MULTIPLE SCLEROSIS -
4AP TOXICITY DATA

E X T O X N E T  -  Extension Toxicology Network

A Pesticide Information Project of Cooperative Extension Offices of Cornell University, Oregon State University, the University of Idaho, and the University of California at Davis and the Institute for Environmental Toxicology, Michigan State University. Major support and funding was provided by the USDA/Extension Service/National Agricultural Pesticide Impact Assessment Program.

E X T O X N E T primary files maintained and archived at Oregon State University

Revised June 1996

Trade and Other Names: Common names include 4-AP, P-aminopyridine, Gamma-aminopyridine, Amino-4-pyridine. Trade names include Avitroland and Avitrol 200.

Regulatory Status: Based on its potential hazard to fish and non-target birds, some 4-aminopyridine formulations are classified by the U.S. Environmental Protection Agency (EPA) as Restricted Use Pesticides (RUPs). RUPs may be purchased and used only by certified applicators. Grain bait formulations of 4-aminopyridine are in toxicity class III and must bear the signal word CAUTION and powder concentrate formulations are in toxicity class I and must bear the signal word DANGER.

Chemical Class: pyridine compound

Introduction: 4-Aminopyridine, a pyridine compound, is an extremely effective bird poison. It is one of the most prominent avicides. It is registered with the EPA for use against red-winged blackbirds, blackbirds in agricultural fields, grackles, pigeons, and sparrows around public buildings, and various birds around livestock feeding pens. Avitrol repels birds by poisoning a few members of a flock, causing them to become hyperactive. Their distress calls signal other birds to leave the site. Only a small number of birds need to be affected to cause alarm in the rest of the flock. After one alarming exposure, birds will usually not return to treated areas. Avitrol is available as grain baits or as a powder concentrate.

Formulation: Avitrol is available as grain baits or as a powder concentrate.

Toxicological Effects: Acute toxicity: 4-Aminopyridine is highly toxic to mammals. The central nervous system is strongly excited by 4-aminopyridine. Based on observations with 2-aminopyridine, a similar compound, individuals with a history of convulsive disorders may be at an increased risk from exposure to 4-aminopyridine [30,31]. The principal action of 4-aminopyridine in the body is to encourage message-carrying (transmitter) substances to be released throughout the nervous system, overstimulating it [68]. While intended strictly for use as a bird repellent, accidental ingestion of as little as 60 mg has caused severe poisoning in adult humans [68]. It is rapidly absorbed from the gastrointestinal tract [8]. Poisonings are characterized by thirst, nausea, dizziness, weakness, and intense sweating, followed by impairment of normal mental functioning (toxic psychosis), lack of muscular coordination, tremors, labored breathing, and generalized seizures [167]. Symptoms of Avitrol poisoning in rats, dogs, and horses include over-production of saliva, tendency to become over-stimulated, and trembling, which can progress to convulsions. Death can result from respiratory arrest or heart failure [23,30]. Skin exposure to Avitrol may lead to systemic intoxication or general overall poisoning [30]. Avitrol may contribute to the excessive formation of a substance called methemoglobin. Methemoglobin is similar to hemoglobin, the oxygen-carrying part of the blood, except that it cannot carry oxygen. When there is excess methemoglobin in the blood, oxygen cannot be transported and blood eventually becomes oxygen depleted, resulting in the condition methemoglobinemia. The LD50 for 4-aminopyridine is 20 to 29 mg/kg in rats, and is 3.7 mg/kg in dogs [8,167]. It is readily absorbed through the skin [23]. The dermal LD50 is 326 mg/kg in rabbits [23,30]. 4-Aminopyridine is an eye irritant. Inflammation of the iris and conjunctivitis were noted in the eyes of albino rabbits 1 hour after 10 mg of 4-aminopyridine hydrochloride were applied. These symptoms disappeared after 7 days [167].
Chronic toxicity: High dietary doses (2 to 3.25 mg/kg/day) caused increased brain weight. Brain appearance remained normal [167]. However, since dietary intake is assumed to be negligible, and because significant repeated exposure is not expected to occur, EPA has not required long-term toxicity studies of 4-aminopyridine [167].
Reproductive effects: No data are currently available.
Teratogenic effects: No data are currently available.
Mutagenic effects: No data are currently available.
Carcinogenic effects: No data are currently available.
Organ toxicity: Chronic exposure to 4-aminopyridine can cause the breakdown of proper liver and brain functioning [8]. No effects were found in the blood and urine of rats and dogs.
Fate in humans and animals: 4-Aminopyridine is rapidly absorbed into the bloodstream from the gastrointestinal tract [8]. It is readily broken down, or metabolized, in the liver into removable compounds excreted in urine [30]. After intravenous and oral doses were given to humans, 90.6% and 88.5% was excreted in the urine [167]. It does not to concentrate or accumulate in skin. Birds killed with Aritrol are not poisonous to predators [8,30].
 

Ecological Effects:  Effects on birds: 4-Aminopyridine is highly toxic to birds. The 8-day dietary LC50 is 447 ppm in Japanese quail, 316 ppm in mourning doves, and 722 ppm in mallard ducks [167]. Avian reproduction studies suggest ingestion of sublethal amounts of 4-aminopyridine is unlikely to cause negative effects on birds' reproductive systems [8]. There is a large potential for exposure of non-target, particularly grain-feeding birds. Migratory birds, finches, and other small seed-feeding birds may ingest lethal doses that are applied to corn and sunflower fields.

Effects on aquatic organisms: 4-Aminopyridine is moderately toxic to warmwater fish. Fish become increasingly sensitive with increased exposure [167]. The LC50 ranges from 4 mg/L (in soft water) to 2.43 mg/L (in hard water) in channel catfish. The LC50 in is 3.40 mg/L (in soft water) to 3.20 mg/L (hard water) in bluegill [37].
Effects on other organisms: Endangered species may be adversely affected by 4-aminopyridine [167]. There is low or nonexistent potential for secondary poisoning in animals such as cats, dogs, or birds of prey that may feed upon birds killed by Avitrol [167].
Environmental Fate:

Breakdown in soil and groundwater: 4-Aminopyridine is readily adsorbed to soil particles and is highly persistent [167]. It is broken down slowly by soil microorganisms. It is more likely to remain near the soil surface where most microbial degradation tends to occur [167]. The half-life of 4-aminopyridine in soil with oxygen ranges from 3 months in clay soil to 32 months in sandy-loam soils. The rate at which 4-aminopyridine is metabolized in aerobic soil increases with greater amounts of organic matter [167]. Studies indicate that 4-aminopyridine is relatively immobile in soils. It is not expected to be present in groundwater as a result of its use on land [167].
Breakdown in water: 4-Aminopyridine is not expected to be present in surface water as a result of land application of formulated products [167].

Breakdown in vegetation: Available plant metabolism data on sorghum indicate that some breakdown of 4-aminopyridine does occur, with three breakdown products; however, no metabolites were found in corn. 4-Aminopyridine is absorbed and moved from one part of a plant to another to varying degrees, depending on the manner in which it is applied. Plant uptake of 4-AP is not expected to be significant in corn and sunflowers [167].
Physical Properties:

Appearance: Technical 4-aminopyridine is a white crystalline solid that contains about 98% active ingredient [8].
Chemical Name: 4-aminopyridine [31]
CAS Number: 504-24-5
Molecular Weight: 94.13
Water Solubility: Soluble [31]
Solubility in Other Solvents: s.s. in benzene and ether [31]
Melting Point: 158 C [31]
Vapor Pressure: Not Available
Partition Coefficient: Not Available
Adsorption Coefficient: Not Available
Exposure Guidelines:

ADI: Not Available
MCL: Not Available
RfD: 0.00002 mg/kg/day [13]
PEL: Not Available
HA: Not Available
TLV: Not Available
Basic Manufacturer:

Avitrol Corporation
7644 East 46th St.
Tulsa, OK 74145

Phone: 918-622-7763
Emergency: Not Available

References:  References for the information on this page can be found in Reference List Number 10