WHO Acute Hazard classification: Not listed

Mechanism of action of Oxyclozanide

The molecular mode of action of salicylanilide, including oxyclozanide, is not completely elucidated. They all are uncouplers of the oxidative phosphorylation in the cell mitochondria, which disturbs the production of ATP, the cellular "fuel". This seems to occur through suppression of the activity of succinate dehydrogenase and fumarate reductase, two enzymes involved in this process. This impairs the parasites motility and probably other processes as well.

Acute Toxicity and Tolerance of Oxyclozanide

• LD50 acute, mice, p.o. 300 mg/kg
• LD50 acute, rats, p.o. 980 to 3519 mg/kg (different studies)
• LD50 acute, rabbits, p.o. 3200 mg/kg
• In cattle and sheep, relatively low oral doses of 15 mg/kg can already cause toxic symptoms, mainly nervous (depression) and gastrointestinal (diarrhea and loss of appetite). At higher doses the same but more severe and persistent symptoms were observed. At doses ≥50 mg/kg fatalities were recorded.
• The safety margin after oral administration is therefore rather low.

Toxic Symptoms caused by Oxyclozanide Poisoning

• Most frequent symptoms of oxyclozanide toxicity in ruminants are:
• Depression
  
• Loss of appetite
  
• Diarrhea
• The most affected organ is the liver.
• In rat studies, toxicity symptoms included pallor, increased respiration, lethargy, fecal and urine staining of perineum, and staining of muzzle.

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

• At therapeutic doses oxyclozanide may cause ADRs as those intoxication symptoms previously described, but in a mild and transient form.

Antidote and Treatment of Oxyclozanide Intoxication

• There is no specific antidote for oxyclozanide.
• Treatment consists in supportive and symptomatic measures.

Pharmacokinetics of Oxyclozanide

• After oral administration oxyclozanide is slowly absorbed into the bloodstream. Maximum blood concentrations in sheep and cattle are reached about 24 hours after treatment. Oxyclozanide binds strongly and almost completely (>99%) to plasma proteins.
• Oxyclozanide is metabolized in the liver and excreted mainly through bile and feces (up to 80%). The rest in urine and <0.1% in milk, mostly as unchanged oxyclozanide. Excretion half-life in sheep is about 7 days. Oxyclozanide excretion in milk of lactating cows is rather low, and several oxyclozanide products are approved for use on dairy animals.

Environmental Toxicity of Oxyclozanide

• Not being used in crop pesticides or in public hygiene, knowledge on its environmental fate and impact is very scarce.
• Nevertheless, it can be assumed that correctly used in livestock, oxyclozanide is unlikely to be detrimental for the environment, including coprophagous insects.

Additional information

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

• Oxyclozanide belongs to the chemical class of the salicylanilides.
• Oxyclozanide is used in human medicines.
  
• Oxyclozanide is used in agriculture as a molluscicide.
• Oxyclozanide is not 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 oxyclozanide.