity (behavioral 

changes imme",iately post-application). 

It is coneluded that the margin of safety in adult dogs (9-20 kg) administered 

simultaneous topical application of test substances IA (8.2 % w/w cyphenothrin and 

9 .• 8% mlw fipronil) and III (8.90% w/w and 2.43% wlw pyriproxifen) was less than IX 

the recommended dose, based on elinical signs oftoxicity (circling and running in one 

dog after application). 

Page 15 ofiS 
109

It is concluded that no Il!argin of safety in adult dogs «9 kg) administered a topical 

application oftest suhstan'ce n (55.16% wfwetofenprox, 8.78% w/w s"methoprene and 

2.31 % wlw pynproxlfen) could be established from the findings ofthis study. 

. . 

This study is unacceptable and cannot be upgraded for either adult dogs or puppies. 

C. STUDY DEFICIENCIES: 

a. The study report states that the purpose of the study is to determine the safety ofa 

combination of three test formulationspot·on products containing three toxicants and two 

insect growth regulators. The Companion Animal Safety Guideline (OPPTS 870.2700) 

requires that a study be conducted With the end-use product using the label dose and 

directions for use,although there is a provision for use of a max/lox product containing 

multiple toxicants at the maximum levels which would be anticipated in formulated 

topical products. However, this does not appear to have been the objective of the study. It 

is also unclear why different combinationsof'products were tested in adult and juvenile 

animals. Pups were administered test substances IA and n, whereas large adult dogs were 

ru4nhUstered test substances lA.and III and smaller dogs were administered test substance 

II alone. 

b. Other Companion Animal Safety Guideline non-compliances are as follows: 

!. The study used three dogs/sex/group, whereas six dogs/sex/group are required. 

2. Individual animal data for clinical signs were not provided. 

3. Group Qlean values for body weight were not.calculated for Days-14, ·7, +1 and +7. 

4. The control formulation is described as "inert control substance". However, it is not 

certain for Which of tile test formulatiohS was this the "inert control substance," as no 

analysis was provided. 

5. The date of birth of the animals was not provided. 

6. Themglkgdose of active ingredients was not calculated. 

7. The laboratory which conducted the hematology and clinical chemistry testing is not 

GLP accredited. 

8. The Guideline allows fur five hourly applications ofa IX dose to achieve the 5X dose. 

However, with the large volumes of test material used on some of the smaller animals, 

it is likely that the material ran off and was not available for abSOrPtion. 

9. The study report states that test substances IA, II,and III were applied separately as 

terminally adjacent stripes, applying .test substance IA anterior to test substance II or 

test substance lA anterior to test substance III. It is unclear" how the second substance 

could be applied anteriorly When both were administered from the neck to the base of 

thetai!. 

10. A certificate of analysis was not provided for each of the test substances. The study 

report states that the concentration of cyphenothrin in test substance IA should have 

been 15% as stated in the protocoi but a certificate of analysis indicated that it was 

8.2%. 

Page16of18 
110

11. The study author's conclusion (page 56) gives different peroentages offipronil in test 

substance IA when discussing the findings in puppies (9.8% mlw) and adults (10.07% 

w/w). 

Page 17 oflS 
111

\ 

, 

~. DP BARCODE: 371676 

2. PC CODES: 128965 (Etofenprox); 129032 (pyriproxyfen) 

3. CURRENT DATE: February 24, 2010 

4. TEST MATERIALS: Blend IA: 8;20% w/w cyPhenothrin, 9.80% w/w fipronil; Blend II: 

55,16% w/wetofenprox, 8.78% w/w methoprene, 2.31 % w/w pyriproxyfen; Blend III: 8.90% 

w/w methoprene, 2.43% w/wpyriproxyfen; Blend IVA: inert control substance 

StudylSpecieslLab MRID Results Tox. Core 

Study # IDate Cat. Grade 

Companion Animal Safety StudylDogs & 47849609 Four groups (each 6M & 6F) of NfA U 

Puppies adult dogs; 3 groups (each 6M & 

6F) of puppies were used. Adull$: 

CUnVet International (Ply) Ltd; Group Ell IX lA&ID; Group B2: 

Bloemfontein, South Africa 5X IA&ID, Group B3: 5X n; 

Group C2 5X IV A. Puppies: 

S!tldy CV 08155 I I August 6, 2009. GroupAIIXLA≪GroupA2: 

5X LA&n;Group CI: 5XIVA. 

Not pos$ible to ad"'luate!ylllterpret data from design of srudy.. 

.. Core Grade Key. A ~ Acceptable, S Supplementary; U Unacceptable, W - WaIV!>d 

Page 18 ofl8 
112

of 1t-Y1'(g;} 

Recommendation of Division Directors ~f1~ 

Negotiated Due Dates 

Decision #: 420097 I Registration #: 2517-RGG I Petition #: 

Fee Category: R310 PRlA Decision Time Frame: 6 months 

Submitted by: Kevin Sweeney Branch: RDIIB I Date: 3/24/2010 

Company: Sergeant's Pet Care Products, Inc. 

Original Due Date: March 31, 2010 I Proposed New Due Date: April 30,2010 

Previous Negotiated Due Dates: None 

Is the "Fix" in-house? No If not, date "Fix" expected: April 2, 2010 for 

rebuttal to EPA reviews 

Issue (describe in detail): 

Registrant submitted new product to treat "Toy Dogs". They cited a product that is registered for use on 

cats. The cited product chemistry data were not accepted because they formulated the new product with an 

alternate formulation of the cited product instead of the basic formulation. Second, the companion animal 

safety study (CAS) was determined to be unacceptable. There were deficiencies with the efficacy studies 

but most of those can be resolved with labeling changes and some more efficacy data. The acute 

toxicology data citations were acceptable. 

Summary of Deficiency Type(s): Not Submitted (N) Deficiencies (D) 

Product Chemistry: (D} Acute Tox: _ Efficacy: (D} Labeling: (D} 

Other (describe): (0) Companion Animal Safety Data 

Describe Interactions with Company (describe when contacted and company's response including 

response to previous negotiated due dates): 

Had nUmerous discussions with the registrant over CSF citations in February. 

On March 2, 2010 all ofthe DERs were sent to the registrant's representative at Exponent and the 

deficiencies discussed with them. A 75 day letter was sent on March 10, then revised and re-sent on 

March 22, 2010 with a new 75 day date. The March 10 letter informed them ofthe CAS and efficacy 

deficiencies. The product chemistry deficiencies were added to the March 22, 2010 letter following an 

extensive discussion with the Technical Review Branch concerning Confidential State of Formula 

(CSF) citations. Met with the registrant face-to-face on March 17 and discussed next steps with the 

registrant on the telephone on March 19,2010. Registrant submitted extension request on March 23, 

2010. They have requested a first extension of only 30 days. No data or rebuttal will be submitted 

before the PRlA due date of March 31, 2010. Instead, they propose to submit a rebuttal by April 2, 

2010. They will also request a meeting at that time to discuss their concerns further. 

"75 Day" Letter sent? 03/22/2009 (Date sent) Yes No and reason for none? 

Rationale for Proposed Due Date: 

I 

Registrant n«#ified that this is the last negotiation? Yes x Not Applicable 

Approve: \j I Disapprove: 

Fonn revised: May 2007 
113

If disapproved, action to be taken: 

: I r I rOD or DOD Signatnre\:, \1 ~ \1 JI Date: , 

- , 

,I wl; \\ i .:3' -3D - I 0 , , ; i \JJJVv 

\ ~ \ \ \jV \ \ 

Fonn revised: May 2007 
114

EXponent" 

March 23, 2010 

Richard Gebken, PM Team 10 

Document Processing Desk 

U.S. Environmental Protection Agency 

Office of Pesticide Programs (7504P) 

Room S-4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202-4501 

Subject: Response to EPA Letter Dated March 22, 2010 

Exponent 

1150 Connecticut Avenue, NW 

Suite 1100 

Washington, DC 200)6 

telephone 202-772-4900 

facsimile 202-772-4979 

www.exponent.com 

EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies (EPA File 

Symbol 2517-RGG) 

Dear Mr. Gebkin, 

On behalf of our client Sergeant's Pet Care Products, Inc. (Sergeant's) (EPA Company Number 

2517), Exponent is SUbmitting a response to EPA's 75-day deficiency letter dated March 22, 

2010 regarding EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies. 

Please find enclosed the following documentation in support ofthis submission: 

(I) Application for Pesticide Form (8570-1). 

At this time, Sergeant's is notifYing the Agency that it plans to continue supporting this pending 

registration application. The current PRIA due date is March 31, 2010. Based upon EPA's recent 

letter iUs our understanding. that additional time will be needed by EPA and Sergeant's to further 

review this pending application. Sergeant's requests an initial 30-day PRIA extension. We 

believe this 30-day extension will be sufficient for the Agency and Sergeant's to review our 

initial response to the EPA letter. 

Sergeant's strategy is to submit a written rebuttal to EPA by April 2, 2010. This letter will 

address the issues identified in the Agency's deficiency letter of March 22, 2010. In addition, 

Sergeant's will submit product-specific product chemistry data to EPA to support this product 

registration. Once all of the above information is submitted to EPA, Sergeant's requests to meet 

with EPA to discuss the support data in detail. 

Sergeant's intends to request a meeting with appropriate EPA staff to discuss our submission in 

April. We will submit a separate meeting request letter to you with our submission. 
115

If after we meet with the Agency there is a need to extend the PRIA date, Sergeant's will submit 

a second PRIA extension request to EPA. 

If you have any questions, please contact me at 202-772-4932. 

Sincerely, 

-.. 

~~l/ IJ~<~lbL/CL)) James Messina 

Authorized Representative of 

Sergeant's Pet Care Products, Inc. 

Enclosure 

cc: Kevin Sweeney, EPA 

Kelly Hoskins, Sergeant's 

Larry Nouvel, Sergeant's 

Rick Tinsworth, Exponent 
116

Please read instructions on reverse before completing form. Form Approved. OMS No. 2070-0060. Approval expires 05-31-98 

United States ~_Registration OPP Identifier Number 

EPA Environ'mental Protection Agency D_Amendment 

Washington, DC 20460 D Other 

Application for Pesticide· Section I 

1. com~5~y/product Number 2. EPA Product Manager 3. Proposed Classification 

2 17-RGG R. Gebken 

4. Company/Product (Name) PM# DNone D EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies PM-10 Restrlcted 

5. Name and Address of Applicant (Include ZIP Code) 6. Expedited Review. In accordance with FIFRASection 3(C)(3)(b)(I), my 

Sergeant's Pet Care Products, Inc. product is similar or identical in composition and labeling to: 

2637 South 158th Plaza, Suite 100 

Omaha, NE 68130-1703 EPA Reg. No. 

Product Name 

o Check if this is a new address 

Section II 

D Amendment - Explain below. D Final printed labels in response to Agency letter dated XX-XX-XX 

~ Resubmission in response to Agency letter dated 3-22-10 D "Me Too" Application 

D Notification - Explain below. D Other - Explain below. 

Explanation: Use additional page(s) if necessary. (For section I and Section II.) 

Submission in response to EPA leHer dated March 22, 2010, requestto extend PRIA due date. 

Section III 

1. Material This Product Will Be Packaaed In: 

Child-Resistant Packaging Unit Packaging Water Soluble Packaging 2. Type of Container 

DYes' DYes DYes o Metal 

DNo o No o No o Plastic 

If "Yes" No. per If "Yes" No. per DGlass 

'Certification must Unit Packaging wgt. Container Package wgt. Container 

DPaper be submitted I I DOther (Specify) Plastic Bag 

3. Location of Net Contents Information 4. Size(s) Retail Container 5. Location of Label Directions 

DLabel o Container TBD DOn Can 

Don Labeling accompanying product 

6. Manner in Which Label is Affixed to Product gLithOgraPh DOther ~-.-,-----~-- _._-----_._--- .. __ .-.. _._.,---- ----0------------.------------- - -- Paper glued 

DStenciled 

Section IV 

1. Contact Point (Como/ete items directly be/ow for identification of individual to be contacted, if necessary, to DrDCesS this aDDlicationJ 

Name Title Telephone No. (include Area Code) 

James Messina Authorized Representative 202-772·4932 

Certification 6. Date Application 

I certify that the statements I have made on this fOlm and aI/ attachments thereto are tlue, accU/ate and complete. I Received 

acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both (Stamped) 

under applicable law, 

2_Sign~ ~ 

/{~~ 3. Title 

~,~ Authorized Representative 

4. Typed Name: James Messina 5. Date: March 23, 2010 
117

DATE OUT: 02/01110 

SUBJECT: FEE PRODUCT CHEMISTRY REVIEW OF MP [I EP [XI 

DP BARCODE No.: D371682 REG. No. IFile Symbol No. 2517-RGG 

PRODUCT NAME: ETOFENPROXYINYLAR SPOT-ON FLEA AND TICK FOR DOGS 

AND PUPPIES 

PCC: 129032,128965 

FOOD USE [I 

Decision No. 420097 

COMPANY: SEARGANT'S PET CARE PRODUCTS, INC. 

FROM: 

\ A -v\v"v\ ' .. ~ . \\0 

~di crairola, Chemist 

Product Chemistry Team 

Technical Review BranchiRD (7505P) 

TO: Kevin SweeneylRichard Gebken PM 13 

Insecticide BranchiRD (7505P) 

INTRODUCTION: 

SEARGANT'S PET CARE PRODUCTS, INC. is seeking registration for the subject product 

ETOFENPROXYINYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES. 

Applicant has submitted a Basic and Alternate CSF both dated 09/10109. Applicant claims the 

product to be a "Me Too" of EPA Reg. # 69332-3. The submitted package was reviewed and 

details will be discussed below: 

SUMMARY OF FINDINGS: 

I. The subject ETOFENPROXYINYLAR SPOT-ON FLEA AND TICK FOR DOGS AND 

PUPPIES contains 55.0% of Etofenprox and 2.2% ofPyriproxyfen. 

2. SEARGANT'S PET CARE PRODUCTS, INC. has cited MRID #s 461613-01,-02 and 

467008-01 for Product Chemistry data to support the registration of 

ETOFENPROXYINYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES. 

3. The sources of active ingredients listed for the subject product are registered. 

4. Basic and Alternate CSF both dated 09110109 meet the label claim of 55.0% of Etofenprox 

and 2.2% ofPyriproxyfen. 
118

5. Inerts used are approved for non-food use. 

6. The subject product is not identical to EPA Reg. # # 69332-3 from product chemistry point 

of view, product chemistry data cannot be cited. Product chemistry product specific data 

for the proposed new product must be submitted. 

CONCLUSIONS: 

TRB has reviewed the aforementioned product chemistry data submitted for the above 

mentioned subject product and has concluded that: 

1. The subject product ETOFENPROXY INYLAR SPOT-ON FLEA AND TICK FOR DOGS 

AND PUPPIES contains 55.0% of Etofenprox and 2.2% ofPyriproxyfen. 

2. Basic and Altemate CSF both dated 0911 0/09 are found acceptable. 

3. The label claim is in compliance with PR Notice 91-2. 

4. Product Chemistry to support the registration of ETOFENPROXY INYLAR SPOT -ON 

FLEA AND TICK FOR DOGS AND PUPPIES cannot be cited. Product chemistry product 

specific data for the proposed new product must be submitted. 
119

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460-0001 

Mr. James B. Messina 

Authorized Representative of 

Sergeant's Pet Care Products, Inc. 

Exponent 

1130 Connecticut Avenue, NW 

Suite 110 

Washington, DC 20036 

Subject: New Product Registration (R31 0) 

EPA File Symbol: 2517-RGG 

OFFICE 

of PREVENTION, PESTICIDES 

AND TOXIC SUBSTANCES 

MAR 2 2 2010 

Product Name: EtofenproxlNylar Spot-on Flea and Tick for Dogs and Puppies 

Date of Submission: September 10,2009 

Dear Mr. Messina: 

The application referred to above has been determined, pursuant to 40 CFR § 152.1 05, not to be 

sufficiently complete to process. Therefore, the application is considered deficient. The companion 

animal safety study is unacceptable and there are a number of deficiencies in the product performance 

studies. You must address these deficiencies, as detailed below, within 75. days of the date of this letter, 

before the processing of the application can be continued. 

If, after 75 days, you do not respond, or you subsequently fail to complete the application within 

the time scheduled for completion as noted below, the Agency will terminate any action on this 

application and will treat the application as if it has been withdrawn by the applicant. Any subsequent 

submission relating to this application must be submitted as a new application. 

The noted deficiencies for this R31 0 new product; non-fast track application are highlighted 

below. Details can be found in the Data Evaluation Reports (DERs) I sent to you on March 2,2010. 

1. The companion animal safety study (MRID 47849609) is unacceptable and cannot be upgraded. 

2. The basic formulation of your product is not similar to the basic formulation of the cited product. 

Therefore, you must generate product specific chemistry data on your product. Citing an alternate 

formulation does not relieve you from the product specific chemistry data requirement because the 

product chemistry data for every product has been generated from the basic formulation only. 

3. The product performance DERs identified problems in the submitted studies with replication, dosage, 
120

and study design. 

The PRIA due date for this product is March 31, 2010. For reference purposes, the timeline 

for your response (provided an extension of the PRIA due date is granted) is June 6, 2010. If you 

have not responded, or you subsequently failed to complete the application within the time scheduled for 

completion, the Agency will terminate any action on the application, and will treat the application as if it 

has been withdrawn. 

If you have any questions, please contact Kevin Sweeney at (703) 305-5063 or via e-mail at 

sweeney. kevin@epa.gov Thank you for your cooperation in this matter. 

S!ncerely, ,1 

1.1 ~. {\. it / / U~· 

/ / I -'~rt; ·vL.----.l ' c.~ 0 '-p~ ~ic 'd 1. Gebken, 

Product Manager 

Insecticide Branch, 

Registration Division (7505P) 
121

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460-0001 

Mr. James B. Messina 

Authorized Representative of 

Sergeant's Pet Care Products, Inc. 

Exponent 

1130 Connecticut Avenue, NW 

Suite 110 

Washington, DC 20036 

Subject: New Product Registration (R31 0) 

EPA File Symbol: 2517-RGG 

OFFICE 

of PREVENTION, PESTICIDES 

AND TOXIC SUBSTANCES 

MAR 1 0 2010 

Product Name: EtofenproxlNylar Spot-on Flea and Tick for Dogs and Puppies 

Date of Submission: September 10, 2009 

Dear Mr. Messina: 

The application referred to above has been determined, pursuant to 40 CFR § 152.1 05, not to be 

sufficiently complete to process. Therefore, the application is considered deficient. The companion 

animal safety study is unacceptable and there are a number of deficiencies in the product performance 

studies. You must address these deficiencies, as detailed below, within 75 days of the date of this letter, 

before the processing of the application can be continued. 

If, after 75 days, you do not respond, or you subsequently fail to complete the application within 

the time scheduled for completion as noted below, the Agency will terminate any action on this 

application and will treat the application as if it has been withdrawn by the applicant. Any subsequent 

submission relating to this application must be submitted as a new application. 

The noted deficiencies for this R31 0 new product; non-fast track application are highlighted 

below. Details can be found in the Data Evaluation Reports (DERs) I sent to you on March 2, 20 I O. 

1. The companion animal safety study (MRID 47849609) is unacceptable and cannot be upgraded. 

2. The product performance DERs identified problems in the submitted studies with replication, dosage, 

and study design. 
122

The PRIA due date for this product is March 31, 2010. For reference purposes, the timeline 

for your response (provided an extension of the PRIA due date is granted) is May 25, 2010. If you 

have not responded, or you subsequently failed to complete the application within the time scheduled for 

completion, the Agency will terminate any action on the application, and will treat the application as if it 

has been withdrawn. 

If you have any questions, please contact Kevin Sweeney at (703) 305-5063 or via e-mail at 

sweeney. kevin@epa.gov Thank: you for your cooperation in this matter. 

Sincerely, n I 

'\- " (\1~' I i 

',./ ! ',')I,-JXi ~- ,I I 

-, C-, ! 

'~ , Ri<l,birrd Jd ebken, 

C Product Manager 

Insecticide Branch, 

Registration Division (7505P) 
123

Efficacy Review 

Date: February 12,2010 

Efficacy Reviewer: 

Risk Manager Rev.: Kevin Sweeney 

Products: EtofenproxINy1ar Spot-on Flea and Tick for Dogs 

EPA Reg. #: 2517-RGG 

A.I.'s: Ethofenprox (55.0%), Pyriproxyfen (2.2%) 

Decision #s: 420097 

DP#s: 371693 

Submission: R31 0, New Products, RD Science Review 

MRIDs: Submitted: 47849607,4789608 

GLP: No 

MRID 47849607: 

Title: Analysis of a Dose Titration to Determine the Relationship between Dose Rate of 

Etofenprox, When Applied as a Spot-On to Dogs, and the Duration of Residual Efficacy Against 

Flea and Tick Reinfestation. 

Guideline: OPPTS 810.3300 

Materials and Methods: 

12 dogs were allocated to 3 treatment groups (4 dogs each, with average size approximately 

equal, using 30-40 Ib dogs). One was an untreated control group, and the other groups were both 

treated with an etofenprox squeeze on, applied at 2 different dosages (approximately 8g and 4g, 

respectively). Rates ofa.i. applied to animals were approximately 381 mg/kg and 178 mg/kg, 

respectively. Infestations (andreinfestations over time) were conducted with 50 ticks (R. 

sanguineus) and 100 cat fleas (c. felis). Fleas were counted via a comb at both 24 hours and 72 

hours after each infestationlreinfestation. Ticks were counted by hand. Removal of both was 

done at 72 hours for mortality assessments. Weekly reinfestations were conducted until 

inadequate efficacy was shown. % Mortality was calculated in comparison to the control. 
124

Regression analysis was conducted to detennine if there was a significant correlation between 

treatment dose and duration of efficacy. 

Study Summary ofthe Results: 

1. Average flea efficacy was >90% for dogs in the 381 mg/kg treatment group through 

31 days. For the 178 mg/kg treatment, average efficacy was 89% at day 23 and 84% 

at day 31. 

2. Average tick efficacy was 89% for dogs in the 381 mg/kg treatment group through 31 

days. For the 178 mg/kg treatment, average efficacy was only 77% at day 31, but 

was adequate through day 23 (96%). 

3. There was no significant correlation between dosage and efficacy duration for fleas 

and ticks, due to insufficient numbers of dogs. 

4. Dose rates in the range of250-300 mg/kg were associated with 90% or higher 

efficacy at 31 days after treatment (looking at reinfestations on the 28th day). This 

observation can be used to generate a hypothetical dosage schedule for the treatment 

of puppies and dogs 151bs or less, with dogs up to 15 Ibs receiving 1.2 mL of a 55% 

etofenprox product, supporting a claim for the product of "up to 28 days" efficacy 

against re-infestation with fleas and ticks. 

Entomologist's ObservationslDiscussion: 

I. Replication was inadequate for the study as typically a minimum of 6 dogs are required 

for each treatment group. Typically, the dogs should be of varying breeds and weights, 

including larger dogs, but this issue isn't as critical for this study, as the proposed product 

is intended only for small dogs less than 20 lbs. 

2. Efficacy was demonstrated for the 381 mg/kg treatment group, but not for the 178 mg/kg 

group. 

3. Despite a statistically insignificant relationship between the dosage and the efficacy 

duration for this product, the authors propose a titration scheme that would support 

efficacy claims for a product applied at a minimum of250 mg/kg a.i. This appears to be 

supported by the efficacy data for this present study, as dogs treated with this rate and 

higher were adequately protected for 30 days (albeit an inadequately small sample size). 

However, according to the study's own titration table, which is a bit confusing, the 

proposed dose (1.6 mL) appears to be inadequate for dogs larger than 6lbs, because the 

ai dosage falls below the threshold of250 mg/kg. 

MRiD 47849608: 

Title: Analyses of Efficacy and Safety Data to Support Label Claims for Sergeant's Squeeze-On 

for Small Dogs Containing Etofenprox and Pyriproxyfen. 

This is a summary document of other studies cited/submitted in support of this product. 

Entomologist's Observations/Discussion: Summarized in other reviews. 
125

Efficacy Review 

Date: February 12,2010 

Efficacy Reviewer: 

Risk Manager Rev.: Kevin Sweeney 

Products: 

EPA Reg. #: 

A.I.'s: 

Decision #s: 

DP#s: 

Submission: 

MRIDs: 

GLP: 

MRID 47849601: 

EtofenproxlNylar Spot-on Flea and Tick for Dogs 

2517-RGG 

Ethofenprox (55.0%), Pyriproxyfen (2.2%) 

420097 

371691 

R31 0, New Products, RD Science Review 

Submitted: 

No 

47849601,47849602,47849603,47849604,47849605, 

47849606 

Title: Efficacy of a Water-Based Etofenprox Spot-on against Fleas and Ticks on Small Dogs 

Guideline: OPPTS 810.3300 

Materials and Methods: 2 experimental groups of dogs, 6 dogs in each group, with weights 

ranging from 4.5-12.2Ibs. One group was a treatment group and one was a control. Treated 

dogs were dosed with 1.5 mL of a 55% etofenprox spot-on. Infestations (and reinfestations over 

time) were conducted with 50 ticks (R. sanguine us) and 100 cat fleas (c. felis). Fleas were 

counted at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted 

by hand. Removal of both was done at 72 hours for mortality assessments. Weekly 

reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated 

in comparison to the control. 

Study Summary of the Results: 
126

I. Due to varying dog weights, the effective dose applied ranged between 150-407 

mg/kg (mean of 231 mg/kg). Dogs ranged in weight from 4.5-12.2 lbs. 

2. Efficacy against fleas was only adequate through 16 days. 

3. Efficacy against ticks was adequate through 31 days (mean efficacy of 94%). 

4. The dose applied is less than proposed on the label (2.0 mL for dogs 4-20 Ibs). 

Entomologist's Observationsilliscussion: 

I. While the data support efficacy claims on dogs for ticks through 30 days, the study is 

limited by the lack of dogs at the upper margin of the weight class, which would be the 

most likely to have an inadequate level of coverage by a 2.0 mL application. 

2. Because the rate applied is less than what is proposed on the product label, an 

approximation can be made based on the titration. For example, if 1.5 mL is adequate for 

a 12 pound dog, then 2.0 mL would only be adequate for dogs up to 16lbs (for ticks 

only). 

3. Flea efficacy was not adequately supported by this study. 

MRID 47849602: 

Title: Efficacy, at Minimum Dose Rate, of an Etofenprox Spot-on against Fleas and Ticks on 

Small Dogs 

Guideline: OPPTS 810.3300 

Materials and Methods: 17 dogs were allocated to 3 treatment groups (5-6 dogs each). One 

was an untreated control group, and the other groups were both treated with an etofenprox 

squeeze on, applied at 2 different dosages (2 mL and 4 mL, respectively). Dogs were grouped by 

size so that all dogs received an approximate dosage of 250 mg/kg of etofenprox, as a minimum. 

Group B dogs were all approximately 7-10 lbs, while Group C dogs were approximately 18-20 

lbs. Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguine us) and 

100 cat fleas (c. felis). Fleas were counted via a comb at both 24 hours and 72 hours after each 

infestationlreinfestation. Ticks were counted by hand. Removal of both was done at 72 hours 

for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was 

shown. % Mortality was calculated in comparison to the control. 

Study Summary of the Results: 

5. For Group B dogs receiving 2.0 mL oftreatrnent, flea and tick efficacy is adequate 

through 22 days after treatment. For Group C dogs receiving 4.0 mL oftreatrnent, 

efficacy is adequate through 29 days after treatment. 

Entomologist's Observationsilliscussion: 

I. While the study was designed to assess a 'minimum' dosage (250 mg etofenprox/kg 

animal), this meant that animals at the upper range of the the weight classification (i.e., 
127

20 Ib dogs) received a treatment that is approximately double the dose instructed on the 

product label (2 mL product for dogs weighing 4-20 Ibs). 

2. Therefore, dogs in group C were treated with more material than what is on the proposed 

product label. The data from this study would only support efficacy claims for dogs 

under 10 Ibs, which received 2 mL per animal, and those claims would only be valid for 

22 days after treatment, not a full 30 days. 

MRID 47849603: 

Title: Efficacy, at Label Dose Volume and at Minimum Dose Rate, of an Etofenprox Spot-on 

against Fleas and Ticks on Small Dogs 

Guideline: OPPTS 810.3300 

Materials and Methods: 18 dogs were allocated to 3 treatment groups (6 dogs each). One was 

an untreated control group, and the other groups were both treated with an etofenprox squeeze 

on, applied at 2 different dosages (2.5 mL and -4.5 mL, respectively). Dogs were grouped by 

size. Group B dogs were all approximately 8-9 lbs, while Group C dogs were approximately 18-

201bs. Group B dogs were treated with 2.5 mL of spot-on per animal. Group C dogs were 

dosed by weight, so that each dog received 247 mg ai/kg, with applications thus varying from 4.3 

mL to 4.7 mL per animal Infestations (and reinfestations over time) were conducted with 50 ticks 

(R. sanguineus) and 100 cat fleas (c. fe/is). Fleas were counted via a comb at both 24 hours and 

72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal of both was 

done at 72 hours for mortality assessments. Weekly reinfestations were conducted until 

inadequate efficacy was shown. % Mortality was calculated in comparison to the control. 

Stndy Summary of the Results: 

6. For Group B, flea efficacy was adequate through 16 days after treatment. 

7. For Group B, tick efficacy was 89% for 23 days after treatment and 85% for 30 days 

after treatment. 

8. For Group C, flea and tick efficacy was adequate through 30 days after treatment. 

Entomologist's ObservationslDiscussion: 

1. Both treatment groups were treated with dosages exceeding that proposed on the 

submitted label, and thus the data are not valid to support efficacy claims for that 

proposed dosage. 

2. For dosages applied as listed in the study, efficacy against fleas in Group B animals was 

only adequate through 16 days after treatment. Efficacy in Group C was maintained at 

89% through 30 days after treatment. 

3. For dosages applied as listed in the study, efficacy against ticks in Group B animals was 

demonstrated to be 89% at 23 days after treatment and 85% at 30 days after treatment. 

Efficacy in Group C was maintained through 30 days after treatment. 
128

MRID 47849604: 

Title: Evaluation of Sergeant's Etofenprox Squeeze-on Against Fleas, Ticks, and Mosquitoes on 

Dogs. 

Guideline: OPPTS 810.3300 

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was 

an untreated control group, and the other group was treated with an etofenprox squeeze on, 

applied at 2.5 mL per animal. Dogs in the treatment group were all 10 lbs or less, while control 

dogs ranged in weight from 11-14.3 lbs. Infestations (and reinfestations over time) were 

conducted with 50 each of 3 species of ticks (R. sanguine us, D. variabilis, and A. americana) at 

various infestation intervals, and 100 cat fleas (c. felis). Fleas were counted via a comb at both 

24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. 

Removal of both was done at 72 hours for mortality assessments. Weekly reinfestations were 

conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to 

the control. In the 3rd and 4th weeks after treatment, all dogs were anesthetized and confined for 

I hour with 25 unfed Aedes aegypti or (separately) with 25 Culex quinquefasciatus mosquitoes, 

inside a screen cage. Landings were counted for 5 minutes. Dogs were removed after I hour 

and mosquitoes were recovered to assess survival and blood feeding status. 

Study Summary of the Results: 

9. Actual dosages applied to dogs ranged from 304-411 mg ai/kg. 

10. Flea efficacy was adequate through 23 days after treatment. 

II. Tick efficacy was adequate through 16 days after treatment. 

12. Treatment was not lethal to either species of mosquitoes, but inhibited blood feeding 

>90% (compared to control) for 30 days for Aedes and 29 days for Culex. 

Entomologist's ObservationslDiscussion: 

I. Dogs were treated with dosages exceeding that proposed on the submitted label, and thus 

the data are not valid to support efficacy claims for that proposed dosage. 

2. For dosages applied as listed in the study (2.5 mL), efficacy against fleas is only 

supported for 23 days after treatment for dogs under 10 lbs. 

3. For dosages applied as listed in the study (2.5 mL), efficacy against ticks is only 

supported for 16 days after treatment for dogs under 10 lbs. 

4. For the 2.5 mL doses, claims against mosquitoes for prevention of blood feeding are valid 

only for dogs less than 10 lbs., and no kills claims are supported for mosquitoes. 

MRID 47849605: 

Title: Efficacy of Sergeant's Etofenprox Squeeze-on against Ixodes scapu/aris Nymphs 
129

Guideline: OPPTS 810.3300 

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was 

an untreated control group, and the other group was treated with an etofenprox squeeze on, 

applied at 2.5 mL per animal. Dogs in the treatment group were all 10 Ibs or less, while control 

dogs ranged in weight from 11-14.3 Ibs. 3 days after treatment, hair was clipped from each dog. 

Ten nymphal ticks placed in petri dishes with each hair sample and mortality was assessed at 24 

hand 48 h after placement. % Mortality was calculated in comparison to the control. 

Study Summary ofthe Results: 

13. Actual dosages applied to dogs ranged from 304-411 mg ailkg. 

14. Efficacy was 100% for ticks exposed to hair taken 3 days after treatment (100% 

mortality was observed at both 24 hand 48 h after placement on hair). 

Entomologist's ObservationslDiscussion: 

I. Distribution of hair samples was not specified, and the randomization scheme was not 

defined (i.e., were multiple samples pooled for each dog, or were sub-replicates 

established for each dog?) 

2. Because hair was clipped 3 days after treatment, claims against Deer ticks would only be 

valid for 3 days after treatment. This data would not support the one-month claim 

proposed on the label. A study that exposed ticks to hair taken 30 days after treatment 

would be required to demonstrate efficacy against deer ticks. 

MRID 47849606: 

Title: Efficacy of a 2 mL Unit Dose of Sergeant's Etofenprox Squeeze-on, Applied at Minimum 

Dose Rates, against Fleas and Ticks on Small Dogs 

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was 

an untreated control group, and the other group was treated with an etofenprox squeeze on 

(55%), applied at 2.0 mL per animal (as proposed on new product label). Dogs in the treatment 

group were all 18-20 Ibs., while control dogs ranged in weight from 20-30 Ibs. Infestations (and 

reinfestations over time) were conducted with 50 each of 3 species of ticks (R. sanguine us, D. 

variabilis, andA. americana) at various infestation intervals, and 100 cat fleas (C.felis). Fleas 

were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. 

Ticks were counted by hand. Removal of both was done at 72 hours for mortality assessments. 

Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was 

calculated in comparison to the control. 

Study Summary of the Results: 

15. Actual dosages applied to dogs ranged from 122-233 mg ai/kg (mean 127 mg/kg). 
130

16. Flea efficacy was adequate through 16 days after treatment and 85% through 23 days 

after treatment. 

17. Tick efficacy was adequate through 23 days after treatment and 80% through 30 days 

after treatment. 

Entomologist's ObservationslDiscussion: 

I. This is the only study where the dosage applied to animals exactly matches the dosage on 

the proposed label, and also used dogs at the upper margin of the 20 lbs. weight class. 

2. Efficacy against fleas is only supported for 16 days after treatment and marginally for 23 

days after treatment 

3. Efficacy against ticks is only supported for 23 days after treatment. 

Overall Review of Label Claims and Directions: 

None of the studies were submitted under GLP standards, and protocols were vague on the exact 

specifications by which parasites were placed on animals (e.g., random anatomical distribution 

per 810.3300 guideline). 

Claims against Deer Ticks, Ixodes, are not supported and must be removed from the label. 

Claims against Mosquitoes are not supported for the application rate of2.0 mL proposed on the 

current label. The dosage would have to be raised to support this claim, and the claim must only 

be for repellence/suppression of mosquito blood feeding. Kills and/or control claims are not 

supported by the data. 

The preponderance of data indicates that a 2.0 mL application of the proposed 55% etofenprox 

product is not adequate to protect dogs on the upper end of the weight class for the 30 day 

retreatment interval from fleas and ticks. If animal safety data are adequate, the registrant should 

label the product for different application rates to different weight classes of dogs. Some 

variability is evident even when the dosage is raised to 2.5 mL for small dogs under 10 lbs. For 

dogs between 10-20 Ibs, the dosage should be raised to 4.5-5.0 mL in order to support the label 

claims of control of fleas and ticks for 30 days. 

Claims against flea eggs and larvae are not supported by this data and must be removed from the 

label. Also, claims regarding breakage of the flea life cycle and prevention of flea eggs from 

developing for up to 9 weeks (70 days) after application are not supported and also must be 

removed. 

Removal of unacceptable claims is deferred to the RM reviewer and PM, as some claims may 

possibly be acceptable under conditional registrations with later submission of acceptable 

efficacy data. 
131

Efficacy Review 

Date: February 12,2010 

Efficacy Reviewer: Clayton Myers, PhD., Entomologis 

m ers.c1a on e a. 0'-' 

703-347-8874 

Risk Manager Rev.: Kevin Sweeney 

Products: EtofenproxlNylar Spot-on Flea and Tick for Dogs 

EPA Reg. #: 2517-RGG 

A.I.'s: Ethofenprox (55.0%), Pyriproxyfen (2.2%) 

Decision #s: 420097 

DP#s: 371693 

Submission: R31 0, New Products, RD Science Review 

MRIDs: Submitted: 47849607,4789608 

GLP: No 

MRID 47849607: 

Title: Analysis of a Dose Titration to Determine the Relationship between Dose Rate of 

Etofenprox, When Applied as a Spot-On to Dogs, and the Duration of Residual Efficacy Against 

Flea and Tick Reinfestation. 

Guideline: OPPTS 810.3300 

Materials and Methods: 

12 dogs were allocated to 3 treatment groups (4 dogs each, with average size approximately 

equal, using 30-40 lb dogs). One was an untreated control group, and the other groups were both 

treated with an etofenprox squeeze on, applied at 2 different dosages (approximately 8g and 4g, 

respectively). Rates ofa.i. applied to animals were approximately 381 mg/kg and 178 mglkg, 

respectively. Infestations (andreinfestations over time) were conducted with 50 ticks (R. 

sanguineus) and 100 cat fleas (c. felis). Fleas were counted via a comb at both 24 hours and 72 

hours after each infestationlreinfestation. Ticks were counted by hand. Removal of both was 

done at 72 hours for mortality assessments. Weekly reinfestations were conducted until 

inadequate efficacy was shown. % Mortality was calculated in comparison to the control. 
132

Regression analysis was conducted to determine ifthere was a significant correlation between 

treatment dose and duration of efficacy. 

Study Summary of the Results: 

1. Average flea efficacy was >90% for dogs in the 381 mg/kg treatment group through 

31 days. For the 178 mg/kg treatment, average efficacy was 89% at day 23 and 84% 

at day 31. 

2. Average tick efficacy was 89% for dogs in the 381 mg/kg treatment group through 31 

days. For the 178 mg/kg treatment, average efficacy was only 77% at day 31, but 

was adequate through day 23 (96%). 

3. There was no significant correlation between dosage and efficacy duration for fleas 

and ticks, due to insufficient numbers of dogs. 

4. Dose rates in the range of250-300 mglkg were associated with 90% or higher 

efficacy at 31 days after treatment (looking at reinfestations on the 28th day). This 

observation can be used to generate a hypothetical dosage schedule for the treatment 

of puppies and dogs 151bs or less, with dogs up to 15 Ibs receiving 1.2 mL ofa 55% 

etofenprox product, supporting a claim for the product of "up to 28 days" efficacy 

against re-infestation with fleas and ticks. 

Entomologist's ObservationslDiscussion: 

1. Replication was inadequate for the study as typically a minimum of 6 dogs are required 

for each treatment group. Typically, the dogs should be of varying breeds and weights, 

including larger dogs, but this issue isn't as critical for this study, as the proposed product 

is intended only for small dogs less than 20 Ibs. 

2. Efficacy was demonstrated for the 381 mg/kg treatment group, but not for the 178 mg/kg 

group. 

3. Despite a statistically insignificant relationship between the dosage and the efficacy 

duration for this product, the authors propose a titration scheme that would support 

efficacy claims for a product applied at a minimum of 250 mg/kg a.i. This appears to be 

supported by the efficacy data for this present study, as dogs treated with this rate and 

higher were adequately protected for 30 days (albeit an inadequately small sample size). 

However, according to the study'S own titration table, which is a bit confusing, the 

proposed dose (1.6 mL) appears to be inadequate for dogs larger than 6 Ibs, because the 

ai dosage falls below the threshold of 250 mglkg. 

MRID 47849608: 

Title: Analyses of Efficacy and Safety Data to Support Label Claims for Sergeant's Squeeze-On 

for Small Dogs Containing Etofenprox and Pyriproxyfen. 

This is a summary document of other studies cited/submitted in support of this product. 

Entomologist's ObservationslDiscussion: Summarized in other reviews. 
133

Efficacy Review 

Date: February 12,2010 

Efficacy Reviewer: 

Risk Manager Rev.: Kevin Sweeney 

Products: EtofenproxlNylar Spot-on Flea and Tick for Dogs 

EPA Reg. #: 2517-RGG 

A.I. 's: Ethofenprox (55.0%), Pyriproxyfen (2.2%) 

Decision #s: 420097 

DP#s: 371691 

Submission: R31 0, New Products, RD Science Review 

MRIDs: Submitted: 47849601,47849602,47849603,47849604,47849605, 

47849606 

GLP: No 

MRID 47849601: 

Title: Efficacy of a Water-Based Etofenprox Spot-on against Fleas and Ticks on Small Dogs 

Guideline: OPPTS 8 I 0.3300 

Materials and Methods: 2 experimental groups of dogs, 6 dogs in each group, with weights 

ranging from 4.5-12.2 Ibs. One group was a treatment group and one was a control. Treated 

dogs were dosed with 1.5 mL of a 55% etofenprox spot-on. Infestations (and reinfestations over 

time) were conducted with 50 ticks (R. sanguine us) and 100 cat fleas (C felis). Fleas were 

counted at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted 

by hand. Removal of both was done at 72 hours for mortality assessments. Weekly 

reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated 

in comparison to the control. 

Study Summary of the Results: 
134

1. Due to varying dog weights, the effective dose applied ranged between 150-407 

mg/kg (mean of231 mg/kg). Dogs ranged in weight from 4.5-12.21bs. 

2. Efficacy against fleas was only adequate through 16 days. 

3. Efficacy against ticks was adequate through 31 days (mean efficacy of 94%). 

4. The dose applied is less than proposed on the label (2.0 mL for dogs 4-20 Ibs). 

Entomologist's Observationsilliscussion: 

1. While the data support efficacy claims on dogs for ticks through 30 days, the study is 

limited by the lack of dogs at the upper margin of the weight class, which would be the 

most likely to have an inadequate level of coverage by a 2.0 mL application. 

2. Because the rate applied is less than what is proposed on the product label, an 

approximation can be made based on the titration. For example, if 1.5 mL is adequate for 

a 12 pound dog, then 2.0 mL would only be adequate for dogs up to 161bs (for ticks 

only). 

3. Flea efficacy was not adequately supported by this study. 

MRID 47849602: 

Title: Efficacy, at Minimum Dose Rate, of an Etofenprox Spot-on against Fleas and Ticks on 

Small Dogs 

Guideline: OPPTS 810.3300 

Materials and Methods: 17 dogs were allocated to 3 treatment groups (5-6 dogs each). One 

was an untreated control group, and the other groups were both treated with an etofenprox 

squeeze on, applied at 2 different dosages (2 mL and 4 mL, respectively). Dogs were grouped by 

size so that all dogs received an approximate dosage of 250 mg/kg of etofenprox, as a minimum. 

Group B dogs were all approximately 7-10 Ibs, while Group C dogs were approximately 18-20 

lbs. Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) and 

100 cat fleas (C fe/is). Fleas were counted via a comb at both 24 hours and 72 hours after each 

infestationlreinfestation. Ticks were counted by hand. Removal of both was done at 72 hours 

for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was 

shown. % Mortality was calculated in comparison to the control. 

Study Summary of the Results: 

5. For Group B dogs receiving 2.0 mL of treatment, flea and tick efficacy is adequate 

through 22 days after treatment. For Group C dogs receiving 4.0 mL of treatment, 

efficacy is adequate through 29 days after treatment. 

Entomologist's Observationsilliscussion: 

1. While the study was designed to assess a 'minimum' dosage (250 mg etofenproxlkg 

animal), this meant that animals at the upper range of the the weight classification (i.e., 
135

20 lb dogs) received a treatment that is approximately double the dose instructed on the 

product label (2 mL product for dogs weighing 4-20 lbs). 

2. Therefore, dogs in group C were treated with more material than what is on the proposed 

product label. The data from this study would only support efficacy claims for dogs 

under 10 lbs, which received 2 mL per animal, and those claims would only be valid for 

22 days after treatment, not a full 30 days. 

MRID 47849603: 

Title: Efficacy, at Label Dose Volume and at Minimum Dose Rate, of an Etofenprox Spot-on 

against Fleas and Ticks on Small Dogs 

Guideline: OPPTS 810.3300 

Materials and Methods: 18 dogs were allocated to 3 treatment groups (6 dogs each). One was 

an untreated control group, and the other groups were both treated with an etofenprox squeeze 

on, applied at 2 different dosages (2.5 mL and -4.5 mL, respectively). Dogs were grouped by 

size. Group B dogs were all approximately 8-9 lbs, while Group C dogs were approximately 18-

20 lbs. Group B dogs were treated with 2.5 mL of spot-on per animal. Group C dogs were 

dosed by weight, so that each dog received 247 mg ai/kg, with applications thus varying from 4.3 

mL to 4.7 mL per animal Infestations (and reinfestations over time) were conducted with 50 ticks 

(R. sanguineus) and 100 cat fleas (c. felis). Fleas were counted via a comb at both 24 hours and 

72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal of both was 

done at 72 hours for mortality assessments. Weekly reinfestations were conducted until 

inadequate efficacy was shown. % Mortality was calculated in comparison to the control. 

Study Summary of the Results: 

6. For Group B, flea efficacy was adequate through 16 days after treatment. 

7. For Group B, tick efficacy was 89% for 23 days after treatment and 85% for 30 days 

after treatment. 

8. For Group C, flea and tick efficacy was adequate through 30 days after treatment. 

Entomologist's ObservationslDiscussion: 

1. Both treatment groups were treated with dosages exceeding that proposed on the 

submitted label, and thus the data are not valid to support efficacy claims for that 

proposed dosage. 

2. For dosages applied as listed in the study, efficacy against fleas in Group B animals was 

only adequate through 16 days after treatment. Efficacy in Group C was maintained at 

89% through 30 days after treatment. 

3. For dosages applied as listed in the study, efficacy against ticks in Group B animals was 

demonstrated to be 89% at 23 days after treatment and 85% at 30 days after treatment. 

Efficacy in Group C was maintained through 30 days after treatment. 
136

MRID 47849604: 

Title: Evaluation of Sergeant's Etofenprox Squeeze-on Against Fleas, Ticks, and Mosquitoes on 

Dogs. 

Guideline: OPPTS 810.3300 

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was 

an untreated control group, and the other group was treated with an etofenprox squeeze on, 

applied at 2.5 mL per animal. Dogs in the treatment group were all 10 Ibs or less, while control 

dogs ranged in weight from 11-14.3 Ibs. Infestations (and reinfestations over time) were 

conducted with 50 each of3 species ofticks (R. sanguineus, D. variabilis, and A. americana) at 

various infestation intervals, and 100 cat fleas (C felis). Fleas were counted via a comb at both 

24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. 

Removal of both was done at 72 hours for mortality assessments. Weekly reinfestations were 

conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to 

the control. In the 3rd and 4th weeks after treatment, all dogs were anesthetized and confined for 

1 hour with 25 unfed Aedes aegypti or (separately) with 25 Culex quinquefasciatus mosquitoes, 

inside a screen cage. Landings were counted for 5 minutes. Dogs were removed after I hour 

and mosquitoes were recovered to assess survival and blood feeding status. 

Study Summary of the Results: 

9. Actual dosages applied to dogs ranged from 304-411 mg ai/kg. 

10. Flea efficacy was adequate through 23 days after treatment. 

11. Tick efficacy was adequate through 16 days after treatment. 

12. Treatment was not lethal to either species of mosquitoes, but inhibited blood feeding 

>90% (compared to control) for 30 days for Aedes and 29 days for Culex. 

Entomologist's Observationsilliscussion: 

1. Dogs were treated with dosages exceeding that proposed on the submitted label, and thus 

the data are not valid to support efficacy claims for that proposed dosage. 

2. For dosages applied as listed in the study (2.5 mL), efficacy against fleas is only 

supported for 23 days after treatment for dogs under 10 Ibs. 

3. For dosages applied as listed in the study (2.5 mL), efficacy against ticks is only 

supported for 16 days after treatment for dogs under 10 lbs. 

4. For the 2.5 mL doses, claims against mosquitoes for prevention of blood feeding are valid 

only for dogs less than 10 Ibs., and no kills claims are supported for mosquitoes. 

MRID 47849605: 

Title: Efficacy of Sergeant's Etofenprox Squeeze-on against Ixodes scapularis Nymphs 
137

Guideline: OPPTS 810.3300 

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was 

an untreated control group, and the other group was treated with an etofenprox squeeze on, 

applied at 2.5 mL per animal. Dogs in the treatment group were all 10 lbs or less, while control 

dogs ranged in weight from 11-14.3 lbs. 3 days after treatment, hair was clipped from each dog. 

Ten nymphal ticks placed in petri dishes with each hair sample and mortality was assessed at 24 

h and 48 h after placement. % Mortality was calculated in comparison to the control. 

Study Summary of the Results: 

13. Actual dosages applied to dogs ranged from 304-411 mg ai/kg. 

14. Efficacy was 100% for ticks exposed to hair taken 3 days after treatment (100% 

mortality was observed at both 24 hand 48 h after placement on hair). 

Entomologist's Observationsilliscussion: 

1. Distribution of hair samples was not specified, and the randomization scheme was not 

defined (i.e., were mUltiple samples pooled for each dog, or were sub-replicates 

established for each dog?) 

2. Because hair was clipped 3 days after treatment, claims against Deer ticks would only be 

valid for 3 days after treatment. This data would not support the one-month claim 

proposed on the label. A study that exposed ticks to hair taken 30 days after treatment 

would be required to demonstrate efficacy against deer ticks. 

MRID 47849606: 

Title: Efficacy of a 2 mL Unit Dose of Sergeant's Etofenprox Squeeze-on, Applied at Minimum 

Dose Rates, against Fleas and Ticks on Small Dogs 

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was 

an untreated control group, and the other group was treated with an etofenprox squeeze on 

(55%), applied at 2.0 mL per animal (as proposed on new product label). Dogs in the treatment 

group were all 18-20 lbs., while control dogs ranged in weight from 20-30 lbs. Infestations (and 

reinfestations over time) were conducted with 50 each of 3 species of ticks (R. sanguineus, D. 

variabilis, andA. americana) at various infestation intervals, and 100 cat fleas (C./elis). Fleas 

were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. 

Ticks were counted by hand. Removal of both was done at 72 hours for mortality assessments. 

Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was 

calculated in comparison to the control. 

Study Summary of the Results: 

15. Actual dosages applied to dogs ranged from 122-233 mg ailkg (mean 127 mglkg). 
138

16. Flea efficacy was adequate through 16 days after treatment and 85% through 23 days 

after treatment. 

17. Tick efficacy was adequate through 23 days after treatment and 80% through 30 days 

after treatment. 

Entomologist's Observationsilliscussion: 

I. This is the only study where the dosage applied to animals exactly matches the dosage on 

the proposed label, and also used dogs at the upper margin of the 20 Ibs. weight class. 

2. Efficacy against fleas is only supported for 16 days after treatment and marginally for 23 

days after treatment 

3. Efficacy against ticks is only supported for 23 days after treatment. 

Overall Review of Label Claims and Directions: 

None of the studies were submitted under GLP standards, and protocols were vague on the exact 

specifications by which parasites were placed on animals (e.g., random anatomical distribution 

per 810.3300 guideline). 

Claims against Deer Ticks, Ixodes, are not supported and must be removed from the label. 

Claims against Mosquitoes are not supported for the application rate of2.0 mL proposed on the 

current label. The dosage would have to be raised to support this claim, and the claim must only 

be for repellence/suppression of mosquito blood feeding. Kills and/or control claims are not 

supported by the data. 

The preponderance of data indicates that a 2.0 mL application of the proposed 55% etofenprox 

product is not adequate to protect dogs on the upper end of the weight class for the 30 day 

retreatment interval from fleas and ticks. If animal safety data are adequate, the registrant should 

label the product for different application rates to different weight classes of dogs. Some 

variability is evident even when the dosage is raised to 2.5 mL for small dogs under 10 Ibs. For 

dogs between 10-20 Ibs, the dosage should be raised to 4.5-5.0 mL in order to support the label 

claims of control of fleas and ticks for 30 days. 

Claims against flea eggs and larvae are not supported by this data and must be removed from the 

label. Also, claims regarding breakage of the flea life cycle and prevention of flea eggs from 

developing for up to 9 weeks (70 days) after application are not supported and also must be 

removed. 

Removal of unacceptable claims is deferred to the RM reviewer and PM, as some claims may 

possibly be acceptable under conditional registrations with later submission of acceptable 

efficacy data. 
139

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

February 26, 2010 

MEMORANDUM 

OFFICE OF PREVENTION, PESTICIDES 

AND TOXIC SUBSTANCES 

SUbject: Name of Pesticide Product: ETOFENPROXINYLAR SPOT-ON FLEA AND 

TICK FOR DOGS AND PUPPIES 

EPA Reg. No./File Symbol: 2517-RGG 

DP Barcode: DP 371681 

Decision No.: 420097 

Action Code: R310 

PC Codes: 128965 (Etofenprox: 55%) 

129032 (Pyriproxyfen: 2.2%) 

From: 

To: 

Byron T. Backus, Ph.D., Toxicologist 

Technical Review Branch 

Registration Division (7505P) 

Kevin Sweeney/Richard Gebken, RM 13 

Insecticide Branch 

Registration Division (7505P) 

Or'-(S~ D 1.-/1.-10 (1.- 0 I 0 

/I tJ--'4i :J;;~<l 

Registrant: SERGEANT'S PET CARE PRODUCTS, INC. 

FORMULATION FROM LABEL: 

Active Ingredient(s): 

128965 Etofenprox 

129032 Pyriproxyfen 

Other Ingredient(s): 

TOTAL 

ACTION REQUESTED: The Risk Manager requests: 

Bywt. 

55.00% 

2.20% 

42.80% 

100.00% 

" ... Please review the cited studies. Registrant claims they are similar to 69332-3." 

Page I of3 
140

BACKGROUND: 

The registrant is citing the acute toxicity studies in MRIDs 46161303 (acute oral LD50), 

46161304 (acute dermal LD50), 46161305 (eye irritation), 46161306 (dermal irritation) and 

46161307 (dermal sensitization) to support the registration of 2517-RGG. These studies were 

previously submitted for the formulation now registered as EPA Reg. No. 69332-3. In addition, 

the material received includes basic and alternate CSFs and proposed label for 2517-RGG. 

COMMENTS AND RECOMMENDATIONS: 

I. After a comparison of the CSFs for 2517-RGG and for 69332-3, TRB concludes that the cited 

acute toxicity studies can be used as supporting data for 2517-RGG. 

2. The cited studies have been previously reviewed and classified as acceptable (memorandum 

dated 10 February 2004 from R. Whiting ofTRB to Kevin Sweeney of PM Team 13). The same 

memorandum accepted the registrant's waiver request for an acute inhalation toxicity study. 

3. The acute toxicity study profile for EPA File Symbol 2517-RGG is as follows: 

Acute oral toxicity IV Cited MRID 46161303 

Acute dermal toxicity IV Cited MRID 46161304 

Acute inhalation toxicity IV Waived 

Primary eye irritation III Cited MRID 46161305 

Primary skin irritation IV Cited MRID 46161306 

Dermal sensitization Negative Cited MRID 46161307 

4. Based on the acute toxicity profile above, the following are the precautionary and first aid 

statements for 2517-RGG, as obtained from the Label Review System: 

PRODUCT ID #: 002517-00133 

PRODUCT NAME: ETOFENPROX/NYLAR SPOT-ON FLEA AND TICK FOR DOGS AND 

PUPPIES 

PRECAUTIONARY STATEMENTS 

SIGNAL WORD: CAUTION 

Hazards to Humans and Domestic Animals: 

Causes moderate eye irritation. Avoid contact with eyes or clothing. [Wear protective eyewear.J* Wash 

thoroughly with soap and water after handling and before eating, drinking, chewing gu·m, or using 

tobacco. 

*[Protective eyewear may be specified, if appropriateJ. 

First Aid: 

If in eyes: 

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

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

Page 2 00 
141

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

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

treatment. You may also contact 1-800-xxx-xxxx for emergency medical treatment information. 

Page 300 
142

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

February 24, 2010 

MEMORANDUM 

OFFICE OF PREVENTION, PESTICIDES 

AND TOXIC SUBSTANCES 

Subject: Name of Pesticide Product: ETOFENPROX/NYLAR SPOT-ON FLEA AND 

TICK FOR DOGS AND PUPPIES 

EPA Reg. No./File Symbol: 2517-RGG 

DP Barcode: DP 371676 

Decision No.: 420097 

Action Code: R310 

PC Codes: 128965 (Etofenprox: 55%) 

129032 (Pyriproxyfen: 2.2%) 

From: Byron T. Backus, Ph.D., Toxicologist 

Technical Review Branch 

Registration Division (7505P) 

n~(?_C . o 1.- - 1..-'"'" - 1.- c l Co 

To: Kevin Sweeney/Richard Gebken, RM 13 

Insecticide Branch 

Registration Division (7505P) 

Registrant: SERGEANT'S PET CARE PRODUCTS, INC. 

FORMULATION FROM LABEL: 

Active Ingredient(s): 

128965 Etofenprox 

129032 Pyriproxyfen 

Other Ingredient(s): 

TOTAL 

ACTION REQUESTED: The Risk Manager requests: 

" ... Please review the attached study and documentation." 

Page 1 of 16 

.~ 

Bywt. 

55.00% 

2.20% 

42.80% 

100.00% 
143

BACKGROUND: 

The material received includes a companion animal safety study (in MRID 47849609) titled: 

"Companion animal safety evaluation on dogs of spot-on products containing multiple toxicants 

and insect growth regulators" as well as a CSF and a proposed label for the product which would 

be applied to small and/or toy breed dogs weighing 4-20 Ibs. The label dosage rate is given as 

2.0 mLidogiapplication. 

COMMENTS AND RECOMMENDATIONS: 

I. An Agency contractor, Oak Ridge National Laboratory, conducted the primary review of the 

companion animal safety study. TRB performed the secondary review and made changes as 

necessary. 

2. The study is not acceptable to support the proposed usee s) on adult dogs and puppies and 

cannot be upgraded. Test groups consisted of 6 (3 male and 3 female) adult dogs or puppies. 

The 870.7200 Companion Animal Safety Guidelines specify that at least 6 animals per sex 

should be used at each dosage level. In addition, the adult dogs that were treated with test 

substance II (containing 55.16% w/w etofenprox, 8.78% w/w methoprene, and 2.31% w/w 

pyriproxyfen) at 5X the dosage rate weighed (on day -1) 4.06, 7.00, 7.98, 8.78, 8.94 and 9.10 kg. 

Since only one dog in this group weighed less than 91bs (4.06 kg = 8.95 Ibs), the data could not 

be used to support the use of this formulation on adult dogs weighing 4-9 Ibs, particularly as the 

ratio of body surface area to mass could be a factor in absorption and toxicity. Cumulative 

dosage rates were 3.08, 3.21, 2.82, 2.56, 2.52 and 2.47 mLlkg (the 4.06 kg dog received a 

cumulative amount of 12.5 mL test material; the others each received 22.5 mL), with a mean of 

2.78 mLlkg; dividing this by 5 (for the 5X margin of exposure) gives 0.555 mLlkg, and dividing 

2.0 mL (the proposed dose) by 0.555 mLlkg gives 3.60 kg (= 7.941bs), which is also 

substantially above the proposed 41b lower weight limit. For the puppies, it is impossible to 

compare and interpret differences in body weight gains between groups when there was such a 

range in ages (10-15 weeks, with no information as to specific ages for individual animals), the 

dogs were mixed breed and the two heaviest puppies (CC7 692 and CD4 7EC), which would be 

expected to show the greatest weight gains, were both in the control group. 

3. TRB considers the behavioral changes (running and circling immediately after application of 

the test substance) in 7 animals (one adult, 6 puppies) as an adverse effect. It is noted that the 

animals showing behavioral changes were all exposed to test material IA (8.20% cyphenothrin, 

9.8% fipronil, either in combination with material III, 8.90% methoprene and 2.43% 

pyriproxyfen, for the one adult, or in combination with material II, 55.16% etofenprox, 8.78% 

methoprene and 2.31 % pyriproxyfen for the puppies). Although the four puppies in group A2 

(receiving 5 applications of material IA and 5 of II) showed running and circling only after the 

first application of the test substance and not after the second, third, fourth or fifth application, 

this may simply be an indication that the application area had been numbed. 

4. Refer to the attached DER for additional comments. 

Page 2 of 18 
144

DATA EVALUATION RECORD 

CYPHENOTHRIN, FIPRONIL, ETOFENPROX, METHOPRENE, 

PYRIPROXIFEN 

COMPANION ANIMAL SAFETY STUDY- DOGSIPUPPIES - (OPPTS 870.7200) 

MRID 47849609 

Primary Reviewer: 

Prepared for 

Registration Division 

Office of Pesticide Programs 

U.S. Environmental Protection Agency 

One Potomac Yard 

2777 S. Crystal Drive 

Arlington, V A 22202 

Prepared by 

Toxicology and Hazard Assessment Group 

Environmental Sciences Division 

Oak Ridge National Laboratory 

Oak Ridge, TN 37831 

Virginia A. Dobozy, V.M.D .. M.P.H. Signature: 

Date: 

Secondary Reviewers: 

Dana F. Glass, D.V.M. Signature: 

Date: 

Robert H. Ross, M.S .. Group Leader Signature: 

Date: 

Quality Assurance: 

Kimberly Slusher, M.S. Signature: 

Date: 

Disclaimer 

This review may have been altered subsequent to the contractor's signatures above. 

Oak Ridge National Laboratory managed and operated by UT_Battelle, LLC., for the U.S. Department of Energy 

under Contract No. DE_AC05_000R22725. 
145

EPA Reviewer: Byron T. Backns, Ph.D. 

Technical Review Branch, Registration Division (7505P) Date: 

Signature: ()~. 0 1... -1.. t -

n 

1. 

~ C> ~ t> 

Template version 02/06 

I DATAEVALUATIONRECORD 

STUDY TYPE: Companion animal safety study· dogs/puppies - OPPTS 870.7200 

PC CODE: 128965· Ethofenprox, 129032· Pyriproxyfen, DP BARCODE: 371676 

TEST MATERIAL (PURITy): Cyphenothrin (8.2% w/w), Fipronil (9.8% mlw), Etofenprox 

(55.16% w/w), S-Methoprene (8.78% w/w), Methoprene (8.90% w/w) and Pyriproxifen (2.31% 

and 2.43% w/w) 

TRADE NAME: Not provided 

CITATION: Delport, P.C. (2009) Companion animal safety evaluation on dogs of spot-on 

products containing multiple toxicants and insect growth regulators. ClinVet International (Pty) 

Ltd., Bloemfontein, Republic of South Africa. Study No. CV 08/551, August 6,2009. MRID 

47849609. Unpublished. 

SPONSOR: Sergeant's Pet Care Products, Plano, Texas 

EXECUTIVE SUMMARY: In a companion animal safety study (MRID 47849609), groups of 

random-source adult (> 6 months of age) and juvenile (10-15 weeks of age) dogs were topically 

administered 3 combinations of insecticides and insect growth regulators or one inert substance. 

Two groups of three male and three female juvenile dogs were administered test substance IA 

(8.2% w/w cyphenothrin and 9.8% m/w fipronil; Batch No. 012003-09) and test substance II 

(55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31 % w/w pyriproxifen; Batch No. 

011901-09) at either IX (recommended dose) or 5X (recommended dose hourly for 5 

applications). The test substances were applied simultaneously as adjacent stripes along the 

dorsum of the dog from behind the ears caudally to the base of the tail. Two groups of three male 

and three female adult dogs weighing 9-20 kg were administered the test substance IA and test 

substance III (8.90% w/w methoprene and 2.43% w/w pyriproxifen; Batch No. 011902-09) at 

either IX (recommended dose) or 5X (recommended dose hourly for 5 applications). The test 

substances were applied as previously described. A group of three male and three female adult 

dogs weighing less than 9 kg was administered test substance II at 5X (recommended dose 

hourly for 5 applications). A group of three male and three female juvenile dogs and another 

group of three male and three female adult dogs were administered control substance IV A (Batch 

No. 012004-09) containing inert ingredients (not otherwise stated) at 5X the recommended dose. 

The groups and test materials they received are shown in the table below: 

Page4ofl8 
146

Group 

A Group AI (n-6) Puppies (10-15 weeks) Group A2 (0-6) Puppies (10-15 weeks) 

Single application of substance IA Five applications of substance IA 

Single application of substance II Five applications of substance II 

B Group B I (0 6) Adults (9-20 kg) Group B2 (n 6) Adults (9-20 kg) Group B3 (0 6) Adults «9 kg) 

Single application of substance IA Five applications of substance IA Five applications of substance II 

Single application of substance III Five applications of substance III 

C Group CI (0-6) Puppies (10-15 weeks) Group C2 (0-6) Adults (9-20 kg) 

Five <ipplications control substance IV A Five applications control of substance IVA 

0 0 Substance IA contams 8.2 Yo w/w cyphenothnn and 9.8 Yo m/w fiproOlL 

Substance II contains 55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.3 1% w/w pyriproxifen. 

Substance III contains 8.90% methoprene, 2.43% w/w pyriproxifen. 

Control substance IV A contains inert control substances. 

The animals were observed for clinical signs of toxicity and dermal irritation for four hours postapplication and then twice daily for the duration of the study (14 days post-application). Body 

weight, body weight gain, food consumption and clinical pathology parameters (hematology and 

clinical chemistry) were measured at the required intervals. 

All animals survived to the end of the study. Immediately after treatment, one adult dog in Group 

BI (IX applications of test substances IA and III) showed behavioral changes (running, circling). 

This behavioral change was not considered treatment-related in adults by the sponsor since it was 

not observed at 5X the recommended dose. Immediately after treatment, two puppies in Group 

Al (IX application of test substances IA and II) showed behavioral changes (running, circling). 

Four puppies in Group A2 (5X application of test substances IA and II) showed similar 

behavioral changes after the first application but not after subsequent applications. These 

behavioral changes are considered to be an adverse effect. White crystallization was observed on 

the hair tips of many adult and juvenile dogs in the treated and control groups. The application 

sites of all dogs in Group B3 (5X application of test substance II) had an oily or wet appearance. 

The sign disappeared from one dog on Day + 14 but was present on all others at the end of the 

study. 

All adult dogs and puppies gained weight from Day -I to Day 14. However, mean weight gain in 

pups in the treated groups (A I and A2) was 15% lower than the control group pups. The mean 

weight gain in the treated adult animals (Groups BI, B2 and B3) was decreased (30-99% as 

compared to the control group). The difference relative to controls was largest in the smaller 

adult dogs in Group B3 (99% decrease as compared to the control group). Food consumption 

was not affected by treatment. No treatment-related hematology or clinical chemistry changes 

were observed. 

It is noted that the 7 animals (one adult, 6 puppies) that showed behavioral changes (running and 

circling) immediately after application of the test substance were all exposed to test material IA 

(8.20% cyphenothrin, 9.8% fipronil, either in combination with material III, 8.90% methoprene 

and 2.43% pyriproxyfen, for the one adult, or in combination with material II, 55.16% 

etofenprox, 8.78% methoprene and 2.31 % pyriproxyfen for the puppies). Although the four 

puppies in group A2 (receiving 5 applications of material IA and 5 of II) showed running and 

circling only after the first application of the test substance and not after the second, third, fourth 

or fifth application, this may simply be an indication that the application area had been numbed. 

Page 5 of 18 
147

Test groups consisted of 6 (3 male and 3 female) adult dogs or puppies. The 870.7200 

Companion Animal Safety Guidelines specify that at least 6 animals per sex should be used 

at each dosage level. In addition, the adult dogs that were treated with test substance II 

(containing 55.16% w/w etofenprox, 8.78% w/w methoprene, and 2.31 % w/w 

pyriproxyfen) at 5X the dosage rate weighed (on day -1) 4.06, 7.00, 7.98, 8.78, 8.94 and 9.10 

kg. Since only one dog in this group weighed less than 9lbs (4.06 kg = 8.95 lbs), the data 

could not be used to support the use of this product/formulation on adult dogs weighing 4-9 

lbs, particularly as the ratio of body surface area to mass could be a factor in absorption 

and toxicity. Also, it was not possible to compare body weight changes between adult 

group B3 (which received the etofenprox-containing formulation) and the control (C2) 

group because initial mean body weights were so different. For the puppies, it is impossible 

to compare and interpret differences in body weight gains between groups when there was 

such a range in ages (10-15 weeks, with no information as to specific ages for individual 

animals), the dogs were mixed breed and the two heaviest puppies (CC7 692 and CD4 

7EC), which would be expected to show the greatest weight gains, were both in the control 

group. 

In addition, it is concluded that the margin of safety in puppies administered simultaneous 

topical application of test substances IA (8.2% w/w cyphenothrin and 9.8% m/w fipronil) 

and II (55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31% w/w pyriproxifen) 

was less than IX the recommended dose, based on clinical signs of toxicity (behavioral 

changes immediately post-application). 

This companion animal safety study in male and female random-source adult dogs and puppies is 

Unacceptable/Guideline and does not satisfy the guideline requirement for a companion animal 

safety study (OPPTS 870.7200) in the dog and cannot be upgraded for either adults or puppies. 

See Study Deficiencies section for details. Major deficiencies include too few animals per group, 

failure to test the end-use product and lack of some required reporting. 

COMPLIANCE: Signed and dated GLP, Quality Assurance and Data Confidentiality 

statements were provided for Clin Vet International. Pathcare Veterinary Laboratory, which 

conducted the hematology and clinical chemistry analyses, is not GLP accredited but is ISO 

15189 certified. 

Page 6 of 18 
148

I. MATERIALS AND METHODS 

A. MATERIALS: 

1. Test materials: 

la. Test substance 1 (code uame IA) 

Description: 

Batch #: 

Purity: 

Storage: 

Compound Stability: 

CAS#: 

Not provided 

012003-09 

8.2% w/w cyphenothrin and 9.8% mlw fipronil* 

At room temperature 

Expiration date: January 20, 2011 

Not provided 

* Batch 2008-Fip.D3, expiration date August 19, 2010, packed in foil and stored at ambient temperature, inside carton 

box, dry 

lb. Test substance 2 (code name II) 

Description: 

Batch #: 

Purity: 

Storage: 

Compound Stability: 

CAS#: 

Not provided 

011901-09 

55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.31 % w/w pyriproxifen 

At room temperature 

Expiration date: January 19, 2011 

Not provided 

Ie. Test substance 3 (code name ITI) 

Description: 

Batch #: 

Purity: 

Storage: 

Compound Stability: 

CAS#: 

Not provided 

011902-09 

8.90% w/w methoprene, 2.43% w/w pyriproxifen 

At room t~mperature 

Expiration date: January 19, 20ll 

Not provided 

ld. Control substance (code name IVA) 

Description: 

Batch #: 

Purity: 

Storage: 

Compound Stability: 

CAS#: 

Not provided 

012004-09 

Inert control substance (no purity provided) 

At room temperature 

Expiration date: January 20,2011 

Not provided 

2. Vehicle control: See control substance described in I d. above. 

Page 7 of 18 
149

3. Test animals: 

Species: 

Strain: 

Age/weight 

Source: 

Housing: 

Diet: 

Water: 

Environmental conditions: 

Temperature: 

Humidity: 

Air changes: 

Photoperiod: 

Acclimation period: 

B. STUDY DESIGN: 

Dog 

Described as "indifferent" 

Groups Al and A2: 10-15 weeks on day 0 (2.12 -7.32 kg or 4.67-16.14Ibs) 

Groups B I and B2: 2: 6 mos on day 0 (> 9 kg 0" 20 kg or > 19:84 lb :s 44.09Ibs) 

Group B3: 2: 6 mos on day 0 (0" 9 kg or 0" 19.84Ib) 

Group CI: 10-15 weeks on day 0 (2.88 - 9.67 kg or 6.35-2I.32Ibs) 

Group C2: 2: 6 mos on day 0 (> 9 kg :s 20 kg or > 19.84 lb :s 44.09 lbs) 

ClinVet International (Pty) Ltd. Colony 

Individually housed in pens 

Adults (>12 months) were fed a commercial dry dog food (example: ULTRADOG 

SUPERWOOF DOG FOOD); puppies « 12 months) were fed an "appropriate 

puppy food" (example: Eukanuba puppy and junior medium breed) 

Tap water, ad libitum 

20 ± 4" C 

Not provided 

12-15 air changes/hr 

12 hours light/12 hours dark 

Fourteen days 

1. In life dates: Start: March 19, 2009; End: April 16, 2009 

2. Animal assignment: Forty-two animals were assigned to the study. The genders were 

separated and the dogs allocated to study groups (Table I) within the body weight 

requirements using randomization through minimization with body weight as the only 

criterion. For medium sized adult dogs, within each gender, animals were blocked into three 

blocks of three dogs each. The three heaviest dogs formed block I; the next three heaviest 

dogs formed block 2 and the next three formed block 3. Within blocks, dogs were allocated 

to one of three groups, I, 2 or 3. The first animal of block I was assigned to group I, the 

second to group 2 and the third to group 3. The first animal of block 2 was assigned to group 

3, the second to group 2 and the third to group I. The first animal of block 3 was assigned to 

group 1, the second to group 2 and the third to group 3. Groups 1,2 and 3 were then 

randomly assigned to the actual groups B I, B2 and C using Excel randbetween. Puppies 

were similarly assigned to groups AI, A2 and Cl. The six dogs in group B3 were allocated; 

no randomization was possible. 

Page 8 of 18 
150

Table 1: Study design 

Groul' 

A Group AI (n 6) Puppies (l0-15 weeks) Group A2 (n 6) Puppies (l0-I5 weeks) 

Single application of substance lA Five applications of substance IA 

Single application of substance II Five applications of substance II 

B Group B I (n-6) Adults (9-20 kg) Group B2 (n-6) Adults (9-20 kg) Group B3 (n-6) Adults «9 kg) 

Single application of substance IA Five applications of substance lA Five applications of substance II 

Single application of substance III Five applications of substance III 

C Group CI (n-6) Puppies (l0-I5 weeks) Group C2 (n-6) Adults (9-20 kg) 

Five applications control substance IV A Five applications control of substance IV A 

Substance IA contams 8.2% w/w cyphenothrm and 9.8% m/w fiproml. 

Substance II contains 55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.31% w/w pyriproxifen. 

Substance III contains 8.90% methoprene, 2.43% w/w pyriproxifen. 

Control substance IV A contains inert control substances. 

3. Dose selection rationale: The dose rates for test substance IA are based on fipronil and 

methoprene on the Frontline Plus label and pyriproxyfen in Sergeant's Gold for Dogs. For 

test substance II, the study report states that the maximum etofenprox small dog dose rate is 

758 mg/kg. For test substance III, the dose ofpyriproxyfen and s-methoprene is based on 

Sergeant's Gold for Dogs and Frontline Plus label. However, none of the dose rates used is 

representative of the proposed label. 

4. Preparation and treatment: The test and control substances were applied as measured 

doses from syringes (without needles) to a furrow in the hair on the back, starting high on the 

neck behind the ears and extending caudally towards the base of the tail. The fur was not 

shaved or clipped. Technicians applying the substances were blinded to the test material. 

Test substances lA, II and III were applied separately as "terminally adjacent stripes, 

applying test substance IA anterior to test substance II or test substance IA anterior to test 

substance III." The placebo control fonnulation IVA was applied separately. Substances lA, 

II and III were not mixed. 

Test substances IA and II were applied as single doses, once only, to the pups in test group 

Al and five times consequently at hourly intervals, each time as a single dose, to the pups in 

test group A2. Substances IA and II were not mixed. 

Test substances IA and III were applied as single doses, once only, to the adult dogs in group 

B I, five times consequently at hourly intervals, each time as a single dose, to the adult dogs 

in group B2. Substances IA and III were not mixed. Test substance II was applied five times 

consequently at hourly intervals, each time as a single dose, to the adult dogs in group B3. 

The control substance IV A was applied five times consequently at hourly intervals, each time 

as a single dose, to pups and dogs in groups CI and C2, respectively. 

The dose volumes of the test and control substances were detennined by the animal's weight 

on Day -1 (Table 2). 

Page 9 of IS 
151

Table 2: Doses 

Group Test substance Total dose administered 

Al (puppies) IA 0.83 - 2.0 mL (IX) 

II 3.1 -7.5 mL (IX) 

A2 (puppies) IA 5.0 - 13.30 mL (1.0 - 2.66 mL x 5) 

II 18.8 - 50.0 mL (3.76 - 10.0 mL x 5) 

BI (adults) IA 1.34 mL (IX) 

III 1.34 mL (IX) 

B2 (adults) IA 3.4 - 6.7 mL (0.68 - 1.34 mL x 5) 

III 3.4 - 6.7 mL (0.68 -1.34 mL x 5) 

B3 (adults) II 12.5 - 22.5 mL (2.5 - 4.5 mL x 5) 

CI (puppies) IVA 13.10 mL (2.62 mL x 5) 

C2 (adults) IVA 5.0 mL (1.0 mL x 5) 

Substance IA contams 8.2% w/w cyphenothnn and 9.8% m1w fiproml. 

Substance II contains 55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.31% w/w pyriproxifen. 

Substance III contains 8.90% methoprene, 2.43% w/w pyriproxifen. 

Control substance IVA contains inert control substances. 

S. Statistics: The emphasis of the statistical analyses was the change from baseline of each of 

the hematology and clinical chemistry parameters. Individual hematology and clinical 

chemistry values on test days were tabulated separately for each variable and each group, 

together with the following descriptive statistics: mean, standard deviation (SD), coefficient 

of variation (CV %), geometric mean, geometric SD, minimum, maximum and the number of 

observations in the group. The individual changes and percentage changes from baseline (test 

day -3) for each of the post-treatment days were calculated and tabulated for each variable 

and each group. The number of post-treatment values that fell outside the reference range 

was calculated. The post-treatment values were compared to the baseline values in an intratreatment comparison by means of an analysis of variance (ANOVA) with an animal and 

observation time as effects. An inter-treatment comparison with respect to the changes from 

baseline was also performed. The post-treatment values of each the three test treatment 

groups (BI, B2 and B3) were compared to the control group (C2) for adult dogs. The posttreatment values of each of the two test treatment groups (AI and A2) were compared to the 

two control groups (CI) for puppies. An analysis of covariance (CO-ANOVA) with a 

treatment effect and the baseline values as covariate was used for the analyses. In addition, 

the change from baseline values of each of the three treatment groups (BI, B2 and B3) were 

compared to those of the control group (C2) for dogs and the two test groups (AI and A2) 

were compared to those of the control group (CI) for puppies by means of an ANOVA with 

a treatment effect. Groups Al and A2 were compared in a similar way. 

C. METHODS: 

1. Observations: 

a. General health observations: The animals were observed daily for general health. 

Specific health observations were observed hourly on the day of application until four 

hours after application of the test material and twice daily, thereafter, for the duration of 

the study. Observations included, but were not limited to, changes in skin and fur, eyes 

and mucous membranes, nervous signs and behavior pattern as well as vomiting and 

diarrhea. Local tolerance observations were also included. 

Page 10 of 18 
152

b. Veterinary examinations: Physical examinations were conducted by a veterinarian on 

Days -14, -3, +1, +7 and +14. The examinations included but were not limited to body 

temperature, pulse rate, auscultation of the heart and lungs, mucous membranes and skin, 

joints, eyes, ears, mouth and genital organs. 

2. Body weight: Animals were weighed on Days -14, -7, -1, +1, +7 and + 14. 

3. Food consumption: The amount of food offered was measured and the food consumption 

was recorded daily and scored using the following scoring system. 

Fc 1 - 0- 25% 

Fc 2 - >25- 50% 

Fc 3 - >50-75% 

Fc 4 - >75-100% 

4. Hematology and clinical chemistry: Blood was collected from the jugular vein for 

hematology and clinical chemistry assessments on fasted animals on the following days: - 3, 

+1, +7 and +14. The tests were conducted by Pathcare, Bloemfontein, South Africa, because 

Clin Vet International did not have the expertise and apparatus to perform the analyses. The 

CHECKED (X) parameters were examined. 

a. Hematology 

X Hematocrit (HCT)' X Leukocyte differential count* 

X Hemoglobin (HOB), X Mean corpuscular HOB (MCH)* 

X Leukocyte count (WBC)' X Mean corpusc. HOB conc.(MCHC)* 

X Erythrocyte count (REC)' X Mean corpusc. volume (MCV)* 

X Platelet count* X Reticulocyte count 

Blood clotting measurements* 

X (Thromboplastin time) 

(Fibrinogen) 

X (Prothrombin time) 

*Recommended for companIon anImals safety evaluatIOn based on OPPIS 870.7200 

Page 11 of IS 
153

b. Clinical chemistry 

ELECTROLYTES OTHER 

X Calcium * X Albumin* 

X Chloride* X Creatinine* 

Magnesium X Urea nitrogen* 

X Phosphorus * Total Cholesterol 

X Potassium' (K) X Globulins* 

X Sodium' (NA) X Glucose* 

ENZYMES (more than 2 hepatic enzymes, eg., *) X Total bilirubin * 

X Alkaline phosphatase (AP)' X Total protein* 

Cholinesterase (ChE) Triglycerides 

Creatine kinase Albumin/Globulin ratio 

Lactic acid dehydrogenase (LDH) X Direct bilirubin* 

X Alanine aminotransferase (ALT/also SGPT)* Indirect bilirubin 

X Aspartate aminotransferase CAST/also SGOT)* BUN/Creatinine ratio 

Gamma glutamyl transferase (GGT) Te02 Bicarbonate 

Amylase 

Sorbitol dehydrogenase 

* Recommended for a compamon animal safety evaluatIOn based on OPPTS 870.7200 

5. Urinalysis: Urinalysis was not conducted. 

6. Sacrifice and pathology: The study did not have a scheduled necropsy. 

II. RESULTS 

A. ACTUAL DOSES ADMINISTERED: The mg/kg doses of active ingredients were not 

calculated. Based on calculations by tbe EPA reviewer, the mLlkg doses to puppies were 

significantly higher than those to adults. For example, adults in Group Bl weighing 1l.3 to 

19.38 kg received 1.34 mL each of test substances IA and III for a 0.12 to 0.07 mLlkg dose 

of each substance. Puppies in Group AI weighing 2.12 to 5.56 kg received 0.83 to 2.0 mL of 

test substance IA for a 0.36 to 0.39 mLlkg dose, approximately 5 times the adult dose. 

Puppies in Group IA received 3.1 to 7.5 mL of test substance II for a l.34 to l.46 mLlkg 

dose, approximately 19 times the adult dog dose. 

B. OBSERVATIONS: 

1. Clinical signs of toxicity: Immediately after treatment, one adult dog in Group B 1 showed 

behavioral changes (running, circling). Another adult dog in Group B3 had skin irritation on 

tbe shaved area of the neck (assumed to be area shaved for blood collection). In Group C2, 

one dog had loose feces three hours post-application, one dog had loose mucoid feces with 

blood on Day +2 and another dog had mucoid feces on Day +2. Minor clinical signs 

observed in adult dogs after treatment included the following: swollen mammary gland 

(Group C2, Days +7 and +14); scab on scrotum (Group C2, Day +14); eczema on neck 

(Group B3, Day +7); hair loss on chin (Group B3, Days +7 and +14); and right eye 

lacrimation (Group B2, Day +7). A female in Group B I came into estrus on Day + 1. 

Page 12 ofl8 
154

Immediately after treatment, two puppies in Group Al showed behavioral changes (running, 

circling). Four puppies in Group A2 showed similar behavioral changes after the first 

application but not after subsequent applications. One pup in Group Al had loose feces on 

Day + 1 with blood on Day +4. A pup in Group A2 had loose feces on Day + 13. Minor 

clinical signs in puppies after treatment included the following: thinning of hair in one pup in 

Group A2 on Day +7 which was diagnosed as demodicosis on Day +14; thinning of hair 

(Group A2, Day +14); and scales (two pups in Group CI, Day +14). While the demodicosis 

(mange) was not life threatening, its occurrence suggests that the overall health of the dogs 

and puppies may have been compromised. 

2. Application site examination: White crystallization was observed on the hair tips of adult 

dogs in Groups B 1 [four dogs at one hour post-application and one dog on Day + 1], B2 

(three dogs at one hour post-application, one dog on Day +1 and two dogs on day +2), B3 

(two dogs at one hour post-application, four dogs at three hours post-application and one dog 

at Day +2) and C2 (three dogs at two hours post-application, one dog at 3 hours postapplication, one dog at four hours post-application and one dog at Day +2). The application 

sites of all dogs in Group B3 had an oily or wet appearance. The sign disappeared from one 

dog on Day + 14 but was present on all other dogs at the end of the study. 

White crystals were observed on the hair tips of pups in Groups Al (two pups at one hour 

post-application and one pup at three hours post-application), A2 (one pup each at one hour 

and two hours post-application) and Cl (three pups at one hour post-application and one pup 

at two hours post-application). 

3. Mortality: All adult and juvenile dogs survived to the end of the study. 

B. BODY WEIGHT AND WEIGHT GAIN: Body weight data are presented in Table 3. All 

adult and juvenile dogs gained weight from Day -1 to Day 14. However, mean weight gain in 

pups in the treated groups (AI and A2) was 15% lower than the control group pups. The 

mean weight gain in the treated adult animals was decreased (30-99% as compared to the 

control group). The change was largest in the smaller adult dogs in Group B3 (99% decrease 

as compared to the control group). 

Page 13 of 18 
155

Table 3: Mean body weight and body weight gain' 

Body weight (kg) 

Group Day-I Day +I b Day +7b Day +14 

Al (puPs) 4.24 4.30 4.78 5.44 

A2 (pups) 4.94 5.06 5.54 6.15 

Cl (pups) 5.24 5.50 5.89 6.66 

Bl (adults) 16.Q7 16.41 16.63 16.62 

B2 (adults) 15.56 15.48 15.75 15.80 

B3 (adults) 7.64 7.62 7.62 7.65 

C2 (adults) 16.05 16.30 16.93 16.84 

a N = 6/group, except where noted. 

b Calculated by the reviewer from data on pages 46-47, MRlD 47849609 

C Decrease compared to control group, calculated by the reviewer 

Body weight gain 

Day-I to+l b Day -I to +7' 

0.06 0.54 

0.12 0.60 

0.26 0.65 

0.34 0.56 

-0.08 0.19 

-0.02 -0.02 

0.25 0.88 

kg) 

Day -I to +14 

1.20 (15%)' 

1.21 (15%)' 

1.42 

0.55 (30%)' 

0.24 (70%)' 

0.01 (99%)' 

0.79 

Group Al treated at IX with Substance IA (8.2% w/w cyphenothrin and 9.8% rn/w fipronil) and Substance II (55.16% w/w 

etofenprox, 8.78% w/w s-methoprene, 2.31 % w/w pyriproxifen) 

Group A2 treated at 5X with Substance IA (8.2% w/w cyphenothrin and 9.8% mlw fipronil) and Substance II (55.16% w/w 

etofenprox, 8.78% w/w s-methoprene, 2.3 1% w/w pyriproxifen) 

Groups CI and C2 treated at 5X with Control substance IVA 

Group B I treated at IX with Substance IA (8.2% w/w cyphenothrin and 9.8% rn/w fipronil) and Substance III (8.90% 

methoprene, 2.43% w/w pyriproxifen) 

Group B2 treated at 5X with Substance IA (8.2% w/w cyphenothrin and 9.8% rnIw fipronil) and Substance III (8.90% 

methoprene, 2.43% w/w pyriproxifen) 

C. FOOD CONSUMPTION: No treatment-related effects were reported. 

D. CLINICAL PATHOLOGY ANALYSES: 

L Hematology: No treatment-related changes were observed in adults or pups. An increase 

(as compared to the control group) in monocyte counts in Group Bl adult dogs on Day 

+ I was not considered toxicologically significant. 

2. Clinical Chemistry: No treatment-related effects were reported in adults or pups. A 

decrease (as compared to the control group) in creatinine in Group B3 on Day +7 and a 

decrease in AST in Group B3 on Day + 14 were not considered toxicologically 

significant. The mean glucose value in Group A2 was increased from baseline (Day -3) to 

Days +1 and +14. The mean chloride values in Groups Al and A2 were increased from 

baseline to Day +7. These deviations are not considered toxicologically significant. 

III DISCUSSION AND CONCLUSIONS 

A. INVESTIGATORS' CONCLUSIONS: The study author concluded that two test 

substances, blend IA containing 8.20% w/w cyphenotillin and 9.80% mlw fipronil and blend 

II containing 55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31 % w/w 

pyriproxifen, were safe to use under the conditions of the study when applied simultaneously 

as a spot-on to puppies at the recommended dose as well as five times (5X) the recommended 

dose. 

Blend II containing 55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31% w/w 

pyriproxifen, was safe to use under the conditions of the study when applied topically to 

adult dogs at five times the recommended dose. 

Page 14 ofI8 
156

Two test substances, blend IA containing 8.20% w/w cyphenothrin and 10.07% w/w fipronil 

and blend III containing 8.90% w/w methoprene and 2.43% w/w pyriproxifen, were safe to 

use under the conditions of the study when applied simultaneously as a spot-on to adult dogs 

at the recommended dose as well as at five times the recommended dose. 

B. REVIEWER COMMENTS: All animals survived to the end of the study. Immediately after 

treatment, one adult dog in Group B1 (IX applications of test substances IA and III) showed 

behavioral changes (running, circling). Immediately after treatment, two puppies in Group 

Al (IX application of test substances IA and II) showed similar behavior. Four puppies in 

Group A2 (5X application of test substances IA and II) showed the same behavior after the 

first application but not after subsequent applications. The behavioral signs are considered 

treatment-related in puppies since they occurred in multiple animals both at IX and 5X the 

recommended dose. The behavioral change in adult dogs is considered treatment-related 

since it also occurred in puppies. 

White crystallization was observed on the hair tips of many adult and puppies in the treated 

and control groups. The application sites of all dogs in Group B3 (5X application of test 

substance II) had an oily or wet appearance. The sign disappeared from one dog on Day + 14 

but was present on all other dogs at the end of the study. Since there was no skin irritation, 

the signs are considered cosmetic. However, the persistence of test substance II on the hair of 

dogs for more than 14 days is of concern due to potential human exposure of owners to pets. 

All adult and juvenile dogs gained weight from Day -1 to Day 14. However, mean weight 

gain in pups in the treated groups (AI and A2) was 15% lower than the control group pups. 

The change is considered treatment-related. The mean weight gain in the treated adult 

animals (Groups B1, B2 and B3) was decreased (30-99% as compared to the control group). 

The change was largest in the smaller adult dogs in Group B3 (99% decrease as compared to 

the control group). The animals were considered adults if they were >6 months of age. Adult 

dogs usually are not expected to change weight in a 14-day period; however, dogs as young 

as 6 months may still be gaining weight. The birth dates of the animals were not provided so 

their exact age is unknown. Since the decreases from the control group were large, the 

decreased body weight gain is considered treatment-related in adults. Food consumption was 

not affected by treatment. No treatment-related hematology or clinical chemistry changes 

were observed. 

It is concluded that the margin of safety in puppies administered simultaneous topical 

applications oftest substances IA (8.2% w/w cyphenothrin and 9.8% m/w fiproniI) and 

II (55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31 % w/w pyriproxifen) was 

less than IX the recommended dose, based on clinical signs of toxicity (behavioral 

changes immediately post-application). 

It is concluded that the margin of safety in adult dogs (9-20 kg) administered 

simultaneous topical application of test substances IA (8.2% w/w cyphenothrin and 

9.8% m/w fipronil) and III (8.90% w/w and 2.43% w/w pyriproxifen) was less than IX 

the recommended dose, based on clinical signs oftoxicity (circling and running in one 

dog after application). 

Page 15 of 18 
157

It is concluded that no margin of safety in adult dogs « 9 kg) administered a topical 

application of test substance II (55.16% w/w etofenprox, 8.78% w/w s-methoprene and 

2.31 % w/w pyriproxifen) could be established from the findings ofthis study. 

This study is unacceptable and cannot be upgraded for either adult dogs or puppies. 

C. STUDY DEFICIENCIES: 

a. The study report states that the purpose of the study is to detennine the safety of a 

combination of three test formulation spot-on products containing three toxicants and two 

insect growth regulators. The Companion Animal Safety Guideline (OPPTS 870.2700) 

requires that a study be conducted with the end-use product using the label dose and 

directions for use, although there is a provision for use of a max/tox product containing 

multiple toxicants at the maximum levels which would be anticipated in fonnulated 

topical products. However, this does not appear to have been the objective of the study. It 

is also unclear why different combinations of products were tested in adult and juvenile 

animals. Pups were administered test substances IA and II, whereas large adult dogs were 

administered test substances IA and III and smaller dogs were administered test substance 

II alone. 

b. Other Companion Animal Safety Guideline non-compliances are as follows: 

I. The study used three dogs/sex/group, whereas six dogs/sex/group are required. 

2. Individual animal data for clinical signs were not provided. 

3. Group mean values for body weight were not calculated for Days -14, -7, + 1 and +7. 

4. The control formulation is described as "inert control substance". However, it is not 

certain for which of the test formulations was this the "inert control substance," as no 

analysis was provided. 

5. The date of birth of the animals was not provided. 

6. The mg/kg dose of active ingredients was not calculated. 

7. The laboratory which conducted the hematology and clinical chemistry testing is not 

GLP accredited. 

8. The Guideline allows for five hourly applications of a IX dose to achieve the 5X dose. 

However, with the large volumes of test material used on some of the smaller animals, 

it is likely that the material ran off and was not available for absorption. 

9. The study report states that test substances lA, II and III were applied separately as 

tenninally adjacent stripes, applying test substance IA anterior to test substance II or 

test substance IA anterior to test substance III. It is unclear how the second substance 

could be applied anteriorly when both were administered from the neck to the base of 

the tail. 

10. A certificate of analysis was not provided for each of the test substances. The study 

report states that the concentration of cyphenothrin in test substance IA should have 

been 15% as stated in the protocol but a certificate of analysis indicated that it was 

8.2%. 

Page 16 of 18 
158

11. The study author's conclusion (page 56) gives different percentages of fipronil in test 

substance IA when discussing the findings in puppies (9.8% m/w) and adults (10.07% 

w/w). 

Page 17 of 18 
159

1. DP BARCODE: 371676 

2. PC CODES: 128965 (Etofenprox); 129032 (Pyriproxyfen) 

3. CURRENT DATE: February 24, 2010 

4. TEST MATERIALS: Blend IA: 8.20% w/w cyphenothrin, 9.80% w/w fipronil; Blend II: 

55.16% w/w etofenprox, 8.78% w/w methoprene, 2.31 % w/w pyriproxyfen; Blend III: 8.90% 

w/w methoprene, 2.43% w/w pyriproxyfen; Blend IVA: inert control substance 

Study/Species/Lab MRID Results Tox. Core 

Study # / Date Cat. Grade 

Companion Animal Safety Study/Dogs & 47849609 Four groups (each 6M & 6F) of N/A U 

Puppies adult dogs; 3 groups (each 6M & 

6F) of puppies were used. Adults: 

ClinVet International (Pty) Ltd; Group B I IX IA&III; Group B2: 

Bloemfontein, South Africa 5X IA&II1, Group B3: 5X II; 

Group C2 5X IVA. Puppies: 

Study CV 08/551 I August 6, 2009. Group AI IX IA&II; Group A2: 

5X IA&II; Group C I: 5X IVA. 

Not possible to adequately interpret data from design of study. 

Core Grade Key. A - Acceptable, S - Supplementary, U - Unacceptable, W - WaIved 

Page 18 of 18 
160

UNITE" hATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

September IS, 2009 

SERGEANT'S PET CARE PRODUCTS, INC. 

SERGEANT'S PET CARE PRODUCTS, INC. 

262S SOUTH IS8TH PLAZA 

OMAHA, NE 68130-1703 

Report of Analysis for Compliance with PR Notice 86-S 

OFFICE OF 

PREVENTION, PESTICIDES AND 

TOXIC SUBSTANCES 

Thank you for your submittal of 1 0-SEP-09. Our staff has completed a preliminary 

analysis of the material. The results are provided as follows: 

Your submittal was found to be in full compliance with the standards for submission of 

data contained in PR Notice 86-S. A copy of your bibliography is enclosed, annotated with 

Master Record ID's (MRIDs) assigned to each document submitted. Please use these numbers in 

all future references to these documents. Thank you for your cooperation. If you have any 

questions concerning this data submission, please raise them with the cognizant Product 

Manager, to whom the data have been released. 
161

September 10, 2009 

Richard Gebken 

Product Manager 10 

Document Processing Desk (REGFEE) 

Office of Pesticide Programs (7504P) 

U.S. Environmental Protection Agency 

Room S-4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202-4501 

SUbject: Submission of a Section 3 Registration Application 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies 

Dear Mr. Gebken: 

Exponent 

1150 Connecticut Avenue, NW 

Suite 1100 

Washington, DC 20036 

telephone 202-772-4900 

facsimile 202-772-4979 

www.exponent.com 

On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158'h Plaza, 

Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a 

Section 3 registration application for the product EtofenproxlNylar Spot-On Flea and Tick for 

Dogs and Puppies. Please find enclosed the following support documents: 

• Transmittal document; 

• EPA 8570-1; 

• EPA 8570-27; 

• Confidential Statement of Formula (three copies); 

• EPA 8570-34; 

• Data Matrix; 

• Draft Label (five copies); and 

• Copy ofPRIA paperwork for 50% waiver/reduction and payment check. 

As discussed with EPA during a meeting on August 19, 2009, Sergeant's is submitting 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies as a substantially-similar product 

to the currently registered pesticide product SPI #8208-55D (EPA Registration Number 69332-

3). The product has been formulated and labeled for application to dogs and puppies 4-20 

pounds. 

The enclosed application for registration is for a new end-use product (substantially-similar 

formulation) with supporting data. This registration application is considered an R31 0, new enduse product, requires review of data package within RD, PRIA review time frame 6 months, and 

a fee of $4,578. Sergeant's qualifies for a PRIA fee waiver/reduction of 50% (refer to OPP 

Decision Number D-408042). 
162

If you have any questions, please contact me at 202-772-4932. 

~~r;t ' 

'. t[jL--· 

;7Js~. Messina 

1,uthorized Representative of 

Sergeant's Pet Care Products, Inc. 

Enclosures 

cc: Kimberly Nesci, EPA 

Bob Scharf, Sergeant's 

Kelly Hoskins, Sergeant's 

Larry Nouvel, Nouvel 

Rick Tinsworth, Exponent 
163

September 10, 2009 

Richard Gebken 

Product Manager 10 

Document Processing Desk (REGFEE) 

Office of Pesticide Programs (7504P) 

U.S. Environmental Protection Agency 

Room S-4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202-4501 

Subject: Submission of a Section 3 Registration Application 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies 

Dear Mr. Gebken: 

47849S"()O 

Exponent 

1150 Connecticut Avenue, NW 

Suite 1100 

Washington, DC 20036 

telephone 202-772-4900 

facsimile 202-772-4979 

www.exponcnt.com 

On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158th Plaza, 

Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a 

Section 3 registration application for the product EtofenproxlNylar Spot-On Flea and Tick for 

Dogs and Puppies. Please find enclosed the following support documents: 

• Transmittal document; 

• EPA 8570-1; 

• EPA 8570-27; 

• Confidential Statement of Formula (three copies); 

• EPA 8570-34; 

• Data Matrix; 

• Draft Label (five copies); and 

• Copy of PRIA paperwork for 50% waiver/reduction and payment check. 

As discussed with EPA during a meeting on August 19,2009, Sergeant's is submitting 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies as a substantially-similar product 

to the currently registered pesticide product SPI #8208-55D (EPA Registration Number 69332-

3). The product has been formulated and labeled for application to dogs and puppies 4-20 

pounds. 

The enclosed application for registration is for a new end-use product (substantially-similar 

formulation) with supporting data. This registration application is considered an R31 0, new enduse product, requires review of data package within RD, PRIA review time frame 6 months, and 

a fee of $4,578. Sergeant's qualifies for a PRIA fee waiver/reduction of 50% (refer to OPP 

Decision Number D-408042). 
164

If you have any questions, please contact me at 202-772-4932. 

~~r;l'y' 

/ _.!//L.~-

Jan1es B. Messina f , 

Authorized Representative of . I 

. Sergeant's Pet Care Products, Inc. 

Enclosures 

cc: Kimberly Nesci, EPA 

Bob Scharf, Sergeant's 

Kelly Hoskins, Sergeant's 

Larry Nouvel, Nouvel 

Rick Tinsworth, Exponent 

~X' , . " H, v J~ 
165

Please read instructrons on reverse bef~ Pfeting form Form Appr ,. OMB No 2070 . 0060 Approval expires 05 . 31 -98 

United States IZLRegistration OPP Identifier Number 

EPA Environmental Protection Agency DAmendment 

Washington, DC 20460 o Other 

Application for Pesticide - Section I 

1. CompanylProduct ~'(§.e<:; 2. EPA Product Manager 3. Proposed Classification 

2517.~ R. Gebken 

4. Company/Product (Name) PM# [ZjNone DRestricted EtofenproxiNylar Spot-On Flea and Tick for Dogs and Puppies 10 

(30%) 

5. Name and Address of Applicant (Include ZIP Code) 6. Expedited Review. In accordance with FIFRA Section 3(C)(3)(b)(I), my 

Sergeant's Pet Care Products, Inc. product is similar or identical in composition and labeling to: 

2625 South 158th Plaza 

Omaha, NE 68130 EPA Reg. No. 69332-3 

Product Name SPI #8208·55D 

o Check if this is a new address , 

Section II 

D Amendment - Explain below. D Final printed labels in response to Agency letter dated XX-XX-XX 

D Resubmission in response to Agency letter dated XX-XX~XX D "Me Too" Application 

D Notification - Explain below. C8J Other - Explain below. 

Explanation: Use additional page(s) if necessary. (For section I and Section II.) 

Submission of a new end-use registration application. 

Section III 

1. Material This Product Will Be Packaged In: 

Child-Resistant Packaging Unit Packaging Water Soluble Packaging 2. Type of Container 

DYes' !2'J Yes DYes o Metal 

DNo o No !2'J No k8J Plastic 

If "Yes" No. per If "Yes" No. per DGlass 

'Certification must Unit Packaging wgt. Container Package wgt. Container 

DPaper be submitted 2.0mL I 1-6 I Dother (Specify) Plastic Bag 

3. Location of Net Contents Information 4. Size(s) Retail Container 5. Location of Label Directions 

!2'JLabel o Container 2.0mL DOn Can 

DOn Labeling accompanying product 

6. Manner in Which Label is Affixed to Product DUthograph DOther 

DPaper glued 

DStenciled 

Section IV 

1. Contact Point (Complete items directly below for identification of individual to be contacted, if necessary, to process this app/icatiQn.) , , , Name Title Tel~p1Clne No. Cr,C';uJe Area Code) 

James Messina Authorized Representative (202) 772-4932 

Certification b. U1:tfe'Application 

I certify that the statements I have made on this form and all attachments thereto are true, accurate and complete. i ~~geived 

acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both (~(amped) 

under.aoutk able law. ' ' - 2. Signte V2 . 3. Title 

BY: /I Authorized Representative 

7T 

4. Typed~e: 5. Date: 

James Messina CJ ;/O/C1 
166
167

EXponent 

September 10,2009 

Richard Gebken 

Product Manager 10 

Document Processing Desk (REGFEE) 

Office of Pesticide Programs (7504P) 

U.S. Environmental Protection Agency 

Room S-4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202-4501 

Subject: Submission of a Section 3 Registration Application 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies 

Dear Mr. Gebken: 

478498·00 

Exponent 

1150 Connecticut Avenue, NW 

Suite 11 00 

Washington, DC 20036 

telephone 202-772-4900 

facsimile 202-772-4979 

www.exponent.com 

On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158th Plaza, 

Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a 

Section 3 registration application for the product EtofenproxlNylar Spot-On Flea and Tick for 

Dogs and Puppies. Please find enclosed the following support documents: 

• Transmittal document; 

• EPA 8570-1; 

• EPA 8570-27; 

• Confidential Statement of Formula (three copies); 

• EPA 8570-34; 

• Data Matrix; 

• Draft Label ( five copies); and 

• Copy ofPRIA paperwork for 50% waiver/reduction and payment check. 

As discussed with EPA during a meeting on August 19,2009, Sergeant's is submitting 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies as a substantially-similar product 

to the currently registered pesticide product SPI #8208-55D (EPA Registration Number 69332-

3). The product has been formulated and labeled for application to dogs and puppies 4-20 

pounds. 

The enclosed application for registration is for a new end-use product (substantially-similar 

formulation) with supporting data. This registration application is considered an R31 0, new enduse product, requires review of data package within RD, PRIA review time frame 6 months, and 

a fee of $4,578. Sergeant's qualifies for a PRIA fee waiver/reduction of 50% (refer to OPP 

Decision Number D-408042). 
168

If you have any questions, please contact me at 202-772-4932. 

~~rely, 

.i' ' /1 / A'/ l '. 

/j /" /. _ fL_--,.- -r; 

JmJes B. Messina 

A)1thorized Representative of 

'. Sergeant's Pet Care Products, Inc. 

Enclosures 

cc: Kimberly Nesci, EPA 

Bob Scharf, Sergeant's 

Kelly Hoskins, Sergeant's 

Larry Nouvel, Nouvel 

Rick Tinsworth, Exponent 
169

Data Transmittal Document: 

Product: 

Submitter: 

Return to: 

Sergeant's EtofenproxlNylar Split-On Flea:md ':'irk for Dogs and Puppies· 

2517-NEW 

Sergeant's Pet Care Products, Ill~, (El'A '~('mrany Number 2517) 

2637 South 158th Plaza 

Suite 100 

Omaha, NE 68130-1703 

James Messina 

Exponent 

1150 Connecticut Ave., NW 

Suite 1100 

Washington, DC 20036 

Submittal Date: September 10, 2009 

Volume Study Title MRID 

I Efficacy of a water-based etofenprox spot-on against 47849801 _. 

fleas and ticks on small dogs 

2 Efficacy, at minimum dose rate, of an etofenprox spot-on 47849802 against fleas and ticks on small dogs 

3 Efficacy, at label dose volume and at minimum dose rate, 

" of an etofenprox spot-on against fleas and ticks on small 47849803 

dogs 

4 Evaluation of Sergeant's etofenprox squeeze-on against 47849804 

fleas, ticks and mosquitoes on dogs 

5 Efficacy of Sergeant's etofenprox squeeze-on against 47849805 

Ixodes scapularis nymphs 

6 Efficacy of a 2 mL unit dose of Sergeant's etofenprox 

squeeze-on, applied at minimum dose rates, against fleas 47849808 

and ticks on small dogs 

7 Data analysis of a dose titration to determine the 

relationship between dose rate of etofenprox, when 47849807 applied as a spot-on to dogs, and the duration of residual 

efficacy against flea and tick reinfestation 

8 Analyses of efficacy and safety data to support labels 

claims for Sergeant's squeeze-on for small.dogs 47849808 

containing etofenprox and pyriproxyfen 

9 Companion animal safety evaluation on dogs of spot-on 

products containing multiple toxicants and insect growth 47849809 

regulators 

10 Residential exposure and risk assessment for a proposed 47849810 

etofenprox spot-on product for dogs 
170

Please read instructions on reverse befe. '] ~ ompleting form Form Appr ..i OMS No 20700060 - Approval expires 05~31 -98 

United States [gJ_Registration QPP Identifier Number 

EPA Environmental Protection Agency D_Amendment 

Washington, DC 20460 D Other 

Application for Pesticide - Section I 

1. Company/Product ~~e'G 2. EPA Product Manager 3. Proposed Classification 

2517-~ R. Gebken 

4. Company/Product (Name) PM# ~None DRestricted EtofenproxiNylar Spot-On Flea and Tick for Dogs and Puppies 10 

(30%) 

5. Name and Address of Applicant (Inc/ude ZIP Code) 6. Expedited Review. In accordance with FIFRA Section 3(C)(3)(b)(I), my 

Sergeant's Pet Care Products, Inc. product is similar or identical in composition and labeling to: 

2625 South 1581h Plaza 

Omaha, NE 68130 EPA Reg. No. 69332-3 

Product Name SPI #8208-55D 

D Check if this is a new address 

Section II 

D Amendment ~ Explain below. D Final printed labels in response to Agency letter dated XX-XX-XX 

D Resubmission in response to Agency letter dated XX~XX-XX D "Me Too" Application 

D Notification ~ Explain below. [ZJ Other ~ Explain below. 

Explanation: Use additional page(s) if necessary. (For section I and Section II.) 

Submission of a new end~use registration application. 

Section III 

1. Material This Product Will Se Packaged In: 

Child~Resistant Packaging Unit Packaging Water Soluble Packaging 2. Type of Container 

DYes' [:g] Yes DYes o Metal 

DNo o No [:g] No cg] Plastic 

II "Yes" No. per II "Yes" No. per DGlass 

'Certification must Unit Packaging wgt. Container Package wgt. Container 

DPaper be submitted 2.0mL I 1-6 I Dother (Specify) Plastic Bag 

3. Location of Net Contents Information 4. Size(s) Retail Container 5. Location of Label Directions 

[:g]Label D Container 2.0mL DOn Can 

DOn Labeling accompanying product 

6. Manner in Which Label is Affixed to Product DLithograph DOther 

DPaper glued 

DStenciled 

Section IV , 

n' 

1. Contact Point (Complete items directly below for identification of individual to be contacted, if necessary, to process this applicatiQ{J.) : ~ , , , Name Title }T:e\tfn~ne No. (trit1t..tle Area Code) 

James Messina Authorized Representative , , (202) 71'2-4932 , , ~ 

Certification ,," , , t1') uate'l\pplication 

I certify that the statements I have made on this torm and all attachments thereto are true, accurate and complete. , )~~cpived 

acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both } J ' , ,(,~t'amped) 

under~ able law. ' , :" :'0- , 

2. Signte VZ 3. Title ' ' 

" ! ) ; 1 

, 

BY: /I Authorized Representative ) } } ~ 

7T , 

, , " , 

4. Typed~e: 5. Date: <J;lo/tJ'f 

,)' , 

James Messina 
171

Tracking 

Create 

FFS Letters 
172

\ 

NEW APPLICATIONS 

DATE: SEP 1 02009 

FILE NUMBER: [)Sf7- RGG 

FEP (OPPIN ENTRY)' jv Cfjll/Or; 

(Initial & date) , 

FILE, ROOM: __ ~ __ _ 

(Initial & date) 

SIG: 

(Initial & date) 

FILE ROOM: __ ..,------__ _ 

(Initial & date) 

/ ASSIGN TO PM -- 13 (NO DATA) 

_ JACKET TO SHELF (DATA) 
173

To the Document Center (ITRMD) 

*Please transfer jacket /mini-jacket to Product 

Manager Team circled below: 

Minor Use Section PM- 5 

Insecticide Branch PM -1 0 PM-13 

Herbicide Branch PM-23 PM-25 

Fungicide Branch PM - 21 PM-22 

Insect /Rodent Br .. PM-l PM-7 

*Reminder to PM - If applicable pick-up data 

from Screening Room. 

Processe by RO's Completeness Check T am 
174

21-Day Screen Completed by 

Contractor 

21-Day Expires on ;0 ---/-09 

Jacket # c2 51 7 - ;(&& 

MRID# L/79 Lf'7t:, 

Content Screen: Recommended to 

BFail 

86-5 Review: lpassed-yFailed/NA 

Transfer This Jacket to: 
175

Memorandum 

Date: 09 / n / 09 

To: ____ P_M __ ( 3 _____ , Regulatory Manager 

From: Information Services Branch, ITRJ\1D 

Your receipt of this data submission is not an 

indication that lVIRIDs for the enclosed studies have 

. been posted to OPPIN. 

We expect that it will be approximately 5 days 

from the above date before the study-level data is 

available in OPPIN. 

If you have any questions about this process, 

please contact Teresa Downs (305-5363). 

This is a: ~fullY accepted submission 

o partially accepted submission 

o rejected submission 
176

September 10, 2009 

Richard Gebken 

Product Manager 10 

Document Processing Desk (REGFEE) 

Office of Pesticide Programs (7504P) 

U.S. Environmental Protection Agency 

Room S·4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202·4501 

Subject: Submission of a Section 3 Registration Application 

EtofenproxlNylar Spot· On Flea and Tick for Dogs and Puppies 

Dear Mr. Gebken: 

478498·00 

Exponent 

1150 Connecticut Avenue, NW 

Suite 1100 

Washington, DC 20036 

telephone 202-772-4900 

facsimile 20.2-712-4979 

w\\,cw.exponent.com 

On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 15Sth Plaza, 

Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a 

Section 3 registration application for the product EtofenproxlNylar Spot-On Flea and Tick for 

Dogs and Puppies. Please find enclosed the following support documents: 

• Transmittal document; 

• EPA 8570-1; 

• EPA 8570·27; 

• Confidential Statement of Fonnula (three copies); 

• EPA 8570·34; 

• Data Matrix; 

• Draft Label (five copies); and 

• Copy of PRIA paperwork for 50% waiver/reduction and payment check. 

As discussed with EPA during a meeting on August 19,2009, Sergeant's is submitting 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies as a substantially-similar product 

to the currently registered pesticide product SPI #8208-55D (EPA Registration Number 69332-

3). The product has been fonnulated and labeled for application to dogs and puppies 4-20 

pounds. 

The enclosed application for registration is for a new end-use product (substantially-similar 

fonnulation) with supporting data. This registration application is considered an R31 0, new enduse product, requires review of data package within RD, PRIA review time frame 6 months, and 

a fee of $4,578. Sergeant's qualifies for a PRIA fee waiverlreduction of 50% (refer to OPP 

Decision Number DA08042). 
177

If you have any questions, please contact me at 202-772-4932. 

~~rely, 

,f' )/] ' .. ,-.. j~.i- pL._-.· 

Janles B. Messina 

Aithorized Representative of ./ 

Sergeant's Pet Care Products, Inc. 

Enclosures 

cc: Kimberly Nesci, EPA 

Bob Scharf, Sergeant's 

Kelly Hoskins, Sergeant's 

Larry Nouvel, Nouvel 

Rick Tinsworth, Exponent 
178

Data Transmittal Document: 

Product: 

Submitter: 

Return to: 

Sergeant's EtofenproxlNylar SpLIt-On Flea and ':'irk fo' Dogs and Puppies 

25 I 7-NEW 

Sergeant's Pet Care Products, In~. (EpA '~('mrany Number 2517) 

2637 South 158th Plaza 

Suite 100 

Omaha, NE 68130-1703 

James Messina 

Exponent 

1150 Connecticut Ave., NW 

Suite 1100 

Washington, DC 20036 

Submittal Date: September 10, 2009 

Volume Study Title MRID 

I Efficacy of a water-based etofenprox spot-on against 47849801 fleas and ticks on small dogs 

. 2 Efficacy, at minimum dose rate, of an etofenprox spot-on 47849802 against fleas and ticks on small dogs 

3 Efficacy, at label dose volume and at minimum dose rate, r of an etofenprox spot-on against fleas and ticks on small 47849803 

dogs 

- 4 Evaluation of Sergeant's etofenprox squeeze-on against 47849804 

fleas, ticks and mosquitoes on dogs 

5 Efficacy of Sergeant's etofenprox squeeze-on against 47849805 

Ixodes scapularis nymphs 

6 Efficacy of a 2 mL unit dose of Sergeant's etofenprox 

squeeze-on, applied at minimum dose rates, against fleas 47849808 

and ticks on small dogs 

7 Data analysis of a dose titration to determine the 

relationship between dose rate of etofenprox, when 47849807 applied as a spot-on to dogs, and the duration of residual 

efficacy against flea and tick reinfestation 

8 Analyses of efficacy and safety data to support labels 

claims for Sergeant's squeeze-on for small dogs 47849808 

containing etofenprox and pyriproxyfen 

9 Companion animal safety evaluation on dogs of spot-on 

products containing multiple toxicants and insect growth 47849809 

regulators 

10 Residential exposure and risk assessment for a proposed 47849810 

etofenprox spot -on product for dogs 
179

Ur.:lfC S:4('1 E"~'liOr,n:-" ,'P'C'it:(I\J..- t..:;'ln:! 

Olilet 0) Pn!JcIG' ":OQ:JJlll 

ir-;!OH"J; Ilor F.., lour:-. i .1IC S.· ...... ,;: II c':"YI1,on 

lroI OlfTH II0ro S';"~IC.tl ei~('"".~, 

& EPA 

AD~1J:N1S1RATIVE ~TO(S),: 

• 

).5'11- ReG 

Pl\.{: --,-!3 ____ -----;:---____ ~ __ 

Cr&~ 

T IT}nc yu AT} TO·· • i ... J..J...../ 1" ,. _________ ~ _____ _ 

The jacket for this action can be 

requested through the JACKETS s·ystem. 
180

PRIA 2 - 21 Day Content Screen Review Worksheet 

(EP NOPP Use Only) 

3/23/09 

21 Day Screen Start Date: 9 - 10 - a 9 ./ 

Experts In-Processing Signature: ME JI;-zaJvAl6/U-v Date 9- -/'>-0'7 Fee Paid: Yes_V 

Division management contacted on issues No Yes Date _____ _ 

EPA Reg. Number: ?. SI, - 12. G G EPA Receipt Date: 9-/0-09 

Items for Review Yes No 

1 Application Form (EPA Form 8570-1 )(link to forn1) signed & complete 

X including package type 

dated 

Confidential 

(EPA Form 

Statement 

8570-4) 

of 

(Link 

Formula 

to form) 

all boxes completed, form signed, and X 

2 a) All inerts (link to http://www.epa.gov/opprd001/inerts/), yes no 

including fragrances, approved for the proposed uses (see 

Footnote A) X ••••• 

Certificatiou with Respect to Citation of Data (EPA Form 8570-34) (Link to X 3 form) completed and signed (N/A if 100% repack) 

Certificate and data matrix consistent >c 

If applicant is relying on data that are compensable, is the offer yes no 

to pay statement included. (see Footnote B) 

If "". nhk is there a letter of Authorization for exclusive use only. 

Formulator's Exemption Statement (EPA Form 8570-27) (Link to fonn) 

4 completed and signed (NI A if source is unregistered or applicant owns the 

-'- -, i1) X 

Data Matrix (EPA Form 8570-35) (Link to fonn) both internal and external 

X copies (PR 98-5) (Link to PR 98-5) completed and signed (N/A if 100% 

N/A* 

"'c) 

5 yes 

no· aJ.i •.. :,,' a) Selective Method (Fee category t;Jl.jJ'" lS use) X 

llif~~~~~ b) Cite-All (Fee category experts use) 

r,;c 

c) Applicant owns all data (Fee category experts use) '7 

. ,-,\,' .•. ",;.' 

5 Copies of Label (link to htt[!:llwww.eI!a.gov/oImfeadlllabelinv'lrmD X 6 (Electronic labels on CD are encouraged and guidance is available)( link to 

http://www.epa.gov/peslicides/regulatinglregislering/submissions/index.hlm#labels 

) 

1 

, 
181

7 Is the data package consistent with PR Notice 86-5 (link to PRN 86-5) X 

Notice of Filing (link to 

8 httn:llwww.ena.gov/nesticides/regulatingLtolerance netitions.htm) included 

with petitions (link to k 

http://www.epa.gov/pesticides/regulating/tolerances.htm) 

9 If applicable for conventional applications, reduced risk rationale (link to 

http://,,,,",w.epa.gov/opprdOOl/workplanireducedrisk.html) X 

Required Data (link to 

httn:II",,",w.ena.gov/nesticides/regulatingLdata reguirements.htm) and/or 

data waivers. See Footnote C. 

a) List study (or studies) not included with application 

10 

! 

2 
182

Comments; 

* NI A - Not Applicable 

Footnotes 

0../V1 0 ~"'-- ~d GO ~ -\-e,- +R:-s 

PIU0 - '2G-S ~v~· 

A. During the 21 day initial content review, all eSFs will be reviewed to determine 

whether all inerts listed, including fragrances, are approved for the proposed uses. If an 

unapproved inert is identified, the applicant must either I) resolve the inert issue by, for 

example, removing the inert, substituting it with an approved inert, submitting 

documentation that EPA approved the inert for the proposed pesticidal uses, correcting 

mistakes on the eSF, etc. or 2) provide the data to support OPP approval of the inert or 3) 

withdraw the application. Removing or substituting an inert ingredient will require a new 

eSF and may require submission of data. All information, forms, data and 

documentation resolving the inert issue must have been received by the Agency or the 

application withdrawn within the 21 day period, otherwise, the Agency will reject the 

application as described below. 

To successfully complete this aspect of the 21 day initial content screen, applicants are 

strongly encouraged to verify that all inert ingredients have been approved for the 

application's uses even if a product is currently registered by consulting the inert Web 

3 
183

i ~ 

site [link to http://www.epa.gov/opprdOOliinertsllists.html] and if the inert is not 

approved, to obtain the necessary inert approval prior to submitting an application 

to register a pesticide product containing that inert ingredient. Some inert 

ingredients are no longer approved for food uses or certain types of uses. The name 

and/or CAS number on a CSFmust match the name and CAS number on this web site. 

Simple typographical errors in the name or CAS number have resulted in processing 

delays. 

If an inert is not listed on the inert ingredient web site and the applicant believes that the 

inert has been approved, the applicant should contact the Inert Ingredient Assessment 

Branch (IIAB) at inertsbranch@epa.gov and resolve the issue. Copies of the 

correspondence with IIAB resolving the issue should accompany the application. All 

new inerts except PIP inerts are reviewed by nAB. The IIAB should also be contacted 

for any questions on what supporting data needs to be submitted for and the Agency's 

inert review process. Questions on PIP inerts should be directed to the Chief of 

Microbial Pesticides Branch [Link to 

http://www.epa.gov/oppbppdllbiopesticides!contactsbppd.htm]. 

When a brand, trade, or proprietary name of an inert ingredient is listed on a CSF, 

additional information such as an alternate name of the inert, CAS number or other 

information [link to http://www.epa.gov/opprd001/inerts/tips.pdt] must also be included 

to enable the Agency to determine if it has been approved. Each component of an inert 

mixture (including a fragrance) must be identified. In some cases, the supplier of the 

mixture or fragrance may need to provide this information to the Agency. Prior to the 

Agency's receipt of an application, applicants must arrange with a proprietary mixture or 

fragrance supplier to provide the component information to the Agency or promptly upon 

EPA's request. If the inert ingredients in a proprietary blend (including fragrances) 

carmot or are not identified or provided within the 21-day content review period, the 

Agency will reject the application. 

During the 21 day content review, applicants should submit information to the individual 

identified by the Agency when the applicant is informed of an unapproved inert. 

Unapproved Inerts Identified on CSFs 

All applications except conventional new products and PIPs 

Once an unapproved inert is identified on a CSF, the Agency will contact the 

applicant with the following options: 

I. Correct the application by, for instance, correcting the inert's identity or CAS 

number, providing documentation that the inert has been approved, or 

removing the unapproved inert from the CSF or replacing it with one that is 

approved for the application's uses; or 

2. Submit the information and data needed for the Agency to approve the 

unapproved inert If this option is selected and implemented, the Agency may 

request an extension in the PRIA decision review timeframe to accommodate 

the inert review/approval process; 

4 
184

3. Withdraw the application (the Agency retains 25% of the full fee for the fee 

category estimated); or 

If none of these options is selected and implemented by the applicant within the 

21 day content review period, the Agency will reject the application and retain 

25% of the full fee of the category identified. 

Conventional New Product Applications 

When the Registration Division identifies an unapproved inert on a CSF with an 

application for a new product that the applicant has not identified as requiring an 

inert approval (R311 , R312 or R313), it will contact the applicant with the 

following options: 

1. Correct the application by, for instance, correcting the inert's identity or CAS 

number, providing documentation that the inert has been approved, or 

removing the unapproved inert from the CSF or replacing it with one that is 

approved for the application's uses; or 

2. Submit the information and data needed for the Agency to approve the 

unapproved inert, including any required petition to establish or amend a 

tolerance or exemption from a tolerance. (This option may change the PRIA 

category for the application, which could require a longer decision review 

time and a larger fee. If additional fees are due, they must be received by the 

Agency within the 21 day content review period.) 

3. Withdraw the application (the Agency retains 25% of the full fee for the fee 

category estimated); or 

If none of the above options is selected and implemented during the 21-day 

content-review period, the Agency will reject the application and retain 25% of 

the appropriate fee for the new product-inert approval category. 

PIP Applications 

When the Biopesticide and Pollution Prevention Division identifies an 

unapproved inert on a PIP CSF and a request to approve the inert does not 

accompany the application, it will contact the applicant with the following 

options: 

1. Correct the application by, for instance, correcting the spelling or name of the 

inert to that in 40 CFR 174, or providing documentation that the inert has been 

approved; or 

2. Submit the information and data needed for the Agency to approve the 

unapproved inert. If an inert ingredient tolerance exemption petition is 

required, the petition must be received by the Agency and the B903 fee paid 

within the 21 day period. If this option is selected and implemented, the 

Agency will discuss harmonizing the timeframe for both actions. 

5 
185

3. Withdraw the application (the Agency retains 25% of the full fee for the fee 

category estimated); or 

If none of the above options is selected and implemented during the 21 day 

content review period, the Agency will reject the application and retain 25% of 

the fee. 

B. A policy on documentation of offers to pay is still being developed, however, for a 

me-too or fast track (similar/identical) new product, R300 or A530, an application 

without the necessary authorizations of offers to pay will be placed into either R30! or 

A53!. The Agency recommends that authorizations of offers to pay be submitted with 

other PRIA applications to avoid delays in the Agency's decision. 

C. Biopesticide applicants are advised to contact the Agency and discuss study waivers 

prior to submitting their application to the Agency. Documentation of such discussions 

should be submitted with the study waiver. 

6 
186

Ms. Balan, 

RE: Submissiou to EPA 

.James Messina to: Aswathy Balan 

Cc; Sree Nair 

As discussed today, please fmd attached the requested pages. 

If you have any questions, please contact me at 202-772A932. 

Best Regards, 

Jim 

-----Original Message-----

From: Balan.Aswathy@epamail.epa.gov 

[mailto:Balan.Aswathy@epamail.epa.gov 1 

Sent: Thursday, September 17, 2009 II: II AM 

To: James Messina 

Cc: Nair.Sree@epamail.epa.gov 

Subject: Submission to EPA 

Hi Mr. James, 

This is a follow-up email regarding your Application for Registration of 

the products Cyphenothrin + Methoprene Squeeze-on for Dogs(30%) (EPA Reg 

No: 2517-REI), and EtofenproxlNylar Spot-on Flea and Tick for Dogs and 

Puppies(30%) (EPA Reg No:2517-RGG). We have found the following 

deficiencies regarding your submissions. 

Cyphenothrin + Methoprene Squeeze-on for Dogs(30%) (EPA Reg No: 

2517-REI) 

1. The Application form (EPA Form 8570-1) is missing. 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies(30%) (EPA 

RegNo:2517-RGG) 

l.ln Study #9: Companion animal safety evaluation on dogs of spot-on 

products containing multiple toxicants and insect growth regulators: 

Your No claim of confidentiality statement is contradicted by the 

marking(s) on pages 112-129 of the study. So please send me the 

confidentiality statement (page 2) with the following statement added to 

it: 

This statement of confidentiality supersedes all confidentiality claims 

that you may fmd elsewhere in this report. 

You can send me the form and corrected page either by fax to 

703-305-5060, Attn: Aswathy Balan or email to balan.aswathy@epa.gov. 

Thanks, 

Aswathy Balan 

Data Analyst (EPA Contractor) 

2777 S. Crystal Drive, S6943 

09117/200901:02 PM 
187

Arlington, VA 22202 

Ph: 703-347-8787 

Fax: 703-305-5060 

Email: balan.aswathy@epa.goY 

8750-1 Cyphenothrin+Methoprene.pdf sergeant no datac::onfstate:ment.pdf 
188

S, )t for Rej,ection Phone calls 

Contact Name: ::Jo.1'V\ u, 8, Mf>:<;,o,., "'-

Phone #: ;'Oc:'{ - '11 Q - lj 9 2> :;J.. 

Email: j ""<' 55;V\.R@ e'lLp" Vle.,1, U:l Iv\. 

First CallIInitWs: AB 

Date: 09 I t'1 r D9 

Time: I r : 05 AN 

Second CallJInitials: 

Date: 

Time: 

This is, __ cA_g_(,{)--=..;<A-!;.;..'-=l-C-f1_:R_0-_1_<A.._Vo-____ --', EPA contractor. 

I'm calling regarding your submission in support of 

fLu lJ<..,\.t'f;y,,-~ ~ b l""O!L"h -;> o>S!/ - R EJ Q",-tf 

We have found the following deficiencies regarding: 

PR Notice 86.5: @r No 

0o~:m~:~~y~~~: ~ .s\'-'-~ ~ 9: tv\- \')1" \\:{- \~~, ~''''''Srl~~~1 '\Ab.'15k:'~ r~"'\: cs~,to t",,>[-iALt ,t~ lVe ,-l<U'N) 6b 

Volume/Study Title: (j ('~ G cl.. v~ U 'oj;, -L1 .0 to- t. (l~ ... t t;~ -\-k, <;' W(j . 

Volume/Study Title: 

Additional volumes continued on back of page: Yes or No 

Application Package@or No ' 

CD \tI<- .Q5T1- R E: 1 =7 Arr\r'La\. d-;"" 16'<Y'<> IS 'vv.. ~ ~ 5, ~D(} , 

These deficiencies have been approved by EPA. A 

The corrections can be faxed to 703-305-5060/ Attn: "\N 0... tt-, '--\ \ 

Second CallIEmail: 

Ifwe do not receive the'corrections by , we will process 

your, submission, accordingly. Please direct all future calls and 

correspondence to the appropriate EPA Risk Manager. 
189

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

September 14, 2009 

OPP Decision Number: D-420097 

EPA File Symbol or Registration Number: 2517 -RGG 

OFFICE OF 

PREVENTION, PESTICIDES AND 

TOXIC SUBSTANCES 

Product Name: ETOFENPROXINYLAR SPOT -ON FLEA AND TICK FOR DOGS & 

PUPPIES(30%) 

EPA Receipt Date: 10-Sep-2009 

EPA Compauy Number: 2517 

Compauy Name: SERGEANT'S PET CARE PRODUCTS, INC.EPA File Symbol or 

Registration Number: 

KELLY R. HOSKINS 

SERGEANT'S PET CARE PRODUCTS, INC. 

2625 SOUTH 158TH PLAZA 

OMAHA, NE 68l30-1703 

SUBJECT: Receipt of Application aud 50% Small Business Waiver Request 

De!jf Registraut: 

The Office of Pesticide Programs has received your application, 50% small business 

waiver re'lllest, aud cerification of payment. If you submitted data with this application, the 

results of the pRN-86-5 screen will be communicated separately. During the administrative 

screen, the Office of Pesticide Programs has determined that this Action is subject to a Pesticide 

Registration Service Fee as defined in the Pesticide Registration Improvement Act. 

The Action has been identified as Action Code: R31 0 

NEW PRODUCT;NON-FAST TRACK (INCLUDES REVIEWS OF PRODUCT 

CHEMISTRY;ACUTE TOXICITY;PUBLIC HEALTH PEST EFFICACY); 

Your request for waiver has been forwarded for review. You will be notified in writing when a 

determination is made regarding your request. If your waiver request is approved, the decision 

review time period will start on the date of approval. If your waiver request is denied, you will 

receive au invoice for the outstauding balauce. 

If you have any questions, please contact the Pesticide Registration Service Fee 

Ombudsmau at (703) 305-6249. ,:/: 
190

IFee for Servicel -' {857902+~ 

This package includes the following for Division 

~ New Registration oAD 

o Amendment oBPPD 

~RD 

~ Studies? ~Fee Waiver? [ill -J Risk Mgr. Dvolpay % Reduction: 50! v 

Receipt No. s-I 857902 I 

EPA File Symbol/Reg. No. I 2517-RGG I 

Pin-Punch Date: I 9/10/2009 I 

o This item is NOT subject to FFS action. 

Parent/Child Decisions: 

Requested: I IZ 3/ D 

Granted: I K '31 0 I 

Amount Due: $ Y~-lt{J'9,JfV 

Uncleared Inert in Product 

Reviewer:_----'-~_==_____==_ ____ _ Date: O(-! If- Dr 

Remarks: 
191

Ap_pli~'Stbn"D,~e,: 

lront~nCl Date: 

FFS'DueOate: 

OPPT~rgatDate: 

"astIrack:. r 

F O-Sep-2009 

~ 1-Sep-2009 

1 

Fee For Servic'e: 'r."'f{~;l r No 

>BaI,sble: it Y~i' C No 

Me To'(f "" , , 

Product Name: jSPI#8208"5SD 

OPPRec'vd Date: 

~isK Man~gerSe'nd Date: 

N¢~QUated',Clue' Date: 

r 

T 

, Receipt''DE;~criPtion: 

~~--------~--~~--~~--------­ ubmission of a new end-use registration application 

FormA r 

Print Letter 

Enter More Information 

.. RecOlplConl"nt 

~OdY····················· 

fSF 

Tracking 

View/Edit 
192

FEE FOR SERVICE 
193

September 10, 2009 

U.S. Bank 

FIFRA Service Fees 

Government Lockbox 979074 

1005 Convention Plaza 

SL-MO-C2-GL 

St. Louis, MO 63197 

(314) 418-4990 

Subject: Submission of EPA Pesticide Registration Improvement Act Fees 

U.S. EPA FIFRA Service Fees: 

Exponent 

1150 Connecticut Avenue, NW 

Suite 1100 

Washington, DC 2C036 

telephone 202-772-4900 

facsimile 202-772-4979 

www.exponent.c0l1l 

On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158th Plaza, 

Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting 

Pesticide Registration Improvement Act Fees for the following new registration applications: 

• R310, $4,578 (50% fee waiver $2,289), Cyphenothrin+Methoprene Squeeze-On for Dogs 

(20%), check #426591; 

• R310, $4,578 (50% fee waiver $2,289), Cyphenothrin+Methoprene Squeeze-On for Dogs 

(30%), check #426592; 

• R310, $4,578 (50% fee waiver $2,289), Cyphenothrin+Pyriproxyfen Squeeze-On for 

Dogs (20%), check #426593; 

• R310, $4,578 (50% fee waiver $2,289), Cyphenothrin+Pyriproxyfen Squeeze-On for 

Dogs (30%), check #426594; 

• R31O, $4,578 (50% fee waiver $2,289), Cyphenothrin Squeeze-On for Dogs (20%), 

check #426595; 

• R310, $4,578 (50% fee waiver $2,289), Cyphenothrin Squeeze-On for Dogs (30%), 

check #426596; and 

• R310, $4,578 (50% fee waiver $2,289), Etofenprox/Nylar Spot-On Flea and Tick for 

Dogs and Puppies, check #426597. 

Each of the registration applications are for a new end-use product (substantially-similar 

formulation) with supporting data. They are all considered an R31 0, new end-use product, 

requires review of data package within RD, PRIA review time frame 6 months, and a fee of 

$4,578. Sergeant's qualifies for a PRIA fee waiverlreduction of 50% (refer to OPP Decision 

Number D-408042). 

The total amount of the combined PRIA fee payments is $11,445. 
194

If you have any questions, please contact me at 202-772-4932. 

Sin,ce~el y, . /' 

( 

James B. Messina 

,.Authorized Representative of 

Sergeant's Pet Care Products, Inc. 

Enclosures 

cc: Kimberly Nesci, EPA 

Richard Gebken, EPA 

Bob Scharf, Sergeant's 

Kelly Hoskins, Sergeant's 

Larry Nouvel, Nouvel 

Rick Tinsworth, Exponent 
195

Pet Care Products, Inc. 

Omaha, Nebraska 

Pay 

fP6 Co 11'1"'111 t/?.; Il- Texas Capital Bank 

Hill Country 

Two Thousand Two Hundred Eighty Nine Dollars And 00/100 

EPA 

1149 

426597 

VOID AFTER 180 DAYS 

TWO SIGNATURES REQUIRED FOR AMOUNTS OVER $25,00000 

to the 

order of 

WASHINGTON FINANCE CTR 

FIFRA SERVICE FEES 

PO BOX 979074 

ST LOUIS, MO 63197-9000 

1I'42bS'l711' 

557541 

*Commercial/financial information may be entitled to confidential treatment*
196

Data Transmittal Document: 

Product: 

Submitter: 

Return to: 

Sergeant's Etofenprox/Nylar Sput-On Flea ond ':'ick fo' Dogs and Puppies 

25 I 7-NEW 

Sergeant's Pet Care Products, In~. (El'A '~Qmpany Number 2517) 

2637 South 158th Plaza 

Suite 100 

Omaha, NE 68130-1703 

James Messina 

Exponent 

1150 Connecticut Ave., NW 

Suite 1100 

Washington, DC 20036 

Submittal Date: September 10, 2009 

Volume Study Title MRID 

I Efficacy of a water-based etofenprox spot-on against 

fleas and ticks on small dogs 

2 Efficacy, at minimum dose rate, of an etofenprox spot-on 

against fleas and ticks on small dogs 

3 Efficacy, at label dose volume and at minimum dose rate, 

of an etofenprox spot -on against fleas and ticks on small 

dogs 

4 Evaluation of Sergeant's etofenprox squeeze-on against 

fleas, ticks and mosquitoes on dogs 

5 Efficacy of Sergeant's etofenprox squeeze-on against 

Ixodes scapularis nymphs 

6 Efficacy of a 2 mL unit dose of Sergeant's etofenprox 

squeeze-on, applied at minimum dose rates, against fleas 

and ticks on small dogs 

7 Data analysis of a dose titration to determine the 

relationship between dose rate of etofenprox, when 

applied as a spot-on to dogs, and the duration of residual 

efficacy against flea and tick reinfestation 

8 Analyses of efficacy and safety data to support labels 

claims for Sergeant's squeeze-on for small dogs 

containing etofenprox and pyriproxyfen 

9 Companion animal safety evaluation on dogs of spot-on 

products containing multiple toxicants and insect growth 

regulators 

10 Residential exposure and risk assessment for a proposed 

etofenprox spot -on product for dogs 
197

Please read instructions on reverse bef6 

) or ;eting form ",- Form Appr " .I. -.../! iJ1B No 20700060 - Approval expires 05 -31 -98 

United States ISLRegistration OPP Identifier Number 

EPA Environmental Protection Agency D.Amendment 

Washington, DC 20460 o Other 

Application for Pesticide - Section I 

1. Company/Product ~~erG 2. EPA Product Manager 3. Proposed Classification 

2517-~ R. Gebken 

4. Company/Product (Name) PM# ~None DRestricted EtofenproxiNylar Spot-On Flea and Tick for Dogs and Puppies 10 

(30%) 

5. Name and Address of Applicant (Include ZIP Code) 6. Expedited Review. In accordance with FIFRA Section 3(C)(3)(b)(I), my 

Sergeant's Pet Care Products, Inc. product is similar or identical in composition and labeling to: 

2625 South 158th Plaza 

Omaha, NE 68130 EPA Reg. No. 69332-3 

Product Name SPI #8208-55D 

D Check if this is a new address 

Section II 

D Amendment - Explain below. D Final printed labels in response to Agency letter dated XX -XX-XX 

D Resubmission in response to Agency letter dated XX-XX-XX D "Me Too" Application 

D Notification - Explain below. ~ Other - Explain below. 

Explanation: Use additional page(s) if necessary. (For section I and Section II.) 

Submission of a new end-use registration application. 

Section III 

1. Material This Product Will Be Packaoed In: 

Child-Resistant Packaging Unit Packaging Water Soluble Packaging 2. Type of Container 

DYes' [8J Yes DYes DMetal 

DNo o No [8J No [8J Plastic 

If "Yes" No. per If "Yes" No. per DGlaSS 

*Certification must Unit Packaging wgt. Container Package wgt. Container 

DPaper be submitted 2.0mL I 1-6 I DOther (Specify) Plastic Bag 

3. Location of Net Contents Information 4. Size(s) Retail Container 5. Location of Label Directions 

[8JLabel D Container 2.0mL DOn Can 

DOn Labeling accompanying product 

6. Manner in Which Label is Affixed to Product DUthograph DOther 

DPaper glued 

DStenciled 

Section IV 

1. Contact Point (Complete items directly below for identification of individual to be contacted, if necessary, to process this app/icatiQn.) \ \ , Name Title T~!ep'')ne No. (':r,c';uJe Area Code) 

James Messina Authorized Representative (202) 712-4932 

Certification b. U1:!(e' Application 

I certify that the statements I have made on this form and all attachments thereto are true, accurate and complete. i ~'2eived 

acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both (stamped) 

under~ able law. -- 2. Signtre v:z '. 3. Title 

BY: II Authorized Representative 

7T 

4. Typed~e: 5. Date: 

James Messina '1;/0/01 
198

Form approved. OMB No. 2070·0060, 2070-006" ... 070-0107, 2070·0122, 2070-0164. 

& EPA 

United States 

Environmental Protection Agency 

Washington, DC 20460 

Formulator's Exemption Statement 

(40 CFR 152.85) 

Applicant's Name and Address EPA File Symbol/Registration Number 

Sergeant's Pet Care Products, Inc. 2517-NEW 

2625 South 158th Plaza Product Name 

Omaha, NE 68130 EtofenproxINylar Spot-On Flea and Tick For Dogb 

Date of COqi;I:~m;nt of Fonnula (EPA Form 8570-4) 

As an authorized representative of the applicant for registration of the product identified above, I certify that: 

(1) This product contains the following active ingredient(s): 

Etofenprox and Pyriproxyfen 

(2) Of these, each active ingredient fisted in paragraph (4) is present solely as the result of the use of that active ingredient in the manufacturing, 

formulation or repackaging another product which contains that active ingredient which is registered under FIFRA Section 3, is purchased by 

us from another person and meets the requirements of 40 CFR section 158.50(e)(2) or (3). 

(3) Indicate by checking (A) or (B) below which paragraph applies: 

71 (A) An accurate Confidential Statement of Formula (EPA FORM 8570·4) for the above identified product is attached to this statement. 

That formula statement indicates, by company name, registration number, and product name, the source of the active ingredient(s) listed in 

paragraph (1). 

OR 

., (8) The Confidential Statement of Formula (CSF)(EPA Form 8570·4) referenced above and on file with the EPA is complete, current, an 

accurate and contains the information required on the current CSF. 

(4) The following active ingredients in this product qualify for the formulator's exemption. 

Source 

Active Ingredient Product Name Registration Number 

Etofenprox 

, 

Pyriproxyfen P' 

, 

, H , )' " " ; t :> 

. • . , , , , , ,}, 1l) i 

, 

} ) '} , 

Sign~re t21. Name and Title Da:J.ioio7 , .. James Messina, Authorized Rep. / ----- D ) ff , } 

EPA FOr570-27 (Rev. 06-2004) Copy 1 -.tF:PI'; , Copy 2 - Applicant copy ) ,; 

j F' 

*Product ingredient source information may be entitled to confidential treatment*
199

Form Approved OMB Nos. 2070-0060; 2070-0057; 2070-0107; 2070-0 t22· 2070-0164 

.............. UNITED STATES ENVIRONMENTAL PROTECTION AGENCY (~) "I._v"#" 1200 Pennsylvania Avenue, N.W. 

WASHINGTON, D.C. 20460 

Paperwork Reduction Act Notice; The public reporting burden for this collection of information is estimated to average 1.25 hours per response for registration 

and 0.25 hours per response for reregistration and special review activities, including time for reading the instructions and completing the necessary fonns. Send 

comments regarding burden estimate or any other aspect of this collection of infonnation, including suggestions for reducing the burden to: Director, Collection 

Strategies Division (2822T), U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, N.W., Washington, DC 20460. Do not send the completed fonn 

to this address. 

Certification with Respect to Citation of Data 

Applicant's/Registrant's Name, Address, and Telephone Number EPA Registration Number/File Symbol 

Sergeant's Pel Care Products, Inc., 2625 South 158th Plaza, Omaha, NE 68130 2517·NEW 

Aclive InQredient(s) and/or representative test compound{s) Date 

Etofenprox and Pyriproxyfen 9/10/09 

General Use Pattern(s) (list all those claimed for this product using 40 CFR Part 158) Product Name 

Indoor non-food EtofenproxlNylar Spot-On Flea and Tick for Dogs D 

NOTE: If your product is a 100% repackaging of another purchased EPA-registered product labeled for all the same uses on your label, you do not need to 

submit this form. You must submit the Formulator's Exemption Statement (EPA Form 8570-27). 

0 I am responding to a Data-Call-In Notice, and have induded with this form a list of companies sent offers of compensation (the Data Matrix form should 

be used for this purpose). 

SECTION I: METHOD OF DATA SUPPORT (Check one method only) 

0 I am using the cite-all method of support, and have included with this form [2] I am using the selective method of support (or cite-all option 

a list of compan·les sent offers of compensation (the Data Matrix form under the selective method), and have included with this form a 

should be used for this purpose). completed list of data requirements (the Data Matrix form must be 

used). 

SECTION 11: GENERAL OFFER TO PAY 

[Required if using the cite-all method or when using the cite-all option under the selective method to satisfy one or more data requirements] 

0 I hereby offer and agree to pay compensation, to other persons, with regard to the approval of this application, to the extent required by FIFRA. 

SECTION Ill: CERTIFICATION 

I certify that this application for registration, this form for reregistration, or this Data-Call-In response is supported by all data submitted or cited in the 

application for registration, the form for reregistration, or the Data-Call-In response. In addition, if the cite-all option or cite-all option under the selective method is 

indicated in Section I, this application is supported by all data in the Agency's files that (1) concern the properties or effects of this product or an identical or 

substantially similar product, or one or more of the ingredients in this product; and (2) is a type of data that would be required to be submitted under the data 

requirements in effect on the date of approval of this application if the application sought the initial registration of a product of identical or similar composition and 

uses. 

I certify that for each exdusive use study cited in support of this registration or reregistration, that I am the original data submitter or that I have obtained 

the written permission of the original data submitter to cite that study. 

I certify that for each study cited in support of this registration or reregistration that is not an exclusive use study, either: (a) I am the original data 

submitter; (b) I have obtained the permission of the original data submitter to use the study in support of this application; (c) all periods of eligibility for 

compensation have expired for the study; (d) the study is in the public literature; or (e) I have notified in writing the company that submitted the study and have 

offered (I) to pay compensation to the extent required by sections 3(c)(1)(F) and/or 3(c)(2)(B) of FIFRA; and (il) to commence negotiations to determine the 

amount and terms of compensation, if any, to be paid for the use of the study. 

I certify that in all instances where an offer of compensation is required, copies of all offers to pay compensation and evidence of Iheir delivery in 

accordance with sections 3(c)(1)(F) and/or 3(c)(2)(B) of FIFRA are available and will be submitted to the Agency upon request. Should I fail to produce such 

evidence to the Agency UpOn request, I understand that the Agency may initiate action to deny, cancel or suspend the registration of my product in conformity with 

FIFRA 

I certify that the statements I have made on this form and all attachments to it are true, accurate, and complete. I acknowledge that any 

knowingly false or misleading statement may be punishable by fine or imprisonment or both under applicable law. 

~ 

Signature ( rL , Date Typed or Printed Name and Title 

9/10/09 James Messina, Authorized Representative 

EPA Form 8570-34 (1213) Electronic and Paper versions available. Submit only Paper version. 
200

EXponenr 

September 10, 2009 

Richard Gebken 

Product Manager 10 

Document Processing Desk (REGFEE) 

Office of Pesticide Programs (7504P) 

U.S. Environmental Protection Agency 

Room S-4900, One Potomac Yard 

2777 South Crystal Drive 

Arlington, VA 22202-4501 

SUbject: Submission of a Section 3 Registration Application 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies 

Dear Mr. Gebken: 

Exponent 

1150 Connecticut Avenue, NW 

Suite 1100 

Washington, DC 20036 

telephone 202~772-4900 

facsimile 202-772-4979 

www.exponent.com 

On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158'h Plaza, 

Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a 

Section 3 registration application for the product EtofenproxlNylar Spot-On Flea and Tick for 

Dogs and Puppies. Please find enclosed the following support documents: 

• Transmittal document; 

• EPA 8570-1; 

• EPA 8570-27; 

• Confidential Statement of Formula (three copies); 

• EPA 8570-34; 

• Data Matrix; 

• Draft Label (five copies); and 

• Copy ofPRIA paperwork for 50% waiver/reduction and payment check. 

As discussed with EPA during a meeting on August 19, 2009, Sergeant's is submitting 

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies as a substantially-similar product 

to the currently registered pesticide product SPI #8208-55D (EPA Registration Number 69332-

3). The product has been formulated and labeled for application to dogs and puppies 4-20 

pounds. 

The enclosed application for registration is for a new end-use product (substantially-similar 

formulation) with supporting data. This registration application is considered an R31 0, new enduse product, requires review of data package within RD, PRIA review time frame 6 months, and 

a fee of$4,578. Sergeant's qualifies for a PRIA fee waiver/reduction of 50% (refer to OPP 

Decision Number D-408042). 
201

If you have any questions, please contact me at 202-772-4932. 

/~relY, 

1".--I41l"---",, 

JMs B. Messina 

4jthorized Representative of 

Sergeant's Pet Care Products, Inc. 

Enclosures 

cc: Kimberly Nesci, EPA 

Bob Scharf, Sergeant's 

Kelly Hoskins, Sergeant's 

Larry Nouvel, Nouvel 

Rick Tinsworth, Exponent 
202

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

"" - 401 M Street, S.W. 

WASHINGTON, D.C. 20460 

Paperwork Reduction Act Notice: The public reporting burden for this collection of information is estimated to average 0.25 hours per response for registration activities 

for reregistration and special review activities, including time for reading the instruction and completing the necessary forms. Send comments regarding the burden estimat

collection of information, including suggestions for reducing the burden to Director: OPPE Information Management Division (2137) U.S. Environmental Protection Agen

Washington, DC 20460. Do not send the form to this address. 

DATAMATRlX 

Date: September 10, 2009 EPA Reg No.lFile Symbol 2517-NEW 

Applicant's/Registrant's Name & Address Product: Etofenprox/Nylar F

Sergeant's Pet Care Products, Inc. 2637 South 158th Plaza, Suite 100, Omaha, NE 68130-1703 Tick for Dogs and Puppies 

Ingredients: Etofenprox and Pyriproxyfen 

Guideline Reference Number Guideline Study Name MRIDNumber Submitter 

830.1550,1600,1620,1650, Product Properties Data 46161301 Sergeant's Pet Care Products, Inc

1670,1750,1800 

830.6302,830.6303,830.6304, Product chemistry 46161302 Sergeant's Pet Care Products, Inc

830.7300, 830.7000, 830.6315, 830.7100,830.6320,830.6317 

830.6317,830.6320 Storage stability and corrosion characteristics 46700801 

870.1100 Acute oral toxicity 46161303 Sergeant's Pet Care Products, Inc

870.1200 Acute dermal toxicity 46161304 Sergeant's Pet Care Products, Inc870.1400 Primary eye irritation 46161305 Sergeant's Pet Care Products, Inc

870.1500 Primary dermal irritation 46161306 Pet Care Products, Inc

870.1600 Dermal sensitization 46161307 Sergeant's Pet Care Products, Inc

870.7200 Companion Animal Safety Evaluation on Dogs New submission Sergeant's Pet Care Products, In

810.3300 Efficacy of a water-based etofenprox against New submission Sergeant's Pet Care Products, Inc

fleas and ticks on small dogs 

Residential exposure and risk assessment for a New submission Sergeant's Pet Care Products, In

-----

proposed etofenprox spot-on product for dogs 

Signature: " 11_ Name and Title James Messina, Authorized Representative _n. _ n __ n" ,_ ,- ., •.. '<. •• - , , - •••• _ 
203

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

"" "''''' 401 M Street, S.W. 

WASHINGTON, D.C. 20460 

Paperwork Reduction Act Notice: The public reporting burden for this collection of information is estimated to average 0.25 hours per response for registration activities 

for reregistration and special review activities, including time for reading the instruction and completing the necessary forms. Send comments regarding the burden estimat

collection of 'lnformation, including suggestions for reducing the burden to Director. OPPE Information Management Division (2137) U.S. Environmental Protection Agenc

Washington, DC 20460. Do not send the form to this address. 

DATA MATRIX 

Date: September 10, 2009 EPA Reg No.lFile Symbol 2517-NEW 

Applicant's/Registrant's Name & Address Product: EtofenproxlNylar Spot-On F

Sergeant's Pet Care Products, Inc. 2637 South 1 58th Plaza, Suite 100, Omaha, NE 68130-1 703 Tick for Dogs and Puppies 

Ingredients: Etofenprox and Pyriproxyfen 

Guideline Reference Number Guideline Study Name MRIDNumber Submitter 

830.1550,1600,1620,1650, Product Properties Data 46161301 Sergeant's Pet Care Products, Inc

1670, 1750, 1800 

830.6302, 830.6303, 830.6304, Product chemistry 46161302 Sergeant's Pet Care Products, Inc

830.7300,830.7000,830.6315, 

830.7100,830.6320,830.6317 

830.6317,830.6320 Storage stability and corrosion characteristics 46700801 

870.1100 Acute oral toxicity 46161303 Sergeant's Pet Care Products, In

870.1200 Acute dermal toxicity 46161304 Sergeant's Pet Care Products, In870.1400 Primary eye irritation 46161305 Sergeant's Pet Care Products, In870.1500 Primary dermal irritation 46161306 Sergeant's Pet Care Products, In

870.1600 Dermal sensitization 46161307 Pet Care Products, In

870.7200 Companion Animal Safety Evaluation on Dogs New submission Sergeant's Pet Care Products, In

810.3300 Efficacy ofa water-based etofenprox spot-on against New submission Sergeant's Pet Care Products, In

fleas and ticks on small dogs 

Residential exposure and risk assessment for a New submission Sergeant's Pet Care Products, In

proposed etofenprox spot-on product for dogs 

Signature: " n. Name and Title 

James Messina, Authorized Representative 

'-"n< 10. <".,n 0< ,n "''' e, ••• •• D. __ • ,, __ ,. __ .... :1."'_ ", .. __ , .. n'_QO "Q •• ' __ 
204

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

" 401 M Street, S.W. 

" WASHINGTON, D.C. 20460 

Paperwork Reduction Act Notice: The public reporting burden for this collection of information is estimated to average 0.25 hours per response for registration activities 

for reregistration and special review activities, including time for reading the inDeregistrationcompleting the necessary forms. Send comments regarding the burden estima

collection of information, including suggestions for reducing the burden to Director: OPPE Information Management Division (2137) U.S. Environmental Protection Agen

Washington, DC 20460. Do not send the form to this address. 

DATAMATRlX 

Date: September 10, 2009 EPA Reg No.lFile Symbol 2517-NEW 

Applicant'slRegistrant's Name & Address Product: EtofenproxlNylar Spot-On F

Sergeant's Pet Care Products, Inc. 2637 South 158'" Plaza, Suite 100, Omaha, NE 68130-1703 Tick for Dogs and Puppies 

Ingredients: Etofenprox and Pyriproxyfen 

Guideline Reference Number Guideline Study Name MRiDNumber Submitter 

810.3300 Efficacy at a minimum dose rate of an etofenprox New submission Sergeant's Pet Care Products, Inc

spot-on against fleas and ticks on small dogs 

810.3300 Efficacy at label dose volume and at minimum dose New submission Sergeant's Pet Care Products, Inc

rate of an etofenprox spot-on against fleas and ticks 

on small dogs 

810.3300 Evaluation of Sergeant's etofenprox squeeze-on New submission Sergeant's Pet Care Products, In

against fleas, ticks and mosquitoes on dogs 

810.3300 Efficacy of Sergeant's etofenprox squeeze-on against New submission Sergeant's Pet Care Products, In

Ixodes scapularis nymphs 

810.3300 Efficacy ofa 2 mL unit dose of Sergeant's etofenprox New submission Sergeant's Pet Care Products, Inc

squeeze-on applied at minimum dose rates, against 

fleas and ticks on small dogs 

810.3300 Data analysis of a dose titration to determine the New submission Sergeant's Pet Care Products, In

relationship between dose rate of etofenprox when 

applied as a spot-on to dogs and the duration of 

residual efficacy against fleas and tick reinfestation 

810.3300 Analyses of efficacy and safety data to support label New submission Sergeant's Pet Care Products, In

claims for Sergeant's squeeze-on for small dogs 

containing etofenprox and pyriproxyfen 

/ 

Signature: \ VL,. Name and Title James Messina, Authorized Representative 

-

. 

-

.. .. .. 

-
205

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

401 M Street, S.W. 

W CTT".rrVIV,."T D.C. 20460 

Paperwork Reduction Act Notice: The public reporting burden for this collection of information is estimated to average 0.25 hours per response for registration activities 

for reregistration and special review activities, including time for rcading the instruction and completing the necessary fonus. Send comments regarding the burden estima

collection of information, including suggestions for reducing the burden to Director: OPPE Information Management Division (2l37) U.S. Environmental Protection Agen

DC 20460. Do not send the fonn to this address. 

Sergeant's Pet Care Products, IncSergeant's Pet Care Products, Inc

Sergeant's Pet Care Products, In
206

for reregistration and 

collection of informa 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

'" 401 M Street, S.W. 

'" W D.C. 

to average 0.25 hours per response for registration activities 

activities, including time for reading the inOeregistrationcompleting the necessary forms. Send comments regarding the burden estima

for reducing the burden to Director: OPPE Information Management Division (2137) U.S. Environmental Protection Agenc

Inc

Inc

Sergeant's Pet Care Products, Inc

Sergeant's Pet Care Products, Inc

Inc

Authorized 
207

Sergeant's _et ~are Products, Inc. ~tla~ter Label 

10 September 2009 EPA Reg. No. 2517-XX 

Information in [ ] is optional. Page I of 4 EPA SAL 

FRON'I'..J'A$r,·/·· .. ;. ...•..••.•.....•..•.. ...........~()(;SQPl!:E2;~;;;-0N 

:Ryripr(Jiifeil&¥tlR),!ttQ(en~~o~ Editors Note: [Optional proposed text appears in brackets - the final label may include some or all of the optional text] 

ETOFENPROXJNYLAR SPOT-ON 

FLEA AND TICK FOR DOGS AND PUPPIES 

{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On} 

{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On for small breed dogs} 

{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On for small and toy breed dogs} 

{ABN: Sergeant's Small Breed Flea and Tick Squeeze-On} 

{ABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small breed dogs} 

{ABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} 

{ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On} 

{ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On for dogs} 

{ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} 

{ABN: SentryPro Small Breed Flea and Tick Squeeze-On for Dogs} 

{ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small breed dogs} 

{ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} 

[One Application:(choose from the following)] 

• [with nylar®] 

• [(One) (Two) (Three) (Four) (XX) Applications] 

• [Bonus] 33% more [now includes 4 tubes] 

• [odorless] [unscented] [ fragrance free] 

• [Quick Acting] [&] [Long Lasting] 

• [Dries quickly] [Quick drying formula] [Quick Drying] 

• [Squeeze-On] [stays on and doesn't rub off] 

• [Spreads by using the dog's natural skin oils] 

• [Breaks the flea life cycle for up to (70 Days) (9 Weeks)] 

• [Controls reinfestation for up to (70 days) (9 weeks)] 

• [For toy breeds 4-20 Ibs.] 

• [For small breeds 4-20 Ibs.] 

• [For toy and small breeds 4-20 Ibs.] 

• [Specially formulated for small breed[s] dogs] 

• [Specially formulated for toy breed[ s] [dogs]] 

• [Specially formulated for [toy breed[s]] and [small breed[s]] dogs] 

• [Toy] [and] [small] breed formula] 

• [Gentle protection for [toy] [small] breed dogs] 

• [5 Way Protection] 

• [Controls fleas, ticks, mosquitoes, flea eggs & larvae] 

• [Kills Fleas, Ticks, Flea Eggs, Larvae] [and repels mosquitoes] 

• [Flea, tick, mosquito, flea egg and larvae control] 

• [Kills ticks] 

• [Kills Ticks] [Before they can] [that] [transmit Lyme Disease] 

• [Kills adult fleas] 

• [Kills Fleas and Ticks] 

• [Flea, Tick and Flea Egg Protection] 

• [Flea, Tick and Mosquito control] 

• [Kills fleas that may cause flea allergy dermatitis, and flea bite anemia] 

• [Kills Flea Eggs and Larvae for up to (9 weeks) (70 days) (per application)] 

. , 

, 

;}} ) 

.. 

J; , 

"') ) 

, ) } } 

)'; , 

,,) 2 

• [prevents flea eggs from developing into biting adults for up to (9 weeks) (70 days) (per application)] 

• [Repels mosquitoes that may transmit [heartworm] [West Nile virus] [from feeding on dogs] 

• [Repels Mosquitoes] [Prevents mosquitoes that transmit West Nile virus and heartworm] [from feeding on 

dogs] 
208

Sergeant's -"- h (:are Products, Inc.J1Cl~ter Label 

10 September 2009 EPA Reg. No. 2517-XX 

Information in [ ] is optionaL Page 2 of 4 EPA SAL 

ACTIVE INGREDIENTS: 

Etofenprox ...................................................................................... 55.00% 

Pyriproxyfen.. .... ........... ......... ..... ..... ... ...... .......... ............ ...... .......... 2.20% 

OTHER INGREDIENTS: ........................................................................ 42.80% 

TOTAL 100.00% 

[Nylar® is a registered trademark of McLaughlin Gonnley King Company] 

KEEP OUT OF REACH OF CHILDREN 

CAUTION 

See [Back][or][Side] Label Panel[s] for Additional Precantionary Statements 

NET CONTENTS: 

[One] [Two][Three][Four][Five][Six] 2.0 mL applicators. {for small dogs 4 to 20 IbsJ 

. . 

. 

. , 

) ;, 

) 1 ) ) ; J -. }- ~ " 

. . 

" , 
209

Sergeant's"", h Care Products, Inc. J1~ster Label 

10 September 2009 EPA Reg. No. 2517-XX 

Information in [ ) is optional. Page 3 of 4 EPA SAL 

BAC:[(P~NEJj. . ····~"i·.;i~.~.~.~9J~~RH)]]"t;-~.~:~k9lY .. :J3iJ:jl!.t;Q,!y:~I)Il.JN¥Jj?~~X:E!()feJlPtox 

{Product Name} 

READ ENTIRE LABEL BEFORE EACH USE 

PRECAUTIONARY STATEMENTS 

HAZARDS TO HUMANS AND DOMESTIC ANIMALS 

CAUTION 

HAZARDS TO HUMANS: Causes moderate eye irritation. Avoid contact with eyes and clothing. Wash 

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

HAZARDS TO DOMESTIC ANIMALS: For External Use Only. Do not use on dogs under 12 weeks of age. 

Consult a veterinarian before using this product on debilitated, aged) medicated, pregnant, or nursing animals. 

Sensitivities may occur after using ANY pesticide product for pets. If signs of sensitivity occur, bathe your pet with 

mild soap and rinse with large amounts afwater. If signs continue, consult a veterinarian immediately. 

FIRST AID 

IF IN EYES: Hold eye open and rinse slowly and gently with water for 15-20 minutes. Remove contact lenses, if 

present, after the first 5 minutes, and then continue rinsing. Call a poison control center or doctor for treatment 

advice. Have the product container or label with you when calling a poison control center or doctor or going for 

treatment. You may also contact 1-800-781-4738 for emergency medical treatment information. 

PHYSICAL OR CHEMICAL HAZARDS: Combustible: Do not use or store near heat or open flame. 

DIRECTIONS FOR USE 

It is a violation of Federal Law to use this product in a manner inconsistent with its labeling. 

Do not get this product in your pet's eyes or mouth. Do not apply more often than [once a month] [once every 30 

days]. Use only on Dogs. FOR EXTERNAL USE ON DOGS ONLY. Do not use on puppies less than 12 weeks 

of age. Weigh your dog to be sure you are applying the right dose formulated for the weight of your pet. Do not 

treat your pet with more than one pesticide product at a time. Over dosing your animal can result in serious illness 

and even death. Best if used year round. Do not bathe pet with in the first 24 hours after squeeze-on has been 

applied. Households with more than one pet should not allow dogs or cats to groom each other until solution has, 

dried. DO NOT USE ON CATS or animals other than dogs. Separate the treated dog from all other dogs and c~ts 

for 24 hours after treatment has been applied. Cats or dogs that actively groom or engage in close physical c~nt~ep , 

with treated dogs may be at risk of serious harmful effects. If your dog is exhibiting signs of anrlJopofO being1re&(~d 

for skin dermatitis, talk to your vet before applying any topical flea and tick control product. sopsidviiies may oc'cur 

after using ANY pesticide product on pets. It is recommended to separate treated dogs from othrl P9viehold PPI")"'; 

24 hours after treatment has been applied. If signs of sensitivity occur, bathe your dog with mild ~oap~and rinse with 

large amounts of water. ' ) } ) t , 

) } , ) , " } , 1 

FOR USE ON DOGS: $ t } % 

Weighing 4 TO 20 LBS. - Apply contents of one (2.0 mL) tube [vial] of [Product Name) [Squeeze-on) as a'sp.?! , ' 

high on the back of the dog's neck behind its head and apply as a stripe to a point midway between the neck "I'd tfit 

tail. ),;)} 

(INSERT DIAGRAM THAT DEPICTS APPLICATION OF PRODUCT ON THE DOG) 

HOW TO APPLY: 

Remove product tube [vial] from the package. Holding tube [vial] with notched end pointing up and away from the 

face and body cut or tear off the narrow end at the notches. While holding the animal with one hand, use the other 

hand to apply the solution. Invert the tube [vial] and use the narrow end to part the animal's hair while gently 

squeezing to apply to the animal's skin. Hold the animal for a few seconds to give the solution time to be absorbed 

into the animal's coat. When finished, wrap the tube [vial] in paper and put into the trash. 
210

Sergeant's ... h tare Products, Inc. ~naster Label 

10 September 2009 EPA Reg. No. 2517-XX 

Information in [ ] is optional. Page 4 of 4 EPA SAL 

STORAGE AND DISPOSAL 

Do not contaminate water, food or feed by storage or disposal. 

PESTICIDE STORAGE: Do not remove tube from the pack until ready to use. Store in a cool (below 25°C) dry 

place out of reach of children. Do not refrigerate. Protect from direct sunlight. 

PESTICIDE DISPOSAL: Nonrefillable container. Do not reuse or refill this container. Offer for recycling or 

reconditioning, if available and appropriate. If empty: Do not reuse this container. Place in trash or offer for 

recycling if available. If partly filled: Call your local solid waste agency for disposal instructions. Never place 

unused product down any indoor or outdoor drain. 

[WARRANTY 

Read the entire Directions for Use and Warranty before using this Product. By using this product, user or buyer 

accepts the following warranty. [[The directions for use of this product are believed to be adequate and must be 

followed carefully. However, it is impossible to eliminate all risks inherently associated with the use ofthis product. 

Unintended consequences may result because of such factors as weather conditions, presence or absence of other 

materials, or the manner of application, all of which are beyond the control of Sergeant's Pet Care Products, Inc .. ]] 

Sergeant's Pet Care Products, Inc. is committed to providing high quality products. To the extent consistent with 

applicable law, Sergeant's Pet Care Products, Inc. makes no warranties, express or implied, of merchantability or of 

fitness for a particular purpose or otherwise, that extend beyond statements on this label. To the extent consistent 

with applicable law, Sergeant's Pet Care Products, Inc., the manufacturer, or the Seller disclaims any liability 

whatsoever for special, incidental, or consequential damages reSUlting from the use of this product. To the extent 

consistent with the law, the exclusive remedy of the user or buyer shall not exceed the purchase price paid.] 

[Sergeant's Care Pet Products, Inc. is committed to providing high quality products. If you have questions or 

comments about this product,.please write: Sergeant's Consumer Response, P.O. Box 540399, Omaha, NE 68154-

0399.] 

In Case of Emergency, call: 1-800-781-4738 

Non-Emergency call: 1-800·224-PETS (7387) 

Distributed by: 

Sergeant's Pet Care Products, Inc. 

PO Box 540224 

Omaha, NE 68154 

{END - BACK / SIDE PANEL) 

[Q.EfFr?M~g:~~~~1 

Front Label 

{Product Name) 

Etofenprox ......... .55.0% W/W 

Pyriproxyfen ........ .2.2% W/W 

2.0mL {label code) 

[For more information] [Visit us at:] www.sergeants.com 

Made in USA 

EPA Reg. No. 2517-XX 

EPA Est. No. XXXXXXX 

{date & label code) 

) t)" 

);)! ,) 

Back Label " " 

KEEP OUT OF REACH OF Chll/,);)REN "" 

CAUTION: Read directions and predutions bef~re ) ~ ; ] ) 

using. , ., EPA REG. No. 2517-XX {label c0t1t1) 
211 -------,.;- - -'''''-'' 

rn Y1 

CONFI.DENTIAL STATEMENT OF FORMUUENCL

Formula,;.,rParts . .,f 

ont"l'hisErivelo

NOTE 

. . 

It shall beunlawfuHC!ranypersontouse

.or to reveal,otherthantc..thil' Secretary, or 

the United States Departinent o'Agrlculture o

or to the courts Inrespone .to a sllbpOena

emergencies to pharinaclsts.and other. qua

the. preparation ·of 

the Secretary 

of 

":,,">,<:"':';'::/,:,,<' ":,<"""",,' 'c" Fungicide, and 

" " ',' ',' \' 
Pages 212 through 214 contain the product confidential statement of formula and is n
Pages 215 through 224 contain the identity of product inert ingredients and are not included in this copy.