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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 65

    FENITROTHION
    HEALTH AND SAFETY GUIDE






    UNITED NATIONS ENVIRONMENT PROGRAMME

    INTERNATIONAL LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION




    WORLD HEALTH ORGANIZATION, GENEVA 1991

    This is a companion volume to Environmental Health Criteria 133:
    Fenitrothion

    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

    Fenitrothion : health and safety guide.

    (Health and safety guide ; no. 65)

    1.Fenitrothion - adverse effects  2.Fenitrothion -  poisoning
    3.Fenitrothion - standards  4.Environmental exposure  I.Series

    ISBN 92 4 151065 X          (NLM Classification: WA 240)
    ISSN 0259-7268

    (c) World Health Organization 1991

    Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention.  For rights of reproduction or
    translation of WHO publications, in part or  in toto, application
    should be made to the Office of Publications, World Health
    Organization, Geneva, Switzerland.  The World Health Organization
    welcomes such applications.

    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. Production and uses

    2. SUMMARY AND EVALUATION
         2.1. Exposure
         2.2. Uptake, metabolism, and excretion
         2.3. Effects on organisms in the environment
         2.4. Effects on experimental animals and  in vitro test systems
         2.5. Effects on human beings

    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. Advice to physicians
                     4.1.1.1  Symptoms of poisoning
                     4.1.1.2  Medical treatment
              4.1.2. Health surveillance advice
         4.2. Explosion and fire hazards
         4.3. Storage
         4.4. Transport
         4.5. Spillage and disposal
              4.5.1. Spillage
              4.5.2. 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. Labelling, packaging, and transport
         6.5. Waste disposal

    BIBLIOGRAPHY

    ANNEX 1.  TREATMENT OF ORGANOPHOSPHATE INSECTICIDE POISONING IN MAN
    

    INTRODUCTION

    The Environmental Health Criteria (EHC) documents 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 table of human health hazards,
    preventive and protective measures, and first aid, 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 Manager
    International Programme on Chemical Safety
    Division of Environmental Health
    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

    (a)   Primary constituent

    Common name:              fenitrothion

    Chemical formula:         C9H12NO5PS

    Chemical structure:

    CHEMICAL STRUCTURE 1

    Relative molecular mass:  277.25

    CAS chemical name:         O,O-dimethyl- O-(3-methyl-4-nitrophenyl)-
                              phosphorothioate
                               O,O-dimethyl- O-(4-nitro- m-tolyl)-
                              phosphorothioate
                               O,O-dimethyl- O-(4-nitro- m-tolyl)-
                              thiophosphate

    CAS Registry number:      122-14-5

    RTECS Registry number:    TG0350000

    Synonyms:                 Bayer 41831, Bayer S 5660, Sumitomo 1102A

    (b)   Technical product

    Major trade names:        Aceothion, Agrothion, Cytel, Cyfen, Dybar,
                              Fenitox, Folithion, MEP, Metathion,
                              Novathion, Nuvanol, Sumithion

    Purity:                   93% (Sumithion)

    Impurities:                O,O-dimethyl- O-3-nitro- m-tolyl-
                              phosphorothioate                        <1.5%
                               O-methyl O,O-bis(4-nitro- m-tolyl)-
                              phosphorothioate                        <2.5%
                               O-methyl S-methyl- O-(4-nitro- m-tolyl)-
                              phosphorothioate ( S-isomer)             <0.8%
                               O,O-dimethyl- O-2-nitro- m-tolyl-
                              phosphorothioate                        <3.0%
                               O,O-dimethyl- O-6-nitro- m-tolyl-
                              phosphorothioate                        <2.5%
                               O,O-dimethyl- O-2,4-dinitro- m-tolyl-
                              phosphorothioate                        <2.0%
                               O,O-dimethyl- O-4,6-dinitro- m-tolyl-
                              phosphorothioate                        <1.5%
                              3-methyl-4-nitrophenol                  <0.5%

    Isomeric composition:     S-isomer <0.8%

    1.2  Physical and Chemical Properties

    Fenitrothion is a yellow-brown liquid with a "chemical" odour.  It is
    poorly soluble in water, but highly soluble in alcohols, esters,
    ketones, and aromatic hydrocarbons.  It is stable at room temperature,
    but decomposes at temperatures exceeding 145C.  It is hydrolysed by
    alkali: the half-time in 0.01N NaOH at 30C is 4 h.

    Some physical properties are given in Table 1.

    1.3  Analytical Methods

    The common analytical procedure for the determination of residues in
    foods and environmental media consists of : (1) extraction, (2)
    partition, (3) chromatographic separation (clean-up), and (4)
    qualitative and quantitative analysis using chromatographic methods.

    Fenitrothion levels in technical products and formulations are mainly
    determined using : the diazo method, colorimetry, or gas-liquid
    chromatography.  The usual procedure consists of: (1) dissolution of
    the extract, (2) separation of impurities, and (3) determination.

    Table 1. Physical properties of fenitrothion

                                                                         

    Melting point                 0.3C
    Boiling point                 140-145C (decomp.) /0.1 mmHg
    Flash point                   157C
    Explosion limit               not available
    Vapour pressure               18 mPa at 20C; 6 x 10-6 mmHg at 20C

                                   25             25
    Density                       d   1.32-1.34; d   1.3227
                                   25             4

    Vapour density                not available
     n-Octanol/water partition
      coefficient (log Pow)       3.16
    Solubility in water (30C)    14 mg/litre 
    Solubility in organic         highly soluble in alcohols, esters,
      solvents                    ketones, and aromatic hydrocarbons:
                                  1000 g/kg in dichloromethane, methanol,
                                  xylene; 193 g/kg in propan-2-ol;
                                  42 g/kg in hexane (20-25C)
    Conversion factors (20C)     1 ppm = 11.5 mg/m3
                                  1 mg/m3 = 0.087 ppm
                                                                         

    1.4  Production and Uses

    Fenitrothion is an organophosphorous insecticide that has been in use
    since 1959.  It is used in agriculture to control insects on rice,
    cereals, fruits, vegetables, stored grains, and cotton.  It is also
    used to control insects in forests and for fly, mosquito, and
    cockroach control in public health programmes.  Fenitrothion is
    formulated as an emulsifiable concentrate, ultra-low-volume
    concentrate, powder, granules, dust, oil-based spray, and in
    combination with other pesticides.  Between 15 000 and 20 000 tonnes
    of fenitrothion are produced per year. 

    2.  SUMMARY AND EVALUATION

    2.1  Exposure

    Fenitrothion enters the air through volatilization from contaminated
    surfaces and may drift beyond the intended target area during
    spraying.  It leaches very slowly from most soils, but some run-off
    can occur.

    Fenitrothion is degraded by photolysis and hydrolysis.  In the
    presence of ultraviolet radiation (UVR) or sunlight, the half-life of
    fenitrothion in water is less than 24 h.  The presence of microflora
    may also accelerate degradation.  Thus, fenitrothion is stable in
    water only in the absence of sunlight or microbial contamination.  In
    soil, biodegradation is the primary route of degradation, though
    photolysis may also play a role.

    Airborne concentrations of fenitrothion can be as high as 5 g/m3,
    directly after spraying, but decrease markedly with time and with
    distance from the site of application.  Levels in water may be as high
    as 20 g/litre, but decrease rapidly.

    Bioconcentration factors for fenitrothion with continuing exposure
    have been estimated to range from 20 to 450 for a number of different
    aquatic species.

    Levels of fenitrothion residues in fruits, vegetables, and cereal
    grains may range from 0.001 to 9.5 mg/kg immediately after treatment,
    but decline rapidly with a half-life of 1-2 days.

    2.2  Uptake, Metabolism, and Excretion

    Fenitrothion is rapidly absorbed from the intestinal tract of
    experimental animals and distributed to various body tissues.  The
    half-life for the dermal absorption of fenitrothion in the monkey was
    found to be 15-17 h.  Fenitrothion has been shown to be metabolized
    through the major pathways of  O-demethylation and by cleavage of the
    the  P-O-aryl bond.  The nitro group of fenitrothion is reduced by
    intestinal microorganisms, in ruminants only.  The major route of
    excretion is via the urine, most of the metabolites being excreted
    within 2-4 days in rats, guinea-pigs, mice, and dogs. 

    The major metabolites that have been reported include demethyl
    fenitrothion, demethyl fenitrooxon, dimethylphosphorothioic acid,
    dimethyl phosphoric acid, and 3-methyl-4-nitrophenol and its
    conjugates.  Differences in the composition of the metabolites found
    among laboratory animals and between sexes of the same species appear
    to be mainly quantitative in nature.  Only rabbits appear to excrete
    fenitrooxon and aminofenitrooxon in small, though quantifiable,
    amounts in the urine.

    Evidence from rabbits and dogs showed the preferential deposition of
    fenitrothion in adipose tissue.

    Residues found in the milk of cows following exposure to fenitrothion
    were not detected two days later.

    Though fenitrothion is readily absorbed via the oral route, it is
    rapidly metabolized and excreted, and is unlikely to remain in the
    body for any prolonged period.

    2.3  Effects on Organisms in the Environment

    At concentrations likely to be found in the environment, fenitrothion
    has no effect on microorganisms in soil or water.

    Fenitrothion is highly toxic for aquatic invertebrates in both
    freshwater and seawater with LC50 values of a few g/litre for most
    species tested.  The no-observed-effect level (NOEL) for  Daphnia in
    48-h tests was <2 g/litre; in life-cycle tests, a maximum acceptable
    toxicant concentration (MATC) of 0.14 g/litre was established.  Field
    observations and studies on experimental ponds showed effects on
    populations of invertebrates.  However, most of the changes observed
    were temporary, even at concentrations considerably higher than those
    likely to occur after recommended usage.

    Fish are less sensitive to fenitrothion than invertebrates and show
    96-h LC50 values in the range of 1.7-10 mg/litre.  The early larval
    stage is the most sensitive.  Long-term studies have established a
    MATC at, or above, 0.1 mg/litre for 3 species of freshwater fish.  In
    field studies, in which fenitrothion was applied in forests, no
    effects were observed on wild populations of fish or on the survival
    of caged test fish with measured water concentrations of fenitrothion
    of up to 0.018 mg/litre.  Repeated applications of fenitrothion in
    forests did not have any effects on fish populations.

    Amphibian tadpoles showed LC50 values in the range of
    1.2-15 mg/litre in laboratory tests.  No field effects were seen after
    forest spraying at 140 g/ha.

    Fenitrothion is highly toxic for bees (topical LD50 at
    0.03-0.04 g/bee).  Large numbers of honey bees and other species have
    been reported killed locally in the field.  However, the total numbers
    of honey bees killed represented only a small percentage of the hive
    population.

    The acute oral LD50 values for birds ranged between 25 and
    1190 mg/kg body weight and most 5-day dietary LC50s exceeded
    5000 mg/kg diet.  NOEL values for reproduction were 10 mg/kg body
    weight for the quail and 100 mg/kg body weight for the mallard. 
    Song-bird deaths, which occurred soon after the application of
    fenitrothion at a rate of 280 g/ha, were markedly higher at 560 g/ha,
    for species living in the forest canopy.  After spraying at 420 g/ha

    followed by 210 g/ha a few days later, the reproductive success of
    white-throated sparrows was reduced.  In many studies, song-birds
    showed inhibition of ChE, soon after the spraying of forests with
    fenitrothion.

    Field observations did not reveal any effects of fenitrothion on
    populations of small, wild mammals.

    2.4  Effects on Experimental Animals and In Vitro Test Systems

    Fenitrothion is an organophosphate and causes cholinesterase activity
    depression in plasma, red blood cells, and brain and liver tissues. 
    It is metabolized to fenitrooxon, which is more acutely toxic.  Its
    toxicity may be potentiated by some other organophosphate compounds.

    Fenitrothion is an insecticide of moderate toxicity with oral LD50
    values in rats and mice ranging from 330 to 2400 mg/kg body weight. 
    The acute dermal toxicity in rodents ranged from 890 mg/kg body weight
    to more than 2500 mg/kg body weight.

    Fenitrothion is only minimally irritating to the eyes and is
    nonirritating to the skin.  The dermal sensitizing potential of the
    chemical was shown in one of two studies on guinea-pigs.

    Fenitrothion has been tested in short-term studies on rats, dogs, and
    rabbits and in long-term carcinogenicity studies on rats and mice.  In
    short-term studies on rats and dogs, the NOAELs, based on brain ChE
    activity, were 10 mg/kg diet and 50 mg/kg diet, respectively. 
    Long-term studies on rats and mice indicated a NOAEL, based on brain
    ChE activity, of 10 mg/kg diet.

    No carcinogenic effects were found in any of the long-term studies
    reported.

    Fenitrothion was not mutagenic in  in vivo tests, with the exception
    of two in which near lethal dosages were used.

    Fenitrothion was found not to be teratogenic at levels of up to
    30 mg/kg body weight in rabbits and up to 25 mg/kg body weight in
    rats.  Dose levels exceeding 8 mg/kg body weight were maternally toxic
    in the rat.

    Developing young rats exhibited behavioural deficits post-natally
    following  in utero exposure.  A NOEL for this effect was established
    at 5 mg/kg body weight per day. 

    Multigeneration reproduction studies in rats did not indicate any
    morphological effects.  NOAELs of 10 and 120 mg/kg diet, based on
    reproductive parameters, were demonstrated in different studies.

    Delayed neurotoxicity has not been reported from exposure to
    fenitrothion.

    2.5  Effects on Human Beings

    Administration of fenitrothion to human volunteers in the form of a
    single oral dose of 0.042-0.33 mg/kg body weight or repeated doses of
    0.04-0.08 mg/kg body weight did not cause inhibition of plasma- and
    erythrocyte-ChE.  The urinary excretion of a metabolite, 3-methyl-
    4-nitrophenol, was complete within 24 h.

    Several cases of poisoning have occurred.  The signs and symptoms were
    those of parasympathic stimulation.  In a few cases, the  onset of
    toxic manifestations was delayed and they recurred for up to a few
    months.  It has been suggested that the slow release of the
    insecticide from the adipose tissue can give rise to a protracted
    clinical course or late symptoms of intoxication.  In some cases,
    contact dermatitis has been attributed to exposure to this
    insecticide.

    There is no evidence of delayed neurotoxicity or of an association
    with Reye's syndrome following exposure to fenitrothion.

    In some programmes of the World Health Organization, indoor residual
    spraying of fenitrothion has been used in a few countries for malaria
    control (application dose 2.0 g active ingredient/m2).  No evidence
    of toxicity was noted among the thousands of inhabitants observed,
    except in one study in which less than 2% of the inhabitants reported
    mild complaints.  However, approximately 30% of the spray applicators
    showed up to 50% inhibition of whole-blood ChE activity.  Following
    the aerial application of a 50% EC formulation, some workers developed
    symptoms of poisoning and decreased whole-blood ChE activity, within
    48 h.  Occupational exposure of male workers in a production plant for
    a period of over 5 years  and female workers in the packaging unit
    produced clinical signs and symptoms of poisoning in 15% of the male
    and 33% of the female workers.  The air concentrations of fenitrothion
    measured in the workplace ranged between 0.028 and 0.118 mg/m3.

    3.  CONCLUSIONS AND RECOMMENDATIONS

    3.1  Conclusions

    Fenitrothion is a moderately toxic organophosphorus ester insecticide. 
    However, overexposure through handling during manufacture or use, or
    through accidental or intentional ingestion, may cause serious
    poisoning.

    Exposure of the general population, mainly through agricultural and
    forestry practices and public health programmes, should not constitute
    a health hazard.

    With good work practices, hygienic measures, and safety precautions,
    fenitrothion is unlikely to present a hazard to those occupationally
    exposed.

    Despite its high toxicity for non-target arthropods, fenitrothion has
    been extensively used for pest control with few, or no, adverse
    effects on populations in the environment.

    3.2  Recommendations

    For the health and welfare of workers and the general population, the
    handling and application of fenitrothion should only be entrusted to
    competently supervised and well-trained operators, who will follow
    adequate safety measures and use fenitrothion according to good
    application practices.

    The manufacture, formulation, use, and disposal of fenitrothion should
    be carefully managed to minimize the contamination of the environment,
    particularly of surface waters.

    Regularly exposed workers should undergo periodic health evaluations.

    The rates of application of fenitrothion should be limited, to avoid
    effects on non-target arthropods.  The insecticide should never be
    sprayed over water bodies or streams.

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

    4.1  Main Human Health Hazards, Prevention and Protection, First Aid

    Fenitrothion is an organophosphorus insecticide.  Technical
    fenitrothion and concentrated formulations are moderately toxic for
    animals (acute oral LD50 for the rat, approximately 503 mg/kg), but
    can be hazardous for human beings, if incorrectly handled. 
    Fenitrothion is hazardous through ingestion and skin contact, because
    of fast absorption.  Typical signs and symptoms of organophosphorus
    poisoning may occur rapidly with over-exposure.

    The human health hazards associated with certain types of exposure to
    fenitrothion, together with preventive and protective measures and
    first aid recommendations are listed in Table 2.

    4.1.1  Advice to physicians

    4.1.1.1  Symptoms of poisoning

    Fenitrothion is an indirect inhibitor of cholinesterase.  In the body,
    it has first to be transformed into the active esterase inhibitor
    fenitrooxon.  As a result, signs and symptoms of overexposure develop
    after a latent period and may continue to increase after exposure has
    been discontinued.  Initially, there may be feelings of exhaustion,
    headache, weakness, muscle fasciculations in the face, and confusion. 
    Nausea, vomiting, abdominal pain, excessive sweating, pinpoint pupils,
    and salivation may develop.  Difficulty in breathing may be
    experienced, due to either congestion of the lungs or weakness of the
    respiratory muscles.  In severe cases of poisoning, muscle spasms,
    unconsciousness, and convulsions may develop.  Death may result from
    respiratory failure.

    For a more complete treatise on the effects of organophosphorus
    insecticides, especially their short- and long-term effects on the
    nervous system, refer to Environmental Health Criteria 63: 
    Organophosphorus insecticides - a general introduction.


        Table 2

                                                                                                                                         

    HAZARDS/SYMPTOMS                        PREVENTION AND PROTECTION                    FIRST AID
                                                                                                                                         

    GENERAL: readily absorbed via           Avoid exposure
    skin, ingestion, and inhalation; 
    may cause organophosphate
    poisoning: weakness, headache, 
    vomiting, excessive sweating and
    salivation, pinpoint pupils; in
    severe cases: convulsions, 
    unconsciousness, and death due
    to respiratory paralysis

    SKIN: irritation; redness; extensive    Wear PVC or neoprene gloves and              Remove and wash contaminated
    contamination may cause poisoning       apron; rubber boots                          clothing; wash contaminated skin
                                                                                         with water and soap; obtain medical
                                                                                         attention immediately

    EYES: irritation; redness               Wear safety goggles or face shield           Flush eyes with clean water for at
                                                                                         least 15 min; if irritation persists,
                                                                                         obtain medical attention immediately

    INHALATION: overexposure may            Avoid breathing the vapour; use              In case of signs and symptoms,
    cause poisoning                         proper (exhaust) ventilation or              remove from contaminated area and
                                            suitable respiratory protection              obtain medical attention immediately

    INGESTION: an unlikely                  Wash hands before eating, drinking,
    occupational hazard                     using the toilet, and after work

    Accidental or intentional ingestion                                                  Obtain medical attention immediately;
    may rapidly lead to severe poisoning                                                 if breathing has stopped, apply 
                                                                                         artificial respiration; induce 
                                                                                         vomiting, except in the case of
                                                                                         an emulsifiable concentrate

                                                                                                                                         

    HAZARDS/SYMPTOMS                        PREVENTION AND PROTECTION                    FIRST AID
                                                                                                                                         

    REPEATED EXPOSURE VIA                   As above                                     As above
    INHALATION OR INGESTION,
    OR THROUGH SKIN may gradually
    lead to signs and symptoms of 
    inhibition of cholinesterase activity

                                                                                                                                         
        4.1.1.2  Medical treatment

    If fenitrothion has been ingested and the formulation did not contain
    petroleum distillates, induce vomiting, or preferably perform gastric
    lavage using 5% sodium bicarbonate.  In the case of ingestion of
    liquid formulations containing hydrocarbon solvents, vomiting involves
    a risk of aspiration pneumonia.  Instead, the stomach should be
    emptied as soon as possible by careful gastric lavage (with a cuffed
    endotracheal tube already in place).  If possible, identify the
    solvents present in the formulation and observe the victim for
    additional toxic effects.  As early as possible, administer 2 mg of
    atropine sulfate iv and 1000-2000 mg pralidoxime chloride or 250 mg
    obidoxime chloride (adult dose) im or iv to patients suffering from
    severe respiratory difficulties, convulsions, or unconsciousness. 
    Repeated doses of 2 mg atropine sulfate should be given, as required,
    based on the respiration, blood pressure, pulse frequency, salivation,
    and convulsion conditions.  For children, the doses are 0.04-0.08 mg
    atropine/kg body weight, 250 mg pralidoxime chloride per child, or
    4-8 mg obidoxime chloride/kg body weight.

    Artificial respiration should be applied, if required.

    Morphine, barbiturates, phenothiazine derivatives, tranquillizers, and
    all kinds of central stimulants are contraindicated.

    The diagnosis of intoxication should be confirmed, as soon as
    possible, by the determination of the cholinisterase (ChE) activity in
    venous blood.

    For more information on the treatment of poisoning with
    organophosphorus insecticides see Environmental Health Criteria 63:
    Organophosphorus insecticides - a general introduction.  The section
    on therapy from this publication is attached as Annex I of this guide.

    4.1.2  Health surveillance advice

    Occupational exposure to organophosphorus insecticides can be
    monitored by measurement of erythrocyte- and whole blood-ChE activity. 
    Simple monitoring kits are available for this purpose.  Physiological
    variations in erythrocyte- and blood-ChE values occur in healthy
    persons.

    Inhibition of acetyl-cholinesterase (AChE) or ChE activity of less
    than 20-25% is considered diagnostic of exposure, but not necessarily
    indicative of hazard.  However, work procedures and hygiene should be
    checked.  Inhibition of 30-50% or more is considered an indication
    that an exposed individual should be removed from further contact with
    ChE-inhibiting pesticides, until values return to normal.  Work
    procedures and hygiene should also be checked.

    4.2  Explosion and Fire Hazards

    Liquid formulations may be flammable.  Inform the fire service that
    skin contamination and the breathing of fumes must be avoided. 
    Protective clothing and self-contained breathing apparatus must be
    worn.

    Extinguish fires with alcohol-resistant foam or powder.  The use of
    water spray should be confined to the cooling of unaffected stock, to
    avoid polluted runoff from the site.

    4.3  Storage

    Technical fenitrothion and its formulations should be stored in
    locked, well-ventilated buildings, preferably specifically used for
    insecticide storage.  Do not expose to direct sunlight.  Keep products
    out of reach of children and unauthorized personnel.  Do not store
    near animal feed or foodstuffs.

    4.4  Transport

    Comply with any local regulations regarding the movement of hazardous
    goods.  Do not load with animal feed or foodstuffs.  Check that
    containers are sound and labels undamaged before despatch.

    4.5  Spillage and Disposal

    4.5.1  Spillage

    Stay upwind, avoid skin contamination and inhalation of vapour. 
    Absorb spilled liquid and cover contaminated areas with a 1:3 mixture
    of sodium carbonate crystals and damp sawdust, lime, sand, or earth. 
    Sweep up and place in a closeable impervious container.  Ensure that
    the container is tightly closed and suitably labelled before transfer
    to a safe place for disposal.

    Prevent liquid from spreading and contaminating other cargo,
    vegetation, or waterways by constructing a barrier of the most
    suitable material available, e.g., earth or sand.  If spillage into a
    waterway occurs and the fenitrothion-containing material is immiscible
    with water and sinks, dam the waterway to stop the flow and to retard
    dissipation by water movement.  Use a bottom pump, dredging, or
    underwater vacuum equipment to remove undissolved material.

    Empty any of the product remaining in the damaged/leaking container
    into a clean empty container, which should then be tightly closed and
    suitably labelled.

    Decontaminate emptied containers with a 10% sodium carbonate solution
    added at the rate of at least 1 litre per 20-litre drum.  Swirl round
    to rinse walls, empty, and add rinsings to absorbent, such as sawdust,
    sand, or earth.  Puncture empty containers to prevent re-use.

    4.5.2  Disposal

    Contaminated absorbents, containers, and surplus product, should be
    burnt in a proper incinerator at high temperatures in a unit with
    effluent gas scrubbing.  When no incinerator is available, bury in an
    approved dump, or in an area where there is no risk of contamination
    of surface or ground water.  Before burying, mix liberally with sodium
    carbonate (washing soda) crystals, to help neutralize the product, and
    mix with soil rich in organic matter.  Comply with any local
    legislation.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    Fenitrothion is moderately toxic for birds and fish, but highly toxic
    for arthropods.  It does not bioaccumulate and breaks down rapidly in
    the environment.

    Avoid contamination of the soil, water, and the atmosphere by proper
    methods of storage, transport, handling, and waste disposal.

    In case of spillage, use the methods advised in section 4.5.1.

    6.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    The information given in this section has been extracted from the
    International Register of Potentially Toxic Chemicals (IRPTC) legal
    file. A full reference to the original national document from which
    the information was extracted can be obtained from IRPTC.  When no
    effective date appears in the IRPTC legal file, the year of the
    reference from which the data are taken is indicated by (r).

    The reader should be aware that regulatory decisions about chemicals
    taken in a certain country can only be fully understood in the
    framework of the legislation of that country.  Furthermore, the
    regulations and guidelines of all countries are subject to change and
    should always be verified with appropriate regulatory authorities
    before application.

    6.1  Previous Evaluations by International Bodies

    Fenitrothion was evaluated by the Joint FAO/WHO Meeting on Pesticide
    Residues (JMPR) in 1969, 1974, 1976, 1977, 1979, 1982, 1983, 1984,
    1986, 1987, 1988, and 1989.  In 1988, the JMPR established an
    Acceptable Daily Intake (ADI) for man of 0-0.005 mg/kg body weight. 
    For Codex Maximum Residue Limits (MRLs) see Table 3.

    The International Programme on Chemical Safety (WHO) has classified
    technical fenitrothion as "moderately hazardous" (Class II).  WHO has
    issued a data sheet on fenitrothion (No. 30).

    6.2  Exposure Limit Values

    Some exposure limit values are given in Table 3.

    6.3  Specific Restrictions

    Fenitrothion has been approved for use as a pesticide in many
    countries.  In some countries, specific uses are defined as well as
    limitations and precautions.

    6.4  Labelling, Packaging, and Transport

    The United Nations Committee of Experts on the Transportation of
    Dangerous Goods classifies fenitrothion in:

    Hazard Class 6.1:        poisonous substance;

    Packing Group III:       a substance presenting a relatively low risk
                             of poisoning in transport, for material
                             containing 48% (liquid).

    The label should be as follows:

    FIGURE 1

    The European Economic Community legislation requires labelling of
    fenitrothion as dangerous substance using the symbol:

    FIGURE 2

    The label must read:

          Harmful by inhalation, in contact with skin and if swallowed;
          keep out of reach of children; keep away from food, drink and
          animal feeding stuffs.

    The European Economic Community legislation on the labelling of
    pesticide preparations classifies fenitrothion in Class IIB for the
    purpose of determining the label.

    WHO gives the following product specification for technical
    fenitrothion for use in public health:

     "The material shall consist of fenitrothion together with related
     manufacturing compounds and shall be in the form of a yellow to brown
     liquid free from extraneous impurities or added modifying agents." 

    It should contain at least 930 g of fenitrothion per kg.  The
    specification gives the required acidity and water content and also
    analytical methods for checking  The specification continues:

     "The technical fenitrothion shall be packed in suitable clean
     containers, as specified in the order."

     "All packages shall bear, durably and legibly marked on the
     container, the following:

          Manufacturer's name
          Technical fenitrothion to specification WHO/SIT/17.R2
          Batch or reference number, and date of test
          Net weight of contents
          Date of manufacture

     and the following minimum cautionary notice:

     "Fenitrothion is an organophosphorus compound that inhibits
     cholinesterase.  It is poisonous if swallowed or inhaled.  It may be
     absorbed through the skin.  Avoid skin contact; wear protective
     gloves, clean protective clothing, and a respirator when handling the
     material.  Wash thoroughly with soap and water after using."

     "Keep out of the reach of children and well away from foodstuffs and
     animal feed and their containers."

     "If poisoning occurs, call a physician.  Atropine and pralidoxime are
     specific antidotes and artificial respiration may be needed."

    Similar specifications and instructions are given for fenitrothion
    water-dispersible powder and emulsified concentrate.

    FAO gives similar product specifications for fenitrothion for its use
    in plant protection.  In this case, the technical material should
    contain at least 95% active material, and containers must comply with
    pertinent national and international transport and safety regulations.

    6.5  Waste Disposal

    In the USA, any waste containing fenitrothion is considered a
    hazardous waste and permits are required for its handling, transport,
    treatment, storage or discharge and disposal.


        Table 3. Exposure limit values

                                                                                                                                         

    Medium      Specification     Country/           Exposure limit description                          Value              Effective
                                  organization                                                                              date
                                                                                                                                         

    AIR         Workplace         Japan              Maximum acceptable concentration (MAC)
                                                     - Time-weighted average (TWA)                       1 mg/m3a           1986

                                  USSR               Maximum allowable concentration (MAC)
                                                     - Ceiling value (CLV) (vapour and aerosol)          0.1 mg/m3          1982

                Ambient           USSR               Maximum allowable concentration (MAC) 
                                                     - average per day                                   0.001 mg/m3        1982
                                                     - 1  /day                                          0.005 mg/m3

    FOOD        Intake from       FAO/WHO            Acceptable daily intake (ADI)                       0-0.005 mg/kg      1988
                                                                                                         body weight

                Residue           FAO/WHO            Maximum residue limit (MRL)                         0.002-20 mg/kg     1989
                                                     (with its oxygen analogue expressed
                                                     as fenitrothion); products specified as follows:
                                                     - milks                                             0.002 mg/kg
                                                     - cucumbers, meat, onions, potatoes                 0.05 mg/kg
                                                     - cauliflower, cocoa beans, egg plants, 
                                                       peppers, soybeans (dry)                           0.1 mg/kg
                                                     - bread (white) leeks, radishes                     0.2 mg/kg
                                                     - apples, cabbage, cabbage red, cherries,
                                                       grapes, lettuce, pear, peas, 
                                                       strawberries, tea (dried, green),
                                                       tomatoes                                          0.5 mg/kg
                                                     - peach, rice (polished)                            1 mg/kg
                                                     - citrus fruit, wheat flour (white),b
                                                       processed wheat bran                              2 mg/kg
                                                     - wheat flour (wholemeal)                           5 mg/kg
                                                     - cereal grains                                     10 mg/kg
                                                     - raw wheat bran, rice bran unprocessed             20 mg/kg

                                                                                                                                         

    Medium      Specification     Country/           Exposure limit description                          Value              Effective
                                  organization                                                                              date
                                                                                                                                         

    WATER       Surface           USSR               Maximum allowable concentration (MAC)               0.25 mg/litre      1983

                Fishing           USSR               Maximum allowable concentration (MAC)               0.00 mg/litre      1983

    SOIL                          USSR               Maximum allowable concentration (MAC)               1.0 mg/kg          1984

                                                                                                                                         

    a Notice : skin absorption.
    b Codex 1990.
        BIBLIOGRAPHY

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

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

    FAO/WHO (1986b)  Guide to Codex recommendations concerning pesticide
    residues. Part 8. Recommendations for methods of analysis of pesticide
    residues. 3rd ed., Rome, Codex Committee on Pesticide Residues.

    FAO/WHO (1986c)  Codex maximum limits for pesticide residues.
    CAC/Vol.XIII - ed. 2, Rome, Codex Alimentarius Commission, Food and
    Agriculture Organization of the United Nations, (+ Annex 2 (1990)).

    GIFAP (1982)  Guidelines for the safe handling of pesticides during
    their formulation, packing, 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 pesticide
    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.

    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 (Unpublished
    document VBC/84.889).

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

    UNITED NATIONS (1986)  Recommendations on the transport of dangerous
    goods. 4th ed., New York, United Nations.

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

    WHO (1986)  Environmental Health Criteria 63: Organophosphorus
    insecticides - a general introduction. Geneva, World Health
    Organization, 181 pp.

    WHO (1990)  The WHO recommended classification of pesticides by hazard
    and guidelines to classification, 1990-91. Geneva, World Health
    Organization (Unpublished document WHO/PCS/90.1).

    WHO (1990)  Environmental Health Criteria 133: Fenitrothion. Geneva,
    World Health Organization.

    WHO/FAO (1977)  Fenitrothion. Data sheets on pesticides, No. 30.
    Geneva, World Health Organization (Unpublished documents VBC,
    DS,77.30).

    WORTHING, C.R. & WALKER, S.B. (1987)  The pesticide manual. 8th ed.,
    Lavenham, Lavenham Press Limited, British Crop Protection Council.

    ANNEX I

    TREATMENT OF ORGANOPHOSPHATE INSECTICIDE POISONING IN MAN

    (From EHC 63: Organophosphorus Insecticides - A General Introduction)

    All cases of organophosphorus poisoning should be dealt with as an
    emergency and the patient sent to hospital as quickly as possible. 
    Although symptoms may develop rapidly, delay in onset or a steady
    increase in severity may be seen up to 48 h after ingestion of some
    formulated organophosphorus insecticides.

    Extensive descriptions of treatment of poisoning by organophosphorus
    insecticides are given in several major references (Kagan, 1977;
    Taylor, 1980; UK DHSS, 1983; Plestina, 1984) and will also be included
    in the IPCS Health and Safety Guides to be prepared for selected
    organophosphorus insecticides.

    The treatment is based on:

    (a) minimizing the absorption;

    (b) general supportive treatment; and

    (c) specific pharmacological treatment.

    I.1  Minimizing the Absorption

    When dermal exposure occurs, decontamination procedures include
    removal of contaminated clothes and washing of the skin with alkaline
    soap or with a sodium bicarbonate solution.  Particular care should be
    taken in cleaning the skin area where venupuncture is performed. 
    Blood might be contaminated with direct-acting organophosphorus esters
    and, therefore, inaccurate measures of ChE inhibition might result. 
    Extensive eye irrigation with water or saline should  also  be
    performed.  In the case of ingestion, vomiting  might be induced, if
    the patient is conscious, by the administration of ipecacuanha syrup
    (10-30 ml) followed by 200 ml water.  This treatment is, however,
    contraindicated in the case of pesticides dissolved in hydrocarbon
    solvents.  Gastric lavage (with addition of bicarbonate solution or
    activated charcoal) can also be performed, particularly in unconscious
    patients, taking care to prevent aspiration of fluids into the lungs
    (i.e., only after a tracheal tube has been put in place).

    The volume of fluid introduced into the stomach should be recorded and
    samples of gastric lavage frozen and stored for subsequent chemical
    analysis.  If the formulation of the pesticide involved is available,
    it should also be stored for further analysis (i.e., detection of
    toxicologically relevant impurities).  A purgative can be administered
    to remove the ingested compound.

    I.2  General Supportive Treatment

    Artificial respiration (via a tracheal tube) should be started at the
    first sign of respiratory failure and maintained for as long as
    necessary.

    Cautious administration of fluids is advised, as well as general,
    supportive and symptomatic pharmacological treatment and absolute
    rest.

    I.3  Specific Pharmacological Treatment

    I.3.1  Atropine

    Atropine should be given, beginning with 2 mg iv and given at
    15-30-min intervals.  The dose and the frequency of atropine treatment
    varies from case to case, but should maintain the patient fully
    atropinized (dilated pupils, dry mouth, skin flushing, etc.). 
    Continuous infusion of atropine may be necessary in extreme cases and
    total daily doses of up to several hundred mg may be necessary during
    the first few days of treatment.

    I.3.2  Oxime reactivators

    Cholinesterase reactivators (e.g., pralidoxime, obidoxime)
    specifically restore AChE activity inhibited by organophosphates. 
    This is not the case with enzymes inhibited by carbamates.  The
    treatment should begin as soon as possible, because oximes are not
    effective on "aged" phosphorylated ChEs.  However, if absorption,
    distribution, and metabolism are thought to be delayed for any
    reasons,  oximes can be administered for several days after
    intoxication.  Effective treatment with oximes reduces the required
    dose of atropine.  Pralidoxime is the most widely available oxime.  A
    dose of 1 g pralidoxime can be given either im or iv and repeated
    2-3 times per day or, in extreme cases, more often.  If possible,
    blood samples should be taken for AChE determinations before and
    during treatment.  Skin should be carefully cleansed before sampling. 
    Results of the assays should influence the decision on whether to
    continue oxime therapy after the first 2 days.

    There are indications that oxime therapy may possibly have beneficial
    effects on CNS-derived symptoms.

    I.3.3  Diazepam

    Diazepam should be included in the therapy of all but the mildest
    cases.  Besides relieving anxiety, it appears to counteract some
    aspects of CNS-derived symptoms, which are not affected by atropine. 
    Doses of 10 mg s.c. or i.v. are appropriate and may be repeated as
    required (Vale & Scott, 1974).  Other centrally acting drugs and drugs
    that may depress respiration are not recommended in the absence of
    artificial respiration procedures.

    I.3.4  Notes on the recommended treatment

    I.3.4.1  Effects of atropine and oxime

    The combined effect far exceeds the benefit of either drug singly.

    I.3.4.2  Response to atropine

    The response of the eye pupil may be unreliable in cases of
    organophosphorus poisoning.  A flushed skin and drying of secretions
    are the best guide to the effectiveness of atropinization.  Although
    repeated dosing may well be necessary, excessive doses at any one time
    may cause toxic side-effects.  Pulse-rate should not exceed 120/min.

    I.3.4.3  Persistence of treatment

    Some organophosphorus pesticides are very lipophilic and may be taken
    into, and then released from, fat depots over a period of many days. 
    It is therefore quite incorrect to abandon oxime treatment after
    1-2 days on the supposition that all inhibited enzyme will be aged. 
    Ecobichon et al. (1977) noted prompt improvement in both condition and
    blood-ChEs in response to pralidoxime given on the 11th-15th days
    after major symptoms of poisoning appeared due to extended exposure to
    fenitrothion (a dimethyl phosphate with a short half-life for aging of
    inhibited AChE).

    I.3.4.4  Dosage of atropine and oxime

    The recommended doses above pertain to exposures, usually for an
    occupational setting, but, in the case of very severe exposure or
    massive ingestion (accidental or deliberate), the therapeutic doses
    may be extended considerably.  Warriner et al. (1977) reported the
    case of a patient who drank a large quantity of dicrotophos, in error,
    while drunk.  Therapeutic dosages were progressively increased up to
    6 mg atropine i.v. every 15 min together with continuous i.v. infusion
    of pralidoxime chloride at 0.5 g/h for 72 h, from days 3 to 6 after
    intoxication.  After considerable improvement, the patient relapsed
    and further aggressive therapy was given at a declining rate from days
    10 to 16 (atropine) and to day 23 (oxime), respectively.  In total,
    92 g of pralidoxime chloride and 3912 mg of atropine were given and
    the patient was discharged on the thirty-third day with no apparent
    sequelae.

    References to Annex I

    ECOBICHON, D.J., OZERE, R.L., REID, E., & CROCKER, J.F.S  (1977) 
    Acute fenitrothion poisoning. Can. Med. Assoc. J., 116: 377-379.

    KAGAN, JU.S.  (1977)  [Toxicology of organophosphorus pesticides.]
    Moscow, Meditsina, pp. 111-121, 219-233, 260-269 (in Russian).

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

    TAYLOR, P.  (1980)  Anticholinesterase agents. In: Goodman, L.S. &
    Gilman, A., ed. The pharmacological basis of therapeutics. 6th ed. New
    York, Macmillan Publishing Company, pp. 100-119.

    UK DHSS  (1983) Pesticide poisoning: notes for the guidance of medical
    practitioners, London, United Kingdom Department of Health and Social
    Security, pp. 41-47.

    VALE, J.A. & SCOTT, G.W.  (1974)  Organophosphorus poisoning. Guy's
    Hosp. Rep., 123: 13-25.

    WARRINER, R.A., III, NIES, A.S., & HAYES, W.J., Jr (1977) Severe
    organophosphate poisoning complicated by alcohol and terpentine
    ingestion. Arch. environ. Health, 32: 203-205.

    


    See Also:
       Toxicological Abbreviations
       Fenitrothion (EHC 133, 1992)
       Fenitrothion (ICSC)
       Fenitrothion (FAO/PL:1969/M/17/1)
       Fenitrothion (WHO Pesticide Residues Series 4)
       Fenitrothion (Pesticide residues in food: 1976 evaluations)
       Fenitrothion (Pesticide residues in food: 1977 evaluations)
       Fenitrothion (Pesticide residues in food: 1979 evaluations)
       Fenitrothion (Pesticide residues in food: 1982 evaluations)
       Fenitrothion (Pesticide residues in food: 1983 evaluations)
       Fenitrothion (Pesticide residues in food: 1984 evaluations)
       Fenitrothion (Pesticide residues in food: 1986 evaluations Part II Toxicology)
       Fenitrothion (Pesticide residues in food: 1988 evaluations Part II Toxicology)
       Fenitrothion (JMPR Evaluations 2000 Part II Toxicological)