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
Publications of the World Health Organization enjoy copyright
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that are not mentioned. Errors and omissions excepted, the names of
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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: ß-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 ß-hexachlorocyclohexane (alpha-
and ß-HCH)
Chemical structure: alpha- and ß- 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 ß-HCH
Chemical formula: C6H6Cl6
Relative molecular mass: 290.85
CAS chemical name: alpha-HCH: 1 alpha, 2 alpha, 3ß, 4 alpha;
5ß, 6ß-hexachlorocyclohexane
ß-HCH: 1 alpha, 2ß, 3 alpha, 4ß, 5 alpha,
6ß-hexachlorocyclohexane
Common synonyms: alpha- and ß-benzenehexachloride
(alpha- and ß-BHC)
CAS registry number: alpha-HCH: 319-84-6
ß-HCH: 319-85-7
RTECS registry number: alpha-HCH: GV3500000
ß-HCH: GV4375000
1.2 Physical and Chemical Properties
Some physical and chemical properties of alpha- and ß-HCH are given in
the Summary of Chemical Safety Information (section 6).
1.3 Analytical Methods
alpha- and ß-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 ß-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% ß-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 ß-), which can be used
as intermediates for the production of trichlorobenzene and other
chemicals.
alpha- and ß-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
0.01-2.7µg/litre, but, more recently, the levels were below
0.1 µg/litre. In the River Elbe, levels decreased from a mean of
0.023 µg/litre in 1981 to below 0.012 µg/litre in 1988. Selected
rivers in the United Kingdom contained 0.001-0.43 µg/litre. In the
North Frisian Wadden Sea, alpha-HCH was found in sediment at
concentrations of between 0.3 and 1.4 µg/kg; and in surface water at
0.002 µg/litre.
alpha-HCH levels in various plant species, from different countries,
varied from 0.5 to 2140 µg/kg on a dry-weight basis, but were much
higher in polluted areas. Even in Antarctica, levels ranging from 0.2
to 1.15 µg/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 µg/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 µg/kg body weight in the years 1977-79,
and 0.003-0.016 µg/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 µg/litre (range nd-0.6 µg/litre). In one
country, however, a mean concentration of 3.5 µg/litre (range
0.1-15.0 µg/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 µg/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 µg/litre.
Inhibition of egg production occurred at 250 µg/litre, and a 50%
reduction in overall reproductivity was found at 65 µg/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: ß-HCH
2.2.1 Environmental transport, distribution, and transformation
Biodegradation and abiotic degradation (dechlorination) of ß-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).
ß-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 ß-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 ß-HCH is higher, and elimination lower, than those of the other HCH
isomers.
2.2.2 Environmental levels and human exposure
ß-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 ß-HCH levels
of 0.14-0.22 µg/litre but, since that time, the levels have been below
0.1µg/litre. Levels in the River Meuse are also less than
0.1 µg/litre. In the River Elbe, levels of ß-HCH decreased from an
average of 0.009 to 0.004 µg/litre between 1981 and 1988.
ß-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. ß-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 ß-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 ß-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 ß-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 ß-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 ß-HCH were determined
in the blood, serum, or plasma of the general population. The
concentrations, which varied between countries, ranged from not
detectable to 25µg/litre.
Many studies were carried out to determine the presence of ß-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. ß-HCH concentrations in adipose tissue are higher than
those of the other HCH-isomers, a phenomenon that reflects the
cumulative properties of ß-HCH. In general, there was no clear trend
towards a decrease in ß-HCH concentrations over the years examined.
ß-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
ß-HCH. The levels ranged from 0.1 to 0.69 mg/kg (on a fat basis).
ß-HCH levels in breast milk appeared to be higher in women living in
rural areas than in those living in urban areas.
The high ß-HCH levels in breast milk exceeded permissible
concentrations temporarily and locally. ß-HCH concentrations in the
blood of babies were in the same range as those of the mothers.
ß-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 ß-HCH was absorbed from the gastrointestinal tract in
mice. Most of the absorbed ß-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, ß-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 µg/litre, but also with concentrations of 540 and 2100 µg/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, ß-HCH concentrations relative to that in the blood were
363 in fat, 3 in brain, and 15 in the liver. ß-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 ß-HCH was excreted by rats over 28 days, one-third being
excreted via the urine. No unchanged ß-HCH was found in the urine;
the major metabolite resulting from cis-dehydrochlorination was
2,4,6-trichlorophenol, in a conjugated form.
Pretreatment with ß-HCH altered the metabolism of gamma-HCH in rats.
From intraperitoneal studies on mice, it seems that ß-HCH is more
slowly metabolized than gamma-HCH.
2.2.4 Effects on organisms in the environment
The toxicity of ß-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 ß-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, ß-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 ß-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 ß-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 ß-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 ß-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 ß-HCH and PCBs, a possible
promoting effect of ß-HCH was noticed.
At 300 mg/kg diet, ß-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 ß-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 ß-HCH
is never justified.
3.1.1 General population exposure
alpha- and ß-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 ß-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 ß-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 ß-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 ß-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
ß-HCH, lindane (>99% gamma-HCH) must be used instead of technical
HCH.
2. In order to avoid environmental pollution with alpha- and ß-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 ß-HCH in food should continue,
and it is essential that a mechanism for setting internationally
acceptable levels of alpha- and ß-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 ß-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 ß-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 ß-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 ß-HCH, surplus product, contaminated
absorbents, and containers should be disposed of in an appropriate
way. alpha-and ß-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 ß-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 ß-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 ß-hexachlorocyclohexane. It
should be displayed at, or near, entrances to areas where there is
potential exposure to alpha- and ß-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) ß-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, 3ß, 4 alpha, 5ß, 6ß- 1 alpha, 2ß, 3 alpha, 4ß, 5 alpha, 6ß-
hexachlorocyclohexane hexachlorocyclohexane
PHYSICAL PROPERTIES alpha-HCH ß-HCH OTHER CHARACTERISTICS
Melting point (°C) 158 309 Both alpha-and ß-HCH are by-products in the manufacture
Boiling point (°C) 288 - of lindane (gamma-HCH); an impure mixture of alpha- and ß-HCH
Density (20°C) (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 ß-HCH are
(20°C) 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) (28°C) 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 ß-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 ß- 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-ß-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-ß-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 ß-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
ß-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 ß-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 ß-HCH.
The manufacturing, importation, formulation, marketing, and use of
alpha- and/or ß-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:
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
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