United States
Environmental Protection Agency
Office of Prevention, Pesticides and Toxic Substances
(7505P)
&EPA Pesticide
Fact Sheet
Name of Chemical: Mammalian Gonadotropin
Releasing Hormone (GnRH)
Reason for Issuance: New Chemical
Nonfood Use
Date Issued: September 2009
1. Description of Chemical
Peptide Chain: pyroGlul -His2-Trp3- Ser4 -Tyr5- Gly6 -Leu7-Arg8-
Pro9- G lylONH2 [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 Type: Mammalian Contraceptive
U.S. Producer: U.S. Department of Agriculture, APHIS, Pocatello
Supply Depot
23 8 East Dillon Street
Pocatello, ID 83201
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2. Use Pattern and Formulations
Mode of Action
Application Sites
Methods of
Application
Application Rate:
3. Science Findings
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.
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).
The vaccine will be administered to restrained female deer
using preloaded syringes with an 18 or 19 gauge stainless steel
hypodermic needle intramuscularly into a large muscle mass by
hand injection only.
GonaCon is classified as a Restricted Use Pesticide. Use is
restricted to USDA APHIS Wildlife Services or state wildlife
management personnel or persons working under their
authority.
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
days after the first injection or during the following year.
Two formulations (basic and alternate) are proposed for
registration.
Available data supporting the use and registration of Mammalian Gonadotropin
Releasing Hormone including product chemistry, toxicology, efficacy, and ecological
effects and environmental fate are summarized below.
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Table 1. Product Chemistry Summary
Peptide structure
Common name
CAS Reg. No.
Color
Physical State
Melting Point
Boiling Point
Odor
Stability to Normal and
Elevated Temperatures,
Metal, and Metal Ions
Oxidation/Reduction
Action
pH
Flammability
Explodability
Vapor pressure
Water Solubility
Storage stability
Corrosion Characteristics
, "ij^x.^
Ly f jif
' i vZ\>p'
GB«S\EBi«9 \ ' /
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) — V- A ftjsrs
Mammalian Gonadotropin Releasing Hormone (GnRH)
9034-40-6
white
Active: solid: powder
EU: liquid: somewhat creamy in appearance
N/A Waiver request
Waiver request: Solid at room temperature.
Active: odorless
EU: odorless
N/A Waiver request
N/A Waiver request
Active: NA
EU: pH = 6.49
N/A Waiver request
N/A Waiver request
N/A Waiver request
N/A Waiver request
N/A product's shelf life will be ^6 months so not necessary
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.
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Acute Toxicity Data GnRH
Table 2. Acute Toxicity
Guideline
No.
OPPTS
870.1100
OPPTS
870.1200
OPPTS
870.1300
OPPTS
870.2400
OPPTS
870.2500
OPPTS
870.2600
Study Type
Acute Oral
Rat
Acute Dermal
Rat
Acute Inhalation
Rat
Primary Eye Irritation
Rabbit
Primary Skin Irritation
Rabbit
Dermal sensitization
Toxicity
Results Category*
All test animals survived 1 mL
exposure. IV
All test animals survived 1 mL
exposure. IV
WAIVED
No cornea! 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 observation. Treated eyes
were free of all eye irritation by
72 -hours.
No edema was observed at any
treated site. Very slight IV
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
was 0.5.
WAIVED
• Toxicity Category IV = No precautions required
Chronic toxicity data requirements were waived. There is no human exposure from use
of GonaCon, therefore no toxicity endpoints were selected because of the very limited
potential worker and dietary exposure.
ECOLOGICAL EFFECTS
Waivers were submitted to fulfill required ecological 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 rapidly metabolized in treated animals, the limited
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potential risks to non-target organisms resulting from the proposed registration of
GonaCon 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-year contraceptive effects are desired, a second vaccination
may be given 30-60 days after the first injection or during the following year. The label
claims that there is a chance that some vaccinated females will become permanently
sterile.
Product performance studies were conducted by APHIS's National Wildlife Research
Center (NWRC) both in the field over a two year period and in a laboratory over multiple
years 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 were 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 vaccination 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 to be more effective than the basic
formulation. The alternate formulation had a 100% success rate (5/5 does remained
contracepted for two years) compared to the basic formulation with a 60% success rate
after two years (3/5 does contracepted). Due to economic 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 by EPA as a public health pest because they are a
host for deer ticks that may cause Lyme disease and they are a cause of vehicle accidents.
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In many urban and suburban areas white-tailed deer populations have become over
abundant and are considered a year-round nuisance causing many human-wildlife
conflicts. Since these areas are typically non hunting areas, where building and
population densities do not allow for 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, golf 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 adversely affect the ecosystem and the wildlife that depend on that
ecosystem.
Since deer in these areas are so well fed, female deer, which normally give birth to twins
may be becoming more fertile which is evident by 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 rapidly increasing populations and problems.
According 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.
Deer 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
Lyme disease. There has been a sharp increase in cases of Lyme 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 Cornell 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 attempts 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 typically
captured. The use of GnRH is also supported by the Humane Society of the United
States and the Wildlife Society as a humane and "necessary" method of deer population
control.
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GonaCon was mentioned in an April 2009 article in the Washington Post 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 imposed:
• Restricted -Use Pesticide classification due to non-target injection hazard.
• Application is restricted to USDA APHIS Wildlife Services or state wildlife
management agency personnel or persons working under their authority only.
• Administration of vaccine is only by hand 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, gloves and shoes
plus socks to mitigate 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 analysis and
certified limits data are necessary. The registrant must submit this data to the Agency
upon completion.
Conditional data required for GonaCon consists of:
• Guideline 830.1700 Validating the method of analysis of the formulation and
additional preliminary analysis
• Guideline 830.1750 Certified Limits
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Contact Person at USEPA
Mailing address:
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 telephone number:
Room S-7224, 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 registration. The
information is believed to be accurate as of the date on the document.
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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 Bioconcentration Factor
CAS Chemical Abstracts Service
ChE Cholinesterase
ChEI Cholinesterase inhibition
cPAD Chronic Population Adjusted Dose
%CT Percent crop treated
DAT Days after treatment
DEEM-FCID Dietary Exposure Evaluation Model - Food Consumption Intake Database
DNA Deoxyribonucleic acid
DNT Developmental neurotoxicity
DIT Developmental immunotoxicity
DWLOC Drinking Water Level of Comparison.
EC Emulsifiable Concentrate Formulation
EEC Estimated Environmental Concentration. The estimated pesticide
concentration in an environment, such as a terrestrial ecosystem.
EPA U.S. Environmental Protection Agency
FQPA Food Quality Protection Act
GLC Gas Liquid Chromatography
GLN Guideline Number
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/1, mg/kg or ppm.
Median Lethal Dose. A statistically derived single dose that can be
expected to cause death in 50% of the test animals when administered by
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 Observed Adverse Effect Level
LOAEC Lowest Observed Adverse Effect Concentration
LOG 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 Exposure
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MRID Master Record Identification (number), EPA's system 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
NOAEC No Observed Adverse Effect Concentration
NPDES National Pollutant Discharge Elimination System
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 Analytical 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 Model
RAC Raw Agriculture Commodity
RBC Red Blood Cell
RED Reregi strati on 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
jig micrograms
|ig/L Micrograms Per Liter
|iL/g Microliter per gram
USDA United States Department of Agriculture
WPS Worker Protection Standard
10
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APPENDIX II
Citations Considered Part of the Data Base Supporting the Registration of
GonaCon.
MRID
47649600
47649601
47649602
47649603
47649604
47649605
47649606
47649607
47649608
47649609
Citation
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.
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, WS:
National Wildlife Research Center. 168 p.
O'Hare, J.; Eisemann, J. (2008) Description of Formulation Process Used
to Manufacture: "GonaCon Immunocontraceptive Vaccine". Project
Number: M8546, BT016/02. Unpublished study prepared by US Dept. of
Agriculture, APHIS, WS: National Wildlife Research Center. 99 p.
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, WS: National Wildlive
Research Center. 56 p.
O'Hare, 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, WS:
National Wildlife Research Center. 9 p.
O'Hare, J.; Eisemann, J. (2008) Enforcement Analytical Method:
"GonaCon Immunocontraceptive Vaccine". Unpublished study prepared
by US Dept. of Agriculture, APHIS, WS: National Wildlife Research
Center. 40 p.
O'Hare, J.; Eisemann, 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, WS:
National Wildlife Research Center. 31 p.
Warren, J.; Stephens, S. (2008) Stability to Normal and Elevated
Temperatures, Metal, and Metal Ions: (Gonadotropin Releasing
Hormone). Unpublished study prepared by US Dept. of Agriculture,
APHIS, WS. 8 p.
Warren, J.; Stephens, S. (2008) Oxidation/Reduction Chemical
Incompatibility: (GonaCon Immunocontraceptive Vaccine). Unpublished
study prepared by US Dept. of Agriculture, APHIS, WS. 8 p.
Warren, J.; Stephens, S. (2008) Flammability: (GonaCon
Immunocontraceptive Vaccine). Unpublished study prepared by USDA
APHIS. 8 p.
Receipt
Date
22-Jan-
2009
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2009
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2009
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2009
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2009
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2009
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2009
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2009
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Warren, J.; Stephens, S. (2008) Explodability: (GonaCon
47649610 Immunocontraceptive Vaccine). Unpublished study prepared by USDA
APHIS. 4 p.
Warren, J.; Stephens, S. (2008) Miscibility: (GonaCon
47649611 Immunocontraceptive Vaccine). Unpublished study prepared by USDA
APHIS. 8 p.
Warren, J.; Stephens, S. (2008) Corrosion Characteristics: (GonaCon
47649612 Immunocontraceptive Vaccine). Unpublished study prepared by USDA
APHIS. 8 p.
Warren, J.; Stephens, S. (2008) Dielectric Breakdown Voltage: (GonaCon
47649613 Immunocontraceptive Vaccine). Unpublished study prepared by USDA
APHIS. 8 p.
47649614
47649615
Warren, J.; Stephens, S. (2008) UV/Visible Absorption: (GonaCon
Immunocontraceptive). Unpublished study prepared by USDA APHIS. 8 p.
Warren, J.; Stephens, S. (2008) Viscosity: (GonaCon
Immunocontraceptive Vaccine). Unpublished study prepared by USDA
APHIS. 8 p.
Warren, J.; Stephens, S. (2008) Melting Point: (GonaCon
47649616 Immunocontraceptive Vaccine). Unpublished study prepared by USDA
APHIS. 8 p.
Warren, J.; Stephens, S. (2008) Boiling Point: (GonoCon
47649617 Immunocontraceptive Vaccine). Unpublished study prepared by USDA
APHIS. 4 p.
Warren, J.; Stephens, S. (2008) Density/Relative Density/Bulk Density:
47649618 (GonaCon Immunocontraceptive Vaccine). Unpublished study prepared
by USDA APHIS. 4 p.
Warren, J.; Stephens, S. (2008) Dissociation Constant in Water:
47649619 (GonaCon Immunocontraceptive Vaccine). Unpublished study prepared
by USDA APHIS. 8 p.
Warren, J.; Stephens, S. (2008) Octanol/Water Partition Coefficient:
47649620 (GonaCon Immunocontraceptive Vaccine). Unpublished study prepared
by USDA APHIS. 8 p.
Warren, J.; Stephens, S. (2008) Water Solubility: (GonaCon
47649621 Immunocontraceptive Vaccine). Unpublished study prepared by USDA
APHIS. 8 p.
Warren, J.; Stephens, S. (2008) Vapour Pressure: (GonaCon
47649622 Immunocontraceptive Vaccine). Unpublished study prepared by USDA
APHIS. 8 p.
Eisemann, J.; O'Hare, J. (2008) Chemical Identity: "GonaCon
47649623 Immunocontraceptive Vaccine". Unpublished study prepared by US Dept.
of Agriculture, APHIS, WS: Natiional Wildlife Research Center. 27 p.
Eisemann, J.; O'Hare, J. (2008) Direction for Use: GonaCon
Immunocontraceptive Vaccine. Unpublished study prepared by US Dept.
of Agriculture, APHIS, WS: National Research Center. 12 p.
47649624
47649625 Lowe, C. (2008) GonaCon Immunocontraceptive Vaccine: Acute Oral
22-Jan-
2009
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2009
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2009
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2009
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2009
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47649626
47649627
47649628
47649629
47649630
47649631
47649632
Toxicity - Limit Dose Procedure in Rats. Project Number: P320/USDA,
23211. Unpublished study prepared by Product Safety Laboratories. 28 p.
Lowe, C. (2008) GonaCon Immunocontraceptive Vaccine: Acute Dermal
Toxicity - Limit Dose Procedure in Rats. Project Number: 23212,
P322/USDA. Unpublished study prepared by Product Safety Laboratories.
28 p.
O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Acute Inhalation Toxicity:
(GonaCon Immunocontraceptive Vaccine). Unpublished study prepared
by USDA APHIS. 4 p.
Lowe, C. (2007) GonaCon Immunocontraceptive Vaccine: Primary Eye
Irritation Study in Rabbits. Project Number: P324, 22806. Unpublished
study prepared by Product Safety Laboratories. 29 p.
Lowe, C. (2008) GonaCon Immunocontraceptive Vaccine: Primary Skin
Irritation Study in Rabbits. Project Number: P326, 22807. Unpublished
study prepared by Product Safety Laboratories. 27 p.
O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Dermal Sensitization:
(GonaCon Immunocontraceptive Vaccine). Unpublished study prepared
by USDA APHIS. 4 p.
O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Chronic Dietary Toxicity:
(GonaCon Immunocontraceptive Vaccine). Unpublished study prepared
by USDA APHIS. 4 p.
O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Gene Mutation: (GonaCon
Immunocontraceptive Vaccine): (Human). Unpublished study prepared by
USDA APHIS. 4 p.
O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Stuctural Chromosomal
47649633 Aberration: (GonaCon Immunocontraceptive Vaccine): (Human).
Unpublished study prepared by USDA APHIS. 4 p.
O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Other Genotoxic Effects:
47649634 (GonaCon Immunocontraceptive Vaccine): (Human). Unpublished study
prepared by USDA APHIS. 4 p.
O'Hare, J.; Eisemann, J.; Stephens, S. (2008) Acute Delayed
47649635 Neurotoxicity: (GonaCon Immunocontraceptive Vaccine): (Hen).
Unpublished study prepared by USDA APHIS. 4 p.
Gionfriddo, J.; Eisemann, J.; O'Hare, J. (2008) Product Performance:
Field Test of a Single-Injection of GonaCon Immunocontraceptive Vaccine
47649636 In Female White-Tailed Deer. Project Number: QA/1112. Unpublished
study prepared by US Dept. of Agriculture, APHIS, WS: National Wildlife
Research Center. 31 p.
2009
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2009
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