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### United States Environmental Protection Agency Office of Prevention, Pesticides and Toxic Substances (7505P)

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# Pesticide Fact Sheet

Nam e of Chemical: Mamm alian Gonadotropin Releasing Hormone (GnRH) Re ason for Issuance: New Chemical Nonfood Use Date Issued: September 2009

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### 1. Description of Chemical Peptide Chain : py roGlu1 - His2 - Trp3 - Ser4 - Ty r5 - Gly6 - Leu7 - Arg8 - Pro9 - G ly 10NH2 [GnRH] Common Name: Mammalian Gonadotropin Releasing Hormone (GnRH) EPA PC Code: 116800 Chemical Abstracts Service (CAS) Number: 9034 - 40 - 6 Chemical Class : Sterilant/Hormone Registration Status: New Chemical, nonfood use Pesticide Ty

pe: Mammalian Contraceptive U.S. Producer : U.S. Department of Agriculture, APHIS, Pocatello Supply Depot 238 East Dillon Street Pocatello, ID 832012



### 2. Use Pattern and Formulations Mode of Action The active ingredient, Mammalian Gonadotropin Releasing Hormone (GnRH) is conjugated into a large protein that initiates an immune response in the animal with its own GnRH resulting in contraceptive effects for a minimum of one year. Application Sites GonaCon will be used to control wild white - tailed deer Odocoileus virginianus ) populations in areas where they have become a nuisance (e.g, urban and suburban settings). Methods of Application The vaccine will be administered t o restrained female deer using preloaded s yringes with an 18 or 19 gauge stainless steel hy podermic needle intramuscularly into a large muscle mass by hand injection only . GonaCon is classified as a Restricted Use Pesticide. Use is restrict ed to USDA APHIS Wildlife Services or state wildlife management personnel or persons working under their authority . Application Rate: Female deer are injected with a single injection containing 1.0 ml of GonaCon at least two to three months prior to the onset of rut for full contraceptive effect. If multi year contraceptive effects are desired, a second vaccination may be given 30 to 60 day s after the first injection or during the following year. Two formulations (basic and alternate) are proposed for registration. 

### 3. Science Findings Available data supporting the use and registration of Mammalian Gonadotropin Releasing Hormone including product chemistry , toxicology , efficacy , and ecological effects and environmental fate are summarize d below .3 Table 1. Product Chemistry Summary Peptide structure

Common name Mammalian Gonadotropin Releasing Hormone (GnRH) C AS Reg. No. 9034 - 40 - 6 Color white Phy sical State Active: solid: powder EU: liquid: somewhat creamy in appearance Melting Point N/A Waiver request Boiling Point Waiver request: Solid at room temperature. Odor Active: odorless EU: odorless Stabili ty to Normal and Elevated Temperatures, Metal, and Metal Ions N/A Waiver request Oxidation/Reduction Action N/A Waiver request pH Active: NA EU: pH = 6.49 Flammability N/A Waiver request Explodab ility N/A Waiver request Vapor pressure N/A Waiver request Water Solubility N/A Waiver request Storage stability N/A product’s shelf life will be < 6 months so not necessary Corrosion Characteristics N/A product’s shelf life will be < 6 months so not necessary TOXICOLOGY SUMMARY The Registrant submitted the studies listed in Tables 2 , which include a number of toxicity studies. The Registrant submitted waiver requests which were granted for acute inhalation and dermal sensitization.4 Acute Toxicity Data Gn RH Table 2. Acute Toxicity Guideline No. Study Type Results Toxicity Category* OPPTS 870.1100 Ac ute Oral

Rat All test animals survived 1 mL exposure. IV OPPTS 870.1200 Ac ute Dermal

Rat All test animals survived 1 mL exposure. IV OPPTS 870.1300 Ac ute Inhalation

Rat WAIVED IV OPPT S 870.2400 Primary Eye Irritation

Rabbit No corneal opacity or iritis was observed. 1 - hour post instillation: 3/3 treated eyes exhibited conjunctival redness (score 1 - 2) and discharge (score 1). No “positive” grade irritation was noted at the 24 - hour o bservation. Treated eyes were free of all eye irritation by 72 - hours. IV

OPPTS 870.2500 Primary Skin Irritation

Rabbit No edema was observed at any treated site. Very slight erythema (score 1) was noted at all 3/3 test sites within 1 - hour post -pad removal. Irritation severity decreased thereafter. No irritation was noted at the 72 - hour observation. The PDII wa s 0.5. IV

OPPTS 870.2600 Dermal sensitization WAIVED

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 Toxicity Category IV = No precautions required Chronic toxicity

data requirements were waived. There is no human exposure from use of GonaCon, therefore n o toxicity endpoints were selected because of the very limited potential worker and dietary exposure. ECOLOGICAL EFFECTS Waivers were submitted to fulfill required ecol ogical effects and environmental fate guideline studies for the registration of GonaCon because of the limited potential for environmental releases. Since the product is labeled only for injection to deer by

hand and the substance is expected to be rapidl y metabolized in treated animals, the limited5

potential risks to non - target organisms resulting from the proposed registration of GonaC on are not expected to exceed the Agency ’s concern levels. The proposed registration of GonaCon is expected to have no effect on endangered or threatened species EFFICACY GonaCon is intended to render a vaccinated female white - tailed deer infertile for a minimum of one year following vaccination. The label claims that GonaCon will not affect existing pregnancies but should cause infertility of the vaccinated animal in subsequent years. If multi - ye ar contraceptive effects are desired, a second vaccination may be given 30 - 60 day s after the first injection or during the following ye ar. The label claims that there is a chance that some vaccinated females will become permanently sterile. Product performance studies were conducted b y APHI S’s National Wildlife Research Center (NWRC) both in the field over a two ye ar period and in a laboratory over multiple ye ars to compare two different formulations. The field test, initiated in 2004 used two sites consisting of fenced federal land near Silver Spring, MD. Female deer in the vaccinated group were dosed with the labeled rate of the vaccine during July and August 2004. All deer w ere marked with ear tags and radio telemetry

collars equipped with mortality sensors. Reproductive status was assessed in the summers of 2005 and 2006 with visual inspection of the udders for signs of lactation. Results showed 88% efficacy in the summer after vaccination with lactation evident in 3 of the 26 does vaccinated (12%). Of the control group, reproductive status was able to be determined in 13 of the 15 deer and lactation was evident in 11 of those 13 doe (85%). In the second summer after vac cination lactation was evident in 10 of the remaining 19 vaccinated deer (53%) equating to an efficacy rate of 47%. In the control group, 10 of the 10 remaining deer (100%) had reproductive success. The lab study

results showed the alternate formulation t o be more effective than the basic formulation. The alternate formulation had a 100% success rate (5/5 does remained contracepted for two ye ars) compared to the basic formulation with a 60% success rate after two ye ars (3/5 does contracepted). Due to econo mic and supply reasons however, it is necessary

for the product to carry

both formulations. 

### 4. Summary of Regulatory Position and Rationale Available data provide adequate information to support the conditional registration of GnRH as an effective population control method for nuisance white - tailed deer. White - tailed deer have been classified b y EPA as a public health pest because they are a host for deer ticks that may cause Lym e disease and they are a cause of vehicle accidents.6

In many urban and s uburban areas white - tailed deer populations have become over abundant and are considered a ye ar- round nuisance causing many human - wildlife conflicts. Since these areas are typically non hunting areas, where building and population densities do not allow fo r safe shooting zones, local laws prohibit guns or shooting or public opinion does not support hunting, there has not been an economically feasible solution to control overabundant deer populations. In many of these urban and suburban areas, deer have been known to inflict significant economic damage to gardens and landscapes of homeowners associations, g olf courses, private residential yards, etc. When deer are in numbers exceeding 20 per square mile, as they are becoming in many

areas, they

can inflict severe damage to resident flora and fauna. This can adversel y affect the ecosystem and the wildlife that depend on that ecos ys tem. Since deer in these areas are so well fed, female deer, which normall y give birth to twins may be becoming more fertile whi ch is evident b y an increase in triplet births. This, and the fact that deer in developed areas appear to be more nocturnal to avoid human contact, is contributing to rapidl y increasing populations and problems. Acc ording to a 2006 study , the National Highway Traffic Safety Administration reported that there are about 1.5 million car accidents with deer resulting in over $1 billion of damage and 150 human fatalities annually . GnRH will not only help prevent increases in deer numbers through contraception, but should decrease the number of car accidents during the fall mating season - which is associated with a surge in car collisions with deer as bucks chase fertile does, sometimes for miles. D eer can also play

a role in spreading disease as they are a main host for blacklegged ticks ( Ixodes scapularis ), more commonly known as deer ticks, which are a carrier of Lym e disease. There has been a sharp increase in cases of Ly me disease in suburban/urban areas with significant deer populations. Contraception of nuisance deer using GnRH is not intended to replace hunting (where it is an option) as a population control method. GnRH is intended to be used in combination with other population management techniques since it cannot alone reduce already over abundant populations. Since GnRH is a nonlethal alternative to population control, many animal rights groups enthusiastically support this registration. The registration of GonaCon has received letters of support from the Department of Natural Resources at Corne ll University and White Buffalo, Inc. a non - profit wildlife organization based out of Connecticut. At Cornell University , deer have caused damages to plants in research and teaching plots as well as dozens of car accidents. Currently , the university attemp ts population management of deer by capturing and surgically

sterilizing deer via tubal ligation. This method however is both time consuming and costly , with expenses of approximately $1,000 per deer along with the impracticality of finding surgery staff and anesthesiologists during the early and late hours that deer are typicall y captured. The use of GnRH is also supported by the Humane Society of the United States as a humane and “necessary” method of deer population control.7

GonaCon was mentioned in an April 2009 article in the Washington P ost Magazine as a possible population control method for deer in Rock Creek Park in Washington, DC and suburban Maryland. 

### 5. Labeling Restrictions To mitigate any risks, the following requirements have been imp osed:

• Restricted - Use Pesticide classification due to non - target injection hazard.

• Application is restricted to USDA APHI S Wildlife Services or state wildlife management agency

personnel or persons working under their authority only.

• Adm inistration o f vaccine is only by h and injection to mitigate any non - target or environmental risks that occur with administration with darts.

• Use restricted to only one species: white - tailed deer ( Odocoileus virginianus ).

• PPE requirements include: long sleeved shirt and long pants, glov es and shoes plus socks to miti gate occupational exposure.

• Children are not allowed in areas where product is used

• A warning that pregnant women should not be involved in handling or injecting GonaCon and that all women should be aware that accidental self - injection may cause infertility . 

### 6. Conditional Data Requirements Because of the unique chemical nature of GnRH additional preliminary analy sis and certified limits data are necessary . The registrant must submit this data to the A genc y upon completion . Conditional data required for GonaCon consists of:

 Guideline 830.1700 Validating the method of analy sis of the formulation and additional preliminary

analy sis  Guideline 830.1750 Certified Limits

Contact Person at USEPA Mailin g address:8

Autumn Metzger Biologist, Insecticide - Rodenticide Branch Environmental Protection Agency Office of Pesticide Programs Registration Division (7505P) Insecticide Branch 1200 Pennsylvania Avenue NW Washington, D.C. 20460 Office location and telep hone number: Room S - 7 2 24 , One Potomac Yard 2777 S. Crystal Drive Arlington, VA 22202 703 - 305 - 5314 DISCLAIMER: The information in this Pesticide Fact Sheet is for information only and is not to be used to satisfy data requirements for pesticide registra tion. The information is believed to be accurate as of the date on the document.9

APPENDIX I GLOSSARY OF TERMS AND ABBREVIATIONS ADNT Acute delayed neurotoxicity a.i. Active Ingredient aPAD Acute Population Adjusted Dose ARI Aggregate Risk Index BCF Bio concentration Factor CAS Chemical Abstracts Service ChE Cholinesterase ChEI Cholinesterase inhibition cPAD Chronic Population Adjusted Dose %CT Percent crop treated DAT Day s after treatment DEEM - FCID Dietary

Exposure Evaluation Model - Food Consumption Int ake Database DNA Deox yribonucleic acid DNT Developmental neurotoxicity DI T Developmental immunotoxicity DWL OC Drinking Water Level of Comparison. EC Emulsifiable Concentrate Formulation EEC Estimated Environmental Concentration. The estimated pesticide

concentration in an environment, such as a terrestrial ecos ys tem. EPA U.S. Environmental Protection Agency FQPA Food Quality Protection Act GL C Gas Liquid Chromatography GLN Guideline Number LC 50 Median Lethal Concentration. A statistically derived concentration of a

substance that can be expected to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm. LD 50 Median Lethal Dose. A statisti cally derived single dose that can be expected to cause death in 50% of the test animals when administered b y the route indicated (oral, dermal, inhalation). It is expressed as a weight of substance per unit weight of animal, e.g., mg/kg. LOAEL Lowest Obs erved Adverse Effect Level LOAEC Lowest Observed Adverse Effect Concentration LOC Level of Concern LOD Limit of Detection LOQ Limit of Quantitation mg/kg/day Milligram Per Kilogram Per Day mg/L Milligrams Per Liter MOE Margin of Exposure10

MRID Mast er Record Identification (number), EPA's sy stem of recording and

tracking studies submitted MTD Maximum tolerated dose NA Not Applicable NOEC No Observable Effect Concentration NOEL No Observed Effect Level NOAEL No Observed Adverse Effect Level NOAE C No Observed Adverse Effect Concentration NPDES National Pollutant Discharge Elimination Sy stem OP Organophosphate OPP EPA Office of Pesticide Programs OPPTS EPA Office of Prevention, Pesticides and Toxic Substances PAD Population Adjusted Dose PAG Pesticide Assessment Guideline PAM Pesticide Analy tical Method PHED Pesticide Handler's Exposure Data PHI Preharvest Interval ppb Parts Per Billion PPE Personal Protective Equipment ppm Parts Per Million PRZM/EXAMS Tier II Surface Water Computer Mo del RAC Raw Agriculture Commodity RBC Red Blood Cell RED Reregistration Eligibility Decision REI Restricted Entry Interval RfD Reference Dose SCI - GROW Tier I Ground Water Computer Model SF Safety

Factor TGAI Technical Grade Active Ingredient UF Uncertainty Factor μg micrograms μg/L Micrograms Per Liter μL/g Microliter per gram USDA United States Department of Agriculture WPS Worker Protection Standard11

APPENDIX II Citations Considered Part of the Data Base Supporting the Registration of Gon aCon. MRID Citation Receipt Date 47649600 United States Department of Agriculture's Animal and Plant Health

Inspection Service (USDA APHIS) (2009) Submission of Product Chemistry , Toxicity, Efficacy and Residue Data in Support of the Application for Registration of GonaCon Immunocontraceptive Vaccine. Transmittal of 36 Studies. 22 - Jan 2009

47649601 O'Hare, J.; Eisemann, J. (2008) Description of Materials Used to Produce:

"GoneCon Immunocontraceptive Vaccine". Project Number: P4417. Unpublished study prepared by US Dept. of Agriculture, APHIS, W S: National W ildlife Research Center. 168 p. 22 - Jan 2009
47649602 O'Hare, J.; Eisemann, J. (2008) De scription of Formulation Process Used

to Manufacture: "GonaCon Immunocontraceptive Vaccine". Project Number: M8546, BT016/02. Unpublished study prepared by US Dept. of Agriculture, APHIS, W S: National Wi ldlife Research Center. 99 p. 22 - Jan 2009
47649603 O 'Hare, J.; Pilon, J.; Eisemann, J. (2008) Discussion of the Formation of

Impurities "GonaCon Immunocontraceptive Vaccine". Unpublished study prepared by US Dept. of Agriculture, APHIS, W S: National W ildlive Research Center. 56 p. 22 - Jan 2009
47649604 O'Ha re, J.; Eisemann, J.; Pilon, J. (2008) Preliminary Analysis and

Certified Limits "GonaCon Immunocontraceptive Vaccine": Final Report. Unpublished study prepared by US Dept. of Agriculture, APHIS, W S: National W ildlife Research Center. 9 p. 22 - Jan 2009
476 49605 O'Hare, J.; Eisemann, J. (2008) Enforcement Analytical Method:

"GonaCon Immunocontraceptive Vaccine". Unpublished study prepared by US Dept. of Agriculture, APHIS, W S: National W ildlife Research Center. 40 p. 22 - Jan 2009

47649606 O'Hare, J.; Eiseman n, J. (2007) Product Chemistry: Color, Physical State,

Odor, and pH - USDA APHIS GonaCon Immunocontraceptive Vaccine (EPA Reg. No. 56228 - xx): Final Report. Project Number: QA/1421. Unpublished study prepared by US Dept. of Agriculture, APHIS, W S: National Wi ldlife Research Center. 31 p. 22 - Jan 2009

47649607 Wa rren, J.; Stephens, S. (2008) Stability to Normal and Elevated

Te mp eratures, Metal, and Metal Ions: (Gonadotropin Releasing Hormone). Unpublished study prepared by US Dept. of Agriculture, APHIS, W S. 8 p. 22 - Jan 2009 47649608 Wa rren, J.; Stephens, S. (2008) Oxidation/Reduction Chemical

Incompatibility: (GonaCon Immunocontraceptive Vaccine). Unpublished study prepared by US Dept. of Agriculture, APHIS, W S. 8 p. 22 - Jan 2009 47649609 Wa rren, J.; Stephen s, S. (2008) Flammability: (GonaCon

Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 8 p. 22 - Jan 200912

47649610 Wa rren, J.; Stephens, S. (2008) Explodability: (GonaCon

Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 4 p. 22 - Jan 2009 47649611 Wa rren, J.; Stephens, S. (2008) Miscibility: (GonaCon

Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 8 p. 22 - Jan 2009 47649612 Wa rren, J.; Stephens, S. (2008) Corrosion Characteristics: (GonaCon

I mmunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 8 p. 22 - Jan 2009 47649613 Wa rren, J.; Stephens, S. (2008) Dielectric Breakdown Voltage: (GonaCon

Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 8 p. 22 - Jan 200 9 47649614 Wa rren, J.; Stephens, S. (2008) UV/Visible Absorption: (GonaCon

Immunocontraceptive). Unpublished study prepared by USDA APHIS. 8 p. 22 - Jan 2009 47649615 Wa rren, J.; Stephens, S. (2008) Viscosity: (GonaCon

Immunocontraceptive Vaccine). Unpubli shed study prepared by USDA APHIS. 8 p. 22 - Jan 2009 47649616 Wa rren, J.; Stephens, S. (2008) Melting Point: (GonaCon

Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 8 p. 22 - Jan 2009 47649617 Wa rren, J.; Stephens, S. (2008) Boiling Point: (GonoCon

Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 4 p. 22 - Jan 2009 47649618 Wa rren, J.; Stephens, S. (2008) Density/Relative Density/Bulk Density:

(GonaCon Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 4 p. 22 - Jan 2009 47649619 Wa rren, J.; Stephens, S. (2008) Dissociation Constant in W ater:

(GonaCon Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 8 p. 22 - Jan 2009 47649620 Wa rren, J.; Stephens, S. (2008) Octanol/W ater Partition Coefficient:

(GonaCon Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 8 p. 22 - Jan 2009 47649621 Wa rren, J.; Stephens, S. (2008) W ater Solubility: (GonaCon

Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 8 p. 22 - Jan 2009 47649622 Wa rren, J.; Stephens, S. (2008) Vapour Pressure: (GonaCon

Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 8 p. 22 - Jan 2009 47649623 Eisemann, J.; O'Hare, J. (2008) Chemical Identity: "GonaCon

Immun ocontraceptive Vaccine". Unpublished study prepared by US Dept. of Agriculture, APHIS, WS : Natiional W ildlife Research Center. 27 p. 22 - Jan 2009 47649624 Eisemann, J.; O'Hare, J. (2008) Direction for Use: GonaCon

Immunocontraceptive Vaccine. Unpublished s tudy prepared by US Dept. of Agriculture, APHIS, WS : National Research Center. 12 p. 22 - Jan 2009 47649625 Lowe, C. (2008) GonaCon Immunocontraceptive Vaccine: Acute Oral 22 - Jan -13 Toxicity - Lim it Dose Procedure in Rats. Project Number: P320/USDA, 23211. Unpublishe d study prepared by Product Safety Laboratories. 28 p. 2009
47649626 Lowe, C. (2008) GonaCon Immunocontraceptive Vaccine: Acute Dermal

Toxicity - Lim it Dose Procedure in Rats. Project Number: 23212, P322/USDA. Unpublished study prepared by Product Safety Laboratories. 28 p. 22 - Jan 2009 47649627 O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Acute Inhalation Toxicity:

(GonaCon Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 4 p. 22 - Jan 2009 47649628 Lowe, C. (2007) GonaCon Im munocontraceptive Vaccine: Primary Eye Irritation Study in Rabbits. Project Number: P324, 22806. Unpublished study prepared by Product Safety Laboratories. 29 p. 22 - Jan 2009 47649629 Lowe, C. (2008) GonaCon Immunocontraceptive Vaccine: Primary Skin Irrita tion Study in Rabbits. Project Number: P326, 22807. Unpublished study prepared by Product Safety Laboratories. 27 p. 22 - Jan 2009 47649630 O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Dermal Sensitization:

(GonaCon Immunocontraceptive Vaccine). Unpublishe d study prepared by USDA APHIS. 4 p. 22 - Jan 2009 47649631 O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Chronic Dietary Toxicity:

(GonaCon Immunocontraceptive Vaccine). Unpublished study prepared by USDA APHIS. 4 p. 22 - Jan 2009 47649632 O'Hare, J.; Eisem ann, J.; Stephens, S. (2008) Gene Mutation: (GonaCon

Immunocontraceptive Vaccine): (Human). Unpublished study prepared by USDA APHIS. 4 p. 22 - Jan 2009 47649633 O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Stuctural Chromosomal

Aberration: (GonaCon Immuno contraceptive Vaccine): (Human). Unpublished study prepared by USDA APHIS. 4 p. 22 - Jan 2009 47649634 O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Other Genotoxic Effects:

(GonaCon Immunocontraceptive Vaccine): (Human). Unpublished study prepared by USDA APHIS. 4 p. 22 - Jan 2009 47649635 O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Acute Delayed

Neurotoxicity: (GonaCon Immunocontraceptive Vaccine): (Hen). Unpublished study prepared by USDA APHIS. 4 p. 22 - Jan 2009
47649636 Gionfriddo, J.; Eisemann, J.; O' Hare, J. (2008) Product Performance:

Field Test of a Single - Injection of GonaCon Immunocontraceptive Vaccine In Female Wh ite - Tailed Deer. Project Number: QA/1112. Unpublished study prepared by US Dept. of Agriculture, APHIS, W S: National W ildlife Research Center. 31 p. 22 - Jan 2009