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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 73

    ROTENONE
    HEALTH AND SAFETY GUIDE






    UNITED NATIONS INTERNATIONAL

    ENVIRONMENT PROGRAMME LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION




    WORLD HEALTH ORGANIZATION, GENEVA 1992

    Published by the World Health Organization for the International
    Programme on Chemical Safety (a collaborative programme of the United
    Nations Environment Programme, the International Labour Organisation,
    and the World Health Organization)

    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization

    WHO Library Cataloguing in Publication Data

    Rotenone : health and safety guide.

    (Health and safety guide ; no. 73)

    1.Rotenone - standards 2.Rotenone - toxicity 
    3.Environmental exposure I.Series

    ISBN 92 4 151073 0          (NLM Classification: WA 240)
    ISSN 0259-7268

    The World Health Organization welcomes requests for permission to
    reproduce or translate its publications, in part or in full. 
    Applications and enquiries should be addressed to the Office of
    Publications, World Health Organization, Geneva, Switzerland, which
    will be glad to provide the latest information on any changes made to
    the text, plans for new editions, and reprints and translations
    already available.

    (c) World Health Organization 1992

    Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention.  All rights reserved.

    The designations employed and the presentation of the material in this
    publication do not imply the expression of any opinion whatsoever on
    the part of the Secretariat of the World Health Organization
    concerning the legal status of any country, territory, city or area or
    of its authorities, or concerning the delimitation of its frontiers or
    boundaries.

    The mention of specific companies or of certain manufacturers'
    products does not imply that they are endorsed or recommended by the
    World Health Organization in preference to others of a similar nature
    that are not mentioned.  Errors and omissions excepted, the names of
    proprietary products are distinguished by initial capital letters.

    CONTENTS

    INTRODUCTION

    1. PRODUCT IDENTITY AND USES
         1.1. Identity
         1.2. Physical and chemical properties
         1.3. Analytical methods
         1.4. Uses

    2. SUMMARY AND EVALUATION
         2.1. Human exposure to rotenone
         2.2. Effects on the environment
         2.3. Uptake, metabolism, and excretion
         2.4. Effects on animals
         2.5. Effects on human beings

    3. CONCLUSIONS AND RECOMMENDATIONS
         3.1. Conclusions
         3.2. Recommendations

    4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION

         4.1. Human health hazards, prevention and protection, first aid
              4.1.1. Prevention and protection
              4.1.2. First aid
         4.2. Advice to physicians
         4.3. Explosion and fire hazards
         4.4. Storage and transport
         4.5. Spillage and disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
         6.1. Exposure limit values
         6.2. Transport and labelling

    BIBLIOGRAPHY
    

    INTRODUCTION

    This Health and Safety Guide is not based on an existing Environmental
    Health Criteria document, but on critical national reviews.  The
    hazard evaluation in the Health and Safety Guide was made on the basis
    of carefully selected studies, after scrutiny of the original
    publications.

    In order to assist the peer-review process of the present Health and
    Safety Guide, a background companion document was prepared by the IPCS
    and can be obtained from the Director on request;  the IPCS does not
    intend that the background document should be published. 

    The first three sections of this Health and Safety Guide present
    essential technical information and the hazard evaluation.  Section 4
    includes advice on preventive and protective measures and emergency
    action; health workers should be thoroughly familiar with the medical
    information to ensure that they can act efficiently in an emergency. 
    The section on regulatory information has been extracted from the
    legal file of the International Register of Potentially Toxic
    Chemicals (IRPTC) and from other United Nations sources.

    The target readership includes occupational health services, those in
    ministries, governmental agencies, industry, and trade unions who are
    involved in the safe use of chemicals and the avoidance of
    environmental health hazards, and those wanting more information on
    this topic.  An attempt has been made to use only terms that will be
    familiar to the intended user.  However, sections 1 and 2 inevitably
    contain some technical terms.

    Revision of the information in this Guide will take place in due
    course, and the eventual aim is to use standardized terminology. 
    Comments on any difficulties encountered in using the Guide would be
    very helpful and should be addressed to:

    The Director
    International Programme on Chemical Safety
    World Health Organization
    1211 Geneva 27
    Switzerland

    THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING POINT
    TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME

    1.  PRODUCT IDENTITY AND USES

    1.1  Identity

    Rotenone is a naturally occurring chemical with insecticidal and
    piscicidal properties obtained from the roots of several tropical and
    subtropical plant species belonging to genus  Lonchocarpus or
     Derris.

    Chemical formula:                  C23H2206

    Chemical structure:

    CHEMICAL STRUCTURE 1

    Plant names:                        Derris elliptica; Lonchocarpus
                                        utilis; L. urucu; L. nicou;
                                       (barbasco; cube; haiari; nekoe;
                                       timbo)

    Common names of plant extracts:    tubatoxin; tuba-root;  derris-root;
                                       aker-tuba; cube-root

    Formulations:                      Formulations of rotenone often
                                       contain various concentrations of
                                       other pesticides

    Trade/trivial names:               Derril, Tubatoxin, Extrax, Mexide

    CAS registry number:               83-79-4

    RTECS registry number:             DJ2800000

    The purity of rotenone preparations varies widely, depending on
    origin.  Identified impurities include dehydrorotenone and rotenonone.

    1.2  Physical and chemical properties

    Rotenone is a colourless, crystalline solid with a melting point of
    165-166 C and has a very low solubility in water at ambient
    temperatures.  It is soluble in acetone, carbon disulfide, ethyl
    acetate, and chloroform.  It is less soluble in ether, carbon
    tetrachloride, and petroleum solvents.  Solutions are readily
    oxidized, in the presence of light and alkali, to products with weaker
    insecticidal properties.

    1.3  Analytical methods

    Rotenone can be extracted with chloroform and determined by
    ultraviolet (UV) spectroscopy, or analysed using HPLC with UV
    detection.

    Paper and thin layer chromatographic as well as colorimetric methods
    have been described both for the analysis of formulations and the
    determination of residues in several crops.

    1.4  Uses

    Rotenone is a selective, nonsystemic insecticide used on fruit trees,
    such as apple, apricot, peach, persimmon, pomegranate, and quince, to
    control aphids, maggots, bagworms, codling moths, Japanese beetles,
    leaf hoppers, Mexican bean beetles, cabbage worms, thrips, stinkbugs,
    flea beetles, and vegetable weevils.  It is also used to control
    grubs, ticks, lice, and fleas on cattle.  Rotenone has been used on
    humans for external treatment of chiggers (2% lotion) and scabies (10%
    emulsion).  Emulsifiable concentrates and wettable powders of rotenone
    are also extensively used in lakes, ponds, and reservoirs to control
    undesirable fish.

    Rotenone is available as a technical-grade solution at concentrations
    of 35%, 90%, or 95%, as a formulation intermediate at a concentration
    of 50%, and as a wettable powder containing 5% or 20% active
    substance.  It is also available as a 5% emulsifiable concentrate.

    2.  SUMMARY AND EVALUATION

    2.1  Human exposure to rotenone

    Human exposure mainly occurs in connection with its extraction and
    formulation, and its use as a pesticide.  No data have been found on
    the extent of human exposure.

    2.2  Effects on the environment

    Rotenone is highly toxic for aquatic life.  Most values for the 96-h
    LC50 for different fish species and for daphnids (water fleas) lie
    in the range of 0.02-0.2 mg/litre.  If used as a piscicide, it may
    also cause a temporary decrease in numbers of other aquatic organisms,
    such as daphnids.  On the other hand, it is readily oxidized on soil
    and plant surfaces to less toxic products and seems to have a low
    persistence.  Its toxicity for birds is very low.  Rotenone is
    non-phytotoxic.

    2.3  Uptake, metabolism, and excretion

    Rotenone may be absorbed by ingestion and by inhalation.  On the basis
    of rabbit studies, absorption through the intact skin is low.  The
    metabolism and pharmacokinetics of rotenone are not completely
    understood, but the compound is metabolized by the mammalian liver. 
    Most of the ingested compound is eliminated in the faeces.

    2.4  Effects on animals

    Rotenone exerts its toxic action by acting as a general inhibitor of
    cellular respiration.  The acute oral toxicity of rotenone is moderate
    for mammals, but there is a wide variation between species. Rotenone
    by the oral route is less toxic for the mouse and hamster than for the
    rat; the pig seems to be especially sensitive.  The reported oral
    LD50 values in the rat vary quite considerably, possibly because of
    differences in the plant extracts used.  Recent studies have shown
    that in rats rotenone is more toxic for females than males. It is
    highly irritating to the skin in rabbits.

    No evidence of carcinogenic action has been found in long-term studies
    on rats and mice, and tests have not revealed any significant
    genotoxic activity.   An NOAEL of 0.4 mg/kg per day has been
    determined for rats (2-year study) and dogs (6-month study).  In
    short-term studies on rats, dose-dependent bone marrow atrophy and
    forestomach lesions were observed.  In dogs, in addition to weight
    loss, haematological effects were found after six months' oral
    administration of rotenone at 10 mg/kg per day.  Fetotoxic effects
    were observed in mice and rats at doses that elicited adverse
    reactions in the mother.  The no-observed-effect level (NOEL) was
    0.4 mg/kg per day.  There were no indications of a teratogenic action
    in rodents below doses that were maternally toxic.

    2.5  Effects on human beings

    Acute poisoning causes nausea, vomiting, numbness, and tremors.  A
    lowest lethal dose of 143 mg/kg has been cited in a child, but it may
    be that the compound is less toxic in adults.  Occupational exposure
    to powdered rotenone containing plant materials has been reported to
    induce dermatitis, ulcers in the nose, and irritation of mucous
    membranes.

    3.  CONCLUSIONS AND RECOMMENDATIONS

    3.1  Conclusions

    The acute oral toxicity of rotenone is moderate in mammals, but there
    is a wide variation between species.  Chronic toxic effects in
    long-term feeding studies have been found in experimental animals.

    Clinical experience seems to indicate that humans, in particular
    children, are rather sensitive to the acute effects of rotenone.

    There is no evidence for any carcinogenic, genotoxic, or teratogenic
    action of rotenone.

    Rotenone is highly toxic for aquatic life.  It is readily oxidized on
    soil and plant surfaces to less toxic products and has a low
    persistence in the environment.

    3.2  Recommendations

    It is recommended that rotenone should be handled with caution,
    particular attention being paid to keeping it away from children. 

    Care should also be taken to avoid unintentional contamination of
    surface waters.

    The use of rotenone for medicinal purposes is to be discouraged.

    4.  HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION

    4.1  Human health hazards, prevention and protection, first aid

    Pure rotenone is moderately toxic for humans, but since the
    concentration of active ingredient in many marketed formulations is
    low, the use of this pesticide has resulted in few intoxications.

    4.1.1  Prevention and protection

    The prevention of occupational poisoning depends on ensuring a safe
    work environment and proper work practices.  The following precautions
    should be observed whenever rotenone is handled and used, in order to
    reduce the risk of accidental contamination.

    *    Avoid contact with the skin and eyes.

    *    Do not smoke, drink, or eat while handling rotenone.  Wash hands
         and any exposed skin before eating, drinking, or smoking, and
         after work.

    *    Avoid breathing dust from powder products.  Disposable dust masks
         should be worn, whenever appropriate.

    *    When unloading and handling containers of concentrates, wear
         protective PVC or neoprene gloves.

    *    When handling leaking containers, or when dealing with leaks and
         spills, wear overalls and PVC or neoprene gloves and boots.  If
         overalls become contaminated, change and wash them thoroughly
         before reuse.

    *    Store products in closed original labelled containers out of
         reach of children and away from food and animal feed.

    4.1.2  First aid

    If material has contaminated the skin, remove all contaminated
    clothing, and wash affected areas with soap and water.  If the
    material is in the eyes, flush with clean water for at least
    5-10 minutes.  In case of ingestion, seek medical aid immediately. 
    Until then, if the patient is conscious, give a glass of water or a
    slurry of activated charcoal, if available, and induce vomiting.

    4.2  Advice to physicians

    Rotenone is moderately toxic for humans.  There is no specific
    antidote.  In cases of ingestion, gastric lavage is indicated, unless
    it can be safely assumed that a non-toxic dose has been taken. 
    Treatment should be symptomatic and supportive.  There is no evidence
    of chronic toxicity in humans.

    4.3  Explosion and fire hazards

    Fight fires with alcohol-resistant foam, carbon dioxide, or dry
    powder.  Confine the use of water sprays to the cooling of unaffected
    stock only, thus avoiding polluted run-off from the site.  Fire
    service personnel should be advised that self-contained breathing
    apparatus may be necessary, because of the generation of noxious
    fumes.

    4.4  Storage and transport

    All products should be stored in secure buildings, out of reach of
    children and animals, and local regulations should be complied with. 
    Containers should be sound and adequately labelled.

    Rotenone should be transported in a separate compartment to prevent
    contamination of any food or animal feed.

    4.5  Spillage and disposal

    Avoid personal contact with rotenone or any of its formulations.  Keep
    spectators away from any leakage.  This pesticide is highly toxic for
    fish.  Prevent contamination of other goods or cargo, and of surface
    waters.

    Absorb spillage of liquid products with sawdust, earth, or sand, sweep
    up and place in separate container.  Activated carbon can also be used
    to adsorb rotenone.  Empty any product remaining in damaged or leaking
    containers into a clean, empty container, which should be suitably
    labelled. Sweep up any spilled powder with damp sawdust, taking care
    not to raise a dust cloud.  Remove trapped material with suction
    hoses.  Place in separate container for subsequent disposal.  As it is
    easily destroyed by heat the compound can be disposed of by simple
    burning.  Empty containers should be punctured to prevent reuse.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    Rotenone is not persistent, as it is readily decomposed in air and
    light.  However, it has a high acute toxicity for aquatic organisms. 
    Therefore, surface waters must not be contaminated.

    6.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    6.1  Exposure limit values

    The Joint FAO/WHO Meeting of Pesticide Residues in Food (JMPR) has not
    reviewed the compound to establish an ADI.  A threshold limit value,
    time weighted average (TWA) for rotenone of 5 mg/m3 has been
    recommended by the US ACGIH and adopted by several countries.
    Some exposure limits for food products are given in Table 1.

    Table 1. Exposure limits for food products in some countries

                                                                         

    Country        Food product      Exposure       Value      Effective
                                     limit          (mg/kg)    date
                                     description
                                                                         

    Austria        All products                     0.05       1988

    Germany        All products      Maximum        0.1        1990
                   of plant          residue
                   origin            limit

    France         Fruits and                       0.05       1989
                   vegetables

    Italy          Specified                        0.04       1985
                   fruits and
                   vegetables

    Netherlands    All products                     0.05       1988
                                                                         

    6.2  Transport and labelling

    The European Community egislation requires labelling as a dangerous
    substance using the symbol:

    FIGURE 1

    The label must read:

          Toxic by inhalation, in contact with skin and if swallowed; 
          keep out of reach of children;  keep away from food, drink and
          animal feeding stuff;  if you feel unwell, seek medical advice
          (show the label where possible).

    BIBLIOGRAPHY

    Cutkomp LK (1943)  Toxicity of rotenone and derris extract
    administered orally to birds.  J Pharmacol expt Therap, 77: 238-246.

    Dorne M & Friedman TB (1940)  Derris root dermatitis. J Am Med Assoc,
    115: 1268-1270.

    Gosselin RE, Smith RP, Hodge HC, & Braddock J (1984)  Clinical
    toxicology of commercial products. 5th ed. Baltimore, Williams and
    Wilkins, pp. III-366-III-368.

    Haley TJ (1978)  A review of the literature of rotenone 1,2,12,12a-
    tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-1-benzopyrano[3,5-b]furo
    [2,3-h][1]benzopyran-6(6h)-one. J Environ pathol Toxicol., 1: 315-337.

    Hayes WJ & Laws, ER (1991)  Rotenone and related materials. In:
    Handbook of pesticide toxicology. New York, Academic Press, Inc.,
    pp. 599-603.

    Oliver W & Roe C (1957)  Rotenone poisoning of swine.  J Am Vet
    Assoc., 130: 410-411.

    Santi R & Toth C (1965) Toxicology of rotenone.  Farmaco Ed Sci,
    20: 270.

    WHO (1992)  The WHO recommended classification of pesticides by hazard
     and guidelines to classification 1992-1993. Geneva, World Health
    Organization, 66 pp. (unpublished document, WHO/PCS/92.14).

    Worthing CR & Hance RJ (1991)  The pesticide manual, 9th ed. Croydon,
    British Crop Protection Council, pp. 758-759.

    


    See Also:
       Toxicological Abbreviations
       Rotenone (ICSC)
       Rotenone (PIM 474)