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                                          ET L'AGRICULTURE

                                          Original:  ENGLISH
                                          Distr.: LIMITED
                                          Date of issue:  February 1994



         It must be noted that the issue of a Data Sheet for a
    particular pesticide does not imply endorsement of the pesticide by
    WHO or FAO for any particular use, or exclude its use for other
    purposes not stated. While the information provided is believed to
    be accurate according to data available at the time when the sheet
    was compiled, neither WHO nor FAO are responsible for any errors or
    omissions, or any consequences therefrom.

    The issue of this document does    Ce document ne constitue pas une
    not constitute formal              publication. Il ne doit faire
    publication. It should not be      l'objet d'aucun compte rendu ou
    reviewed, abstracted or quoted     résumé ni d'aucune citation sans
    without the agreement of the       l'autorisation de l'Organisation
    Food and Agriculture               des Nations Unies pour
    Organization of the United         l'Alimentation et l'Agriculture
    Nations or of the World Health     ou de l'Organisation Mondiale de
    Organization.                      la Santé.


Primary use:          Herbicide

Secondary use:        Plant growth regulator

Chemical group:       Triazole


1.1   COMMON NAME:                   Amitrole (E-ISO, F-ISO).

1.1.1  Identity

      IUPAC chemical name:             1-H-1,2,4-triazol-3-ylamine,
                                     (formerly 1-H-3-amino-1,2,4-triazole)

      CAS chemical name:           1-H-1,2,4-triazol-3-amine,
                                   (formerly 3-amono-s-triazole).

      CAS registry number:             61-82-5

      RTECS registry number:       XZ 3850000

      Chemical formula:                C2H4N4

      Relative molecular mass:         84.08

      Structural formula:
                                    Structural Formula

1.1.2  Synonyms:  Aminotriazole;  Triazolamine;  ATA;
      Amitril;  Amitrol;  AmizolR; CytrolR;  DomatolR;  ElmasilR;
      ENT 25455;  VoroxR;  WeedarR; WeedazolR; 3A-T.

1.2   SYNOPSIS Amitrole is a non-selective foliage-
      absorbed herbicide that inhibits chlorophyll formation and regrowth
      from buds.  The acute mammalian toxicity is low.  Repeated exposure
      induces goitre and repeated high doses resulted in thyroid tumours
      in rats.  Its use is restricted to non-food and non-feed stuff crops.


1.3.1  Physical characteristics:  Pure amitrole is a
      colourless crystalline powder with a bitter taste.  It is a strong
      chelating agent with a melting point of 153-159 °C and a specific
      gravity of 1.138 at 20 °C.  Corrosive to iron, aluminium, copper and
      copper alloys.

1.3.2  Solubility:  300 g/L water at 20 °C;  260 g/kg
      ethanol at 75 °C; moderately soluble in methylene chloride,
      chloroform;  insoluble in acetone, diethyl ether and hydrocarbons.

1.3.3  Stability:  Amitrole is thermally stable.  It is
      also stable in neutral or alkaline media, but it forms salts.  It
      breaks down in ultraviolet light.  Forms chelates with metals, and is
      thus corrosive to aluminium, copper and iron.

1.3.4  Vapour pressure:  Negligible (55 nPa, at 20 °C).


1.4.1  Common formulations:  Available as water soluble
      powder (50-95%) as well as liquids, water soluble concentrate and
      aerosol sprays.  Often used with an activator, ammonium thiocyanate
      and with other herbicides like simazine.

1.4.2  Pests controlled:  Used against perennial
      broadleaf weeds, annual grasses such as bermuda grass, Canada
      thistle, cattails, poison oak, poison ivy, quackgrass.  Particularly
      effective in the control of water hyacinth.

1.4.3  Use pattern:  Foliar application to non-feed and
      non-food crop locations, such as industrial land.  Used around
      established fruit trees after harvest, for spot application to
      control Tussock grass.  Applied while weeds in vigorous growth.

1.4.4  Unintended effects:  Amitrole has high potential
      mobility in soil.  Degradation of amitrole in soil is usually
      fairly rapid but variable with soil type and temperature.  Therefore,
      its retention in moist soils by absorption makes high leaching
      potential very unlikely to be realised in practice.  The few reports
      of effects on non-target vegetation support this view.

      No recommended usage reported.


1.6.1  Common formulations:  Technical grade solutions (200
      g/L) and as water soluble powder (10%), and in combination with
      simazine and/or other herbicides.

1.6.2  Pests controlled:  Amitrole has a wide spectrum
      of activity against annual and perennial broad leaf and grass type

1.6.3  Use pattern:  Foliar application, but amitrole
      is also translocated to the roots to kill deep rooted perennials.
      May take up to three weeks for full effect.  Do not plant vegetable
      crops within eight months of autumn spraying of garden plots.



2.1.1  Absorption route:  Amitrole is absorbed from the
      gastro-intestinal tract, by inhalation of spray-mists and to a
      lesser extent through intact skin.

2.1.2  Mode of action:  Amitrole has been shown to be
      goitrogenic in several animal species. Biochemical mechanisms
      include reduced thyroid uptake of iodine and inhibition of peroxidase
      activity of the thyroid.  The resulting reduction of thyroid hormones
      induces a hypothalamus mediated TSH stimulation on the thyroid
      itself.  This prolonged stimulation is thought to be responsible for
      the induction of thyroid cancers in animals treated with high doses
      of amitrole.

2.1.3  Excretion products:  Little metabolic
      transformation of amitrole occurs in mammals and it is excreted in
      the urine mainly unchanged within a few hours.  Two urinary
      metabolites have been identified in rats, i.e.
      3-amino-5-mercapto-1,2,4-triazole and 3-amino-1,2,4-triazolyl-(5)-
      mercapturic acid.

2.1.4  Toxicity, single dose:

Oral LD50
   Rat                 5 000 mg/kg b.w.
   Rat                25 000 mg/kg b.w.
   Mouse     11 000 - 14 700 mg/kg b.w.
   Rabbit            >2 150 mg/kg b.w.

Intraperitoneal LD50
   Mouse             >4 000 mg/kg b.w.

Intravenous LD50
   Mouse               5 000 mg/kg b.w.
   Rat               >2 500 mg/kg b.w.

Dermal LD50 (24h)
   Rabbit           >10 000 mg/kg b.w.

Inhalation LC50 (4h)
   Rat                 >439 mg/L

      Signs of toxicity include dyspnoea, ataxia and diarrhoea with
      vomiting.  Coma and death appeared to be associated with respiratory
      insufficiency.  Gastrointestinal irritation and haemorrhage were the
      only macroscopic findings.  Single doses of amitrole (10 mg/kg s.c.
      to rats) were shown to decrease iodine uptake and thyroid hormone

     Dermal irritancy:  Cutaneous application of 10 000 mg/kg b.w.
     to rabbits or 2500 mg/kg b.w. to rats produced a temporary mild

      Ocular irritancy:  A mild irritation of 28 - 48 hour duration
      was observed following application of 3 mg to the conjunctival sac
      of rabbits.  No permanent damage was observed.

2.1.5  Toxicity, repeated doses:

      Oral:  Gavage administration of 100, 200 or 400 mg/kg b.w./day,
      five days/week for four weeks, to rats resulted in a reduced growth
      rate, reduced iodine content of the thyroid and an increased relative
      thyroid weight.

      Male and female beagle dogs showed no adverse effects in growth,
      behaviour, haematology, histopathology (including thyroid), or in
      liver and kidney function tests following exposure to gelatin capsule
      doses of up to 12.5 mg/kg b.w./day, six days/week for 52 weeks.

      Intraperitoneal:  Increased thyroid weights (300-400%) were
      noted in male and female rats receiving 21 intraperitoneal injections
      of 1000 mg/kg b.w. over a period of 45 days.  No effect on growth or
      food consumption was observed.  Liver catalase activity was reduced
      more than 90% in rats receiving 1000 mg/kg b.w, 14 times over a
      period of 30 days.

      Amitrole (500 or 1000 mg/kg day), five days per week for five weeks
      to chicks increased relative thyroid weight from day 10 onward.
      Histopathology indicated hyperplasia and disappearance of the
      colloid.  The reversibility of the lesions was shown in birds treated
      only for 17 days and allowed to recover for two weeks after the end
      of treatment.

      Inhalation:  Exposure of rabbits, guinea pigs, rats or mice to
      4 mg/L air, 2 hour/day for 10 weeks caused a reduction in body weight
      in rabbits and guinea pigs, and a slight reduction in body weight in
      rats and mice.  Slight anaemia, lymphocytopenia and neutropenia were
      observed in rabbits.

      Rats were exposed to amitrole (0, 0.1, 0.32, 0.99 or 4.05 mg/L for
      five hours/day, 5 times per week for 4 weeks).  Blood levels of
      thyroid hormones were found to be decreased and thyroid hyperplasia
      was noted at all but the lowest dose level.

2.1.6  Dietary studies:

      Short term:  Numerous investigations have shown that amitrole
      administered in drinking water or in the diet, may cause decreased
      body weight gain, increased thyroid weight related with changes of
      thyroid function in rats.

      Amitrole was given to rats at a dose of 1000 mg/kg/diet for 83 days.
      Thyroid weight and iodine content of thyroid were increased, starting
      3 days after the beginning of treatment.  Amitrole was given to rats
      (0, 30, 100 or 300 mg/kg/diet) for 28 days followed by a recovery
      period of 28 days.  At dose levels of 100 mg/kg/diet or more,
      amitrole rapidly suppressed T3 and T4 hormone levels and maintained
      the depressed levels during treatment.  Both T3 and T4 levels
      returned to control values within three weeks following withdrawal of
      amitrole from the diet.  The NOEL was 30 mg/kg/diet.

      Groups of rats were administered amitrole in the diet at dose levels
      of 0, 2, 10 and 50 mg/kg/diet for 13 weeks.  The only significant
      findings were the histopathological changes found in the 10 and 50
      mg/kg groups.  The number of blood vessels per thyroid section was
      found to be a good indication of histopathological changes in the
      thyroid.  The NOEL was 2 mg/kg/diet.

      In a series of experiments in rats giving amitrole at various dose
      levels (0 through 200 mg/kg/diet for 6 to 13 weeks) it was found that
      measurement of iodine uptake is a sensitive method for assessing the
      effects  of amitrole on the thyroid.  The NOEL was 2 mg/kg/diet.

      Long term:  Reversible thyroid hyperplasia has been reported
      with long term feeding of mice with amitrole at levels of
      1000 mg/kg/diet.  In another study in mice (0, 1, 10, 100
      mg/kg/diet), infective thyroid weights were elevated at the highest
      dose level.

      Amitrole was given to rats (0, 10, 50 or 100 mg/kg/diet for two
      years) and found to cause thyroid hyperplasia after 68 weeks of
      treatment.  The NOEL was 10 mg/kg/diet.  In another study in rats (0,
      1, 10 and 100 mg/kg/diet) similar findings were reported including
      dysplasia of the thyroid and reduced iodine uptake.  The NOEL was 10

      Authors who have detailed the time-course of the response of the
      thyroid to amitrole treatment have shown that after a short lag phase
      of a few days there is a rapid rise in TSH that is paralleled by
      thyroid hypertrophy and hyperplasia.  These effects peak and plateau
      after 3-4 months and thereafter remain relatively stable despite
      further exposure.  A number of studies have shown that the
      goitrogenic action of amitrole is reversible on withdrawal of the
      herbicide exposure.

2.1.7  Supplementary studies of toxicity:

      Carcinogenicity:  In a mouse long-term study of over 100
      chemicals, amitrole was used as a positive control compound at the
      maximum tolerated dose level (1000 mg/kg b.w. by gavage from one to
      four weeks of age, then 2192 mg/kg/diet for life).  The majority of
      male and female mice of two strains developed carcinoma of the
      thyroid, and hepatomas.  This dosage regimen reduced longevity.
      Another study in mice confirmed a high incidence of hepatocellular
      carcinomas and hepatomas following long term exposure to amitrole at
      the highest dose.

      In a study in rats (0, 10, 50 and 100 mg/kg/diet) showed an increased
      incidence of thyroid tumours at the higher doses only.

      In a study in rats amitrole was given in the drinking water (0.1%
      corresponding to 1000 mg/kg/diet) for 18-20 months.  All animals
      developed follicular adenomas and some animals developed follicular
      carcinomas as well.  In another similar experiment (same dose level)
      the latency for developing thyroid tumors was estimated to be one

      Teratogenicity:  No malformations were observed in mice
      foetuses removed on day 18. There was a marked decrease in body
      weight gain in dams receiving over 1000 mg/L in drinking water from
      days 6 to 18.  Maternal body weight was reduced at and above 1000
      mg/L and the foetuses of these mice were small and underdeveloped.

      No teratogenic effects have been detected in rats given up to 1000
      mg/kg b.w. day on days 6 to 15 gestation.

      Reproduction:  No effects on reproduction were observed in a
      multi-genarian study where rats were fed amitrole at dietary levels
      of 0, 25 or 100 mg/kg/diet for 61 and 173 days before mating to
      produce the F1a and F1b generation respectively.  Hyperplasia of the
      thyroid was observed in all animals at the 100 mg dose but not at the
      25 mg dose.

      Mutagenicity:  Amitrole was not mutagenic to the repair deficient
      strains of  Escherichia coli nor to several strains of  Salmonella 
       typhimurium , with or without metabolic activation.  Weak mutagenic
      activity was observed with  Streptomyces coelicolor . No evidence of
      chromosomal damage was observed following  in vitro incubation of
      human leucocytes with 0.2 - 1% (w/v) amitrole.  Concentrations over
      0.2% were cytotoxic, inhibiting lymphoblast transformation.

      Male and female  Drosophila melanogaster reared on 10 mg amitrole/kg
      media showed no evidence of amitrole induced sex-chromosome non-
      disjunction or sex-linked dominant lethal mutations.

      Other:  The inhibition of many haem containing enzymes has been
      demonstrated  in vivo and  in vitro .  Amitrole inhibits thyroid,
      liver, kidney, eye and blood catalases and the incorporation of both
      59Fe and 14C-aminolevulinic acid into haem.


2.2.1  Absorption:  Amitrole is absorbed from the
      gastrointestinal tract.  It may be absorbed by inhalation of spray
      mists and minimally through intact skin.

2.2.2  Dangerous doses:

      Single:  The intentional ingestion of 20 mg/kg amitrole by a
      female subject did not cause symptoms of poisoning.

      Repeated:  No published information available.

2.2.3  Observations in occupationally exposed workers:
      A single case report describes the development of a chemical
      pneumonitis after one exposure to an amitrole spray containing 19%
      aminotriazole, 17% ammonium thiocyanate, less than 1% sodium
      diethylsulfosuccinate and less than 1% ethylene oxide.

      At an estimated dermal exposure of 340 mg/day/man over a 10 day
      spraying operation no thyroid dysfunctions were detected.

      Prolonged exposure for up to 16 years to unknown levels of amitrole
      during its production and packaging did not cause thyroid

2.2.4  Observations on exposure of the general public:
      No published information available.

2.2.5  Observations on volunteers:  A single oral dose
      of 100 mg of amitrole inhibited 131I intake of the thyroid for 24
      hours in healthy and hyperthyrotid individuals.  A dose of 10 mg
      produced only slight effects.

      Amitrole had no irritant effect in a 4 - 8 hour exposure dermal patch
      test, and had only slight irritancy after 24 hours exposure.

2.2.6  Reported mishaps:  In a suicide attempt, a
      37-year old woman ingested a formulation of 30% amitrole and 56%
      diuron.  The amitrole dose was estimated to be 20 mg/kg b.w. and no
      signs of intoxication were observed.  Unchanged amitrole was excreted
      in the urine within a few hours at a concentration of 1 g/L.


2.3.1  Birds:
Oral LD50
   Coturnix quail      >316 mg/kg b.w.

Dietary LC50 (5 days)
   Japanese quail        >5000 mg/kg diet
   Ring-necked pheasant  >5000 mg/kg diet
   Mallard duck          >5000 mg/kg diet

2.3.2  Other species:   Drosophila melanogaster 
      (larvae) LC5040 mg/kg diet. prolongation of development time
      occurred in this species at doses above 10 mg/kg diet.  No mutagenic
      effect was seen.



      Risks associated with dietary exposure led to the cancellation of all
      food and feed uses of amitrole in 1971 in the United States of
      America.  For definition of categories see "Introduction to Data Sheets".

      All liquid formulations over 25%, Category 4.

      All other liquid formulations, all solid formulations, Category 5.


      Formulations in Category 4:  Should be transported in clearly
      labelled, rigid and leakproof containers, kept out of reach of
      children, and away from food and drink. Storage should be under lock
      and key and secure from access by children and other unauthorized

      Formulations in Category 5:  Should be transported and stored
      in clearly labelled, leakproof containers, out of reach of children,
      away from food and drink.


      Formulations in Category 4:  Protective clothing should be
      used by all persons handling the compound.  Adequate washing
      facilities should be available at all times during the handling and
      they should be close to the site of handling.  Eating, drinking and
      smoking should be prohibited during handling and before washing of
      hands and face after handling.

      Formulations in Category 5:  No facilities other than those
      needed for the handling of any chemical are required.


      All formulations:  Containers may be decontaminated (for
      method see Section 4.3).  Decontamination procedures must be
      especially thorough to avoid subsequent contamination of food and
      feed crops and decontaminated containers should not be used for
      transportation or storage of food or drink.  Discarded containers
      that are not decontaminated should be burned or crushed and buried
      in a deep (more than 0.5 m) dry pit.  Care must be taken to avoid
      subsequent contamination of water sources.


      Formulations in Categories 4 and 5:  Special account should be
      taken of the workers' ability to comprehend and follow instructions.
      Training of workers in techniques to avoid contact is essential.
      Pre-employment and periodic medical examinations are required,
      including a check-up on thyroid function.


      Amitrole is not usually recommended for distribution by aircraft.


      Formulations in Category 4 - Minimum cautionary statement:

      Amitrole is a triazole herbicide.  Avoid ingestion and inhalation of
      amitrole.  Avoid skin contact; wear protective clothing and
      impermeable gloves when handling the material.  Wash thoroughly with
      soap and water after using the product.  Keep the material out of
      reach of children and well away from food stuffs, animal feed and
      food containers.  If poisoning occurs, call a physician. There are no
      specific antidotes.

      Formulations in Category 5 - Minimum cautionary statement:
      This formulation contains amitrole, it may be poisonous if swallowed.
      Keep the material out of reach of children and well away from food
      stuffs, animal feed and food containers.


      As it is recommended only for non-edible crops, no MRLs are
      recommended by FAO/WHO Joint FAO/WHO Meeting on Pesticide Residues
      (JMPR).  In 1993 the JMPR established a Temporary Acceptable Daily
      Intake (TADI) of 0-0.0005 mg/kg b.w.



4.1.1    General:  Amitrole is a triazole herbicide of low
          acute mammalian toxicity.  It is absorbed from the
          gastrointestinal tract and may also be absorbed through intact
          skin or by inhalation of mist during spraying.  Due to the
          goitrogenic effect and carcinogenic action in laboratory tests,
          use of amitrole in the United States of America has been
          restricted to non-edible crops or non-crop land.

4.1.2  Manufacture and formulation - TLV:  0.2 mg/m3.
      Closed systems and forced ventilation are required to reduce, as much
      as possible, the exposure of workers to the chemical.

4.1.3  Mixers and applicators:  When opening the
      container and when mixing, protective impermeable boots, clean
      overalls, gloves and respirator should be worn.  Mixing, if not
      mechanical, should always be carried out with a paddle of appropriate
      length.  When spraying tall crops a face mask should be worn, as well
      as an impermeable hat, clothing, boots, and gloves.  The applicator
      should avoid working in spray mist and avoid contact with the mouth.
      Particular care is needed when equipment is being washed after use.
      All protective clothing should be washed immediately after use,
      including the insides of gloves.  Splashes must be washed immediately
      from the skin, or eyes with large quantities of water.  Before
      eating, drinking, or smoking, hands and other exposed skin should be

4.1.4  Other associated workers:  Persons exposed to
      amitrole and associated with its application should wear protective
      clothing and observe the precautions described above in 4.1.3. under
      "Mixers and Applicators".

4.1.5  Other populations likely to be affected:  With
      correct use in agriculture, and in the home gardens, the general
      population should not be exposed to hazardous amounts of amitrole.


      Unprotected persons may enter treated area once application has


      Residues in containers should be emptied in diluted form into a dry
      deep pit (more than 0.5 m), taking care to avoid contamination of
      groundwaters.  Empty containers may be decontaminated by filling them
      completely with water and by allowing them to stand for 24 hours
      before emptying.  The procedure should be repeated three times.
      Impermeable gauntlets should be worn during the work and an adequate
      soakage pit should be provided for the rinsings. Decontaminated
      containers should not be used for transportation and storage of food
      or drink. Spillage of amitrole and its formulations should be removed
      by washing with a water and detergent solution and then rinsing with
      large quantities of water.


4.4.1    Early symptoms of poisoning:  Not known.

4.4.2  Treatment before person is seen by physician, if these
        symptoms appear following exposure:
      The person should stop work immediately, remove contaminated clothing
      and wash contaminated skin with water, and soap if available, and
      flush with large quantities of water.  Vomiting may be induced if a
      large dose has been ingested provided that the person is conscious.



5.1.1   General information:  Amitrole is a triazole
          herbicide of low acute mammalian toxicity which may be absorbed
          from the gastrointestinal tract, through the intact skin, and by
          inhalation of aerosols or mists during spray application.
          Chronic high exposure may cause changes in the thyroid function.

5.1.2  Symptoms and signs:  Unknown.

5.1.3  Laboratory:  Urinary levels of amitrole could be
         used as a measure of exposure.

5.1.4  Treatment:  Symptomatic.

5.1.5  Prognosis:  Unknown.

5.1.6  References to previously reported cases:

      Geldmacher-V. Mallinckrodt M, Schmidt HP (1970), Arch Toxikol 27:

      PIMS (1978)  Pesticide Incident Monitoring Service.  Summary of
      reported incidents involving Amitrole.  No. 114.  Office of Pesticide
      Programs, USEPA.




      (References only are given.)

5.3.1  Detection and assay of compound:

      Agrawal BBL, Margoliash E (1970), A spectrophotometric method for the
      determination of aminotriazole and other aromatic amines.  Anal
      Biochem 34: 505-516.

      Demint RJ, Frank PA, Comes RD (1970), Amitrole residues and rate of
      dissipation in irrigation water.  Weed Sci 18, 439-442.

      Storherr RW, Burke J (1961), Determination of 3-amino-1,2,4-triazole
      in crops. J Assoc Off Anal Chem 44: 196-199.

5.3.2  Other tests in case of poisoning:  None.


1.    WHO (1994), Environmental Health Criteria 158;  Amitrole;  Geneva,
      World Health Organization.

2.    WHO (1994), Health and Safety Guide 85;  Amitrole;  Geneva, World
      Health Organization.

3.    FAO/WHO (1978), Pesticide Residues in Food:  1977 evaluations.  FAO
      Plant Production and Protection Paper 10 Sup, 1978.

4.    The Pesticide Manual, A World Compendium (9th edition 1991),
      Worthing, C.R. and Hance, eds., British Crop Protection Council, 20
      Bridport Road, Thornton Heath, CR4 7QG, United Kingdom.

5.    IARC (1986), IARC Monographs on the Evaluation of the Carcinogenic
      Risk of Chemicals to Humans;  Some Halogenated Hydrocarbons and
      Pesticide Exposures, Volume 41, Lyon, IARC.

                                   = = =

See Also:
        Amitrole (EHC 158, 1994)
        Amitrole (IARC Summary & Evaluation, Supplement 7, 1987)
        Amitrole (IARC Summary & Evaluation, Volume 41, 1986)
        Amitrole (IARC Summary & Evaluation, Volume 7, 1974)
        Amitrole (ICSC)
        Amitrole (PIM 648)