INFORMATION REGARDING CHLOROFORM AND WATER TREATMENT
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~oFmQwc:1
CHLOROFORM
CASRN: 67-66-3
Effluent Concentrations :
Chloroform was
detected at 245 ppm in the gas effluent emitted from a Municipal Landfill Site
(MLS) in Palos Verdes, CA(1). A study of compounds found in automobile exhaust
revealed that chloroform was not present(2). During the
chlorite bleaching of kraft pulp, a variety of organic chlorinated compounds can
be formed(3). Of these, chloroform has been found to be
the main volatile organochlorine compound formed(3). The effluent from a kraft
pulp mill using chlorite bleaching prior to treatment
and the effluent following activated sludge waste water
treatment revealed chloroform
concns at 180 and 34 ug/l, respectively(3). At another mill, concns before and
after treatment were 6.2 and 1.6 ug/l while at a third
mill concns were 16 ug/l and not detected(3). In 1993, the Toxic Release
Inventory (TRI) System reported that 175 facilities had emissions of 13.8
million lb of chloroform to air, another 450,000 lb to water,
and 70,000 lb to land(4). The facilities with the largest emission (100,000 to
700,000 lb) were pulp and paper plants(4).
Atmospheric Concentrations :
URBAN/SUBURBAN: Airborne concns and sources of
chloroform were evaluated in two urban areas in
Illinois: southeast Chicago and East St. Louis between May 1986-April 1990(1).
The avg concn of chloroform found in 103 air samples
from Chicago was 0.3 ug/cu m (max 1.6 ug/cu m) and from 83 air samples from East
St. Louis was 0.5 ug/cu m (max 6.6 ug/cu m)(1). The contribution of chloroform
to Chicago's atmosphere was due to both waste water treatment
and chemical plant emissions(1). The Illinois Department of Energy and Natural
Resources estimate that Southeast Chicago contributes 12 tons of chloroform
per year while East St. Louis contributes 9 tons/year(1). Twelve hour avg
outdoor concns of chloroform in California (from
1984-1987) ranged from 0.2 to 0.6 ug/cu m while outdoor air concns in New Jersey
(from 1981-1983) ranged from 0.1 to 1.5 ug/cu m(2). In another study of air from
Los Angeles, CA, 2,251 24-hr air samples had an avg concn of 0.16 ug/cu m
between the years 1986-1991(2). Outdoor air measurements made in chemical
manufacturing areas sometimes show higher chloroform
values(2). Studies in the Kanawha Valley from 1986-1988 indicated mean outdoor
concns of 11.5 ug/cu m near a major chemical manufacturing facility in Belle,
WV(2). Mean values of 3 ug/cu m were observed at two other sites (Institute, WV
and South Charleston, WV)(2). Compared to mean personal exposures of indoor air
concns, these outdoor values are often lower by factors of 2 to 8(2).
Environmental Water Concentrations :
DRINKING WATER: US
Federal Survey of Finished Waters find a 70.3%
occurrence in drinking water from groundwater
supplies(9); 30 Canadian Treatment Facilities (treated water)
35 ppb avg summer, 21 ppb avg winter (93-97% pos, 110 ppb max - raw water
had 2-6 ppb avg concn)(1); US 5 City Survey 1-301 ppb(2); Drinking Water
wells in NY and NJ 67-490 ppb(3); Other cities report values between 0-190
ppb(4-7) with the values highest in summer and lowest in winter(4) and
increasing on contact with residual chlorine(7). National Organic Reconnaissance
Survey (80 US water supplies, 1975) 0-311 ppb, National
Organics Monitoring Survey (113 finished water
supplies, 1976-1977) 32-68 ppb median of positive supplies, 92-100% pos(8).
Environmental Water Concentrations :
DRINKING WATER: Chloroform
is prevalent in tap water throughout much of the
country(1). About 50% of the U.S. population uses chlorinated surface water
and another 25% consume chlorinated groundwater(1). In a study of 35 water
utility plants(including 10 in California), median chloroform
levels in distributed water ranged from 9.6-15 ug/l by
quarter(1). In another study, chloroform concn was
determined in drinking water in Los Angeles from Feb
1987 to July 1987 at 6.8 ug/l and 11 ug/l, respectively(1). The mean concn of chloroform
in New Jersey drinking water avgd about 50 ug/l,
ranging from 17 ug/l in the winter of 1983 to 70 ug/l in the fall of 1981(1).
Los Angeles had rather lower levels of 14 and 29 ug/l in the winter and spring
of 1984, and even lower levels of 7 and 11 ug/l in winter and summer of 1987(1).
Mean values were very low in Devils Lake, ND (1.4 ug/l) because the water
supplies were from private wells and were not chlorinated(1). In a similar
study, both treatment plant and tap water
samples from three community water systems were
analyzed for chloroform concn(1). Chloroform
ranged from 11 to 100 ug/l at the plants and from 21 to 160 ug/l at the tap(1).
Environmental Biodegradation :
AEROBIC: No marine biodegradation of CHC (chlorohydrocarbons
including chloroform) has been reported(1). Chloroform,
present at 100 mg/l, reached 0% of its theoretical BOD in 2 weeks using an
activated sludge inoculum at 30 mg/l and the Japanese MITI test(2). Among the
aerobic microorganisms, chloroform has been shown to be
degradable only by methanotrophic bacteria(3). When it is introduced into an
aerobic bioreactor for treatment, it appears in the
effluent and is not degraded(3). The disappearance of chloroform
from a wastewater treatment plant was studied(4). At an
air/water flow rate of 0.10 cu cm/cu m min, chloroform,
at an initial concn of 43.3 ug/l had an avg effluent concn of 3.6 ug/l with
32.5% being air stripped and 59.2% being degraded(4).
Non-Human Toxicity Excerpts :
The effects of lifetime exposure to chloroform
... were studied in Wistar rats. ... Treatment was
initiated with weanlings at 2 ml chlorofrom per liter of water.
Concentrations were halved at 72 weeks because of increasing water
intake among the test animals. ... Treated rats weighed less than unexposed
controls at all ages. At about 15 to 17 weeks, females had a high consumption of
water and ... /chloroform/
than males. The incidence of neoplastic nodules was significantly increased in
females. ... /Both/ males /and females/ treated with chlorofrom had a high
incidence of hepatic adenofibrosis.
Environmental Fate :
AQUATIC FATE: Based on a classification
scheme(1), a Koc value ranging from 153-196(2,3) indicates that chloroform
is not expected to adsorb to sediment and suspended solids in water(SRC).
Volatilization from water surfaces is expected(3) based
upon a Henry's Law constant of 3.67X10-3 atm-cu m/mole(4). Using this Henry's
Law constant and an estimation method(3), volatilization half-lives for a model
river and model lake are 1.3 hrs and 4.4 days, respectively(SRC). In a field
study of chloroform volatilization, it was found that
the volatilization half-life from the Rhine River was 1.2 days while in a lake
located in the Rhine basin the half-life was 31 days(5). In another study, chloroform
from a municipal treatment plant injected into an
estuarine arm of Chesapeake Bay entirely disappeared within 4 km in the spring
and within 11 km in winter under ice(6). The decrease in concn could not be
entirely due to dilution(6). Chloroform was found to
have a maximum water-to-air flux from an estuary of 350
tons/year based on its Henry's Law constant and diffusion(7). Based on available
experimental data, aquatic degradation and transfer to the biotic mass or into
the aquatic sediment are not expected to be major removal mechanisms for chloroform(7).
The major process to be considered in the study of fate processes for chloroform
is the diffusive air/water exchange(7). Biodegradation
of chloroform in environmental aqueous environments is
not well understood. Various reports have both supported and refuted anaerobic
biodegradation in water(8). According to a
classification scheme(9), a BCF ranging from 2.9-10.35(7) suggests the potential
for bioconcentration in aquatic organisms is low. Although base catalyzed
hydrolysis is expected to occur, the estimated rate constant of 6.4X10-5
L/mol-sec predicts that this will not be an environmentally important
degradation process(10).
Antidote and Emergency Treatment :
Basic treatment:
Establish a patent airway. Suction if necessary. Watch for signs of respiratory
insufficiency and assist ventilations if necessary. Administer oxygen by
nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if
necessary ... . Monitor for shock and treat if necessary ... . Anticipate
seizures and treat if necessary ... . For eye contamination, flush eyes
immediately with water. Irrigate each eye continuously
with normal saline during transport ... . Do not use emetics. For ingestion,
rinse mouth and administer 5 ml/kg up to 200 ml of water
for dilution if the patient can swallow, has a strong gag reflex, and does not
drool. Administer activated charcoal ... . Cover skin burns with sterile
dressings after decontamination ... . /Halogenated aliphatic hydrocarbons and
related compounds/
Toxicity Summary :
... The general population is exposed to chloroform
principally in food, drinking-water and indoor air in
approximately equivalent amounts. The estimated intake from outdoor air is
considerably less. ... Water use in homes contributes
considerably to levels of chloroform in indoor air and
to total exposure. ... Chloroform is well absorbed in
animals and humans after oral administrations but the absorption kinetics are
dependent upon the vehicle of delivery. ... The primary factors affecting the
absorption kinetics of chloroform following inhalation
are its concentration and species-specific metabolic capacities. It is readily
absorbed through the skin of humans and animals and significant dermal
absorption of chloroform from water
while showering has been demonstrated. Hydration of the skin appears to
accelerate absorption of chloroform. Chloroform
distributes throughout the whole body. Highest tissue levels are reached in the
fat, blood, liver, kidneys, lungs and nervous system. Distribution is dependent
on exposure route; extrahepatic tissues receive a higher dose from inhaled or
dermally absorbed chloroform than from ingested chloroform.
Placental transfer of chloroform has been demonstrated
in several animal species and humans. Chloroform is
eliminated primarily as exhaled carbon dioxide. Unmetabolized chloroform
is retained longer in fat than in any other tissues. The oxidative
biotransformation of chloroform is catalyzed by
cytochrome P-450 to produce trichloromethanol. Loss of HCl from
trichloromethanol produces phosgene as a reactive intermediate. ... The reaction
of phosgene with tissue proteins is associated with cell damage and death. ...
The liver is the target organ for acute toxicity in rats and several strains of
mice. Liver damage is characterized by early fatty infiltration and balloon
cells, progressing to centrilobular necrosis and then massive necrosis. The
kidney is the target organ in male mice of other more sensitive strains. The
kidney damage starts with hydropic degeneration and progresses to necrosis of
the proximal tubules. ... In mice the oral LD50 values range from 36 to 1366 mg chloroform/kg
body weight, whereas for rats, they range from 450 to 2000 mg chloroform/kg
body weight. ... The carcinogenic effects of chloroform
on the liver and kidney of rodents appear to be closely related to cytotoxic and
cell replicative effects observed in the target organs. ... The weight of the
available evidence indicates that chloroform has
little, if any, capability to induce gene mutation or other types of direct
damage to DNA. ... There are some limited data to suggest that chloroform
is toxic to the fetus but only at doses that are maternally toxic. ... In
humans, anesthesia may result in death due to respiratory and cardiac
arrhythmias and failure. Renal tubular necrosis and renal dysfunction have also
been observed in humans. ... The mean lethal oral dose for an adult is estimated
to be about 45 g, but large interindividual differences in susceptibility occur.
There is some weight of evidence for an association between exposure to
disinfection byproducts in drinking water and
colorectal and bladder cancer in some epidemiological studies. ... The evidence
for the carcinogenicity of chlorinated drinking water
in humans is inadequate. In addition, the disinfection byproducts cannot be
attributed to chloroform per se. ... However, it is
cautioned that where local circumstances require that a choice must be made
between meeting microbiological limits or limits for disinfection byproducts
such as chloroform, the microbiological quality must
always take precedence. ... Levels of chloroform in
surface waters are generally low and would not be
expected to present a hazard to aquatic organisms. However, higher levels of chloroform
in surface water resulting from industrial discharges
or spills may be hazardous to the embryo-larval stages of some aquatic species.
Environmental Fate/Exposure Summary :
Chloroform's
production and use in the production of hydrochlorofluorocarbon 22 (HCFC-22) may
result in its release to the environment through various waste streams. Chloroform
has been shown to occur naturally in the environment as a plant volatile and in
peat bogs. If released to air, a vapor pressure of 197 mm Hg at 25 deg C
indicates chloroform will exist solely as a vapor in
the ambient atmosphere. Vapor-phase chloroform will be
degraded in the atmosphere by reaction with photochemically-produced hydroxyl
radicals; the half-life for this reaction in air is estimated to be 151 days. If
released to soil, chloroform is expected to have
moderate mobility based upon a Koc value ranging from 153-196. Volatilization
from moist soil surfaces is expected to be an important fate process based upon
a Henry's Law constant of 3.67X10-3 atm-cu m/mole. Chloroform
may volatilize from dry soil surfaces based upon its vapor pressure. Under
normal environmental conditions, chloroform is not
expected to undergo biodegradation in soil. However, several studies have
demonstrated that at low concns, chloroform can be
anaerobically degraded by methanogenic bacteria in the presence of a primary
substrate such as acetic acid. If released into water, chloroform
is not expected to adsorb to sediment and suspended solids in water
based upon its Koc values. Biodegradation of chloroform
in environmental aqueous environments is not well understood. Various reports
have both supported and refuted anaerobic biodegradation in water.
Volatilization from water surfaces is expected to be an
important fate process based upon this compound's Henry's Law constant.
Estimated volatilization half-lives for a model river and model lake are 1.3 hrs
and 4.4 days, respectively. BCF values ranging from 2.9-10.35 suggests
bioconcentration in aquatic organisms is low. Since chloroform
has a hydrolysis half-life of 1850 yrs at 25 deg C and pH 7, hydrolysis will not
be an environmentally important loss process. Occupational exposure to chloroform
may occur through inhalation and dermal contact with this compound at workplaces
where chloroform is produced or used. The general
population may be exposed to chloroform via inhalation
of ambient air, ingestion of food and drinking water. Chloroform
is widely detected in drinking water where the drinking
water is chlorinated. (SRC)
DOT Emergency Guidelines :
Fire: Small fires: Dry chemical, CO2 or water
spray. Large fires: Water spray, fog or regular foam.
Move containers from fire area if you can do it without risk. Dike fire control water
for later disposal; do not scatter the material. Use water
spray or fog; do not use straight streams. Fire involving tanks or car/trailer
loads: Fight fire from maximum distance or use unmanned hose holders or monitor
nozzles. Do not get water inside containers. Cool
containers with flooding quantities of water until well
after fire is out. Withdraw immediately in case of rising sound from venting
safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in
fire. For massive fire, use unmanned hose holders or monitor nozzles; if this is
impossible withdraw from area and let fire burn.
Atmospheric Concentrations :
INDOOR: Studies have shown that chloroform
in indoor air was present at four to five times the outdoor air level, and that
levels could be higher still in the shower(1). Subsequent studies verified that
inhalation exposure during showers might be comparable to ingestion of 1 to 6 L
of drinking water a day(1). Mean indoor air concns of chloroform
over 12 hr periods during June 1987 in Los Angeles, CA were found to be 1.4 ug/cu
m at night in the kitchen, 1.1 ug/cu m during the day in the kitchen and 0.90
during the day in the living room(1). In another study, chloroform
concns in air from a shower using water from a
municipal water supply revealed that chloroform
concns increased from 2 to 100 ppb (10 to 500 ug/cu m) during the 10 minute
shower(1). In a similar study, 19 10-minute showers using water
at 40 deg C and chloroform concns ranging from 12.9 to
40.0 ug/l resulted in air concns in the shower stall ranging from 69-327 ug/cu
m(1). The ultimate source of most of the chloroform in
indoor air in most homes is evaporation from chlorinated water(1).
Major uses of water in the home include showers, baths,
clothes washing and dish washing(1). Several studies of indoor swimming pools
indicate that inhalation can provide substantial amounts of chloroform(1).
Hazards Summary :
The major hazards encountered in the use and
handling of chloroform stem from its toxicologic
properties. Toxic effects may be exerted from all routes of exposure (ie,
ingestion, dermal, or inhalation). Aside from possible contact burns or
irritation to the skin and eyes, the range of acute effects from exposure to chloroform
include dizziness, headache, nausea, CNS depression, cardiac arrhythmia, and
death. Chronic exposure may result in damage (sometimes fatal) to the liver and
kidneys. OSHA has set the PEL at 50 ppm, while the ACGIH recommends a TLV of 10
ppm. These levels notwithstanding, contact with chloroform
also should be protected against by wearing impervious clothing (PVC and rubber
are not suitable), and a full facepiece self-contained breathing apparatus
operated in positive pressure mode. Non-impervious clothing which becomes wet
with chloroform should be promptly removed and any
contaminated skin washed with soap and water. Only
authorized personnel should be permitted in areas where chloroform
exposure may occur. Chloroform will not ignite easily,
but it may burn with the emission of highly toxic (eg, phosgene) and irritating
gases. If chloroform is involved in a fire, extinguish
the fire using an agent suitable for the type surrounding material. Wear
protective equipment as stated above. Fire-control water
should be diked, as necessary, to prevent chloroform
from entering water sources and sewers. Chloroform
reacts explosively with chemically-reactive metals (eg, aluminum or magnesium
powder, sodium, and lithium), strong oxidizers, and strong caustics (eg,
alkalis), and decomposes in sunlight. Therefore, chloroform
should be stored away from such materials and in a dark, cool, dry,
well-ventilated areas. While chloroform has a pleasant,
etheric odor, this clear, colorless liquid also has the ability to cause
olfactory fatigue and, therefore, warning of its presence is not assured. For
this reason, and because its decomposition by prolonged exposure to air can
result in accumulation of phosgene, chloroform should
be kept in tightly closed containers affixed with the label, "Poison".
Containers may be transported by air, rail, road, or water.
Small spills of chloroform should be absorbed with
vermiculite, dry sand, or earth and collected for disposal. Large land spills
should be diked (eg, with soil or sand bags) and the bulk liquid absorbed (eg,
with fly ash or cement powder), or contained in an excavated pit, pond, or other
holding area that has been sealed with an impermeable flexible membrane liner.
Spills of chloroform in bodies of water
may first need to be trapped at the bottom with sand bag barriers and treated
with activated carbon. Trapped material is then removed by suction hose,
mechanical lifts, or dredges. Collected chloroform is a
candidate for liquid injection, rotary kiln, or fluidized bed incineration.
Before implementing any plans for permanent land disposal, consult with
environmental regulatory agencies.
Non-Human Toxicity Excerpts :
The carcinogenic activity of chloroform
administered at 0, 200, 400, 900, and 1800 mg/l in drinking water
was studied in male Osborne-Mendel rats and female B6C3F1 mice. A second control
group was included in the study and was restricted to the water
consumption of the high-dose group. Animals were maintained on study for 104
weeks. ... Chloroform increased the yield of renal
tubular adenomas and adenocarcinomas in male rats in a dose-related manner. For
the high-dose group, which corresponded to a time-weighted average dose of 160
mg/kg per day for 104 weeks, there was a 14% incidence of renal tubular adenomas
and adenocarcinomas, vs 1% in the control group. This compares to a 24%
incidence observed when 180 mg/kg per day of chloroform
was administered for 78 weeks in earlier studies. In contrast, chloroform
in the drinking water of mice failed to increase the
incidence of hepatocellular carcinomas in female B6C3F1 mice. The highest dose
group received a time-weighted average dose of 263 mg/kg per day for 104 weeks,
resulting in a 5% combined incidence of hepatocellular adenomas and carcinomas
relative to a 6% incidence in the control groups. In a prior National Cancer
Institute study an 80% incidence of hepatocellular carcinomas was observed at
270 mg/kg per day for 78 weeks. Chloroform administered
in drinking water evidently is capable of inducing
cancer in the rat kidney. However, the lack of response in the mouse liver when chloroform
is supplied in the drinking water suggests that earlier
reports of chloroform hepatocarcinogenesis may be
related to some interaction with the mode of administration (corn oil gavage).
Disposal Methods :
The following wastewater treatment
technologies have been investigated for Chloroform:
Concentration process: Biological treatment.
National Toxicology Program Studies :
The effect of chloroform
on fertility & reproduction in Swiss CD-l mice was evaluated by use of a
Continuous Breeding protocol. Chloroform was admin via
gavage using corn oil as the vehicle. Based on a 14-day, dose-finding study, 8,
20, & 50 mg/kg bw were chosen to test its effect on fertility &
reproduction. Based on the reference analyses of representative aliquots of
dosing soln, it was estimated that the actual doses received were 6.6, 16, &
41 mg/kg bw in the low, mid & high dose groups, respectively. Both male
& female mice (20 pairs/treatment group, 40 pairs
for control animals) were dosed daily for 7 days prior to & during a 98-day
cohabitation period. The F1 generation from the control & high dose groups
was also evaluated. At the high dose, chloroform treatment
had no apparent effect on fertility or reproduction in either parental (F0) or
F1 generation. F1 generation males in the high dose group showed significantly
increased epididymal weights & degeneration of epididymal ductal epithelium.
However, epididymal sperm motility, sperm count & sperm morphology were not
affected. F1 females in the high dose group showed increased liver weight &
there were signs of hepatocellular degeneration. It is concluded that chloroform
is not a selective reproductive toxicant in Swiss CD-1 mice.
Interactions :
Cysteine treatment
reduced both covalent binding and hepatotoxicity, while diethyl maleate treatments
incr both the hepatotoxicity of chloroform and the
covalent binding of chloroform metabolites to hepatic
proteins.
Other Chemical/Physical Properties :
The azeotrope with water
boils @ 56.1 deg C and contains 97.2% chloroform. The
ternary azeotrope with ethanol and water boils @ 55.5
deg C and contains 4 mol% alcohol and 3.5 mol% water.
At 25 deg C, chloroform dissolves 3.59 times its volume
of carbon dioxide.
Environmental Water Concentrations :
SURFACE WATER:
Various estuaries were studied for the concns of several pollutants. From
1987-89, chloroform was detected in the Scheldt,
Netherlands/Belgium estuary ranging from <10-1640 ng/l whereas in 1993, it
was detected at 42.6 ng/l(1). In 1992, chloroform was
detected in the Humber, Tees, Tyne, Wear, and Tweed estuaries (all located in
the U.K.) ranging from <10-16.2, <10-11,500, <10-239, <10-199, and
<10 ng/l, respectively(1). In 1990, chloroform was
detected in the Forth (U.K.) and Rhine (Netherlands) estuaries ranging from
<500 and 3-10 ng/l, respectively(1). From 1987-89, chloroform
was detected in the Mersey(U.K.) estuary ranging from 200-5,200 ng/L(1). In
February and May of 1977, chloroform was detected in
Back River (U.S.A.) ranging from <120-49000 and 120-12500 ng/l,
respectively(1). The main factor determining the estuarine VOC concn is the
proximity of industrial sites(1). Chloroform was also
detected in fjord waters at Stenungsundfjorden (Sweden)
in 1988 ranging from 5.4-14.8 ng/l and in shelf sea waters
off the Belgian Continental Shelf in 1993 ranging from 11.3-17.4 ng/l(1). In
August 1972, chloroform concns in the North East
Atlantic were measured ranging from 4-13 ng/l(1).
Probable Routes of Human Exposure :
Several experiments indicate that dermal
absorption of chloroform during a shower is roughly
equivalent to inhalation exposure during the shower(1). It has been estimated
that about half the exposure from a 10-min shower is due to dermal
absorption(1). The major source of exposure to chloroform
is chlorination of water supplies(1). The results in
exposure through ingestion of drinking water, but also
through inhalation and skin absorption as a result of the myriad other uses of
chlorinated water in the home: showers, baths, washing
clothes and dishes, etc supports this(1). At a typical personal exposure to chloroform
of about 3 ug/cu m(not including exposure during the shower), this results in an
estimated intake of about 24 ug/day for women and 30 ug/day for men(1). A
typical chloroform level in soft drinks is about 23 ug/l(1).
For an avg soft drink intake of 289 ml/day, this corresponds to a chloroform
intake of about 6 ug/day(1). Limited data on levels of trihalomethanes
(including chloroform) in food suggest that the
additional intake from other foods and dairy products will be small(1). Thus,
total intake from food and beverages appears to be approximately 10 ug/day for
someone who drinks an avg amount of soft drinks(1).
Disposal Methods :
Generators of waste (equal to or greater than
100 kg/mo) containing this contaminant, EPA hazardous waste number U044, must
conform with USEPA regulations in storage, transportation, treatment
and disposal of waste.
Disposal Methods :
Generators of waste (equal to or greater than
100 kg/mo) containing this contaminant, EPA hazardous waste number D022, must
conform with USEPA regulations in storage, transportation, treatment
and disposal of waste.
Disposal Methods :
PRECAUTIONS FOR "CARCINOGENS": HEPA
(high-efficiency particulate arrestor) filters ... can be disposed of by
incineration. For spent charcoal filters, the adsorbed material can be stripped
off at high temp & carcinogenic wastes generated by this treatment
conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal
should be carried out by incineration at temp that ... ensure complete
combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid
wastes ... should be disposed of by incineration at temp high enough to ensure
destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/
Disposal Methods :
PRECAUTIONS FOR "CARCINOGENS": ...
Small quantities of ... some carcinogens can be destroyed using chem reactions
... but no general rules can be given. ... As a general technique ... treatment
with sodium dichromate in strong sulfuric acid can be used. The time necessary
for destruction ... is seldom known ... but 1-2 days is generally considered
sufficient when freshly prepd reagent is used. ... Carcinogens that are easily
oxidizable can be destroyed with milder oxidative agents, such as saturated soln
of potassium permanganate in acetone, which appears to be a suitable agent for
destruction of hydrazines or of compounds containing isolated carbon-carbon
double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an
oxidizing agent. /Chemical Carcinogens/
Disposal Methods :
The following wastewater treatment
technologies have been investigated for Chloroform:
Concentration process: stripping.
Disposal Methods :
The following wastewater treatment
technologies have been investigated for Chloroform:
Concentration process: activated carbon.
Disposal Methods :
The following wastewater treatment
technologies have been investigated for Chloroform:
Concentration process: resin adsorption.
Disposal Methods :
SRP: At the time of review, criteria for land treatment
or burial (sanitary landfill) disposal practices are subject to significant
revision. Prior to implementing land disposal of waste residue (including waste
sludge), consult with environmental regulatory agencies for guidance on
acceptable disposal practices.
Antidote and Emergency Treatment :
Advanced treatment:
Consider orotracheal or nasotracheal intubation for airway control in the
unconscious patient. Positive pre s sure ventilation techniques with a bag valve
mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as
necessary ... . Start an IV with D5W /SRP: "To keep open", minimal
flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Consider
drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia,
administer fluid cautiously. Consider vasopressors if hypotensive with a normal
fluid volume. Watch for signs of cardiac irritability and fluid overload ... .
Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to
assist eye irrigation ... . /Halogenated aliphatic hydrocarbons and related
compounds/
Non-Human Toxicity Excerpts :
GROUPS OF 5 STRAIN A MICE OF EACH SEX, 3 MO
OLD AT THE BEGINING OF THE EXPERIMENT WERE GIVEN 30 ORAL DOSES OF 0.1, 0.2, 0.4,
0.8 OR 1.6 ML/KG (0.15-2.4 G/KG BODY WT) CHLOROFORM IN
OLIVE OIL AT 4-DAY INTERVALS. SURVIVORS WERE KILLED 1 MO AFTER LAST TREATMENT.
ALL FEMALES AT THE 3 HIGHEST DOSES AND ALL MALES AT THE 3 HIGHEST DOSES DIED
EARLY IN THE EXPERIMENT. NONMETASTASIZING HEPATOMAS & CIRRHOSIS WERE FOUND
IN ALL SURVIVING FEMALES GIVEN 0.8 OR 0.4 ML/KG BODY WEIGHT PER DOSE. NO
HEPATOMAS WERE OBSERVED IN THOSE AT THE TWO LOWEST DOSE LEVELS OR IN THE
CONTROLS.
Mechanism of Action :
Mechanisms of chloroform
and carbon tetrachloride toxicity to primary cultured male B6C3F1 mouse
hepatocytes were investigated. The cytotoxicity of both chloroform
and carbon tetrachloride was dose and duration dependent. Maximal hepatocyte
toxicity, as determined by lactate dehydrogenase leakage into the culture
medium, occurred with the highest concentrations of chloroform
(5 mM) and carbon tetrachloride (2.5 mM) used and with the longest duration of treatment
(20 hr). Carbon tetrachloride was approximately 16 times more toxic than chloroform
to the hepatocytes. The toxicity of these compounds was decreased by adding the
mixed function oxidase system inhibitor, SKF-525A (25 microM) to the cultures.
The addition of diethyl maleate (0.25 mM), which depletes intracellular
glutathione (GSH)-potentiated chloroform and carbon
tetrachloride toxicity. The toxicity of chloroform
carbon tetrachloride could also be decreased by adding the antioxidants
N,N'-diphenyl-p-phenylenediamine (25 microM), alpha-tocopherol acetate (Vitamin
E) (0.1 mM), or superoxide dismutase (100 U/ml) to the cultures. These results
suggest that: in mouse hepatocytes, both chloroform and
carbon tetrachloride are metabolized to toxic components by the mixed function
oxidase system; GSH plays a role in detoxifying those metabolites; free radicals
are produced during the metabolism of chloroform and
carbon tetrachloride and free radicals may be important mediators of the
toxicity of these two halomethanes.
Interactions :
Exposure to chlordecone (CD, Kepone) is known
to increase the hepatotoxicity of chloroform in rats. A
time-course analysis was conducted relating several indices of biotransformation
capacity with the ability of chlordecone to potentiate chloroform-induced
hepatotoxicity. Male Sprague-Dawley rats were given a single administration of
corn oil alone or chlordecone (50 mg/kg, po) dissolved in corn oil. At 2, 4, 8,
16, 20, 24, or 32 days posttreatment, groups of rats were killed and their
livers were analyzed for (i) cytochrome p450, NADPH-dependent cytochrome c
reductase, cytochrome b5 and glutathione content or (ii) in vitro irreversible
binding of (14)CHCl3-derived radiolabel to microsomal protein. Similarly treated
rats were challenged (2-32 days posttreatment) with chloroform
(0.5 ml/kg po); 24 hr later, liver damage was assessed by plasma alanine
aminotransferase, plasma ornithine carbamyl transferase, plasma bilirubin, and
hepatic glucose-6-phosphatase. Chlordecone potentiation was maximal &
persisted up to 20-24 days post-chlordecone treatment.
Formulations/Preparations :
Chloroform water:
chloroform 0.25% vol/vol in freshly boiled and cooled water
Formulations/Preparations :
Concentrated chloroform
water: chloroform 10 ml,
alcohol (90%) 60 ml, water to 100 ml
Formulations/Preparations :
Double-strength chloroform
water: chloroform 0.5% vol/vol
in freshly boiled and cooled water
Protective Equipment & Clothing :
Facilities for quickly drenching the body
should be provided within the immediate work area for emergency use where there
is a possibility of exposure. [Note: It is intended that these facilities
provide a sufficient quantity or flow of water to
quickly remove the substance from any body areas likely to be exposed. The
actual determination of what constitutes an adequate quick drench facility
depends on the specific circumstances. In certain instances, a deluge shower
should be readily available, whereas in others, the availability of water
from a sink or hose could be considered adequate.]
Preventive Measures :
Skin that becomes wet with liquid chloroform
should be promptly washed or showered with soap or mild detergent and water
to remove any chloroform. Employees who handle chloroform
should wash their hands thoroughly with soap and mild detergent and water
before eating, or smoking.
Preventive Measures :
Personnel protection: Keep upwind. ... Avoid
breathing vapors or dusts. Wash away any material which may have contacted the
body with copious amounts of water or soap and water.
Cleanup Methods :
Do not touch spilled material. Use water
spray to reduce vapors. For small spills, take up with absorbent material then
flush area with water. For large spills, dike far
ahead.
Cleanup Methods :
Environmental considerations - Water
spill: Use natural deep water pockets, excavated
lagoons, or sand bag barriers to trap material at bottom. Remove trapped
material with suction hoses. If dissolved, in region of 10 ppm or greater
concentration, apply activated carbon at ten times the spilled amount. Use
mechanical dredges or lifts to remove immobilized masses of pollutants and
precipitates.
Non-Human Toxicity Excerpts :
MICE WERE GIVEN ACCESS TO DEIONIZED WATER
FOR 30 MIN DAILY. WHEN FLUID CONSUMPTION STABILIZED, THEY WERE GIVEN 30 MIN
ACCESS TO 0.3% SACCHARIN FOLLOWED BY ORAL DOSES OF 3, 10 OR 30 MG/KG CHLOROFORM
OR VEHICLE (EMULPHOR). BEGINNING 24 HR LATER SUBJECTS WERE GIVEN 2-BOTTLE CHOICE
TEST SACCHARIN VS WATER FOLLOWED BY ADMIN OF CHLOROFORM.
30 MG/KG PRODUCED TASTE AVERSION ON 1ST CHOICE TEST & REDUCTION OF TOTAL
FLUID INTAKE. DOSES OF 3 & 10 MG/KG OR VEHICLE DID NOT AFFECT EITHER
MEASURE. ALSO IT PRODUCED TASTE AVERSIONS WHEN GIVEN AT RELATIVELY LOW DOSES BY
IP ROUTE.
Ecotoxicity Values :
LC50 Salmo gairdneri (rainbow trout) 2030 ug/l
soft water, 1240 ug/l hard water
(40% teratogenesis), 27 day flow-through tests (20 min after fertilization to 8
days after hatching)
Artificial Pollution Sources :
Emissions from its production and indirect
production (in the manufacture of ethylene dichloride); chlorination of drinking
water, municipal sewage, cooling water
in electric power generating plants; produced during the atmospheric
photodegradation of trichloroethylenes; auto exhaust; from its use as an
extractant or solvent, chemical intermediate, dry cleaning agent, fumigant
ingredient, in fluorocarbon 22 production, synthetic rubber production (1-2).
Volatilization from Water/Soil :
The Henry's Law constant for chloroform
is 3.67X10-3 atm-cu m/mole(1). This Henry's Law constant indicates that chloroform
is expected to volatilize rapidly from water
surfaces(2). Based on this Henry's Law constant, the volatilization half-life
from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is
estimated as 1.3 hrs(SRC). The volatilization half-life from a model lake (1 m
deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 4.4
days(SRC). Three laboratory studies of the evaporation of chloroform
from water gave half-lives of 3-5.6 hrs with moderate
mixing conditions(3-5). Chloroform's Henry's Law
constant(1) indicates that volatilization from moist soil surfaces may occur(SRC).
The potential for volatilization of chloroform from dry
soil surfaces may exist(SRC) based upon a vapor pressure of 197 mm Hg(6).
Environmental Water Concentrations :
SURFACE WATER: Ohio
River Basin (1980-81, 11 stations, 4972 samples) 72% pos, 832 samples 1-10 ppb,
27 samples >10 ppb(1). 14 Heavily Industrialized River Basins in US (204
sites) 1-120 ppb, 79% pos(2). US - 5 industrial cities 9-31 ppb avg, 394 ppb
max(3). 11 Water Utilities on Ohio River 0.8 ppb avg,
4.8 ppb max, 68% pos(4); Delaware River and tributaries - 30 sites 93% of
samples >1 ppb(5); Ohio River and tributaries 232 samples 0.1-22 ppb, 72%
pos(6); Lakes Erie, Michigan and Huron 1-30 ppb, 11 of 13 sites pos(7).
Body Burden :
The largest existing data set on chloroform
concns in the body has been provided by the TEAM Study measurements of exhaled
breath(1). About 800 people provided more than 1250 breath samples with mean
concns generally in the range of 0.5-3 ug/cu m with generally lower levels in
California compared with other sites (New Jersey, Maryland, North Dakota, and
North Carolina)(1). In a study of 163 people at indoor swimming pools, exposed
individuals had a mean chloroform concn in the higher
alveolar of 83 ug/cu m(1). Breath exposures were also studied from a single
subject who swam for 30 mins on 3 occasions, rested in the water
for the same length of time on one occasion and stayed near the pool but out of
the water for 30 mins on the final occasion(1).
Pre-exposure breath concns were less than 2 ug/cu m on all occasions, rising to
15 to 25 ug/cu m 2.5 mins after completing the swimming periods, but only to 11
mg/cu m after the poolside exposure period(1). A study of chloroform
found in blood revealed that out of 979 people sampled between 1988-1992, the
mean chloroform concn was 0.0444 ng/ml(1). This
suggests that a large percentage of the U.S. population is exposed to chloroform,
but that very large exposures are rare(1). Chloroform
was also detected in 40 out of 42 breast milk samples at levels ranging from 0.1
to 65 ng/ml from nursing mothers in two New Jersey hospitals and from three
other hospitals in Pennsylvania, Louisiana, and West Virginia(1).
Clean Water Act Requirements :
Chloroform is
designated as a hazardous substance under section 311(b)(2)(A) of the Federal Water
Pollution Control Act and further regulated by the Clean Water
Act Amendments of 1977 and 1978. These regulations apply to discharges of this
substance. This designation includes any isomers and hydrates, as well as any
solutions and mixtures containing this substance.
RCRA Requirements :
U044; As stipulated in 40 CFR 261.33, when chloroform,
as a commercial chemical product or manufacturing chemical intermediate or an
off-specification commercial chemical product or a manufacturing chemical
intermediate, becomes a waste, it must be managed according to Federal and/or
State hazardous waste regulations. Also defined as a hazardous waste is any
residue, contaminated soil, water, or other debris
resulting from the cleanup of a spill, into water or on
dry land, of this waste. Generators of small quantities of this waste may
qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).
Impurities :
A representative technical quality chloroform
contains the following amounts of the indicated substances (maximums): Water
(50 ppm), acid as HCL (10 ppm), methylene chloride (200 ppm), bromochloromethane
(300 ppm), carbon tetrachloride (250 ppm), 1,2-dichloroethylene (100 ppm),
vinylidene chloride (100 ppm), residue on evaporation at 110 deg C (10 ppm), and
dissolved chlorine (not detectable).
Formulations/Preparations :
Chloroform emulsion: chloroform
5 ml, quillaia liquid extract 0.1 ml, tragacanth mucilage 5 ml, water
to 100 ml
Formulations/Preparations :
Chloroform and
morphine tincture: chloroform 12.5 ml, morphine
hydrochloride 229 mg, alcohol (90%) 12.5 ml, liquorice liquid extract 12.5 ml,
treacle of commerce 12.5 ml, water 5 ml, anesthetic
ether 3 ml, peppermint oil 0.1 ml, syrup to 100 ml.
Solubilities :
Water solubility =
7,710 mg/l at 25 deg C
Solubilities :
In water, 3.81 g/kg @
25 deg C
Spectral Properties :
[Lillian D et al; Environ Sci Technol 9:
1042-8 1975) as cited in USEPA; Water-Related Environ
Fate of 129 Priority Pollutants p.40-2 (1979) USEPA 440/4-79-0296] Absorbs UV
maximally at 175 nm
Other Chemical/Physical Properties :
Liquid-Water
Interfacial Tension: 32.8 dynes/cm= 0.0328 N/m at 20 deg C
Other Chemical/Physical Properties :
Chloroform forms
azeotropes with acetone, 2-bromopropane, 2-butanone, ethanol, ethyl formate,
formic acid, n-hexane, isopropanol, methanol, methyl acetate, and water.
DOT Emergency Guidelines :
Health: Highly toxic, may be fatal if inhaled,
swallowed or absorbed through skin. Avoid any skin contact. Effects of contact
or inhalation may be delayed. Fire may produce irritating, corrosive and/or
toxic gases. Runoff from fire control or dilution water
may be corrosive and/or toxic and cause pollution.
DOT Emergency Guidelines :
Spill or leak: Do not touch damaged containers
or spilled material unless wearing appropriate protective clothing. Stop leak if
you can do it without risk. Prevent entry into waterways, sewers, basements or
confined areas. Cover with plastic sheet to prevent spreading. Absorb or cover
with dry earth, sand or other non-combustible material and transfer to
containers. DO NOT GET WATER INSIDE CONTAINERS.
DOT Emergency Guidelines :
First aid: Move victim to fresh air. Call 911
or emergency medical service. Apply artificial respiration if victim is not
breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the
substance; induce artificial respiration with the aid of a pocket mask equipped
with a one-way valve or other proper respiratory medical device. Administer
oxygen if breathing is difficult. Remove and isolate contaminated clothing and
shoes. In case of contact with substance, immediately flush skin or eyes with
running water for at least 20 minutes. For minor skin
contact, avoid spreading material on unaffected skin. Keep victim warm and
quiet. Effects of exposure (inhalation, ingestion or skin contact) to substance
may be delayed. Ensure that medical personnel are aware of the material(s)
involved, and take precautions to protect themselves.
Hazardous Decomposition :
The products of oxidative breakdown include
phosgene, hydrogen chloride, chlorine, carbon dioxide, and water.
Hazardous Decomposition :
On prolonged heating with water
@ 225 deg C, decomp to formic acid, carbon monoxide, and hydrogen chloride
occurs.
Odor Threshold :
Odor thresholds of 85 ppm and 2.4 ppm have
been reported for chloroform in air and water,
respectively.
Preventive Measures :
If material not involved in fire: Keep
material out of water sources and sewers. Build dikes
to contain flow as necessary.
Storage Conditions :
PVC bottles should not be used for storing or
dispensing chloroform and morphine tincture, aqueous
mixtures containing more than 5% thereof, mixtures or dispersions in which chloroform
was present in excess of its aqueous solubility, aqueous mixtures containing chloroform
and high concn of electrolytes, or chloroform water
or mixtures containing it if the period of use would exceed six wk.
Cleanup Methods :
Flush spill area with water.
Disposal Methods :
PRECAUTIONS FOR "CARCINOGENS":
Carcinogens that are alkylating, arylating or acylating agents per se can be
destroyed by reaction with appropriate nucleophiles, such as water,
hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various
alkylating agents varies greatly ... & is also influenced by sol of agent in
the reaction medium. To facilitate the complete reaction, it is suggested that
the agents be dissolved in ethanol or similar solvents. ... No method should be
applied ... until it has been thoroughly tested for its effectiveness &
safety on material to be inactivated. For example, in case of destruction of
alkylating agents, it is possible to detect residual compounds by reaction with
4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/
Non-Human Toxicity Excerpts :
Hepatocytes isolated from male Sprague-Dawley
rats (Harlan, 200-275 g) were exposed to halogenated hydrocarbons including chloroform.
Cell suspensions contained 2-3X10+6 cells/ml and were viable for 6 hr as
indicated by a < 10% increment in the fractional release of aspartate
aminotransferase (AST) activity. The addition of chloroform
(20 mM) caused a rapid release of AST into the incubation medium. The release
peaked within 20 min and approximately 20% (n= 4) of the total activity was
found in the medium. Only 3% of the activity was in the medium of control cells.
Untreated cells or cells treated with vehicle did not exhibit an increase of AST
release with time. The amount of AST release was concentration dependent (tested
at 10 and 20 mM) and related to the oil/water partition
coefficient. Cellular oxygen consumption was reduced by approximately 50% (n= 8)
by 20 mM chloroform, and the reduction was dose
dependent. The effects of cellular respiration were completely reversible within
one hr. A dose-related decrease of DNP stimulated oxygen consumption was
observed when chloroform was present. Succinate-stimulated
oxygen consumption was not abolished by up to 10 mM chloroform.
Absorption, Distribution & Excretion :
Distribution of radioactivity in pregnant mice
was registered at different time intervals (0-24 hr) after a 10 min period of
inhalation of (14)C-labeled chloroform and methyl chloroform.
Autoradiographic and liquid scintillation methods were used to make possible the
distinction between volatile (non-metabolized), water-soluble
and firmly tissue-bound radioactivity. Methyl chloroform
was retained longer in fat as compared to chloroform.
Metabolites of chloroform were present in a much
greater abundancy than those of methyl chloroform and
they were found preferentially in the respiratory tract (nasal mucosa, trachea
and bronchi), liver and excretory organs. Tissue-bound activity after Chloroform
inhalation or ip injection to newborn mice was found in the respiratory tract
and centrilobular areas of the liver. Volatile radioactivity was observed in the
placenta and fetuses at short time intervals after inhalation of both chloroform
and methyl chloroform at all stages of gestation. ...
Metabolites accumulated in the embryonic neural tissues. Tissue-bound
metabolites of chloroform were observed in the fetal
respiratory epithelium.
Artificial Pollution Sources :
Chloroform's
production and use in the synthesis of hydrochlorofluorocarbon 22 (HCFC-22)(1)
may result in its release to the environment through various waste streams. Chloroform
is also released into the environment by the chlorination of drinking or waste-water(2,3).
Hypochlorous acid is formed during chlorination which reacts with organic
precursors forming chloroform(3). Another source of chloroform
is from the use of household liquid bleach containing sodium hypochlorite(3).
Some researchers calculated the total mass of sodium hypochlorite used in bleach
in the U.S. in 1984 to be about 150 million lbs(3). Using an emission factor of
0.00168 lb chloroform produced per pound of chlorine
equivalent, the researchers calculated total emissions of chloroform
annually in the South Coast basin to be 5.3 tons which would be the equivalent
of about 100 tons nationwide(3). Chloroform has also
been detected as a contaminant in products including stain removers, spot
removers, correction fluid, fabric softeners and rodenticides(3). Of 19 building
materials and other products used in a new building, four emitted chloroform:
two insecticides, a rodenticide and a scouring powder(3). Swimming pools have
also shown to be important sources of chloroform due to
their repeated chlorination(3).
Environmental Abiotic Degradation :
The rate constant for the vapor-phase reaction
of chloroform with photochemically-produced hydroxyl
radicals has been estimated as 1.03X10-13 cu cm/molecule-sec at 25 deg C(1).
This corresponds to an atmospheric half-life of about 151 days at an atmospheric
concn of 5X10+5 hydroxyl radicals per cu cm(1). Some studies have shown that chloroform
has an atmospheric half-life of 80 days with reaction with hydroxyl radicals
which amounts to a 0.9% loss per sunlit day(2,3). Chloroform
is more reactive in photochemical smog situations (presence of NOx) with an avg
degradation rate of 0.8%/hr(4). A base-catalyzed second-order hydrolysis rate
constant of 6.5X10-5 L/mole-sec(SRC) was estimated using a structure estimation
method(5); this corresponds to half-lives of 3400 and 340 yrs at pH values of 7
and 8, respectively(5). Based on this estimation, base catalyzed hydrolysis is
not expected to be environmentally important degradation process(SRC). Another
study has determined a hydrolysis half-life of 1850 yrs at 25 deg C and pH 7(6).
Under oxidative degradation, chloroform has been shown
to produce phosgene, hydrogen chloride, water, carbon
dioxide and chlorine(7). Chloroform decomposes at
ordinary temperature in sunlight in the absence of air, and in the dark in the
presence of air(8). Photodegradation does not appear to be a significant loss
process in aquatic systems(9).
Environmental Water Concentrations :
GROUNDWATER: Contaminated wells in NY and NJ
67-490 ppb(1); Groundwater in the Netherlands 5 ppb(2). Water
samples taken from 50 different groundwater sources located within the state of
Kansas had an avg chloroform concn of 13.5 ug/l (range
<0.1-91.2 ug/l)(3). Most of the samples were collected between mar 7 and Apr
11, 1986(3).
Environmental Water Concentrations :
RAIN/FOG/SNOW: Detected in rain and snow in
Japan(1,2) and 250 parts per trillion rain in West Los Angeles(3). Chloroform
concns in clouds was investigated from samples collected above the canopy of a
coniferous forest during several days between May and October 1987 and May and
July 1988 at Mt. Mitchell State Park, NC(4). The avg concn detected in the cloud
water samples was 2.41 ng/ml (range 0-10 ng/ml) while
avg air concns were 1.19 ng/l and avg rain concns 241 ng/l(4). The deposition
via clouds was estimated to be 1.27X10+6 ng/sq m yr(4).
Probable Routes of Human Exposure :
NIOSH (NOES Survey 1981-1983) has
statistically estimated that 95,773 workers (41,397 of these are female) are
potentially exposed to chloroform in the US(1).
Occupational exposure to chloroform may occur through
inhalation and dermal contact with this compound at workplaces where chloroform
is produced or used(SRC). The general population may be exposed to chloroform
via inhalation of ambient air(2,3), ingestion of food(2) and drinking water(2,4).
Probable Routes of Human Exposure :
Personal air concns of chloroform
were studied for 12 hr exposure periods(1). Forty eight people in New Jersey
during Feb 1983 had a mean personal exposure of 4.0 ug/cu m during day and
nighttime while 40 individuals in Los Angeles, CA during June 1987 had a mean
personal exposure of 3.8 ug/cu m during the day and 0.92 ug/cu m during
nighttime(1). In Antioch-Pittsburg, CA during June 1984, 68 people had a mean
personal exposure to chloroform of 0.47 ug/cu m during
the day and 0.80 during nighttime(1). Several studies of indoor swimming pools
indicate that inhalation can provide substantial amounts of chloroform(1).
A study of 3 indoor swimming pools and 3 life guards resulted in increases of
personal air exposures to chloroform(1). Personal air
exposures for the 3 lifeguards at the indoor pool were 95, 68, and 46 ug/cu m
while at home exposures dropped to 2.2, 2.0 and 5.2 ug/cu m(1). However, outdoor
pools showed no difference in personal air exposure to chloroform(1).
A pilot study carried out in Japan measured the intake of chloroform
from air, food, and tap water for 7 Japanese housewives
on 3 consecutive days in each of two seasons. For all 7 subjects in winter and 6
out of the 7 in summer, food contributed the most to their daily intake,
accounting for about half of the daily intake of 37 ug in the summer and 70% of
the smaller winter intake of 14 ug(1).
Clean Water Act Requirements :
Based on the consumption of 2 l of drinking water
and consumption of 6.5 g of fish and shellfish, the corresponding cancer risk
levels and criteria are 1X10-7: 0.019 ug/l; 1X10-6: 0.19 ug/l; 1X10-5: 1.90 ug/l.
Based on consumption of fish and shellfish only, the corresponding cancer risk
levels and criteria are 1X10-7: 1.57 ug/l; 1X10-6: 15.7 ug/l; 1X10-5: 157 ug/l.
Clean Water Act Requirements :
Toxic pollutant designated pursuant to section
307(a)(1) of the Federal Water Pollution Control Act
and is subject to effluent limitations.
Clean Water Act Requirements :
The maximum contaminant level (MCL) set forth
by the National Primary Drinking Water Regulations for
organic chemicals including total trihalomethanes (the sum of the concentrations
of bromodichloromethane, dibromochloromethane, tribromomethane (bromoform) and trichloromethane
(chloroform)) is 0.10 mg/l. /Total trihalomethanes/
Analytic Laboratory Methods :
EPA Method EMSLC 551. Determination of
Chlorination Disinfection Byproducts and Chlorinated Solvents in Drinking Water
by Liquid-Liquid Extraction and Gas Chromatography with Electron-Capture
Detection.
Special Reports :
USEPA; Ambient Water
Quality Criteria Doc: Chloroform (1980) EPA
440/5-80-033
TSCA Test Submissions :
Chloroform (CAS #
67-66-3) was evaluated for developmental toxicity in pregnant Wistar rats
(23-25/group) exposed by inhalation at concentrations of 0, 30, 100, and 300 ppm
for 7 hours/day during Days 7-16 postconception. Treatment
was associated with dose-related depression of maternal food consumption and
bodyweight gains, primarily during the first week of treatment;
no further signs of maternal toxicity and no gross pathology were observed.
Signs of embryotoxicity included dose-dependent early intrauterine loss of
primordia with slightly stunted development (slightly reduced crown-rump length)
among the remaining live fetuses at all treatment
levels. No toxicologically significant incidence of malformations was observed
on Day 21 terminal necropsy of treated and control fetuses relative to
spontaneous occurrence in experimental controls.
TSCA Test Submissions :
Chloroform (CAS #
67-66-3) bioactivation and toxicity in the kidney and liver was investigated in
B6C3F1 mice and in male Osborne-Mendel rats exposed in an environmental chamber
to target vapor concentrations of 0, 10 (mice only), 100 (mice only), 400, and
1100 ppm for approximately 6 hours. Groups of 4 mice and 4 rats from each treatment
level were sacrificed for quantification of nonprotein sulfhydryl (NPSH, to
approximate glutathione) levels in liver and kidney tissues at 0, 2, 4, and 6
hours into the exposures and at 6, 12, 24, 46, and 48 hours following final
exposures. In mice, treatment was associated with
significant mortality 36 hours following 400 and 1100 ppm exposures, lethargy
and perineal staining (400, 1100 ppm), and light anesthesia (1100 ppm). Upon
necropsy, livers and kidneys appeared pale as compared to those of sham
controls. In rats, light anesthesia upon 1100 ppm exposures alone characterized
the clinical toxicity and no gross pathology was identified upon terminal
necropsy. Renal NPSH levels were statistically significantly (Winer's paired
t-test) depressed for prolonged periods following exposures of 100 ppm and above
in mice, while NPSH levels either equalled or slightly exceeded those of sham
control animals in rats of exposures below 1100 ppm. Conversely, mouse hepatic
NPSH levels dropped markedly at isolated sampling times only, the NPSH
depressions inconsistent and not dose related, but more profound in association
with 400 and 1100 ppm than with 10 and 100 ppm exposures. In rats, both renal
and liver NPSH levels were statistically significantly (Winer's paired t-test)
depressed at 4-hour sampling following 1100 ppm exposures. These studies
contributed to derivation of metabolic and bioactivation rate constants in
design of a physiologically-based pharmacokinetic (PB-PK) model of chloroform
toxicity.
TSCA Test Submissions :
Chloroform (CAS #
67-66-3) was evaluated for clastogenicity in Chinese Hamsters (5/sex/treatment
group) exposed by oral gavage to doses of 0 (solvent control), 40, 120, and 400
mg/kg bw with subsequent harvest, preparation and analysis of metaphase bone
marrow cells (100 cells/animal) at 6 (high dose), 24 (all doses), and 48 (high
dose) hours post-treatment. Hamsters of 400 mg/kg doses
exhibited signs of toxicity including hypoactivity, closed eyes, and arrested
food consumption. Slight enhancement of chromosomal aberrations was
statistically significant (Mann-Whitney-U-test) 6 and 24 hours after doses of
400 mg/kg, although the rate was still within the range of historical negative
controls. Further, outside the range of historical controls, no dose-response
relationship was demonstrated. The study authors noted an inference of chloroform
mutagenicity, however, based on the nature of marked damage (multiple
aberrations, chromosomal disintegration, and exchanges) associated with oral chloroform
at doses of 120 and 400 mg/kg (6-, 24-, and 48-hour assessments). In repeat
study, exposing groups of hamsters to doses of 0 (solvent control), 120, and 400
mg/kg bw, 24-hour cytogenetic assay again revealed a slight but statistically
significant increase in chromosome aberrations in association with 400 mg/kg
doses, failing again to demonstrate a dose-response relationship for rates of
damage (chromosome breaks) beyond the range of historical controls. Distinctly
heavy damage (multiple aberrations and exchanges) characterized the chloroform-induced
aberrations at 400 mg/kg in 6/6000 metaphase bone marrow cells.
TSCA Test Submissions :
The rate of chloroform
(CAS # 67-66-3, CHCl3) metabolism was evaluated in 6-hour in vitro bioassay with
microsomal fractions of liver and kidney from B6C3F1 mice, F344 rats, Syrian
Golden hamsters, and humans. Microsomal protein preparations of each species
were incubated for 30 minutes with labeled 14CHCl3 in dimethyl formamide, a
NADPH regenerating system and a potassium phosphate buffer (pH 7.4). Boiled
enzyme preparations containing equivalent amounts of protein served as controls.
The reaction terminated at 30 minutes, CO2 generated by the enzymatic reaction
was measured and the solution's unreacted substrate (14CHCl3) and water-soluble
reaction products separated by solvent extraction (unlabeled CHCl3). Liquid
scintillation assay in combined species analysis (mice, rats, hamsters, and
humans) documented a rate of 14CHCl3 biotransformation to water-soluble
metabolite proportional to time for 10-30 min and proportional to protein
concentration up to 1-2 mg protein per incubation. This reaction was wholly
inhibited by boiling the enzyme prior to incubation. Reaction rates or MFO
(mixed function oxidase) activities (nmoles oxidized/min/mg protein at
0.049-0.058 mM CHCl3) in liver microsomes of mouse, rat, and hamster ranged from
0.0199 (rat) to 0.133 (hamster) nmoles/min/mg protein. Human liver microsomes
demonstrated a broad activity range from 0.003 - 0.017 nmoles/min/mg protein
(mean +/- s.d. = 0.00816 +/- 0.00448), the slowest rates among tested mammals.
Descending rates of CHCl3 metabolism in the kidney were found in mice (0.0102
nmoles/min/mg protein), hamsters (0.00562 nmoles/min/mg protein), and rats
(0.000928 nmoles/min/mg protein). Human kidney samples were limited and failed
to demonstrate microsomal rates of CHCl3 metabolism above the minimal detection
limit (0.0003 nmoles/min/mg protein at 0.06 mM CHCl3). Species-specific
metabolic indices were subsequently derived by computer optimization of kinetics
study data associated with 1-20 mM 14CHCl3 for development of a
physiologically-based pharmacokinetic (PB-PK) model of chloroform
toxicity.
TSCA Test Submissions :
The toxicokinetics of chloroform
(CAS # 67-66-3, CHCl3) was systematically evaluated and interpreted in various
species including B6C3F1 mice, Fischer 344 and male Osborne-Mendel rats, and
male Syrian Golden hamsters for development and validation of a
physiologically-based pharmacokinetic (PB-PK) model of prospective dose-,
species- and route-specific disposition of CHCl3. This model assumes total chloroform
metabolism within target organs, liver and kidney, solely by a mixed function
oxidase (MFO) metabolic pathway following Michaelis-Menten kinetics. Metabolic
rate constants (Vmax, Km, and V/S), calculated by computer optimization of
multispecies enzyme activity and kinetics studies in liver and kidney, allowed
extrapolation of results between species. The model facilitates determination of
a "delivered dose" (macromolecular binding, MMB) of chloroform
metabolites to chloroform-sensitive internal organs to
imply a potential cytotoxicity and tumorigenicity associated with chronic CHCl3
exposure. Toxicologically-significant descending relative rates of chloroform
sensitivity in mice, rats, and humans were revealed. In chronic inhalation study
with B6C3F1 mice, tumorigenicity correlated better with the rate of MMB (and a
cellular regenerative response) than with absolute metabolite or MMB levels.
Inclusion of historical absorption rates through digestive, respiratory, and
circulatory compartments in the mammalian model allowed toxicological
simulations based on route of administration. A homologous biochemical response
provides a basis for the extrapolation of toxicity associated with the
relatively high chronic exposures in studies with laboratory animals to that
expected in humans chronically exposed to lower levels of chloroform
typically encountered in the environment. Phase two studies will attempt to
correlate rates of cytotoxicity and cell death to MMB. The authors offered that
such a PB-PK model might be used for quantification of the potential biohazard
to humans chronically exposed to low level trichloromethane
found in chlorine-pretreated drinking water.
GLCC
RELATED TOXIC SUBSTANCES FOUND IN THE CAMP POND AND CAMP WATER WELL 2003 AND
2004
GREAT LAKES CHEMICAL CORPORATION AND THE PATHFINDERS CAMP