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    WORLD HEALTH ORGANIZATION             FOOD AND AGRICULTURE
                                          ORGANIZATION
    ORGANISATION MONDIALE DE LA SANTE     ORGANISATION POUR L'ALIMENTATION
                                          ET L'AGRICULTURE

                                                      VBC/DS/77.26

                                                      ORIGINAL: ENGLISH






    DATA SHEETS ON PESTICIDES No. 26

    HEXACHLOROBENZENE






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

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

                                CLASSIFICATION:

                                Primary Use:  Fungicide

                                Secondary Uses:  None

                                Chemical Group:  Organochlorine compound

    1.  GENERAL INFORMATION

    1.1  COMMON NAME:

    Hexachlorobenzene

    Identity: Hexachlorobenzene

    Synonyms: Perchlbrobenzene, HCB

    Local synonyms:

    CHEMICAL STRUCTURE

    1.2  SYNOPSIS

    An organochlorine compound, of low acute toxicity; however it is
    persistent and accumulates in body tissues. Chronic poisoning with
    this compound can occur, giving rise to cutaneous porphyria.

    1.3  SELECTED PROPERTIES

    1.3.1  Physical characteristics

    A colourless white powder or needles m.p. 229°C, b.p. 326°C.
    Technical agricultural grade contains 98% hexachlorobenzene, 1.8%
    pentachlorobenzene with 0.2% 1,2,4,5 tetrachlorobenzene. M.p. over
    200.

    1.3.2  Solubility

    Practically insoluble in water, slightly soluble in cold alcohol;
    soluble in benzene, chloroform or ether.

    1.3.3  Stability

    Stable.

    1.3.4  Vapour pressure

    1.089 x 10-5 = Hg at 20°C.

    1.4  AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1  Common formulations

    10-40% dust to prevent fungus attack, often in combination with
    other seed protectants particularly lindane (0.5-1.0%) to prevent
    insect attack on stored seed.

    1.4.2  Susceptible pests

    Soil pests, sucking and biting insects and many glass-house pests.

    1.4.3  Use pattern

    As a selective fungicide for the control of bunt on wheat by seed
    pre-treatment. It should be noted that a Joint FAO/WHO Meeting in
    1974 recommended as follows: Hexachlorobenzene should be used to
    dress cereal seed only if the need for such a treatment has been
    investigated and assessed and the possible use of an alternative has
    been ruled out. It should not be used for the treatment of cereal
    seed to be exported for the production of seed.

    1.4.4  Unintended effects

    May irritate the skin mildly.

    1.5  PUBLIC HEALTH PROGRAMMES:

    No public health use.

    1.6  HOUSEHOLD USE:

    No household use.

    2.  TOXICOLOGY AND RISKS

    2.1  TOXICOLOGY - MAMMALS

    2.1.1  Absorption route

    Can be absorbed from the gastrointestinal tract or by inhalation. It
    does not appear to be absorbed through the intact skin to any
    extent, but there have been some reports of skin irritation with
    this compound.

    2.1.2  Mode of action

    Hexachlorobenzene causes liver injury and porphyria in man, rat,
    mouse, guinea-pig and rabbit. In man, these changes are the cause of
    death. Neurological Changes have not been reported, although they do
    occur in rodents.

    2.1.3  Excretion products

    Hexachlorobenzene does not appear to be metabolised. Five days after
    an oral dose given to rabbits the main portion of the dose was found
    in the gut contents, only 6% had appeared in the faeces. There was
    no significant urinary or pulmonary excretion of metabolites.

    2.1.4  Toxicity, single dose

    Oral LD50 - rat* - 3500-10 000 mg/kg
                                                     (*sex not stated)
    Most susceptible species - cat* - 1700 mg/kg

    2.1.5  Toxicity, repeated doses

    Oral:  Experimental porphyria was produced within one month in
    rats dosed orally by stomach tube at 0.8-1.0 g/kg/day for 10 days
    and then at 1.2-1.3 g/kg/day thereafter. Mortalities on this dosing
    regime were few and porphyria could be maintained for some time.

    Inhalation:  A single exposure of rats to hexachlorobenzene vapour
    at 3.6 mg/l and 1.2 mg/l (duration not given) caused symptoms of
    irritation followed by an increase in haemoglobin and erythrocytes
    count and later a gradual decrease in these parameters.

    Cumulation of compound: Hexachlorobenzene is stored in body fat.
    Studies on the omental fat of sheep have shown that it is stored to
    a level seven to nine times the concentration at which it is fed. It
    has a half-life of from 10-18 weeks depending on the level at which
    it is ingested. A plateau level in tissues is reached when
    elimination balances intake.

    Cumulation of effect: Alterations in liver size and porphyrin are
    observed in cases of prolonged ingestion of hexachlorobenzene. The
    alterations in porphyrin metabolism and excretion are not
    immediately reversible on cessation of feeding as has been shown for
    both man and animals. Photosensitivity may re-occur for several
    years after exposure in man.

    2.1.6  Dietary studies

    Short-term:  0.5% hexachlorobenzene fed in the diet to guinea-pigs
    and mice caused marked neurological symptoms in 8-10 days. Rabbits
    given the same dose died in 8-12 weeks and were generally more
    resistant to this compound.

    Female rats were fed a diet containing 2000 ppm hexachlorobenzene;
    in seven days weight loss and general debility were observed and
    from 3-8 weeks all rats showed increased urinary porphyria
    excretion. Rats with well-established porphyria were expose
    continuously to ultraviolet light. If an area of about 25 cm2 or
    larger was plucked or shaved at the beginning of the exposure period
    most of the animals died in 3 to 14 days. Prolonged exposure to the
    same ultraviolet irradiation had no effect on porphyric rats fully
    covered with hair or on normal rats that were plucked or shaved
    repeated. When the ultraviolet bulbs in the cages were replaced by
    daylight bulbs, there was no injury 116 plucked or shaved porphyric
    rats. Hexachlorobenzene usually produces no irritation or sensation
    in unirradiated rodents.

    Long-term:  No information.

    2.1.7  Supplementary studies of toxicity

    Carcinogenicity:  No information.

    Teratogenicity: In rat foetuses whose dams were given single oral
    doses on days 10-13: 6-16, or 6-21 of gestation, the incidence of
    uni- and bilateral fourteenth ribs were increased, relative to the
    duration of treatment and dose. Sternal defects were found in those
    from dams dosed on days 6-24. No significant differences were found
    in value for live and dead foetuses resorption sites, foetal weight,
    or other viscera or skeletal abnormalities.

    Mutagenicity: In a dominant lethal test where male rats were dosed
    at various levels to 60 mg/kg for 10 days, no significant
    differences in reproduction were found in the succeeding 14
    generation.

    Neurotoxicity:  Neurological disturbances have been observed in
    guinea-pigs, mice, rabbits and to a certain extent in rats; however
    no histopathological lesions been found. Symptoms have included
    course tremor hyper-excitability, clonic convulsion and paralysis.
    However, none of these symptoms have been observed in man, possibly
    due to differences in dosage levels.

    2.1.8  Modification of toxicity

    Hexachlorobenzene at a dietary level of 20 000 ppm produces
    cutaneous lesions as well as other signs of intoxication in rats.
    When some of these rats were given 10 or 20 mg of
    adenosine-5-monophosphoric acid daily after illness had begun and
    while exposure to the fungicide was continued, most showed healing
    of skin lesions, recovery of lost weight, practical disappearance of
    neurological signs decrease in excretion of porphyrins, and
    reduction of liver injury. Some treated rats died in spite of
    visible improvements in skin lesions and the condition of the fur.
    Controls that received the fungicide but no treatment showed a
    gradual progression of the disease.

    2.2  TOXICOLOGY - MAN

    2.2.1  Absorption

    Toxicity with this compound is normally associated with ingestion in
    the diet, however inhalation of dust is possible, and though it is
    probably not absorbed through the intact skins to any extent, dermal
    and ocular irritation have been observed.

    2.2.2  Dangerous doses

    Single:  No information.

    Repeated:  5-2000 mg a day, if ingested for a sufficient length of
    time, is hazardous to man.

    2.2.3  Observations of occupationally exposed workers

    No reported cases.

    2.2.4  Observations on exposure of the general population

    Levels of hexachlorobenzene have been found in samples of human milk
    in Australia from both rural and urban communities: of 66 samples
    examined all were positive at levels of 0.042 to 0.063 ppm. A second
    study in Australia revealed levels of 1.25 ppm in 75 samples of
    human perirenal fat. The source was thought to be eggs from chickens
    fed contaminated seed corn. See also 2.2.6 below.

    2.2.5  Observations of volunteers

    No information.

    2.2.6  Reported mishaps

    A major outbreak of poisoning due to ingestion of hexachlorobenzene
    has occurred in South-East Turkey where there were estimated to be
    3000-5000 cases over a five-year period from 1955-59. The outbreak
    was traced to the consumption of wheat intended as seed corn and
    pretreatment with hexachlorobenzene. The poisoning occurred as a
    cutaneous porphyria which was manifest as a photosensitive
    blistering and epidermolysis of the skin. Hyperpigmentation and
    hypertrichosis were common features. The urine contained large
    quantities of porphyrins and weight loss and hepatomegaly were
    frequently present. Abdominal pain also occurred. Neurological
    symptoms were not evident, but bone and joint changes were apparent
    in some cases giving rise to osteaorosis of the extremities and
    interphalangeal arthritis. The overall mortality ratel was 10%.
    Children born to mothers who had eaten the grain developed skin
    lesions that proved fatal in 95% of cases. Analysis of the maternal
    milk showed the presence of hexachlorobenzene.

    On cessation of intake most features of this disease disappeared in
    20-30 days, though photosensitive relapses during the summer months
    were often seen up to three to five years later; arthritic joint
    changes did not regress. The estimated intake of hexachlorobenzene
    was from 50-2000 mg/day for a long period.

    A second outbreak of poisoning occurred in Saudi Arabia; out of 490
    persons hospitalized seven died. The source was a bakery using
    hexachlorobenzene as a poison to control rodents. The organochlorine
    content of bread baked there was 220 ppm.

    2.3  TOXICITY TO NON-MAMMALIAN SPECIES

    2.3.1  Fish

    Harmful.

    2.3.2  Birds

    No information.

    2.3.3  Other species

    Harmful to bees and livestock.

    3.  FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATIONS OF
    COMPOUND

    3.1  RECOMMENDED RESTRICTIONS ON AVAILABILITY

    (for definition of categories, see introduction)

    All formulations, Category 3

    Hexachlorobenzene has been the subject of a special study by a
    WHO/FAO meeting (WHO Technical Report Series No. 555, 1974). It
    was recommended that it should be used for seed dressing only when
    there was no satisfactory alternative and dressed cereal seed should
    not be exported (see Section 1.4.3).

    3.2  TRANSPORTATION AND STORAGE

    All formulations - Should be transported or stored in clearly
    labelled rigid and leak-proof containers. No food or drink should be
    transported or stored in the same compartment. Storage should be
    under lock and key, and secure from access by unauthorized persons
    and children.

    Treated grain - Should be distinctly coloured or made unpalatable,
    and should be transported or stored in clearly labelled leakproof
    containers. No food or drink should be transported or stored in the.
    same compartment and it should be kept well away from untreated
    grain. Storage should be under lock and key, and secure from access
    by unauthorized persons and children. It should not be fed to
    animals even if diluted with undressed seed.

    3.3  HANDLING

    All formulations - Protective gloves should be worn when handling
    this compound, and excessive dust should be avoided. Adequate
    washing facilities should be available at all times during handling
    of this compound and should be close to the site of handling.
    Eating, drinking and smoking should I be prohibited during handling
    and before washing after handling.

    Treated grain - Dressed seed should not be handled more than
    necessary. Wash hands and exposed skin before meals and after work.

    3.4  DISPOSAL AND/OR DECONTAMINATION OF CONTAINER

    Container must either be burned or crushed and buried below the
    topsoil. Care must be taken to avoid subsequent contamination of
    water sources. Decontamination of containers in order to use them
    for other purposes should not be permitted. Sacks or containers that
    have been used for dressed seed should not be used for other
    purposes.

    3.5  SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS

    All formulations - Pre-employment medical examination of workers
    desirable. Workers suffering from active hepatic or renal disease
    should be excluded from contact if exposure is considerable and
    prolonged, routine estimations of urinary porphyrin excretion for
    workers desirable. Training of workers in techniques to avoid
    contact essential.

    3.6  ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT

    All formulations - Not applicable.

    3.7  LABELLING

    All formulations - Minimum cautionary statement

    Hexachlorobenzene is an organochlorine fungicide. It is poisonous if
    swallowed and can cause skin and eye irritation. Avoid skin contact;
    wear protective gloves and clean protective  clothing whet handling
    the material. Wash thoroughly with soap and water after use. Keep
    the material out of reach of children and well away from foodstuffs,
    animal feed and their containers if poisoning occurs call a
    physician.

    Treated grain - Minimum cautionary statement

    Seed treated with hexachlorobenzene must not be used as food for
    humans, animals or birds.

    3.8  RESIDUES IN FOOD

    Maximum residue limits for hexachlorobenzene have been recommended
    by the Joint FAO/WHO Meeting on Pesticide Residues.

    4.  PREVENTION OF POISONING IN MEN AND EMERGENCY AID

    4.1  PRECAUTIONS IN USE

    4.1.1  General

    Hexachlorobenzene is an organochlorine fungicide of low acute
    toxicity which may be absorbed by inhalation of dusts or from the
    gastrointestinal tract and can cause skin irritation. It accumulates
    in body tissues and is a chronic poison. All formulations should be
    handled by trained personnel wearing protective clothing.

    4.1.2  Manufacture and formulation

    TLV: (ACGIH) (USSR) 0.9 g/m3. Vapour and dusts should be
    controlled preferably by mechanical means. Protective equipment for
    the skin and respiratory protection is usually necessary. Mixing as
    far as possible should be in a closed system.

    4.1.3  Mixers and applicators

    When opening the container and when mixing care should be taken to
    avoid contact with the mouth and eyes. A facial visor and gloves
    should be worn. The mixer, and those associated with the process,
    should as far as possible avoid working in dust and avoid contact
    with the mouth. Before eating, drinking or smoking, hands and other
    exposed skin should be washed.

    4.1.4  Other associated workers

    Persons exposed to hexachlorobenzene and associated with its
    application should observe the precautions described above in 4.1.3
    under "mixers and applicators".

    4.1.5  Other populations likely to be affected

    With good agricultural practice other populations should not be
    exposed to hazardous amounts of hexachlorobenzene.

    4.2  ENTRY OF PERSONS INTO TREATED AREAS

    Not applicable.

    4.3  DECONTAMINATION OF SPILLAGE AND CONTAINERS

    Containers should be emptied in a diluted form into A pit, taking
    care to avoid contamination of ground waters. Decontamination of
    containers in order to use them for other purposes should not be
    permitted. Spillage should be removed as much as possible into a
    deep dry pit and the remainder washed away with large quantities of
    water.

    4.4  EMERGENCY AID

    4.4.1  Early symptoms of poisoning

    Acute poisoning with hexachlorobenzene is very unlikely. However,
    early symptoms might include stomach pain, nausea, vomiting,
    weakness; neurological symptoms have been reported in animals.

    4.4.2  Treatment before person is seen by a physician, if these
    symptoms appear following exposure

    The person should stop work immediately, remove contaminated
    clothing, wash the affected skin with soap and water if available,
    and flush the area with large quantities of water. If swallowed,
    vomiting should be induced if the person is conscious.

    5.  FOR MEDICAL AND LABORATORY PERSONNEL

    5.1  MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING

    5.1.1  General information

    Hexachlorobenzene is an organochlorine fungicide of low acute
    toxicity, but is persistent and stored in body tissues. It is mainly
    absorbed from the gastrointestinal tract but inhalation is possible.
    It is not absorbed to any extent through the intact skin, but has
    been known to cause dermal irritation. Chronic exposure has resulted
    in interference with porphyrin metabolism, which is not necessarily
    reversible on cessation of exposure.

    5.1.2  Symptoms and sign

    There is very little information on symptoms resulting  from acute
    exposure to hexachlorobenzene and due to its low toxicity this form
    of poisoning is unlikely. Prolonged ingestion of levels of from 50
    to 200 ppm. have caused increased excretion of porphyrin metabolites
    in urine and faeces; port-wine coloured urine is typical of this
    type of effect. Severe photosensitization of the skin with bullae
    milia, extensive-scars, loss of elasticity, atrophy,
    hyperpigmentation and sclero-dermatous change, hypertrichosis
    abdominal vain, weakness, hepatomegaly and cirrhotic changes, and a
    painless arthritis of the terminal finger digits.

    5.1.3  Laboratory

    Toxic porphyria caused by hexachlorobenzene gives rise to symptoms
    closely resembling those seen in Porphyria Cutanea Tarda but with
    more emphasis on liver damage. However, laboratory data are unique
    and include urine characterized by marked increase of uro and
    coproporphyrins, but with normal amounts of porphyrobilinogen and
    ALA. Levels of urine coproporphyrin of from 77 to 401 µg/day and
    urine uroporphyrin from 679 to 435 µg/day may be found in
    chronically poisoned patients. Increases in liver function values
    may be observed, with regard to GOT, GPT, and dehydrogenases. Levels
    of hexachlorobenzene will be found in fat and can be used to confirm
    the diagnosis.

    5.1.4  Treatment

    A poisoning is usually due to ingestion. Unless the patient is
    vomiting rapid gastric lavage should be performed using 5% sodium
    bicarbonate if available. For skin contact the skin should be washed
    with soap and water. If the compound has entered the eyes they
    should be washed with isotonic saline or water. Acute intoxication
    has not been described for this compound, so treatment must of
    necessity be symptomatic.

    In chronic exposure the source of the hexachlorobenzene should be
    ascertained and the patient removed from any further exposure.
    Treatment is mainly symptomatic, the patient should be kept away
    from direct sunlight. Chelating agents have been used on a limited
    scale with some success (Peters, H. A. et al., see 5.1.6 below).
    Treatment with EDTA (disodium salt) was given intravenously (1.5 g
    EDTA in 1000 ml 5% glucose in water daily for five days) followed by
    disodium EDTA orally (1.5 g daily for 16 weeks, 1.0 g for 10 weeks,
    0.5 g for eight weeks, none for four weeks and then 1 g daily for 10
    weeks).

    5.1.5  Prognosis

    In chronic poisoning the prognosis is poor with regard to a complete
    cure. Photosensitivity can reappear up to five years after cessation
    of exposure and arthritic joint changes are probably permanent once
    established. If exposure has not been too prolonged there may be
    complete recovery 20-30 days after exposure has ceased.

    5.1.6  References to previously reported cases

    Peters, H. A. et al. (1966) Amer. J. Med. Sci., 251, 314

    Cam, C. & Nigogosyan, G. (1963) J. Am. Med. Assn., 183, 88

    Dogramaci, I. et al. (1962) Turkish Journal of Pediatrics, 4(3),
    129-150

    5.2  SURVEILLANCE TESTS

    Urine coproporphyrin and uroporphyrin may be useful or surveillance
    of patients and  the appearance of the skin lesions will also be of
    assistance. Liver cirrhosis often accompanies poisoning with this
    compound, so tests of liver function may prove useful. Levels of
    hexachlorobenzene will be found in fat and can be used to
    confirm diagnosis.

    5.3  LABORATORY METHODS

    5.3.1  Detection and assay of compound

    Detection and assay of hexachlorobenzene is not straightforward, as
    this compound is exceptionally non-polar and extraction by the
    normal method for organochlorine compounds is not successful. In
    addition the column normally used in GLC for separation of
    organochlorine compounds does not adequately distinguish between
    hexachlorobenzene and alpha-benzene hexachloride.

    However, these problems are discussed and methods suggested in the
    following publications:

    Taylor, I. S. et al. (1970) J. Assoc. Offic. Anal. Chemists,
    53(6), 1293-1295

    Smyth, R. J. (1972) J. Assoc. Offic. Anal. Chemists, 55(4),
    806-808

    Collins, G. B. et al. (1972) J. Chromatogr., 69(1), 198-200

    5.3.2  Other tests in cases of poisoning

    Tests for uro- and coproporphyrin in urine can be made to confirm
    and monitor exposure. Tests of liver function, by estimation of
    serum transaminases and dehydrogenases may also be useful.
    Porphyrin: references for methods of estimation.

    1.   Laboratory Medicine. Hematology. John B. Miale, 1958, published
              by C. V. Mosby Company, p. 660

    2.   Disorders of the blood. Whitby & Briton. 10th Edition, 1969,
              published by J. A. Churchill Ltd., p. 750

See Also:
        Hexachlorobenzene (EHC 195, 1997)
        Hexachlorobenzene (PIM 256)