EPA 560/6-76-014
ENVIRONMENTAL CONTAMINATION
FROM
HEXACHLOROBENZENE
APRIL 1976
OFFICE OF TOXIC SUBSTANCES
U.S. ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
EPA560/6-76-014
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Document is available to the public through the National
Technical Information Service, Springfield, Virginia 22151
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EPA 560/6-76-014
ENVIRONMENTAL CONTAMINATION
FROM
HEXACHLOROBENZENE
by the
EARLY WARNING BRANCH
OFFICE OF TOXIC SUBSTANCES
U.S. ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
July 20, 1973
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PREFACE
The following report, prepared by the Office of Toxic Substances in
July 1973, represents the first Agency aggregation of data concerning
the problems associated with environmental exposure to hexachlorobenzene.
The plan of action by the Environmental Protection Agency and other
Federal and State agencies to gather even more data for regulatory
decision-making has now been implemented. Even though this document is
somewhat out of date, demand for it has been constant over the past two
years; it is therefore being made generally available to the public.
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TABLE OF CONTENTS
Summary 1
Contamination of Cattle in Louisiana 3
National and International Dimensions of the Program 7
Chemistry and Analysis of Hexachlorobenzene 11
Toxicology Aspects of Hexachlorobenzene 13
Guidelines for Permissible Residue Levels 19
Conclusions and Current Activity 22
Bibliography 26
n
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Summary
Recent discovery of hexachlorobenzene (HCB) in the fat of
animals brought to slaughter has focused attention on the
hazards of this material. The most serious case involved
cattle in central Louisiana. Other incidents of HCB con-
tamination in the past year have involved sheep in western
Texas and in eastern California. Sources of HCB in Louisiana
appear to be airborne emissions of manufacturing plants
which produce chlorinated hydrocarbons and waste disposal
practices of these plants. The Texas and California situations
have been associated with pesticides which were contaminated
with HCB.
Hexachlorobenzene is a stable and persistent chemical. A
solid at normal temperatures, it sublimes (vaporizes) rather
readily. It is only very slightly soluble in water.
An epidemic of HCB poisoning in man occurring in Turkey
in the 1950's was associated with consumption of treated
wheat containing 20 ppm HCB. Up to 5000 cases of a condition
called porphyria cutanea tarda resulted. In addition to dis-
turbance in porphyrin metabolism, clinical manifestations of
photosensitization, hypertrichosis (abnormal hair growth),
hepatomegaly (enlarged liver), weight loss, and enlargement
of the thyroid gland and lymph nodes were reported.
Appreciable residues of HCB have been found in wild and
domestic animals from a variety of locations in North America.
It has also been detected in municipal water supplies in the
United States.
The largest source of HCB is the waste stream (byproducts)
from the manufacture of chlorine and many chlorinated hydro-
carbons. It is also a registered fungicide, and is a major
impurity in some pesticides, specifically dimethyl tetrachloro-
terephthalate (Dacthal) and pentachloronitrobenzene (PCNB).
Two domestic producers of HCB for sale have been identified,
Dover Manufacturing and Stauffer Chemical. In the past, HCB
had been an intermediate for production of pentachlorophenol,
but apparently this process has not been used in this country
for several years.
Existing Federal controls over HCB are very limited, and
stem from its registration as a fungicide. Because of this
registration, the government can move against foodstuffs
contaminated with HCB. However, there are no controls on the
industrial use of the material nor on methods of disposal for
waste HCB.
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The large number of potential sources of HCB and their
geographic dispersion suggest that HCB contamination may be a
national problem. Despite serious current problems in a few
localities, indications are that HCB has not yet reached
environmental levels on a broad scale that will cause serious
health or food-supply problems. This does not mean the threat
is not serious, but rather that we have caught it early enough
that preventive measures may still be effective.
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Contamination of cattle in Louisiana
The incident in Louisiana came to light when routine
fat samples from beef carcasses for pesticide analysis
were taken from the Stevens Meat Company by the U.S.
Department of Agriculture on December 12, 1972. The
laboratory analysis revealed the presence of 1.52 ppm
hexachlorobenzene. Three additional cattle from the
same herd from the Darrow, Louisiana, area were then
slaughtered and tested. All carcasses were condemned
because of excessive residues.
The Department of Agriculture was using a guide-
line of a maximum of 0.3 ppm HCB in fat as a basis for
passing carcasses. This value had been set some years
previously, but prior to 1972 it had not been necessary
to invoke it with regard to domestic meat products.
The basis for the figure is not clear, but it appears
to have been set by analogy to the acceptable levels
for dieldrin.
Since the very high HCB residues found could not
be associated with any malpractice on the part of the
rancher involved, USDA proposed placing a "hold order"
prohibiting the shipment of beef from Louisiana unless
each animal was tested for HCB residue. In order to pre-
vent this, the Louisiana Department of Agriculture estab-
lished a quarantine area covering parts of Ascension and
Iberville Parishes just south of Baton Rouge. None of
the animals in the areas could go to slaughter without
pre- or post-slaughter evidence that they did not contain
violative residues of HCB. The area quarantined center-
ed on Geismar, La. It included the part of Ascension
parish that is south and west of U.S. highway 61; and
that part of Iberville parish bounded by highway 1 on
the southwest portion, then northwest on highway 1 to
Bayou Gorda, then a line following highway U05 north-
east through St. Gabriel until it intersects highway 61.
Since HCB is registered for use as a fungicide seed
treatment, an investigation was undertaken by the Pesti-
cide Branch of EPA in Region VI. This involved deter-
mining that (1) the high residues found in the cattle
were not due to a fungicidal use since the cattle were
grass fattened and no supplemental feed was used,
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(2) high concentrations of HCB in the soil, grass and
air had been detected, (3) HCB is a normal byproduct
of perchlorethylene production as well as the production
of chlorine using graphite anodes. The tarry residue
from perchlorethylene and carbon tetrachloride production
reportedly contains 10-15% HCB.
It was estimated that there were 20,000 cattle in
the quarantine area and 25,000 immediately to the south.
It was suspected that about half of the latter may have
been contaminated at the same levels as in the quarantine
area. Assumption was also made that the split between
calves and adult cattle was 50/50.
A cooperative program, involving EPA, USDA, the
state Department of Agriculture, and the state Extension
Service, for the survey of the area in Ascension and
Iberville Parishes which had been quarantined was under-
taken in April, 1973. Biopsy fat samples were collected
from cattle within the quarantine area to determine the
status of the herds as this affected restrictions placed
on their movement to slaughter. These were supplemented
by soil, grass, and surface water samples taken from
the involved pastures. For these purposes, a field
headquarters office was established in Gonzales.
Under the scheme established, three cows and three
calves were sampled from each herd. If all six animals
showed acceptable HCB levels, the herd would have been
released from quarantine and could be shipped without
restriction. Animals from herds under quarantine could
be shipped only if the particular animal was analyzed
for HCB (either before or after slaughter) and showed
an acceptable level (less than 0.3 ppm in fat) of HCB.
Unfortunately, most herds involved were small, and did
not have six animals suitable for biopsy, cancelling
any chance that they could be released under this
system.
There have been 555 animals tested from 157 herds.
Fat samples above 0.5 ppm were found in 29% of the
cattle and 34% of the herds.
In response to USDA's petition of April 3, 1973,
to establish an official tolerance for HCB, EPA recom-
mended an action guideline of 0.5 ppm on June 1, 1973.
This is discussed further below.
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Since the action level guideline was set the quarantine
area has been reduced to parts of Ascension parish, leaving
about 5,000 cattle in the quarantine area. Those herds
which were previously tested and shown to be free of con-
tamination are now free from quarantine. USDA has recommend-
ed that herds may be released from quarantine if the com-
posite of ten animals tested from the herd is no greater
than .35 ppm. If it is known that any animals are over
3.0 ppm they must be included in the sample first. Those
known to be between 0.5 and 3.0 must then be included.
The remaining animals to make ten may be a random sample.
The USDA feels they have 95% confidence that at least
15% of the herds will be in violation using this method.
Calves can be released to go to feeder lots if in a three-
animal sample no animal is greater than 1.5 ppm. This allows
for a dilution factor.
Individual biopsies will permit any individual animal
to go to slaughter even if the herd level is violative.
However, the administration of the quarantine is the
responsibility of the State Department of Agriculture.
USDA can test only carcasses after slaughter, and if the
animal is in violation, it cannot be reclaimed by the
owner for other purposes. The local county agent has
indicated that due to the expense and the fact that
they had difficulty obtaining animals with enough fat
to sample, three cows and three calves from each herd
are being sampled as previously. The highest value of
those tested would be the HCB level assigned to the herd
to determine if the herd could be freed from quarantine.
It has been realized that the air sampling techniques
used by the Louisiana State Air Control Commission and by
private contractors last winter did not give samples that
accurately reflected the concentrations of HCB in the air.
An improved sampling technique was developed at the EPA
Perrine Laboratory and is now being used by the State
and by EPA Region VI.
It was suspected that disposal of HCB-containing
"hex" waste from a perchlorethylene plant in the area
may have been a major source of HCB to the environment.
The cattle with the highest concentrations of HCB in their
fat were located along the 12-mile road which open trucks
purportedly traversed with "hex" waste from the plant to
the dump. Results of analyses of soil samples taken near
the end of April from this landfill showed concentrations
of 5000 ppm HCB. Air samples taken at the landfill on
May 14 using the new technique showed concentrations in the
air of 14 ppb or 16 micrograms/cubic meter.
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In the June 4, 1973, status report of hexachlorobenzene
emissions, the Louisiana Air Control Commission and the
Division of Health Maintenance and Ambulatory Patient
Services indicated that they had listed and reviewed the
records of all possible HCB sources which may have con-
tributed to the environment of the cattle in the quarantined
areas. On-site inspections of all suspect facilities were
made, and the list was limited to those capable of being
the source of HCB. The remaining list includes Vulcan
Materials, BASF Wyandotte, Ascension Parish Sanitary Land-
fill (Darrow), Monochem, Uniroyal, Stauffer Chemical,
CIBA-Geigy, Browning-Ferris Landfill, and Rubicon. These
will be required to provide emission test data from their
installations.
The Louisiana Air Control Commission at a special
meeting on May 30, 1973, moved to "...initiate action
aimed at legal proceedings to issue a cease and desist
order and if possible go into emergency cease and desist
to those industries who are emitting this material,
hexachlorobenzene, for any amount, setting a zero tolerance
and that this be based on the Air Control Commission
Statutes, Section 2202, Sub-Section C, until such time
as standards for hexachlorobenzene be established by
this Commission to regulate emission for this material."1
The Louisiana Air Control Commission and EPA Region VI
are continuing to collect air samples in attempts to determine
sources. The EPA Mississippi Test Facility has been author-
ized to do analyses of samples that Region VI has been
obtaining.
1. Status Report Hexachlorobenzene Emissions in Geismar,
Louisiana Vicinity 4 June 73, Louisiana Air Control
Commission and Louisiana Department of Health
Maintenance and Ambulatory Patient Services.
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National and International Dimensions of the Problem
Besides the incident in Louisiana, sizeable numbers of
violative sheep have been found in California and in Texas.
(The sheep taken to slaughter in Texas were actually raised
in Mew Mexico.) Additionally, numerous positive but "non-
violative" findings of HCB have been reported in virtually
all kinds of meat animals from many parts of the country.
There are large numbers of such reports from California and
Colorado, but many other states are also represented. All
of these have been found since July, 1972, when USDA first
started checking animals for HCB residues.
These samples were taken in USDA's statistically designed
spot checking program. In a given year, this program actually
involves only small fractions of the animals marketed and of
the slaughterhouses in the country.
The Food and Drug Administration's "market basket" surveys
have also detected HCB, but generally at low levels. Worrisome
residues have been found in some samples of butter and cheese,
however. The. data do not demonstrate any clear trends.
Because of the nature of the survey, the significance of these
findings is hard to assess.
As more data from ongoing surveys of agricultural products
conducted by USDA and FDA become available, we will be better
able to judge the magnitude and extent of HCB contamination of
the food supply.
The three-most serious incidents (in Louisiana, New Mexico,
and California) are currently under investigation. In
Louisiana, the source of HCB is almost certainly industrial
byproducts; in New Mexico and California, HCB residues appear
to result from the use of the herbicide Dacthal, which contains
HCB as an impurity. Samples of Dacthal obtained in California
contained up to 10% HCB. There is presently no evidence
linking HCB contamination of food to the approved use of HCB
as a fungicidal seed treatment.
Fungicidal treatments of seed grains such as wheat,
barley, oats and rye are the most important pesticidal uses
of HCB. The major use is to control bunt in wheat. A.
typical rate of application for seed treatment is
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about 1-3 ounces of a 30% du~t per bushel of wheat seed
equivalent to 330-990 ppm on the seed. Minor uses include
seed treatments for onions and for sorghum. Technical
grade materials used for fungicidal seed treatment contain
about 98% HCB and 1.8% pentachloronitrobenzene' (PCNB).
Commercial dusts for similar purposes contain 10-10% HCB
and 0.5 to 1.0% Lindane. In 1971, such uses consumed
15,000 pounds of HCB.
Dacthal is popular with homeowners for lawns and gardens.
Large quantities are applied by commercial growers to onions,
cabbage, strawberries, and vegetable seeds; smaller amounts are
used on soybeans, green peppers, cotton, snap beans, Irish
potatoes, watermelon, and other crops.
PCNB is used for cotton, peanuts, and nectarines, and in
nurseries. It is also added to fertilizer and sold to ranchers
and homeowners in this form.
The possibility that HCB could reach the environment from
industrial installations, as in Louisiana, raises some serious
questions. A number of industrial processes can release HCB,
including those for manufacture of chlorine gas, perchlorethylene,
carbon tetrachloride, and other chlorinated hydrocarbons.
Available information suggests that the plants in Louisiana
followed common industrial practices for control and disposal
of waste HCB; there is no reason to believe that the problem
resulted from failure to follow normal procedures or from
accidents leading to discharge of HCB. There, therefore, exists
the possibility, even the likelihood, that similar problems
could appear in the vicinity of any installation using the same
technology.
Hexachlorobenzene is formed during the reaction of
chlorine and hydrocarbons at a temperature greater than 150°C
(300°F). HCB is a normal byproduct of perchlorethylene and
carbon tetrachloride production, chlorine production using
graphite anodes and mercury cathodes and other hydrocarbon
chlorination processes. The tarry residue "hex" waste from
perchlorethylene and carbon tetrachloride production is re-
ported to contain 10-15% HCB, 70-75% hexachlorobutadiene (HCBD) ,
and 10-20% hexachloroethane. (Dow; Vulcan).
Hexachlorobenzene as byproduct could possibly be
emitted directly into the air from processes which produce HCB.
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Improper containment during transport of "hex" waste can
result in contamination as HCB can enter the air via sub-
limation, or appear as a dust which can contaminate soil and
water and settle onto vegetation surfaces.
Certain means of disposal of "hex" waste such as dumping
in a landfill can lead to migration via water and sublimation
into the air. HCB has been detected in the air at the
Ascension Parish Landfill in Louisiana where "hex" waste is
known to have.been dumped (air concentrations ranged from
13-14 ppb or 16-18 /Mg/m3) . (Enos, EPA, 1973)
Only a limited amount of work has been directed toward
the development of environmentally sound disposal methods
for "hex" wastes and other HCB-containing waste streams.
The Dow Chemical Co. has been using a "thermal oxidizer"
(a steam-oxygen feed incinerator) for disposal of their "hex"
waste. Dow's production manager at the Louisiana Division
in Plaquemine stated that the products of incineration are
water, hydrogen chloride, and carbon dioxide and that the
scrubbing process is better than 99% efficient. This incin-
erator is more or less a prototype and Dow does not feel it
is marketable technology in its present form. Further develop-
ment at present involves the quenching of hot gases, the design
of the burner nozzle, and materials of construction. Recycling
of hydrogen chloride using a water scrubber is a possibility
which has not yet been exploited. Dow claims that at capacity
total loss of "hex" waste to air and water is about 10 pounds
per day, thus HCB loss is about 1 pound/day. The environmental
adequacy of this treatment should be determined.
Landfill disposal is used by many chemical manufactur-
ers for "hex" waste disposal. This method of disposal
seems questionable from an environmental standpoint.
Plants of the types that can produce HCB are scattered
throughout the.country, and there are several concentrations
of plants similar to the Geismar complex. The locations of
these plants are currently being plotted, and plans have been
proposed for concentrating HCB surveillance activities in the
areas of such facilities.
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Problems of contamination with HCB are not limited to the
United States. Residues of HCB in human tissue have been found
in studies in Australia, Japan, and Germany. At least one
country, New Zealand, has completely banned the use of HCB.
Hams from the Netherlands and cheeses from several European
countries have been refused entry into this country because of
excessive HCB levels. Australia and the United Kingdom have
also found high HCB levels in cheese and grain imported into those
countries.
World-wide concern with HCB became serious enough to
warrant consideration of the problem by the World Health Organi-
zation (WHO). In 1969, WHO proposed interim recommendations
for HCB tolerances in a number of foodstuffs, including 1.0 ppm
in the fat of meat and poultry, 0.3 ppm in fat content of dairy
products, 0.01 ppm in cereal products, and 1.0 ppm in eggs
(shellfree basis). It was recognized at that time that sufficient
information on the effects of HCB was not available. Unfortu-
nately, little more is known now than was known then, although
a few studies have been conducted, mainly in the United States
and New Zealand. The WHO recommendations expired on July 1, 1973,
and have not been extended.
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Chemistry and Analysis of Hexachlorobenzene
Hexachlorobenzene can be encountered in a number
of forms, including crystals, powder, vapor, suspended
particulates in either air or water, and dissolved in
related organic materials.
All evidence, at present, indicates HCB to be a very
stable, unreactive compound, even under relatively severe
laboratory conditions. Physical and/or chemical degrada-
tion has not been shown to occur. Worthy of note, however,
is that HCB is volatile in water vapor even at low tempera-
tures. Such co-distillation or vaporization provides
a physical mechanism for environmental dispersal of HCB.
It also sublimes readily, and will evaporate if exposed
to air under conditions of adequate ventilation.
Hexachlorobenzene (CgClg) should not be confused with
"benzene hexachloride" (Lindane, BHC), which is actually
hexachlorocyclohexane (CgHgClg).
Physical properties are shown in table I..
Table I
Chemical Structure
(1) Hexachlorobenzene (also known as HCB and perchloro-
benzene) CgClg
Physical properties of pure material (Kirk-Othmer (1966);
Hawley (1971))
(1) boiling point 326°C
(2) melting point 229°C
(3) flash point 468°F
(4) solubility insoluble in H20
(5) vapor pressure 1.089 X10~5mm Hg at 20°C
(6) appearance colorless (white) powder or
colorless needles
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•
Procedures for analyzing for HCB in air, water, soil,
vegetation, and fatty tissue have been developed and are
being used by FDA, USDA, and EPA. The preferred method
of analysis is by gas chromatography with mass spectrometric
verification of HCB.
Problems with collection of air samples for HCB
analysis were noted by the EPA Perrine laboratory at the
inception of the current activity. The standard technique
using ethylene-glycol impingers did not give samples that
accurately reflected the amount of HCB in the air. A new
technique for collecting samples was developed and is now
being used by the State of Louisiana and by Region VI.
Older procedures for analysis of chlorinated hydro-
carbon residues did not distinguish between HCB and the
alpha isomer of benzene hexachloride. Consequently, many
of the older reports of both HCB and <.-BHC must be considered
suspect. Procedures now in use do make this distinction,
however.
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Toxicology Aspects of Hexachlorobenzene
Human Health Aspects
An outbreak of porphyria cutanea tarda in southeastern
Turkey in 1955 was traced to the inadvertent consumption of
HCB-contaminated seed grain (wheat) distributed by the Turkish
government for planting purposes. Estimates of the total
number of cases over a five-year period are from 3000-5000
with approximately 80 percent of the cases in children 4-]U
years of age. The estimated dose was approximately 50 to
200 mg/day for a presumably long period of time before
manifestations of the disease became apparent. (Schmid, R.,
1960; Cam, Nigogosyan 1963)
Clinical manifestations observed included: '•
a. blistering and epidermolysis of the skin in areas
exposed to sunlight, particularly face and hands.
b. poor healing of these lesions
c. hyperpigmentation (discoloration of skin)
accompanied by hypertrichosis (excess hair)
which was not limited to the exposed skin areas
d. urine containing large quantities of porphyrins
e. hepatomegaly (liver enlargement) in approximately
35 percent of the cases
f. weight loss
g. in some cases, osteoporosis (bone deterioration) of
extremities and interphalangeal (fingers or toes)
athritis
h. thyroid enlargement in 30 percent of cases, but no
signs or symptoms of hyperfunction
t
i. enlargement of lymph nodes
Acute skin manifestations disappeared within 20 to 30 days
after discontinuation of intake of HCB. However, relapses were
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often seen during the summer months. A predilection of the
disease for males was observed (about 76 percent of cases).
(Cam and Nigogosyan, 1963).
An Australian study of occupationally exposed individuals
showed levels in blood ranging from 0 to 410 ppb. A control
group with no known exposure showed blood levels ranging from
0 to 95 ppb. HCB was detected in 95 percent .of the people
tested (the minimum detectable level was 10 ppb). No toxic
effects were reported. (Brady, 1972).
Another Australian study of a random selection of perirenal
fat samples taken at autopsy revealed 100 percent positive
samples with levels from "trace" to 8.2 ppm; 33 percent of the
samples contained greater than 1 ppm. The mean for all samples
was 1.25 ppm. No toxic effects were reported. (Brady £ Siyali,-
1972).
A German study detected residues in human fat of 6.3 ppm
and 5.3 ppm in human milk. No toxic effects were reported. .
(Acker, and Schulte, 1971).
A recent Japanese study has shown levels in human adipose
tissue to range from 0.30 to 1.48 ppm. No toxic effects were
reported. (Curley, e_t al. , 1973).
Animal Studies
A 90-day feeding study was performed in 1962 by the Hazleton
Laboratories for the Diamond Alkali Company. Rats were fed
diets containing HCB at levels of 0,5,25,125, and 625 ppm for
13 weeks. There were no deaths reported at any dose level.
At 625 ppm the rats displayed signs of marked respiratory
involvement and slight tremors which were not observed at any
of the other dose levels. The 625 ppm group also showed reduced
growth rate, elevated total leukocyte counts and increased organ
weights in liver, spleen, and adrenals. Microscopic examination'
showed consistent adverse effects in the liver. At the 125 ppm
level, liver weight increased and microscopic examinations showed
adverse effects in the liver. In addition, at both the 125 ppm
and 625 ppm levels, some, less distinct and inconsistent changes
were observed in thyroid, kidneys, adrenals, and bone-marrow. At
5 and 25 ppm, no significant effects were observed in organs
and tissues.
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In a study by the Dow Chemical Company (Kociba, et al.,
1971) HCB was fed in feed to female weanling rats f or~3(T~days.
Doses ranged from 1 to 100 mg/kg/day (0, 1, 3, 10, 30, 65,
100). Rats at 30, 65, and 100 mg/kg/day dose levels showed
gross and histopathologic alterations in the liver. Ex-
amination of tissues from the 1, 3, and 10 mg/kg/day rats
showed no definitive pathological changes.
Administration of HCB at 5000 parts per million to
two female rats (De Matteis ejt aJL 1961) showed apparent
excretion of HCB and/or its metabolites in milk. One
animal died, but the other delivered normally and reared
the young until they died with convulsions after 7 to 8
days. She was then placed with three normal week-old
pups to foster. The pups died 3 to 4 days later exhibit-
ing convulsive seizures, and the foster mother died
similarly 4 weeks later.
Other animal studies are summarized in Tables II and III.
Bioaccumulation
Hexachlorobenzene has been shown to be quite stable even
under severe laboratory test conditions. (Allis, EPA, 1973).
It apparently undergoes relatively little biotransformation,
or degradation and is thus a highly persistent chemical.
Residues have been detected in foods, various organisms (wild
and domestic) including man, and various media. Detectable levels
have been found in municipal water supplies in Louisiana and
Indiana (EPA report, 1972).
Tissue residue data haye revealed that HCB will bioconcentrate
and indicates potential biomagnification up the food chain,
since predatory birds have been found with detectable levels of
HCB (Zitco and Choi, 1972); Gilbertson and Reynolds, 1972).
Experimentally, in sheep the storage of HCB in body fat is
7 to 9 times the concentration in feed at all levels of intake
from 0.1 ppm to 100 ppm. (Avrahami and Steele, 1972).
In the chicken, HCB can accumulate in the body fat to at
least 20 times the concentration fed in the diet. (Avrahami and
Steele, 1972).
Studies by Metcalf, et al., in model ecosystems showed
bioconcentration of HCB by algae, snails, mosquitoes, water fleas,
and fish to part-per-million levels while in an aquatic environ-
ment with 3 ppb HCB. (Metcalf, 1973, in press).
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Table II
t
ACUTE TOXICITY OF HEXACHLOROBENZENE FOLLOWING
SINGLE DOSE ORAL ADMINISTRATION, MG/KG1
Minimum ' Minimum Average Absolute
Species
Mice
Rats
Rabbits
Cats
Guinea pig3
Toxic Dose Lethal Dose Lethal Dose
400 2000 about 4000
500 2000 3500
2600
about 1700
innn
Lethal Dose
about 7500
6000
1Savitskii/ 1964.
3 The signs of intoxication associated with a minimum toxic
dose were not described.
3Mel1s, (1955)
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Route
Species
# Animals
TABLE III (Cont)
Sex Dose
Duration
Observations
Oral5(Continued)
Oral6
0.5% in feed
Inhalation2
0.03 mg/1
2
Inhalation
0.009 mg/1
Oral7
(in feed
60% HCB)
commercial
fungicide
Oral7
in feed
(60% HCB in
commercial
fungicide)
Guinea Pig
Mouse
Rabbit
Rabbit
Rabbit
and Cat
Sheep
1 yr old
(22-24 kg)
food consumption
about 1 kg/day
Chicken
12 days old
Chicken - 8 mo. old
egg laying
X
X
X
X
X
5
5
5
5
20
20
X
X
F
X
X
F
F
F
F
F
F
X
X
X
X
X
0.1 mg HCB day (.1 ppm)]
1 mg HCB day (1 ppm) >
10 mg HCB day (lOppmy
8-10 daysT
8-10 daysj
6 weeks
8-12 weeks
dally
exposure
68-78 dally
exposure
18 weeks
100 mg HCB day(lOOppm)18 weeks
0.1,1,10,100 mg/day
0.1,1,10,100 mg/day
180 days
180 days
symptoms. Decreased egg produc-
tion and hatchabllity. Por-
phyria. Increased liver wt.
Liver and kidney pathology.
marked neurological symptoms-
tremors, convulsions, death
increased urinary porphyrins
tremors, paralysis, death
alteration of red blood cell and
hemoglobin content of the blood
no apparent effects
no apparent effects
1/3 reduction in growth rate
no apparent effects
no apparent effects on birds,
or fertility or hatchabHlty
of eggs.
•
Unpublished data. The Dow Chemical Company.
20ckner and Schmid (1961)
3Savitskii (1964)
Gurfeln and Pavlova (1960)
5Vos, ft al- (1971)
5DeMatteis, et al (1961)
7Avrahami and Steele
(1972)
xInformation hot given
in paper
-------
Oral' Rats
(in feed)
TABLE III
SUBACUTE AND CHRONIC TOXICITY OF HEXACHLOROBENZENE
Route Species
Oral1 Rats
(in feed)
# Animals
5
5
5
5
5
Sex
M
M
M
M
M
Dose Duration
2 mg/ kg/day 13 days
6 mg/ kg/day
20 mg/ kg/day
60 mg/ kg/day
200 mg/ kg/day
Observations
No toxic effects.
Very slight skin twitching and
nervousness. Significant inc.
in liver weight.
Neuro toxic symptoms. Increase
in liver weight.
Neurotoxic symptoms. Increase
in liver and kidney weights.
Neurotoxic symptoms. Increase
in liver and kidney weights.
33
100 mg/kg/day
51 days
13 deaths in one month. Neuro-
toxic symptoms. Increased liver
weight Porphyria.
Oral3 Rats
(in feed)
Oral4 Rats
(in water)
Oral5 Quail
(in feed)
•t
10
10
10
13
3 males
and
12 females
(per
feeding
rate)
300 mg/ kg/day
150 mg/ kg/day
50 mg/ kg/day
0.025 mg/ kg/day
0.1 mg/kg/day
0.5 mg/kg/day
1.8 mg/kg/day
7.2 mg/kg/day
10 days
30 days
30 days
4-8 mos.
90 days
30% mortality
60% mortality
30% mortality
No toxic symptoms. Possible
effect on conditioned reflexes.
No toxic effects.
Slight increase in liver weight.
Minimal liver pathology and
porphyria.
Increased liver wt. Liver and
kidney path. Decreased egg
production. Porphyria.
5 (4 females & 1 male) deaths-
18 to 62 day period. Neurotoxic
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-19-
Guidelines for Permissible Residue Levels
In response to a request from USDA, EPA reviewed available
data on the toxicology of HCB, and concluded that it was not
adequate to permit establishment of a tolerance level for HCB
in food. This was confirmed by consultations with scientists
in USDA and the Department of Health, Education, and Welfare,
and with members of the scientific community.
0
Nevertheless, HCB occurs in food frequently enough that
some guidance is necessary to protect public health. The
experience in Turkey vividly demonstrates the health effects
of HCB when ingested over a long period. There is, however,
no experience which indicates the effects of low doses on
humans. Attempts in the United States and abroad to determine
the safe level of HCB in experimental animals have been extremely
limited and sporadic, and at present there is a lack of
authoritative data. Experiments on a variety of animals have
been limited in design, scope, and duration. Meaningful
inferences are difficult to draw although there are indications
that repeated dosages of HCB at low levels may be harmful.
Related to these uncertainties is the unknown extent
which meat products with low levels of HCB residues are likely
to reach individual consumers on a repetitive basis. The sources
of HCB of immediate concern are confined to very small geographic
pockets which traditionally disperse a significant portion of
their products to markets around the country.
Similarly, little information is available for assessing
the economic impact of alternative tolerance levels. In the
original Louisiana quarantine area, for example, there were
up to 20,000 food animals with HCB in their fat at levels
ranging from 0.1 to 6.0 ppm. However, the extent that these
levels could be reduced through fattening with clean feed and
through natural processes prior to slaughter is uncertain.
Similarly, the cost and success of biochemical methods to
reduce the levels are difficult to assess. There are many other
economic costs related to establishing a tolerance including
the impact on the value of contaminated land, the costs of
alternative feed supplies and the long-term impact on animal
herds. Data are not available to assess these types of impact.
Furthermore, the extent and levels of HCB residues which will
appear in the months and years ahead in many areas of the
country cannot be predicted.
-------
-20-
An analysis of some of the short-term economic
implications of various tolerance levels is given in
Table IV. The analysis considers only direct short-term
cattle losses and does not address many other implications
related to factors such as land values, longer term
cattle losses and costs of feed. Data are not available
for such analyses at this time.
On June 1, 1973, EPA recommended an interim action
guideline of 0.5 ppm HCB in fat of cattle, swine, sheep,
horses, and goats at the time of slaughter. This is based
on analysis of the best data available, including toxico-
logical studies and economic considerations. The recom-
mended guideline is designed to protect the consumer under
any reasonable set of assumptions concerning the likelihood
that meat with the maximum allowable level of HCB will be
continuously consumed. The guideline will be reviewed
every 90 days with the view to establishing a tolerance
within three years should adequate technical data become
available. If sufficient technical data are developed in
the meantime which indicate a need to alter the guideline,
the guideline will be adjusted accordingly.
The Food and Drug Administration, taking into account
similar considerations, has adopted an interim guideline of
0.3 ppm HCB residues in fat for milk and dairy products.
At present, no guideline exists for HCB residues in
poultry or eggs.
-------
TABLE IV
Economic Effects of Various Guideline Levels on Cattle in the Geismar Area
(based on data to May 31, 1973)
Level % and no. of cattle %
(ppm) above level
0.3 36* 11,700 22%
0.5 24% 7,800 17%
1.0 17% 5,525 11%
1.5 14% 4,550 7%
and no. of cattle above level assuming dilution factor of:
2:1 3:1 4:1 6:1
7,150
5,525
3,575
2,275
17% 5,525 16% 5,200 12% 3,900
14% 4,550 11% 3,575 7% 2,275
7% 2,275 2% 650 0.7% 288
2% 650 0.7% 228
NEAR TERM CATTLE LOSSES
(in millions)
Level Assuming no dilution
0.3 $5.85
0.5 $3.90
1.0 $2.76
1.5 $2.28
Assuming dilution factor of:
2:1
$3.58
$2.78
$1.79
$1.14
3:1
$2.76
$2.28
$1.14
$ .33
4:1
$2.60
$1.79
$ .33
$ .11
6:1
$1.95
$1.14
$ .11
N.B. See text (p. 20) for assumptions used In calculating these figures,
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-22-
Conclusions and Current Activity
The following conclusions seem consistent with the minimal
data available on HCB.
HCB is a compound of low acute toxicity, but significantly
higher subacute toxicity. Available toxicological data indicates
that, while a single large dose may have no lasting effects,
repeated administration of much smaller doses over periods ranging
from ten to ninety days can result in serious physiological effects.
The material is very stable and defies metabolic and/or
environmental degradation. It is known to bioaccumulate in cattle,
sheep, and other animals. Preliminary studies suggest it will
also bioconcentrate in food chains.
Sources of contamination are not limited to pesticidal use
or misuse. Indications are that industrial sources may be a
significant factor in at least one situation in this country with
many more areas exhibiting the potential for such contamination.
The situation which has precipitated the present concern does not
appear to be the result of a unique set of circumstances.
The persistence of HCB and its demonstrated high toxicity at
repeated low level doses in animal studies justifies a high level
of concern with regard to the residue which should be.permitted
to accumulate in any segment of the environment (food, biota, man,
air, water, soil) and the overall hazard posed to the total
environment.
The following activities to be carried out by the
Environmental Protection Agency and other concerned Federal and
State agencies are planned or already underway:
Toxicological Research
1. A lifetime feeding study in rats to improve understanding
of the effects of long-term exposure to low level dosages of HCB.
This study is underway at the USDA laboratory in College Station,
Texas.
2. A three-generation reproduction study in rats to provide
a measure of the effects of HCB on growth and reproduction. This
study is underway at the EPA laboratory in Chamblee, Georgia.
-------
-23-
Epidemiological Research
3. A study of human populations in a limited geographical
area to determine if effects characteristic of HCB intoxication
are present. This will include analysis of blodd for HCB and
for ALA enzyme "activity and of urine for porphyrin content.
4. A similar study of workers in factories producing
chlorinated hydrocarbons (tentative).
Other Research
5. A study of the effects of various methods to reduce HCB
levels in the tissues of living animals, including natural and
drug-induced elimination, and analyses of the dilution of HCB in
fat during normal growth of a young animal.
6. Development of improved methodology and techniques for
detection, collection, and analysis of HCB in air. This work is
underway at the EPA laboratory in Perrine, Florida.
Monitoring
7. Monitoring of air, water, soil, and vegetation in the
Geismar area in order to assist in identifying the source of HCB
contamination in that area. This effort is being done by the
State of Louisiana and by EPA.
8. Monitoring of air and soil in the neighborhood of other
industrial complexes were chlorinated materials are produced to
determine if HCB is being released to the environment. This
activity is being initiated in Louisiana and Texas by EPA Region VI,
and may be expanded to other regions if it appears desirable to
do so.
9. Analysis for HCB residues of samples of soil, water, plants
and tissues (human and animal) collected in nationwide pesticide .
monitoring activities. This work will be done initially at the
EPA laboratory at Bay St. Louis, Mississippi.
10. Analysis of samples collected under 7, 8, and 9 above for
hexachlorobutadiene (HCBD) which is another potential problem.
Also, its occurrence with HCB assistrs in determining if industrial
waste is the source-of HCB in specific areas.
-------
-24-
Control Technology
11. Review of methods being used to control wastes containing
HCB and evaluation of their environmental safety.
12. A study of the effects of disposing of industrial
'wastes containing HCB in sanitary landfills.
Other
13. A review of the use of registered pesticides known to
contain HCB (Dacthal and PCNB) to determine if their uses could
lead to hazardous environmental levels of HCB.
14. Referral of available toxicological data on HCB to an
expert scientific advisory group (the Hazardous Materials Advisory
Committee) for review and recommendations.
15. A study of the economic impact of various tolerance
levels for HCB in food, including effects on the food supply and
on farmers and ranchers.
16. A nationwide analysis of the potential industrial sources
of HCB and related compounds of particular concern.
17. Systematic analyses by FDA for HCB in the following
sampling programs: market basket surveys, surveillance of raw
agricultural products, and surveillance of imported products.
Additional activities which might be considered include the following:
1. A study to determine the levels of HCB which produce in-
animals the biochemical aberrations associated with porphyria
cutanea tarda (the syndrome observed in Turkey). This would be
especially valuable since the earliest clinical manifestation
of HCB poisoning in man appears to be hyperphotosensitization, an
effect which cannot be observed with laboratory animals.
2. Metabolic studies in animals, including identification of
the substance responsible for fatalities in nursing animals when
the nurse is fed HCB. (This substance could be HCB itself, but
this has not been demonstrated.)
3. A study of the teratogenic potential of HCB.
-------
-25-
4. A study of the mutagenic potential of HCB.
5. Development of environmentally acceptable and economically
practical methods for disposal of "hex" wastes. Problems with HCB
are bound to recur until this is done.
-------
Bibliography
Acker, L., and Schulte, E. (Orqanochlorine Compounds in the
Human Body) Umschau 71 (23), 848 (1971).
Allis, J.W. - EPA-ORM-Molecular Biology Branch (May 1973)
Avrahami, M., and Steele, R. T.
Hexachlorobenzene I. Accumulation and Elimination of HCB in
Sheep after Oral Dosing. N.Z.J. Agr. Res. 15 (3), 476-481
(1972)
Hexachlorobenzene II. Residues in Laying Pullets Fed HCB in
Their Diet and the Effects on Egg Production, Egg Hatcha-
bility, and on Chickens. N.Z.J. Agr. Res. 15 (3), 480-488
(1972)
Hexachlorobenzene III. The Effects of Feeding HCB to Grow-
ing Chickens. N.Z.J. Agr. Res. 15 (3), 489-494 (1972)
Brady, M. N. and Siyali, D. S., Hexachlorobenzene in Human Body
Fat. Med. J. Aust. (1972) 1, 158-161.
Cam, C. & Nygogosyan, G., Acquired Porphyrin Cutanea Tarda due
to Hexachlorobenzene. J. Am. Med. Assoc., 183, 88-91 (1963)
Curley, e_t aj_. , Nature 242, 333 (1973)
DeMatteis, F. e_t aj_. Nervous and Biochemical Disturbance follow-
ing Hexachlorobenzene Intoxication. Nature 191, 363-6 (1961)
Dow Chemical Co., Plaquemine, La. personal communication
(May 1973)
Enos, H., EPA-Perrine Laboratory (May 1973)
EPA (1972) report - "Industrial Pollution of the Lower
Missippi River in Louisiana, April 1972". - Indiana -
(Evansville) - communication with Dr. R. Tardiff-EPA-
Water Supply Research Lab., Cincinnati
Gilbertson, M., and Reynolds, L.M., (1972) Bulletin of Env.
Contamination and Toxicology Vol. 7, No. 6
Gurfein, L.N. and Pavlova, Z.K. Maximum allowable concentration
of chlorinated benzenes in water reservoirs. Sanitarnaya
Okhrana Vodoemov of Zagryazneniya Promyshlennymi Stochnymi
Vodami. No. 4: 117-127, (1960)
Hawley, G.G., Ed. Condensed Chemical Dictionary, 8tn ed. Van
Nostrand Rheinhold (1971 )
Kirk-Othmer, Encylopedia of Chemical Technology, 2nd Ed.,
Interscience (1966)
-------
-27-
Kociba, R. J. , e_t aJL Toxicologic study of Female Rats
Administered Hexachlorcbutadiene or Hexachlorobenzene
for Thirty Days. Dov; Chemical Co. Midland, Mich.,
Aug. 27 (1971)
Melis, R. Toxic Action of Hexachlorobenzene for Warm-blood-
ed Animals. Nuovi Ann. Ig. 6, 361-7 (1955) (chem. Abstr.)
50, 5170g (1956)
Metcalf, R. L., "Model Ecosystem studies of the environmental
fate of six organochlorine pesticides", in press,
Env. Health Perspectives (1973),
Ockner, R. K. and Schmid, R. Acquired porphyria in man and
rat due to hexachlorobenzene intoxication.
Nature 189:499, (1961 )
Savitskii, I.U., The Basis for Determining Safe Permissible
Concentrations of Hexachlorobenzene and Pentachloronitroben-
zene in the Air. (Russian) Vopr. Prom. i. Selskokhozyais-
trennoi Toksikologii Kievsk, Med. Inst. 158-173 (1964)
(Chem. Abstr. 63, 8952d (1965)
Schmid, R. Cutaneous Porphyria in Turkey. New England J. Med.,
263, 397-398 (1960)
Vulcan Materials Co, Geismar, La. personal communication
(May 1973)
Weir, R. J., Experimental Pre-Emergence Herbicide HCB pure
(new), 90-day dietary Administration - Rats. Unpub.
Report of Hazleton Laboratories, Inc. Sponsored by
Diamond Alkali Co. (1962)
Zitco, V. and Choi, P.M.K. (1972), PCS, and p,p -DDE in Eggs
of Cormorants, Gulls, and Ducks from the Bay of Fundy,
Canada, Bulletin of Env. Contamination and Toxicology
Vol. 7, No. 1.
-------
TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
EPA 560/6-76-014
3. RECIPIENT'S ACCESSION-NO.
4. TITLE AND SUBTITLE
5. REPORT DATE
April 1976
6. PERFORMING ORGAMIZAT'ON CODE
Environmental Contamination from Hexachlorobenzene
7. AUTHOR(S)
Early Warning Branch
Office of Toxic Substances
8. PERFORMING ORGANIZATION REPORT NO
9. PERFORMING ORGANIZATION NAME AND ADDRESS
U.S. Environmental Protection Agency
Office of Toxic Substances
401 M Street SW
Washington, DC 20460
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
U.S. Environmental Protection Agency
Office of Toxic Substances
401 M Street SW
Washington, DC 20460
13. TYPE OF REPORT AND PERIOD COVERED
Final 7/20/73
14. SPONSORING AGENCY CODE
15. SUPPLEMENTARY NOTES
16. ABSTRACT
A series of episodes around the world resulted in recognition of the fact that man
and his environment are being exposed to Hexachlorobenzene (HCB). The finding of
grossly elevated levels in domestic animals, such as at Geismar, Louisiana,
elicited the attention of local State, and Federal officials.
This report summarizes available information in the production, use, and toxicity
of HCB and presents conclusions and activities undertaken to gain a fuller
understanding of the problems associated with this substance so as to formulate
a regulatory posture on this toxic substance.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
Hexachlorobenzene (HCB)
8.
!V,IBUTiO\ STATEMENT
Release Unlimited
h.IDENTIFIERS/OPEN ENDED TERMS
Env. Analysis
Usage
Hazard Assessment
Contamination
19. SECURITY CLASS (This Report/
20. SECURITY CLASS (Thispage)
Unclassified
c. COSAT! Field/Group
21. NO. OF PAO-:d
.32..
22. PRICE
EPA Form 2220-1 (9-73)
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