EPA-540/1-86-053
Environmental Protection
Agency
A Emergency and
Remedial Response
Washington DC 20460
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
EPA
HEALTH EFFECTS ASSESSMENT
FOR HEXACHLOROBUTADIENE
Do not remove. This document
should be retained in the EPA
Region 5 Library Collection.
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EPA/540/1-86-053
September 1984
HEALTH EFFECTS ASSESSMENT
FOR HEXACHLOROBUTADIENE
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
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DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and 1t has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with
hexachlorobutadlene. All estimates of acceptable Intakes and carcinogenic
potency presented 1n this document should be considered as preliminary and
reflect limited resources allocated to this project. Pertinent toxlcologlc
and environmental data were located through on-Hne literature searches of
the Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data
bases. The basic literature searched supporting this document 1s current up
to September, 1984. Secondary sources of Information have also been relied
upon 1n the preparation of this report and represent large-scale health
assessment efforts that entail extensive peer and Agency review. The
following Office of Health and Environmental Assessment (OHEA) sources have
been extensively utilized:
U.S. EPA. 1980a. Ambient Water Quality Criteria for Hexachloro-
butadlene. Environmental Criteria and Assessment Office,
Cincinnati, OH. EPA-440/5-80-053. NTIS PB 81-117640.
U.S. EPA. 1983a. Review of Toxlcologlc Data 1n Support of Evalua-
tion for Carcinogenic Potential of Hexachlorobutadlene. Prepared
by the Carcinogen Assessment Group, OHEA, Washington, DC for the
Office of Solid Waste and Emergency Response, Washington, DC.
The Intent 1n these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited In
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the Interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer 1s not the endpolnt of concern).
The first, the AIS or acceptable Intake subchronlc, 1s an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval (I.e., for an Interval that
does not constitute a significant portion of the llfespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants In ambient air or water where lifetime exposure 1s
assumed. Animal data used for AIS estimates generally Include exposures
with durations of 30-90 days. Subchronlc human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
111
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The AIC, acceptable Intake chronic, Is similar 1n concept to the ADI
(acceptable dally Intake). It 1s an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the Hfespan [see U.S. EPA (1980b) for a discussion
of this concept]. The AIC 1s route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes is insignificant.
Composite scores (CSs) for noncarcinogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development is explained In U.S. EPA (1983b).
For compounds for which there is sufficient evidence of cardnogenidty,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980b). Since cancer is a
process that is not characterized by a threshold, any exposure contributes
an increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-|*s have been computed based on oral
and inhalation data if available.
1v
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ABSTRACT
In order to place the risk assessment evaluation in proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates presented.
Hexachlorobutadlene was treated as a carcinogen by U.S. EPA (1980a).
Limited data are available concerning the carcinogenicity of this compound.
In the only study available, oral exposure to hexachlorobutadlene resulted
in Increased incidence of renal tumors in rats at the highest dose level.
No human data are available. U.S. EPA (1980a), using the data for both male
and female Incidence of renal tubular adenomas and carcinomas in male rats
derived a q-j* for oral exposure of 7.75xlO~2 (mg/kg/day)"1. This risk
assessment has been extensively peer reviewed.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was»the Project
Officer. The final documents 1n this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of Air Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1. ENVIRONMENTAL CHEMISTRY AND FATE
2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . . .
2.1.
2.2.
ORAL
INHALATION
3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.
3.2.
3.3.
3.4.
SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
CHRONIC
3.2.1. Oral
3.2.2. Inhalation ,
TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . . ,
3.3.1. Oral
3.3.2. Inhalation
3.3.3. Other
TOXICANT INTERACTIONS
4. CARCINOGENICITY
4.1.
4.2.
4.3.
4.4.
5. REGUL
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
WEIGHT OF EVIDENCE
ATORY STANDARDS AND CRITERIA
Page
1
, . 3
, . . 3
3
4
4
, . . 4
4
8
. . . 8
8
8
. . . 8
. . . 9
9
9
10
10
. . . 10
10
10
. . . 10
10
. . . 10
10
. . . 13
V11
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TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT 14
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 14
6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 14
6.2.1. Inhalation 14
6.3. CARCINOGENIC POTENCY (q^) 14
6.3.1. Oral 14
7. REFERENCES 16
APPENDIX A: Summary Table for Hexachlorobutadlene 21
APPENDIX B: Cancer Data Sheet for Derivation of qj* 22
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LIST OF TABLES
No. Title Page
3-1 Subchronic Oral Toxldty of Hexachlorobutadlene 5
3-2 Subchronic Inhalation Toxlcity of Hexachlorobutadlene .... 7
4-1 Response to Hexachlorobutadlene Feeding 1n Male and
Female Rats 11
6-1 Basis for q-)* for Hexachlorobutadlene 15
1x
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
BCF B1oconcentrat1on factor
bw Body weight
CAS Chemical Abstract Service
CS Composite score
ppm Parts per million
TLV Threshold limit value
TWA Time-weighted average
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1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
hexachlorobutadlene (CAS No. 87-68-3} are as follows:
Chemical class:
Molecular weight:
Vapor pressure:
Water solubility:
Log octanol/water
partition coefficient:
BCF:
Half-lives 1n water:
chlorinated aliphatic
hydrocarbon
260.72
0.15 mm Hg at 20°C
2 mg/8. at 20°C
4.78
2.3xl03
29-2300
3-30 days 1n river
3-300 days 1n lakes and
groundwater
Callahan et al., 1979
Callahan et al., 1979
Banerjee et al., 1980
calculated from the
equation of Velth
et al., 1979
U.S. EPA, 1980a
Zoeteman et al., 1980
No data regarding the half-life of this compound 1n the atmosphere could be
located 1n the available literature; however, 1t Is likely that the compound
will react with hydroxyl radicals 1n the atmosphere (Singh et al., 1983).
In the absence of any rate constant data for this reaction, 1t Is speculated
that the half-life of this compound will be several weeks 1n the atmosphere,
based on the estimated residence times for the chlorinated ethylenes given
by Singh et al. (1981).
The half-life of hexachlorobutadlene 1n soils could not be located In
the available literature; Based on the expected volatility (Callahan et
al., 1979) and blodegradabUHy 1n aquatic media (Mabey et al., 1981),
significant volatilization and blodegradatlon may not occur In soils.
-1-
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The compound may, however, be sorbed significantly onto soils containing a
high content of organic carbon (U.S. EPA, 1980a). In the absence of
significant loss processes, the persistence of hexachlorobutadiene in soil
may allow some leaching of the compound into groundwater, particularly from
sandy soils.
-2-
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Pertinent data regarding the absorption of hexachlorobutadlene from the
gastrointestinal tract could not be located 1n the available literature.
The available toxldty data Indicate that some absorption does occur
(Chapter 3) (U.S. EPA, 1980a).
2.2. INHALATION
Pertinent data regarding the absorption of Inhaled hexachlorobutadlene
could not be located 1n the available literature.
-3-
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. The subchronlc oral toxldty of hexachlorobutadlene are
summarized In Table 3-1. Most of the Information 1s from the Russian
literature and 1s available only as abstracts; therefore, H cannot be fully
evaluated.
Koclba et al. (1971) administered diets resulting In doses of 1, 3, 10,
30, 65 or 100 mg hexachlorobutadiene/kg bw/day to female rats for 30 days.
The major hlstopathologlcal change observed was degeneration of the renal
tubular epithelium at doses of >30 mg/kg bw/day. In the 10 mg/kg bw/day
group, there was decreased body weight gain with no pathologic alterations.
A marginal change 1n the kidney-to-body weight ratio was observed at 3 mg/kg
bw/day and no effects were observed at 1 mg/kg bw/day.
Schwetz et al. (1977) administered diets resulting 1n doses of 0.2, 2.0
or 20 mg/kg bw/day to male (groups of 10-12) and female (groups of 24) rats
for 140 days. Again, hlstopathologlcal lesions in the -kidneys were the
major effects noted, occurring at doses of >2.0 mg/kg bw/day.
3.1.2. Inhalation. The subchronic Inhalation toxiclty of hexachlorobuta-
dlene 1s summarized 1n Table 3-2. Gage (1970) exposed groups of four male
and four female rats to atmospheres containing 5, 10, 25 or 100 ppm (53,
107, 267 or 1060 mg/m3) hexachlorobutadlene, 6 hours/day, for 12-15 days.
A dose of 1060 mg/m3 produced severe toxiclty and death. Renal damage was
observed 1n the two highest dose groups, but the only effect observed at an
exposure of 107 mg/m3 was a reduced weight gain in the females. No
effects were observed at a concentration of 53 mg/m3.
-4-
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TABLE 3-1
Subchronlc Oral Toxlclty of Hexachlorobutadlene*
Route
Oral
(diet)
Oral
(diet)
Species/
Sex
rat/F
rat/F
rat/F
rat/F
rat/F
rat/F
rat/N
rat/F
rat/N
No. of
Animals
4
4
4
4
4
4
12
24
10
% Hexachlorobutadlene
Purity
99
99
99
99
99
99
99
99
99
Dose
1 mg/kg/day
3 mg/kg/day
10 mg/kg/day
30 mg/kg/day
65 mg/kg/day
100 mg/kg/day
0.2 mg/kg/day
0.2 mg/kg/day
2.0 mg/kg/day
Duration
30 days
30 days
30 days
30 days
30 days
30 days
148 days
148 days
148 days
Observations Reference
No effects. Koclba et al.,
Marginal change In kidney-to-body weight 1971
ratio; no pathologic alterations.
Decreased body weight gain; no patho-
logic alterations.
Renal tubular epithelial degeneration,
Individual cell necrosis and regenera-
tion, decreased body weight gain;
Increase In mean kidney-to-body weight
ratio; Increase In hemoglobin concen-
tration.
No effects among adults or neonates. Schwetz et al.,
No effects among adults or neonates. 1977
Kidney "roughened,* mottled cortex;
rat/N
rat/N
rat/F
Oral
Oral
rat/NR
rat/NR
rat/NR
rat/NR
20
12
24
NR
NR
NR
NR
99
99
99
2.0 mg/kg/day
20 mg/kg/day
20 mg/kg/day
NR
NR
NR
NR
0.0005 mg/kg/day
0.004 mg/kg/day
0.02 mg/kg/day
8.4 mg/kg
100 mg/kg
other kidney changes that normally occur
appeared to be accentuated.
148 days Accentuation of normal kidney changes;
one had renal lesions Identical to those
on 20 mg/kg/day; no effects on neonates.
148 days Change In kidney-to-body weight ratio;
kidney roughened with mottled cortex;
renal tubular dilation and hypertrophy
with foci of renal tubular epithelial
degeneration and regeneration.
148 days Renal tubular dilation and hypertrophy
with foci of renal tubular epithelial
degeneration and regeneration; decreased
values of body and heart weight, Increased
values for relative weight of brain and,
kidney; slight decrease In body weight
of neonates at time of weaning.
6 months Was at threshold level with respect to
toxlclty.
4 months Weakly toxic.
2 months Highly toxic.
NR Severe necrotlc nephrosls, as well as
NR abnormal changes In the brain, liver and
other Internal organs.
Poteryaeva, 1973
Dlmltrlenko and
Vasllos, 1972
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TABLE 3-1 (cont.)
Route
Oral
Oral
Oral
Species/ No. of X Hexachlorobutadlene
Sex Animals Purity
dog/NR NR NR
dog/NR NR NR
guinea NR NR
plg/NR
Dose
1 mg/kg/day
0.05 mg/kg/day
0.004-2
mg/kg/day
Duration Observations 1
6 months Administered to puppies from birth to
6 months. Increased secretion of total
N-contalnlng compounds.
Increased vol. and total acidity of the
gastric juice.
45 days Administered 1.5-3 months postnatal;
Increased total vol., acidity, and
amount of HC1 and chloride secreted
by the stomach.
7 months 2 mg dose caused a decrease In -SH
group cone. In blood plasma without
change In blood protein plasma spectrum.
Reference
Boranova,
1974a.b
Kratvltskaya and
Boroanova, 1974
Murzakaev, 1965
'Source: U.S. EPA. 1980a
NR = Not reported
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TABLE 3-2
Subchronlc Inhalation Toxlclty of Hexachlorobutadlene*
Species/
Sex
Rat/NR
Hlce/NR
Rat/NR
Rat/M
Rat/F
Rat/H
Rat/F
Rat/M
Rat/F
No. of
Animals
NR
NR
NR
4
4
4
4
4
4
X Hexachlorobutadlene
Purity
NR
NR
NR
NR
NR
NR
NR
NR
NR
Dose
24 mg/m»-a1r
24 mg/m»-a1r
0.01 imj/m'-alr
25 ppm (267 mg/ra»)
25 ppm (267 mg/ma)
100 ppm (1060 mg/m')
100 ppm (1060 mg/m*)
10 or 5 ppm
(107 or 53 mg/ma)
10 or 5 ppm
(107 or 53 mg/m»)
Duration
7 months
7 months
6 months
(5 hours dally)
15 dally
for 6 hours
12 dally
for 6 hours
15 dally
for 6 hours
Observations Reference
Caused no alterations. Gulko
et al.. 1964
No effects observed Poteryaeva.
1972
Caused respiratory difficulty; Gage, 1970
decreased weight gain and patho-
logic Injury to the tubular
epithelium of the kidneys.
Severe toxlclty Including death.
Caused no toxlclty except for
retarded weight gain In females
at 10 ppm.
*Source: U.S. EPA, 19BOa
NR = Not reported
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3.2. CHRONIC
3.2.1. Oral. Koclba et al. (1977a,b) administered diets resulting in
doses of 0, 0.2, 2.0 or 20 mg hexachlorobutadiene/kg bw/day to groups of 40
male and 40 female rats for 22-24 months. In the high dose group, body
weight gain In both sexes was depressed. Both relative and absolute kidney
weights were Increased in males and relative kidney weight In females.
Survival was decreased In the males. Urinary coproporphyrin excretion was
significantly Increased 1n male rats by 12 months and in females by 24
months. Histologlcal examination revealed significant abnormalities,
including neoplasms (Section 4.2.1.), in the urinary system.
The effects of 2.0 mg/kg bw/day were much less severe. Urinary copro-
porphyrin excretion was Increased in females after 14 months, and slight
hlstofoglcal changes in the kidneys, possibly including renal tubular
epithelial hyperplasla, were observed at necropsy. No effects were observed
in animals receiving 0.2 mg/kg bw/day.
3.2.2. Inhalation. Pertinent data regarding the chronic inhalation
toxicity of hexachlorobutadlene could not be located 1n the available
literature.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Schwetz et al. (1977) administered diets resulting in doses
of 0.2, 2.0 or 20 mg hexachlorobutadlene/kg bw/day for 90 days before
mating, 15 days during mating, and throughout gestation and lactation. The
only effect on the offspring was a slight decrease in body weight at 21 days
postpartum in the high-dose group. No gross malformations were reported and
neonatal growth, survival and development were normal in the low- and
mid-dose groups.
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3.3.2. Inhalation. Pertinent data regarding the teratogenlcity or other
reproductive effects of Inhaled hexachlorobutadlene could not be located 1n
the available literature.
3.3.3. Other. Female rats were given a single 20 mg/kg subcutaneous
Injection of hexachlorobutadlene prior to breeding (Poteryaeva, 1966).
Toxic effects reported 1n the dams Included glomerulonephrltis and degen-
erative red blood cell changes. An Increase 1n neonatal mortality and
depressed pup body weights were reported. A lack of detail In the reporting
of experimental design and results, combined with poor control pup survival
(79%) make this study difficult to evaluate. In addition, this route of
administration has limited relevance to the present assessment.
3.4. TOXICANT INTERACTIONS
Murzakaev (1967) reported that treatment with hexachlorobutadlene
decreased the sulfhydryl content of blood serum and cerebral cortex homo-
genate. Mlzyukova et al. (1973) subsequently found that administration of
thlols (mercaptlde, cystelne, "unlthlol") 20-30 minutes before a dose of
hexachlorobutadlene significantly reduced the resulting toxic effects, as
determined by survival rates.
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the oral cardnogenlcHy of hexa-
chlorobutadlene 1n humans could not be located 1n the available literature.
4.1.2. Inhalation. Pertinent data regarding the cardnogenlcHy of
Inhaled hexachlorobutadlene 1n humans could not be located 1n the available
literature.
4.2. BIOASSAYS
4.2.1. Oral. Koclba et al. (1977a,b) fed diets resulting 1n doses of 0,
0.2, 2.0 or 20 mg hexachlorobutadiene/kg bw/day to male and female Sprague-
Dawley rats for 2 years (Table 4-1). Total tumor Incidences In control and
treated groups were similar; however, the Incidence of renal tubular neo-
plasms was significantly Increased 1n both sexes at the highest dose level.
No other treatment-related tumors were found.
4.2.2. Inhalation. Pertinent data regarding the cardnogenlcHy of
Inhaled hexachlorobutadlene 1n experimental animals could not be located in
the available literature.
4.3. OTHER RELEVANT DATA
Taylor (1978) tested hexachlorobutadlene for mutagenldty in Salmonella
typhimurlum TA100, both with and without metabolic activation. The low
solubility of hexachlorobutadlene limits the interpretation of this test;
however, hexachlorobutadlene did not appear to be mutagenlc 1n this system.
4.4. WEIGHT OF EVIDENCE
Data are not available regarding the cardnogenlcHy of hexachlorobuta-
dlene 1n humans. The cardnogenldty of this compound has been demonstrated
In animals, but only in one strain of rats. Hence, the overall evidence for
the cardnogenlcHy In animals is best designated as "limited." Applying
-10-
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TABLE 4-1
Response to Hexachlorobutadlene Feeding In Hale and Female Rats3
Doseb
(mg/kg/day)
20.0
2.0
0.2
Control
Numbers
Hale Rat
9/39
0/40
0/40
1/90
% Response
Hale Rat
23
0
0
1.1
Numbers
Female Rat
3/40
0/40
0/40
1/90
% Response
Female Rat
7.5
0
0
1.1
Observations
renal tubular
adenocarclnomas;
undlfferentlated
carcinoma;
metastasis to the
lung
none
none
nephroblastoma
aSource: Kodba et al., 1977a,b
bDose administered for 669 days of a 730-day experimental period.
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the criteria for evaluating the overall weight of evidence for the cardno-
genldty to humans proposed by the Carcinogen Assessment Group of the U.S.
EPA (Federal Register, 1984), hexachlorobutadlene 1s most appropriately
designated a Group C chemical - Possible Human Carcinogen.
-12-
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5. REGULATORY STANDARDS AND CRITERIA
The ACGIH (1980) has recommended a TLV of 0.02 ppm (-0.24 mg/m3),
based on the 2-year feeding study by Koclba et al. (1977a,b). The U.S. EPA
(1980a) estimated that a concentration of 4.47 yg/8. In ambient water
would result 1n an Increased cancer risk of 10~5.
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
Hexachlorobutadlene is a chemical shown to be carcinogenic 1n male rats
and for which a q * has been calculated. It Is Inappropriate, therefore,
to calculate an AIS for this chemical.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
Hexachlorobutadlene 1s a chemical shown to be carcinogenic 1n male rats
and for which a q * has been calculated. It Is Inappropriate, therefore,
to calculate an AIC for this chemical.
6.2.1. Inhalation. Pertinent data regarding the chronic inhalation
toxicity of hexachlorobutadlene could not be located in the available
literature.
6.3. CARCINOGENIC POTENCY (q^)
6.3.1. Oral. Koclba et al. (1977a,b) demonstrated the Induction of renal
tubular adenomas and carcinomas in rats. The U.S. EPA (1980a), using the
tumor incidence in male rats and a linearized multistage model (Table 6-1),
has derived a human q * of 7.75xlO~2 (mg/kg bw/day)"1.
-14-
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TABLE 6-1
Basis for q-j* for Hexachlorobutadlene*
Dose
(mg/kg bw/day)
Incidence
(No. Responding/No. Tested)
0.0
0.2
2.0
20.0
Duration of Experiment = 730 days
Length of Treatment = 669 days
Llfespan of Animals = 730 days
Average Weight = 0.610 kg
1/90
0/40
0/40
9/39
^Source: U.S. EPA, 1980a
-15-
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7. REFERENCES
AC6IH (American Conference on Governmental Industrial Hyg1en1sts). 1980.
Documentation of the Threshold Limit Values. 4th ed. (Includes Supple-
mental Documentation, 1981, 1982, 1983). Cincinnati, OH.
Banerjee, S., S.H. Yalkowsky and S.C. Valvan. 1980. Water solubility and
octanol/water partition coefficient of organlcs. Limitations of the sol-
ubility-partition coefficient correlation. Environ. Sc1. Techno!. 14:
1227-1229.
Boranova, T.I. 1974a. Nitrogen releasing function of the stomach 1n onco-
genesls under the effect of hexachlorobutadlene. Eksp. Issled. Khlm. B1ol.
(no vol.): 198. (Cited 1n U.S. EPA, 1980a)
Boranova, T.I. 1974b. Effect of hexachlorobutadlene on the secretory func-
tion of the stomach of puppies of various ages. Protsessy Obmena Veshchestv
S-kh. Zhlvotn. Uslovlyakh Normy Vozdelstv. Vysokochast. Elektromagn. Pol.
(no vol.): 83. (Cited 1n U.S. EPA, 1980a)
Callahan, M.A., M.W. Sllmak, N.W. Gabel, et al. 1979. Water-Related
Environmental Fate of 129 Priority Pollutants. Vol. II. U.S. EPA, Office
of Water Planning and Standards, Office of Water and Waste Management,
Washington, DC. EPA-440/4-79-029b.
-16-
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D1m1tr1enko, V.D. and A.F. Vasllos. 1972. Kidney damage during experi-
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APPENDIX A
Summary Table for Hexachlorobutadlene
Carcinogenic
Potency
Species
Experimental Effect qi*
Dose/Exposure
Reference
^ Inhalation ND
i
Oral rat 0, 0.2, 2.0 or renal tumors 7.75x10 2 Koclba et al.,
20 mg/kg bw/day (mg/kg but/day)'1 1971; U.S. EPA,
1980a
ND = Not derived
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APPENDIX B
Cancer Data Sheet for Derivation of q-|*
Compound: hexachlorobutadlene
Reference: Koclba et al., 1977a,b
Species, Strain, Sex: rat, Sprague-Dawley, male
Body weight: 0.610 kg (measured)
Length of exposure (le) = 669 days
Length of experiment (Le) = 730 days
Llfespan of animal (L) = 730 days
Tumor site and type: kidney tubules, adenomas and carcinomas
Route, vehicle: oral, diet
Incidence
Transformed Dose*
(mg/kg/day) No. Responding/No. Tested
or Examined
0 1/90
0.18 0/40
1.83 0/40
18.33 9/39
transformed dose expanded for treatment on 669 of 730-day experimental
period.
Unadjusted q-|* from study = 1.598xlO~2 (mg/kg/day)"1
Human q-j* = 7.75xlO~2 (mg/kg/day)'1
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