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Rotenone

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names, main trade names
   1.6 Main manufacturers, main importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/Form
      3.3.3 Description
   3.4 Hazardous characteristics
4. USES/CIRCUMSTANCES OF POISONING
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstance of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. TOXICOLOGY
   7.1 Mode of Action
   7.2 Toxicity
      7.2.1 Human data
      7.2.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central Nervous System (CNS)
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    ROTENONE

    International Programme on Chemical Safety
    Poisons Information Monograph 474
    Chemical

    1.  NAME

        1.1  Substance

             Rotenone

        1.2  Group

             Insecticide

        1.3  Synonyms

             Derrin;
             Nicouline;
             Rotenonum;
             Tubatoxin;

        1.4  Identification numbers

             1.4.1  CAS number

                    83-79-4

             1.4.2  Other numbers

        1.5  Main brand names, main trade names

        1.6  Main manufacturers, main importers

    2.  SUMMARY

        2.1  Main risks and target organs

             Inhalation or ingestion of large doses may cause
             numbness of oral mucous membranes, nausea and vomiting,
             muscle tremors, tachypnea.  With lethal doses respiratory
             paralysis occurs.  Chronic poisoning may produce fatty
             changes in liver and kidneys.  Direct contact occasionally
             causes mild irritation of skin or eyes.  Rotenone is more
             toxic when inhaled than when ingested.
    
             Target organs:  central nervous system, skin, mucous
             membrane.

        2.2  Summary of clinical effects

             Respiratory effects mainly after inhalation are
             coughing, sneezing, rhinorrhoea, respiratory stimulation
             followed by depression, and severe pulmonary irritation from
             inhalation of dusts.  Pulmonary oedema and pneumonitis may
             occur due to the aspiration of solvents or vehicle, which is
             often kerosene.  The immediate cause of death is
             asphyxia.
    
             Digestive symptoms include numbness of oral mucous membranes,
             vomiting, and gastric pain.
    
             Central nervous manifestations are muscle tremors,
             incoordination, clonic convulsions, and lethargy.  Skin and
             conjunctival irritation from local contact.

        2.3  Diagnosis

             Nausea, vomiting, abdominal pain, numbness of the oral
             mucosa, respiratory depression, tremors, lethargy and
             convulsions occur following ingestion or inhalation.
    
             Laboratory analysis of blood may show hypoglycaemia.
    
             Vomitus or gastric aspirate should be collected in clean
             bottles for identification.

        2.4  First-aid measures and management principles

             Ingestion:  Induce vomiting unless the product vehicle
             is a petroleum distillate (see the treatment protocol on
             decontamination procedures)
    
             Gastric lavage may be performed if a large amount of rotenone
             was ingested even if it is dissolved in kerosene or a related
             petroleum distillate.
    
             A slurry of powdered activated charcoal in water should be
             given by mouth after vomiting, or after about 30 minutes if
             the patient does not vomit. Avoid ingestion of oils and fats,
             which promote the absorption of rotenone.
    
             Administer glucose intravenously.
    
             If agitation or seizures occur, administer diazepam IV.
    
             Inhalation: Provide symptomatic and supportive treatment.
             Ensure patient's airway and ventilation.
    
             Skin and eye contact: Wash thoroughly with water.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             Rotenone is extracted from plants, particularly from
             Derris spp grown in Malaya, East Indies, and South America,
             and Lonchocarpus also known as "cub", grown in Central and
             South America. Examples are e.g  Derris Amazonica Killip and
             Derris Pterocarpus Killip. Other genera are Tephrosia,
             Milletia, Mundulea, Spatholobus, and Pachyrhizus. These
             plants have been known for centuries to be toxic to fish and
             used to poison arrowheads. Rotenone is present mainly in the
             roots of the plants.  The roots are dried, ground, and the
             active principle extracted with solvents such as chloroform
             and benzene (Gosselin, 1984; Hayes, 1982).

        3.2  Chemical structure

             Chemical name:  [2R-(2a, 6a alpha, 12a alpha)] - 1, 2,
             12, 12a-tetrahydro-8,9-dimethoxy-2-(1-methylethyl)[I]
             benzopyranol [3,4-b] furo 12,3-h] [I]benzopyran-6(6aH)-one
             (Windholz, 1983).
    
             Molecular weight = 394, 41
    
             (C 70.04% H 5.62% 0 24.34%)
    
             Structural formula:

        3.3  Physical properties

             3.3.1  Colour

             3.3.2  State/Form

             3.3.3  Description

             Melting points 165 to 166C (dimorphic form 181'C)
             Vapour pressureless than 0.00001 mbar at 20C
             SolubilityPractically insoluble in water;
             soluble 1 in 300 of alcohol, 1 in 12 of acetone, 1 in 3 of
             chloroform, and 1 in 200 of ether (Reynolds, 1989).

        3.4  Hazardous characteristics

             The normal state at room temperature is colourless to
             brownish crystals, or a white or brownish-white, odourless,
             tasteless, crystalline powder. Unstable in the presence of
             air or light. Colourless solutions of rotenone in organic
             solvent, when exposed, become successively yellow, orange,
             and finally deep red as a result of oxidation.  Rotenone is
             readily racemised by alkali and readily oxidized especially

             in the presence of light and alkali. Store in airtight
             container in temperatures not exceeding 25C and protect from
             light.
    
             Environmental risks:  the effects are short-lived. Rotenone
             is not toxic to plants but extremely toxic to fish.  Residues
             must not be allowed to drain into streams (Windholz, 1983;
             Reynolds, 1989; Hayes, 1982).

    4.  USES/CIRCUMSTANCES OF POISONING

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    Rotenone is a widely used insecticide of
                    botanical origin.  It is a selective non-systemic
                    insecticide with some acaricidal properties. Rotenone
                    is used alone or in combination with pyrethrins,
                    pyrethrum, and piperonyl butoxide to control a wide
                    variety of insects on food crops. In human and
                    veterinary medicine the compound has been applied
                    directly to treat lice, ticks, scabies and other
                    ectoparasites.

        4.2  High risk circumstance of poisoning

             Rotenone is a very safe compound when properly used. 
             The formulations are presented in low concentrations, (1 to
             5%), have low solubility in water, and decompose rapidly when
             exposed to light and air.  The irritating properties to
             mucous membranes provoke prompt vomiting, avoiding further
             absorption.
    
             Accidents have been reported in children who ingest large
             doses.  Gosselin (1984) reported no fatalities.  De Wilde
             (1986) reported one death in a child.

        4.3  Occupationally exposed populations

             Agricultural workers and pesticide applicators are
             occupationally exposed.  Factory workers processing rotenone
             without proper protection have developed rhinitis and
             dermatitis (Hayes, 1982).

    5.  ROUTES OF ENTRY

        5.1  Oral

             Accidental or deliberate ingestion of the product may
             occur.Gastrointestinal absorption is slow and incomplete. Its
             irritant effect on mucous membranes induces immediate
             vomiting (Gosselin, 1984).

        5.2  Inhalation

             Inhalation of dusts of rotenone produces is a more
             common cause of poisoning than ingestion and causes severe
             pulmonary irritation (Gosselin, 1984).

        5.3  Dermal

             Direct contact with the skin occasionally causes mild
             irritation.

        5.4  Eye

             Direct eye contact occasionally causes mild irritation
             of conjunctiva.

        5.5  Parenteral

             Unknown

        5.6  Others

             Unknown

    6.  KINETICS

        6.1  Absorption by route of exposure

             Gastrointestinal absorption is low and incomplete. In
             animals, rotenone is hundreds of times more toxic
             intravenously than orally. Fats and oils increase absorption
             (Gosselin, 1984).
    
             Inhalation of dusts or fine powders cause immediate pulmonary
             irritation. Data on pulmonary or dermal absorption are not
             available.

        6.2  Distribution by route of exposure

             No data are available concerning distribution after oral
             ingestion or inhalation or dermal exposure.

        6.3  Biological half-life by route of exposure

             Unknown

        6.4  Metabolism

             Rotenone is metabolized by the liver. It inhibits the
             oxidation of NADH to NAD, and blocks the oxidation by NAD of
             substrates such as glutamate, alpha-ketoglutarate, and
             pyruvate (Goodman, 1985).
    
             After intravenous injection in the rat and mouse, rotenone is
             metabolized by NADP-linked hepatic microsomal enzymes.
             Several metabolites have been identified as rotenoids
             (rotenolone I and II, hydroxy and dihydroxyrotenones, etc.)
             with a toxicity similar to rotenone.  One mechanism of
             metabolism was demethylation (Hayes, 1982;  Gosselin,
             1984).

        6.5  Elimination by route of exposure

             In the mouse and rat, approximately 20% of a dose is
             recovered in urine within 24 hours of oral administration
             (Hayes, 1982).

    7.  TOXICOLOGY

        7.1  Mode of Action

             Rotenone inhibits the oxidation of NADH to NAD, blocking
             the oxidation by NAD of substrates such as glutamate,
             alpha-ketoglutarate, and pyruvate. Rotenone inhibits the
             mitochondrial respiratory chain between diphosphopyridine
             nucleotide and flavine.  This blockade is overcome by Vitamin
             K3 (menadione sodium bisulphite), which apparently activates
             a bypass of the rotenone sensitive site.  Rotenone is a
             powerful inhibitor of mitochondrial electron transport. The
             regulation of fatty acid synthesis in mitochondria by
             rotenone may be altered after chronic administration,
             resulting in fatty changes in the liver (Hayes, 1982;
             Gosselin, 1984; Goodman & Gilman, 1985).

        7.2  Toxicity

             7.2.1  Human data

             7.2.1  Adults

                    <7.2.1.>Mean lethal oral dose is about 0.3 to 0.5 g/kg
                    (Gosselin, 1984).

                    7.2.1.2  Children

                             Mean lethal oral dose is estimated
                             from 0.3 to 0.5 g/kg (Gosselin, 1984).
    
                             In one fatal case, postmortem concentrations
                             of rotenone in the stomach and blood were
                             1,260 and 2.4 ppm (De Wilde, 1986).

             7.2.2  Relevant animal data

                    The lethal dose in mammals range from 50 mg to
                    3000 g/kg (Ellenhorn and Barceloux, 1988).
    
                    Lethal Dose 50 (mg/kg)
    
                    Rat  (oral) 60 to 132
    
                    Rat  (intravenous) 0.2 to 0.3
    
                    Mouse (intraperitonial) 5.4
    
                    Rabbit (oral) 1.5
    
                    Rabbit (dermal) 100 to 200
    
                    Rabbit (intravenous) 0.35 to 0.65 (Hayes, 1982)
    
                    In the rat and dog, experimental inhalation of
                    rotenone dust produced symptoms within minutes. The
                    onset of poisoning was more rapid than after oral
                    administration and the fatal dose was lower (Hayes,
                    1982).
    
                    Rotenone is highly toxic to fish.

             7.2.3  Relevant in vitro data

                    In isolated rat liver mitochondria, the aerobic
                    oxidation of pyruvate is almost completely inhibited
                    by rotenone.  yolitic effects are also described
                    (Hayes, 1982).

             7.2.4  Workplace standards

                    The TLV-TWA (Threshold limit Value-time
                    Weighted Average) for commercial rotenone is 5 mg/m3
                    (American Conference of Governmental Industrial
                    Hygienists, 1987-8).  This indicates that an
                    occupational intake of 0.7 mg/kg/day is considered
                    safe (Hayes, 1982).

             7.2.5  Acceptable daily intake (ADI)

                    The proposed No-Adverse-Response Level (SNARL)
                    for chronic exposure to rotenone:  0.014 mg/l
                    (National Research Council, 1983).

        7.3  Carcinogenicity

             The carcinogenicity of rotenone is a controversial
             issue. It has been suggested that rotenone may cause tumours
             only in vitamin-deficient animals (Gosalvez, 1983). 

        7.4  Teratogenicity

             No data available.

        7.5  Mutagenicity

             No mutagenic effects were reported in mouse bone marrow
             (Waters et al, 1982). Rotenone is non-mutagenic in bacterial
             reversion tests (Moriya et al, 1983)

        7.6  Interactions

             When applied in low concentrations to plant foliage,
             rotenone catalyses photoisomerization of dieldrin and other
             cyclodiene insecticide residues. However, photodecomposition
             was a predominant effect when residues of rotenone were
             combined with those of methylcarbamate and phosphothionate
             insecticides (Hayes, 1975).

    8.  TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                    8.1.1.2  Biomedical analyses

                    8.1.1.3  Arterial blood gas analysis

                    8.1.1.4  Haematological analyses

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                    8.1.2.2  Biomedical analyses

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

                    8.1.3.1  Toxicological analyses

                    8.1.3.2  Biomedical analyses

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

        8.2  Toxicological Analyses and Their Interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple Qualitative Test(s)

                    8.2.1.2  Advanced Qualitative Confirmation Test(s)

                    8.2.1.3  Simple Quantitative Method(s)

                    8.2.1.4  Advanced Quantitative Method(s)

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple Qualitative Test(s)

                    8.2.2.2  Advanced Qualitative Confirmation Test(s)

                    8.2.2.3  Simple Quantitative Method(s)

                    8.2.2.4  Advanced Quantitative Method(s)

                    8.2.2.5  Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                    8.3.1.2  Urine

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses

             8.3.4  Interpretation of biomedical investigations

        8.4  Other biomedical (diagnostic) investigations and their 
             interpretation

        8.5  Overall Interpretation of all toxicological analyses and 
             toxicological investigations

             Sample collection
    
             Collect blood and gastric aspirate/vomitus for analysis.
    
             Biomedical analysis
    
             Determine blood glucose, acid base status, and serum
             electrolytes.
    
             Blood:  Full blood count (red cells), white cell and platelet
             count).
    
             Urine:  Urinalysis to detect red and white blood cells.
    
             In animals, chemical investigations in blood and urine showed
             severe hypoglycaemia.  In man, electrolytes may be altered
             after convulsions.  Liver failure has been reported in
             animals.
    
             Arterial blood gases and acid-base balance may be altered
             because severe overdoses may cause hypoxemia and hypercapnia
             due to respiratory depression and seizures.  Acid-base
             abnormalities follow hypoxemia.
    
             Experimentally, myocardial contractile force is impaired
             (Hayes, 1982).

    
             Toxicological analysis
    
             No information available.
    
             Other investigations
    
             No information available.

        8.6  References

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    After ingestion, signs and symptoms are:
                    numbness of oral mucous membranes, pharyngitis,
                    nausea, vomiting, and gastric pain. Muscle tremors,
                    lethargy, respiratory stimulation followed by
                    depressed respiration (Hayes, 1982; Gosselin, 1984).
                    In one case (De Wilde, 1986 cardiopulmonary arrest was
                    the cause of death. Animal experiments indicate that
                    hypoglycaemia may occur.

             9.1.2  Inhalation

                    Rhinitis, coughing, and sneezing occur.  In
                    experimental acute poisoning, onset of symptoms is
                    fast when dusts or fine powders are inhaled.  Severe
                    pulmonary irritation and asphyxia were present (Hayes,
                    1982).

             9.1.3  Skin exposure

                    Skin irritation is observed after local
                    application.

             9.1.4  Eye contact

                    Conjunctivitis and photophobia.

             9.1.5  Parenteral exposure

                    Experimentally:  vomiting, incoordination,
                    muscle tremors, clonic convulsions, and respiratory
                    failure (Gosselin, 1984).

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    In animals, chronic ingestion causes growth
                    depression (Gosselin, 1984).

             9.2.2  Inhalation

                    Ulcerative rhinitis and complete but transient
                    loss of smell. Irritation of the throat with partial
                    destruction of the soft palate as well as of the
                    anterior pillars (Hayes, 1982).

             9.2.3  Skin exposure

                    Occupational chronic exposure produces
                    important immediate dermatitis characterized by a
                    red-violet colour, slight oedema, and some itching. 
                    If contact is stopped, desquamation occurs and
                    dermatitis became worse,with large papules (Hayes,
                    1982).

             9.2.4  Eye contact

                    Conjunctivitis

             9.2.5  Parenteral exposure

                    No data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             Exposure to low doses of rotenone causes numbness of
             oral mucous membranes, nausea, vomiting, and gastric pain. 
             In acute cases, large doses cause early respiratory
             stimulation followed by depression and stupor. Terminal
             symptoms of rotenone poisoning involve convulsions and
             cardiorespiratory arrest (Gosselin, 1984; Ellenhorn, 1988). 
             In animals, most effects are due to severe
             hypoglycaemia.

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Acute:  Tachycardia, hypotension, impaired
                    myocardial contractility (experimentally).
    
                    Chronic:  No data available.

             9.4.2  Respiratory

                    Acute:  tachypnea, followed by respiratory
                    depression, cyanosis, hypoxemia, mainly after
                    convulsions.  Asphyxia from respiratory arrest. 

                    Severe pulmonary irritation from inhalation of dusts
                    or fine powders.
    
                    Chronic:  Pharyngitis, bronchitis.

             9.4.3  Neurological

                    9.4.3.1  Central Nervous System (CNS)

                             Acute:  Incoordination, tremors,
                             clonic convulsions, stupor.
    
                             Chronic:  No data available.

                    9.4.3.2  Peripheral nervous system

                             Rotenone causes a definite
                             anaesthetic effect when brought into intimate
                             contact with nerve axon, efferent fibres
                             being more sensitive than efferent ones
                             (Hayes, 1982).

                    9.4.3.3  Autonomic nervous system

                             No data available.

                    9.4.3.4  Skeletal and smooth muscle

                             Muscular tremor.

             9.4.4  Gastrointestinal

                    Acute:  Nausea, vomiting, abdominal cramps.

             9.4.5  Hepatic

                    Chronic poisoning may produce fatty changes in
                    liver (Windholz, 1983).

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Chronic poisoning may produce fatty
                             changes in the kidneys (Windholz,
                             1983).

                    9.4.6.2  Others

                             No data available.

             9.4.7  Endocrine and reproductive systems

                    No data available.

             9.4.8  Dermatological

                    Acute: skin irritation results from local
                    application.
    
                    Chronic:  contact dermatitis with erythema, itching,
                    desquamation, papules.

             9.4.9  Eye, ears, nose, throat: local effects

                    Acute:  rhinitis, sneezing, irritation of the
                    conjunctiva.
    
                    Chronic: sneezing and coryza-like symptoms.  Severe
                    irritation of the throat, partial destruction of the
                    soft palate and anterior pillars.
    
                    Ulcerative keratitis.

             9.4.10 Haematological

                    No data available.

             9.4.11 Immunological

                    No data available.

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             Acid-base disturbances may occur
                             after hypoxemia following
                             seizures.

                    9.4.12.2 Fluid and electrolyte disturbances

                             Vomiting may result in loss of
                             fluids in severe poisoning.

                    9.4.12.3 Others

                             No data available.

             9.4.13 Allergic reactions

                    Skin sensitization after local contact.

             9.4.14 Other clinical effects

                    No data available.

             9.4.15 Special risks

                    No data available.

        9.5  Others

             No data available.

        9.6  Summary

    10. MANAGEMENT

        10.1 General principles

             Remove from exposure.  Wash contaminated skin or eyes
             thoroughly. Maintain airway and respiration.  Administer
             oxygen if cyanosis is present. If large amounts have been
             ingested, perform cautious gastric lavage after intubation. 
             Emesis is contraindicated in case of convulsions or when the
             product contains a petroleum distillate.  Control agitation
             and seizures with diazepam.  Administer intravenous glucose
             and vitamin K3 (menadione). Correct dehydration.  Do not
             administer lipids.  After chronic poisoning, discontinue
             exposure.

        10.2 Life supportive procedures and symptomatic treatment

             Assess the airway, respiration, circulation and
             neurological status of the patient.
    
             Monitoring cardiac rhythm, respiration and blood pressure.
    
             Monitor fluid and electrolyte balance and acid-base balance.
    
             If respiration is impaired maintain clear airway, aspirate
             secretions, administer oxygen and support ventilation using
             appropriate mechanical device.
    
             Control convulsions with intravenous diazepam.
    
             If cardiac arrest develops perform cardio-respiratory
             resuscitation.

        10.3 Decontamination

             Gastric lavage may be indicated if a large amount of
             rotenone was ingested, even if the product contains kerosene
             or other petroleum distillate (Gosselin, 1984) (consult the  
             treatment protocol on decontamination procedures).
    

             A slurry of activated charcoal in water is administered by
             mouth or gastric lavage hose after emesis or lavage (or after
             20 minutes if vomiting did not occur).  The usual dose of 1
             g/kg body weight in a dilution at least of 1.4 in water.
    
             Avoid administration of oils and fats, which promote
             absorption of rotenone. After inhalation, management is
             symptomatic and supportive:  remove from exposure, ensure a
             clear airway and ventilate.  Supportive measures include
             oxygen and artificial respiration.
    
             Wash skin and eyes thoroughly with running water.  Control of
             agitation and seizures with intravenous diazepam.  Correct
             hypoglycaemia with IV glucose 5%.

        10.4 Enhanced elimination

             No data available.

        10.5 Antidote treatment

             10.5.1 Adults

                    There is no specific antidote available.

             10.5.2 Children

                    There is also no specific antidote available.

        10.6 Management discussion

             Management is mainly symptomatic.  Experimentally,
             menadione (Vitamin K3) antagonises the inhibition by rotenone
             of mitochondrial respiration. Some authors therefore propose
             a trial with large doses of menadione (Gosselin, 1984).
    
             Hypoglycaemia has not been reported in man, but in the rabbit
             and dog some of the neurological effects are due to severe
             hypoglycaemia (Gosselin, 1984).

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             A 3.5 year-old child swallowed a pesticide containing
             rotenone and developed stupor, vomiting, and depressed
             respiration.  At hospital, she had a cardiopulmonary arrest. 
             The postmortem concentrations of rotenone in the stomach and
             blood were 1260 and 2.4 ppm (De Wilde, 1986).
    

             Some cases of ingestion of the roots of plants (mainly
             "derris") are reported by Hayes (1982) as common means of
             suicide by natives of New Ireland.  Acute congestive heart
             failure was found at autopsy.

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

             Wear suitable protective equipment (dust mask)
             Do not work in strong winds
             Do not blow out clogged nozzles with the mouth
             Avoid all contact by mouth
             Avoid contact with skin and eyes
             Wash off splashes immediately
             Avoid inhaling spray or dusts
             Wash hands and exposed skin after use
             Keep away from children
             Keep away from food and drink
             Keep in closed original containers, and store in a safe place
             Wash out container thoroughly and dispose of safely
             Ensure that all the safety precautions on the product label
             are observed
             In case of accident, seek medical advice immediately

        12.2 Other

             No data available.

    13. REFERENCES

        American Conference of Governmental Industrial Hygienists
        (1987)  Threshold Limit Values and Biological Exposures Indices
        for 1987-1988. Cincinnati, Ohio 114p.
    
        De Wilde AR, Heyndrickx A, Carton D (1986)  A case of fatal
        rotenone poisoning in a child.  J Forensic Sci, 31:1492-8.
    
        Ellenhorn MJ and Barceloux DG (1988). Medical Toxicology.
        Diagnosis and treatment of human poisoing. New York. Elsevier
    
        Goodman LS, Gilman AG, Rall TW, Murad F (1985) Goodman and
        Gilman's The Pharmacological Basis of Therapeutics 7th ed. New
        York, Toronto, London:  Macmillan 1839 p.
    
        Gosalvez M (1983). Carcinogenesis with the insecticide rotenone.
        Life Science. 32: 809 - 816.
    
        Gosselin RE, Smith RP, Hodge HC (1984)  Clinical Toxicology of
        Commercial Products. 5th ed. Baltimore/London:  Williams &
        Wilkins, p.111-366-7.
    

        Hayes WJ Jr (1982) Pesticides studied in man.  Baltimore/London:
        Williams & Wilkins, 81-6.
    
        Hayes Jr WJ (1975)  Toxicology of pesticides.  Baltimore: 
        Williams & Wilkins, p 271.
    
        Moriya M, Ohta T, Watanabe K et al (1983). Further mutagenicity
        studies on pesticides in bacterial reversion assay system. Mutat.
        Res. 116: 185 - 216.
    
        Reynolds JEF (1989) Martindale The Extra Pharmacopoeia.  29th ed.
        London, Pharmaceutical Press, 1896 p.
    
        National Research Council (1983)  Drinking Water and Health Vol. 5
        Washington, D.C.: National Academy Press p.98.
    
        Waters MD, Sandhu SS, Simon VF et al. (1982) Study of pesticide
        genotoxicity.  Basic Life Sci. 21; 275 - 326.
    
        Windholz M. (1983) The Merck Index: an encyclopedia of chemicals,
        drugs, and biologicals.  10th ed. Rahway, New Jersey,  Merck and
        Co., Inc.

    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE 
        ADDRESS(ES)

        Author:     Prof. Alberto Furtado Rahde
                    Poison Centre of Porto Alegre
                    Rua Riachuelo 677, ap. 201
                    90010 Porto Alegre
                    Brazil
    
                    Tel: 0512 275 419
                    Fax: 55 512 391 564
    
        Date:       December 1989
    
        Revised:    London Group
    
        Date:       March 1990
    
        Revised:    Prof. A.F. Rahde
    
        Date:       April 1990.
    


    See Also:
       Toxicological Abbreviations
       Rotenone (HSG 73, 1992)
       Rotenone (ICSC)