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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 99

    DIFLUBENZURON
    HEALTH AND SAFETY GUIDE






    UNITED NATIONS ENVIRONMENT PROGRAMME

    INTERNATIONAL LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION




    WORLD HEALTH ORGANIZATION, GENEVA 1995

    This is a companion volume to Environmental Health Criteria 184:
    Diflubenzuron

    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

    Health and safety guide for diflubenzuron

         (Health and safety guide ; no. 99)

         1.Diflubenzuron - toxicity  2.Insecticides
         3.Environmental exposure  4.  I.Series

         ISBN 92 4 151099 4          (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. 
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    (c) World Health Organization 1995

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    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. Production and uses

    2. SUMMARY AND EVALUATION

         2.1. Summary
               2.1.1. Identity, physical and chemical properties, and
                       analytical methods
               2.1.2. Sources of human and environmental exposure
               2.1.3. Environmental transport, distribution, and
                       transformation
               2.1.4. Environmental levels and human exposure
               2.1.5. Kinetics and metabolism in laboratory animals
               2.1.6. Effects on experimental mammals, and  in vitro
                       test systems
               2.1.7. Effects on humans
               2.1.8. Effects on non-target organisms in the laboratory
                       and field
         2.2. Evaluation
               2.2.1. Toxicological assessment
               2.2.2. Environmental assessment
               2.2.3. Toxicological criteria for setting guideline values

    3. CONCLUSIONS AND RECOMMENDATIONS

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

         4.1. Main 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
         4.6. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

         6.1. Previous evaluations by international bodies
         6.2. Exposure limit values
         6.3. Specific restrictions
         6.4. Waste disposal

    BIBLIOGRAPHY
    

    INTRODUCTION

    The Environmental Health Criteria (EHC) monographs produced by the
    International Programme on Chemical Safety include an assessment of
    the effects on the environment and on human health of exposure to a
    chemical or combination of chemicals, or physical or biological
    agents. They also provide guidelines for setting exposure limits.

    The purpose of a Health and Safety Guide is to facilitate the
    application of these guidelines in national chemical safety
    programmes. The first three sections of a Health and Safety Guide
    highlight the relevant technical information in the corresponding EHC.
    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. Within the Guide is a Summary of Chemical Safety
    Information which should be readily available, and should be clearly
    explained, to all who could come into contact with the chemical. 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. A bibliography has been included for
    readers who require further background information.

    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

    Chemical structure:

    CHEMICAL STRUCTURE 1

    Molecular formula:       C14H9ClF2N2O2

    Common name:             diflubenzuron (accepted by ISO, BSI, ANSI,
                             ESA)

    Common trade names:      Dimilin; Micromite; Vigilante

    Common abbreviation:     DFB

    IUPAC name:              1-(4-chlorophenyl)-3-
                             (2,6-difluorobenzoyl)-urea

    CAS chemical name:        N-[[(4-chlorophenyl) amino]
                             carbonyl]-2,6-difluorobenzamide

    CAS registry number:     35367-38-5

    RTECS registry number:   YS6200000

    Technical diflubenzuron contains > 95% pure compound.

    1.2  Physical and Chemical Properties

    Diflubenzuron is an odourless, white, crystalline solid. It is almost
    insoluble in water and poorly soluble in apolar organic solvents. In
    polar to very polar solvents, the solubility is moderate to good,
    e.g., in acetone 6.5 g/litre at 20C. Diflubenzuron is highly soluble
    in  N-methylpyrolidone (200 g/litre), dimethylsulfoxide, and
    dimethylformamide (both 120 g/litre).

    Some physical and chemical properties of diflubenzuron are given in
    Table 1.


        Table 1.  Physical and chemical properties of diflubenzuron
                                                                                

    Relative molecular mass                           310.7
    Melting point technical       > 95%               210-230C
                                  > 99% pure          230-232C
    Vapour pressure at 25C                           0.00012 mPa
    Volatility:  solid material                       <4%
                 from water pH 5.6                    <2% virtually non-volatile
    Specific gravity                                  1.56
    Partition coefficient n-octanol/water (log Kow)   5000
    Solubility in water (25C) (pH 5.6)               8  10-5 g/litre
    Stability in water   after 3 weeks at pH 5        4% decomposition
      (0.0001 g/litre)   after 3 weeks at pH 7        8% decomposition
      in the dark        after 3 weeks at Ph 9        26% decomposition
                                                                                
    
    Conversion factor: 1 ppm = 12.7 mg/m3 at 25C

    1.3  Analytical Methods

    Two general types of assay procedures for residues of diflubenzuron in
    crops, soil, water, and biological samples are available, i.e.,
    high-pressure liquid chromatography and gas chromatography with
    detection limits of approximately 0.01-0.05 mg/kg. The detection limit
    in water is 0.1 g/litre.

    The Joint FAO/WHO Codex Alimentarius Commission has made
    recommendations for the methods of analysis to be used for the
    determination of diflubenzuron residues (FAO/WHO, 1989).

    1.4  Production and Uses

    The production figures are not available. Diflubenzuron is effective
    as a stomach and contact insecticide, acting by inhibition of chitin
    synthesis. It is usually applied directly on plants and in forest
    areas, and in water for mosquito control.

    2.  SUMMARY AND EVALUATION

    2.1  Summary

    2.1.1  Identity, physical and chemical properties, and analytical
           methods

    Diflubenzuron is a member of the benzoylphenylurea group of
    insecticides. Its insecticidal action is due to interaction with
    chitin synthesis and/or deposition. It forms odourless white crystals
    with a melting point of 230-232C. It is sparingly soluble in water
    (0.2 mg/litre at 20C) and is virtually non-volatile. It is relatively
    stable in acidic and neutral media but hydrolyses under alkaline
    conditions.

    Diflubenzuron is produced by the reaction of 2,6-difluorobenzamide
    with 4-chlorophenylisocyanate.

    Diflubenzuron residues may be measured in water, biological samples,
    and soils using HPLC with UV detection, or GC with ECD for analysis of
    the intact molecule or following derivatization of the liberated
    4-chloroaniline with trifluoroacetic anhydride.

    2.1.2  Sources of human and environmental exposure

    Diflubenzuron is a synthetic compound used in agriculture, forestry,
    and public health programmes to control insect pests and vectors.
    Different formulations of diflubenzuron are available for these uses.
    There is no relevant information on human exposure to diflubenzuron.

    2.1.3  Environmental transport, distribution, and transformation

    Diflubenzuron is usually applied directly to plants and water. Uptake
    of diflubenzuron through plant leaves does not occur.

    The adsorption of diflubenzuron on soil is rapid. It is immobilized in
    the top 10-cm layer of soil to which it is applied and is unlikely to
    leach. Diflubenzuron is degraded in soils of various types and origin
    under aerobic or anaerobic conditions with a half-life of a few days.
    The rate of degradation depends greatly on the diflubenzuron particle
    size. The main metabolic pathway (over 90%) is hydrolysis leading to
    2,6-difluorobenzoic acid and 4-chlorophenylurea; these are degraded
    with half-lives of about 4 and 6 weeks, respectively. Free
    4-chloroaniline has not been detected in soils.

    Diflubenzuron degrades rapidly in neutral or alkaline waters. Studies
    on the application of diflubenzuron to water showed rapid partition to
    sediment; the parent compound and 4-chlorophenylurea may persist on
    sediment for more than 30 days.

    Diflubenzuron does not bioaccumulate in fish.

    2.1.4  Environmental levels and human exposure

    Exposure of the general population to diflubenzuron via water or food,
    as a result of its use in agriculture, against forest insects, or in
    mosquito control, is negligible.

    2.1.5  Kinetics and metabolism in laboratory animals

    In experimental animals, diflubenzuron is absorbed from the digestive
    tract and to a lesser extent through the skin. There is a saturable
    absorption mechanism in the rat gastrointestinal tract. Consequently,
    a large proportion of orally administered diflubenzuron is found in
    the faeces. Diflubenzuron is widely distributed in the tissues, but it
    does not accumulate.

    The metabolic fate of diflubenzuron has been studied in various
    species. The major route of metabolism in mammals is via
    hydroxylation. Hydrolysis of diflubenzuron may occur at any of the
    three carbon-nitrogen bonds. In pigs and chickens, the major route of
    hydrolysis is at the ureido bridge. In rats and cows, the major
    metabolic pathway is hydroxylation. The major metabolites in sheep,
    swine, and chickens are 2,6-difluorobenzoic acid and
    4-chlorophenylurea; minor metabolites are 2,6-difluorobenzamide and
    4-chloroaniline. In rats and cattle, 80% of the metabolites are
    2,6-difluoro-3-hydroxydiflubenzuron, 4-chloro-2-hydroxy-diflubenzuron
    and 4-chloro-3-hydroxydiflubenzuron. The metabolic studies indicate
    that little or no 4-chloroaniline is formed in rats or cattle.

    The major route of elimination is via the faeces, ranging from 70 to
    85% in cats, pigs, and cattle. In sheep, elimination is roughly
    equally distributed between the urine and faeces. Urinary excretion in
    rats and mice decreases proportionally with increasing dosage level.
    Less than 1% of an oral dose is recovered in exhaled air. Only trace
    residues are found in milk.

    No human studies on the kinetics and metabolism of diflubenzuron,
    including the extent of biotransformation to 4-chloroaniline, are
    available.

    2.1.6  Effects on laboratory mammals, and in vitro test systems

    The acute toxicity of diflubenzuron is low, by any route of exposure.
    It has been classified by WHO as a "product unlikely to present an
    acute hazard in normal use", based on an acute oral LD50 of more
    than 4640 mg/kg body weight in rats. The acute dermal LD50 in rats
    is greater than 10 000 mg/kg body weight, while the acute inhalation

    LC50 for rats is greater than 2.49 mg/litre. No signs of
    intoxication have been observed during the 14-day period following a
    single administration of diflubenzuron, by various routes, to a
    variety of animal species.

    Diflubenzuron is neither a skin irritant (in rabbits) nor a skin
    sensitizer (in guinea-pigs). It is marginally irritant to the eyes of
    rabbits.

    Diflubenzuron causes methaemoglobinaemia and sulfhaemoglobinaemia.
    Dose-related methaemoglobinaemia has been demonstrated in various
    species after oral, dermal, or inhalation exposure to diflubenzuron.
    This effect is the most sensitive toxicological end-point in
    experimental animals. The no-observed-effect level (NOEL), based on
    methaemoglobin formation, is 2 mg/kg body weight per day in rats and
    dogs and 2.4 mg/kg body weight per day in mice. In long-term toxicity
    studies on mice and rats, treatment-related changes were principally
    associated with oxidation of haemoglobin or with hepatocyte changes.

    In carcinogenicity studies on mice and rats given dietary levels of up
    to 10 000 mg/kg, there were no treatment-related effects on tumour
    incidence. Specifically, there were no mesenchymal neoplasms of the
    spleen or liver, as observed in carcinogenicity studies with
    4-chloroaniline.

    In several reproductive toxicity studies on rats, mice, rabbits, and
    three avian species, no effects were seen on reproduction and there
    was no embryotoxicity. Teratogenicity studies on rats and rabbits did
    not reveal teratogenic effects.

    Diflubenzuron and its main metabolites have been examined in a variety
    of  in vitro and  in vivo mutagenicity tests. Neither diflubenzuron
    nor its major metabolites have produced any mutagenic effects.

    The minor metabolite, 4-chloroaniline, was shown to be positive in
    several  in vitro mutagenicity assays using various end-points. It is
    carcinogenic in rats and mice. The neoplastic lesions related to
    administration of 4-chloroaniline were benign and malignant
    mesenchymal tumours in the spleens of male rats and haemangiomas and
    haemangiosarcomas, primarily in the spleen and liver of male mice.

    2.1.7  Effects on humans

    The diflubenzuron metabolite, 4-chloroaniline, has been reported to
    cause methaemoglobinaemia in exposed workers and in neonates
    inadvertently exposed. Some individuals who are deficient in
    NADH-methaemoglobin reductase may be particularly sensitive to
    4-chloroaniline and, hence, to diflubenzuron exposure.

    2.1.8  Effects on non-target organisms in the laboratory and field

    All chitin-synthesizing organisms showed susceptibility to
    diflubenzuron.

    Bacteria were not affected by diflubenzuron at a concentration of
    500 mg/kg soil; some stimulation of nitrogen fixation was seen.
    Diflubenzuron acetone solutions were degraded; the acetone was used as
    carbon source. Algal biomass increased at a diflubenzuron
    concentration of 1 g/litre. There were no adverse effects at
    concentrations above the limit of diflubenzuron solubility. Fungi were
    temporarily affected at 0.1 g/litre in laboratory streams.

    Aquatic invertebrates showed variable responses to diflubenzuron.
    Molluscs were insensitive, the LC50 being greater than 200 mg/litre.
    LC50s for other invertebrates ranged from 1 to > 1000 g/litre,
    reflecting the effects of the compound on juvenile, moulting stages. A
    Maximum Acceptable Toxicant Concentration (MATC) for  Daphnia has
    been estimated at > 40 and < 93 ng/litre; as expected, larval
    mayflies and other aquatic insect juveniles were highly susceptible.
    Overspray of water bodies would be expected to kill some aquatic
    invertebrates.

    In ecosystems and field experiments, where diflubenzuron was applied
    directly to the water, the effects on most taxa were less severe than
    predicted from acute laboratory tests. No effects on aquatic organisms
    have been found after aerial applications to forests.

    The LC50s for fish are > 150 mg/litre. Fish kills have never been
    recorded in field experiments.

    The oral and contact LD50s for honey-bees were greater than
    30 g/bee. Honey-bee colonies were not affected after aerial
    application of 350 g diflubenzuron/ha.

    A 5-day dietary study on the mallard duck and bobwhite quail with
    levels of up to 4640 mg/kg did not reveal any observable signs of
    toxicity. Small songbirds in the forest ecosystem were not affected
    after aerial application of diflubenzuron at 350 g/ha.

    Small mammal species in a forest did not show any reductions in
    numbers after application of diflubenzuron at 67 g/ha.

    2.2  Evaluation

    2.2.1  Toxicological assessment

    The primary manifestation of diflubenzuron toxicity, i.e.,
    methaemoglobin induction, occurred in a range of test animal species.

    It is attributable to the metabolite, 4-chloroaniline, which is known
    to induce methaemoglobin formation in several animal species and in
    humans.

    Diflubenzuron did not cause any other toxic effects following
    long-term dietary administration. It was not mutagenic or carcinogenic
    in mice or rats. However, its metabolite, 4-chloroaniline, is
    mutagenic  in vitro and is carcinogenic in mice and male rats.
    Although 4-chloroaniline is a minor urinary metabolite of
    diflubenzuron in rats, the extent to which it is formed  in vivo in
    various animal species remains unknown. Similarly, the comparative
    extent of absorption of its parent compound in various species is not
    known.

    The sensitivity of human haemoglobin to methaemoglobin formation by
    4-chloroaniline  in vivo is not known. However, since induction of
    methaemoglobinaemia has consistently been the most sensitive measure
    of diflubenzuron toxicity in the various animal species tested, it may
    be used as a basis to estimate levels causing no toxicological
    effects.

    2.2.2  Environmental assessment

    Diflubenzuron adsorbs readily on soil particles with little subsequent
    desorption. Its mobility in soil is very low, practically all residues
    remaining within 15 cm of the surface, even in sandy loam soils;
    diflubenzuron does not leach. It is only partly removed from foliage
    by heavy rainfall. Nevertheless, some diflubenzuron may be present in
    surface water shortly after application, due to flooding of treatment
    areas or agricultural run-off.

    Dissipation of diflubenzuron from water is rapid. Adsorption on
    sediment occurs within 4 days; both the parent compound and the
    metabolite, 4-chlorophenylurea, may persist on sediment for at least
    30 days.

    Uptake of diflubenzuron through the leaves of plants, after aerial
    application, does not occur. Some uptake of soil residues does occur
    in plants and this may be translocated. At the highest application
    rate (1 kg a.i./ha), following 1 month of aging of residues, up to
    1 mg residue/kg was found in various crops.

    Photolysis of diflubenzuron is slow with a calculated half-life of
    40 days. Under environmental conditions, abiotic degradation in water
    and soil represents a minimum route of break-down. Aerobic degradation
    in water is a microbial process with a half-life of a few days, under
    both laboratory and field conditions. In the field, degradation of
    diflubenzuron, applied at practical rates, is influenced by pH,
    temperature, formulation, organic matter content, and depth of the
    water.

    Degradation in soil through microbial hydrolysis is a rapid process,
    with a half-life of a few days, depending on diflubenzuron particle
    size. The major break-down products are 2,6-difluorobenzoic acid and
    4-chlorophenylurea; a minor metabolite is parachloroaniline. All these
    are irreversibly bound to soil and/or further metabolized.

    The half-life of diflubenzuron residues on citrus fruits was
    significantly decreased by high temperature and humidity.

    Anaerobic degradation in water and sediment is slower than aerobic
    degradation.

    Fish bioconcentrate diflubenzuron and some bioaccumulation takes place
    during extended exposure up to a plateau, depending on the water
    concentration, due to fast degradation of diflubenzuron and the
    excretion of metabolites; the depuration half-life is less than one
    day. The 4-chloroaniline metabolite has not been detected in fish.

    Fish are not sensitive to diflubenzuron. The toxicity of metabolites
    of diflubenzuron for fish is also low. Long-term exposure to
    diflubenzuron at recommended application rates did not produce any
    effects on fish; the compound does not persist in water and no
    long-term exposure is expected.

    Diflubenzuron, at the solubility limit concentration, was not
    phytotoxic for duckweed.

    Honey-bees were not affected by topical applications of > 30 g/bee
    or dietary concentrations of up to 1000 mg/kg. Broods in hives were
    reduced when bees were fed syrup at 59 mg diflubenzuron/kg. Broods
    were also reduced following exposure of flying colonies.

    Earthworms were not affected at a concentration of 780 mg
    diflubenzuron/kg soil, which is at least three orders of magnitude
    above reported soil residues.

    The acute toxicity of diflubenzuron for birds is low with oral and
    dietary LD(LC)50s greater than 3000 mg/kg. At recommended
    application rates, diflubenzuron is not expected to pose a hazard for
    birds.

    Extensive field studies have shown minimal or reversible effects on
    most aquatic invertebrates; daphnids were most seriously affected,
    with short-term reductions in population of up to 75% following a
    single application of diflubenzuron. Fish were not affected by water
    overspraying. Neither bird nor mammal populations were adversely
    affected following forest spraying with diflubenzuron.

    Risk quotients for avian and fish risk categories are summarized in
    Table 2.

        Table 2.  Toxicity-exposure ratios for birds and fish based on application rates
              of 2.5 kg diflubenzuron a.i./ha to soybeans (worst case)
                                                                                     
    Risk category            LC50 as        Estimated exposurea,b    Toxicity/exposure
                             mg/litre or    as mg/litre or           ratio (TER)c
                             mg/kg diet     mg/kg diet
                                                                                     

    Acute bird                 3762             73.7-535.7              51.0-7.0
    Acute fish (stream)        150              0.0007                  214 300
    Acute fish (pond)          150              0.01                    15 000
    Acute aquatic
      invertebrate (stream)    0.005            0.0007                  7.1
    Acute aquatic
      invertebrate (pond)      0.005            0.01                    0.5
                                                                                     

    a  Estimated environmental concentration in the terrestrial environment
       (for bird exposure) is based on the stated application rate and the assumption
       of deposition on short grass, using the US EPA nomogram.

    b  Aquatic exposure concentrations were taken from the STEAM model, based on
       a single application and estimated runoff into water; no direct
       overspray is included.

    c  TER is the toxicity (as LC50) divided by the exposure; values at, or below,
       1.0 indicate the likely exposure to toxic concentrations of organisms in
       the different risk categories.
    

    2.2.3  Toxicological criteria for setting guideline values

    The toxicological studies on diflubenzuron of relevance for setting
    guideline values are shown in Table 3.

        Table 3.  Toxicological criteria for estimating guideline values for diflubenzuron
                                                                                          

    Exposure scenario             Relevant route/effect/             Result/remarks
    (technical diflubenzuron)     species
                                                                                          

    Short-term                    dermal, irritation, rabbit         non-irritant
    (1-7 days)                    ocular, irritation, rabbit         marginal, high dose
                                  dermal, sensitization,             non-sensitizing
                                    guinea-pig
                                  inhalational, toxicity, rat        LC50  2.49 mg/litre
                                                                       (single exposure)

    Mid-term (1-26 weeks)
      3 weeks; 5 days/week        dermal, irritation, rabbit         NOEL = 70 mg/kg body
                                                                       weight per day
      3 weeks; 5 days/week        inhalational, methaemoglobin       NOAEL = < 0.12 mg/litre
                                    formation, rat

    Long-term                     dietary, methaemoglobin            NOEL = 2 mg/kg body
                                    formation, rat                     weight per day
                                  dietary, methaemoglobin            NOEL = 2.4 mg/kg body
                                    formation, mouse                   weight per day
                                  dietary, methaemoglobin            NOEL = 2 mg/kg body
                                    formation, dog                     weight per day
                                                                                          
    
    3.  CONCLUSIONS AND RECOMMENDATIONS

    Considering the toxicological characteristics of diflubenzuron, both
    qualitatively and quantitatively, the CAG concluded, on the basis of
    the NOEL of 2 mg/kg body weight per day in long-term toxicity studies
    on mice, rats, and dogs, and applying a 100-fold uncertainty factor,
    that 0.02 mg/kg body weight per day will probably not cause adverse
    effects in humans, whatever the route of exposure.

    Biomonitoring of 4-chloroaniline during occupational exposures should
    be carried out.

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

    For general information see ILO (1993).

    4.1  Human Health Hazards, Prevention and Protection, First Aid

    The acute oral and dermal toxicities of diflubenzuron for humans
    appear to be low. Diflubenzuron is not a skin irritant or a
    sensitizer; it was marginally irritant when tested on rabbit eyes.

    4.1.1  Prevention and protection

    The following precautions should be observed during handling and use,
    in order to reduce the risk of accidental contamination.

    *    Avoid contact with skin and eyes.

    *    Do not smoke, drink, or eat in the workplace. Wash hands and any
         exposed skin before eating, drinking, or smoking, and after work.

    *    Avoid raising a dust cloud when handling wettable powder
         formulations.

    *    Avoid breathing the dust from powder products.

    *    When unloading and handling containers, 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 re-use.

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

    4.1.2  First aid

    Acute poisoning by diflubenzuron is unlikely because of its low acute
    toxicity.

    When considering human health hazards and first aid, it is essential
    to determine which product the victim has been exposed to. It is
    essential to differentiate between dry products (diflubenzuron
    technical, the 90% concentrate, the 25% wettable powder and other dry
    products, such as wettable powders with lower active ingredient and
    low percentage granular products, which may be available locally),
    water-based products (DIMILIN SC-48, DIMILIN SC-15, DIMILIN 4L), and
    oil-based products (DIMILIN ODC-45, DIMILIN OF 6 and DIMILIN 2F).

    In cases of overexposure, apply routine first aid measures. If
    material has been spilled on the skin, immediately remove the victim
    from the source of contamination, remove all contaminated clothing,
    and wash affected areas with soap and running water. If the material
    is in the eyes, flush with clean water for at least 5-10 min. In case
    of ingestion of significant quantities, medical attention should be
    sought.

    4.2  Advice to Physicians

    The acute oral toxicity of diflubenzuron for humans is low. There is
    no specific antidote. Treat symptomatically, when required. If
    oil-based products have been ingested and the victim starts vomiting,
    it may be advisable to perform gastric lavage, in order to avoid
    aspiration into the lungs.

    4.3  Explosion and Fire Hazards

    Diflubenzuron is not flammable. If diflubenzuron is involved in a
    small fire, extinguish with carbon dioxide, dry powder, or
    alcohol-resistant foam.

    4.4  Storage and Transport

    All products should be stored under dry conditions under lock and key,
    out of reach of children and animals, and local regulations should be
    complied with. Containers should be sound and adequately labelled.

    4.5  Spillage

    Avoid contact with solid or dust. Keep spectators away from any
    leakage. The pesticide is highly toxic for aquatic invertebrates.

    Absorb any spillage with sand or any other inert absorbent, collect
    the mixture into a clean, empty container, which should be adequately
    labelled and sent for incineration. Empty any product remaining in
    damaged or leaking containers in a clean, empty container, which
    should be suitably labelled.

    4.6  Disposal

    Proper incineration is the method of choice for this compound.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    Diflubenzuron is not persistent and is readily degraded in soil and
    water. However, it is highly toxic for aquatic invertebrates. Water
    surfaces should not be oversprayed when diflubenzuron is applied for
    mosquito control.

    6.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    6.1  Previous Evaluations by International Bodies

    Diflubenzuron was classified by WHO (1992) as "a product unlikely to
    present an acute hazard in normal use", on the basis of an acute oral
    LD50 for rat greater than 4640 mg/kg body weight.

    Diflubenzuron was evaluated by the FAO/WHO Joint Meeting on Pesticide
    Residues (JMPR) in 1981, 1984, and 1985. An acceptable daily intake
    (ADI) for man for diflubenzuron was estimated at 0-0.02 mg/kg body
    weight per day in 1985.

    A guideline value of 22.5 g/litre for drinking-water was recommended,
    on the basis of allocation of the tolerable daily intake (TDI) of
    0.0075 mg/kg body weight (WHO, 1991).

    In the WHO Recommended Classification of Pesticides by Hazard,
    technical diflubenzuron has been classified as a product unlikely to
    present an acute hazard in normal use.

    6.2  Exposure Limit Values

    Some tolerances for food and animal feed products are given in
    Table 4.

    For all agricultural uses, "pre-harvest intervals" have been defined
    in most countries.

    6.3  Specific Restrictions

    Diflubenzuron is approved as a pesticide in many countries. Specific
    uses, limitations, and precautions are listed in national regulatory
    documents.

    6.4  Waste Disposal

    Incineration at high temperature in a unit with effluent gas scrubbing
    is the method of choice.


        Table 4.  Tolerances and Maximum Residue Limits for food products
                                                                                                                          
    Country/            Food product                            Exposure limit description         Value        Effective
    Organization                                                                                   (mg/kg)        date
                                                                                                                          

    Brazil              Specified plant products                Acceptable limit                   0.1-0.2        1984

    FAO/WHO             Apples, blackcurrants, brussels         Maximum residue limit              1.0            1988
                        sprouts, cabbage, citrus fruits,
                        pears, plums, tomatoes

                        cottonseed                                                                 0.2

                        mushrooms, soybeans                                                        0.1

                        carcass meat, eggs, milk,
                        meat by-products, poultry meat                                             0.05

    Finland             Mushrooms                               Maximum residue limit              0.1            1992

    Germany             Wild strawberries,                                                         2.0            1989
                        stone fruits, cabbage                                                      1.0
                        mushrooms                                                                  0.2

    USA                 Raw agricultural products               Acceptable residue limit           0.05-1.0       1984
                        (specified plant and animal
                        products)

                        Soybean hulls and soap stock                                               0.1-0.5

    USSR                Specified food products                 Maximum residue limit              0.1            1988
                                                                                                                          
        BIBLIOGRAPHY

    CEC (1987)  Legislation in dangerous substances - Classification and
     labelling in the European Communities - Vol. 1 & 2. Commission of
    the European Communities, London, Graham & Trotman, Ltd.

    FAO (1985a)  Guidelines for the packaging and storage of pesticides.
    Rome, Food and Agriculture Organization of the United Nations.

    FAO (1985b)  Guidelines for the disposal of waste pesticides and
     pesticide containers on the farm. Rome, Food and Agriculture
    Organization of the United Nations.

    FAO (1985c)  Guidelines on good labelling practice for pesticides.
    Rome, Food and Agriculture Organization of the United Nations.

    FAO (1986)  International code of conduct on the distribution and use
     of pesticides. Rome, Food and Agriculture Organization of the United
    Nations.

    FAO/WHO (1964-present)  Evaluations of pesticide residues in food.
    Rome, Food and Agriculture Organization of the United Nations.

    FAO/WHO (1986)  Codex Maximum Limits for pesticide residues. Codex
     Alimentarius Commission, CAC/Vol. XIII., Supplement 1 & 2, 3rd ed.
    Rome, Food and Agriculture Organization of the United Nations.

    FAO/WHO (1989)  Guide to Codex recommendations concerning pesticide
     residues. Part 8. Recommendations for methods of analysis of
     pesticide residues. 4th ed. Rome, Codex Commission on Pesticide
    Residues, Food and Agriculture Organization of the United Nations.

    GIFAP (1982)  Guidelines for the safe handling of pesticides during
     their formulation, packaging, storage and transport. Brussels,
    Groupement International des Associations Nationales des Fabricants de
    Produits Agrochimiques.

    GIFAP (1983)  Guidelines for the safe and effective use of pesticides.
    Brussels, Groupement International des Associations Nationales des
    Fabricants de Produits Agrochimiques.

    GIFAP (1984)  Guidelines for emergency measures in cases of pesticides
     poisoning. Brussels, Groupement International des Associations
    Nationales des Fabricants de Produits Agrochimiques.

    GIFAP (1987)  Guidelines for the safe transport of pesticides.
    Brussels, Groupement International des Associations Nationales des
    Fabricants de Produits Agrochimiques.

    HAYES, W.J., Jr & LAWS, E.R. Jr (1991)  Handbook of pesticide
     toxicology (3 vol.). New York, Academic Press.

    IARC (1972-present)  IARC Monographs on the evaluation of carcinogenic
     risk of chemicals to man. Lyon, International Agency for Research on
    Cancer.

    ILO (1991)  Safety and health in the use of agro-chemicals - a guide.
    Geneva, International Labour Office.

    ILO (1993)  Safety and health in the use of chemicals at work - A
     training manual, prepared by Abu Bakar Che Man & David Gold. Geneva,
    International Labour Office.

    IPCS (in preparation)  Environmental Health Criteria No. 184
     Diflubenzuron, Geneva, World Health Organization.

    IRPTC (1985)  IRPTC file on treatment and disposal methods for waste
     chemicals. Geneva, International Register of Potentially Toxic
    Chemicals, United Nations Environment Programme.

    IRPTC (1987)  IRPTC legal file 1986. Geneva, International Register
    of Potentially Toxic Chemicals, United Nations Environment Programme.

    PLESTINA, R. (1984)  Prevention, diagnosis, and treatment of
     insecticide poisoning. Geneva, World Health Organization (WHO
    unpublished document VBC/84.889).

    SAX, N.I. (1984)  Dangerous properties of industrial materials. New
    York, van Nostrand Reinhold Company, Inc.

    UNEP/IEO (1990)  Storage of hazardous materials: a technical guide for
     safe warehousing of hazardous materials. Paris, United Nations
    Environment Programme, Industry and Environment Office, 80 p.

    UNITED NATIONS (1991)  Consolidated list of products whose consumption
     and/or sale have been banned, withdrawn, severely restricted or not
     approved by Governments. 4th ed. New York, United Nations.

    UNITED NATIONS (1989)  Recommendations on the transport of dangerous
     goods. 6th ed., New York, United Nations.

    US NIOSH/OSHA (1981)  Occupational health guidelines for chemical
     hazards. 3 Vol., Washington DC, US Department of Health and Human
    Services, US Department of Labor (Publication No. DHHS(NIOSH) 01-123).

    WHO (1992)  The WHO recommended classification of pesticides by hazard
     and guidelines to classification 1992-93, Geneva, World Health
    Organization (unpublished document WHO/PCS/92.14).

    WORTHING, C.R. & HANCE, R.J. (1991)  The pesticide manual. 9th ed.,
    Farnham, United Kingdom, British Crop Protection Council.
    


    See Also:
       Toxicological Abbreviations
       Diflubenzuron (EHC 184, 1996)
       Diflubenzuron (Pesticide residues in food: 1981 evaluations)
       Diflubenzuron (Pesticide residues in food: 1983 evaluations)
       Diflubenzuron (Pesticide residues in food: 1984 evaluations)
       Diflubenzuron (Pesticide residues in food: 1985 evaluations Part II Toxicology)
       Diflubenzuron (JMPR Evaluations 2001 Part II Toxicological)