WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/DS/77.26
ORIGINAL: ENGLISH
DATA SHEETS ON PESTICIDES No. 26
HEXACHLOROBENZENE
It must be noted that the issue of a Data Sheet for a
particular pesticide does not imply endorsement of the pesticide by
WHO or FAO for any particular use, or exclude its use for other
purposes not stated. While the information provided is believed to
be accurate according to data available at the time when the sheet
was compiled, neither WHO nor FAO are responsible for any errors or
omissions, or any consequences therefrom.
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without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
CLASSIFICATION:
Primary Use: Fungicide
Secondary Uses: None
Chemical Group: Organochlorine compound
1. GENERAL INFORMATION
1.1 COMMON NAME:
Hexachlorobenzene
Identity: Hexachlorobenzene
Synonyms: Perchlbrobenzene, HCB
Local synonyms:
1.2 SYNOPSIS
An organochlorine compound, of low acute toxicity; however it is
persistent and accumulates in body tissues. Chronic poisoning with
this compound can occur, giving rise to cutaneous porphyria.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
A colourless white powder or needles m.p. 229°C, b.p. 326°C.
Technical agricultural grade contains 98% hexachlorobenzene, 1.8%
pentachlorobenzene with 0.2% 1,2,4,5 tetrachlorobenzene. M.p. over
200.
1.3.2 Solubility
Practically insoluble in water, slightly soluble in cold alcohol;
soluble in benzene, chloroform or ether.
1.3.3 Stability
Stable.
1.3.4 Vapour pressure
1.089 x 10-5 = Hg at 20°C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
10-40% dust to prevent fungus attack, often in combination with
other seed protectants particularly lindane (0.5-1.0%) to prevent
insect attack on stored seed.
1.4.2 Susceptible pests
Soil pests, sucking and biting insects and many glass-house pests.
1.4.3 Use pattern
As a selective fungicide for the control of bunt on wheat by seed
pre-treatment. It should be noted that a Joint FAO/WHO Meeting in
1974 recommended as follows: Hexachlorobenzene should be used to
dress cereal seed only if the need for such a treatment has been
investigated and assessed and the possible use of an alternative has
been ruled out. It should not be used for the treatment of cereal
seed to be exported for the production of seed.
1.4.4 Unintended effects
May irritate the skin mildly.
1.5 PUBLIC HEALTH PROGRAMMES:
No public health use.
1.6 HOUSEHOLD USE:
No household use.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route
Can be absorbed from the gastrointestinal tract or by inhalation. It
does not appear to be absorbed through the intact skin to any
extent, but there have been some reports of skin irritation with
this compound.
2.1.2 Mode of action
Hexachlorobenzene causes liver injury and porphyria in man, rat,
mouse, guinea-pig and rabbit. In man, these changes are the cause of
death. Neurological Changes have not been reported, although they do
occur in rodents.
2.1.3 Excretion products
Hexachlorobenzene does not appear to be metabolised. Five days after
an oral dose given to rabbits the main portion of the dose was found
in the gut contents, only 6% had appeared in the faeces. There was
no significant urinary or pulmonary excretion of metabolites.
2.1.4 Toxicity, single dose
Oral LD50 - rat* - 3500-10 000 mg/kg
(*sex not stated)
Most susceptible species - cat* - 1700 mg/kg
2.1.5 Toxicity, repeated doses
Oral: Experimental porphyria was produced within one month in
rats dosed orally by stomach tube at 0.8-1.0 g/kg/day for 10 days
and then at 1.2-1.3 g/kg/day thereafter. Mortalities on this dosing
regime were few and porphyria could be maintained for some time.
Inhalation: A single exposure of rats to hexachlorobenzene vapour
at 3.6 mg/l and 1.2 mg/l (duration not given) caused symptoms of
irritation followed by an increase in haemoglobin and erythrocytes
count and later a gradual decrease in these parameters.
Cumulation of compound: Hexachlorobenzene is stored in body fat.
Studies on the omental fat of sheep have shown that it is stored to
a level seven to nine times the concentration at which it is fed. It
has a half-life of from 10-18 weeks depending on the level at which
it is ingested. A plateau level in tissues is reached when
elimination balances intake.
Cumulation of effect: Alterations in liver size and porphyrin are
observed in cases of prolonged ingestion of hexachlorobenzene. The
alterations in porphyrin metabolism and excretion are not
immediately reversible on cessation of feeding as has been shown for
both man and animals. Photosensitivity may re-occur for several
years after exposure in man.
2.1.6 Dietary studies
Short-term: 0.5% hexachlorobenzene fed in the diet to guinea-pigs
and mice caused marked neurological symptoms in 8-10 days. Rabbits
given the same dose died in 8-12 weeks and were generally more
resistant to this compound.
Female rats were fed a diet containing 2000 ppm hexachlorobenzene;
in seven days weight loss and general debility were observed and
from 3-8 weeks all rats showed increased urinary porphyria
excretion. Rats with well-established porphyria were expose
continuously to ultraviolet light. If an area of about 25 cm2 or
larger was plucked or shaved at the beginning of the exposure period
most of the animals died in 3 to 14 days. Prolonged exposure to the
same ultraviolet irradiation had no effect on porphyric rats fully
covered with hair or on normal rats that were plucked or shaved
repeated. When the ultraviolet bulbs in the cages were replaced by
daylight bulbs, there was no injury 116 plucked or shaved porphyric
rats. Hexachlorobenzene usually produces no irritation or sensation
in unirradiated rodents.
Long-term: No information.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: No information.
Teratogenicity: In rat foetuses whose dams were given single oral
doses on days 10-13: 6-16, or 6-21 of gestation, the incidence of
uni- and bilateral fourteenth ribs were increased, relative to the
duration of treatment and dose. Sternal defects were found in those
from dams dosed on days 6-24. No significant differences were found
in value for live and dead foetuses resorption sites, foetal weight,
or other viscera or skeletal abnormalities.
Mutagenicity: In a dominant lethal test where male rats were dosed
at various levels to 60 mg/kg for 10 days, no significant
differences in reproduction were found in the succeeding 14
generation.
Neurotoxicity: Neurological disturbances have been observed in
guinea-pigs, mice, rabbits and to a certain extent in rats; however
no histopathological lesions been found. Symptoms have included
course tremor hyper-excitability, clonic convulsion and paralysis.
However, none of these symptoms have been observed in man, possibly
due to differences in dosage levels.
2.1.8 Modification of toxicity
Hexachlorobenzene at a dietary level of 20 000 ppm produces
cutaneous lesions as well as other signs of intoxication in rats.
When some of these rats were given 10 or 20 mg of
adenosine-5-monophosphoric acid daily after illness had begun and
while exposure to the fungicide was continued, most showed healing
of skin lesions, recovery of lost weight, practical disappearance of
neurological signs decrease in excretion of porphyrins, and
reduction of liver injury. Some treated rats died in spite of
visible improvements in skin lesions and the condition of the fur.
Controls that received the fungicide but no treatment showed a
gradual progression of the disease.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption
Toxicity with this compound is normally associated with ingestion in
the diet, however inhalation of dust is possible, and though it is
probably not absorbed through the intact skins to any extent, dermal
and ocular irritation have been observed.
2.2.2 Dangerous doses
Single: No information.
Repeated: 5-2000 mg a day, if ingested for a sufficient length of
time, is hazardous to man.
2.2.3 Observations of occupationally exposed workers
No reported cases.
2.2.4 Observations on exposure of the general population
Levels of hexachlorobenzene have been found in samples of human milk
in Australia from both rural and urban communities: of 66 samples
examined all were positive at levels of 0.042 to 0.063 ppm. A second
study in Australia revealed levels of 1.25 ppm in 75 samples of
human perirenal fat. The source was thought to be eggs from chickens
fed contaminated seed corn. See also 2.2.6 below.
2.2.5 Observations of volunteers
No information.
2.2.6 Reported mishaps
A major outbreak of poisoning due to ingestion of hexachlorobenzene
has occurred in South-East Turkey where there were estimated to be
3000-5000 cases over a five-year period from 1955-59. The outbreak
was traced to the consumption of wheat intended as seed corn and
pretreatment with hexachlorobenzene. The poisoning occurred as a
cutaneous porphyria which was manifest as a photosensitive
blistering and epidermolysis of the skin. Hyperpigmentation and
hypertrichosis were common features. The urine contained large
quantities of porphyrins and weight loss and hepatomegaly were
frequently present. Abdominal pain also occurred. Neurological
symptoms were not evident, but bone and joint changes were apparent
in some cases giving rise to osteaorosis of the extremities and
interphalangeal arthritis. The overall mortality ratel was 10%.
Children born to mothers who had eaten the grain developed skin
lesions that proved fatal in 95% of cases. Analysis of the maternal
milk showed the presence of hexachlorobenzene.
On cessation of intake most features of this disease disappeared in
20-30 days, though photosensitive relapses during the summer months
were often seen up to three to five years later; arthritic joint
changes did not regress. The estimated intake of hexachlorobenzene
was from 50-2000 mg/day for a long period.
A second outbreak of poisoning occurred in Saudi Arabia; out of 490
persons hospitalized seven died. The source was a bakery using
hexachlorobenzene as a poison to control rodents. The organochlorine
content of bread baked there was 220 ppm.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish
Harmful.
2.3.2 Birds
No information.
2.3.3 Other species
Harmful to bees and livestock.
3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATIONS OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(for definition of categories, see introduction)
All formulations, Category 3
Hexachlorobenzene has been the subject of a special study by a
WHO/FAO meeting (WHO Technical Report Series No. 555, 1974). It
was recommended that it should be used for seed dressing only when
there was no satisfactory alternative and dressed cereal seed should
not be exported (see Section 1.4.3).
3.2 TRANSPORTATION AND STORAGE
All formulations - Should be transported or stored in clearly
labelled rigid and leak-proof containers. No food or drink should be
transported or stored in the same compartment. Storage should be
under lock and key, and secure from access by unauthorized persons
and children.
Treated grain - Should be distinctly coloured or made unpalatable,
and should be transported or stored in clearly labelled leakproof
containers. No food or drink should be transported or stored in the.
same compartment and it should be kept well away from untreated
grain. Storage should be under lock and key, and secure from access
by unauthorized persons and children. It should not be fed to
animals even if diluted with undressed seed.
3.3 HANDLING
All formulations - Protective gloves should be worn when handling
this compound, and excessive dust should be avoided. Adequate
washing facilities should be available at all times during handling
of this compound and should be close to the site of handling.
Eating, drinking and smoking should I be prohibited during handling
and before washing after handling.
Treated grain - Dressed seed should not be handled more than
necessary. Wash hands and exposed skin before meals and after work.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER
Container must either be burned or crushed and buried below the
topsoil. Care must be taken to avoid subsequent contamination of
water sources. Decontamination of containers in order to use them
for other purposes should not be permitted. Sacks or containers that
have been used for dressed seed should not be used for other
purposes.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
All formulations - Pre-employment medical examination of workers
desirable. Workers suffering from active hepatic or renal disease
should be excluded from contact if exposure is considerable and
prolonged, routine estimations of urinary porphyrin excretion for
workers desirable. Training of workers in techniques to avoid
contact essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations - Not applicable.
3.7 LABELLING
All formulations - Minimum cautionary statement
Hexachlorobenzene is an organochlorine fungicide. It is poisonous if
swallowed and can cause skin and eye irritation. Avoid skin contact;
wear protective gloves and clean protective clothing whet handling
the material. Wash thoroughly with soap and water after use. Keep
the material out of reach of children and well away from foodstuffs,
animal feed and their containers if poisoning occurs call a
physician.
Treated grain - Minimum cautionary statement
Seed treated with hexachlorobenzene must not be used as food for
humans, animals or birds.
3.8 RESIDUES IN FOOD
Maximum residue limits for hexachlorobenzene have been recommended
by the Joint FAO/WHO Meeting on Pesticide Residues.
4. PREVENTION OF POISONING IN MEN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General
Hexachlorobenzene is an organochlorine fungicide of low acute
toxicity which may be absorbed by inhalation of dusts or from the
gastrointestinal tract and can cause skin irritation. It accumulates
in body tissues and is a chronic poison. All formulations should be
handled by trained personnel wearing protective clothing.
4.1.2 Manufacture and formulation
TLV: (ACGIH) (USSR) 0.9 g/m3. Vapour and dusts should be
controlled preferably by mechanical means. Protective equipment for
the skin and respiratory protection is usually necessary. Mixing as
far as possible should be in a closed system.
4.1.3 Mixers and applicators
When opening the container and when mixing care should be taken to
avoid contact with the mouth and eyes. A facial visor and gloves
should be worn. The mixer, and those associated with the process,
should as far as possible avoid working in dust and avoid contact
with the mouth. Before eating, drinking or smoking, hands and other
exposed skin should be washed.
4.1.4 Other associated workers
Persons exposed to hexachlorobenzene and associated with its
application should observe the precautions described above in 4.1.3
under "mixers and applicators".
4.1.5 Other populations likely to be affected
With good agricultural practice other populations should not be
exposed to hazardous amounts of hexachlorobenzene.
4.2 ENTRY OF PERSONS INTO TREATED AREAS
Not applicable.
4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS
Containers should be emptied in a diluted form into A pit, taking
care to avoid contamination of ground waters. Decontamination of
containers in order to use them for other purposes should not be
permitted. Spillage should be removed as much as possible into a
deep dry pit and the remainder washed away with large quantities of
water.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning
Acute poisoning with hexachlorobenzene is very unlikely. However,
early symptoms might include stomach pain, nausea, vomiting,
weakness; neurological symptoms have been reported in animals.
4.4.2 Treatment before person is seen by a physician, if these
symptoms appear following exposure
The person should stop work immediately, remove contaminated
clothing, wash the affected skin with soap and water if available,
and flush the area with large quantities of water. If swallowed,
vomiting should be induced if the person is conscious.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information
Hexachlorobenzene is an organochlorine fungicide of low acute
toxicity, but is persistent and stored in body tissues. It is mainly
absorbed from the gastrointestinal tract but inhalation is possible.
It is not absorbed to any extent through the intact skin, but has
been known to cause dermal irritation. Chronic exposure has resulted
in interference with porphyrin metabolism, which is not necessarily
reversible on cessation of exposure.
5.1.2 Symptoms and sign
There is very little information on symptoms resulting from acute
exposure to hexachlorobenzene and due to its low toxicity this form
of poisoning is unlikely. Prolonged ingestion of levels of from 50
to 200 ppm. have caused increased excretion of porphyrin metabolites
in urine and faeces; port-wine coloured urine is typical of this
type of effect. Severe photosensitization of the skin with bullae
milia, extensive-scars, loss of elasticity, atrophy,
hyperpigmentation and sclero-dermatous change, hypertrichosis
abdominal vain, weakness, hepatomegaly and cirrhotic changes, and a
painless arthritis of the terminal finger digits.
5.1.3 Laboratory
Toxic porphyria caused by hexachlorobenzene gives rise to symptoms
closely resembling those seen in Porphyria Cutanea Tarda but with
more emphasis on liver damage. However, laboratory data are unique
and include urine characterized by marked increase of uro and
coproporphyrins, but with normal amounts of porphyrobilinogen and
ALA. Levels of urine coproporphyrin of from 77 to 401 µg/day and
urine uroporphyrin from 679 to 435 µg/day may be found in
chronically poisoned patients. Increases in liver function values
may be observed, with regard to GOT, GPT, and dehydrogenases. Levels
of hexachlorobenzene will be found in fat and can be used to confirm
the diagnosis.
5.1.4 Treatment
A poisoning is usually due to ingestion. Unless the patient is
vomiting rapid gastric lavage should be performed using 5% sodium
bicarbonate if available. For skin contact the skin should be washed
with soap and water. If the compound has entered the eyes they
should be washed with isotonic saline or water. Acute intoxication
has not been described for this compound, so treatment must of
necessity be symptomatic.
In chronic exposure the source of the hexachlorobenzene should be
ascertained and the patient removed from any further exposure.
Treatment is mainly symptomatic, the patient should be kept away
from direct sunlight. Chelating agents have been used on a limited
scale with some success (Peters, H. A. et al., see 5.1.6 below).
Treatment with EDTA (disodium salt) was given intravenously (1.5 g
EDTA in 1000 ml 5% glucose in water daily for five days) followed by
disodium EDTA orally (1.5 g daily for 16 weeks, 1.0 g for 10 weeks,
0.5 g for eight weeks, none for four weeks and then 1 g daily for 10
weeks).
5.1.5 Prognosis
In chronic poisoning the prognosis is poor with regard to a complete
cure. Photosensitivity can reappear up to five years after cessation
of exposure and arthritic joint changes are probably permanent once
established. If exposure has not been too prolonged there may be
complete recovery 20-30 days after exposure has ceased.
5.1.6 References to previously reported cases
Peters, H. A. et al. (1966) Amer. J. Med. Sci., 251, 314
Cam, C. & Nigogosyan, G. (1963) J. Am. Med. Assn., 183, 88
Dogramaci, I. et al. (1962) Turkish Journal of Pediatrics, 4(3),
129-150
5.2 SURVEILLANCE TESTS
Urine coproporphyrin and uroporphyrin may be useful or surveillance
of patients and the appearance of the skin lesions will also be of
assistance. Liver cirrhosis often accompanies poisoning with this
compound, so tests of liver function may prove useful. Levels of
hexachlorobenzene will be found in fat and can be used to
confirm diagnosis.
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound
Detection and assay of hexachlorobenzene is not straightforward, as
this compound is exceptionally non-polar and extraction by the
normal method for organochlorine compounds is not successful. In
addition the column normally used in GLC for separation of
organochlorine compounds does not adequately distinguish between
hexachlorobenzene and alpha-benzene hexachloride.
However, these problems are discussed and methods suggested in the
following publications:
Taylor, I. S. et al. (1970) J. Assoc. Offic. Anal. Chemists,
53(6), 1293-1295
Smyth, R. J. (1972) J. Assoc. Offic. Anal. Chemists, 55(4),
806-808
Collins, G. B. et al. (1972) J. Chromatogr., 69(1), 198-200
5.3.2 Other tests in cases of poisoning
Tests for uro- and coproporphyrin in urine can be made to confirm
and monitor exposure. Tests of liver function, by estimation of
serum transaminases and dehydrogenases may also be useful.
Porphyrin: references for methods of estimation.
1. Laboratory Medicine. Hematology. John B. Miale, 1958, published
by C. V. Mosby Company, p. 660
2. Disorders of the blood. Whitby & Briton. 10th Edition, 1969,
published by J. A. Churchill Ltd., p. 750