 |
|
| Record No |
736 |
| CAS Registry No |
87-68-3 |
| CAS Search Date |
1995-02-01 |
| Common Name |
Hexachlorobutadiene |
| CAS Name |
1,3-Butadiene, 1,1,2,3,4,4-hexachloro-, |
| Synonyms |
Hexachlorobutadiene
C-46
GP-40-66:120
HCBD
Perchlorobutadiene
1,3- hexachlorobutadiene
Hexachloro-1,3-butadiene |
| RTECS Number |
EJ0700000 |
| Molecular Formula |
C4 C16 |
| Atomic Elements |
C |
- Topics Available
- 01 Properties
03 Manufacture
04 Acute Toxicity - Terrestrial Animals
06 Acute Toxicity - Aquatic Animals
07 Chronic Toxicity - Terrestrial Animals
08 Chronic Toxicity - Human
09 Chronic Toxicity - Aquatic
10 Phytotoxicity
11 Carcinogenicity
12 Mutagenicity
13 Reproductive and Developmental Effects
14 Other Adverse Effects
15 Pharmacokinetics/Metabolism
16 Bioaccumulation/Bioconcentration
17 Transport Process
18 General Fate Processes
19 Transformation Processes
20 Analysis and Treatment
21 References
-
Physical/chemical hazards:
Toxic when inhaled, ingested, injected ipr or absorbed through the
skin. Moderate acute toxicity, but it is more toxic after chronic
exposure, thus indicating a cumulative effect. (R-1), (R-38) Non
flammable (R-13)
Molecular weight:
261 (R-83)
Physical state at STP:
Liquid (R-12), (R-80)
Color of the pure material:
Clear, colorless (R-12) (R-80)
Odor of the pure material:
Mild (R-13) (R-80) Odor of turpentine (R-61)
Melting point (C.):
-22 to -19 (R-11)
Boiling point (C.):
210 to 220 (R-11), (R-80)
Flash point (C.):
None (R-13), (R-80)
Specific gravity:
15.5/15.5 D=1.675 (R-11), (R-80)
Henry's law constant:
1 ppm=10.7 mg/m3 at 25 C., 760 torr (R-83)
Odor threshold - water:
0.006 ppm (R-28)
Other physical/chemical properties:
Partition coefficient water/air (20 C.)=0.97 (R-59) Spectroscopy
Data: UV spectra maximum wave lengths at 249 and 220 nm (R- 1)
Freezing range: -19 to -22 C; refractive index: 1.552; nonflammable
(R-80) nonflammable (R-13)
Aqueous solubility
Solubility (mg/L):
Temperature (C):
Measured/estimated:
Method used:
References:
Sol | Temp.(C) | Meas/Est | Method | Ref.
--------------------------------------------------------------------
2 | 20 | | | (R-54)
Solubility; other solvents:
Soluble in alcohol and ether. (R-13), (R-80)
Vapor pressure
Vapor pressure (mmHg):
Temperature (C):
Measured/estimated:
Method used:
References:
VP | Temp.(C) | Meas/Est | Method | Ref.
---------------------------------------------------------------------
0.15 | 25 | | | (R-54)
| | | | (R-59)
22 | 100 | | | (R-11)
| | | | (R-80)
n-Octanol/water partition coefficient
Log Kow:
Measured/estimated:
Method used:
References:
Log Kow | Meas/Est | Method | Ref.
----------------------------------------------------------------
4.74 | m | | (R-62)
4.14 | | | (R-14)
3.74 | e | | (R-54)
4.63 | e | | (R-62)
|
-
Common uses of the chemical:
Solvent for natural rubber, synthetic rubber and other polymers.
Used in transformer fluid, heat transfer fluid, hydraulic fluid, and
washing liquor for removing hydrocarbons. (R-11) Used for recovery
of "snift" or chlorine containing gas in chlorine plants. (R-48)
Fumigant against Phylloxera on grapes. (R-1) Solvent for elastomers;
wash for removing C4 and higher hydrocarbons. (R-80) Solvent for
many organic substances (relatively low vapor pressure) used by
chlorine producers intermediate in the manufacture of rubber
compounds and lubricants (R- 94) produced deliberately as a
byproduct in the manufacture of chlorinated hydrocarbons (R-94)
Production of the chemical
Manufacturer (U.S.):
Location (U.S.):
Year (U.S.):
Quantity (U.S.):
References (U.S.):
Manufacturer | Location | Year | Quantity | Ref.
----------------------------------------------------------------------------
NG | U.S. | | 7.3 to 8 | (R-36)
| | | mill. |
| | | lbs./yr. |
NG | U.S. | | 14.5 mill. | (R-36)
| | | lbs./yr. |
NG | U.S. | 1970 to | none | (R-61)
| | date | produced |
Dynamic Nobel, | Imported from | 1974 | 200,000 to | (R-61)
America | Germany | | 500,000 |
| | | lbs sold |
| | | in U.S. |
Chemical synthesis methods:
HCBD is produced deliberately in the U.S. as a by-product of the
manufacture of chlorinated hydrocarbons such as tetrachloroethylene,
trichloroethylene, and carbon tetrachloride. (R-36) Produced by
catalytic chlorination of butadiene. (R-66)
|
|
| ACUTE TOXICITY - TERRESTRIAL ANIMALS |
-
Acute oral toxicity
Species tested:
LD50 (mg/kg):
References:
Species | LD50 | Ref.
------------------------------------------
mus | 87 | (R-36)
rat | 350 | (R-36)
gpg | 90 | (R-36)
rat | 200 | (R-36)
Test conditions: Six animals were used. Compound was administered in
corn oil as a 3% solution.
mus | 87 | (R-36)
Test conditions: Female mice used.
mus | 80 | (R-36)
Test conditions: Male mice used.
rat | 270 | (R-36)
Test conditions: Female rats used.
rat | 64 | (R-36)
Test conditions: Twenty-one day old, male rats used.
rat | 250 | (R-36)
Test conditions: Male rats used.
rat | 82 | (R-16)
rat | 65 | (R-36)
Test conditions: Twenty-one day old, female rats were used.
cat | 187 | (R-16)
mus | 116 | (R-36)
rat | 298 | (R-36)
Test conditions: Male rats were used.
rat | 580 | (R-47)
Test conditions: Adult male rats were given HCBD by gavage in a corn
oil solution. Five to six rats were used per dose level and were
observed until they no longer showed signs of toxicity. The
Litchfield and Wilcoxon method was used to determine the LD50.
Results: The LD50 with 95% confidence limits is 580 (504 to 667).
rat | 65 | (R-97)
rat | 46 |
Test conditions: Neonatal (21- to 22-day old) Sprague- Dawley rats
were used. Five to six rats per group dosed with a corn oil solution
and observed until no signs of toxicity were seen. The Litchfield
and Wilcoxon method was used. Males and females were tested
separately.
Results: The LD50 for males and females with 95% confidence limits
is 65 (46 to 91) mg/kg and 46 (26 to 81) mg/kg, respectively.
Acute dermal toxicity
Species Tested:
LD50 (mg/kg)
References:
Species | LD50 | Ref.
----------------------------------
rbt | 2981 | (R-36)
rat | 4330 |
rbt | 1206 | (R-40)
Results: Value reported as 0.72 mL/kg.
Acute inhalation toxicity
Species Tested:
LC50 (mg/m3)
Duration (hrs):
References:
Species | LC50 | Duration | Ref.
---------------------------------------------
rat | 81,600 | 4.58 | (R-36)
Test conditions: Four rats exposed to 6800 ppm (estimated
concentration, aerosol dose).
Results: Lethal inhalation time for 50% of rats was 275 minutes.
mus | 81,600 | 5.16 | (R-36)
Test conditions: Mice were exposed to 6800 ppm (estimated
concentration, aerosol dose).
Results: Lethal inhalation time for 50% of the mice was 310 min.
gpg | 81,600 | 3.33 | (R-36)
Test conditions: Guinea pigs were exposed to 6800 ppm (estimated
concentration, aerosol dose).
Results: Lethal inhalation time for 50% of the guinea pigs was 200 min.
Acute Toxicity - Terrestrial; Other Studies:
STUDY # 1
A 6-hour LC50 of 10 ppm was determined in a study using mice injected ipr.
(R-9)
STUDY # 2
Dermal exposure of 4 rabbits to 126 mg/kg for 24 hours produced 50%
mortality in all four animals exposed. Propylene glycol was the
solvent.
(R-36)
STUDY # 3
Dermal exposure of 2 rabbits to 126 mg/kg for 4 hours resulted in no
deaths. Propylene glycol was the solvent.
(R-36)
STUDY # 4
Dermal exposure of 2 rabbits to 126 mg/kg for 7 hours produced 50%
mortality. Propylene glycol was the solvent.
(R-36)
STUDY # 5
Inhalation of 500 ppm for 4 hours resulted in the death of all 3
rats used.
(R-36)
STUDY # 6
Inhalation by 6 rats of 133 ppm for 7 hours resulted in death of all
animals.
(R-36)
STUDY # 7
A dose of 100 mg was administered ipr to Sprague-Dawley rats. Urine
osmolality and body weights were reduced. Urine flow rate was
slightly increased. Significant increases in urinary protein,
glucose and ketones were observed. PAH accumulation was reduced.
Transport of other organic compounds was slightly affected.
(R-51)
STUDY # 8
Rats injected ipr with 300 mg/kg showed nephrotoxicity. Four hours
after dose administration, urine osmolality, glomerular filtration,
and drug excretion were reduced. At 24 hours, elevated blood urea
nitrogen was detected. Within 48 hours after HCBD administration, no
hepatotoxic signs were observed.
(R-52)
STUDY # 9
Female mouse, ipr injection, LD50 = 76 mg/kg
(R-36)
STUDY # 10
Male mouse, ipr injection, LD50 = 105 mg/kg.
(R-36)
STUDY # 11
Female rat, ipr injection, LD50 = 175 mg/kg
(R-36)
STUDY # 12
Male rat ipr, injection, LD50 = 216 mg/kg
(R-36)
STUDY # 13
Puppies administered 5 mg/kg orally showed signs of acute toxicity.
Administration at 20 mg/kg was lethal.
(R-19)
STUDY # 14
The oral LD50 in neonatal rats is 1/4 that it is in adult animals.
Female rats were more sensitive to hexachlorobutadiene than males.
(R-1)
STUDY # 15
Decompensatory acidosis resulted in guinea pigs given an oral dose
of 60 or 90 mg HCBD.
(R-17)
STUDY # 16
Minimum lethal dose to mice and rats is 13.6 and 110 mg/kg,
respectively. Mouse and rat LD100 values are 41 and 65 mg/kg,
respectively. Mouse and rat LD50 values are 116 and 270 mg/kg,
respectively (routes of administration not given).
(R-47)
STUDY # 17
Rats administered 100 mg/kg ipr injection had renal tubular necrosis
within 24 hours, damage to proximal tubules, diuresis, increased
proteinuria, and increased excretion of N-acetyl-B-D-
glucosaminidase and alkaline phosphatase. A dose of less than 100
mg/kg resulted in only a mild increase, in protein excretion.
Twenty-four hours after exposure, glomerular filtration rate
(insulin clearance) decreased, clearance of PAH and
N-bromo-acetamide by kidney decreased, and PAH in renal cortical
slices decreased but, N-bromo-acetamide did not.
(R-53)
STUDY # 18
All newborn rats from mothers receiving a single scu injection of 20
mg/kg body weight HCBD before mating died during the next 3 months,
compared with 21.3% in the control group.
(R-1)
STUDY # 19
Oral administration of 30 mg/kg to rats resulted in degeneration of
the protein, fat, and carbohydrate relations in cells and impaired
cell function up to 6 hours later.
(R-8)
STUDY # 20
Fifty female rabbits were given 0.25, 0.50, 0.75, or 1.00 mL/kg
dermally for an 8 hour exposure period. Animals were observed 4
hours later and daily for 2 weeks. Half the remaining rabbits were
killed on the 15th day; the rest were killed 3 weeks later.
Results: Using Bliss' method, the LD50 was calculated to be 0.72
mL/kg. During exposure and for a short time after, treated animals
showed a moderate depression of the CNS. Four animals, 2 each at
1.00 and 0.75 mL/kg, displayed dyspnea and cyanosis and died within
24 hours. During the 14 day observation period, 8 of 11 rabbits died
at the 1.0 mL/kg dose level, 6/10 at 0.75 mL/kg, 2/10 at 0.5 mL/kg,
0/10 and 0/9 at 0.25 mL/kg and control, respectively. At the end of
the exposure period, the skin was hemorrhagic and necrotic; this
process increased with time. Animals that died within 24 hours
showed main lesions in the lungs (congestion and hemorrhage), liver
(congestion and unusual fluidity), and in kidneys (congestion and
pale color). In 3 to 9 days, they showed dermal scar formation, more
pronounced liver fatty degeneration, and kidney damage. In 2 to 5
weeks they showed no liver abnormalities, healed skin lesions, and
slight fibrosis of kidneys. Skin lesions did not increase with
increasing doses, but with time.
(R-40)
STUDY # 21
HCBD was administered to male Sprague-Dawley rats at 300 mg/kg ipr.
Within 4 hours, compromised kidney function was found as decreased
urine osmolality, glomerular filtration rate and drug excretion. At
24 hours, elevated blood urea nitrogen was found. No definitive
signs of hepatotoxicity were observed up to 48 hours after HCBD.
(R-52)
STUDY # 22
A single ipr injection of HCBD (100 mg/kg or greater) produced renal
tubular necrosis in the rat by 24 hours. Damage was to the straight
portion of the proximal tubule. Urine analysis showed diuresis,
increased proteinuria and increased excretion of an alkaline
phosphatase at doses above 100 mg/kg. At doses below 100 mg/kg only
a mild, increase in protein excretion was observed. Twenty four
hours after an ipr injection of 200 mg/kg there was a marked
decrease in the glomerular filtration rate and in the clearance of
the organic ion p- aminohippuric acid and the organic cation
tetraethyl ammonium bromide.
(R-42)
|
| ACUTE TOXICITY - AQUATIC ANIMALS |
-
Acute fish toxicity
Species tested:
Duration (hours):
LC50 (mg/L):
95% Confidence interval (mg/L):
References:
Species | Duration | LC50 | 95% CI | Ref.
------------------------------------------------------------
goldfish | 96 | 0.09 | 0.06 to | (R-21)
(Carassius | | | 0.14 |
auratus) | | | |
Test conditions: Renewal test, concentrations measured.
fathead minnow | 96 | 0.102 | | (R-36)
(Pimephales | | | |
promelas) | | | |
Test conditions: Flow-through test, measured concentrations.
rainbow trout | 96 | 0.320 | | (R-36)
(Salmo | | | |
gairdneri) | | | |
Test conditions: Flow-through test, measured concentrations.
bluegill | 96 | 0.326 | | (R-36)
(Lepomis | | | |
macrochirus) | | | |
Test conditions: Flow-through test, measured concentrations.
guppy (Poecilia | 336 | 0.047 | | (R-85)
reticulata) | | | |
Test conditions: This was a static renewal, unmeasured toxicity
test. Hardness, dissolved oxygen concentration, and temperature of
test water were 25 mg/L as CaCO3, GT 5 mg/L, and 22 +/- 1 C.,
respectively. At each test concentration, eight 2- to 3-month-old
guppies were exposed in 1 L of toxicant in a carrier solvent
(acetone as propanol:2).
goldfish | 24 | 9.0 | | (R-86)
(Carassius | | | |
auratus) | | | |
Test conditions: This was a static renewal, unmeasured toxicity
test. Test water temperature was 20 C. Average weight of goldfish
used was 2 g.
rainbow trout | 96 | 0.320 | 0.268 to | (R-97)
(Salmo | | | 0.381 |
gairdneri) | | | |
bluegill | 96 | 0.324 | 0.312 to |
(Lepomis | | | 0.337 |
macrochirus) | | | |
Test conditions: A flow-through, measured test where the following
water quality parameters were monitored regularly: for rainbow
trout: temperature = 11.9 +/- 0.4 C.; DO = 81.2 +/- 0.7%; hardness =
45.9 +/- 0.6 mg/L CaCO3; alkalinity = 45.7 +/- 0.8 mg/L CaCO3,
acidity = 2.0 +/- 0.1 mg/L CaCO3, and pH = 7.5. For bluegill the
water quality parameters were: temperature = 25.2 +/- 0.2 C.; DO =
93 +/- 3.2%; hardness = 41.7 +/- 2.7 mg/L CaCO3; alkalinity = 46.5
+/- 6.0 mg/L CaCO3, acidity = 2.2 +/- 0.5 mg/L CaCO3; and pH = 7.6
+/- 0.2. Rainbow trout were 5.6 +/- 0.6 cm in length and weighed 2.6
+/- 0.9 g, where as bluegill sunfish were 3.9 +/- 0.5 cm. in length
and weighed 1.5 +/- 0.6 g.
Results: Ninety-six hour LC50s for rainbow trout and bluegill were
reported as 0.320 mg/L (0.268 to 0.3810 and 0.324 mg/L (0.312 to
0.337) (95% confidence interval), respectively.
fathead minnow | 96 | 0.10 | 0.09 to | (R-99)
(Pimephales | | | 0.11 |
promelas) | | | |
Test conditions: Two 2-L/cycle proportional diluters with dilution
factors of 0.6 were used to deliver five toxicant concentrations and
a control, in duplicate, to randomly arranged exposure chambers.
These chambers were all glass aquaria with a working volume of 41 L.
A 16-hour photoperiod was used. Lake Superior water was used for
dilution water. The pH ranged from 6.7 to 7.6 and the means and
ranges for DO, hardness and alkalinity were 8.0 (7.6 to 9.2), 45.1
mg/L as CaCO3 (45.0 to 45.5) and 41.8 mg/L as CaCO3 (35.6 to 43.4),
respectively. The fish were 30 to 35 days old and were held at a
temperature of 25 +/- 2C. The fish were not fed during the exposure
period.
Results: The 96-hour LC50 for fathead minnows was 0.10 mg/L with a
95% confidence interval of 0.09 to 0.11 for hexachlorobutadiene.
fathead minnow | 96 | 0.090 | 0.09 to | (R-98)
(Pimephales | | | 0.10 |
promelas) | | | |
Test conditions: The chemical was 98% pure in a tank volume of 41 L.
The fish were 31 days old. Water quality parameters were:
temperature = 24.9 C.; dissolved oxygen = 8.0 mg/L; hardness = 45.0
mg/L CaCO3; alkalinity = 41.4 mg/L CaCO3; and pH = 7.42.
Results: Affected fish lost schooling behavior and equilibrium prior
to death. The 96-hour LC50 was 0.090 mg/L with a confidence interval
of 0.09 to 0.10 mg/L.
Acute macroinvertebrate toxicity
Species tested:
Duration (hours):
EC50 (mg/L):
95% Confidence interval (mg/L):
References:
Species | Duration | EC50 | 95% CI | Ref.
------------------------------------------------------------
snail | 96 | 0.21 | | (R-21)
Test conditions: Renewal test, measured concentrations.
sow bug | | 0.13 | | (R-20)
(Asellus | | | |
aquaticus) | | | |
snail (Lymnaea | | 0.21 | |
stagnalis) | | | |
Acute toxicity: Saltwater fish
Species tested:
Duration (hours):
LC50 (mg/L):
95% Confidence interval (mg/L):
References:
Species | Duration | LC50 | 95% CI | Ref.
------------------------------------------------------------
sheepshead | 96 | 0.557 | | (R-36)
minnow | | | |
(Cyprinodon | | | |
variegatus) | | | |
Test conditions: Static test, unmeasured concentrations.
molly (Poecilia | 26.5 | 4.2 | | (R-20)
latipinna) | | | |
gulf killifish | 20 | 1.7 | | (R-20)
(Fundulus | | | |
grandis) | | | |
dab flatfish | 96 | 0.45 | | (R-21)
pinfish | 96 | 0.399 | | (R-36)
(Lagodon | | | |
rhomboides) | | | |
Test conditions: Static test, unmeasured concentrations.
Acute toxicity: Saltwater macroinvertebrates
Species tested:
Duration (hours):
LC50 (mg/L):
95% Confidence interval (mg/L):
References:
Species | Duration | LC50 | 95% CI | Ref.
------------------------------------------------------------
mysid shrimp | 96 | 0.059 | | (R-36)
grass shrimp | 96 | 0.032 | |
Test conditions: Static test, unmeasured concentrations.
barnacle | 48 | 0.87 | | (R-21)
nauplii | | | |
Acute toxicity: Other saltwater studies
Species tested:
Duration (hours):
Effect level (mg/L):
95% Confidence interval (mg/L):
References:
Species | Duration | Eff.level | 95% CI | Ref.
--------------------------------------------------------------
sheepshead | 24 | 0.24 | | (R-36)
minnow | | | |
(Cyprinodon | | | |
variegatus) | | | |
pinfish | 24 | 0.18 | |
(Lagodon | | | |
rhomoboides) | | | |
Test conditions: Sheepshead minnow and fish were exposed to
concentrations of GE 0.24 and GE 0.18 mg/L of HCBD.
Results: Within 24 hours, some swam in spirals at the surface of the
water, while others swam on their sides or lay motionless, except
for opercular movement on the bottom.
|
| CHRONIC TOXICITY - TERRESTRIAL ANIMALS |
-
Subchronic/chronic toxicity to terrestrial animals
Species tested:
Route:
Dose (mg/kg/d):
Dosing schedule:
References:
Species | Route | Dose | Schedule | Ref.
-------------------------------------------------------------------
mus | orl | 0.17 | 1 ppm for 13 wk | (R-96)
mus | orl | 0.51 | 3 ppm for 13 wk |
mus | orl | 1.7 | 10 ppm for 13 wk |
mus | orl | 5.1 | 30 ppm for 13 wk |
mus | orl | 17 | 100 ppm for 13 wk |
Test conditions: Thirteen-week studies were conducted in which group
of ten mice/sex received 0, 1, 3, 10, 30 or 100 ppm HCBD in feed.
The mice were seven weeks old and were fed ad libitium. All animals
were observed twice/day and detailed clinical signs were recorded at
least once per week. Body weights and food consumption rates were
also obtained weekly. A necropsy was performed on all animals,
including those found dead. During necropsy all organs and tissues
were examined for grossly visible lesions. The reviewer converted
dose based on the assumption B6C3F1 mice consume 0.171 kg/kg bwt per
day (R-101).
Results: A reduction in kidney weight in the three highest dose
groups of males and in the highest dose group of females was
reported. Female mice were more susceptible to the toxicity of HCBD
than male mice. Based on the histopathological evaluation of the
kidneys, a no-observed adverse effect level was estimated for male
mice at or slightly below 10 ppm; a no-effect level was not seen for
female mice which had renal lesions even at the lowest exposure
level of 1 ppm.
rat | orl | 0.2 | once | (R-82)
rat | orl | 20 | |
Test conditions: Male Sprague-Dawley rats, 4 to 6 per treatment
group were lightly anesthetized, shorn of hair between the shoulder
blades and a small incision was made with a pouch constructed
anterior to the incision. A model 200 L Alzet capsule loaded with
200 uL of a [6-3H) thymidine solution (100 uCi, 0.98 ug in distilled
water) was placed inside the pouch. The animal was allowed to
recover at least 6 hours prior to dosing. HCBD was administered in
corn oil by gavage at a volume of 1 mL/kg body weight. Animals were
sacrificed 7 days after dosing. Livers and kidneys were removed,
processed, and from these tissues DNA was isolated and quantitated.
The 3H content of isolated DNA representative of [6-3H] thymidine
incorporation was assayed for determination of DNA synthesis and
ultimately to determine if HCBD is a genotoxic carcinogen.
Results: There were no statistically significant differences in
weight gain, the kidney weight:body weight ratio, the amount of
DNA/gram of tissue or the rate of DNA synthesis.
rat | orl | 0.2 | daily 7 d/wk for 3 | (R-82)
| | | wk |
rat | orl | 20 | daily 7 d/wk for 3 |
| | | wk |
Test conditions: Male Sprague-Dawley rats, five per group, weighing
180 to 260 grams were dosed by gavage. They were implanted 7 days
prior to termination with [6-3H] thymidine-loaded Alzet osmotic
pumps. After sacrifice, livers and kidneys were removed and
processed for histological exam, DNA was also isolated and
quantitated. The 3H content of isolated DNA was assayed.
Results: Animals dosed at 20 mg/kg had a statistically significant
decrease in weight gain, an increase in kidney-to-body weight ratio
(1.3-fold) and the presence of histopathological changes in renal
tissue. A 1.8-fold increase in renal DNA synthesis was also noted in
these rats, however, the difference was not statistically
significant. Histopathological changes in the kidney were noted in 3
out of five rats. No changes were noted in low dose animals.
rat | orl | 0.2, | daily for 2 yr | (R-45)
rat | orl | 2 | daily for 2 yr |
rat | orl | 20 | daily for 2 yr |
Test conditions: Thirty-nine to 40 Sprague-Dawley rats/sex/dose
level plus 90/sex for controls were used. Males were necropsied at
22 months and females at 24 months.
Results: Ingestion of 20 mg/kg for up to 2 years caused decreased
body weight gain and survival, increased urinary excretion of
coproporphyrin, increased weights of kidneys, increased renal
tubular epithelial hyperplasia/proliferation and renal tubular
adenomas and adenocarcinomas, some of which metastasized to the
lungs. The mid-dose animals exhibited similar but lesser degrees of
toxicity including an increase in urinary coproporphyrin excretion
and an increase in renal tubular epithelial
hyperplasia/proliferation. No neoplasms were attributable to HCBD
ingestion. No effects were seen at the low dose level.
rat | orl | 7.5 | 150 ppm for 18 wk | (R-37)
rat | orl | 75 | 1,500 ppm for 18 wk |
Test conditions: Specific pathogen-free Wistar-derived, 10-week-old
rats were used in a reproduction study.
Results: High dose adult females lost weight progressively and
displayed weakness of hind legs that progressed to ataxia and
paralysis. After week 8 the condition of the animals deteriorated
rapidly and necropsies were performed early at week 10. Extensive
renal tubular degeneration, slight proliferation of bile duct
epithelial cells in the liver, and fragmentation/demyelinization of
nerve fibers were found. Animals from the low-dose group exhibited
the following: significantly lower body weights, relative kidney
weights were markedly increased and in the kidney, hypercellularity
of epithelial lining cells and hydropic degeneration and necrosis of
individual cells in the straight limbs of the proximal tubules. The
reviewer converted ppm to mg/kg/d by assuming that a rat will
consume 0.05 g food/d. (R-79)
rat | orl | 2.5 | 50 ppm 2 wk | (R-37)
rat | orl | 7.5 | 150 ppm 2 wk |
rat | orl | 22.5 | 450 ppm 2 wk |
Test conditions: A range-finding study was conducted with groups of
24 male and female weanling Wistar rats. HCBD was administered in
feed.
Results: Dose-related inhibition of growth was seen in both males
and females. Relative kidney weights were increased in both males
and females at the two highest doses. Histopathologic changes were
seen in all treated animals and were characterized by degeneration
of tubular epithelial cells which occurred in a dose-related manner.
The reviewer converted ppm to mg/kg/d by assuming that a rat will
consume 0.05 g food/d. (R-79)
rat | orl | 0.2 | daily for 2 yr | (R-45)
| | | | (R-44)
rat | orl | 2.0 | daily for 2 yr |
rat | orl | 20 | daily for 2 yr |
Test conditions: Groups of 39 to 40 female and male rats were
administered HCBD at the above dose levels. Control groups consisted
of 90 male and 90 female rats. All rats were 7 weeks old. Terminal
necropsy exams were performed after 22 months for males, and 24
months for females.
Results: Lifetime ingestion of the highest dose level (20 mg/kg)
caused increased mortality (males), decreased body weight gains
(male and female), increased urinary excretion of coproporphyrin
(male and female), and increased terminal weights of kidneys (male
and female). Changes in the kidney included hyperplasia and
neoplasia of the renal tubular epithelium. Some of the nodular
neoplasms in the kidney were determined to be renal tubular adenomas
or adeno-carcinomas, some of which metastasized to the lungs. About
23% of males and 15% of females from the high dose group had renal
tubular neoplasms. At 2.0 mg/kg/day, urinary high dose group had
renal tubular neoplasms. At 2.0 mg/kg/day, urinary excretion of
coproporphyrin (females) and increased hyperplasia of renal tubular
epithelium was found. No neoplasms related to treatment at this dose
were found. Administration of 0.2 mg/kg/day caused no ill effects.
gpg | orl | 0.004 | daily for 7 mo | (R-46)
gpg | orl | 2.0 | daily for 7 mo |
Results: The 2 mg/kg dose caused a decrease of SH group
concentration in blood plasma without any change in blood plasma
protein spectrum. Hexachlorobutadiene probably affected the SH
groups directly. Small HCBD doses increased the ascorbic acid
concentration in internal organs and lowered the phagocytic activity
of blood leukocytes. The doses were reported as a range from 0.004
to 2.0 mg/kg. Non-english primary reference; data are cited from
Chemical Abstracts.
qal | orl | | 0.3 ppm of diet for | (R-50)
| | | 90 d |
qal | or | | 3 ppm of diet for 90 |
| | | d |
qal | orl | | 10 ppm of diet for |
| | | 90 d |
qal | orl | | 30 ppm of diet for |
| | | 90 d |
Results: Adult male and female Japanese quail were fed diets
containing the above dose levels of HCBD. No effects on body weight,
demeanor, food consumption, egg production, percent fertility and
hatchability of eggs, survival of chicks or eggshell thickness were
seen. There were no signs of toxicity or altered behavior during the
study and there were no gross or histopathological alterations noted
in organs or tissues at autopsy which could be attributed to
treatment. The authors concluded the no-effect dose level was
greater than 5 to 6 mg/kg/day. The concentration of HCBD in the eggs
at the termination of the study was approximately 0.1 to 0.2 times
the concentration that was in the diet.
rbt | orl | 10 | daily for 20 d | (R-18)
Results: Caused uncompensated acidosis. Non-english primary
reference; data are cited from Chemical Abstracts.
rbt | skn | NG | | (R-24)
gpg | skn | NG | |
Results: HCBD was a moderate irritant to the skin and ocular mucous
membranes of rabbits and was a contact allergen in guinea pigs.
Non-english primary reference; data are cited from Chemical
Abstracts.
rbt | | NG | | (R-25)
mus | | NG | |
gpg | | NG | |
cat | | NG | |
Results: HCBD was poisonous by inhalation, oral administration and
topical application to rabbits, mice, guinea pigs and cats. It
caused leukocytosis and lymphocytosis along with decreased
erythrocytic osmosis resistance. There was also evidence of acidosis
and a reduction in vitamin B1 and C levels in the internal organs.
HCBD increased residual serum N and decreased total blood protein
levels along with enhanced internal organ transaminase and decreased
blood peroxidase and catalase activities. Also observed were
immunological depression and decreased antibody formation.
Non-english primary reference; data are cited from Chemical
Abstracts
rat | orl | NG | NG | (R-26)
gpg | orl | NG | NG |
Results: HCBD administered to rats and guinea pigs caused
disturbances in the metabolism of vitamins B1 and C, resulting in
excessive loss of vitamins. Vitamin B1 was shown to be an effective
antidote for HCBD poisoning, lessening acidosis and pathological
changes in the peripheral blood and internal organs. Non-english
primary reference; data are cited from Chemical Abstracts.
mus | NG | NG | NG | (R-23)
Results: Behavioral studies with mice show that HCBD probably
affects the central nervous system. It also causes severe renal and
hepatic effects. Non-english primary reference; data are cited from
Chemical Abstracts.
rbt | orl | 1 | daily for 3 mo | (R-18)
Results: Caused compensated metabolic acidosis and changes in blood
electrolyte levels. Non-english primary reference; data are cited
from Chemical Abstracts.
dog | orl | 0.05 | daily for 45 d | (R-19)
| | | | (R-29)
Results: HCB caused an increase in total volume acidity, an increase
in the amount of HC and Cl secreted by the stomach, and irritated
the gastric mucosa. Growth rates of the puppies were not affected.
Non-english primary reference; data are cited from Chemical
Abstracts.
rat | orl | 0.4 | daily for 13 wk | (R-37)
rat | orl | 1.0 | daily for 13 wk |
rat | orl | 2.5 | daily for 13 wk |
rat | orl | 6.3 | daily for 13 wk |
rat | orl | 15.6 | daily for 13 wk |
Test conditions: Ten male and ten female weanling Wistar rats per
group were dosed by gavage. Blood and urine samples were analyzed
and a complete necropsy was conducted.
Results: The general health of the rats was unaffected except for a
dose-related decrease in body weights of animals given 6.3 and 15.6
mg HCBD/kg/day. At 15.6 mg/kg/day, the weight gain of animals of
both sexes was less than 60% of the controls. Degeneration of
proximal renal tubules occurred at doses of 2.5 and 6.3 mg/kg or
more in males and females, respectively. Urine-concentrating ability
was significantly reduced in females at doses of 2.5 mg/kg or more
and in males at 15 mg/kg. Relative kidney weights were increased at
the 2 highest doses. Increased liver weights were noted at these
levels, also. In females, liver weights were increased only at 15.6
mg/kg dose. No-effect-levels were determined to be 1 mg/kg/day in
females and 2.5 mg/kg/day in males.
rat | orl | 1.0 | daily for 30 d | (R-39)
rat | orl | 3.0 | daily for 30 d |
rat | orl | 10 | daily for 30 d |
rat | orl | 30 | daily for 30 d |
rat | orl | 65 | daily for 30 d |
rat | orl | 100 | daily for 30 d |
Test conditions: Twenty-eight female weanling rats, 4 rats per dose
level, were tested. All rats were killed on day 30. Blood samples
were taken, organ weights were recorded and tissues were
histologically examined. The student t-test was used to compare
treated and control animals.
Results: The animals displayed no abnormalities in appearance or
behavior. There was a significant decrease in food consumption at
the 30, 65, and 100 mg/kg/day dose levels. Consumption rates at 1
and 3 mg/kg/day were similar to controls. At 30, 65 and 100
mg/kg/day, there was also a decrease in body weight as early as the
first or second week. The 1 and 3 mg/kg/day groups were comparable
to controls. Animals receiving 100 or 165 mg/kg/day exhibited a
depletion in abdominal fat deposits. Renal tubular degeneration
occurred in rats receiving 30, 65 or 100 mg/kg/day HCBD. There were
no compound-related pathologic alterations in rats receiving 1, 3 or
10 mg/kg/day. Rats receiving 30, 65 or 100 mg/kg/day also displayed
hepatic alterations. Rats receiving 10, 30, 65, or 100 mg/kg/day had
increased hemoglobin concentrations. Rats that received 20, 65 or
100 mg/kg/day had a significant increase in the mean kidney weight:
body weight ratio. The mean brain weight: body weight ratio and mean
liver weight: body weight ratios also increased. The authors
considered 3 mg/kg/d to be the NOAEL, but 1 mg/kg/d may be more
appropriate.
rat | ihl | 6.1 | 15 6-hour exposures | (R-72)
rat | ihl | 12.15 | 15 6-hour exposures |
rat | ihl | 30.4 | 15 6-hour exposures |
rat | ihl | 121.5 | 12 6-hour exposures |
rat | ihl | 202.5 | 2 4-hour exposures |
Test conditions: Four male and 4 female Alderly Park rats (200 g)
were used.
Results: No toxic effects were seen at the low dose. Retarded weight
gain in females was seen at 10 ppm. At 25 ppm, the following effects
were seen: decreased weight gain in females and pale, enlarged
kidneys, respiratory difficulties and damage to renal proximal
tubules. At 100 ppm: eye and nose irritation, decreased body
weights, respiratory difficulty, slight anemia in females and pale
and enlarged kidneys as well as degeneration of renal cortical
tubules with epithelial regeneration were noted. At 250 ppm, eye and
nose irritation, respiratory difficulties, degeneration of middle
renal proximal tubules and of the adrenal cortex occurred. Females
were affected more than males. The reviewer converted ppm to mg/kg/d
by assuming that a 380 g rat will breathe 0.173 m3/d. (R-72)
rat | skn | | 3.0 to 3.5 g/kg | (R-5)
Results: Dermal application at the above concentrations stimulated
motility and evoked aggressive behavior. Later, animals lost weight,
motility decreased and ceased, and their extremities became
paralyzed. Blood concentrations of hemoglobin, adrenal ascorbic
acid, and plasma albumins decreased. Concentration of plasma
globulins increased and the number of red cells decreased.
Non-english primary reference; data are cited from Chemical
Abstracts.
rat | NG | 2 | 6 mo | (R-7)
rat | NG | 7 | 6 mo |
Results: Morphological changes (parenchymatous dystrophic lesions)
in liver, kidneys and myocardium and circulation disturbances were
observed. Seven mg/kg slowed down the formation of positive
conditioned reflexes and accelerated the elaboration of
differentiation. Non-english primary reference; data are cited from
Chemical Abstracts.
rat | orl | 0.2 | daily for 90 d prior | (R-35)
| | | to mating, then |
| | | daily for 15 d and |
| | | during and |
| | | throughout gestation |
| | | and lactation |
rat | orl | 2.0 | daily for 90 d prior |
| | | to mating, then |
| | | daily for 15 d and |
| | | during and |
| | | throughout gestation |
| | | and lactation |
rat | orl | 20 | daily for 90 d prior |
| | | to mating, then |
| | | daily for 15 d and |
| | | during and |
| | | throughout gestation |
| | | and lactation |
Test conditions: Ten male and 20 female Sprague-Dawley rats were in
the control and low-dose groups. The middle-dose and high-dose
groups consisted of 12 males and 24 females. After 21 days of
lactation the females and their young were killed and necropsies
performed.
Results: Body weights and food consumption were significantly
decreased in high and low dose rats. Kidney and liver weights were
significantly increased in high dose male rats. High-dose females
had significantly increased relative brain and kidney weights. High
dose males and females had renal tubular dilatation and hypertrophy
with foci of renal tubular epithelial degeneration and regeneration
in kidneys. One female rat at the mid-dose level had identical renal
lesions. Low-dose rats did not exhibit any effects.
rat | ipr | | | (R-51)
HCBD administered ipr to male Sprague-Dawley rats caused a reduction
in urine osmolality and body weight-urine flow rate increased
slightly and marked increases in urinary protein, glucose and
ketones were observed. After daily administration of successive days
with various doses, a graded response was observed on both transport
and overall renal function.
Terrestrial animals-NOAELs
Species tested:
NOAEL (mg/kg/d):
References:
Species | NOAEL | Ref.
-------------------------------------------------------
rat | 1 mg/kg/d (f) and 2.5 | (R-37)
| mg/kg/d (m) |
rat | 0.2 mg/kg/d | (R-45)
rat | 3.0 mg/kg/d | (R-39)
qal | 5 to 6 mg/kg/d | (R-50)
rat | 0.2 mg/kg | (R-82)
rat | 0.2 mg/kg | (R-35)
rat | 5 ppm | (R-72)
|
| CHRONIC TOXICITY - HUMANS |
-
Subacute/chronic toxicity; humans:
Route:
Dose:
Dosing schedule:
References:
Route | Dose | Schedule | Ref.
---------------------------------------------------------------
ihl | 0.8 to 30 mg/m3 | seasonally | (R-1)
A group of 205 vineyard workers exposed seasonally to HCBD and
polychlorobutane-80 (HCBD concentration = 0.8 to 30 mg/m3 showed
multiple toxic effects contributing to the development of
hypotension, cardiac disease, chronic bronchitis, disturbances of
nervous function and chronic hepatitis.
|
| CHRONIC TOXICITY - AQUATIC ANIMALS |
-
Chronic toxicity; freshwater species
Species tested:
Study type:
Highest no observable adverse effect level (mg/L):
Lowest observable adverse effect level (mg/L):
Maximum adverse toxicant concentration (mg/L):
References:
Species | Study type | HNOAEL | LOAEL | MATC | Ref.
-------------------------------------------------------------------------------
fathead minnow | E-L | 0.0065 | 0.013 | 0.0092 | (R-84)
(Pimephales | | | | |
promelas) | | | | |
Test conditions: This was a flow-through, measured toxicity test.
Toxicant was 98 to 99% pure and was administered without a carrier
solvent. Water temperature was 25 +/- 1 C. Mean total hardness,
alkalinity, and acidity were 45, 42, and 3 mg/L as CaCO3,
respectively. Mean dissolved oxygen concentration and pH were 7.0
mg/L and 7.4, respectively. Four replicates of 30 eggs, 2 to 8 hours
old, were used at each test concentration. The test was terminated
28 days after hatching.
Results: MATC is based both on reduced larval survival and growth
(weight).
goldfish | PLC | 0.003 | | | (R-21)
(Carassius | | | | |
auratus) | | | | |
Test conditions: Groups of 5 goldfish were exposed to added
concentrations of 0, 0.5, 5, 16 and 5 ppb HCBD in a static bioassay
for 49 or 67 days. Test solutions were renewed daily. Average
concentrations measured were 0, 0.3, 3, 9.6 and 30 ppb. Water pH was
7.6 and temperature averaged 19 C.
Results: In the 30 and 9.6 ppb groups, loss of equilibrium and
incoordination were observed in the test. Thirty ppb resulted in
diminished weight gain. Exposure to 9.6 ppb also resulted in
increased relative liver weight. Statistical analysis was made with
Wilcoxon's test. Hematologic data revealed no differences between
controls and treated groups. A no-toxic effect level was established
as 3 ppb. Authors suggest additional studies to determine
reproductive success of freshwater organisms and the development of
small fry should be conducted.
largemouth bass | | | 0.00343 to | | (R-20)
(Micropterus | | | 0.03195 | |
salmoides) | | | | |
Test conditions: A concentration of 0.00343 to 0.03195 was tested
for 10 d.
Results: Fish had elevated blood corticosteroid levels, suggesting a
stressful effect.
molly (Poecilia | | | | 1.2 | (R-20)
latipinna) | | | | |
Results: A 138-hour test, reported as an LC50 value.
Chronic toxicity: other freshwater life
Species tested:
Duration (hours):
Effect level (mg/L):
References:
Species | Duration | Eff.level | Ref.
-----------------------------------------------------
water flea | NG | 3 | (R-4)
(Daphnia magna) | | |
Results: One percent of the population survived and produced
resistant descendants.
crayfish | 5 d | 0.336 | (R-20)
(Procambarus | | |
clarki) | | |
Results: Reported as LC50 value.
|
-
Phytotoxicity: Terrestrial plants:
STUDY # 1
Immersion of sugar beet seeds at concentrations of 60 to 240 ug
HCBD/seed resulted in increased root length and stem length in
seedlings. Immersion of corn seeds in concentrations of 39 to 1,500
ug/seed stimulated germination and growth. Wheat seeds immersed in
concentrations of 2.2 to 70.4 ug/seed resulted in stimulated root
growth. When applied to soil at a concentration of 25 mg/kg,
thematic stems and roots increased in length. Fifty ug/kg in soil
increased total and root weight of tomatoes. One-hundred mg/kg
applied to soil increased tobacco seedling weight.
(R-31)
STUDY # 2
One-2 mg/tomato seedling or 60 mg/kg applied to sod resulted in
increased yield of early fruit by GE 20%.
(R-32)
STUDY # 3
Bean cuttings immersed in 12.5 to 800 mg for 4.5 hours resulted in
increased number, weight and length of roots.
(R-33)
STUDY # 4
Fumigation of growing grapes with HCBD increased the activity of
certain enzymes and increased leaf dry weight and leaf chlorophyll.
(R-34)
|
|
-
IARC determination:
There is limited evidence that hexachlorobutadiene is carcinogenic
in rats. (R-1)
Carcinogenicity positive references:
(R-45)
Carcinogenicity negative references:
(R-41) (R-43) (R-82)
Animal carcinogenicity studies
Species tested:
Exposure route:
Dose (mg/kg or mg/m3):
Dosing schedule:
References:
Species | Route | Dose | Schedule | Ref.
------------------------------------------------------------------
rat | orl | 0.2 | daily for 24 mo | (R-45)
rat | orl | 2.0 | daily for 24 mo |
rat | orl | 20 | daily for 24 mo |
Test conditions: Thirty-nine to 40 eight-week-old Sprague-Dawley
rats/sex/dose label plus 90/sex for controls were used. Males were
necropsied at 22 months and females at 24 months.
Results: Ingestion of 20 mg/kg HCBD was associated with the
development of renal tubular adenomas and adenocarcinomas. They
developed as singular or multiple neoplasms within one or both
kidneys: two of these metastasized to the lungs. Twenty-three
percent (9/39) of the males developed tumors (controls = 1.1%) and
15% (6/40) of the females developed tumors (control = 0/90). Total
tumor incidences in males were 39/90 for controls, 24/40 for the low
dose group, 14/40 for the mid-dose group and 15/39 for the high dose
group. Total tumor incidences in females were 82/90 for controls,
35/40 for the low-dose group, 37/40 for the mid-dose group and 39/40
for the high dose group.
rat | orl | 0.2 | once | (R-82)
rat | orl | 20 | once |
Test conditions: Male Sprague-Dawley rats, 4 to 6 per treatment
group were lightly anesthetized, shorn of hair between the shoulder
blades and a small incision was made with a pouch constructed
anterior to the incision. A model 200 L Alzet capsule loaded with
200 uL of a [6-H] thymidine solution (100 uCi, 0.98 ug in distilled
water) was placed inside the pouch. The animal was allowed to
recover at least 6 hours prior to dosing. HCBD was administered in
corn oil by gavage at a volume of 1 mL/kg body weight. Animals were
sacrificed 7 days after dosing. Livers and kidneys were removed,
processed, and from these tissues DNA was isolated and quantitated.
The 3H content of isolated DNA representative of [6-3H] thymidine
incorporation was assayed for determination of DNA synthesis and
ultimately to determine if HCBD is a genotoxic carcinogen.
Results: There were no statistically significant differences in
weight gain, the kidney weight:body weight ratio, the amount of
DNA/gram of tissue or the rate of DNA synthesis.
mus | skn | 64 | 3 times wk | (R-41)
mus | skn | 192 | 3 times wk |
Test conditions: Groups of 30 female Ha:ICR Swiss mice received
repeated skin application at the above dose levels for life.
Controls consisted of a solvent control group of 30 mice receiving
0.1 mL acetone dermally and an untreated group of 100 mice.
Results: No skin papillomas were observed in any of the test or
control groups. Additionally, no significant differences between
controls and treated animals were observed for the incidence of
distance tumors. The reviewer converted mg/mus to mg/kd/d by
assuming a 3,125g bwt/mouse (R-79).
mus | ipr | 4 | 3 times wk | (R-43)
| | | equaling 13 |
| | | injections |
mus | ipr | 8 | 3 times wk |
| | | equaling 12 |
| | | injections |
Test conditions: HCBD was injected ipr 3 times a week into groups of
20 strain A male mice. A solvent control group of 20 mice received
injections of tricarpylin 3 times/week for a total of 24 injections.
Twenty-four weeks after the first injection, mice were sacrificed
and their lungs were examined for adenomas. The student t- test was
used to compare treated and control groups.
Results: HCBD did not significantly increase the number of lung
adenomas in HCBD-treated mice.
Other carcinogenicity studies:
STUDY # 1
This was an initiation-promotion experiment. A group of 30 female
Ha:ICR Swiss mice received a single dermal application of 15.0 mg
HCBD in 0.2 mL acetone followed 14 days later by 5 ug PMA (phorbol
myristate acetate) in 0.2 mL acetone 3 times weekly. PMA controls
consisted of one group of 120 receiving 2.5 ug PMA/application and
another group of 90 mice receiving 5 ug/application.
Results: Initiation with HCB produced papillomas in 5/30 mice. The
first tumor appeared after 63 days. In the controls, 9/120 mice
dosed with 2.5 ug PMA/application developed papillomas, and 6/90
controls dosed with 5.0 ug/application developed papillomas. The
incidence of skin papillomas in the test group was not significant
(p LT 0.05).
(R-41)
STUDY # 2
An in vitro morphological transformation assay using Syrian hamster
embryo fibroblasts was conducted at doses of 5, 10, 15 and 20 ug/mL
HCBD. The lowest dose at which HCBD induces morphological
transformation is greater than or equal to 10 ug/mL.
(R-91)
|
-
Gene mutation; positive references:
(R-49) (R-91) (R-93)
Gene mutation; negative references:
(R-92)
Gene mutation studies
Assay type:
Species and cell type:
Exposure route:
Dose:
References:
Assay type | Species | Route | Dose | Ref.
----------------------------------------------------------------------------
Ames assay | Salmonella | | NG | (R-49)
| typhimurium | | |
| TA1535, TA100 | | |
Results: HCBD was positive in Ames test with and without activation.
(No study details available).
Ames assay | Salmonella | in vitro | 0 to 10 ug/L | (R-92)
| typhimurium | | |
| TA98 and TA100 | | |
Test conditions: A modified Ames assay was used to determine the
mutagenic properties of HCBD in strains TA98 and TA100 in the
presence or absence of S9 mix.
Results: HCBD was not mutagenic with or without S9-mix.
Bacterial | Salmonella | in vitro | 0.001, 0.01, | (R-93)
mutation assay | typhimurium | | 0.1, 1, 10 |
| TA100 | | ug/plate |
Test conditions: The mutagenicity system used was a preincubation
method similar to that described by Yohagi, et al., (1975). The test
was conducted with and without S9 mix.
Results: After metabolic activation, HCBD elicits a dose-dependent
mutagenic effect at concentrations of 0.1 to 1.0 ug/plate. The
effect was achieved only by adding S9 mix with an increased protein
content.
DNA damage/repair; positive references:
(R-91)
DNA damage/repair studies
Assay type:
Species and cell type:
Exposure route:
Dose:
References:
Assay type | Species | Route | Dose | Ref.
-----------------------------------------------------------------------
UDS assay | Syrian hamster | in vitro | | (R-91)
| embryo | | |
| fibroblast | | |
Test conditions: The genotoxicity of HCBD was investigated via
induction of unscheduled DNA synthesis both in the presence and
absence of an exogenous metabolizing system. The exact doses were
not presented but from a graph they appear to be approximately 2, 5;
approximately 7.5, 10; and approximately 12 ug/mL.
Results: The lowest effective dose for UDS induction was 2 ug/mL.
HCBD induced UDS in SHE cells without application of a metabolizing
system. With an exogenous metabolizing system, the intensity of UDS
induction is increased 3-fold.
|
| REPRODUCTIVE AND DEVELOPMENTAL EFFECTS |
-
Reproductive effects; positive references:
(R-35) (R-37)
Reproductive effects; negative references:
(R-35)
Mammalian studies
Species tested:
Exposure route:
Dose (mg/kg/d):
Dosing schedule:
References:
Species | Route | Dose | Schedule | Ref.
-----------------------------------------------------------------------
rat | orl | 0.2 | daily for 90 d | (R-35)
| | | prior to |
| | | mating, then |
| | | daily for 15 d |
| | | and during and |
| | | throughout |
| | | gestation and |
| | | lactation |
rat | orl | 2.0 | daily for 90 d |
| | | prior to |
| | | mating, then |
| | | daily for 15 d |
| | | and during and |
| | | throughout |
| | | gestation and |
| | | lactation |
rat | orl | 20 | daily for 90 d |
| | | prior to |
| | | mating, then |
| | | daily for 15 d |
| | | and during and |
| | | throughout |
| | | gestation and |
| | | lactation |
Test conditions: Ten male and 20 female Sprague-Dawley rats were
used in the control and low-dose groups. Twelve male and 24 female
rats were used in the middle and high-dose groups.
Results: There was no effect on pregnancy or neonatal survival and
development.
rat | orl | 7.5 | 18 wk | (R-37)
rat | orl | 75 | 18 wk |
Test conditions: Eighteen female and 6 male, specific pathogen-free
Wistar-derived, 10-week-old rats were divided into 3 groups. After 4
weeks of dosing the females, two untreated males were placed with
the females for 3 weeks. Females were allowed to produce litters and
at week 18 all animals were sacrificed. Major organs and tissues
were histopathologically examined.
Results: None of the high-dose females conceived. Low-dose pups
exhibited significantly decreased body weights at day 0, day 10 and
day 20. The adult females from the high dose lost weight
progressively and weakness of the hind legs developed into ataxia
and paralysis. Necropsies were performed during week 10. Abnormal
pathology included extensive renal tubular degeneration,
proliferation of bile duct epithelial cells and
fragmentation/demyelination of nerve fibers. Kidney changes were
noted in low dose females (adults). The reviewer converted ppm
values to mg/kg/d by assuming that rats eat 0.05 g/100g bwt/d (R-
79).
rat | orl | 0.2 | 90 d plus | (R-35)
rat | orl | 2 | 90 d plus |
rat | orl | 20 | 90 d plus |
Test conditions: Seven-week-old male and female Sprague-Dawley rats
were used. There were 10 males and 20 females at the two lower dose
levels plus 12 males and 24 females at the high dose and 17 males
and 34 females as controls. The animals received treated diets for
90 days after which each male was placed with 2 females for 15 days.
They were then separated and test diets were continued throughout
gestation and for 21 days following parturition.
Results: The two high dose groups exhibited signs of toxicity,
decreased weight gain and food consumption as well as alterations in
kidney structure. There was no effect on pregnancy or neonatal
survival and development. High dose neonates had significantly lower
body weights at weaning and at 21 days of age. The NOAEL for
neonates is 2.0 mg/kg and 0.2 mg/kg for adults.
Teratogenicity NOAELs
Species tested:
No observable adverse effect level:
References:
Species tested | NOAEL | Ref.
-----------------------------------------------------------------
rat | 2.0 mg/kg | (R-35)
|
-
Other adverse effects:
STUDY # 1
HCBD at 500 to 1000 kg/ha was very effective against phylloxera (a
genus of insect especially damaging to grapes), but was toxic to
vine and soil microflora.
(R-30)
STUDY # 2
Organoleptic limit = 0.01 mg/L in the USSR, 1970.
(R-11)
STUDY # 3
Rats treated with 300 mg/kg (route not specified) showed ascorbic
acid and glutathione in liver increased by 26.8% and 57%,
respectively. Glutathione content in kidneys increased by 29%.
Succinate oxidase and cytochrome oxidase activity in internal organs
decreased by 2.7 to 33.8%.
(R-6)
|
| PHARMACOKINETICS/METABOLISM |
-
Pharmacokinetics/metabolism studies:
STUDY # 1
In rats, hexachlorobutadiene was found in lung, blood, liver, brain,
kidney, spleen and mesentery after a single injection (dose
unspecified) and was excreted in the urine for 7 days.
(R-1)
STUDY # 2
In the kidney, the highest concentration was observed in the
proximal section of the nephron.
(R-1)
STUDY # 3
HCBD was detected in rat tissues and in the blood and urine after
single (71 g/mL) and repeated (3 ug/mL) injections. HCBD was found
in the blood, liver and brain 3 hours after a single injection and
in the kidneys, spleen and mesentery after 6 hours. HCBD was
retained in lung tissue for 3 days and excreted in the urine for 7
days. Rats were almost free of HCBD after 2 weeks. HCBD was absent
in rats 1 weeks after termination of chronic administrations. HCBD
was not found in the cardiac or skeletal muscles, skin, or
gastro-intestinal tract.
(R-48)
STUDY # 4
Oral doses of a mixture of seven chlorinated hydrocarbons (2
mg/kg/component and 4 mg/kg/component) were given to rats daily for
up to 12 weeks. Rats sacrificed at 4, 8, and 12 weeks had roughly 7
mg/kg or less HCBD accumulated in fatty tissue taken from the inner
genital and kidney regions. Concentrations of HCBD in tissues were
apparently the same at both dose levels. The quantity found in the
liver, heart, kidney and blood was less than that found in the fatty
tissue. These results showed that HCBD did not have a strong
tendency to accumulate in fatty tissue of selected organs if
administered in a mixture with other chlorinated hydrocarbons, some
of which were aromatic and accumulated significantly in the fat.
(R-36)
|
|
| BIOACCUMULATION/BIOCONCENTRATION |
-
Aquatic bioaccumulation studies
Species tested:
BCF value reported:
Test type:
Test duration (days):
Tissue type:
Percent lipid content:
Exposure concentration (mg/L):
References:
Species | BCF | Type | Dur. | Tissue | % fat | Conc. | Ref.
-------------------------------------------------------------------------------
dab (Limanda | 700 | FT | 27 | fil | | 0.0016 | (R-90)
limanda) | | | to | | | |
| | | 39 | | | |
dab (Limanda | 10,000 | FT | 27 | liv | | 0.0016 |
limanda) | | | to | | | |
| | | 39 | | | |
plaice | 500 | FT | 21 | fil | | 0.0017 |
(Pleuronectes | | | to | | | |
platessa) | | | 106 | | | |
plaice | 7,000 | FT | 21 | liv | | 0.0017 |
(Pleuronectes | | | to | | | |
platessa) | | | 106 | | | |
mussel | 2,000 | FT | 38 | WB | | 0.0013 |
(Mytilus | | | | | | |
edulis) | | | | | | |
mussel | 900 | FT | 50 | WB | | 0.0016 |
(Mytilis | | | | | | |
edulis) | | | | | | |
mussel | 500 | FT | 21 | foot | | 0.0017 |
(Mytilis | | | to | | | |
edulis) | | | 106 | | | |
mussel | 1,000 | FT | 21 | gill | | 0.0017 |
(Mytilis | | | to | | | |
edulis) | | | 106 | | | |
mussel | 2,000 | FT | 21 | gonad | | 0.0017 |
(Mytilus | | | to | | | |
edulis) | | | 106 | | | |
mussel | 3,000 | FT | 21 | org | | 0.0017 |
(Mytilis | | | to | | | |
edulis) | | | 106 | | | |
Test conditions: These saltwater species were exposed to
hexachlorobutadiene and analyzed by GLC. When plaice were tested for
bioaccumulation potential, they were fed mussels which had been
previously exposed and had a mean concentration level of 1.8 ppm.
The fish were fed daily with minced mussel tissue equivalent to 5%
of their wet mass. Very few details about the study were reported.
Results: Overall laboratory accumulation factors were similar to
those that the authors calculated from Liverpool Bay sampling. The
liver/flesh ratios were also the same in both lab and field data.
rainbow trout | 4,000 | FLD | | WB | 7.9 | 0.00000005 | (R-100)
(Salmo | | | | | | |
gairdneri) | | | | | | |
Test conditions: Using the concentration of hexachlorobutadiene in
Lake Ontario waters sampled in the fall of 1980, residue
concentrations were estimated for Rainbow trout on the basis of the
BCFs derived from this study. These values were compared with
residue concentrations of the same chemicals that were monitored in
adult Rainbow trout collected from Lake Ontario in the spring of
1981.
Results: Using the concentration in Lake Ontario waters of 0.05 ng/L
and the mean concentration in Lake Ontario fish of 0.2 +/- 0.08
ng/g, a field-derived BAF of 4,000 was reported.
pike | | | | | | | (R-61)
perch | | | | | | |
tench | | | | | | |
common bream | | | | | | |
white bream | | | | | | |
roach | | | | | | |
Results: When HCBD residues in various fish (pike, perch, tench,
common bream, white bream and roach) were compared to fat content,
higher residue levels were found in common bream and roach. These
results were significant and were positively correlated with fat
content (r = +0.862 and LT 0.5%).
crayfish | 6.27 | FT | 10 | WB | | 0.0022 | (R-78)
(Procambarus | | | | | | |
clarki) (m) | | | | | | |
crayfish | 45.36 | FT | 10 | WB | | 0.0022 |
(Procambarus | | | | | | |
clarki) (f) | | | | | | |
crayfish | 11.11 | FT | 10 | WB | | 0.0037 |
(Procambarus | | | | | | |
clarki) (m) | | | | | | |
crayfish | 3.86 | FT | 10 | WB | | 0.0037 |
(Procambarus | | | | | | |
clarki) (f) | | | | | | |
sailfin | 22.7 | FT | 10 | WB | | 0.01054 |
mollies | | | | | | |
(Poecilia | | | | | | |
latipinna) | | | | | | |
sailfin | 22.7 | FT | 10 | WB | | 0.01203 |
mollies | | | | | | |
(Poecilia | | | | | | |
latipinna) | | | | | | |
largemouth | 4.4 | FT | 10 | WB | | 0.0057 |
bass | | | | | | |
(Micropterus | | | | | | |
salmoides) | | | | | | |
largemouth | 4.2 | FT | 10 | WB | | 0.0078 |
bass | | | | | | |
(Micropterus | | | | | | |
salmoides) | | | | | | |
largemouth | 2.2 | FT | 10 | WB | | 0.0049 |
bass | | | | | | |
(Micropterus | | | | | | |
salmoides) | | | | | | |
largemouth | 19.1 | FT | 10 | WB | | 0.0044 |
bass | | | | | | |
(Micropterus | | | | | | |
salmoides) | | | | | | |
largemouth | 2.5 | FT | 10 | WB | | 0.0591 |
bass | | | | | | |
(Micropterus | | | | | | |
salmoides) | | | | | | |
largemouth | 112.9 | FT | 10 | WB | | 0.05712 |
bass | | | | | | |
(Micropterus | | | | | | |
salmoides) | | | | | | |
Test conditions: All laboratory assays were carried out in a
proportional diluter system with a flow rate of 60 to 120 liters/day
(30 L tanks). Water quality parameters were consistent (except for
salinity) throughout all experiments: temperature, 22.2 to 23.9 C.;
pH, 6.5 to 7.9; and D.O. 7.6 to 8.5 mg/L. Salinity was between 0.8
and 1.0 ppt. In the assay with HCBD in bass diet, the bass were fed
contaminated mollies. Laboratory exposure periods were followed by
10 days of depuration. Analysis of tissue and water was by GC-ECD.
Results: Crayfish appeared to be approaching steady-state
conditions. Tests with bass and mollies showed erratic concentration
patterns, there were high levels in blank and carrier solvent
controls, and steady-state did not appear to be reached. Male
crayfish had lower BCFs equaling 6.27 and 11.11 at 2.2 and 3.7 ug/L,
respectively, than females with BCFs of 45.36 and 3.86. Authors
noted that specimen variations of uptake, and higher residue levels
during depuration were not readily explained.
mosquito fish | 125 to | MON | | WB | | 0.0009, | (R-58)
(Gambusi | 435 | | | | | 0.0014, |
affinis) | | | | | | 0.0019 |
Results: Environmental monitoring along the Mississippi River near
Baton Rouge, LA of water and mosquito fish resulted in HCBD levels
of 0.9, 1.4 and 1.9 ug/L in the water. The corresponding levels in
fish were 112.8, 197.4 and 827.3 ug/kg.
goldfish | | ST, | 1 | | | 0.200 | (R-21)
(Carassi | | REN | | | | |
auratus) | | | | | | |
goldfish | | ST, | 49 | | | 0.0003 to |
(Carassi | | REN | | | | 0.030 |
auratus) | | | | | | |
Test conditions: In the first experiment, goldfish were exposed for
24 hours and then transferred to a clean FT system (20 C.). Samples
were taken on days 0, 1, 2, 6, 9 and 15 after exposure. Elimination
was fit to a log concentration (ppm) fish-time regression curve of
the formula log c = A - Bt. The second study was performed to
determine the semichronic toxicity. The exposure period was 49 days
in which the test solutions were renewed daily. On day 49, fish
tissue was analyzed by GC-ECD (as in previous test). The water
quality parameters were: pH = 7.6 +/- 0.2; temperature = 19 +/- 1
C.; and D.O. = 6.3 to 3.2 mg/L.
Results: The residue concentration in goldfish after 24 hours
exposure to 200 ug/L was approximately 100 ppm. The confidence
limits of A and B were calculated to be 1.8 to 2.1., and 0.03 to
0.07, respectively and the correlation coefficient was 0.749. The
residue levels found in the second test after 49 days of exposure to
0.3, 3, 9.6 and 30 ppb were 0.69, 7.0, 17.8 and 27.6 ppm,
respectively.
|
-
Sorption studies:
STUDY # 1
In an environmental monitoring study of the Mississippi Delta region
it was found that the level of HCBD in water was less than 2 ug/L
while the concentration in mud or soil samples exceeded 200 ug/L. In
this same study, water samples from the waste of an industrial
company in Geismar, Louisiana, contained less than 0.1 ug/L to 4.5
ug/L while levels of HCBD in the mud reached a maximum of 2,370
ug/kg indicating selective concentration of several orders of
magnitude.
(R-54)
STUDY # 2
In laboratory experiments, bottom sediments, exposed to a regular
flow of 3.6 ppb HCBD in water for one day, accumulated 725 ppb HCBD,
a concentration factor of 201.4. After four days of exposure to the
same concentration, sediments contained 938-ppb HCBD, a
concentration factor of 260.5. Depuration for four days resulted in
a loss of 306 ppb HCBD from the sediment.
(R-27) (R-61)
STUDY # 3
In one study it was determined that the concentration of HCBD in
uncontaminated sediment after equilibration with water that
contained HCBD was 100 times that found in the water. The experiment
was conducted with 200 mg of sorbent mixed with 25 mL demineralized
water at pH 5.5. HCBD was added in acetone solutions at
concentrations of 50, 125, 375 and 1000 ppb. Equilibrium was reached
after 48 hours. The distribution ratio between solid and liquid
phases was described via the Freundlich equation with K = 200 and
1/n = 0.9.
(R-21)
|
-
Field studies:
STUDY # 1
Soil was treated with [14C]-labeled hexachlorobutadiene at 6.17
kg/ha. Potatoes were planted immediately, followed by carrots the
next year. Most of the radioactivity was volatilized in one season
and no accumulation occurred in either the carrots or potatoes.
(R-10)
STUDY # 2
In an environmental monitoring study of inland waters fed by the
Rhine River, HCBD was found in fish, mollusc species, oligochaete
worms, detritus and water samples. Levels of HCBD in water were 3
orders of magnitude lower than those found in aquatic animals
sampled in the same area, but not at the same time. The
investigators indicated that there was no significant
bioaccumulation via the food chain to higher trophic levels in this
ecosystem.
(R-57)
|
-
Reduction/oxidation studies:
STUDY # 1
Perhalogenated hydrocarbons are typically very stable with respect
to oxidation.
(R-54)
Hydrolysis studies:
STUDY # 1
If hydrolysis of HCBD takes place on the clay surfaces of recently
deposited sediments, the first expected product would be a
chlorinated butenoic acid, based on results of studies on solvolysis
of HCBD in ethanol.
(R-54)
Photolysis studies:
STUDY # 1
The absorption coefficient of HCBD in the solar spectral region may
be too small to make direct photolysis an important aquatic fate
process.
(R-54)
STUDY # 2
HCBD in solution with benzene (1 ug/mL) exhibits a dramatic change
after irradiation for 15 minutes at a wave length of 273.5 nm.
Numerous products having a molecular weight higher than HCBD were
reported as being evident, but no compounds were named.
(R-61)
STUDY # 3
Irradiation of a 0.4 ppm concentration in flasks exposed to outdoor
diurnal and climatic variations, resulted in a half- life of about
one week. The authors questioned the data because heterogeneous
reactions on the vessel wall may have been occurring.
(R-59)
|
-
Analytical methods
Sample type:
Sample preperation:
Detection method:
Detection limit:
References:
Type | Sample Prep. | Method | Limit | Ref.
------------------------------------------------------------------------
fish | grind, extract | GC/ECD | 5 ug/kg | (R-69)
| (petroleum | | |
| ether), cc | | |
soil | extract | GC/ECD | | (R-1)
| (acetone), add | | |
| benzene | | |
fish | (see narrative) | biological | 0.05 mg/L | (R-55)
water | trap on XAD | GC/FID | | (R-56)
| resin, extract | | |
| (acetone, | | |
| chloroform) | | |
water | trap on XAD | GC/FLD, GC/ECD | | (R-65)
| resin or | | |
| activated | | |
| carbon, extract | | |
| (diethyl ether | | |
| or chloroform- | | |
| acetone) | | |
air | trap on | GC/ECD | | (R-60)
| Chromosorb 101, | | |
| extract | | |
| (hexane) | | |
air | trap on Tenax | GC/ECD | | (R-1)
| GC, extract | | |
| (hexane) | | |
air | trap on silica | U.V. | 0.2 mg/m3 | (R-1)
| gel or in | | |
| solvent | | |
| (cyclohexane- | | |
| hexane- | | |
| petroleum | | |
| ether) | | |
air | trap on silica | colorimetry | 5 mg/m3 | (R-1)
| gel, extract | | |
| (ether), | | |
| prepare | | |
| derivative with | | |
| pyridine | | |
water | extract | GC/ECD | | (R-1)
| (hexane) | | |
water | extract | GC/ECD | | (R-1)
| (benzene) | | |
water | extract | colorimetry | 0.2 mg/L | (R-1)
| (ether), | | |
| prepare | | |
| derivative with | | |
| pyridine | | |
fish | homogenize with | GC/ECD | | (R-1)
| sodium sulfate | | |
| and acetone, | | |
| filter, add | | |
| sodium chloride | | |
| to filter, | | |
| extract | | |
| (hexane), | | |
| evaporate, take | | |
| up in hexane, | | |
| cc, transfer to | | |
| benzene | | |
sediment | extract | GC/ECd | 10 ppb | (R-68)
and soil | (acetone, | | |
| benzene) | | |
water | purge, trap on | GC/MS | | (R-70)
| Tenax-GC, | | |
| desorb with | | |
| heat | | |
Waste/wastewater treatment:
STUDY # 1
The efficacy of a pilot water reclamation plant to remove HCBD from
feed water containing the compound at a concentration of 110 ug/L
was determined. The pilot plant used in the study operated on
secondary, biologically purified, sewage effluent at a flow rate of
80 kL/day. The efficacy of the different process units of the pilot
plant to remove HCBD were: high lime treatment (110 ug/L feed
concentration), 71.8% removal; stabilization (31 ug/L feed
concentration), 96.8% removal, GT 99.1 overall removal; sand
filtration (LT 1 ug/L feed concentration), GT 99.1 overall removal;
chlorination GT 99.1 overall removal; and active carbon filtration,
GT 99.1 overall removal. (R-64)
STUDY # 2
Sealed tube pyrolysis of HCBD at 380 C. showed the simultaneous
initial formation of C2C14, C2C16, and C6C16; CC14 was subsequently
produced and increased as C2C16 decreased. Steady-state
concentrations of products appeared to be achieved at 3,000 h. The
thermal stability of HCBD was also determined using sealed-tube
experiments. The half-life for HCBD at 380 C. was 53h and less than
0.2 mole-% remained after 150%. (R-67)
|
|
-
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Chemical Abstracts volumes searched; beginning:
56
Chemical Abstracts volumes searched; ending:
122
CAS Registry number: 87-68-3
Common name: Hexachlorobutadiene
SEARCH DATE: 30-3-90
SYNONYMS: 1,3-Butadiene, 1,1,2,3,4,4-hexachloro-;
Hexachlorobutadiene; Hexachloro-1,3-butadiene;
Perchlorobutadiene; 1,1,2,3,4,4-Hexachloro-1,3-butadiene;
Perchloro-1,3-butadiene; Butadiene, hexachloro-; HCB
RTECS NO: EJ0700000
Environmental Transport Score : 4E
Discussion: The score is based on the Level I Fugacity Model
estimate: 91.76% partitions to air, 2.93% partitions to water,
4.92% partitions to soil, and 0.39% partitions to sediment. Data
used in model: temp (C): 25, Sol (mg/L): 3.20, VP (mm Hg): 0.076,
and Log Kow: 4.78.
Data:
* MW: 260.74 (R-2) (R-4)
* MW: 260.76 (R-3) (R-17)
* MW: 260.7 (R-6)
* sol: "insoluble in water" (R-3) (R-17) (R-21)
* sol: 2 ppm at unr temperature (R-5)
* sol: 3.20 ppm at 25 C (R-24)
* sol: 2.55 mg/L at 20 C (R-27)
* VP: 22 mm Hg at 100 C (R-3) (R-5) (R-6)
* VP: 0.3 mm Hg at 25 C (R-12)
* VP: 0.076 mm Hg at 25 C (R-24)
* VP: 0.15 mm Hg at 25 C (R-27)
* log Kow: 4.90 (R-3) (R-27)
* log Kow: 4.14 (R-21)
* log Kow: 4.78 (R-21) (R-24)
Persistence Score : 10
- Aquatic: 10
- Air: 10
- Soil: 10
Discussion: The aquatic score is based on possible 300 day half-
life in lake and ground water. Due to high log Kow, HCB may
readily partition to sediments. Air score is based on 1.6 year
half-life. Less than half of the compound was degraded in the
vineyard soil in 24 months without additional application of
hexachlorobutadiene.
Data:
* water: 100% degradation: 7 d: 5 and 10 mg/L,
sewage seed, 7 d static incubation followed by 3
weekly subcultures at 25 C (R-24): 56% and 21%
degradation: 7 d incubation: 5 and 10 mg/L:
sewage seed, serial shake flask at 25 C (R-26)
* water: T 1/2: 3-30 d: Rhine River, estimated
half-life from monitoring data (R-26)
* water: volatilization: "will be rapid and that
the liquid phase will control the volatilization
rate...because of its high Kow and Log Kow,
volatilization from water may be decreased due
to adsorption to sediments, suspended sediments
and biota" (R-27)
* water: anaerobic: did not biodegrade...batch
culture incubated for 48 hrs at 37 C (R-27)
* water: lake and groundwaters: T 1/2: 30-300 d:
based on monitoring data (R-27)
* soil: dune infiltration study, The Netherlands:
mobile in sandy soil: avg residence time 100 d:
low biodegradation (R-27)
* soil: vineyard fumigant: 8 months, 4.36 ppm at
75-100 cm, 7.3 ppm at 50-75 cm: 32 months, 2.99
ppm at 75-100 cm, 0.65 ppm at 50-75 cm (R-27)
* soil: "soil surfaces, evaporation is expected to
be a significant transport mechanism...may not
biodegrade in anaerobic zones of soil" (R-27)
* "no information was found on hydrolysis or
photolysis, but based on structure, hydrolysis
should not be an important process" (R-27)
* air: reactive with OH and O3: T 1/2: LT 1 d: T
1/2 in atm (calc): 3.24 hr (R-3)
* air: HCB has been found in air at remote sites
(R-27)
* air: T 1/2 (troposphere): 1.6 yr (northern
hemisphere)..."long-lived in the atmosphere and
considerable dispersion would be
expected...degrade primarily by addition of
photochemically derived hydroxyl radicals to its
double bonds." (R-27)
Bioaccumulation Score : 10
Discussion: Score is based on BCF values of 17000 and 11400 in
rainbow trout. Mosquito fish BCF data indicate a lower score.
High log Kow values support the score.
Data:
* mosquito fish: BCF: unr duration: 435 (R-19):
calc from given concentrations (R-27)
* rainbow trout: BCF: unr duration: 11400: log
BCF: 4.057 (R-24)
* rainbow trout: BCF: unr duration: 0.1 ng/L and
3.4 ng/L: 5800 and 17000 (R-27)
* log Kow: 4.90 (R-3) (R-27)
* log Kow: 4.14 (R-21)
* log Kow: 4.78 (R-21) (R-24)
Acute Lethality Score : 10
- Aquatic: 10
- Oral: 6
- Inhalation: 2L
- Dermal: 4Q
Discussion: Score is based on aquatic LC50 data in the fathead
minnow (0.09 mg/L) and is further supported by a goldfish study.
Other aquatic studies also indicate high toxicity. The oral
score is based on a rat LD50 of 26 mg/kg. Other oral studies in
rat, mice, hamsters and guinea pigs indicate a lower score. No
inhalation LC50 data was found, but based on limited data for
several species a score of 2 would be appropriate. Dermal score
is based on one rabbit study indicating the LD50 is between 63
and 126 mg/kg. Another rabbit study supports lower score, hence
a "Q" tag was assigned.
Data:
* rat (neonatal): orl: LD50: 1/4 of adult (R-6)
* rat: orl: LD50: 26-667 mg/kg (R-5)
* rat: orl: LD50: 90 mg/kg (R-2) (R-4)
* mus: orl: LD50: 110 mg/kg (R-2) (R-4)
* gpg: orl: LD50: 90 mg/kg (R-2) (R-5) (R-4) (R-
17)
* ham: orl: LD50: 960 mg/kg (R-2) (R-4)
* mus: orl: LD50: 87-116 mg/kg (R-5)
* rat: orl: LD50: 200-350 mg/kg (R-5)
* rat: orl: LD50: 250 (male) and 270 (female)
mg/kg (R-6)
* mus: orl: LD50: 80 (male) and 65 (female) mg/kg
(R-6)
* rbt: skn: LD0: 24 hr: 63 mg/kg: LD0: 4 hr: 126
mg/kg: 4 of 4: 24 hr: 126 mg/kg: 1 of 2: 7 hr:
126 mg/kg (R-5)
* rbt: skn: LD50: 1211 mg/kg (R-2) (R-4)
* mus: ihl: LCLo: 4 hr: 235 ppm (2515 mg/m3) (R-
4)
* rat: ihl: 4 hr and 7 hr exposures: 133 to 500
ppm (1423.1 to 5350 mg/m3): death to some or all
rats: (R-12) (R-17)
* gpg, cat: ihl: 0.88 hr: 161 ppm (1723 mg/m3):
most died: or 34 ppm (364 mg/m3) for 7.5 hr (R-
17) (R-12)
* rat: ihl: LC0: 0.88 hr: 161 ppm (1723 mg/m3): or
34 ppm (364 mg/m3) for 3.3 hr: all survived (R-
17) (R-12)
* fathead minnow: LC50: 96 hr: 0.09 mg/L (R-3) (R-
8)
* goldfish: LC50: 96 hr: 0.09 mg/L (R-5) (R-19)
* guppy: LC50: 14 d: 0.4 ppm (R-5)
* rainbow trout: LC50: 96 hr: 0.250 mg/L (R-11)
* channel catfish: LC50: 96 hr: 0.760 mg/L (R-11)
* bluegill: LC50: 96 hr: 0.760 mg/L (R-11)
* great pond snail (Lymnaea stagnalis): LC50: 96
hr: 0.210 mg/L (R-19)
* aquatic sowbug (Asellus aquaticus): LC50: 96 hr:
0.13 mg/L (R-19)
* zebrafish: LC50: 48 hr: 1 mg/L (R-19)
* silver or golden orfe: LC50: unr duration: 470
mg/L (R-19)
Non-mammalian Sublethality Score : 6
- Aquatic: 6
- Terrestrial: *
Discussion: The score is based on MATC of 0.013 mg/L in the
fathead minnow.
Data:
* fathead minnow (egg): MATC: 13 ug/L: toxic
effects on early developmental stages
demonstrated 18% weight decrease in 28 d
exposure study (R-3) (R-19): 27 ug/L: highest
conc tested (R-19)
* goldfish: 67 d: 0.030 mg/L: 6% significant
increase in body wt: 40 d: 0.0096 mg/L: 5.4%
significant difference in lvr wt: 49 d: 0.096
mg/L: significant difference in G-6-P (glucose-
6-phosphate) and G-6-PDH (intermediates of
respiration) activity (R-19)
* sea lamprey (larvae), rainbow trout, bluegill:
no effect observed: 24 hr: 5 mg/L (only conc
tested) (R-19)
* Japanese quail: orl (diet): 90 d: up to 30 ppm
(approximately 5 mg/kg/d): no deleterious effect
on reproduction (R-5) (R-6)
Plant Sublethality Score : 0
- Aquatic: 0
- Terrestrial: *
Discussion: The score is based on 2 algae studies indicating
thresholds and 5% effects at concentrations greater than 25 mg/L
and greater than 10 mg/L, respectively.
Data:
* green algae (Scenedesmus quadricauda): cell
multiplication inhibition test: unr duration:
LT50: GT 25 mg/L (R-19)
* algae (Cryptomonad): 5% decreased cell count: 48
hr: GT 10 mg/L (R-19)
Mammalian Sublethality Score : 8
- Oral: 8
- Inhalation: 6
Discussion: The score is based on a rat oral NOAEL of 0.2
mg/kg/d in 2 year and 90 day studies. Inhalation score based on
no effects at 1 ppm over a 184-day period.
Data:
* rat: orl: 13 wk: 0, 0.4, 1.0, 2.5, 6.3 and 15.6
mg/kg/d: no effect levels of 1.0 and 2.5 mg/kg/d
were established for females and males,
respectively: inhibition of growth occurred in
both sexes at the two highest doses and
degeneration of proximal renal tubules occurred
at doses of 2.5 and 6.3 mg/kg/d or more in
females and males, respectively: urine
concentrating ability was significantly reduced
in females at doses of 2.5 mg/kg/d or more and
in males at 15 mg/kg/d. (R-3)
* rat: ihl: 15 exposures 6 hr each: 5 ppm: no
effect level (R-5)
* rat: orl (diet): 30 d: 1 or 3 mg/kg/d, no
effect: 10 mg/kg/d, marginal changes: 30, 65 and
100 mg/kg/d, increase in the kdy-body wt ratio
as well as renal tubular degeneration, necrosis
and regeneration, decreased food consumption and
body wt gain (R-5) (R-17)
* rat: ihl: short-term repeated studies, unr
duration: 4 hr: 250 ppm (2675 mg/m3): 6 hr: 100,
25, 10, 5 ppm (1070, 268, 107 and 54 mg/m3): 15
exposures to 5 or 10 ppm resulted in no observed
toxic effect for retarded wt gain at 10 ppm: 15
exposures to 25 ppm, 2 exposures to 100 and 250
ppm resulted in respiratory irritation and
injury and had a pronounced effect on renal
tubules (R-12) (R-17)
* rat, gpg: ihl: 7 hr/d, 5 d/wk: 8 or 30 ppm: 10
of 10 rats and 4 of 5 gpg survived 19 7-hr
exposures to 8 ppm, but lvr and kdy injury were
grossly apparent on necropsy (R-12)
* rat, rbt, gpg: ihl: 7 hr/d: 100 exposures to 3
ppm (32 mg/m3) in 143 d: 4.2, 3.1 and 3.7
mg/kg/d for rat, rbt and gpg, respectively:
adversely affected lvr and kdy of animals: 129
exposures to 1 ppm (11 mg/m3) in 184 d: 1.5, 1.1
and 1.3 mg/kg/d for rat, rbt and gpg,
respectively: not adversely affected (R-12)
* rat, mus: ihl: 7 months: unr dosing schedule and
frequency of exposure: 0.024 mg/L (2.2 ppm, 24
mg/m3): animals "tolerated" dose, caused no
alteration in animals (R-12) (R-17)
* rat: orl (diet): 2 yr: 0.2 mg/kg/d: caused no
effects that could be attributed to treatment; 2
mg/kg/d: caused a slight degree of renal
toxicity; 20 mg/kg/d (highest dose): caused
multiple and substantial toxicological effects,
including renal tubular neoplasms (R-12) (R-5)
(R-6)
Teratogenicity Score : 6
Discussion: The score is based on central nervous system (CNS)
terata observed in one recent rat oral study. Other oral studies
did not indicate that CNS effects were investigated.
Data:
* rat: orl (diet): 90 d prior to mating and during
gestation and lactation: 20, 2 or 0.2 mg/kg/d:
observed no deleterious effects on fertility or
health of pups but other toxic effects to
kidneys of parents at 20 mg/kg/d (R-6): no
effects were observed at 0.2 mg/kg/d (R-12)
* rat: orl: gestation day 1-22: TDLo: 178 mg/kg
(total dose): 8.1 mg/kg/d: specific
developmental abnormalities: central nervous
system (This is 1985 study not reported in
other reviews) (R-2)
* rat: ipr: gestation day 1-15: TDLo: 150 mg/kg
(total dose): 10 mg/kg/d: fetotoxicity (except
death, eg. stunted fetus) (R-2)
* rat: orl: 13 wk: unr dose schedule: 0, 0.4, 1.0,
2.5, 6.3 and 15.6 mg/kg: decreased body wts at
birth and weaning, no effects on fertility or
progeny were found (R-3)
* rat: orl: unr duration: 150 ppm in diet (7.5
mg/kg body wt/d based on a daily feed
consumption rate of 5 g/100 g/d): no effect on
fertility or progeny except for decreased body
wt at birth and weaning in rats: grossly
observable malformations were not seen in this
small study (R-12)
Mutagenicity Score : 10
Discussion: The score is based on evidence of mutagenicity in
in vitro assays for both pro- and eukaryotic systems and
clastogenic effects in vivo systems.
Data:
* sat (TA100): mmo: pos (R-6) (R-2) (R-25)
* sat (TA100): mma: pos (R-2) (R-25)
* rat: orl: dns: pos (R-2) (R-4)
* ham: emb cells: dns: (with and without
activation): pos (R-2) (R-4)
* ham: ovr: sce: pos (R-2)
* dmg: inj or orl: slrl: neg (R-3)
* sat: mma (Ames assay-rat kdy S9): pos (cysteine
conjugates of HCBD) (R-3)
* ham: emb: fbr: morphological transformation: pos
(R-3)
* sat: mmo: questionable (R-18)
Carcinogenicity Score : 10L
Discussion: The score is based on positive cancer data in rats
and oncogenic test in hamster cells and positive mutagenicity
data. IARC concluded limited animal evidence and no adequate
human data. The "L" tag was as assigned, as only one good animal
study was available.
Data:
* ACGIH: "an industrial substance suspect of
carcinogenic potential to humans" (R-17)
* ham: emb: otr: pos (R-2) (R-4)
* rat: orl (diet): 2 yr: 0.2, 2.0, or 20 mg/kg
body wt/d: TDLo: 15000 mg/kg (total dose) (C):
statistically significant increase (p LT 0.05)
of kdy tumours was observed in male and female
rats fed at highest dose (R-6) (R-25):
carcinogenic by RTECS criteria (R-2) (R-4)
* IARC: limited evidence in animals, 1979: no
adequate data for humans...overall IARC
evaluation-Group 3 (the agent is not
classifiable as to its carcinogenicity to
humans) (R-6)
* NTP Program 1988 - "Selected for general
toxicology study, prechronic studies completed
(mus: orl): chemicals in review for further
testing" (R-10) (R-2)
References:
(R-2) Registry of Toxic Effects of Chemical Substances.
(computerized database produced by the National Library
of Medicine, interactive version of the National
Institute of Occupational Safety and Health (NIOSH)
publication). #
(R-3) TOXNET - Computerized database (Toxicology Data
Network). National Library of Medicine. U.S.
Department of Health and Human Services. #
(R-4) Sax, N.I. 1988. Dangerous Properties of Industrial
Materials. 7th Edition. Van Nostrand Reinhold Co.,
New York, NY. #
(R-5) Verschueren, K. 1983. Handbook of Environmental Data
on Organic Chemicals. 2nd Edition. Van Nostrand
Reinhold Co., New York, NY. #
(R-6) International Agency for Research on Cancer. 1978.
IARC Monographs on the Evaluation of Carcinogenic Risk
of Chemicals to Man. World Health Organization, Lyon,
France. #
(R-8) Center for Lake Superior Environmental Studies. 1987.
Acute Toxicities of Organic Chemicals to Fathead
Minnows (Pimephales promelas). Volumes 1, 2 and 3.
University of Wisconsin-Superior. #
(R-10) National Toxicology Program (U.S.). 1980-1986.
Bioassay for Possible Carcinogenicity. Bethesda, MD.:
U.S. Dept. of Health and Human Services, Public Health
Service, National Institutes of Health. #
(R-11) Mayer, F.L. and M.R. Ellersieck. 1986. Manual of
Acute Toxicity: Interpretation and Data Base for 410
Chemicals and 66 Species of Freshwater Animals. U.S.
Department of the Interior. Report No. 160. #
(R-12) Clayton, George D. and Florence E. Clayton (Eds.).
1982. Patty's Industrial Hygiene and Toxicology. 3rd
Edition, Vol. 2 a-c. John Wiley and Sons, New York,
NY. #
(R-13) Packer, Kingsley. 1975. Nanogen Index. A Dictionary
of Pesticides. Nanogens International, Freedom, CA. #
(R-17) American Conference of Governmental Industrial
Hygienists, Inc. (ACGIH). 1986. Documentation of the
Threshold Limit Values for Substances in Workroom Air.
5th Edition. ACGIH, Cincinnati, OH. #
(R-18) Soderman, Jean V. (Ed.). 1982. CRC Handbook of
Identified Carcinogens and Noncarcinogens:
Carcinogenicity - Mutagenicity Database, Volume I. CRC
Press Inc., Boca Raton, Florida. #
(R-19) AQUIRE - Aquatic Information Retrieval Computerized
database. (Computerized database developed by U.S.
EPA). #
(R-21) ISHOW - Information System for Hazardous Organics in
Water. (Computerized database developed by U.S. EPA's
Environmental Research Laboratory and the University of
Minnesota, Sponsored by U.S. EPA's Office of Toxic
Substances. #
(R-24) CHEMFATE - Computerized database. The Environmental
Fate Database, Technical Database Services
Incorporated, New York, NY. #
(R-25) CCRIS - Chemical Carcinogenesis Research Information
System. (Computerized database sponsored by the
National Cancer Institute of the National Institutes of
Health). #
(R-26) BIODEG - Computerized database. The Environmental Fate
Database, Technical Database Services Incorporated, New
York, NY. #
(R-27) Howard, P.H. 1989. Handbook of Environmental Fate and
Exposure Data For Organic Chemicals. Lewis Publishers,
Chelsea, Michigan. #
Chelsea, Michigan. #
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- The current database reflects the last update provided by the Michigan Department of Environmental Quality and the Ontario Ministry of the Environment in August, 1999.
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©2001 Canadian Centre for Occupational Health & Safety 