WHO Acute Hazard classification: Class II, moderately hazardous.

Mechanism of action of Propoxur

As all carbamate insecticides propoxur acts on the nervous system of the parasites (but also of mammals, birds, fish and many organisms!) as inhibitor of acetylcholinesterase (also known as AchE), an enzyme that hydrolyzes acetylcholine (Ach). Ach is a molecule involved in the transmission of nervous signals from nerves to muscles (so-called neuromuscular junctions) and between neurons in the brain (so-called cholinergic brain synapses).

AchE's role is to terminate the transmission of nervous signals where Ach is the neurotransmitter (there are several other neurotrasmitters). By inhibiting the activity of AchE, carbamates prevent the termination of those nervous signals, i.e. the neurons remain in constant activity and excitation, massively disturbing the normal movements of the parasites. The bottom line for the parasites is that they are paralyzed and die more or less quickly.

Carbamates bind reversibly to AchE, in contrast with organophosphates, another chemical class of parasiticides, which bind irreversibly to AchE.

Acute Toxicity and Tolerance of Propoxur

• LD50 acute, rats, p.o. 50 mg/kg
• LD50 acute, mice, p.o. ~100 mg/kg
• LD50 acute, rats, dermal 4000 mg/kg
• LD50 acute, rabbits, dermal 4000 mg/kg
• Dogs tolerated daily oral doses of 20 mg/kg/day during months without toxic symptoms.
• In chickens delayed neurotoxic effects with degeneration of the spinal cord has been reported.
• As a general rule, dogs, cats and livestock tolerate topically applied propoxur very well (shampoos, soaps, baths, aerosols, lotions, creams, dusts, collars, etc.)

Toxic Symptoms caused by Propoxur Poisoning

• Toxic symptoms caused by carbamate intoxications are the same as those of organophosphate intoxication, but are usually less severe and recovery is faster because carbamates bind reversibly to acetylcholinesterase, whereas organophosphate binding is irreversible. This means that the organism can hydrolyze carbamates, which allows the enzyme to retake its normal function in a few hours. However, in case of massive overdose the organism cannot break down the poisonous substance fast enough.
• Ingested propoxur affects mainly the nervous system and the liver.

• Acute intoxication. Is caused by inhibition of the acetylcholinesterase: as a consequence acetylcholine accumulates in the neuromuscular synapses (including those in skeletal, smooth and cardiac muscles), in the neuroglandular connections, and in the CNS (Central Nervous System). This causes hyperexcitation in all the muscarinic and nicotinic cholinergic receptors, which disturbs the normal functioning of the affected organs.
• After accidental ingestion or massive dermal overdose, intoxication follows an acute development. Ingested propoxur is vastly and quickly absorbed into blood. The symptoms appear a few minutes to 2 hours after ingestion, often dramatically. If the patient survives the first 24-48 hours, prognosis is favorable.
• Usually muscarinic symptoms are the first to manifest, followed by hyperexcitation of the nicotinic receptors of vegetative ganglions and motor end plates. If the intoxication crosses the blood-brain barrier the CNS becomes hyperexcited as well.
• Main muscarinic symptoms:
• Exocrine glands: salivation (drooling), lacrimation (excessive secretion of tears), sudoration (excessive sweating).
• Eyes: miosis (constriction of the pupil), in swine nystagmus (uncontrolled eye movements).
• Digestive system: nausea, vomit (particularly in dogs), diarrhea, tenesmus (need for imperative defecation), fecal incontinence.
• Cardiovascular system: bradycardia (low heart rate), low blood pressure.
• Respiratory system: bronchoconstriction, bronchospasms, cough, tachypnea (low breathing rate), dispnea (shortness of breath).
• Urinary system: frequent urination.
• Main nicotinic symptoms
• Muscles: anxiety followed by depression, trembling, ataxia (uncoordinated movements), muscular stiffness, generalized muscular spasms, paralysis.
• Main CNS symptoms:
• Lethargy, fatigue, trembling, spasms and coma with respiratory paralysis. Death is mostly a consequence of paralysis of the respiratory muscles, of the inhibition of the respiratory center and of excessive bronchial constriction and secretion. In swine death can follow within 15 to 30 minutes after exposure to the lethal dose.

• <DIAGNOSIS. An important diagnostic parameter is the global acetylcholinesterase (AchE) activity in blood. A drop below 25% of the normal value indicates intoxication with an AchE inhibitor (not necessarily an organophosphate or carbamate pesticide).

Propoxur Side Effects, Adverse Drug Reactions (ADRs) and Warnings

• After slight overdose the following effects have been reported: reduced heart rate and vascular dilatation, increase of bronchial secretion and contraction, salivation (drooling), sphincter relaxation (gastrointestinal and urinary), miosis.
• In case of large skin injuries topical treatment with propoxur can lead to excessive cutaneous absorption with development of paraysmpathetic symptoms.
• Propoxur-impregnated collars for dogs and cats can cause local skin irritation. During the first 3 days after getting the collar, a reduction in the number of red blood cells and of the plasmatic cholinesterase levels has been reported.
• Propoxur should not be administered to animals suffering digestive (particularly mechanical intestinal or urinary obstruction), respiratory (mainly bronchial asthma) and cardiovascular disturbances.
• Propoxur should not be administered to pregnant dams during the last third of gestation.
• Certain solvents in the formulation can enhance the toxicity of Propoxur because they accelerate its cutaneous or mucosal absorption.
• Carbamates must not be administered together with other acetylcholinesterase inhibitors such as organophosphates, levamisole, morantel, pyrantel and neostigmine.

Antidote and Treatment of Propoxur Intoxication

• Atropine (a parasympatholytic drug) is the antidote for the acute muscarinic symptoms, the most dangerous ones. It is an antagonist of acetylcholine in the muscarinic receptors of the nervous system.
• Recommended atropine dosing (one third i.v. the rest s.c.), or otherwise at the physician's discretion:
• Cattle; 0.6 mg/kg
• Sheep: 1.0 mg/kg
• Horses: 0.1 mg/kg
• Dogs: 0.3 mg/kg
• Cats: 0.3 mg/kg
• Atropinization efficacy peaks when the pupils dilate and salivation stops. If necessary treatment can be repeated every 4 to 6 hours up to a max. dose of 6 mg/kg.

• Causal antidotes that act upon the toxic mechanisms can also be used. Pralidoxime (2 to 5 mg/kg i.v., maybe i.m.) and obidoxime (20 to 100 mg/kg) can reactivate the cholinesterase but not later than 24 hours after ingestion, and treatment should not be repeated more than once or twice. Both should be administered after atropine. Re-treatment not earlier than 20 minutes, usually after 2 hours. WARNING: obidoxime can also act as a cholinesterase inhibitor!
• Symptomatic and support measures may be advisable:
• Breathing support: artificial respiration and aspiration of bronchial secretions
• After oral poisoning: vomit or stomach lavage, administration of active charcoal or mineral oil.
• After dermal poisoning: rinse the injury with abundant water with alkaline detergent
• Treatment of acidosis and spasms
• Administration of electrolytes and multivitamins to support the hepatic metabolism.

Pharmacokinetics of Propoxur

• Topically administered propoxur remains mostly on the hair-coat of the treated animals and is very poorly absorbed through the skin. Treated animals can ingest propoxur through licking or grooming.
• Absorption of ingested propoxur into blood is very fast. It is also quickly excreted through urine. Rats eliminated up to 85% of the administered dose within 16 hours.

Environmental Toxicity of Propoxur

• Propoxur is highly to moderately toxic to birds, depending on the species.
• Propoxur is only slightly toxic to fish and many aquatic invertebrates, but is highly toxic to numerous insects.
• Propoxur is unlikely to bioaccumulate in the aquatic food chain.
• Propoxur is moderately persistent in the soil. Half-life in soil is 14 to 50 days. It hardly binds to soil particles. For these reasons and because it is quite soluble in water it has potential for contaminating groundwater.
• In aqueous environment propoxur degrades at a speed of ~1.5%/day.

Additional information

Click here for a list and overview of all safety summaries of antiparasitic active ingredients in this site.

• Propoxur belongs to the chemical class of the carbamates.
• Propoxur is not used in human medicines.
  
• Propoxur is used in crop pesticides.
• Propoxur is used in public or domestic hygiene as a biocide.
• Click here for General safety of antiparasitics for domestic animals.
• Click here for General safety of antiparasitics for humans.
• Click here for General safety of antiparasitics for the environment.
• Click here for technical and commercial information on propoxur.