Draft Human Health and Ecological Risk Assessment

for the Use of Wildlife Damage Management Methods

by APHIS-Wildlife Services

Chapter XXV

USE OF 4-AMINOPYRIDINE

IN WILDLIFE DAMAGE MANAGEMENT

March 2023

Peer Reviewed Final

June 2023
i

EXECUTIVE SUMMARY

The active ingredient 4-aminopyridine or 4-AP in Avitrol products (Avitrol Corporation) is an

avian frightening agent formulated as mixed grain or corn bait. Birds that consume treated bait

produce distress calls causing flocks of the same species to disperse from an area; the birds 

that eat treated bait usually die. The USDA-APHIS evaluated the potential human health and 

ecological risks from Wildlife Services (WS) use of Avitrol to deter target bird species from 

damage sites.

WS used four Avitrol products to control bird damage from fiscal years 2011–2020: mixed grain 

(0.5% 4-AP), corn chops (0.5% 4-AP), double strength corn chops (1.0% 4-AP), and whole corn 

(0.5% 4-AP). A fifth product, double strength whole corn (1.0% 4-AP), is labeled for use to 

frighten crows. Avitrol products are restricted use pesticides, and only certified applicators or 

persons under their direct supervision can apply them and only for those uses stated on the 

labels. 

The labels include restrictions to prevent exposure to the public, pets, and nontarget species. 

They require applicators to prebait sites to ensure target species take the bait and nontarget 

species are not present. If nontarget species feed on the untreated bait, the label does not allow 

the use of treated bait at that site. WS often uses bait trays instead of applying bait directly to 

the ground; this makes it easier for the applicator to remove unused bait. As part of the current 

registration review cycle, the U.S. Environmental Protection Agency (USEPA) states they intend 

to amend the labels further to require the use of bait trays at all urban and industrial use sites 

and agricultural use sites when feasible. In areas accessible to the public, when possible, WS 

conducts baiting at elevated sites that are out of reach of the public. When applicators cannot 

treat at elevated sites in publicly accessible areas, the label requires them to remain at the 

treatment site and remove all dead or dying birds and unused bait before they leave the site. 

WS prefers to apply treated bait when the fewest people are in the vicinity, as seeing distressed 

birds can be upsetting. As part of the registration review, USEPA also intends to amend the 

labels further, requiring applicators to remove all uneaten bait in the application area within 24 

hours.

4-AP is a nervous system toxicant and is highly toxic to most vertebrates. 4-AP is acutely toxic 

through oral, dermal, and inhalation exposure routes (Toxicity Category I for oral and Toxicity 

Category II for dermal and inhalation). Although the hazard potential for the technical active 

ingredient could be high, the potential exposure and risk to the public is negligible due to the

WS use pattern and label restrictions and requirements, as well as the lack of dietary exposure 

through food, feed, and drinking water. Exposure is greatest for workers who handle and apply 

the bait material; however, limiting use to certified applicators and the required personnel 

protective equipment reduces the potential for exposure and minimizes risk. APHIS is unaware 

of any reports of exposure to WS personnel or the public from WS’s use of Avitrol products.

Label requirements minimize the risks to nontarget species. Exposure to aquatic species is not 

expected as the label does not permit Avitrol use within 25 feet of permanent water bodies. As 

part of the registration review, USEPA also intends to amend the labels further to recommend 

that applicators do not apply the product if rain is predicted within 24 hours to ensure the 

product does not enter groundwater or surface water sources. Since applicators remove dead 

and dying birds at the end of the treatment period or sundown, secondary exposure to predatory 

or scavenging nontarget species is minimized. WS expects some take of target species that 

ingest 4-AP-treated bait. WS also expects minor take of nontarget species that are attracted to 
ii

the bait or distressed and dying birds. The release of 4-AP into the environment is expected to 

have no or negligible cumulative impacts on nontarget species, the public, and the environment. 
iii

1 TABLE OF CONTENTS

1INTRODUCTION ..................................................................................................................... 1

1.1 Labels and Usage............................................................................................................. 1

1.2 Use Pattern ...................................................................................................................... 3

2 PROBLEM FORMULATION................................................................................................ 5

2.1 Chemical Description and Product Use ............................................................................ 5

2.2 Physical and Chemical Properties .................................................................................... 5

2.3 Environmental Fate .......................................................................................................... 5

2.4 Hazard Identification......................................................................................................... 6

2.4.1 Mode of Action and Metabolism ................................................................................. 6

2.4.2 Acute Toxicity............................................................................................................. 7

2.4.3 Subchronic and Chronic Toxicity ................................................................................ 7

2.4.4 Developmental and Reproductive Effects................................................................... 8

2.4.5 Carcinogenicity and Mutagenicity............................................................................... 8

2.4.6 Immunotoxicity Effects ............................................................................................... 8

2.4.7 Endocrine Effects....................................................................................................... 8

3 DOSE-RESPONSE ASSESSMENT.................................................................................... 9

3.1 Human Health Dose-Response Assessment.................................................................... 9

3.2 Ecological Effects Analysis ............................................................................................... 9

3.2.1 Aquatic Species ......................................................................................................... 9

3.2.2 Terrestrial Species ....................................................................................................10

4 EXPOSURE ASSESSMENT..................................................................................................12

4.1 Human Health .................................................................................................................12

4.1.1 Potentially Exposed Human Populations and Complete Exposure Pathways............12

4.1.2 Human Health Exposure Evaluation and Risk Characterization ................................13

4.2 Ecological Exposure Assessment....................................................................................14

4.2.1 Aquatic Exposure Assessment..................................................................................14

4.2.2 Terrestrial Exposure Assessment..............................................................................14

4.2.3 Secondary Exposure.................................................................................................15

5 RISK CHARACTERIZATION .............................................................................................16

5.1 Human Health Risks........................................................................................................16

5.2 Ecological Risks ..............................................................................................................17

6 UNCERTAINTIES AND CUMULATIVE IMPACTS .............................................................17

7 SUMMARY ........................................................................................................................18

8 LITERATURE CITED.........................................................................................................19
iv

9 PREPARERS.........................................................................................................................21

Appendix 1. Additional 4-Aminopyridine Use Data. ...................................................................26

LIST OF TABLES

Table 1. Summary of Avitrol product labels. All are labeled for use in, on, or in the area of 

structures, feeding, nesting, loafing, and roosting sites, in such a way that a part of a flock may 

react and frighten the rest away. ................................................................................................ 2

Table 2. Avitrol products used by WS in WDM from FY16 to FY20, the annual average target 

species killed and repelled, the amount of product used, and the states where used................. 4

Table 3. The annual average number of target species killed and repelled with Avitrol products 

used by WS in WDM from FY16 to FY20. .................................................................................. 4

Table 4. Acute toxicity data of technical and end-use 4-AP formulations.................................... 7

Table 5. 4-AP acute toxicity values in aquatic species. .............................................................10

Table 6. 4-AP acute toxicity values in bird species....................................................................11
1

1 INTRODUCTION

The U.S. Department of Agriculture (USDA), Animal and Plant Health Inspection Service 

(APHIS), Wildlife Services (WS) uses Avitrol bait products (containing the active ingredient 4-

aminopyridine or 4-AP, a chemical frightening agent) to deter target bird species from creating 

problems in certain areas. The Avitrol Corporation currently manufactures five different grain 

bait end-use products containing 4-AP. These products cannot be used in food crops. This 

human health and ecological risk assessment provides a qualitative evaluation of the potential 

risks and hazards to human health and the environment, including nontarget fish and wildlife,

from WS’ use of 4-AP. The methods used to assess potential human health effects follow 

standard regulatory guidance and methodologies (National Research Council 1983) and 

conform to other Federal agencies such as the U.S. Environmental Protection Agency (USEPA)

(USEPA 2022). The methods used to assess potential ecological risk to nontarget fish and 

wildlife generally follow USEPA (2022) methodologies.

The risk assessment has four sections: problem formulation (identifying hazard), toxicity 

assessment (dose-response assessment), exposure assessment (identifying potentially 

exposed populations and determining potential exposure pathways for these populations), and 

risk characterization (determining whether there is adverse human health or ecological risk

based on information from the toxicity and exposure assessments). A discussion of the 

uncertainties associated with the risk assessment and cumulative effects is included. 

1.1 Labels and Usage

Avitrol products are classified as restricted-use pesticides because they have a higher potential 

to cause harm to public health, the environment, and wildlife compared to other pesticides. Only 

certified applicators or persons under their direct supervision can apply these products, and only 

for those uses allowed on the labels. Avitrol products are registered for use to control flocking

pest birds, specifically European starlings1

, rock doves (feral pigeons), house sparrows, redwinged, yellow-headed and Brewer’s blackbirds, great-tailed, boat-tailed, and common 

grackles, brown-headed and bronzed cowbirds, and American2 and fish crows. Avitrol bait is 

applied to nesting, feeding, loafing, and roosting sites on or in structures, feedlots, landfills, and 

airports across urban, rural, agricultural, and non-agricultural use sites (USEPA 2017b). Five 

registrations are currently available for use, containing 0.5% or 1.0% 4-AP (Table 1). Section 

2(ee) of the Federal Insecticide, Rodenticide, and Fungicide Act (FIFRA) is a provision that 

presents special circumstances where it is permissible to use a pesticide in a manner for which 

it is not specifically labeled. For some projects, WS uses Avitrol products at lower ratios than the 

label allows, which falls under Section 2(ee) of FIFRA.

WS personnel, per the product labels, survey the problem, identify the target pest species and 

number causing a conflict, and determine the best solution to resolve that particular problem. If 

it is determined that 4-AP is the best choice, WS personnel determine if 4-AP can be used per 

the label restrictions, would be low risk (e.g., no access to the public, pets, or livestock) and 

effective, and where and when the target species are feeding. That site or a nearby site at a 

1 Scientific names are given in the Risk Assessment Introduction Chapter I, unless first time used is in this 

Chapter.

2 The American and northern crows were grouped together taxonomically and are now considered one 

species. Northern crows (Corvus caurinus) were allowed on the double strength whole corn label.
2 

safer location is then prebaited. WS personnel adhere to product labels to determine the 

quantity of Avitrol bait to use based on the number of untreated grains of the same composition 

as the Avitrol bait consumed by target birds during prebaiting. If target birds are using the site 

with no nontarget species, then Avitrol bait is put out at the recommended mix (usually 1:9 or 

greater for most species but house sparrows up to 1:5 depending on the situation) (Table 1). 

Bait is provided in bait trays or sometimes scattered by hand at the site (usually in small piles). 

Bait trays make cleanup easier but may require a few more days of prebaiting due to the target 

species’ wariness to the tray. As part of the registration review, USEPA will amend labels to 

require bait trays to be used at all urban and industrial sites and also at agricultural sites when 

feasible (USEPA 2020b). In addition, USEPA will require that bait trays are constructed of aged 

plywood or hardwood with a 1-inch lip to prevent spillage (USEPA 2020b). 

Table 1. Summary of Avitrol product labels. All are labeled for use in, on, or in the area of structures, 

feeding, nesting, loafing, and roosting sites, in such a way that a part of a flock may react and frighten the 

rest away.

Product Information Target Species

Dilution ratio 

(4-AP bait:untreated 

grains)

Avitrol Mixed Grains 

0.5% 4-AP

EPA Reg. No. 11649-4 

Label version 

9/24/2013

House sparrow 1:5

Rock pigeon (feral pigeon); red-winged, yellowheaded, rusty1, and Brewer’s blackbirds; greattailed, boat-tailed, and common grackles; brownheaded and bronzed (Molothrus aeneus) cowbirds; 

and European starling

1:5 (minimum), 

commonly 1:9

Avitrol Corn Chops

0.5% 4-AP

EPA Reg. No. 11649-6 

Label version 

9/24/2013

House sparrow 1:5

Red-winged, yellow-headed, rusty1, and Brewer’s 

blackbirds; great-tailed, boat-tailed, and common 

grackles; brown-headed and bronzed cowbirds; 

and European starling

1:5 (minimum), 

commonly 1:9

Avitrol Double Strength 

Corn Chops

1.0% 4-AP

EPA Reg. No. 11649-5 

Label version 

9/24/2013

Red-winged, yellow-headed, rusty1, and Brewer’s 

blackbirds; great-tailed, boat-tailed, and common 

grackles; brown-headed and bronzed cowbirds; 

and European starling

1:9 (minimum)

Avitrol Whole Corn

0.5% 4-AP

EPA Reg. No. 11649-7 

Label version 

9/24/2013

Rock pigeon (feral pigeon)

1:29 (common), where 

other bird food is 

available, this ratio 

may be adjusted to 

1:19 or 1:14; the 

minimum dilution rate 

is 1:5

Avitrol Double Strength 

Whole Corn

1.0% 4-AP

EPA Reg. No. 11649-8 

Label version 

9/24/2013 

American, northern2, and fish crows 1:9

1 As a result of a declining population, WS does not target rusty blackbirds. In general, rusty blackbirds are not found in areas where 

WS treats. Instead, they are primarily found in bottomland hardwoods, where they feed on invertebrates (Greenberg et al. 2011, 

Avery 2020). 

2 The northern or northwestern crow (Corvus caurinus) was grouped taxonomically with the American crow and is no longer a 

separate species.
3

On treatment day, WS personnel monitor the presence of people, place baits, and monitor the 

bait application from a distance to watch bait for target bird activity and nontarget species. Once 

birds have consumed Avitrol baits and reacted, which often scares other birds away, and 

feeding stops, the remaining uneaten bait is retrieved and disposed of per label instructions 

(deep burial or incineration). As part of the registration review, USEPA intends to amend the 

labels further to require applicators to remove all uneaten bait in the application area within 24 

hours (USEPA 2020b). WS typically completes a project by sunset and picks up the remaining 

bait. WS collects birds that died from treatment and disposes of them through incineration or 

deep burial. 

When an Avitrol bait is ingested, 4-AP causes behaviors similar to an epileptic seizure. 4-AP is 

a potassium (K) channel blocker. Birds that ingest treated bait emit distress calls that frighten

other birds, except feral pigeons, which are mostly silent. Most birds, including pigeons, fly in 

circles upwards (towering) while emitting distress calls and return to the ground. During this 

process, the birds are in convulsions and are unaware of their actions. This may include flying 

erratically, vocalizing, trembling, dilating pupils, and other symptoms which may be offensive to 

people. An assessment was completed on the humaneness of 4-AP, concluding it was a 

humane method similar to changes produced by dissociative anesthetics. During this phase,

birds do not feel pain (Roswell et al. 1979). No pathological changes to organs or other tissues 

occurred that would indicate pain and distress, and electroencephalogram results were fairly 

identical to the use of anesthetics such as ketamine hydrochloride and chloral hydrate. Thus, it 

was found that while birds may appear in pain and distress, similar to observing an epileptic 

seizure, all study parameters found that they were not (Roswell et al. 1979). 

As far as a repellent, starlings and blackbirds vocalize the most, and flocks disperse relatively 

quickly from the damage site, often traveling far away. On the other hand, pigeons and house 

sparrows generally roost nearby and do not vocalize as loudly; they often retreat to their roost or 

another feeding site and do not disperse as far as the blackbirds. They may come back to feed 

again, whereas blackbirds and starlings usually leave the area, making it a longer-lasting

repellent for them. 

1.2 Use Pattern 

WS used three Avitrol bait products from FY16 to FY20, including Avitrol Mixed Grains (0.5%) 

(EPA Reg. No. 11649-4), Avitrol Double Strength Corn Chops (1.0%) (EPA Reg. No. 11649-5), 

and Avitrol Corn Chops (0.5%) (EPA Reg. No. 11649-6) (Table 2). Avitrol Whole Corn (0.5%) 

(EPA Reg. No. 11649-7) was used from FY11 to FY15 (Appendix 1: Table 1a). Another product

label is available for use to manage crows (Avitrol Double Strength Whole Corn, 1.0%; EPA 

Reg. No. 11649-8) but was not used by WS. WS applies 4-AP baits by placing the bait into trays

or by hand scatter (spot) placement. WS applicators prefer to use bait trays at urban structures 

and airports because removing the bait at the end of the application is easier. Going forward, 

EPA will require the use of bait trays at these use sites. WS considers applications at airports as 

public areas, and applicators remain onsite during the entire application period. At airports and 

other public areas, applicators use Avitrol baits when the fewest people are in the vicinity

because seeing treated birds can be upsetting. Between FY16 and FY20, WS annually used a 

total of 49 ounces of Avitrol bait (0.5% Avitrol Mixed Grains, 1.0% Avitrol Double Strength Corn 

Chops, and 0.5% Avitrol Corn Chops) with annual average 1,338 target species killed and 273

repelled in 7 states (Tables 2 and 3). Applicators report the numbers of each species killed and 

repelled for each application. The number of birds repelled is not always documented due to 

difficulties in determining the number of birds in the vicinity. Of the birds lethally taken with 4-AP, 
4 

92% were house sparrows and 7% feral pigeons, whereas blackbirds (86%) and house 

sparrows (14%) accounted for all birds repelled. 

Table 2. Avitrol products used by WS in WDM from FY16 to FY20, the annual average target species 

killed and repelled, the amount of product used, and the states where used.

Table 3. The annual average number of target species killed and repelled with Avitrol products used by 

WS in WDM from FY16 to FY20. 

ANNUAL AVERAGE 4-AP BAIT USE AND SPECIES TAKE

Species* Killed Repelled Ounces Used States Where Used

Rock Dove (Feral Pigeon)* 89 - 3 TX

European Starling* 1 - 0.1 KY

House Sparrow* 1,236 38 43 CT IA KY MO OK TX

Red-winged Blackbird 12 235 3 NH

TOTAL (4 sp.) 1,338 273 49 7 States

* Introduced species

Between FY16 and FY20, WS averaged 6 projects per year, sometimes with multiple treatments 

at the same site. WS applied Avitrol grain baits at 5 electrical utilities (4 car parking lots/plug-ins 

for electric vehicles and 1 electrical substation) to prevent damage to equipment, 5 food plants 

to prevent contamination and consumption of food items, 4 airports to control birds caught 

indoors and to prevent flock interference with aircraft, 4 feedlots to reduce consumption of grain, 

2 industrial plants and 1 fruit orchard to prevent bird damage to fruit. The average hours spent 

per treatment site was 2.7 hours, which indicates that relatively little time was spent on the 

project day waiting for birds to feed, indicating the usefulness of prebaiting. WS applicators stay 

onsite during the treatment. When birds have been prebaited to an area, the bait and birds 

generally disappear quickly.

WS conducted fewer projects from FY16 to FY20 (Tables 2 and 3) than from FY11 to FY15

(Appendix 1: Table 1a and 1b). The ounces of Avitrol grain baits applied and take decreased 

from FY11–15 to FY16–20.

ANNUAL AVERAGE 4-AP BAIT USE BY WS

Product EPA 

Registration Killed Repelled OuncesApplied States

Avitrol Mixed Grains (0.5%) 11649-4 1,162 8 21 CT TX

Avitrol Double Strength Corn 

Chops (1.0%) 11649-5 12 235 3 NH

Avitrol Corn Chops (0.5%) 11649-6 164 30 25 IA KY MO OK

TOTAL 3 Products 

Used 1,338 273 49 7 States
5

2 PROBLEM FORMULATION

WS uses 4-AP (Avitrol baits) to control bird damage. The following sections cover the chemical 

description, product use, physical and chemical properties, environmental fate, and hazard 

identification for 4-AP. 

2.1 Chemical Description and Product Use 

The active ingredient in Avitrol baits is 4-aminopyridine (4-AP). 4-AP was first registered with 

USEPA in 1963 as an avicide (USEPA 2020b). Currently, Avitrol products are labeled as

poisons with flock alarming properties. 4-AP (C5H6N2, CAS No. 504-24-5) is a member of the 

pyridine family, which acts as a neurotoxin by blocking potassium channels and increasing 

acetylcholine levels at synapses and neuromuscular junctions. These characteristics result in 

convulsions, hyperactivity, and seizures (USEPA 2020a). Birds that ingest Avitrol baits will 

behave distressed and give warning calls that frighten other birds from the area. 4-AP is lethal 

to most all birds that ingest treated baits as a result of cardiac and respiratory arrest (USEPA 

2020a). 

2.2 Physical and Chemical Properties

4-AP has a molecular weight of 94.1 grams (g)/mol and a melting point between 155–

158 ̊Celcius ( ̊C) (USEPA 2016c, Avitrol Corporation nd). It has a vapor pressure of 1.64 x 10-4

to 2.09 x 10-4 torr at 25 ̊C (USEPA 2016c, NIH 2023) and an estimated Henry’s law constant 

of 2.3 x 10-10 atm-m3

/mol at 20 ̊C (USEPA 2007b, NIH 2023). Its water solubility is 112 g/Liter 

(L) at 25 ̊C (USEPA 2016a). Its octanol/water partition coefficient (log Kow) is 0.146-0.320 at 

25 ̊C (USEPA 2016c, NIH 2023). 

2.3 Environmental Fate

The environmental fate describes the processes by which 4-AP moves and degrades in the 

environment. The environmental fate processes include 1) persistence, degradation, and 

mobility in soil; 2) movement to air; 3) migration potential to groundwater and surface water; 4) 

degradation in water; and 5) plant uptake.

Environmental fate data is limited for 4-AP. 4-AP is expected to be persistent in the open 

environment with an aerobic soil degradation half-life of 3–32 months (USEPA 2020a); it is 

stable to hydrolysis and photolysis and is stable under anaerobic conditions (USEPA 

2007b;2016c). USEPA (2020a) summarized that when 4-AP is washed off treated bait, it may 

be mobile in soil and dissolve in water. 4-AP would not volatilize in water (estimated air-water 

partition coefficient or log Kaw of 1 x 10-7

), but would rapidly volatilize in field runoff due to the 

vapor pressure of 1.64 x 10-4 to 2.09 x 10-4 torr, which suggests intermediate to high volatility in 

the field, and low Kaw from surface water (USEPA 2020a). Degradates of 4-AP have not been 

identified in environmental fate studies.

4-AP is likely to be mobile in soil and has the potential to leach to groundwater or runoff to 

surface water based on its high solubility in water, low Kow, and low Koc (Koc of 34.6 mL/g) 

(USEPA 2020a). However, its mobility in soil would decrease because it may also be 

susceptible to aged sorption (USEPA 2007b). 

4-AP has a low potential to bioaccumulate in fish based on low log Kow<3 (USEPA 2007b). Plant 

uptake is greatly reduced since 4-AP is tied up in a bait formulation. Most of the bait is expected 
6

to be removed by the target species or applicator following a project reducing the amount of 4-

AP available for any potential plant uptake. 

The primary route of dissipation or transportation of 4-AP appears to be through the food chain,

where birds, mammals, or other organisms consume bait products, carry the chemical within 

their bodies, and move to offsite locations. However, 4-AP toxicity is relatively fast-acting, with 

treated birds reacting within 5–15 minutes after ingestion (USEPA 2020a). During the period 

from exposure to mortality, birds that succumb to the toxic effects could become secondary 

sources for predators and scavengers because not all treated grain may be digested (USEPA 

2016d). However, WS applicators are present at the site and can generally pick up many 

carcasses for disposal. Thus, it is anticipated that secondary risks are minimal.

2.4 Hazard Identification

4-AP is a central nervous system toxicant that is highly toxic to mammals (USEPA 2017b). 

People ingesting low levels of 4-AP (5–30 milligrams (mg)/day) experienced nervousness, 

nausea, giddiness or dizziness, memory alteration, cramps, arterial vasospasm, and peripheral 

paresthesia. In an accidental poisoning case, a person who ingested a high dose (~60 mg) 

experienced weakness, intense sweating, a feeling of impending doom, labored breathing, 

agitation and combative behavior, and profound thirst (Spyker et al. 1980).

USEPA (2016a) evaluated human incident reports for 4-AP during the product registration

review. USEPA consulted two databases:

• Office of Pesticide Program Main Incident Data Systems (IDS) for pesticide incident data 

on the active ingredient 4-aminopyridine between January 1, 2011 and June 10, 2020,

and 

• SENSOR-Pesticides, a pesticide surveillance program and database managed by the 

Center for Disease Control’s National Institute for Occupational Health for cases 

involving 4-aminopyridine between 1998 and 2015. 

No human adverse effects incident cases were reported for 4-AP in either database during 

these time periods.

4-AP is the active ingredient in several human drugs. Its potassium channel-blocking property 

has been used to help patients restore function in nerve fibers that have been traumatically 

injured and have lost the myelin sheath (USEPA 2007a). Fampridine treats multiple sclerosis 

and spinal cord injury by blocking potassium channels. The orally administered version of 4-AP, 

Ampydin, treats chronic functional motor and sensory deficits. Other medicinal uses of 4-AP in 

humans include reverse neuromuscular blockage resulting from non-depolarizing 

neuromuscular blocking agents and certain antibiotics and an experimental treatment for 

botulism, myoneural disorders, and Alzheimer’s disease (USEPA 2016b).

2.4.1 Mode of Action and Metabolism

4-AP is a nervous system toxicant that blocks potassium ion channels and increases 

acetylcholine levels at synapses and neuromuscular junctions, causing hyperactivity, 

convulsions, and seizures. Within 5–15 minutes of ingesting 4-AP bait, birds will behave 

erratically and emit distress calls, causing a distress display that frightens flocks of target bird 

species away from the treatment site. The distress display can occur for 30 minutes or more 

(USEPA 2020a). Birds either die or recover within 1–15 hours (USEPA 2020a). Birds are 
7 

frightened away from the treatment site, and birds that recover from ingesting 4-AP bait do not 

usually return to the treatment site (USEPA 2020a). 

4-AP is readily absorbed through the skin and gastrointestinal tracts of animals. Human studies 

showed that 4-AP is quickly eliminated from the body with effects proportional to the serum 

levels of 4-AP in the body (USEPA 2007a). 

2.4.2 Acute Toxicity

4-AP is highly toxic to most vertebrates (USEPA 2007a;2020a). 4-AP has high acute toxicity to 

mammals by the oral route of exposure (Category I) in rats and the dermal and inhalation routes 

of exposure (Category II) in rabbits (Table 4) (USEPA 2007a). The acute toxicological effects of 

4-AP in animals include hyperexcitability, salivation, tremors, muscular incoordination, clonic 

and tonic convulsions, cardiac or respiratory arrest, and death. 

Table 4. Acute toxicity data of technical and end-use 4-AP formulations.

Test Species Scientific Name Test Technical 4-AP

Rat Rattus norvegicus Oral LD501 20 mg/kg-bw 2

Rabbit Oryctolagus cuniculus domesticus Dermal LD50 (0.017% a.i.) 327 mg/kg-bw

Rat Rattus norvegicus Inhalation LC503 (50% a.i.) 0.53 mg/L

Rabbit Oryctolagus cuniculus domesticus Eye Irritation (1.0% a.i.) Not irritating

Rabbit Oryctolagus cuniculus domesticus Dermal Irritation (0.017% Not irritating

Guinea Pig Cavia porcellus Dermal Sensitization Not required

1 LD50 = acute median lethal dose

2 mg/kg = milligrams/kilogram body weight

3 LC50 = acute median lethal concentration

References: (USEPA 2007a, Avitrol Corporation 2018)

2.4.3 Subchronic and Chronic Toxicity

Subchronic animal studies of 4-AP included a 90-day oral toxicity study in rats (MRID 00131328 

and 00004026, 1968) and a 90-day oral toxicity study in dogs (MRID No. 00131329 and 

00004027, 1968) (USEPA 2007a). The study in rats reported a No Observable Adverse Effect 

Level (NOAEL) of 0.21 mg/kilogram-body weight (kg-bw)/day and a Lowest Observable Adverse 

Effect Level (LOAEL) of 2.15 mg/kg-bw/day (males) and 2.54 mg/kg-bw/day (females) based on 

hyperirritability to noise and touch. The study in dogs reported a NOAEL of 1 mg/kg-bw/day and 

a LOAEL of 2 mg/kg-bw/day based on occasional minimal salivation and muscular weakness in 

the hindquarters. USEPA (2007a) considers these studies unacceptable/non-guideline studies 

that do not meet the current guideline requirements for 90-day studies in rodents and nonrodents due to deficiencies in the test substance characterization.

Subchronic human studies of 4-AP included clinical studies to investigate the safety and efficacy 

of 4-AP in patients with spinal cord injury and multiple sclerosis (USEPA 2007a). Segal et al.

(1999), in a controlled long-term human clinical study (MRID 47093602), tested an oral dose of 

30 mg/day for 3 months to treat spinal cord injury patients (both male and female) who were 

otherwise healthy. The observed common adverse side effects during the study were
8

nervousness, giddiness or dizziness, and gastrointestinal upset manifested as mild abdominal 

cramping or nausea.

Grijalva et al. (2003), in a randomized, double-blind, placebo-controlled study (MRID 

47093601), tested an initial oral dose of 5 mg/day, increasing to 30 mg/day, for 3 months in 

patients with long-term spinal cord injury. The observed mild adverse reactions in patients at the 

dose range of 5–10 mg/day included dry mouth, dizziness, nausea, and gastritis. Only at the 30 

mg/day dose did patients show paresthesia (abnormal sensation of tingling or pricking).

Van Diemen et al. (1993) (as cited in (USEPA 2007b;2020c)) in a randomized, double-blind, 

placebo-controlled study (MRID 47093603) tested intravenous dosing infused gradually up to 5 

mg/kg-bw and oral dosing from 5 mg/day up to 30 mg/day of 4-AP in patients with multiple 

sclerosis for dosage and serum level related to efficacy and safety. Paresthesia occurred at a 

minimal dose of 1 mg in the intravenous phase. Adverse side effects observed in patients who 

received a minimum daily dose of 5 mg in the oral phase included paresthesia, dysesthesias,

dizziness, lightheadedness, gait instability, nausea, vomiting, restlessness, and anxiety.

2.4.4 Developmental and Reproductive Effects

USEPA (2007a) did not find valid studies for reproductive or developmental toxicity.

2.4.5 Carcinogenicity and Mutagenicity

USEPA (2017b) classified the carcinogenic potential of 4-AP as “not classifiable to human 

carcinogenicity” based on the lack of human or animal data and the weight of evidence. 

USEPA determined that chronic or carcinogenicity studies are not required based on the nonfood uses of 4-AP and the negative findings in the reverse mutation assays (not mutagenic) in 

Salmonella typhimurium (USEPA 2017a).

2.4.6 Immunotoxicity Effects

A literature review did not identify any 4-AP mammalian studies indicating immunotoxicity. 

2.4.7 Endocrine Effects

A literature search did not identify any mammalian studies indicating the potential of 4-AP to 

affect the endocrine system. USEPA developed a screening program to determine whether 

certain substances may affect humans’ estrogen, androgen, and thyroid hormone systems

(USEPA 2017c). 4-AP is not among the chemicals screened under the USEPA Endocrine 

Disruptor Screening Program. 4-AP is not among the European Union (EU) list of chemicals 

with the potential to impact the endocrine system (Danish Centre on Endocrine Disrupters 

2018). It was excluded in the second literature screening for endocrine disruptor effects due to 

the lack of endocrine disruptor mode of action. The EU list includes three categories: Category 1 

– endocrinal effect recorded at least on one type of animal; Category 2 – a record of biological 

activity in vitro leading to disruption; and Category 3 – not enough evidence or no evidence of 

data to confirm or disconfirm endocrinal effect of tested chemicals (Hrouzková and Matisova 

2012).
9

3 DOSE-RESPONSE ASSESSMENT

3.1 Human Health Dose-Response Assessment

A dose-response assessment evaluates the dose levels (toxicity criteria) for potential human 

health effects, including acute and chronic toxicity. 

For short-term incidental oral, dermal, and inhalation exposures, USEPA (2007a) selected a 5 

mg daily dose (0.07 mg/kg-bw/day) as a minimal LOAEL for a point of departure (POD). The 

LOAEL was based on human clinical studies with 4-AP. A total of 30x uncertainty factor (an 

uncertainty factor of 10x for individual variability (intraspecies) in the human population, and an 

additional uncertainty factor of 3x for the use of a POD based on a minimal LOAEL with 

transient mild adverse effects) applies to the LOAEL yielding a reference dose of 0.002 mg/kgbw/day. For route-to-route extrapolation, USEPA assumes 100% dermal and inhalation 

absorption factors. USEPA uses an occupational level of concern of 30 as a margin of exposure

(USEPA 2016b).

USEPA did not establish a tolerance for 4-AP because it is not registered for food or agricultural 

crop uses. The maximum contaminant level has not been established for drinking water.

3.2 Ecological Effects Analysis

This section discusses available ecological effects data for terrestrial and aquatic biota.

Available acute and chronic toxicity data are summarized for all major taxa and will be 

integrated with the exposure analysis section to characterize the risk of 4-AP to nontarget

wildlife and domestic animals. Information in this section was gathered from on-line databases 

and searches for relevant peer-reviewed and other published literature.

3.2.1 Aquatic Species

4-AP has high acute toxicity to freshwater invertebrates and moderate acute toxicity to 

freshwater fish and amphibians (Table 5). 4-AP is highly toxic to the freshwater juvenile glass 

shrimp3 with a 96-h LC50 of 0.37 mg active ingredient (ai)/L (USEPA 2020a). The 24-h and 48-h 

LC50 in the water flea are 17 mg/L and 3.2 mg/L, respectively (Marking and Chandler 1981). In 

the most sensitive fish species tested, channel catfish, 4-AP is moderately toxic, with an acute

96-h LC50 of 2.43 in very hard water to 5.8 mg ai/L in soft water (USEPA 2020a). Although 

exposure to 4-AP did not affect the hatching of leopard frog eggs, it did affect larvae survival 

(Marking and Chandler 1981). 4-AP has moderate acute toxicity in Southern leopard frog larvae 

with a 24-h and 96-h LC50 of 7.2 and 2.4 mg/L, respectively (Marking and Chandler 1981, 

USEPA 2020a). Mayfly nymphs were highly sensitive to 4-AP, with a 24-h and 96-h LC50 of 5.3 

and 0.58 mg/L, respectively (Marking and Chandler 1981). The adult river horn snail had lower 

sensitivity than other freshwater invertebrates with a 24-h and 96-h LC50 of >100 and 62 mg/L, 

respectively (Marking and Chandler 1981). Similarly, the adult Asiatic clams had lower 

sensitivity with a 24-h and 96-h LC50 of 78 and 45 mg/L, respectively (Marking and Chandler 

1981). At the 96-h exposure, sublethal effects were observed in the clams; they could not right 

themselves or cling to the sidewalls of the vessel (Marking and Chandler 1981). In a study on

3 Scientific names are given in Table 5 for this section.
10

marine/estuarine fish, 4-AP has high acute toxicity, with a 72-h LC50 of 7.6 mg/L for cowfish and 

globefish (USEPA 2016d). In the same study, the No Observable Adverse Effect Concentration 

(NOAEC) for both the cowfish and globefish was 4.6 mg/L, and the Lowest Observable Adverse

Effect Concentration (LOAEC) was 6.8 mg/L based on mortality and sublethal effects (USEPA 

2016d). No acute or chronic toxicity information is available for marine or estuarine 

invertebrates.

Table 5. 4-AP acute toxicity values in aquatic species. 

Species Scientific Name Toxicity Value Reference

Channel catfish Ictalurus punctatus 96-h LC50 2.43 mg/L (very hard 

water)

96-h LC50 = 5.8 mg/L (soft water)

(USEPA 2020a)

Glass shrimp 

(juvenile)

Palaemonetes 

kadiakensis

96-h LC50 = 0.37 mg/L (USEPA 2016c)

Water flea Daphnia magna 24-h LC50 = 17 mg/L

48-h LC50 = 3.2 mg/L

(Marking and 

Chandler 1981)

Crayfish (juvenile) Procambarus acutus 96-h LC50 = 2.2 mg/L (USEPA 2020a)

Southern leopard frog 

(larvae)

Lithobates (Rana) 

sphenocephala

24-h LC50 = 7.2 mg/L

96-h LC50 = 2.4 mg/L

(Marking and 

Chandler 1981, 

USEPA 2020a)

Mayfly (nymphs) Isonychia sp. 24-h LC50 = 5.3 mg/L

96-hr LC50 = 0.58 mg/L

(Marking and 

Chandler 1981)

Caddisfly (larvae) Hydropsyche sp. 24-h LC50 = 30 mg/L

96-h LC50 = 15 mg/L

(Marking and 

Chandler 1981)

River horn snail 

(adult)

Oxytrema catenaria 24-h LC50 = >100 mg/L

96-h LC50 = 62 mg/L

(Marking and 

Chandler 1981)

Asiatic clam (adult) Corbicula manilensis 24-h LC50 = 78 mg/L

96-h LC50 = 45 mg/L

(Marking and 

Chandler 1981)

Cowfish Lactophyrys tricornis 72-h LC50 = 7.6 mg/L (USEPA 2016d)

Burrfish or Globe fish Chilomycterus sp. 72-h LC50 = 7.6 mg/L (USEPA 2016d)

3.2.2 Terrestrial Species

3.2.2.1 Mammals

4-AP has high acute toxicity in mammals with an acute oral LD50 of 28.7 mg/kg-bw in laboratory

rats with a very steep dose-response curve and 3.7 mg/kg-bw in dogs (Schafer et al. 1973, 

USEPA 2020a). No chronic toxicity studies in mammals are available (USEPA 2020a). 

3.2.2.2 Birds

4-AP has high acute toxicity in birds with LD50 values ranging from 2.4 mg/kg-bw for red-wings 

blackbirds and 15 mg/kg-bw for bobwhite quail (Table 6). The rose-ringed parakeet had a LD50

of 3 mg/kg-bw; the birds gave distress calls at an average of 39 minutes and 15 minutes after 

gavage with 5 mg/kg-bw and 10 mg/kg-bw, respectively (Sultana et al. 1986). Acute dietary and 

subchronic studies indicate 4-AP is slightly toxic to birds, with LC50 values of 361 and 681 

mg/kg-diet for the mourning dove and mallard duck, respectively (USEPA 2020a). One avian 

chronic toxicity study resulted in a NOAEC of 31.6 mg/kg-diet in coturnix quail (Coturnix 
11

coturnix) (USEPA 2020a). Subchronic exposure of dove and coturnix quail to 4-AP did not result 

in cumulative toxicity (Schafer and Marking 1975). One non-guideline reproductive study 

indicates some chronic toxicity in Japanese quail based on reductions in male weight gain 

(NOAEL = 31.6 mg ai/kg-diet, LOAEL = 100 mg ai/kg-diet (Schafer et al. 1975, USEPA 2020a). 

In birds (pigeons, sparrows, and red-winged blackbirds) that survived ingesting 4-AP bait, 

incapacitation lasted up to 90 minutes (Frank et al. 1981); during this time, they may be 

vulnerable to predators.

Table 6. 4-AP acute toxicity values in bird species.

Species Scientific Name LD50 Value Reference

Red-winged blackbird Agelaius assimilis 2.4 mg/kg-bw (USEPA 2016c)

Black-billed magpie Pica hudsonia 2.4 mg/kg-bw (USEPA 2016c)

Yellow-billed magpie Pica nutalli 2.4 mg/kg-bw (USEPA 2016c)

European starling Sturnus vulgaris 4.9 mg/kg-bw (USEPA 2020a)

Northern bobwhite Colinus virginianus 15.0 mg/kg-bw (USEPA 2016c)

Rock dove Columba livia 2.5 mg/kg-bw (Sultana et al. 1986)

Mourning dove Zenaida macroura 8.1 mg/kg-bw (USEPA 2020a)

Rose-ringed parakeet Psittacula krameri 3.02 mg/kg-bw (Sultana et al. 1986)

House sparrow Passer domesticus 4.2 and 7.5 mg/kg-bw (Sultana et al. 1986)

White-rumped munia Lonchura striata 2.97 mg/kg-bw (Sultana et al. 1986)

Mallard duck Anas platyrhynchos 4.36–5.19 mg/kg-bw (USEPA 2020a)

3.2.2.3 Reptiles and Terrestrial Phase of Amphibians

Acute and chronic toxicity data is unavailable for terrestrial reptiles and amphibians (USEPA 

2020a). Based on surrogacy from birds, 4-AP would be toxic to reptiles and amphibians. 

3.2.2.4 Terrestrial Invertebrates

Acute and chronic toxicity studies for adult and larval honeybees and other terrestrial 

invertebrates are unavailable (USEPA 2020a). Bees are not attracted to the bait (USEPA 

2020a). The label suggests using bait trays, which reduces bait contact with the ground and 

potential subsequent exposure to ground- and soil-dwelling invertebrates. Invertebrates are not

likely to be harmed by treatments. 

3.2.2.5 Terrestrial Plants

Information on the toxicity of 4-AP to terrestrial plants is limited (USEPA 2020a). USEPA 

(2020a) summarized one study where a reduction in fresh weight (less than 25%) was observed 

in corn seeds and seedlings after two applications of 4-AP.
12

4 EXPOSURE ASSESSMENT

4.1 Human Health

The exposure analysis evaluates the potential for exposure of humans to WS use of Avitrol. The 

exposure assessment begins with the use pattern for Avitrol. An exposure pathway for Avitrol 

includes (1) a release from an Avitrol source, (2) an exposure point where human contact can 

occur, and (3) an exposure route such as ingestion, inhalation, or dermal contact. Exposures for 

the identified human populations are evaluated qualitatively for each identified exposure 

pathway.

4.1.1 Potentially Exposed Human Populations and Complete Exposure Pathways

Avitrol products are all “restricted-use pesticides,” and only certified applicators or persons 

under their direct supervision may use the product (Avitrol Corporation 2013d;b;a;e;c, USEPA 

2017b). The baits are applied by hand using a scoop and cannot be applied by air or 

mechanical equipment designed to broadcast baits or other pesticides (Avitrol Corporation 

2013d;b;a;e;c). The Avitrol products are for non-food or non-agricultural crop use.

WS handlers and applicators (occupational workers) adhere to label requirements as they

prepare and apply (including placement, monitoring, and retrieval of) treated baits to prevent 

contact with themselves and the public directly or through drift. Based on the expected use 

patterns for Avitrol products, WS applicators are the most likely subgroup of the human 

population to be exposed to 4-AP.

Exposure of the public to Avitrol products is unlikely when applicators follow label requirements 

concerning application sites, entry restrictions, use restrictions, and post-treatment cleanup 

requirements. The product labels require baiting at elevated sites in populated areas and areas 

open to the public and continuously monitored ground baiting in public areas when baiting at 

elevated sites is not feasible (Avitrol Corporation 2013d;b;a;e;c). Only certified applicators

wearing personal protective equipment (PPE) are allowed in the treatment area during bait 

application. In ground-baited public areas, applicators must remain onsite during treatment and 

remove all dead or dying birds and unused bait after treatment. WS applicators dispose of 

collected birds by burial or incineration. Between FY16 and FY20, WS applicators completed 

about 6 treatments nationally per year. They spent an average of 2.7 hours at treatment sites, 

which for Avitrol treatments is enough time to place baits, wait for birds to react and leave the 

area, and pick up baits and dead birds.

After ground-baiting in public areas, the post-treatment cleanup requirement minimizes the 

potential for human exposure to uneaten baits. In public areas, WS applicators prefer to place 

Avitrol bait in bait trays for ease of bait removal after treatment. WS applicators prefer to treat 

when few people are around because seeing distressed birds can be disturbing. The labels 

require product containers and unused, spoiled, or unconsumed bait to be disposed of at an 

approved waste disposal facility, deep burial, or by incineration. The product labels also have 

restrictions on storage (including temporary placement).

A complete exposure pathway is not identified for dietary exposure. There are no registered 4-

AP uses for food or agricultural crops (USEPA 2017b). The Avitrol labels (Avitrol Corporation 

2013d;b;a;e;c) prohibit the following:
13

• applying the treated baits to growing food crops,

• using the treated baits as food, feed, or in any way used such that they could 

contaminate human food or animal feed,

• feeding, or mixing with grains for livestock or poultry, and 

• applying where livestock or poultry may be exposed (users must keep livestock away 

from the bait storage location and application areas).

A complete exposure pathway is not identified for drinking water because of the use pattern of

Avitrol formulations and label requirements not to use bait within 25 feet of permanent water 

bodies. Bait intake by the target species further reduces the chance of offsite transport via 

runoff. In addition, in publicly accessible areas that WS ground-treats, the labels require the 

applicator to retrieve unconsumed bait. Any bait left on the ground after cleanup would be 

minor. Bait trays reduce the potential runoff of bait should precipitation events occur. WS 

applicators avoid treating areas when precipitation is forecast to reduce the chance of bait 

effectiveness being degraded and the need for retreatment, reducing the likelihood of bait 

runoff. The use patterns preclude contamination of surface and groundwater that could be used 

for drinking water. During registration review, the label amendments proposed by USEPA will 

further specify these use restrictions and methods to protect the public and nontarget animals 

and prevent surface and groundwater contamination.

4.1.2 Human Health Exposure Evaluation and Risk Characterization

This section qualitatively evaluates worker exposure from direct contact while handling and 

applying bait in the field and re-entering treated sites for post-treatment cleanup activities. 

Avitrol formulations are restricted-use pesticides handled by certified applicators or persons 

under their direct supervision. The end-use products are mixed with untreated bait grains of the 

same composition, so ratios of treated baits to untreated grains are approximately 1:9 or greater 

for most projects to 1:5 for some. Exposure from direct contact to 4-AP in Avitrol baits for 

applicators and handlers is minimized under normal conditions with proper worker hygiene and

PPE. PPE requirements for all mixers, loaders, applicators, persons picking up the dead birds 

and unused bait, and other handlers include:

• Long-sleeved shirt and long pants,

• Chemical-resistant gloves, such as those made from waterproof material, and

• Socks and shoes.

Applicators use a scoop when mixing and applying Avitrol products. Following treatment, which 

at the maximum is at the end-of-the-day or sundown, applicators retrieve dead birds and 

unused bait and dispose of these appropriately.

Other user safety requirements on the labels include:

• Properly cleaning PPE after use, such as washing in detergent and hot water,

• Keep and wash PPE separately from other laundry,

• Washing hands before eating, drinking, chewing gum, using tobacco, or using the toilet,

• Removing clothing and PPE immediately if pesticide gets inside, washing exposed skin 

surfaces thoroughly, and putting on clean clothing,

• Removing PPE immediately after handling the product, and

• Washing the outside of gloves before removal.
14

Accidental exposure may occur during the handling and application of baits. This type of 

exposure is low since only certified applicators or persons under their supervision who are 

trained are allowed to use Avitrol products. The infrequent and limited use of Avitrol products

reduces the potential for accidental exposure. A quantitative exposure is not further evaluated.

4.2 Ecological Exposure Assessment

USEPA summarized 4-AP incident data for the years 1981–2018 reported in the Ecological

Incident Data System (IDS), the USEPA Office of Pesticide Program’s database that contains 

nontarget animal adverse effects incidents reported to the agency. A total of 180 incidents were 

reported, with 31 incidents related to registered uses, 106 incidents with unknown legality of the 

application, and 43 incidents that were illegal uses. Take of birds represented 99% of the 

incidents. No incidents involved aquatic species or plants. Most of the birds taken are listed as 

target species on the products’ labels. No incidents were reported after 2012 (USEPA 2020a). 

None of the reports in the IDS was from a WS application.

4.2.1 Aquatic Exposure Assessment

Exposure of aquatic species to 4-AP is limited. The 4-AP labels require a minimum 25-foot 

buffer from permanent water bodies. Due to these label restrictions, runoff into surface or 

groundwater of 4-AP into aquatic environments is not expected. Using bait trays would reduce 

the potential for bait to run off during or following a rain event. WS avoids applying bait when 

precipitation events are predicted due to the chance bait would wash away, requiring them to 

repeat the treatment. The USEPA (2020a) estimated the amount of bait that would need to 

enter a waterbody to reach a concentration of 4-AP that would be toxic to freshwater fish and 

invertebrates is all of >1,000 and >500 applications worth of bait, respectively. These levels are 

magnitudes greater than what WS uses during applications and their frequency, which is

unlikely to pose a risk.

Other potential aquatic exposure scenarios could involve birds dropping or regurgitating bait 

offsite or poisoned animals dying in a water resource. The labels require applicators to remove 

dying or dead birds in and around publicly accessible areas to reduce secondary exposure. 

Removal of these birds would reduce aquatic exposure potential. Additionally, the 4-AP is 

relatively fast acting (5–15 minutes), which limits the areas where birds can travel.

The label language, WS’ use patterns, and aquatic exposure scenarios indicate exposure of

aquatic vertebrates, invertebrates, and plants to 4-AP is not expected.

4.2.2 Terrestrial Exposure Assessment

Exposure to terrestrial species is through the consumption of 4-AP bait. Based on the 

formulation, exposure through dermal and inhalation routes are not significant exposure 

pathways. Wildlife attracted to the grains used in the Avitrol products are most at risk of 

exposure. As aquatic exposure is not expected, as previously discussed, ingestion of water 

containing 4-AP is not an expected route of exposure for wildlife. Honeybees and other 

pollinators are not attracted to the 4-AP baits (USEPA 2020a). USEPA waived the requirements 

for acute and chronic toxicity tests for the honeybee due to this lack of exposure. WS’ use 

patterns result in minimal exposure to terrestrial plants and no exposure to plants for human 

consumption, as the label restricts applications in areas where food crops grow. For example, 

WS treated red-winged blackbirds on the periphery of an orchard instead of within the orchard.
15

4-AP presents a primary hazard to nontarget birds and mammals because of its acute toxicity,

lack of selectivity, and attractiveness of the Avitrol grain baits. All but two of the IDS incident 

reports between 1981 and 2018 involved birds; 129 incidents were primary exposure of 

nontarget songbirds and one eagle (USEPA 2020a). None of the incident reports in the IDS 

were from WS applications, and WS has no reports of a nontarget bird or mammal taken

through its use of 4-AP (Tables 2 and 3, Appendix 1: Tables 1a and 1b).

A search of the ASPCA Animal Poison Control Center database from 2002 to 2011 found 29 

exposures of nontarget species to 4-AP (none of these were from WS applications): 89% were 

dogs, 10% cats, and 3% bovines (McLean and Khan 2013). The animal’s outcome was known 

in 6 of the cases; all but one animal lived after veterinary care. The amount of 4-AP ingested in 

these exposures was unknown.

The current Avitrol product labels impose requirements to mitigate the risk to nontarget species. 

The labels require prebaiting in the proposed treatment area to determine that no nontarget 

birds feed on the prebait and to ensure the target species will take the bait where it is placed. 

Treated bait is not applied if the target species do not feed on the prebait or if nontarget species 

feed on it. In areas accessible to the public that are ground-treated, the label instructs the 

applicator to remain on site until all dead and dying birds and unused bait are retrieved from the 

site. This reduces the potential for primary and secondary poisoning of nontarget birds and 

other animals that may be attracted to the bait and potentially affected and prevents the public 

from attempting to rescue a bird.

4.2.3 Secondary Exposure

Predators and scavengers are at risk of exposure to undigested or unassimilated gut contents of 

species poisoned with 4-AP while intoxicated or after dying. USEPA (2020a) summarized 

incident data reported in the Incident Data System for 1981-2018. Seven incidents involved 

raptors. Two of these (Cooper’s hawk and peregrine falcon) likely involved ingesting birds 

poisoned with 4-AP. One lethal incident involved the primary exposure of one eagle; however, 

WS suspects this poisoning was not from primary exposure because corn is not known to be 

part of the eagle diet (scavenger). The other 3 raptors that died had no necropsy done. One 

raptor (not identified) fed on mourning doves which had concentrations of strychnine and may 

not have been poisoned by 4-AP (USEPA 2020a). One incident involved mammals; however, 4-

AP may not have been the cause of death. The incident involved a dog mortality (the dog’s 

weight was not provided) that had consumed a poisoned dove; however, strychnine was 

detected in the dove, and 4-AP was not mentioned in the necropsy report (USEPA 2020a).

None of these incidents were the result of WS applications. From the summarization by USEPA 

(2020a), it appears the incidents involved mostly strychnine and not 4-AP.

Studies on secondary exposure risk are limited. In a laboratory study evaluating secondary 

poisoning, 2 out of 20 kestrels died after exposure to red-winged blackbirds that fed on 1% 

Avitrol bait diluted 1:9 (Holler and Schafer 1982). All kestrels in the study consumed gut 

contents. Sharp-shinned hawks displayed no treatment-related effects (Holler and Schafer 

1982). USEPA (2020a) reviewed one study where blackbirds killed with 4-AP were fed to dogs, 

American kestrels, and red-tailed hawks. No effects in the study were observed; however, the 

estimated amount of 4-AP ingested by the blackbirds was not provided, and secondary 

exposure concentrations were unknown (USEPA 2020a). In another study, no effects were 

observed in the adult male beagle and adult female beagle-coyote hybrid, magpies, rats, and 

three species of hawks fed 4-AP killed red-winged blackbirds (Schafer et al. 1974). The 

estimated amount of 4-AP ingested by eating red-winged blackbirds was 5.8 mg/kg-bw and 8.2 
16

mg/kg-bw for the adult male beagle and the adult female beagle-coyote hybrid, respectively

(Schafer et al. 1974). In the rat, no symptoms were observed at the highest dose, estimated at 

67 mg/kg-bw based on the amount of red-winged blackbirds given to the rats (Schafer et al. 

1974). Similarly, magpies displayed no effects at the highest dose of 7.5 mg/kg-bw (estimated). 

The female sharp-shinned hawk and American kestrels exposed to an estimated 6.4 mg/kg-bw

and 5.5-6.1 mg/kg-bw 4-AP per day through consumption of 4-AP-poisoned red-winged 

blackbirds did not display symptoms (Schafer et al. 1974). The authors conclude the lack of 

effects is due to the rapid metabolizing of 4-AP in red-winged blackbirds. 

USEPA (USEPA 2007b;2020a) found that 4-AP could be a risk to nontarget predators and 

scavengers, particularly bird species, in areas where 4-AP is used due to 4-AP’s mode of

action and toxicity to birds. The removal of dead or dying birds from the treatment area at the 

end of the project or at sundown would reduce secondary exposure. WS has no reports of 

secondary exposure from their use of 4-AP. This does not mean that no take of nontarget 

predators or scavengers has occurred, as some target birds may fly off and die offsite. In one 

study, 10 dead or dying herring gulls poisoned with 4-AP were collected up to 5 km away from 

the treatment site with 4-AP residues of 2.2-92 mg/kg-bw detectable in the crop and gut 

contents (the amount of 4-AP detected was for all herring gulls, not specifically for those 

collected at 5 km) (Frank et al. 1981).

5 RISK CHARACTERIZATION

5.1 Human Health Risks

Risks to human health are characterized qualitatively in this section. WS’ use of Avitrol 

products is limited (Table 2), and applications are extremely controlled to prevent exposure. 

Under WS’ use patterns, Avitrol baits should pose minimal risks to human health.

Adherence to label requirements regarding PPE minimizes risk to WS workers who handle and 

apply Avitrol products. Although 4-AP is a hazard to humans due to its acute toxicity via the 

ingestion, dermal, and inhalation routes, the low potential for exposure to 4-AP when following 

label requirements during handling and application of bait formulations suggest adverse health 

risks to workers are not expected. Any exposure and risk would be short-term based on the 

methods for baiting and the low quantity of Avitrol baits used by WS. Exposure of the general 

public to 4-AP is not anticipated based on the limited use pattern (e.g., entry restriction and preoperation monitoring for bait disappearance rate), and the post-treatment cleanup requirements

(e.g., remove unconsumed baits, monitor the bait area periodically and collect dead/dying birds

for proper disposal). Therefore, adverse health risk to the public is not expected, which is 

supported by the lack of adverse incidents that have been reported to date.

4-AP is rapidly metabolized in birds and excreted in the urine in the target species (Extoxnet 

1996). Therefore, the amount of chemical that remains in killed birds is unlikely to present a 

hazard to people. A person would have to ingest the internal organs of birds found dead from 4-

AP ingestion to have any chance of receiving even a minute amount of the chemical into their

system. This is highly unlikely to occur. In addition, people do not commonly consume the 

species of birds that are the target of baiting with Avitrol products. No reports of poisoning in 

humans from 4-AP exposure were documented by USEPA (2020c).
17

5.2 Ecological Risks

WS assumes birds that are attracted to Avitrol bait and those that ingest the bait will likely ingest 

enough 4-AP to receive a toxic dose. Secondary exposure is a concern for predators and 

scavengers of birds poisoned with 4-AP. The label requirements to prebait the treatment area 

with untreated grains of the same composition reduces exposure to nontarget birds and other 

wildlife. In treatment areas accessible to the public where ground-baiting occurs, the removal of 

leftover bait and dead or dying birds at the end of the project or sundown reduces exposure to 

nontarget species, including scavengers and predators. However, WS expects some predators

and scavengers will enter the treatment area before cleanup, but the typical treatment site is not 

conducive to many raptors and other scavengers. WS uses Avitrol products to treat a subpopulation of flocking birds to create a frightening response and agitation disturbance to cause 

the flock of birds to disperse. The entire flock of birds does not ingest treated baits. In a field 

study, researchers observed 82 dead birds with estimated flocks of 30,700 after broadcast 

treating cornfield experimental plots (total of 89 acres) with a 1:99 dilution rate of 3% 4-AP 

chopped corn baits (Besser and DeGrazio 1985). Avitrol products are poisons with flock 

alarming properties. WS dilutes baits further than the label requirements for large flocks to 

reduce mortality rates. WS expects the target birds that ingest Avitrol baits will die, although this 

is not always the case. Birds that do not receive a lethal dose may still be at risk of predation 

because of the neurological effects that may make them susceptible to predators.

Mammals in the treatment area attracted to the Avitrol bait are also at risk of lethal exposure. 

Although WS prebaits the treatment area and will not apply the Avitrol bait if nontarget species 

take the untreated bait, there is still a possibility for nontarget species to be present during 

treatment. In treatment areas accessible to the public where ground-baiting occurs, removing

leftover bait and dead or dying birds at the end of the project or sundown reduces exposure to 

other nontarget species, including mammals. This would reduce the exposure risk to domestic 

pets, such as dogs, as pet owners are aware of the area’s hazards.

Although 4-AP is toxic to freshwater, marine, and estuarine fish and freshwater invertebrates, 

label restrictions, and WS’ use patterns result in a low exposure potential. Chronic and 

subchronic toxicity studies are lacking for aquatic species; USEPA waived these studies due to 

lack of aquatic exposure because of label mitigations. The overall risk to aquatic species from 

WS uses of 4-AP products is negligible. 

The risk of nontarget species ingesting water contaminated with 4-AP is also negligible. 4-AP 

bait is not expected to impact terrestrial and aquatic plants due to lack of exposure and 4-AP’s 

mode of action. 

6 UNCERTAINTIES AND CUMULATIVE IMPACTS

The uncertainties associated with this risk assessment arise primarily from a lack of recent 

information about the effects of 4-AP, its product formulations, and potential mixtures to 

nontarget organisms that can occur in the environment because much of the information came 

from studies when 4-AP products were first registered. These uncertainties are not unique to 

this assessment but are consistent with uncertainties in human health and ecological risk 

assessments with any environmental stressor.
18

Another potential uncertainty in this risk assessment is the potential for cumulative impacts on

human health and the environment from the use of Avitrol products. The potential for cumulative 

impacts is expected to be low based on the low amount of Avitrol baits that WS uses. WS used 

an annual average of 49 ounces of Avitrol baits from FY16 to FY20 and 221 ounces between 

FY11 and FY15. Areas, where cumulative impacts may occur include: 1) repeated worker and 

environmental exposures to 4-AP from program activities and other sources; and 2) exposure to 

other chemicals with a similar mode of action.

Repeated exposures that could lead to significant risk from 4-AP are not expected due to label 

requirements that prevent significant exposure and reduce use. Accidental exposure may occur 

from improper use of PPE, but the potential for this is unlikely because Avitrol products are used 

only by certified applicators or those under their direct supervision.

Cumulative impacts may occur from 4-AP use in relation to other chemicals with a similar mode 

of action, as well as others with a different mode of action but could result in synergistic, 

additive, or antagonistic effects. This is an area of uncertainty since it’s unknown what other 

stressors, including chemicals, humans, and nontarget wildlife, may be exposed to during a 4-

AP application. 

From a human health perspective, WS’ low volume and minor uses of Avitrol products is 

expected to result in negligible cumulative impacts and low potential for cumulative impacts from 

exposure to other chemicals. Avitrol products are restricted use of pesticides, and only certified 

applicators and those under their direct supervision may use these products. Avitrol products 

are not sold to the public. Avitrol products are not registered for use on food crops and are

unlikely to impact surface or groundwater, so risks are negligible for the public. Treatments may 

occur in areas accessible to the public. During these applications, the certified applicator 

remains onsite to ensure the public and pets do not enter the treatment area or consume baits. 

The lack of exposure and risk to the public suggests that cumulative impacts would also be 

incrementally negligible when factoring in other stressors.

7 SUMMARY

WS uses Avitrol products to reduce bird nuisance and damage. The WS use pattern and their 

classification as restricted use pesticides result in negligible risk for the public. The dietary risk 

from 4-AP exposure to the public is negligible since Avitrol products have no registered food 

uses and do not pose a threat to drinking water. The risk to WS applicators is low because they 

receive training in the products’ use, are certified by the State pesticide regulatory agencies to 

use restricted-use pesticides, and follow label instructions, including the use of appropriate PPE. 

WS expects some take of target species that ingest Avitrol baits. WS also expects minor take of 

nontarget species that are attracted to the baits or to distressed and dying birds. The minimal 

release of 4-AP into the environment is expected to have no or negligible cumulative impacts on

nontarget species, the public, and the environment. 
19

8 LITERATURE CITED

Avery, M. L. 2020. Rusty Blackbird (Euphagus carolinus), version 1.0. in A. F. Poole, editor. 

Birds of the World. Cornell Lab of Ornithology, Ithaca, NY, USA.

Avitrol Corporation. 2013a. Avitrol Corn Chops label, EPA registration No. 11649-6. Issue date 

September 24, 2013. Pages 5 pp.

_____. 2013b. Avitrol Double Strength Corn Chops label, EPA registration No. 11649-5. Issue 

date September 24, 2013. Pages 5 pp.

_____. 2013c. Avitrol Double Strength Whole Corn label, EPA registration No. 11649-8. Issue 

date September 24, 2013.

_____. 2013d. Avitrol Mixed Grains label, EPA registration No. 11649-4. Issue date September 

24, 2013. Pages 5 pp. 

_____. 2013e. Avitrol Whole Corn label, EPA registration No. 11649-7. Issue date September 

24, 2013. Pages 5 pp. 

_____. 2018. Safety Data Sheet for Avitrol Mixed Grains, Avitrol Corn Chops, Avitrol Whole 

Corn. Date of Issue: September 4, 2018. 

_____. nd. Technical data sheet, Avitrol, Avitrol Corporation, Tulsa, Oklahoma, USA.

Besser, J. F., and J. W. DeGrazio. 1985. Reformulated 4-aminopyridine baits cost-effectively 

reduce blackbird damage to ripening cornfields. Proceedings of the Eastern Wildlife Damage 

Control Conference 2:125-134.

Danish Centre on Endocrine Disrupters. 2018. Centre on Endocrine Disrupters, List of 

Endocrine Disrupting Chemicals, Final report, December 21th, 2017 (some mainly editorial 

chances were made in September 2018).

Extoxnet. 1996. 4-Aminopyridine, Pesticide Information Profiles. in Extension Toxicology 

Network.

Frank, R., G. J. Sirons, and D. Wilson. 1981. Residues of 4-aminopyridine in poisoned birds. 

Bulletin of Environmental Contamination and Toxicology 26:389-392.

Greenberg, R., D. W. Demarest, S. M. Matsuoka, C. Mettke-Hofmann, D. Evers, P. B. Hamel, J. 

Luscier, L. L. Powell, D. Shaw, M. L. Avery, K. A. Hobson, P. J. Blancher, and D. K. Niven. 

2011. Understanding Declines in Rusty Blackbirds. Pages 107– 126 in J. V. Wells, editor. 

Boreal birds of North America. Studies in Avian Biology (no. 41). University of California Press, 

Berkeley, CA.

Grijalva, I., G. Guízar-Sahagún, G. Castañeda-Hernández, D. Mino, H. Maldonado-Julián, G. 

Vidal-Cantú, A. Ibarra, O. Serra, H. Salgado-Ceballos, and R. Arenas-Hernández. 2003. 

Efficacy and Safety of 4-Aminopyridine in Patients With Long-Term Spinal Cord Injury: A 

Randomized, Double-Blind, Placebo-Controlled Trial. Pharmacotherapy 23:823-834.

Holler, N. R., and E. W. Schafer. 1982. Potential secondary hazards of Avitrol baits to sharpshinned hawks and American kestrels Potential Secondary Hazards of Avitrol Baits to SharpShinned Hawks and American Kestrels (jstor.org). Journal of Wildlife Management 46:57-462.
20

Hrouzková, S., and E. Matisova. 2012. .Endocrine disrupting pesticides, Chapter 5. Pages 99-

126 in Pesticides - Advances in Chemical and Botanical Pestic.

Marking, L. L., and J. H. Chandler. 1981. Toxicity of six bird control chemicals to aquatic 

organisms Bulletin of Environmental Contamination and Toxicology 26:705-716.

McLean, M. K., and S. Khan. 2013. A review of 29 incidents involving 4-aminopyridine in nontarget species reported to the ASPCA Animal Poison Control Center. Journal of Medical 

Toxicology 9:418-421.

National Research Council. 1983. Risk assessment in the Federal government: managing the 

process. National Academy Press, Washington, DC.

NIH. 2023. 4-Aminopyridine. PubChem CID 1727. in National Institutes of Health, National 

Library of Medicine.

Roswell, H. C., J. Ritcey, and F. Cox. Assessment of humaneness of vertebrate pesticides, 

Pages 1-12 in Conference Assessment of humaneness of vertebrate pesticides.

Schafer, E. W., R. B. Brunton, and D. J. Cunningham. 1973. A summary of acute toxicity of 4-

aminopyridine to birds and mammals. Toxicology and Applied Pharmacology 26:532-538.

Schafer, E. W., R. B. Brunton, and N. F. Lockyer. 1974. Hazards to animals feeding on 

blackbirds killed with 4-aminopyridine baits. Journal of Wildlife Management 38:424-426.

_____. 1975. The effects of subacute and chronic exposure to 4-Aminopyridine on reproduction 

in coturnix quail. Bulletin of Environmental Contamination and Toxicology 13:758-764.

Schafer, E. W., and L. L. Marking. 1975. Long-Term effects of 4-aminopyridine exposure to 

birds and fish. Journal of Wildlife Management 39:807-811.

Segal, J., M. Pathak, J. Hernandez, P. L. Himber, S. R. Brunnemann, and R. S. Charter. 1999. 

Safety and efficacy of 4-aminopyridine in humans with spinal cord injury: A long term, controlled 

trial. Pharmacotherapy 19:713-723.

Spyker, D. A., C. Lynch, J. Shabanowitz, and J. Sinn. 1980. Poisoning with 4-Aminopyridine: 

Report of Three Cases. Clinical Toxicology 16:487-497.

Sultana, P., J. E. Brooks, and R. L. Bruggers. 1986. Repellency and toxicity of bird control 

chemicals to pest birds in Bangladesh. Tropical Pest Management 32:246-248.

USEPA. 2007a. 4-Aminopyridine: HED Chapter of the Reregistration Eligibility Decision 

Document (RED). PC Code: 069201, Case #: 0015, DP Barcode: D336326. August 6, 2007. 

U.S. Environmental Protection Agency.

_____. 2007b. Reregistration Eligibility Decision for 4-aminopyridine. EPA-738-R-07-013. 

September 27, 2007. U.S. Environmental Protection Agency, Prevention, Pesticides, and Toxic 

Substances.

_____. 2016a. 4-aminopyridine (Avitrol): Tier I (Scoping) Review of Human Incidents and 

Epidemiology. May 12., U.S. Environmental Protection Agency.

_____. 2016b. 4-AP: Human Health Scoping Document in Support of Registration Review. Aug. 

4. Docket Number EPA-HQ-OPP-2016-0030-0002. U.S. Environmental Protection Agency.
21

_____. 2016c. Registration Review: Problem Formulation for 4-Aminopyridine (AvitrolTM). United 

States Environmental Protection Agency, Office of Chemical Safety and Pollution Prevention.

_____. 2016d. Registration Review: Problem Formulation for 4-aminopyridine (AvitrolTM). Aug. 

23. Docket Number EPA-HQ-OPP-2016-0030. U.S. Environmental Protection Agency.

_____. 2017a. 4-Aminopyridine (CAS RN 504-24-5). Integrated Risk Information System. in 

U.S. Environmental Protection Agency.

_____. 2017b. 4-aminopyridine Final Work Plan Registration Review, Case Number 0015, 

March 2017, Docket Number EPA-HQ-OPP-2016-0030. U.S. Environmental Protection Agency.

_____. 2017c. Endocrine Disruption. U.S. Environmental Protection Agency.

_____. 2020a. 4-aminopyridine (Avitrol): Draft Ecological Risk Assessment for Registration 

Review, September 17, PC Code: 069201, DP Barcode: 458647. U.S. Environmental Protection 

Agency, Office of Chemical Safety and Pollution Prevention.

_____. 2020b. 4-Aminopyridine Proposed Interim Registration Review Decision, Case Number 

0015. U.S. Environmental Protection Agency.

_____. 2020c. 4-Aminopyridine: Human Health Risk Assessment for Registration Review. 

United States Environmental Protection Agency, Office of Chemical Safety and Pollution 

Prevention.

_____. 2022. Overview of Risk Assessment in the Pesticide Program. U.S. Environmental 

Protection Agency https://www.epa.gov/pesticide-science-and-assessing-pesticiderisks/overview-risk-assessment-pesticide-program Accessed December 22, 2022.

Van Diemen, H. A., C. H. Polman, J. C. Koetsier, A. C. Van Loenen, J. J. Nauta, and F. W. 

Bertelsmann. 1993. 4-aminopyridine in patients with multiple sclerosis: Dosage and serum level 

related to efficacy and safety. Clinical Neuropharmacology 3:195-204.

9 PREPARERS

9.1 APHIS WS Methods Risk Assessment Committee

Writers for “Use of 4-Aminopyridine in Wildlife Damage Management Risk Assessment”:

Primary Writer: Jim Warren 

Position: USDA-APHIS-Policy and Program Development (PPD), Environmental and Risk 

Analysis Services (ERAS), Environmental Toxicologist, Little Rock, AR 

Education: B.S. Forest Ecology and M.S. Entomology – University of Missouri; Ph.D. 

Environmental Toxicology – Clemson University

Experience: Sixteen years of experience working for APHIS preparing ecological risk 

assessments and providing assistance on environmental compliance. Prior experience 

before joining APHIS includes other government and private sector work regarding 

ecological risk assessments related to various environmental regulations.

Primary Writer: Andrea Lemay 
22

Position: USDA-APHIS-Policy and Program Development (PPD), Environmental and Risk 

Analysis Services (ERAS), Biological Scientist, Raleigh, NC

Education: B.S. Plant and Soil Science (Biotechnology) - University of Massachusetts; M.S. 

Plant Pathology - North Carolina State University 

Experience: Fifteen years of service in APHIS conducting risk analysis. Seven years of 

experience in preparing environmental analyses in compliance with the National 

Environmental Policy Act.

Writer: Thomas C. Hall

Position: USDA-APHIS-WS, Operational Support Staff, Staff Wildlife Biologist, Fort Collins, CO

Education: BS Biology (Natural History) and BA Psychology – Fort Lewis College; MS Wildlife 

Ecology – Oklahoma State University

Experience: Special expertise in wildlife biology, identification, ecology, and damage 

management. Thirty-seven years of service in APHIS Wildlife Services including operations 

and research in CO for research and OR, GU, CA, OK, and NV for operations conducting a 

wide variety of programs including bird damage research and management, livestock 

protection (predators and birds), invasive species management, wildlife hazard 

management at airports, property and natural resource protection including waterfowl, 

brown tree snake, feral swine, rodent, and beaver damage management. Researched, 

applied, and supervised the use of 4-AP. 

Editors/Contributors for “Use of 4-Aminopyridine in Wildlife Damage Management Risk 

Assessment”:

Editor/Contributor: Shelagh DeLiberto 

Position: USDA-APHIS-WS Operational Support Staff, Environmental Management 

Coordinator, Fort Collins, CO

Education: BA Biology and Environmental Science – Ithaca College; MS Wildlife Biology –

Colorado State University 

Experience: Nineteen years of service in APHIS conducting wildlife research. Six years of 

experience in preparing categorical exclusions and environmental analyses in compliance 

with the National Environmental Policy Act. 

Editor/Contributor: Michael McCaskill 

Position: USDA-APHIS-Policy and Program Development (PPD), Environmental and Risk 

Analysis Services (ERAS), Toxicologist, New Market, MD

Education: B.S. Environmental Science – University of Florida; MPH Industrial HygieneUniversity of South Carolina, Ph.D. Toxicology-Florida Agriculture and Mechanical 

University

Experience: Ten years of experience conducting human toxicological research at Florida 

Agriculture and Mechanical University, University of Nebraska Medical Center, and Tulane 

University. Four years of experience conducting human health and environmental 

toxicological risk assessments and assisting environmental compliance programs at the 

Florida Department of Health, Commonwealth of Pennsylvania, and USDA.

Editor/Contributor: Emily Ruell 

Position: USDA-APHIS-WS, NWRC, Registration Specialist, Fort Collins, CO

Education: B.S. Zoology and Biological Aspects of Conservation – University of Wisconsin -

Madison; M.S. Ecology – Colorado State University (CSU); M.A. Political Science – CSU
23

Experience: Nine years of experience with WS NWRC preparing and reviewing vertebrate 

pesticide registration data submissions and other registration materials and providing 

pesticide regulatory guidance to WS, WS NWRC, and collaborators. Prior experience 

before joining APHIS includes seven years of conducting field and laboratory wildlife 

research at CSU and environmental policy research for the U.S. Geological Survey.

Editor: Ryan Wimberly 

Position: USDA-APHIS-WS, Operational Support Staff, Staff Wildlife Biologist, Madison, TN

Education: BS Wildlife Management and Ecology – Northwest Missouri State University

Experience: Special expertise in wildlife biology, ecology, and damage management. 

Seventeen years of service with APHIS Wildlife Services, including operations and research, 

conducting a wide variety of programs, including bird damage research and management, 

livestock protection, invasive species management, wildlife hazard management at airports, 

property and natural resource protection. Expert in preparing environmental documents for 

WS programs to comply with the National Environmental Policy Act and the Endangered 

Species Act.

9.2 Internal Reviewers 

Reviewer: David Marks

Position: USDA-APHIS-WS, Assistant State Director, Missouri and Iowa

Education: BS in Wildlife Biology and MS in Environmental Science and Policy, University of 

Wisconsin Green Bay

Experience: Twenty years experience with APHIS Wildlife Services in Wisconsin, Michigan, 

and Iowa. Specialized experience in all levels of WS Operations, including pesticide use, 

NEPA, FOIA, ESA, predator control, feral swine damage management, wildlife hazards at 

airports, wildlife disease sampling, invasive reptiles, and urban wildlife damage. Pesticide 

experience mostly with avian species including pigeons, European starlings, and house 

sparrows using DRC-1339 and Avitrol.

Reviewer: Joshua A. Janicke

Position: USDA-APHIS-WS, Wildlife Biologist, Concord, NH

Education: BS Wildlife Management, University of New Hampshire

Experience: Twenty-five years of service with USDA-APHIS-Wildlife Services in New 

Hampshire. Experience includes urban wildlife damage management, wildlife hazards at 

airports, wildlife disease sampling, invasive species control, controlled material inventory 

tracking, restricted-use pesticides, NEPA and ESA. Supervisory pesticide applicator 

license holder in NH. Train WS-NH employees on procedures for use of DRC-1339 and 

Avitrol within NH. Conducted bait efficacy trials for pesticide work with blackbirds in sweet 

corn fields. Experience with DRC-1339 to control damage caused by European starlings 

and Red-winged blackbirds. Experience with Avitrol to control damage caused by redwinged blackbirds.

Reviewer: John Cummings

Position: EDM International Inc, Wildlife Biologist, Fort Collins, CO. Retired Wildlife Biologist 

from USDA National Wildlife Research Center, Fort Collins, CO

Education: B.S. in Wildlife Biology (Research), Colorado State University. Completed 

Ornithology graduate courses. Colorado State University.

Experience: At the National Wildlife Research Center, as a research biologist and project 

leader, was responsible for research leadership and supervision for projects addressing 

agriculture crop depredations from birds, bird hazards to aircraft, predation on endangered 
24

and threatened species and bird ecology. Was involved in developing Avitrol as a bird 

frightening agent for agriculture crops, specifically sunflowers and DRC-1339 for staging 

area baiting. The research was designed to provide an ecological understanding of bird 

species, develop management tools, improve existing management techniques and provide 

sound data in support of the Environmental Protection Agency registration issues. Since 

2014, worked on a variety of projects with Southern California Edison, PPL/PSEG, 

Rockwood Lithium, Xcel Energy, Alabama Power, PNM New Mexico, National Park Service 

and state wildlife agencies. Projects ranged from developing and evaluating wildlife 

deterrent tools, developing wildlife mitigation plans, avian protection plans, impact analysis 

of aircraft on wildlife, telemetry of bald eagles, raptor monitoring and development of 

repellent tools for woodpecker damage to utility poles. A Certified Wildlife Biologist and a 

Certified Airport Wildlife Biologist.

9.3 Peer Review

The Office of Management and Budget requires agencies to have peer review guidelines for 

scientific documents. The APHIS guidelines were followed to have “Use of Carcass Disposal

in Wildlife Damage Management” peer reviewed. WS worked with the Association of Fish and 

Wildlife Agencies to have experts review the documents.

9.3.1 Peer Reviewers Selected by the Association of Fish and Wildlife Agencies

South Dakota Game, Fish and Parks

Louisiana Department of Wildlife and Fisheries

Michigan Department of Natural Resources

9.3.2 Comments

1. I found 1 typographical error. P.10 3.2.2.2, the paragraph above the table denotes 

“morning dove” instead of “mourning dove.”

Response: We have corrected this error.

2. While it is useful and appreciated that the risk assessment provided exposure 

information in non-target species from the ASPCA Animal Poison Control Center 

database and the USEPA Ecological Incident Data System, it would be beneficial to 

include information from state wildlife agencies that perform necropsies and ancillary 

diagnostic testing such as toxicology. State veterinary diagnostic laboratories with a 

toxicology service will also have useful results that could be included in future risk 

assessments. Collectively, this will capture more information about exposure and 

toxicosis in free-ranging wildlife species.

Response: We appreciate this comment and agree that results from state veterinary 

diagnostic laboratories may be informative regarding exposure of 4-aminopyridine to 

free-ranging wildlife species. However, state veterinary diagnostic laboratory testing 

results are not readily available without contacting individual laboratories for such data. 

In addition, the Risk Assessment covers WS use and risk associated with the use of 4-
25

Aminopyridine, not the use of the product by the general public or other pesticide 

applicators. We provide the ASPCA Animal Poison Center and USEPA Ecological 

Incident Data System exposure information as a comparison to the exposure due to use 

by WS. 

Comments received not requiring a response.

1. This document provides thorough coverage of the use of 4-Aminopyridine (Avitrol) in 

Wildlife Damage Management. We have no comments except to say we appreciate the 

opportunity to participate in the review process.

2. The document was thorough and fully informative, addressing all aspects of my concern 

including but not limited to: toxicity to non-target bird species, toxicity to scavengers and 

predators of poisoned birds, human toxicity, environmental toxicity, and past accidental 

exposure histories.

3. Due to the small amount of use of this product, I see it of little impact to the overall 

health and well-being of wildlife. Additionally, the product is a very useful tool to have in 

situations where large flocks of birds can cause agricultural damage or threaten human 

life. 

4. The authors explained the methodology of efficient use very well. This concise 

explanation should lead to good results with the product while ameliorating negative 

effects. In addition, the authors explained assumptions and limitations of the product as 

well.

5. The methodologies of application protect the user, non-target mammalian species, and 

amplify the non-lethal frightening effect of the bait.

6. The references seemed complete and supported many facets of the document.

7. The risk assessment provided information on the purpose and consequences of using 

Avitrol. This product is a restricted use pesticide utilized to control flocking pest birds 

such as passerines and corvids as a poison with flock alarming properties. It is lethal to 

most all birds that ingest treated baits, resulting in seizures/ convulsions/ hyperactivity, 

cardiac and respiratory arrest. The use pattern is clearly defined and includes allowing 

only certified applicators to use the product, bait trays, occupational workers remaining 

on site during the application period and post-treatment cleanup (e.g., removing unused 

bait and dead or dying birds) and proper disposal of carcasses. The standard operating 

procedures and mitigations to prevent adverse impacts are defined and include prebaiting to ensure target species take the bait and nontarget species are not present, and 

in-person monitoring of the site to reduce the potential for primary and secondary 

poisoning of nontarget birds and other animals. Assumptions and uncertainties are 

stated in the risk assessment, such as the expectation that target birds that ingest Avitrol 

baits will die but recognizing that some birds will display neurological signs and may be 

at increased risk of predation. The assessment also acknowledges that there are 

uncertainties due to a lack of recent scientific studies regarding the effects of Avitrol, 

effects of co-occurring toxic exposures, and cumulative or repeated impacts to people 

and animals. The selection of references in the risk assessment seemed appropriate. 
26

Appendix 1. Additional 4-Aminopyridine Use Data.

Additional data is given for FY11 through FY15 because of the limited use of Avitrol products. 

Generally, for the risk assessments, only five years are summarized. The data for the two fiveyear time spans was similar, except that four products (Table A1) were used from FY11 to 

FY15, and more starlings were targeted during projects (Table A2). Additionally, brown-headed 

cowbirds were targeted but apparently left the area, so the treatment was not successful. In 

FY16–FY20, red-winged blackbirds were targeted (Table 3) but were not during FY11–FY15 

(Table A-2). It should be noted that birds hazed may not necessarily be documented and cannot 

be estimated.

Table 1a. Avitrol labels used by WS in WDM from FY11 to FY15, the annual average target 

species killed and repelled, the amount of product used, and the states where used.

Table 1b. The annual average number of target species killed and repelled with Avitrol products 

used by WS in WDM from FY11 to FY15. 

ANNUAL AVERAGE 4-AP PRODUCT USE AND SPECIES TAKE

Species* Killed Repelled Oz. Used States Where Used

Rock Dove (Feral Pigeon)* 24 7 39.6 MA OR TX

European Starling* 1,137 2,682 75.8 KY MA MD OR TN VA

House Sparrow* 1,880 62 104.3 IL MA NC OK OR TN TX 

VA WA

Brown-headed Cowbird 0 0 1.2 VA

TOTAL (4 sp.) 3,041 2,751 220.9 11 States

* Introduced species

ANNUAL AVERAGE 4-AP PRODUCT USE BY WS

Product EPA 

Registration No. Killed Repelled Oz. 

Applied States

Avitrol Mixed Grains

(0.5%)

11649-4 2,226 2,455 138.6 MA MD NC OR TN 

TX VA

Avitrol Double Strength 

Corn Chops (1.0%)

11649-5

0.2

2 11.2 MA

Avitrol Corn Chops 

(0 5%)

11649-6 811 287 50.7 IL KY MA OK TN WA

Avitrol Whole Corn 

(0 5%)

11649-7 4 7 20.4 MA

TOTAL 4 Products 

Used 3,041 2,751 220.9 11 States