WHO Acute Hazard classification of pesticides: Class III, slightly hazardous.

Mechanism of action of Spinosad

The molecular mechanism of action of spinosad and other spinosyns has not yet been completely elucidated. They act on both GABA and nicotinic acetylcholine receptors of the membranes of nerve cells of insects, but they target different subunits than other known insecticides. The nervous system of exposed parasites (fleas, ticks, mites, etc.) is overexcited (e.g. they suffer from involuntary muscle contractions), which kills them rather quickly.

Acute Toxicity and Tolerance of Spinosad

• LD50 acute, rats, p.o. >3600 mg/kg
• LD50 acute, mice, p.o. >5000 mg/kg
• LD50 acute, geese, p.o. >2000 mg/kg
• LD50 acute, rabbit, dermal >5000 mg/kg
• LD50 acute, rabbits, dermal 354 mg/kg
• As a general rule, dogs and livestock (sheep, goats) tolerate spinosad very well.
• In a study on dogs treated orally at 2.5x the therapeutic dose (=30-60 mg/kg), close to 85% of the animals vomited 20 to 120 minutes after administration, most of them more than once. In a study on puppies (6 months old) treated once at 90 mg/kg (~3x the therapeutic dose), 45% of the animals vomited within 60 minutes after administration.
• Reproductive studies in pregnant and nursing bitches and lactating puppies did not completely confirm the harmlessness of spinosad during pregnancy and lactation. Use should be decided after a risk/benefit analysis.
• Spinosad is not approved for directly treating poultry, but is approved for off-animal use on poultry houses against various parasites. Such use is not detrimental for the health and performance of the birds.

Toxic Symptoms caused by Spinosad Poisoning

• The most frequent symptom of intoxication in dogs is vomit, which also happens as adverse side effect after correct treatment at the therapeutic dose.
• In rodents exposed to high overdosing exhaustion and cachexia (wasting: loss of weight, muscle atrophy, etc.) were reported.
• In toxicity studies on rats, deaths were recorded at the highest doses tested. Pathological analysis showed vacuolization (phospholipidosis) of epithelial cells in numerous organs (liver, lymphatic nodes, kidneys, stomach, lungs, etc.).
• As a general rule, young animals are more sensitive to overdosing and react stronger.
• A frequent administration error in dogs that can lead to overdosing and subsequent poisoning is partial administration to small dogs of tablets approved for larger animals.

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

• The most frequently reported side effect is vomiting (~12.5% of dogs). At a dose of 30 to 90% mg/kg there is a linear increase in the vomiting frequency. Between 70 and 90 mg/kg about 17% of the dogs showed vomiting.
• Other relatively frequent side effects of spinosad are loss of appetite (~9%), lethargy (~7.5%), diarrhea (~7%), cough (~4%) and excessive thirst (~2.5). Less frequent side effects reported are redness of the skin, drooling, itching and trembling.
• In epileptic dogs treatment at a dose higher than the therapeutic one can cause seizure.
• Spinosad can enhance the toxicity of ivermectin when used at a high dose (e.g. 0.6 mg/kg, against demodicosis): they should not be administered concomitantly.
• Spinosad can be problematic when used in dogs with the MDR-1 mutation (e.g. Collies), as all macrocyclic lactones. Nevertheless, tolerance studies have shown that dogs sensitive to ivermectin treated with spinosad at 300 mg/kg (~4.5x the therapeutic dose) or with spinosad and milbemycin oxime at 5x the therapeutic dose showed no neurotoxic symptoms.
• Never use 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 other ingredients that are toxic to cats.
• Spinosad is approved for use on dips and pour-ons for sheep and goats in some countries (e.g. Australia, New Zealand). It is well tolerated by these animals.
• 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 Spinosad Intoxication

• There is no antidote for spinosad poisoning.
  
• Treatment consists in preventing further exposure together with supportive and symptomatic measures.

Pharmacokinetics of Spinosad

• After oral administration, spinosad is quickly absorbed into blood. Maximum plasma levels are reached 2 to 4 hours after administration. Bioavailability is >70% and increases if administered together with food.
• Spinosyn A and spinosyn D (the two major components of spinosad) are vastly metabolized. Excretion is achieved by >80% through the feces. 

Environmental Toxicity of Spinosad

• Toxicity of spinosad to fish, birds and wildlife in general is quite low.
• Spinosad breaks down in the soil. Half-life in well-oxygenated silt loam soil is ~2 weeks. Half-life in soil without oxygen is 5 to 8 months.
• Spinosad solved in water is broken down by sunlight rather quickly (half-life ~20 hours).
• Microorganisms in the soil are able to break down spinosad.
• Spinosad does not bioaccumulate.
• Correct use on dogs is unlikely to cause environmental pollution.
• There is a certain environmental risk of water pollution from run-off after pour-on administration to large sheep flocks, or after undue disposal of old dip wash. However this risk seems lower than the one associated with the use of spinosad in crop pesticides.

Additional information

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

• Spinosad belongs to the chemical class of the spinosyns.
• Spinosad is used in human medicines (e.g. against head lice)
  
• Spinosad is used in crop pesticides.
• Spinosad is used in public and 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 spinosad.