4-aminopyridine

This chemical does not meet GHS hazard criteria for 1.2% (1 of 82) of reports.

H300 (98.8%): Fatal if swallowed [Danger Acute toxicity, oral]

H311 (18.3%): Toxic in contact with skin [Danger Acute toxicity, dermal]

H315 (87.8%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (89%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (82.9%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

H411 (26.8%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P261, P262, P264, P264+P265, P270, P271, P273, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P316, P319, P321, P330, P332+P317, P337+P317, P361+P364, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 82 reports by companies from 16 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 1 of 82 reports by companies.

There are 15 notifications provided by 81 of 82 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

H401: Toxic to aquatic life [Hazardous to the aquatic environment, acute hazard]

H411: Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P273, P391, and P501 (click each P-code to see the statement)

H300: Fatal if swallowed [Danger Acute toxicity, oral]

H311: Toxic in contact with skin [Danger Acute toxicity, dermal]

H370: Causes damage to organs [Danger Specific target organ toxicity, single exposure]

H372: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

P260, P262, P264, P270, P280, P301+P316, P302+P352, P308+P316, P316, P319, P321, P330, P361+P364, P405, and P501 (click each P-code to see the statement)

Warning: Ingestion of as little as 0.6 mg/kg may produce toxic symptoms that require hospitalization.

Signs and Symptoms of Pyridine, 4-Amino- Exposure: Signs and symptoms of acute exposure to pyridine, 4-amino- may include intense perspiration, weakness, dizziness, disorientation, and thirst followed by psychotic-like behavior, tremors, dyspnea (difficult or labored breathing) and seizures. Cardiac arrhythmia and respiratory arrest may be noted. Gastrointestinal effects include disagreeable taste, immediate burning of the throat associated with abdominal discomfort, nausea, and metabolic acidosis.

Emergency Life-Support Procedures: Acute exposure to pyridine, 4-amino- may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination.

Inhalation Exposure:

1. Move victims to fresh air. Emergency personnel should avoid self-exposure to pyridine, 4-amino-.

2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support.

3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures.

4. Rush to a health care facility.

Dermal/Eye Exposure:

1. Remove victims from exposure. Emergency personnel should avoid self-exposure to pyridine, 4-amino-.

3. Remove and isolate contaminated clothing as soon as possible.

4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes.

5. Wash exposed skin areas thoroughly with soap and water.

6. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures.

7. Rush to a health care facility.

Ingestion Exposure:

1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support.

2. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures.

3. Vomiting may be induced with syrup of Ipecac. If elapsed time since ingestion of pyridine, 4-amino- is unknown or suspected to be greater than 30 minutes, do not induce vomiting and proceed to Step

4. Ipecac should not be administered to children under 6 months of age.Warning: ingestion of pyridine, 4-amino- may result in sudden onset of seizures or loss of consciousness. Syrup of Ipecac should be administered only if victims are alert, have an active gag-reflex, and show no signs of impending seizure or coma. If ANY uncertainty exists, proceed to Step

4.The following dosages of Ipecac are recommended: children up to 1 year old, 10 mL (1/3 oz); children 1 to 12 years old, 15 mL (1/2 oz); adults, 30 ml (1 oz). Ambulate (walk) the victims and give large quantities of water. If vomiting has not occurred after 15 minutes, Ipecac may be readministered. Continue to ambulate and give water to the victims. If vomiting has not occurred within 15 minutes after second administration of Ipecac, administer activated charcoal.

4. Activated charcoal may be administered if victims are conscious and alert. Use 15 to 30 g (1/2 to 1 oz) for children, 50 to 100 g (1-3/4 to 3-1/2 oz) for adults, with 125 to 250 mL (1/2 to 1 cup) of water.

5. Promote excretion by administering a saline cathartic or sorbitol to conscious and alert victims. Children requires 15 to 30 g (1/2 to 1 oz) of cathartic; 30 to 100 g (1 to 3-1/2 oz) is recommended for adults.

6. Rush to a health care facility. (EPA, 1998)

Wear positive pressure self-contained breathing apparatus and special protective clothing. Move container from fire area if you can do so without risk. Fight fire from maximum distance possible. Control runoff water with dikes and prevent material from scattering.

The material may burn but will not ignite easily. To extinguish use dry chemical, carbon dioxide, water spray, fog, or foam. (EPA, 1998)

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special protective equipment for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

If material on fire or involved in fire: Extinguish fire using agent suitable for type of surrounding fire. (Material itself does not burn or burns with difficulty.) Use water in flooding quantities as fog. Use foam, dry chemical, or carbon dioxide. Keep run-off water out of sewers and water sources. /Aminopyridines/

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.

SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.

FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

Personal precautions: Wear respiratory protection. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number P008, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. /Aminopyridines/

Personnel protection: Avoid breathing dusts, and fumes from burning material. Keep upwind. ... Avoid bodily contact with the material. ... Do not handle broken packages unless wearing appropriate personal protective equipment. /Aminopyridines/

Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.

For more Preventive Measures (Complete) data for 4-AMINOPYRIDINE (6 total), please visit the HSDB record page.

Keep unnecessary people away; isolate the hazardous area and deny entry. Stay upwind. Do not touch spilled material; stop leak if possible without risk. Use water spray to reduce vapors.

Small spills: absorb with sand or other noncombustible absorbent material and place into containers for later disposal.

Small dry spills: with clean shovel place material into clean, dry container and cover; move containers from spill area.

Large spills: dike far ahead of spill for later disposal. (EPA, 1998)

Keep container tightly closed in a dry and well-ventilated place.

0.063 [mg/m3]

0.69 [mg/m3]

4.2 [mg/m3]

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

Approved respirator. Chemical-resistant gloves. long-sleeved shirt and long pants.

Depending on the extent of possible contact, workers should be provided with personal protective equipment. A charcoal gas mask canister respirator has been found to be effective against a 2% pyridine concentration at 30 l/min for 1 hr. Rubber and plastic gloves should not be relied upon to prevent skin contact because pyridine and many of its derivatives penetrate these materials ... . /Pyridine, homologs, and derivatives/

Hand protection: Handle with gloves.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

For more Personal Protective Equipment (PPE) (Complete) data for 4-AMINOPYRIDINE (6 total), please visit the HSDB record page.

Pyridine, 4-amino- is a white crystalline material with no odor. Used as an avicide, an intermediate and as a fixer for some textile dyes. (EPA, 1998) It has been approved by the FDA for use as a treatment for multiple sclerosis.

White crystals; [CAMEO] Formulated as grain bait or powder concentrate; [EXTOXNET]

White crystalline material with no odor.

White crystals

Crystals

Fine white powder

Needles from benzene

Odorless

524.3 °F at 760 mmHg (EPA, 1998)

524.3 °F

273 °C @760 [mm Hg]

318 °F (EPA, 1998)

157-161°C

159.0 °C

604.4 °F

328 °F (USCG, 1999)

In water, 112 g/L at 20 °C

Soluble in ethyl ether, benzene; slightly soluble in ligroin; very soluble in ethanol

Soluble in oxygenated solvents

Soluble in methanol, acetone, tetrahydrofuran, isopropanol, acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, and ethanol

1.2607 at 77.54 °F (USCG, 1999) - Denser than water; will sink

0.00034 [mmHg]

2.09X10-4 mm Hg at 20 °C

0.0003 [mm Hg] @25 °C

log Kow = 0.32

Stable under recommended storage conditions.

Stable to light.

When heated to decomposition it emits toxic fumes of /nitrogen oxides/.

Positive

Agilent XCT

Electrospray ionization

formic acid (5.3nM)

MeCN (80%)

DOI:10.1038/s41598-020-62573-z

pKa = 9.17

117.8 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

111.77 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Stable to light

Crystal structure

Formula unit

No rapid reaction with air. No rapid reaction with water.

Amines, Phosphines, and Pyridines

PYRIDINE, 4-AMINO- neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides.

Strong oxidizing agents, Strong acids, Acid chlorides, Acid anhydrides

4-Aminopyridine blocks potassium channels and thereby increases acetylcholine, and possibly noradrenaline, release at nerve terminals (A316). In MS, axons are progressively demyelinated which exposes potassium channels. As a result, there is a leak of potassium ions which results in the repolarization of cells and a decrease in neuronal excitability. The overall impact is the impairment of neuromuscular transmission as it is harder to trigger an action potential.

Dalfampridine inhibits voltage-gated potassium channels in the CNS to maintain the transmembrane potential and prolong action potential. In other words, dalfampridine works to make sure that the current available is high enough to stimulate conduction in demyelinated axons that are exposed in MS patients. Furthermore, it facilitates neuromuscular and synaptic transmission by relieving conduction blocks in demyelinated axons.

4-Aminopyridine

Dalfampridine has been associated with infrequent serum aminotransferase elevations during therapy and has not been convincingly linked to instances of clinically apparent liver injury. In analyses of safety of dalfampridine in pre-registration controlled trials with 1922 patients with multiple sclerosis, there were no reports of hepatic injury or laboratory evidence of a hepatotoxicity signal. Among a few instances of clinically apparent liver injury in patients receiving dalfampridine have appeared in the published literature, in each instance attribution to dalfampridine was not convincing. In large registries of patients taking dalfampridine, hepatic adverse events have not been reported. Finally, in large prospectively collected registries of drug-induced liver injury, there have been no cases attributed to dalfampridine or other formulations of fampridine.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Drug Induced Liver Injury Rank (DILIrank 2.0)

Dalfampridine

vNo-DILI-concern

No match

DOI:10.1016/j.drudis.2016.02.015

Cancer Classification: Group D Not Classifiable as to Human Carcinogenicity

CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR CLASSIFICATION: No human data and no animal data available. HUMAN CARCINOGENICITY DATA: None.

No indication of carcinogenicity to humans (not listed by IARC).

Conditions associated with overdose have included parasthesias, seizures, and atrial fibrillation. Human systemic effects by ingestion include hallucinations and distorted perceptions, and dyspnea (L1082).

◉ Summary of Use during Lactation

Because no information is available on the use of dalfampridine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Inhalation (T52, T14) ; oral (T52, T14) ; dermal (T52, T14) ; intravenous (T52, T14)

Orally-administered dalfampridine is rapidly and completely absorbed from the gastrointestinal tract.

Tmax, immediate release form = 1 hour;

Tmax, extended release form = 3.5 hours;

Cmax, 10 mg extended release = 17.3 - 21.6 ng/mL;

Relative bioavailability of 10 mg extended-release tablets compared to aqueous oral solution = 96%

Local irritation on contact with the skin, mucous membranes and cornea. Symptoms floowing ingestion include vomiting, Weakness, dizziness, disorientation, hyperexcitability, tremors, periorbital paresthesias and tonic-clonic seizures may be noted (T36, T52, T14).

Neurotoxin - Other CNS neurotoxin

Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect

Dermatotoxin - Skin burns.

PDF Document

See the IRIS entry for 4-Aminopyridine

HEAST Archive

LD50, oral, mouse = 19 mg/kg

LD50, oral, rat = 21 mg/kg

LD50: 20-29 mg/kg (Oral, Rat) (L1090)

LD50: 3.7 mg/kg (Oral, Dog) (L1090)

LD50: 326 mg/kg (Dermal, Rabbit) (L1090)

LD50 Dog oral 3.7 mg/kg

LD50 Rat oral (males) 14 mg/kg

LD50 Mouse oral 50 mg/kg

LD50 Rat oral (females) 22 mg/kg

For more Non-Human Toxicity Values (Complete) data for 4-AMINOPYRIDINE (12 total), please visit the HSDB record page.

Administer charcoal as a slurry. Consider gastric lavage after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in Trendelenburg and left lateral decubitus position or by endotracheal intubation. Control any seizures first. Following inhalation, move patient to fresh air and monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. In case of eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If the exposure occurs through dermal exposure, remove contaminated clothing and wash exposed area thoroughly with soap and water. (T36)

The depressant effects of morphine (0.1-1 uM) on sensory-evoked dorsal-horn network responses in explants of mouse spinal cord with attached dorsal root ganglia (DRGs) were rapidly restored after addition of 4-aminopyridine (4-AP; 0.1 mM) and major components of these cord responses were stably maintained in the presence of the opiate. Moreover, prior exposure of cord-DRG explants to 0.1 mM 4-AP prevented the depressant effects of 0.1 uM morphine on DRG-evoked dorsal-horn responses, and the effects of 1-10 uM morphine were at least partly antagonized. Increased Ca++ levels (5 uM) attenuated the depression of dorsal horn responses by 1-10 uM morphine and these effects of Ca++ were greatly enhanced in the presence of 4-AP--in some cultures, concentrations of morphine as high as 100 uM were strongly antagonized during test periods up to 2 hours. Receptor assays showed that 0.1 mM 4-AP +/- 5 mM Ca++ had no effect on stereospecific opiate binding, indicating that the antagonist actions of these agents in our cultures do not occur at the level of the opiate receptor. The relevance of our in vitro studies of 4-AP antagonism of opiate-depressant effects on sensory-evoked dorsal-horn network responses for analyses of problems in opiate analgesia has been strengthened by a recent report demonstrating that 4-AP does, in fact, reverse morphine analgesia in rats, as determined by tail flick tests.

The treatment of verapamil toxicity was examined in lightly sedated dogs. Verapamil, administered as a bolus (0.72 mg/kg) followed by a continuous infusion (0.11 mg/kg/min), decreased cardiac output (CO) ... heart rate (HR) ... left ventricular derivative of pressure with respect to time (LV dP/dt) ... mean aortic pressure (AO) ... and stroke volume. ... 4-Aminopyridine (4-AP) increased heart rate, cardiac output, LV dP/dt, and mean aortic pressure. When administered prior to verapamil, 4-AP prevented the development of verapamil toxicity as shown by the significantly higher mean aortic pressure (P less than 0.001), cardiac output (P less than 0.01), and LV dP/dt (P less than 0.01) when 4-AP followed by verapamil was compared to verapamil alone. In conclusion, there does not appear to be a single specific therapy for verapamil toxicity, however it can be partially correctedly presently available pharmacologic therapy and 4-AP.

Because of increased risk of dose-related adverse effects, dalfampridine should not be used in patients receiving other aminopyridines, including extemporaneously prepared formulations; dalfampridine formerly was known as fampridine (4-aminopyridine, 4-AP). Prior to initiation of dalfampridine therapy, any product containing fampridine or 4-aminopyridine should be discontinued, since the active ingredient is the same.

Pancuronium is a pharmacologic antidote and is recommended in severely poisoned human patients. Propranolol appears to block some of the cardiac toxicity (such as cardiac arrhythmias) of 4-aminopyridine. Seizures can be treated with diazepam. In severe cases, phenobarbital or phenytoin can be given, if no response to diazepam. In case of avitrol ingestion, general symptomatic and supportive treatment includes emesis, gastric lavage, activated charcoal, and cathartic sodium thiosulfate. Bicarbonate should be added tot he fluids to treat acidosis.

Skin decontamination: If skin or eye contamination has occurred, thorough washing of the skin or eyes is indicated. Gastrointestinal decontamination: If the patient is seen within an hour of ingestion of a significant quantity of this compound, gastrointestinal decontamination should be considered, ... . If treatment is delayed, immediate oral administration of charcoal and sorbitol may represent reasonable management. Seizures may require anticonvulsant medication. Muscular spasms: Neuromuscular blockade with drugs such as d-tubocuarine, metocurine and pancuronium bromide have been used successfully to relieve the muscular spasms that occur with this agent. Such therapy must be provided in an intensive care setting. Dehydration should be treated with intravenous fluids if oral fluids cannot be retained.

Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Aromatic hydrocarbons and related compounds/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Aromatic hydrocarbons and related compounds/

LD50; Species: /Anas platyrhynchos/ (Mallard) male, age 3-4 mos; oral 4.36 mg/kg (95% confidence limits: 3.36 - 5.66 mg/kg)

LD50; Species: /Anas platyrhynchos/ (Mallard) male, age 3-4 mos; oral 5.19 mg/kg (95% confidence limits: 4.00 - 6.73 mg/kg)

LC50; Species: Coturnix coturnix (Quail) adult, captive breeding colony; chemical incorporated into food 479 ppm for 28 days (95% confidence interval: 354-645 ppm)

LC50; Species: Coturnix coturnix (Quail) adult, captive breeding colony; chemical incorporated into food >316 ppm for 40 days

For more Ecotoxicity Values (Complete) data for 4-AMINOPYRIDINE (26 total), please visit the HSDB record page.

/BIRDS and MAMMALS/ ... Non-target species including mammals are equally sensitive to the toxicity of avitrol. In mammals, avitrol produces symptoms like epileptic seizures. Doses near LD50 exert a usual sequence of symptoms including hyperexcitability, salivation, tremors, muscle incoordination, convulsion, and cardiac and respiratory failure. Most of these symptoms are associated with hypercholinergic activity. In general, onset of signs occurs within 10-15 min and death occurs within 15 min to 4 hr. ... Predators such as raptors, foxes, hawks, cats and dogs die from secondary poisoning after feeding on the dead or dying birds. Secondary poisoning has also been found in endangered birds, including red-tailed hawks and peregrine falcons, as they died by ingesting the remains of pigeons and other birds poisoned with avitrol.

4-Aminopyridine's production and use as a chemical intermediate for pharmaceuticals and agrochemicals may result in its release to the environment through various waste streams; its use as a bird repellent and avicide will result in its direct release to the environment. If released to air, a vapor pressure of 2.09X10-4 mm Hg at 20 °C indicates 4-aminopyridine will exist solely as a vapor in the ambient atmosphere. Vapor-phase 4-aminopyridine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 19 hrs. 4-Aminopyridine absorbs UV light above 290 nm, but it is reported to be stable to direct photolysis. If released to soil, 4-aminopyridine is expected to have very high mobility based upon an estimated Koc of 39. The pKa of 4-aminopyridine is 9.17, indicating that this compound will exist predominantly in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. In addition, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group, suggesting that mobility may be much lower in some soils. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 2.3X10-10 atm-cu m/mole. Although 4-aminopyridine's vapor pressure suggests volatilization from dry soil surfaces will not be an important fate process, a screening study using sterilized soil measured a 14.9% loss of 4-aminopyridine to volatilization over a 64-day observation period. Aerobic and anaerobic degradation occurs very slowly in soil. Aerobic biotic half-lives of 4-aminopyridine in soil are reported to range between 3 and 32 months. If released into water, 4-aminopyridine is not expected to adsorb to suspended solids and sediment in water based upon the estimated Koc. However, 4-aminopyridine cations and reactivity of the amino group may result in some aquatic adsorption. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. A measured BCF range of <0.2-7.2 in carp (Cyprinus carpio) suggests bioconcentration in aquatic organisms is low. 4-Aminopyridine is expected to be stable to hydrolysis under environmental conditions. Available data indicates biodegradation in water is slow. Sensitized photo-oxidation may occur in shallow natural waters exposed to sunlight with a half-life on the order of one month. Occupational exposure to 4-aminopyridine may occur through inhalation and dermal contact with this compound at workplaces where 4-aminopyridine is produced or used. The general population may be exposed through dermal contact with bird repellent products containing 4-aminopyridine. Small children and toddlers could accidentally ingest treated granules when 4-aminopyridine is applied in residential or public areas. 4-Aminopyridine's use as a drug in treatment of multiple sclerosis results in a limited population direct exposure through ingestion. (SRC)

4-Aminopyridine's production and use as a chemical intermediate for pharmaceuticals and agrochemicals(1) may result in its release to the environment through various waste streams; its use as a bird repellent and avicide(2) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 39(SRC), determined from a structure estimation method(2), indicates that 4-aminopyridine is expected to have very high mobility in soil(SRC). The pKa of 4-aminopyridine is 9.17(3), indicating that this compound will exist predominantly in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). In addition, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(5,6), suggesting that mobility may be much lower in some soils(SRC). Volatilization of 4-aminopyridine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.3X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 2.09X10-4 mm Hg(7), and water solubility, 1.12X10+5 mg/L(7). Although 4-aminopyridine's vapor pressure suggests volatilization from dry soil surfaces will not be an important fate process(SRC), a screening study using sterilized soil measured a 14.9% loss of 4-aminopyridine to volatilization over a 64-day observation period(8). Aerobic and anaerobic degradation occurs very slowly in soil(8,9). Aerobic biotic half-lives of 4-aminopyridine in soil are reported to range between 3 and 32 months(7).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 45(SRC), determined from an estimation method(2), indicates that 4-aminopyridine is not expected to adsorb to suspended solids and sediment in water(SRC). The pKa of 4-aminopyridine is 9.17(3), indicating that this compound will exist predominantly in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). In addition, aromatic amines are expected to bind strongly to humus or organic matter due to the high reactivity of the aromatic amino group(5,6), suggesting that some adsorption to suspended solids and sediment may occur(SRC). Volatilization from water surfaces is not expected(7) based upon an estimated Henry's Law constant of 2.3X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 2.09X10-4 mm Hg(8), and water solubility, 1.12X10+5 mg/L(8). According to a classification scheme(9), a BCF range of <0.2-7.2 measured in carp (Cyprinus carpio)(10) suggests the potential for bioconcentration in aquatic organisms is low. A 0% of theoretical BOD using activated sludge in the Japanese MITI test(10) suggests that 4-aminopyridine is not readily biodegradable under environmental conditions(SRC). Another screening test found very slow biodegradation in both aerobic and anaerobic conditions(11). 4-Aminopyridine is expected to be stable to hydrolysis under environmental conditions(8). Aromatic amines are susceptible to sensitized photo-oxidation via peroxy, hydroxyl and singlet oxygen radicals in natural waters exposed to sunlight with shallow surface water half-lives on the order of one month(12); therefore, some sensitized photo-oxidation of 4-aminopyridine may occur in natural water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-aminopyridine, which has a vapor pressure of 2.09X10-4 mm Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 4-aminopyridine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 19 hrs(SRC), calculated from its rate constant of 2.0X10-11 cu cm/molecule-sec at 25 °C(SRC), determined using a structure estimation method(3). 4-Aminopyridine absorbs UV light above 290 nm(4), but it is reported to be stable to direct photolysis(5).

AEROBIC: 4-Aminopyridine, present at 100 mg/L, reached 0% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(1). In a screening test, which utilized 5 mL garden soil suspensions with glucose, yeast extract and mineral salts, 4-aminopyridine completely degraded in greater than 170 days under both aerobic and anaerobic conditions(2). For flooded soils, 76.4 and 79.0% of the original radio labeled 4-aminopyridine was mineralized to CO2 within 60 days in a Fargo clay and Barnes sandy loam soil at 20 °C and pHs of 7.7, and 7.4, respectively(3). In addition, only 6, 18 and 24% of the original radio labeled 4-aminopyridine was mineralized to CO2 within 60 days in a Barnes sandy loam, Towner loamy fine sand and Fargo clay at 20 °C and pHs of 7.4, 7.2 and 7.7, respectively(3). An aerobic biological screening study, which utilized a 10 mg/L yeast extract and an Aeric Ochraqualf soil for inocula, indicated that 4-aminopyridine is not readily biodegradable(4); at 28 °C and a pH of 7, less than 1% of an initial 14.6 ppm of 4-aminopyridine was mineralized in greater than 30 days as evidenced via the release of inorganic nitrogen(4). An acclimated aerobic soil grab sample study demonstrated slow biodegradation of 4-aminopyridine(5). 4-Aminopyridine was added to Fincastle silt loam (Aeric Ochraqualf) with a pH of 6.7 and incubated at 25 °C(5); within 64 days, 6.1% of the available nitrogen was released to inorganic forms(5); sterilized controls lost 14.9% of the starting material to volatilization, but did not release inorganic nitrogen(5). Aerobic biotic half-lives of 4-aminopyridine in soil are reported to range between 3 and 32 months(6).

ANAEROBIC: Soil grab sample data also demonstrates that biodegradation of 4-aminopyridine under anaerobic conditions will be slow(1). In a 90 day period, 54.6, 10.74 and 4.88% of original radio-labeled concentration of 10 ppm were mineralized to CO2 from a loamy sand, sandy clay loam and sandy clay loam at 30 °C and pHs of 7.8, 7.7 and 7.6, respectively, which correspond to half-lives of 90, 330 and 960 days(1). For a loam soil with pHs of 5.8, 5.6 and 4.1, losses of 5.95, 16.52 and 0.35% corresponded to half-lives of 660, 240 and greater than 660 days(1).

The rate constant for the vapor-phase reaction of 4-aminopyridine with photochemically-produced hydroxyl radicals has been estimated as 2.0X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 19 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 4-Aminopyridine absorbs UV-light at wavelengths >290 nm(2,3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). However, 4-aminopyridine is reported to be stable to light(4). Aromatic amines are susceptible to sensitized photo-oxidation via peroxy, hydroxyl and singlet oxygen radicals in natural waters exposed to sunlight with shallow surface water half-lives on the order of one month(5); therefore, some sensitized photo-oxidation of 4-aminopyridine may occur in natural water(SRC). 4-Aminopyridine is expected to be stable to hydrolysis under environmental conditions(6).

BCF values of <0.2-0.6 (at 50 mg/L) and <1.8-7.2 (at 5 mg/L concentration) were measured in carp (Cyprinus carpio) which were exposed over an 8-week period for 4-aminopyridine(1). According to a classification scheme(2), these BCF ranges suggest the potential for bioconcentration in aquatic organisms is low.

Using a structure estimation method based on molecular connectivity indices(1), the Koc for 4-aminopyridine can be estimated to be 35(SRC). According to a classification scheme(2), this estimated Koc value suggests that 4-aminopyridine is expected to have very high mobility in soil. The pKa of 4-aminopyridine is 9.17(3), indicating that this compound will exist predominantly in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). In addition, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(5,6), suggesting that mobility may be much lower in some soils(SRC).

The Henry's Law constant for 4-aminopyridine is estimated as 2.3X10-10 atm-cu m/mole(SRC) derived from its vapor pressure, 2.09X10-4 mm Hg(1), and water solubility, 1.12X10+5 mg/L(1). This Henry's Law constant indicates that 4-aminopyridine is expected to be essentially nonvolatile from water surfaces(2). 4-Aminopyridine's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Although 4-aminopyridine's vapor pressure suggests volatilization from dry soil surfaces will not be an important fate process(SRC), a screening study using sterilized soil measured a 14.9% loss of 4-aminopyridine to volatilization over a 64-day observation period(3).

No reports of surface water or ground water monitoring studies that included 4-aminopyridine were found in searches of the United States Geological Survey (USGS) online National Water Quality Assessment Data Warehouse (NAWQA) database, the EPA publication, EPA Pesticides in Ground Water, A Compilation of Monitoring Studies 1971-1991 National Summary(1).

SOURCE DOMINATED: 4-Aminopyridine was detected as a product of the thermal decomposition of epoxy powder paint(1).

4-Aminopyridine was identified as a volatile component of baked potatoes(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 4,618 workers are potentially exposed to 4-aminopyridine in the US(1). Occupational exposure to 4-aminopyridine may occur through inhalation and dermal contact with this compound at workplaces where 4-aminopyridine is produced or used(SRC). The general population may be exposed through dermal contact with bird repellent products containing 4-aminopyridine(SRC). Small children and toddlers could accidentally ingest treated granules when 4-aminopyridine is applied in residential or public areas(2). 4-Aminopyridine's use as a drug in treatment of multiple sclerosis(3) results in direct exposure through ingestion(SRC).

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number P008, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Health: TOXIC; inhalation, ingestion, or skin contact with material may cause severe injury or death. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution. /Aminopyridines/

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Fire or Explosion: Combustible material: may burn but does not ignite readily. When heated, vapors may form explosive mixtures with air: indoors, outdoors, and sewers explosion hazards. Those substances designated with a "P" may polymerize explosively when heated or involved in a fire. Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form. /Aminopyridines/

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Public Safety: CALL Emergency Response Telephone Number ... As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate enclosed areas. /Aminopyridines/

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. /Aminopyridines/

For more DOT Emergency Guidelines (Complete) data for 4-AMINOPYRIDINE (8 total), please visit the HSDB record page.

UN 2671; Aminopyridines

IMO 6.1; Aminopyridines

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./

The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.

The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.