Chemicals / Complex Chemical Agents/ Chemical:
Amitraz (with special reference to Hedgehogs, Bears and Ferrets)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
Acaricide and insecticide. Used in veterinary medicine for treatment of external parasites, particularly in treatment of demodecosis; also a pesticide used on certain crops.

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Names and Formulae
Type A triazapentadiene compound. (W180.Sept04.w1) A diamide topical antiparasitic. (B263)
Alternative Names
  • N,N'-[(methylimino) dimethylidyne]di-2,4-xylidine. (W180.Sept04.w1)
  • Product names include Aazdieno, Acarac, Amitraze, Baam, Edrizan, Mitac, Maitac, Triatox, Triatix, Vapcozin Taktic, Triazid, Topline, Tudy, Ectodex, Garial, Danicut, Ovidrex, Acadrex, Bumetran, and Ovasyn. (W180.Sept04.w1)
  • 1,5-Di(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene; Amitraz; Baam; Formamidine, N-methyl-N'-2,4-xylyl-N-(N-2,4-xylylformimidoyl)-; Methyl-bis(2,4-xylyliminomethyl)amine; Mitac; Ovasyn; Taktic; Triazid. (W324.Sept04.w1)
Chemical Formula C19H23N3 (W324.Sept04.w1)
Chemical Structure --
Molecular Weight 293.4108 (W324.Sept04.w1)
Related Chemicals --

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Physical Properties / Chemistry
Appearance

Straw coloured or pale yellow, odourless crystalline solid. (B263, W180.Sept04.w1)

Melting point 86-87C. (B263, W180.Sept04.w1, W324.Sept04.w1)
Boiling point --
Density --
Water solubility About 1 mg/L. (W180.Sept04.w1) Sparingly soluble. (B263)
Other solubility Soluble in common organic solvents such as acetone, toluene, and xylene. (B263, W180.Sept04.w1)
Acid/Base --

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Pharmacology & General Information
Pharmacology
  • Action is not well understood. (B263)
  • May effect the CNS of susceptible organisms. (B263)
  • Appears to have an alpha-2 adrenergic activity. (B263)
  • Can cause a significant increase in plasma glucose levels; this effect is thought to be due to inhibition of insulin release via the alpha-2 adrenergic activity. (B263)
    • This effect can be antagonised by the alpha-2 adrenergic inhibitor yohimbine. (B263)
Storage / Stability
  • Non-corrosive. (W180.Sept04.w1)
  • Non-hygroscopic. (B263)
  • Relatively stable to heat. (B263, W180.Sept04.w1)
  • NOTE: some pharmaceutical products containing amitraz are flammable (e.g. Aludex (Intervet, UK)). (B266)
  • Stability apparently little affected by UV light. (W180.Sept04.w1)
  • Slow decomposition occurs when amitraz is stored for prolonged periods under moist conditions. (W180.Sept04.w1)
  • Should not be mixed with other antiparasitic agents; compatibility with other compounds has not been determined. (B263)

Aludex (Intervet, UK):

  • Store in the original container, tightly closed, in a safe place, away from human or animal food or drink. (B266)
  • Shake the container before use. (B266)
  • Wash made by diluting concentrate product in water must be made up immediately before use and unused product discarded. (B266)
Legal Category (In UK) POM. (B266)

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5)
Referees Suzanne I. Boardman (V.w6)

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Therapeutic Information

Uses/Indications
Activity  
Appropriate Use
  • For treatment of demodectic mange and sarcoptic mange in dogs. (B266)
Limitations --
Notes --

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Pharmacokinetics and Drug Interactions
Absorption /Bioavailability Some absorption into the blood occurs following topical application. (W180.Sept04.w1)
Distribution Not readily absorbed into tissues. (W180.Sept04.w1)
Plasma Protein binding / Storage --
Elimination Route Mainly excreted unchanged via the urine. (W180.Sept04.w1)
Elimination half-life / Clearance Rate --
Drug Interactions
  • Use concurrently with other alpha-2 adreno-receptor agonists is not recommended. (B266)
  • Can be used with other dermatological preparations, except for preparations which are water repellent. (B266)
  • Can be used with anthelmintics. (B266)

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Administration
Formulations available In UK:
  • Aludex ( Intervet, UK), a clear, emulsifiable concentrate containing 5% w/v amitraz as Amitraz technical, BP (Vet). Forms an emulsion when diluted with water. (B266)

In USA: 

Doses / Administration Routes / Frequencies

Use of Drugs (Medication):

  • Before administration of any pharmaceutical product the manufacturer's datasheet must be consulted regarding operator safety, relevant withdrawal times etc.
  • Many drugs are not registered for use in particular species and additional care should be taken in their use, with proper regard for possible toxic effects. 
  • Consideration should be given to relevant legislation regarding the use of drugs.
  • In the UK, guidelines regarding the use of drugs are set out in the Royal College of Veterinary Surgeons' Guide to Professional Conduct 2000: (See: LCofC1 - RCVS Guide to Professional Conduct 2000 - Choice of Medicinal Products).
Erinaceus europaeus - West European Hedgehog:
  • Amitraz washes may be used (1:400 dilution applied to the skin every three days) for treatment of Demodex Infection in Hedgehogs. (B284.6.w6)
  • Amitraz washes may be used in the treatment of Sarcoptic mange
    • 1:400 dilution applied to the skin every three days. (B284.6.w6)
    • 50g/litre concentrate, diluted 1 in 250 in water, applied as a bath or sprayed onto the hedgehog. (B337.3.w3)

Atelerix albiventris - Four-toed hedgehog:

In bears:

  • For the treatment of Audycoptic Mange in Bears
  • Spraying with amitraz. (B22.32.w15)
    • Spray with amitraz in a 250 ppm solution (one 10.6 ml bottle of Mitaban, Upjohn Co. liquid concentrate) in two gallons of warm water. (B10.48.w43)
  • Amitraz, applied topically to affected areas at a standard dilution, repeated at two- to three-week intervals for four treatments (negative scrapes for mites at the third and fourth treatment, therefore used until two skin scrapes were negative for mites), was used successfully in an Ursus americanus - American black bear. (J4.185.w4, P1.1984.w2)

In dogs: 

  • One part 5% concentrate to 100 parts water (i.e. to give 0.05% amitraz). Therefore 50 ml per 5 litres of water (for a small dog), or 100 ml per 10 litres of water (for a larger dog). (B266)
    • Preparation of the dog: shampoo if required to remove dirt and grease; long-coated dogs may be clipped.
    • Preparation of the wash solution: either outside or in a well-ventilated place, add the required volume of solution to the appropriate volume of clean warm water and mix well by stirring.(B266)
      • Prepare sufficient to completely immerse the paws of the dog ant to allow complete wetting of the coat (usually five to 10 litres). (B266)
      • Do not prepare excess solution; the solution is unstable and must be discarded after six hours. (B266)
    • Application: In a well ventilated area, stand the dog in a bath/sink, pour the wash over the dog, working the solution into the skin and hair using a soft brush or sponge to ensure that all areas of the skin are thoroughly wetted. (B266)
      • Avoid excess contact with mucous membranes. (B266)
    • DO NOT RINSE. Remove the dog from the bath/sink and allow it to dry naturally in a warm, draught-free area; the dog may be taken for a short walk to allow it to start to dry while stopping the animal from licking itself (and thereby ingesting the wash), and also assists in dispersal of the solvent fumes. (B266)
      • An Elizabethan collar may be used to stop the dog licking the solution from its coat. (B266)
      • Do NOT dry using a hair dryer. (B266)
    • Avoid handling the dog until the coat is dry. (B266)
    • REPEAT WEEKLY FOR TWO TO SIX WEEKS. (B266)

In ferrets - Mustela putorius furo - Ferret:

  • 0.3% solution, apply topically every seven days. (B602.41.w41, B631.21.w21) For demodecocics; for treatment of small areas, use full strength. (B631.21.w21)
  • For treatment of demodectic mange: 3% solution applied topically every 14 days for three to six treatments. Ivermectin is a safer drug. (B626.App.w22)
  • Dip three to six times, at intervals of two weeks. (J213.3.w1)
Monitoring parameters --

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Withdrawal period / Withholding time
Notes --

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • For external use only. (B266)
  • Can be toxic to cats and rabbits. (B263)
    • If used in cats with demodecosis, greater dilution than usual is recommended. (B263)
  • Toxic to horses. (B266)
  • If using near the eyes, the eyes should be protected, e.g. by application of petrolatum-based ophthalmic ointment. (B263)
  • Do not use on Chihuahuas. (B266)
  • Do not use on dogs suffering from heat stress. (B266)
Adverse Effects / Side Effects / Warnings
  • Sedation may occur, usually for up to 24 hours but sometimes persisting as long as 72 hours. (B263)
    • Sedation, lethargy, CNS depression, bradycardia, and slow, shallow breathing may occur in a small number of dogs; these signs usually last less than 24 hours. (B266)
      • Signs are mainly due to alpha-2 adrenergic activity. (B266)
      • If signs persist, wash the dog in warm soapy water (NOT disk-washing detergent), dry it and warm it. (B266)
  • Ataxia, bradycardia, vomiting, diarrhoea, hypothermia and transient hyperglycaemia may occur. (B263)
  • Debilitated and geriatric animals, and dogs of very small breeds, are more likely to show adverse effects. (B263)
  • Do not use on individuals with deep pyoderma with drainage tracts; treat only after lesions have improved due to e.g. antibiotic treatment and shampooing. (B263)
Operator Warnings
  • Prepare and use the diluted product in a well-ventilated area. (B266)
  • When handling and applying the product, wear waterproof gloves, apron and a face shield. (B266)
    • Following application, the protective clothing, particularly the inside of the gloves, should be thoroughly washed. (B266)
  • Avoid contact of the product with the skin or eyes; if contamination occurs, wash thoroughly with soap and water. (B266)
  • "Do not eat, drink or smoke while using this product." (B266)
  • "When treatment is completed, wash hands thoroughly before eating, drinking or smoking." (B266)
  • Avoid handling a treated animal until its coat is dry. (B266)
Overdose / Acute Toxicity
  • May be toxic if swallowed. (B263)
  • Significant toxicity may occur if a collar containing amitraz is swallowed. (B263)
    • Treatment: induce vomiting, if possible retrieve the collar by endoscopy, administer activated charcoal and a cathartic to remove remaining fragments of collar from the digestive tract.
    • Yohimbine (0.11 to 0.2 mg/kg intravenously, starting at the lower dose) may be beneficial for treatment of effects of overdose. Treatment may need to be repeated since the half-life of yohimbine is short. (B263)
    • Atipamezole has been used in the treatment of amitraz toxicity. (B263)
      • Atipamezole may be given at 0.2 mg/kg intramuscularly to reverse side effects. (B266)

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Detailed Toxicological Information
Classification EPA classified as Class III - slightly toxic. In the USA, products containing amitraz bear the SIGNAL WORD: CAUTION. (W180.Sept04.w1)
Acute Toxicity
  • Slightly toxic to mammals if ingested orally: (W180.Sept04.w1)
    • Oral LD50 in rats is 523-800 mg/kg. (W180.Sept04.w1)
    • Oral LD50 in mice is greater than 1,600 mg/kg. (W180.Sept04.w1)
  • Dermal exposure gave an LD50 of greater than 1,600 mg/kg for rats and greater than 200 mg/kg for rabbits. (W180.Sept04.w1)
  • Inhalation LC50 (for six hours exposure) of amitraz for rats is 65 mg/l of air. (W180.Sept04.w1)
  • Not a skin irritant and does not sensitise skin. (W180.Sept04.w1)
  • Signs of acute amitraz poisoning in male and female rats (treated with 440 mg/kg and 365 mg/kg respectively) included coolness to touch, reduced spontaneous activity, episodes of increased induced activity such as aggression in response to handling, and signs of general debilitation. (W180.Sept04.w1)
  • May produce a slowly reversible emaciation in survivors following acute toxicity. (W180.Sept04.w1)
Chronic Toxicity
  • In two-year feeding trials no ill-effects were observed in rats given 50 mg/kg/day amitraz in their diet or in dogs given 0.25 mg/kg/day amitraz. (W180.Sept04.w1)
  • Beagles given 4 mg/kg orally daily for 90 days showed transient ataxia, CNS depression, hyperglycemia, decreased pulse rates and lowered body temperature. No animals died.  (B263)
Reproductive effects
  • In male and female rats, doses of 200 mg/kg/day ten weeks decreased fertility. (W180.Sept04.w1)
  • Female mice, treated orally for 5 days with 50 mg/kg/day and then mated, showed a slight increase in loss of fetuses and a decrease in the number of living offspring. (W180.Sept04.w1)
  • When male mice were given 50 mg/kg/day orally for 5 days and then mated, the resulting embryos were significantly less likely to grow in the mother's uterus. (W180.Sept04.w1)
  • Female mice given 400 mg/kg/day in their diet for up to 33 weeks, showed a significant increase in the time they were sexually receptive.(W180.Sept04.w1)
  • The highest dose of amitraz which has no observable effect on the death of unborn rats (fetotoxic NOEL) is 3 mg/kg/day. (W180.Sept04.w1)
  • The highest dose of amitraz that does not cause an observable effect in the death of rat embryos (Embryotoxic NOEL) is 5 mg/kg/day.(W180.Sept04.w1)
  • Rats given 12 mg/kg/day of amitraz from day one of pregnancy until 21 days old when the young were weaned had a reduced number of young born and alive at day four.(W180.Sept04.w1)
  • Rabbits given 25 mg/kg/day of amitraz from days six to 18 of pregnancy produced fewer and smaller litters. (W180.Sept04.w1)
  • Risk to humans: reproductive effects have been observed in laboratory animals at some dose levels, however, likely human exposures are very much less than those which produced effects. These effects are unlikely in humans under normal circumstances. (W180.Sept04.w1)
Teratogenic effects
  • An EPA study indicated that the highest dose at which amitraz has no observable effect on test rats' offspring (teratogenic NOEL) is 12 mg/kg/day and the teratogenic NOEL of rabbits is 25 mg/kg/day. (W180.Sept04.w1)
    • In another study in rats treated with 12 mg/kg/day of amitraz from days 8 to 20 of pregnancy, the offspring were heavier but had less bone development than the offspring of untreated rats. (W180.Sept04.w1)
  • Studies indicated that amitraz exposure at high doses during pregnancy resulted in adverse effects in laboratory animals.
  • Likely human exposures are very much less than those which produced effects on laboratory animals, and these effects are unlikely in humans under normal circumstances. (W180.Sept04.w1)
Mutagenic effects
  • A variety of tests have indicated that amitraz is not mutagenic and that it does not cause damage to DNA. (W180.Sept04.w1)
Carcinogenic effects
  • In long term feeding studies amitraz was shown not to be carcinogenic in rats. (W180.Sept04.w1)

  • Fed to mice at 57 mg/kg/day over 20 months it caused an increase in tumours of the lungs and lymph nodes in female mice, but not males. A two-year study in female mice given amitraz at 57 mg/kg/day also showed an increase in hepatocellular tumours. (W180.Sept04.w1)

  • "Because amitraz causes cancer in female mice, but not male mice or male or female rats, it is unclassifiable as to human carcinogenicity."  (W180.Sept04.w1)

Organ toxicity
  • At high doses, amitraz can reduce the function of the hypothalamus, which helps regulate the metabolism by controlling hormone release in the body. (W180.Sept04.w1)
  • A daily dose of 200 mg per kilogram of body weight for ten weeks [species not stated] caused decreased growth and food consumption. (W180.Sept04.w1)
Bird Toxicity
  • Slightly toxic to birds. (W180.Sept04.w1)
    • Dietary LC50 (8 day) is 7,000 mg/kg for mallard ducks. (W180.Sept04.w1)
    • Dietary LC50 (8 day) is 1,800 mg/kg for Japanese quail. (W180.Sept04.w1)
    • Oral LD50 for bobwhite quail is 788 mg/kg. (W180.Sept04.w1)
  • May affect reproduction in birds; avian reproduction NOEL is less than 40 ppm. (W180.Sept04.w1)
Aquatic organism activity
  • Moderately toxic to fish: (W180.Sept04.w1)
    • LC50 (96-hour exposure) 1.3 mg/l for bluegill sunfish, 3.2-4.2 mg/l for harlequin fish. (W180.Sept04.w1)
    • For a 48-hour exposure of rainbow trout, a cold water species, the LC50 is 2.7-4.0 mg/l. (W180.Sept04.w1)
  • Daphnia, a fresh water invertebrate, showed toxic effects at 35 ppb of amitraz in water. (W180.Sept04.w1)
Other organism toxicity
  • Relatively non-toxic to bees; LD50 is 12 micrograms per bee by ingestion or 3.6 mg/l by direct spraying. (W180.Sept04.w1)

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater
  • Broken down rapidly in soil containing oxygen. 

  • The half-life in soil, the amount of time needed for the chemical to degrade to half its original concentration, is less than one day. 

  • Degradation occurs more rapidly in acidic soils than in alkaline or neutral soils.

Breakdown in water --
Breakdown in vegetation Amitraz may cause crop injury to young peppers and pears during high temperature conditions--

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