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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 53

    ALPHA- AND BETA-HEXACHLOROCYCLOHEXANES
    (Alpha- and beta-HCHs)
    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 123:
    Alpha- and beta-hexachlorocyclohexanes

    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

    [Alpha]- and [beta]-hexachlorocyclohexanes ([alpha]- and [beta]-HCHs]: 
    health and safety guide.

    (Health and safety guide ; no. 53)

    1. Benzene hexachloride - standards  I. Series

    ISBN 92 4 151053 6          (NLM Classification: WA 240)
    ISSN 0259-7268

    (c) World Health Organization 1991

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    welcomes such applications.

    The designations employed and the presentation of the material in this
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    concerning the legal status of any country, territory, city or area or
    of its authorities, or concerning the delimitation of its frontiers or
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    The mention of specific companies or of certain manufacturers'
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    that are not mentioned.  Errors and omissions excepted, the names of
    proprietary products are distinguished by initial capital letters.

    CONTENTS

    INTRODUCTION

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

    2. SUMMARY AND EVALUATION
         2.1. Summary and evaluation: alpha-HCH
              2.1.1. Environmental transport, distribution,
                     and transformation
              2.1.2. Environmental levels and human exposure
              2.1.3. Kinetics and metabolism
              2.1.4. Effects on organisms in the environment
              2.1.5. Effects on experimental animals and
                     in vitro test systems
              2.1.6. Effects on human beings
         2.2. Summary and evaluation: -HCH
              2.2.1. Environmental transport, distribution,
                     and transformation
              2.2.2. Environmental levels and human exposure
              2.2.3. Kinetics and metabolism
              2.2.4. Effects on organisms in the environment
              2.2.5. Effects on experimental animals and
                     in vitro test systems
              2.2.6. Effects on human beings

    3. CONCLUSIONS AND RECOMMENDATIONS
         3.1. Conclusions
              3.1.1. General population exposure
              3.1.2. Subpopulations at special risk
              3.1.3. Occupational exposure
              3.1.4. Environmental effects
         3.2. Recommendations

         4.5. Spillage and disposal
              4.5.1. Spillage
              4.5.2. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. INTERNATIONAL CHEMICAL SAFETY CARD

    7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
         7.1. Previous evaluations by international bodies
         7.2. Exposure limit values
         7.3. Specific restrictions
         7.4. Labelling, packaging, and transport
         7.5. Waste disposal

    BIBLIOGRAPHY
    

    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 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 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

    Common name:             alpha- and -hexachlorocyclohexane (alpha-
                             and -HCH)

    Chemical structure:      alpha- and - are stereoisomers of gamma-HCH,
                             the active ingredient of lindane (>99%
                             gamma-HCH).  They differ in the spatial
                             orientation of the hydrogen and chlorine
                             atoms on the carbon atoms.

         alpha-HCH           -HCH

    CHEMICAL STRUCTURE 1

    Chemical formula:        C6H6Cl6

    Relative molecular mass: 290.85

    CAS chemical name:       alpha-HCH:  1 alpha, 2 alpha, 3, 4 alpha;
                             5, 6-hexachlorocyclohexane

                             -HCH: 1 alpha, 2, 3 alpha, 4, 5 alpha,
                             6-hexachlorocyclohexane

    Common synonyms:         alpha- and -benzenehexachloride 
                             (alpha- and -BHC)

    CAS registry number:     alpha-HCH: 319-84-6
                             -HCH: 319-85-7

    RTECS registry number:   alpha-HCH: GV3500000
                             -HCH: GV4375000

    1.2  Physical and Chemical Properties

    Some physical and chemical properties of alpha- and -HCH are given in
    the Summary of Chemical Safety Information (section 6).

    1.3  Analytical Methods

    alpha- and -HCH can be determined separately from the other isomers,
    by gas chromatography with electron-capture detection, and other
    methods, after extraction by liquid/liquid partition and purification
    by column chromatography.

    1.4  Uses

    alpha- and -HCH are basically by-products (and impurities) in the
    manufacture of lindane (>99% gamma-HCH).  Technical HCH, as
    synthesized from benzene and chlorine in the presence of ultraviolet
    radiation, could consist of:

         65-70%              alpha-HCH;

          7-10%              -HCH;

         14-15%              gamma-HCH (lindane);

         approx. 7%          delta-HCH;

         approx. 1-2%        epsilon-HCH;

         approx. 1-2%        other components.

    Purification of lindane produces a residue containing nearly 100% of
    non-insecticidal HCH isomers (mainly alpha- and -), which can be used
    as intermediates for the production of trichlorobenzene and other
    chemicals.

    alpha- and -HCH were used in admixture with gamma-HCH, when HCH or
    "fortified HCH" was used in agriculture and in wood protection.

    2.  SUMMARY AND EVALUATION

    2.1  Summary and Evaluation:  alpha-HCH

    2.1.1  Environmental transport, distribution, and transformation

    Biodegradation and abiotic degradation (dechlorination) by ultraviolet
    radiation (UVR) occur in the environment, with the production of 
    delta-3,4,5,6-tetrachlorohexene, and pentachlorocyclohexene,
    respectively.  The breakdown process is slower than in the case of
    lindane.  The persistence of alpha-HCH in soils is determined by
    environmental factors, such as the action of microorganisms, organic
    matter content, and co-distillation and evaporation from soils.  No
    isomerization occurred from lindane into alpha-HCH.

    Rapid bioconcentration takes place in microorganisms (1500-2700 , or
    approximately 12000  on a lipid basis, in 30 min), invertebrates
    (60-2750  or >8000  on a lipid basis, in 24-72 h), and fish
    (313-1216  in 4-28 days; up to 50 000  in the River Elbe), but
    biotransformation and elimination are rather fast in these organisms
    (15 min-72 h).

    2.1.2  Environmental levels and human exposure

    alpha-HCH is found in the air over oceans at concentrations of
    0.02-1.5 ng/m3.  In Canada, alpha-HCH was found in rain-water at
    concentrations of 1-40 ng/litre, but only traces were present in snow.

    The River Rhine and its tributaries contained alpha-HCH levels of
    0.01-2.7g/litre, but, more recently, the levels were below
    0.1 g/litre.  In the River Elbe, levels decreased from a mean of
    0.023 g/litre in 1981 to below 0.012 g/litre in 1988.  Selected
    rivers in the United Kingdom contained 0.001-0.43 g/litre.  In the
    North Frisian Wadden Sea, alpha-HCH was found in sediment at
    concentrations of between 0.3 and 1.4 g/kg; and in surface water at
    0.002 g/litre.

    alpha-HCH levels in various plant species, from different countries,
    varied from 0.5 to 2140 g/kg on a dry-weight basis, but were much
    higher in polluted areas.  Even in Antarctica, levels ranging from 0.2
    to 1.15 g/kg were found.

    alpha-HCH is regularly detected in fish and aquatic invertebrates, as
    well as in ducks, herons, and barn-owls.  In reindeer and Idaho moose,
    living in areas where the use of pesticides is negligible, average
    amounts of alpha-HCH, found in subcutaneous fat, were approximately
    70-80 g/kg.  The adipose tissue of the Canadian polar bear contained
    0.3-0.87 mg alpha-HCH/kg (on a fat basis).

    In a number of countries, important food items were analysed for the
    presence of alpha-HCH.  The levels, mainly in fat-containing food
    products, were in the range of not detectable (nd) to 0.05 mg/kg
    product, except in milk and milk products in which the range was nd to
    0.22 mg/kg, and in fish and processed meat products, which contained
    up to 0.5 mg alpha-HCH/kg (on a fat basis).  A slow decrease was noted
    over the years.

    Food is the main source of alpha-HCH for the general population.  In
    total diet studies in the Netherlands and the United Kingdom, mean
    concentrations of 0.01 and 0.002-003 mg/kg food were found,
    respectively.  The United Kingdom data indicate a downward trend since
    1967.  In the USA, the average daily intake of alpha-HCH was
    determined to be 0.009-0.025 g/kg body weight in the years 1977-79,
    and 0.003-0.016 g/kg body weight in the years 1982-84.

    In a few countries, the concentration of alpha-HCH was determined in
    blood, serum, or plasma.  The mean (in some cases median)
    concentration was <0.1 g/litre (range nd-0.6 g/litre).  In one
    country, however, a mean concentration of 3.5 g/litre (range
    0.1-15.0 g/litre) was reported.  The blood of approximately one third
    of the persons tested contained alpha-HCH.

    The concentrations in adipose tissue and breast milk were rather low,
    i.e., <0.01-0.1 and <0.001-0.04 mg/kg (on a fat basis),
    respectively.  Total diet studies showed daily intake levels of the
    order of 0.01 g/kg body weight or lower.  However, these
    concentrations have decreased slowly over the years.

    alpha-HCH appears to be a universal environmental contaminant, the
    levels of which are only slowly decreasing, in spite of the measures
    taken against its spread into the environment.

    2.1.3  Kinetics and metabolism

    In rats, alpha-HCH is rapidly and nearly completely absorbed from the
    gastrointestinal tract.  After intraperitoneal injection,
    approximately 40-80% of the alpha-HCH was eliminated via the urine and
    5-20%, via the faeces.  In rats, the highest concentrations were found
    in the liver, kidneys, body fat, brain, and muscles, and substantial
    deposition occurred in the fatty  tissue.  The  alpha-HCH
    concentrations in the liver of sucklings were twice as high as those
    observed in the liver of the mothers.  In rats, the brain:blood and
    depot fat:blood ratios were 120:1 and 397:1, respectively.

    The biotransformation of alpha-HCH in rats involves dechlorination,
    the major urinary metabolite being 2,4,6-trichlorophenol.  Other
    identified metabolites include: 1,2,4-, 2,3,4-, and 2,4,5-
    trichlorophenol, and 2,3,4,5- and 2,3,4,6-tetrachlorophenol;
    1,3,4,5,6-pentachlorocyclohex-1-ene was found in the kidneys of rats. 
    This metabolite was also found in  in vitro studies on chicken liver.
    A glutathione conjugate is formed in the liver.

    The half-life for clearance from depot fat is sex-dependent; i.e., 6.9
    days in female rats and 1.6 days in male rats.

    2.1.4  Effects on organisms in the environment

    The toxicity of alpha-HCH for algae is low; the no-observed-effect
    level was generally 2 mg/litre.

    In a long-term study on  Daphnia magna, the no-observed-effect level
    was 0.05 mg/litre.  alpha-HCH is moderately toxic for invertebrates
    and fish.  The acute LC50 and EC50 values for these organisms were
    of the order of 1 mg/litre.  In short-term studies on guppies and
     Oryzia latipes, a concentration of 0.8 mg/litre did not produce any
    effects.

    Treatment of  Salmo gairdneri with alpha-HCH at dose levels ranging
    from 10 to 1250 mg/kg, for 3 months, did not produce any effects on
    mortality, behaviour, growth, or enzyme activity in the liver and
    brain.

    Short- and long-term studies on the snail  (Lymnea stagnalis) showed
    an EC50 (based on mortality and immobilization) of 1200 g/litre. 
    Inhibition of egg production occurred at 250 g/litre, and a 50%
    reduction in overall reproductivity was found at 65 g/litre.

    No data were available on effects on populations and ecosystems.

    2.1.5  Effects on experimental animals and in vitro test systems

    The acute oral LD50 values for alpha-HCH in mice and rats ranged
    between 1000 and 4000 mg/kg body weight and between 500 and
    4670 mg/kg, respectively.  The signs of poisoning were mainly those of
    stimulation of the central nervous system.

    A 90-day study on rats showed growth depression with 250 mg
    alpha-HCH/kg diet.  Histological and enzyme-level changes in the liver
    indicated enzyme induction in groups administered 50 mg/kg or more. 
    At these dose levels, there were also indications of
    immunosuppression.  Liver weights were already increased with 10 mg/kg
    diet (equivalent to 0.5 mg/kg body weight).   The no-observed-effect
    level in this study appeared to be 2 mg/kg diet (equivalent to
    0.1 mg/kg body weight) per day.  The quality of the only long-term
    toxicity study available was inadequate.

    No studies on reproduction and teratogenicity have been reported.

    The results of mutagenicity studies on different strains of
     Salmonella typhimurium were negative, with and without metabolic
    activation.  Tests on  Saccharomyces cerevisiae were also negative,
    but a test for unscheduled DNA synthesis in rat hepatocytes,  in
     vitro, gave an equivocal result.

    Studies to determine the carcinogenic potential of alpha-HCH have been
    carried out on mice and rats at dose levels in the range of
    100-600 mg/kg diet.  Hyperplastic nodules and/or hepatocellular
    adenomas were found in studies on mice.  In one study, the dose levels
    exceeded the MTD.  In two studies on mice and one on rats, with dose
    levels of up to 160 mg/kg diet and 640 mg/kg diet, respectively, the
    incidence of tumours did not increase.

    The results of studies on initiation-promotion and mode of action, and
    mutagenicity studies indicate that the tumorigenic response observed
    with alpha-HCH in mice results from a non-genetic mechanism.

    Special studies showed that alpha-HCH induced a clear increase in the
    activity of liver enzymes, even at 5 mg/kg diet (equivalent to
    0.25 mg/kg body weight).  A dose of 2 mg/kg body weight did not affect
    aminopyrine demethylation and the DNA contents of the liver.

    2.1.6  Effects on human beings

    In a lindane-producing factory, workers with a geometric mean exposure
    of 7.2 years (1-30 years) were investigated.  It was concluded that
    occupational exposure to HCH did not induce signs of neurological
    impairment or perturbation of neuromuscular function.

    2.2  Summary and Evaluation:  -HCH

    2.2.1  Environmental transport, distribution, and transformation

    Biodegradation and abiotic degradation (dechlorination) of -HCH by
    UVR occur in the environment, with the production of
    pentachlorocyclohexane, but the degradation rate is much slower than
    that for lindane (gamma-HCH).

    -HCH is the most persistent HCH isomer.  Its persistence in soils is
    determined by environmental factors, such as the action of
    microorganisms, the  soil contents of organic matter and water, and
    co-distillation and evaporation from soils.

    Because of its persistence, bioconcentration of -HCH is rapid:
    approximately 125 , in 3 days, in invertebrates, 250-1500  or
    approximately 500 000 , on a lipid basis, in 3-10 days, in fish, and
    approximately 525 , in birds and human beings.  The bioconcentration
    of -HCH is higher, and elimination lower, than those of the other HCH
    isomers.

    2.2.2  Environmental levels and human exposure

    -HCH is found in the air over the oceans at concentrations of
    0.004-0.13ng/m3.

    Up to 1974, the River Rhine and its tributaries contained -HCH levels
    of 0.14-0.22 g/litre but, since that time, the levels have been below
    0.1g/litre.  Levels in the River Meuse are also less than
    0.1 g/litre.  In the River Elbe, levels of -HCH decreased from an
    average of 0.009 to 0.004 g/litre between 1981 and 1988.

    -HCH concentrations, determined in birds, such as sparrowhawks,
    kestrels, owls, herons, and grebe, over a number of years, ranged from
    0.1 to 0.3 mg/kg.  -HCH levels (on a fat basis) of up to 0.87 mg/kg
    were found in the liver and adipose tissue of the polar bear.

    In a few countries, important food items were analysed for the
    presence of -HCH. The mean concentrations, mainly in fat-containing
    food products, ranged from not detectable to 0.03 mg/kg (on a fat
    basis).  However, levels were found in milk products of up to 4 mg/kg
    (on a fat basis).  Concentrations of -HCH in non-fatty food items
    were less than 0.005 mg/kg product.  In general, levels are slowly
    decreasing.

    Food is the main source of -HCH for the general population.  In total
    diet studies in the United Kingdom, levels of 0.003, 0.0005, and
    <0.0005mg/kg were found in the years 1966/67, 1975/77, and 1981,
    respectively.  In the USA, the average daily intake of -HCH ranged
    from <0.1 to 0.4 ng/kg body weight, for various age groups, in
    1982-84.

    In a number of countries, the concentrations of -HCH were determined
    in the blood, serum, or plasma of the general population.  The
    concentrations, which varied between countries, ranged from not
    detectable to 25g/litre.

    Many studies were carried out to determine the presence of -HCH in
    human adipose tissue.  The concentrations found in Canada, the Federal
    Republic of Germany, Kenya, the Netherlands, and the United Kingdom
    ranged from not detectable to 4.4 mg/kg (on a fat basis).  A gradual
    increase with age was found up to approximately 50 years, followed by
    a decrease.  -HCH concentrations in adipose tissue are higher than
    those of the other HCH-isomers, a phenomenon that reflects the
    cumulative properties of -HCH.  In general, there was no clear trend
    towards a decrease in -HCH concentrations over the years examined. 
    -HCH concentrations in adipose tissue were related to concentrations
    in mothers' milk and to the consumption of meat products and animal
    fat and fatty fish.

    In a few countries, including Canada, the Federal Republic of Germany,
    the Netherlands, and the United Kingdom, breast milk was analysed for
    -HCH.  The levels ranged from 0.1 to 0.69 mg/kg (on a fat basis). 
    -HCH levels in breast milk appeared to be higher in women living in
    rural areas than in those living in urban areas.

    The high -HCH levels in breast milk exceeded permissible
    concentrations temporarily and locally.  -HCH concentrations in the
    blood of babies were in the same range as those of the mothers.

    -HCH appears to be a universal environmental contaminant, the levels
    of which are only decreasing very slowly, in spite of measures taken
    against its spread into the environment.

    2.2.3  Kinetics and metabolism

    Up to 95% of -HCH was absorbed from the gastrointestinal tract in
    mice.  Most of the absorbed -HCH was accumulated in adipose tissue. 
    Elimination followed a 2-stage mechanism, the half-life for the first
    stage being 2.5 days and that for the second stage, 18 days.

    After absorption, -HCH is rapidly distributed to the liver, brain,
    kidneys, and adipose tissue. The maximum concentration in the liver is
    reached, in rats, after 4 days. At an average blood concentration of
    92 g/litre, but also with concentrations of 540 and 2100 g/litre,
    the brain/blood and adipose tissue/blood ratios were 2:1 and 170:1,
    respectively.  In human beings, after lethal acute poisoning with
    HCH-isomers, -HCH concentrations relative to that in the blood were
    363 in fat, 3 in brain, and 15 in the liver.  -HCH passes the
    blood/brain barrier much less readily than the other HCH-isomers.

    In pregnant mice, about 2% of the dose was transferred
    transplacentally  to the fetus, while 40% was transferred in rats.  In
    rats, transfer from dams to sucklings via the milk was about 60% of
    the dose.

    Some 70% of -HCH was excreted by rats over 28 days, one-third being
    excreted via the urine.  No unchanged -HCH was found in the urine;
    the major metabolite resulting from  cis-dehydrochlorination was
    2,4,6-trichlorophenol, in a conjugated form.

    Pretreatment with -HCH altered the metabolism of gamma-HCH in rats. 
    From intraperitoneal studies on mice, it seems that -HCH is more
    slowly metabolized than gamma-HCH.

    2.2.4  Effects on organisms in the environment

    The toxicity of -HCH is generally moderate for algae, invertebrates,
    and fish.  The acute LD50 values for these organisms are of the
    order of 1 mg/litre, but the EC50s are lower (of the order of
    0.05-0.5 mg/litre).  The no-observed-effect level for  Oryzia latipes
    and  Poecilia reticulata, two freshwater fish, exposed for 1 or 3
    months, was 0.03 mg/litre.

    No data were available on effects on populations and ecosystems.

    2.2.5  Effects on experimental animals and in vitro test systems

    The acute oral LD50 values for mice and rats were between 1500 and
    2000 mg/kg body weight.  More recent figures have been obtained of
    16 g/kg body weight for mice and 8 g/kg body weight for rats.  Signs
    of intoxication have mainly been of neurological origin.

    Three short-term studies on mice are available.  Two of these studies
    with dose levels of up to 600 mg -HCH/kg diet, for 26-32 weeks,
    showed increased liver weight, nodular hyperplasia, and atypical
    proliferations in the liver.  In the third study, dose levels of up to
    500 mg/kg diet, for 24 weeks, did not produce any liver tumours or
    nodular hyperplasia.

    In a 90-day study, rats fed 50 or 250 mg/kg diet showed liver changes,
    including hypertrophy and proliferation of SER and increased activity
    of microsomal enzymes.  Changes in the gonads occurred at the higher
    dose level, but these were associated with severe effects on body
    weight.  Hormonal changes associated with the gonadal atrophy did not
    show any consistent endocrine effect.  A dietary level of 2 mg/kg
    (equivalent to 0.1 mg/kg body weight) did not produce any adverse
    effects.

    In an old, long-term study on rats, -HCH at concentrations of
    10 mg/kg diet (equivalent to 0.5 mg/kg body weight), or more, produced
    enlargement of, and histological changes in, the liver.

    In a two-generation reproduction study on rats, the effects of -HCH
    were the same as those in the 90-day study reported earlier.  A
    dietary level of 2 mg/kg (equivalent to 0.1 mg/kg body weight) did not
    produce any effects, but administration of 10 mg/kg diet resulted in
    increased mortality and infertility.  No compound-related teratogenic
    effects were found in an extension of this study.

    A weak "estrogenic" effect of -HCH has been described.  The effect
    demonstrated was related to the uterus as a target organ and there
    were no clear effects on endocrine control systems.  The mechanism and
    significance of this effect are uncertain.

    The available mutagenicity studies on -HCH did not show any increase
    in mutations in  Salmonella typhimurium strains.  In rats treated
    with the compound, the results of  in vivo bone marrow metaphase
    analysis were reported to be positive.

    Two studies were carried out on mice to determine the carcinogenic
    potential of -HCH.  In one study, a dietary level of 200 mg/kg was
    administered for 110 weeks; in the other study, dietary levels of up
    to 500 mg/kg were administered for 24 weeks.  In the first study,
    liver enlargement, hyperplastic changes, and increases in benign and
    malignant tumours were reported.  In the other study, which was of
    shorter duration, no tumours were observed.

    In studies on rats fed combinations of -HCH and PCBs, a possible
    promoting effect of -HCH was noticed.

    At 300 mg/kg diet, -HCH caused significant changes in several immune
    functions in mice, within one month.

    2.2.6  Effects on human beings

    In a lindane-producing factory, workers with a geometric mean exposure
    of 7.2 years (1-30 years) were investigated.  It was concluded that
    occupational exposure to HCH did not induce signs of neurological
    impairment or perturbation of neuromuscular function.

    3.  CONCLUSIONS AND RECOMMENDATIONS

    3.1  Conclusions

    In the case of alpha- and -HCH, potential adverse effects on human
    beings, and on the environment, cannot be balanced against benefits,
    since these isomers do not have any insecticidal action.  Thus, their
    presence in the environment is of serious concern and the use of
    technical products containing high concentrations of alpha- and -HCH
    is never justified.

    3.1.1  General population exposure

    alpha- and -HCH are circulating in the environment and present in the
    food-chains, and human beings will continue to be exposed.  The level
    of exposure is low and is expected to decrease gradually over the
    coming years.  Therefore, there is no serious health concern for the
    general population.

    3.1.2  Subpopulations at special risk

    While levels of alpha-HCH in breast milk are low, the exposure of
    breast-fed babies to present levels of -HCH in breast milk is a
    matter of concern.  However, this is not a limiting factor for the use
    of natural breast-feeding.

    Nevertheless, every possible effort should be made to decrease dietary
    and all other exposures to these isomers.  Decreased dietary exposure
    is expected to result in decreased levels of alpha- and -isomers in
    human breast milk.

    3.1.3  Occupational exposure

    As long as recommended precautions to minimize worker exposure are
    observed in lindane manufacturing, alpha- and -HCH do not pose any
    health risks for process operators.

    3.1.4  Environmental effects

    Apart from spills in the aquatic environment, there is no evidence to
    suggest that the presence of alpha- and -HCH in the environment poses
    a significant hazard for organisms in the environment.

    3.2  Recommendations

    1.  In order to minimize environmental pollution with alpha- and
    -HCH, lindane (>99% gamma-HCH) must be used instead of technical
    HCH.

    2.  In order to avoid environmental pollution with alpha- and -HCH,
    by-products and effluents resulting from the manufacture of lindane
    must be disposed of in an appropriate way, and contamination of
    natural waters and soil must be avoided.

    3.  Monitoring of levels of alpha- and -HCH in food should continue,
    and it is essential that a mechanism for setting internationally
    acceptable levels of alpha- and -HCH in food should be initiated.

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

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

    alpha- and -HCH are organochlorine compounds. They are toxic and can
    be hazardous for human beings, if incorrectly or carelessly handled. 
    It is, therefore, essential that the correct precautions are observed
    in the handling and use of these compounds.

    For details see the Summary of Chemical Safety Information (section
    6).

    4.1.1  Advice to physicians

    4.1.1.1  Symptoms of poisoning

    alpha- and -HCH are readily absorbed and may be toxic by mouth, by
    inhalation, and by skin contact.  They act primarily on the liver and
    the central nervous system.  In experimental animals, symptoms of
    over-exposure include decreased activity, trembling, dyspnoea, and
    convulsions.  Chlorinated by-products may possibly contribute to the
    symptomatology, e.g., effects on the skin.

    4.1.1.2  Medical advice

    Medical treatment is largely symptomatic and supportive, and directed
    against convulsions and hypoxia.  If the compound has been swallowed,
    the stomach should be emptied, as soon as possible, by careful gastric
    lavage (with a cuffed endotracheal tube already in place), avoiding
    aspiration into the lungs.  In a rural situation, where this is not
    feasible, vomiting should be induced immediately.  This should be
    followed by intragastric administration of up to 50 g (3-4
    tablespoons) of activated charcoal and 30 g of magnesium or sodium
    sulfate in a 30% aqueous solution.  Oily purgatives are
    contraindicated.  No fats, oils, or milk should be given.

    If convulsions occur, anticonvulsants should be given, e.g., diazepam,
    10 mg slowly, intravenously (children 1-5 mg), repeated as necessary; 
    or thiopental sodium, or hexobarbital sodium, slowly, intravenously,
    in a dose of 10 mg/kg, with a maximum total dose of up to 750 mg for
    an adult, or paraldehyde (5 ml) by intramuscular injection. 

    The short-acting anticonvulsants should always be followed by
    phenobarbital given orally at 3 mg/kg (up to 200 mg for an adult), or
    phenobarbital sodium given intramuscularly at 3 mg/kg (also up to
    200 mg for an adult).

    Morphine and its derivatives, atropine, adrenaline, and noradrenaline,
    should never be given.

    An unobstructed airway must be maintained.  Respiratory inadequacy,
    which may be accentuated by barbiturate anticonvulsants, should be
    corrected, and oxygen and/or artificial ventilation may be needed.

    4.1.2  Health surveillance advice

    Pre-employment and annual general medical examinations are advised for
    regularly exposed workers.

    4.2  Explosion and Fire Hazards

    Liquid products containing organic solvents may be flammable. 
    Extinguish fires with alcohol-resistant foam, carbon dioxide, or
    powder.  With sufficient burning or external heat, alpha- and -HCH
    will decompose, emitting toxic fumes, e.g., phosgene, hydrogen
    chloride, and carbon monoxide.  Fire-fighters should be equipped with
    self-contained breathing apparatus, eye protection, and full
    protective clothing.

    The use of water spray should be confined to the cooling of unaffected
    stock, thus avoiding the accumulation of polluted run-off from the
    site.

    4.3  Storage

    Keep products out of reach of children and unauthorized personnel.  Do
    not store near foodstuffs or animal feed.

    4.3.1  Damaged containers in store

    Take precautions and use appropriate personal protection.  Empty any
    product remaining in damaged or leaking containers into a clean empty
    drum, which should then be tightly closed and suitably labelled.

    Sweep up spillage with sawdust, sand, or earth (moisten for powders),
    and dispose of safely.

    Emptied containers should be rinsed 3 times with at least 1 litre of
    water per 20-litre drum.  Swirl round to rinse the walls, empty, and
    add the rinsings to the sawdust or earth.  Do not re-use containers
    for any other purpose.  Puncture or crush the containers to prevent
    re-use.

    4.4  Transport

    Comply with any local requirements regarding movements of hazardous
    goods or wastes. Do not transport in the same compartment as animal
    feed or foodstuffs.  Make sure that containers are in good condition
    and the labels undamaged, before despatch.

    4.5  Spillage and Disposal

    4.5.1  Spillage

    Before dealing with any spillage, precautions should be taken, as
    required, and appropriate personal protection should be used.

    Sweep up solid products and absorb any remaining spilled product with
    moist sawdust, sand, or earth, and transfer, in a suitable container,
    to a safe place for disposal.

    Prevent material from spreading or contaminating other cargo and
    vegetation, and avoid pollution of surface waters and ground water by
    using the most suitable available material, e.g., earth or sand.

    Absorb spilled liquid with sawdust, sand, or earth, sweep up and place
    it in a closeable container for later transfer to a safe place for
    disposal.

    Care should be taken to avoid run-off into water-courses.

    4.5.2  Disposal

    Residues containing alpha- and -HCH, surplus product, contaminated
    absorbents, and containers should be disposed of in an appropriate
    way.  alpha-and -HCH are not readily decomposed chemically or
    biologically and are relatively persistent.  Waste material should be
    burned only in a proper incinerator designed for organochlorine waste
    disposal, with effluent gas scrubbing.  If this is not possible, bury
    in an approved dump or landfill, where there is no risk of
    contamination of surface or ground water, as long as local legislation
    is not contravened.  Puncture empty containers to prevent re-use.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    alpha-and -HCH may pose a toxic hazard for aquatic and terrestrial
    species.  Industrial discharges and indiscriminate waste disposal have
    caused death of fish.  Both alpha-and -HCH may readily enter the
    food-chain and may give rise to bioaccumulation and biomagnification. 
    They are rather persistent in the environment.  In the event of a
    major environmental contamination incident, appropriate monitoring
    should be carried out.

    Industrial discharges from manufacturing, formulation, and technical
    applications should not be allowed to pollute the environment, and
    should be treated properly.

    Any spillage or unused product should be prevented from spreading to
    vegetation or waterways, and should be treated and disposed of
    properly.

    6. SUMMARY OF CHEMICAL SAFETY INFORMATION

     This summary should be easily available to all health workers
     concerned with, and users of, alpha- and -hexachlorocyclohexane. It
     should be displayed at, or near, entrances to areas where there is
     potential exposure to alpha- and -hexachlorocyclohexane, and on
     processing equipment and containers.  The summary should be
     translated into the appropriate language(s).  All persons potentially
     exposed to the chemicals should also have the instructions in the
     summary clearly explained.

     Space is available for insertion of the National Occupational
     Exposure Limit, the address and telephone number of the National
     Poison Control Centre, and for local trade names.


        alpha-hexachlorocyclohexane (-HCH)          -hexachlorocyclohexane (-HCH)

    C6H6Cl6                                     C6H6Cl6
    CAS registry number:  319-84-6              CAS registry number:  319-85-7
    RTECS registry number:  GV3500000           RTECS registry number:  GV4375000

    CAS chemical name:                          CAS chemical name:
    1 alpha, 2 alpha, 3, 4 alpha, 5, 6-      1 alpha, 2, 3 alpha, 4, 5 alpha, 6-
    hexachlorocyclohexane                       hexachlorocyclohexane

                                                                                                                                         

    PHYSICAL PROPERTIES                alpha-HCH      -HCH        OTHER CHARACTERISTICS
                                                                                                                                         

    Melting point (C)                 158            309          Both alpha-and -HCH are by-products in the manufacture
    Boiling point (C)                 288            -            of lindane (gamma-HCH); an impure mixture of alpha- and -HCH
    Density (20C) (g/ml)              1.87           1.89         results from the purification of lindane; they are also
    Vapour pressure (mmHg)             0.02           0.005        used as chemical intermediates; both alpha- and -HCH are
      (20C)                                                       very stable in the presence of acids, but are unstable in
    Relative molecular mass            290.85         290.85       the presence of alkali 
     n-Octanol/water partition
      coefficient (log Pow)            3.82           3.80
    Solubility in water
      (mg/litre) (28C)                2              0.2
    practically insoluble)
    Solubility (g/litre) in:
    -  acetone                         139            103
    -  chloroform                      63             3
    -  ethyl alcohol                   18             11
    -  petroleum ether                 10             1.5
    -  xylene                          85             33

                                                                                                                                         

    HAZARDS/SYMPTOMS                     PREVENTION AND PROTECTION                  FIRST AID
                                                                                                                                         

    SKIN: Overexposure may               Avoid skin contact, wear                   Remove contaminated clothing and launder
    cause poisoning                      protective clothing, PVC or                before re-use; wash skin with water and soap
                                         neoprene gloves, neoprene boots

    EYES: Irritation, redness            Wear face-shield or goggles                Flush with clean water for 15 minutes; if
                                                                                    irritation persists, seek medical attention

    INHALATION: Dust may                 Wear appropriate dust mask or 
    irritate                             respirator; use appropriate
                                         ventilation in buildings

    INGESTION: Unlikely                  Do not eat, drink, or smoke
    occupational hazard                  during work

    Accidental or intentional                                                       Obtain medical attention immediately; if gastric
    ingestion may cause poisoning                                                   lavage is not possible, e.g., in a rural situation, 
                                                                                    induce vomiting; keep at rest, face down

    ENVIRONMENT: Toxic for               Do not spill in water ways
    aquatic and terrestrial life; 
    bioaccumulates

                                                                                                                                         

    SPILLAGE                             STORAGE                                    FIRE AND EXPLOSION
                                                                                                                                         

    Take appropriate personal            Keep out of reach of children              Extinguish fires with alcohol-resistant foam,
    precautions; prevent liquid from     and unauthorized personnel; do             carbon dioxide, or powder; with sufficient burning
    spreading or contaminating other     not store in dwellings or near             or external heat, the products will decompose,
    cargo, vegetation, or waterways,     foodstuffs or animal feed                  emitting toxic fumes; the smoke and fumes 
    with a barrier of the most suitable                                             could be injurious through inhalation, or
    available material, e.g., earth                                                 absorption through the skin; therefore, 
    or sand; absorb spilled liquid                                                  protective clothing and self-contained 
    with sawdust, sand, or earth;                                                   breathing apparatus will be required; 
    sweep up and place it in a                                                      confine the use of water spray to the cooling of
    closeable container for later safe                                              unaffected stock; contaminated water should not
    disposal                                                                        be allowed to pollute the environment 
                                                                                    and should be disposed of properly

                                                                                                                                         

    WASTE DISPOSAL                       NATIONAL INFORMATION
                                                                                                                                         

    alpha- and -HCH are not readily     National occupational exposure  limit:
    decomposed chemically or
    biologically and are rather
    persistent; waste material should
    be burned in a proper incinerator
    designed for organochlorine waste
    disposal; if this is not possible, 
    bury in an approved dump or          National poison control centre:
    landfill, where there is no risk
    of contamination of surface or 
    ground water; comply with any 
    local legislation regarding disposal
    of toxic wastes

                                                                                                                                         
    

    7.  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.  The regulations and
    guidelines of all countries are subject to change and should always be
    verified with appropriate regulatory authorities before application

    7.1  Previous Evaluations by International Bodies

    The International Agency for Research on Cancer (IARC) evaluated the
    hexachlorocyclohexanes in 1987 and concluded that there was sufficient
    evidence for carcinogenicity in animals for the technical grade and
    the alpha-isomer; this evidence was limited for the - and
    gamma-isomer.  There was inadequate evidence for their carcinogenicity
    in human beings.  Hexachlorocyclohexanes were classified in group 2B.

    7.2  Exposure Limit Values

    The European Economic Community (EEC) legislation has fixed maximum
    levels of HCH residues in, and on, foodstuffs of animal origin.  In
    fat contained in meat, meat preparations, offal, and animal fats:

         HCH-alpha-isomer              0.2 mg/kg

         HCH--isomer                  0.1 mg/kg

         HCH-gamma-isomer              2 mg/kg

    for raw cows' milk and whole cream:

         HCH-alpha-isomer              0.004 mg/kg

         HCH--isomer                  0.003 mg/kg

         HCH-gamma-isomer              0.008 mg/kg

    The EEC legislation has fixed a maximum level for HCH in, and on,
    cereals:

         HCH  alpha-isomer and -isomer          sum: 0.02 mg/kg

         HCH  gamma-isomer (lindane)                  0.1 mg/kg

    The EEC legislation requires that hexachlorocyclohexane (HCH) in
    animal nutrition be limited:

       alpha-isomer   all feeding stuffs, with the
                      exception of:                            0.02
                           - fats                              0.2

       -isomer       compound feeding stuffs, with the
                      exception of:                            0.01

                           - feeding stuffs for dairy cattle   0.005

                      straight feeding stuffs, with the
                      exception of:                            0.01
                           - fats                              0.1

       gamma-isomer   all feeding stuffs, with the
                      exception of:                            0.2
                           - fats                              2.0

    The marketing of cosmetic products containing alpha- and/or -HCH is
    forbidden.

    7.3  Specific Restrictions

    Agricultural uses of technical HCH have been discontinued in most
    countries, because of the risk of environmental pollution with
    alpha-HCH and -HCH.

    The manufacturing, importation, formulation, marketing, and use of
    alpha- and/or -HCH are forbidden in Argentina (1980) and the USA
    (1978).

    7.4  Labelling, Packaging, and Transport

    The EEC legislation requires the labelling of HCH as a dangerous
    substance using the symbol:

    FIGURE 1

    The label must read:

        Toxic in contact with skin and if swallowed; possible risks of
        irreversible effects; danger of serious damage to health by
        prolonged exposure; do not breathe dust; wear suitable protective
        clothing and gloves; if you feel unwell, seek medical advice (show
        the label where possible).

    7.5  Waste Disposal

    In the USA, hexachlorocyclohexanes are classified as toxic pollutants
    and acute hazardous wastes, subject to handling, transport, treatment,
    storage, and disposal regulations, and permit and notification
    requirements.  An owner or operator of a hazardous waste incinerator
    must achieve 99.99% destruction and removal efficiency for this
    substance.

     Aquatic environment

    The EEC legislation has established limit values for the discharge of
    HCH, during normal production, into the aquatic environment.

    The limit values for emission standards (as of 1 October 1988) are:

                                     g/1000 kg of Product   mg/litre water

    HCH production plant                       2                  2

    Lindane extraction plant                   4                  2

    Production + extraction plant              5                  2

    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/WHO  (1986)  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.

    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.

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

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

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

    PLESTINA, R.  (1984)  Prevention, diagnosis, and treatment of
     insecticide poisoning.  Geneva, World Health Organization
    (Unpublished report No.VBC/84.889).

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

    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  (in preparation)   EHC No.123: Alpha- and
     hexachlorocyclohexanes. Geneva, World Health Organization.

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

    


    See Also:
       Toxicological Abbreviations