WHO Acute Hazard classification: Not listed

Mechanism of action of Abamectin

As all macrocyclic lactones, abamectin acts as agonist of the GABA (gamma-aminobutyric acid) neurotransmitter in nerve cells and also binds to glutamate-gated chloride channels in nerve and muscle cells of invertebrates. In both cases it blocks the transmission of neuronal signals of the parasites, which are paralyzed and expelled out of the body, or they starve. It also affects the reproduction of some parasites by diminishing oviposition or inducing an abnormal oogenesis.

In mammals the GABA receptors occur only in the central nervous system (CNS), i.e. in the brain and the spinal chord. But mammals have a so-called blood-brain barrier that prevents microscopic objects and large molecules to get into the brain. Consequently macrocyclic lactones are much less toxic to mammals than to parasites without such a barrier, which allows quite high safety margins for use on livestock and pets. A notable exception to this are dog breeds that carry the MDR-1 gene defect (see later).

Acute Toxicity and Tolerance of Abamectin

• LD50 acute, mice, p.o. 13.5 mg/kg; 14 - 24 mg/kg (different study)
• LD50 acute, rats, p.o. 10 mg/kg
• Dogs: NEL (no effect level) in chronic toxicity studies during 1 year: 1.5 mg/kg/day, p.o.
• Cattle treated subcutaneously with abamectin at 1.0 mg/kg showed signs of neurotoxicity. At 2 to 8 mg/kg and above treated animals showed severe signs of toxicosis
• Sheep treated p.o. at 3x the therapeutic dose showed no adverse effects.
• In most countries abamectin is not approved for use on dogs and cats. As a consequence safety studies on pets are rather scarce.

Toxic Symptoms caused by Abamectin Poisoning

General symptoms

• The symptoms of abamectin poisoning are similar to those of ivermectin poisoning and are the consequence of an excessive concentration of the molecule in the CNS (Central Nervous System) and the subsequent increase of GABA activity. Abamectin stimulates the release of the GABA neurotransmitter (gamma-Aminobutyric acid) in the presynaptic neurons and enhances its postsynaptic binding to its receptors. This increases the flow of chloride ions in the neurons, which causes hyperpolarization of the cell membranes. This on its turn disturbs normal nervous functions and causes a general blockage of the stimulus mechanisms in the CNS. The resulting cerebral and cortical deficits include mainly
• Ataxia (uncoordinated movements)
• Hypermetria (excessive or disproportionate movements)
• Disorientation
• Hyperesthesia (excessive reaction to tactile stimuli)
• Tremor (uncoordinated trembling or shaking movements)
• Mydriasis (dilatation of the pupils); in cattle and cats also myosis (contraction of the pupils)
• Recumbency (inability to rise)
• Depression
• Blindness
• Coma (persistence unconsciousness)
  

• As a general rule, young animals are more sensitive to overdosing, react stronger and prognosis is worse than for adult animals. 
• Besides erroneous dosing, overdosing can occur due to excessive licking after pour-on delivery to livestock (usually licking of other animals in the same herd) or spot-on delivery to dogs and cats (particularly in cats due to intense grooming).
• Frequent administration errors in livestock include intramuscular or intravenous instead of subcutaneous injection. Another frequent error is repeated unintended treatment in short intervals due to animal mistaking. These errors result in excessive blood levels.
• A frequent administration error in dogs is partial administrating to small dogs of tablets or spot-ons approved for large animals.
• A frequent administration error in cats is partial administration to cats of tablets or spot-ons approved only for dogs.

Poisoning Symptoms in Dogs

• In dogs without the MDR-1 gene defect, the dominant poisoning symptom with macrocyclic lactones is extreme mydriasis (dilatation of the pupils) together with incomplete and deregulated pupillary reflex. Mydriasis in both eyes is the most sensitive indicator of ivermectin intoxication and the most frequent symptom in dogs. 
• At higher doses and in dogs with the MDR-1 gene defect other symptoms have been observed as well: weakness, lethargy, hypothermia (too low body temperature), hypersalivation (drooling), vomit, difficult breathing, behavioral disturbances, confusion, seizure, death.
• Symptoms develop usually 5 to 24 hours after treatment and can last for several days until coma. As a general rule, poisoning is more serious and prognosis is worse if the symptoms develop faster.

Poisoning Symptoms in Cattle

• Reported symptoms in cattle after s.c. overdose with abamectin include ataxia (uncoordinated movements), recumbency (inability to rise), hypersalivation (drooling), mydriasis (dilatation of the pupils), decreased lip and tongue tone, coma and death.

Poisoning Symptoms in Sheep, Swine, Goats and Horses

• Those general symptoms previously described.

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

• Calves younger than 4 months are more susceptible to abamectin and should not be treated.
• After subcutaneous injection swelling may develop at the injection site. It usually recedes in a few days.
• Never use spot-ons or tablets for dogs in cats, and never use spot-ons or tablets for large dogs in small dogs. It happens that some users want to save money buying large tablets or spot-ons for treating smaller dogs (or even cats!) twice or more times. The risk of overdosing is considerable, either due to erroneous calculations or to unskilled manipulation. In addition, dog medicines may sometimes contain ingredients that are toxic to cats.
• WARNING: Dogs of some breeds do not tolerate abamectin, other macrocyclic lactones or other drugs (e.g. emodepside) that can cross the blood-brain barrier. They can suffer more or less serious adverse effects if treated at dose rates slightly higher than the recommended ones. Consequently dosing must be as accurate as possible. This is the case for Collies and related breeds, which have a mutation in the MDR-1 gene that affects the blood-brain barrier and makes it more permeable to such compounds than in dogs without this mutation. Besides Collies, other dog breeds have shown similar problems, although the MDR-1 mutation has not been confirmed in all of them. The breeds more affected by this mutation are (% frequency): Collie (70%), Long-haired Whippet (65%), Australian Shepherd (50%, also mini),  McNab (30%), Silken Windhound (30%), English Shepherd (15%), Shetland Sheepdog (15%), English Shepherd (15%), German Shepherd (10%), Herding Breed Cross (10%). Other less affected breeds are: Old English Sheepdog, Border Collie, Berger Blanc Suisse, Bobtail, Wäller. The only way to be sure that a dog is affected or not is to test for it. As more dogs are tested it is likely that the mutation is discovered in other breeds, or that the frequencies change.
• Complications in dogs, cats and horses due to Dirofilariasis
• Most products with abamectin and other macrocyclic lactones are effective against heartworm larvae in the blood. Heartworm infection (Dirofilaria spp) is a common disease in dogs in regions with hot or mild weather. The disease is called dirofilariasis and is transmitted by mosquitoes. It is less frequent in cold regions but can occur there as well. Cats and horses can be affected too. Heartworm preventatives hinder larvae (microfilariae) in the pet's blood to develop to adult worms. The sudden death of microfilariae releases enormous amounts of allergens that can cause an allergic shock. The following symptoms may develop about 5 hours after treatment: pale mucosae, tachypnea (rapid breathing), dispnea (difficult breathing), vomit, weak and accelerated pulse, weakness, fever and ataxia (uncoordinated movements). Therapy requires shock treatment, including administration of corticosteroids and fluid supply.
• Another possible complication is that treatment at the therapeutic dose against larvae they can also kill some adult worms, if not all. Now, dead adult worms or their rests in the heart or in the pulmonary artery can physically obstruct the pulmonary blood vessels with the consequent damage to the lungs, which can be fatal. This means that any dog that is treated with a macrocyclic lactone should be checked for already existing heartworm infection. If the check is positive, the heartworm infection has to be treated with other specific heartworm products under strict supervision of a veterinary doctor.

• Unless prescribed by a veterinary doctor, never use in dogs or cats products for livestock that are not explicitly approved for such use. There is a high risk of overdosing or of adverse drug reactions due to ingredients that are not tolerated by pets or are even toxic to them.
  

Antidote and Treatment of Abamectin Intoxication

• There is no antidote for abamectin poisoning.
  
• Treatment consists in supportive and symptomatic measures.
• It can be helpful to read the safety summary for ivermectin, the most used macrocyclic lactone.

Pharmacokinetics of Abamectin

• After topical administration abamectin is poorly absorbed through the skin.
• After oral administration to sheep, peak plasma levels were observed 12 to 36 hours after treatment. Half-life plasma elimination was 50 to 90 hours. Excretion was almost completely through feces, <0.5% through urine.
• After subcutaneous injection to cattle half-life plasma elimination was ~5 days and excretion was mainly through feces, only 1-2% through urine.

Environmental Toxicity of Abamectin

• Abamectin is highly toxic to fish and extremely toxic to aquatic invertebrates. For this reason disposal of abamectin remains (e.g. in empty containers) in watercourses must be absolutely avoided. There is a certain environmental risk of water pollution from run-off after pour-on administration to large herds.
• Abamectin is photodegradable.
• Abamectin is almost insoluble in water and binds strongly to soil particles. Groundwater contamination is therefore unlikely.
• Abamectin degrades quickly in soil and water. Photodegradation half-life in surface soil is ~1 day, in deep soil half-life was 2 weeks to 2 months.
• Abamectin does not bioaccumulate
• Abamectin administered to livestock is partially excreted in the feces and has a negative impact on coprophagous invertebrates (fly larvae, dung beetles, etc.) that feed or breed on dung of cattle or other livestock. Several environmental studies following use on livestock concluded that such use is not detrimental for soil organisms.

Additional information

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

• Abamectin belongs to the chemical class of the macrocyclic lactones.
• Abamectin is not used in human medicine.
• Abamectin is used in crop pesticides.
• Abamectin 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 abamectin.