820K87001
March 31, 1987
TETRACHLOROETHYLENE (PCE)
Health Advisory
Office of Drinking Water
U.S. Environmental Protection Agency
I. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Drinking
Water (ODW), provides information on the health effects, analytical method-
ology and treatment technology that would be useful in dealing with the
contamination of drinking water. Health Advisories describe nonregulatory
concentrations of drinking water contaminants at which adverse health effects
would not be anticipated to occur over specific exposure durations. Health
Advisories contain a margin of safety to protect sensitive members of the
population.
Health Advisories serve as informal technical guidance to assist Federal,
State and local officials responsible for protecting public health when
emergency spills or contamination situations occur. They are not to be
construed as legally enforceable Federal standards. The HAs are subject to
change as new information becomes available.
Health Advisories are developed for One-day, Ten-day, Longer-term
(approximately 7 years, or 10% of an individual's lifetime) and Lifetime
exposures based on data describing noncarcinogenic end points of toxicity.
Health Advisories do not quantitatively incorporate any potential carcinogenic
risk from such exposure. For those substances that are known or probable
human carcinogens, according to the Agency classification scheme (Group A or
B), Lifetime HAs are not recommended. The chemical concentration values for
Group A or B carcinogens are correlated with carcinogenic risk estimates by
employing a cancer potency (unit risk) value together with assumptions for
lifetime exposure and the consumption of drinking water. The cancer unit
risk is usually derived from the linear multistage model with 95% upper
confidence limits. This provides a low-dose estimate of cancer risk to
humans that is considered unlikely to pose a carcinogenic risk in excess
of the stated values. Excess cancer risk estimates may also be calculated
using the One-hit, Weibull, Logit or Probit models. There is no current
understanding of the biological mechanisms involved in cancer to suggest that
any one of these models is able to predict risk more accurately than another.
Because each model is based on differing assumptions, the estimates that are
derived can differ by several orders of magnitude.
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This Health Advisory (HA) is based on information presented in the
Office of Health and Environmental Assessment Criteria Document (CD) for
Tetrachloroethyiene (U.S. EPA, I985a). Individuals desiring further informa-
tion on the toxicological data base or rationale for risk characterization
should consult the CD. The CD is available for a fee from the National
Technical Information Service, U.S. Department of Commerce, 5285 Port Royal
Rd., Springfield, VA, 22161. The toll-free number is (800) 336-4700; in the
Washington, D.C. areas (703) 487-4650.
II. GENERAL INFORMATION AND PROPERTIES
CAS No. 127-18-4
Structural Formula
Cl - C = C - Cl
I I
Cl Cl
Synonyms^ •
PCE, Perchloroethylene, 1,1,2,2-Tetrachloroethylene, Perc
Uses
Solvent for many organic substances
In drycleaning processes
Metal degreaser
Intermediate in the synthesis of certain fluorocarbons
In the textile industry (Fuller, 1976)
Properties (Verschueren, 1977; Torkelsen and Rowe, 1981; Windholz, 1983)
Chemical Formula
Molecular Weight 165.85
Physical State liquid
Boiling Point 121.2°C
Melting Point
Density —
Vapor Pressure 19 mm Hg
Specific Gravity 1.623
Water Solubility 150 mg/L (258C)
Log Octanol/Water Partition 2.86
Coefficient
Taste Threshold —
Odor Threshold (water) 300 ug/L
1 ppm in air 6.78
Conversion Factor —
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Tetrachloroethylene March 31, 1987
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Occurrence
0 Tetrachloroethylene (PCE) is a synthetic chemical with no natural sources.
0 Production of PCE was 550 million pounds in 1982 (U.S. ITC, 1983).
0 The majority of PCE is not consumed during its various uses, but is
released directly to the atmosphere. Tetrachloroethylene that does
not evaporate during use becomes heavily contaminated with grease and oil
and is disposed of in the forms of solid and liquid wastes. During
disposal, PCE is dischrarged directly to land and surface water.
Because metal and fabric cleaning industries are widely dispersed,
PCE releases occur nationwide.
0 PCE released to air degrades in a matter of days or weeks. PCE
released to water degrades slowly; volatilization appears to be the
major transport process for removal of PCE from aquatic systems (U.S.
EPA, 1979). It is very mobile in soil and readily migrates to ground
water. In ground water, where volatilization does not occur, PCE
remains for months or years. Under certain conditions, PCE in ground
water has been reported to degrade to trichloroethylene and then to
dichloroethylene and vinyl chloride (Parsons et al., 1984; Vogel and
McCarty, 1985).
0 Tetrachloroethylene is ubiquitdus in the air with levels in the ppt
to ppb range. It is also a common contaminant in ground and surface
waters with higher levels found in ground water. Surveys of drinking
water supplies have found that 3% of all public systems derived from
well water contain PCE levels of 0.5 ug/L or higher. A small
number of systems (0.7%) have levels higher than 5 ug/L. Public
systems derived from surface water have also been found to contain
tetrachlorethylene but at lower levels.
0 The major sources of exposure to tetrachloroethylene are from contami-
nated water and to a lesser extent air. Tetrachloroethylene has been
reported to occur in some foods in the ppm range, but food is considered
only a minor source of exposure (U.S. EPA, 1983).
III. PHARMACOKINETICS
Absorption
Single oral doses of (36d)-pcE were absorbed completely when admini-
stered to rats at a concentration of 189 mg/kg (Daniel, 1963) as were
doses of (14c)-PCE administered to mice at a dose of 500 mg/kg (Schu-
mann et al., 1980).
- Human volunteers at rest absorbed about 25 percent of PCE admini-
stered by inhalation exposure at 72 or 144 ppm over a four-hour
period. The compound initially was absorbed rapidly, with decreasing
uptake as exposure continued. Absorption was determined by measuring
PCE and its metabolites (trichloroethanol, trichloroacetic acid) in
exhaled air, blood and urine (Monster, 1979; Monster et al., 1979;
Monster and Houtkooper, 1979).
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Distribution
0 Once in the bloodstream, PCE tends to distribute to body fat. In
human tissue at autopsy, ratios of fat to liver concentrations are
greater than 6:1 (McConnell et al., 1975). The fat to blood ratio
is about 90 and the half-life for saturation of the fat to 50% of its
equilibrium concentration is about 25 hours (Monster, 1979).
0 In rats exposed via inhalation, PCE levels rise more or less continu-
ously with duration of exposure in brain, lungs, and fat, but tend to
level off in blood and liver after a 3-hour exposure. Brain cerebrum
concentrations of PCE exceed blood levels by about four-fold, and
brain cerebellum by about three-fold, independent of the duration of
exposure (Savolainen et al., 1977).
Metabolism
0 Only small amounts of PCE (less than 4% of the estimated absorbed dose)
are metabolized and excreted as trichloroacetic acid in humans (Ogata
et al., 1971; Fernandez et al., 1976).
0 Oxidative metabolism is proposed to proceed via an epoxide intermediate
which can lead to the major metabolite, trichloroacetic acid. (U.S.
EPA, 1985a). In humans, PCE is metabolized to trichloroethanol,
trichloroacetic acid and unidentified chlorinated products (Ikeda and
Ohtsuji, 1972; Ikeda, 1977).
0 Workers exposed occupationally reached a plateau rate of urinary
metabolite excretion (measured as total trichloro-compounds) when the
workplace air concentrations of PCE approached 100 ppm. Metabolite
excretion did not increase when air concentrations rose to 400 ppm
(Ikeda et al., 1972).
Excretion
PCE itself is eliminated primarily via the lungs. The respiratory
half-life for PCE elimination has been estimated at 65 to 70 hours
(Stewart et al., 1970; Ikeda and Imamura, 1973).
Trichloroacetic acid, as a metabolite of PCE, is eliminated with a
half-life of 144 hours via the urine (Ikeda and Imamura, 1973).
IV. HEALTH EFFECTS
Humans
Liver, kidney, and CNS effects have been observed in humans occupationally
exposed to tetrachloroethylene (U.S. EPA, 1985a).
Hookworm treatment with oral PCE was prevalent in the 1920s and 1930s
in India and the Pacific Islands. Thousands of individuals received
oral doses of approximately 0.15 mL/kg (Kendrtck, 1929) or a total
dose of about 4 mL for adults (Fernando et al., 1939). No-effect
levels for oral exposure cannot be derived from these clinical reports,
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Tetrachloroethylene March 31, 1987
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although they suggest that PCE Is relatively nontoxic by the oral
route at these doses.
0 Stewart et al. (1974) exposed 19 volunteers to PCE (20 to 150 ppm) for a
5-week period and noted deleterious effects (decreased odor perception,
diminished response on the modified Romberg test) at 100 ppm but not
at 20 ppm.
Animals
Short-term Exposure
0 In mice, the 24-hour LD50s/LC5os are: 8.8 to 10.8 gAg by the oral
route (Wenzel and Gibson, 1951), 5,200 ppm with 4 hours inhalation
exposure (Friberg et al., 1953) and 4.7 gAg intraperitoneal (Klaassen
and Plaa, 1966).
0 In rats, the 24-hour LD50s/LC5os are 13 gAg oral (Smyth et al., 1969)
and 4,000 ppm with four hours inhalation exposure (Carpenter et al.,
1949).
0 Single oral gavage doses of 2,158 mgAg pCE to rabbits resulted in a
50% increase in serum lipoprotein levels and mild transient elevations
of serum enzymes (alkaline phosphatase, SCOT, SGPT) which were indica-
tive of liver damage (Fujii, 1975).
0 A dose-response related increase in fatty infiltration of the livers
of mice was observed after four hours of exposure to 200 to 3,000 ppm
(1400 to 20,000 mg/m3) via inhalation (Kylin et al., 1963). Decreased
hepatic ATP and increased total lipid and triglyceride levels were
observed in mice exposed to 800 ppm PCE in air for three hours (Ogata
et al., 1968).
0 Schumann, et al. (1980) administered tetrachloroethylene in corn oil
to rats and mice via gavage for 11 consecutive days at does of 100,
250, 500 and 1000 mgAg- F°r mice, histopathological changes (centrilobu-
lar swelling) were observed at all dose levels and increased body weight/
liver weight ratios were observed at doses of 250 mgAg/day and higher.
Rats were more resistant with toxicity (increased liver weight and
serum enzyme levels) apparent only at the highest dose. A LOAEL of
100 mgAg/dav was identified based on histopathological changes in
mice.
Longer-term Exposure
8 Rats were exposed to 70, 230 or 470 ppm PCE (470, 1600, or 3200 mg/m3)
by inhalation 8 hours/day, 5 days/week for 150 days. No significant
changes were observed at 70 ppm; renal and liver congestion and swelling
were observed at 230 and 470 ppm (Carpenter, 1937).
0 Rats, rabbits and monkeys were exposed via inhalation to PCE at 400 ppm
(2700 mg/m3) 7 hours/day, 5 days/week for up to 179 days (Rowe, et
al., 1952). . Histopathological examination of the liver, kidney and spleen
revealed no significant changes at this exposure level.
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0 Guinea pigs showed a dose dependent increase in liver weight and
fatty infiltration of the liver when exposed to 100, 200 or 400 ppm
(680, 1400, or 2700 mg/m3) for up to 169 exposures over 236 days
(Rowe et al., 1952).
0 Kylin et al. (1965) observed fatty infiltration in livers of mice
exposed to 200 ppm (1400 mg/m3), 4 hours/day, 5 days/week for 8 months.
0 In a study by Buben and O1Flaherty (1985), male Swiss-Cox mice were
exposed to tetrachloroethylene in corn oil via gavage at doses of 0,
20, 100, 200, 500, 1000, 1500, and 2000 mg/kg» 5 days/week for 6 weeks.
Liver toxicity was evaluated by several parameters including liver weight
/body weight ratio, hepatic triglyceride concentrations, DNA content,
histopathological evaluation and serum enzyme levels. Increased
liver triglycerides were first observed in mice treated with 100 mg/kg.
Liver weight/body weight ratios were significantly higher than controls
for th 100 mg/kg group, and slightly higher than controls in the 20
mg/kg group. A NOAEL of 20 mg/kg/<3ay was identified based on the
absence of hepatotoxic effects.
0 Toxic nephropathy was observed in mice exposed to 386 and 1072 mg/kg
in corn oil via gavage, 5 days/week, for 78 weeks (NCI, 1977).
Reproductive Effects
0 Rabbits showed liver enzyme changes and renal function alterations
following 200 to 300 ppm exposures (1400 to 20,000 mg/m3), 4 hours/day,
5 days/week for 9 weeks (Brancaccio et al., 1971; Mazza, 1972).
0 Pregnant rats exposed to 300 ppm PCE (20,000 mg/m3) for 7 hours/day,
on days 6 through 15 of gestation had 4 to 5% reduction in body weight
and twice the number of resoprtions per implantation compared with
controls (Schwetz et al. (1975).
Developmental Effects
0 Schwetz et al. (1975) assayed for reproductive and developmental
effects in rats and mice exposed to 300 ppm PCE (20,000 mg/m3) by
inhalation for 7 hours/day on gestational days 6 through 15. Pregnant
mice exhibited a significant increase in the mean relative liver
weights and their fetuses weighed significantly less than controls.
In the mouse pups, significant subcutaneous edema, delayed skull
ossification and ^he presence of split sternebrae were observed.
0 Offspring of rats exposed to PCE (900 ppm [6100 mg/m3], days 7-13
of gestation; 900 ppm, days 14-20 of gestation; 100 ppm [680 mg/m3],
days 14-20 of gestation) were evaluated with respect to brain histo-
pathoiogy and biochemistry and several behavioral parameters. No
significant differences were found between controls and the 100 ppm
dose group. Differences in neurotransmitter levels and some altera-
tions on behavioral tests were noted in the 900 ppm dose groups.
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Tetrachloroethylene March 31, 1987
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Mutagenicity
0 Several mutagenicity studies have been performed on PCE which -employ
the Ames Salmonella/microsome test or modifications of this test.
Most tests reveal little or no evidence of mutagenic activity by PCE
except at concentrations which result in greater than 90% bacterial
toxicity (U.S. EPA, 1985a).
Carcinogenicity
8 PCE containing stabilizers was concluded by NCI (1977) to be a liver
carcinogen in B6C3F-] mice administered 386 to 1,072 mgAg by gavage
for 78 weeks. No conclusion concerning the effects on Osborne-Mendel
rats administered 471 to 949 mg/kg by gavage could be made because of
high mortality rates (median survival for treated animals was less than
68 weeks compared to greater than 88 weeks for controls).
0 In the NTP (1985) inhalation bioassay, rats and mice of both sexes
were exposed to 0, 200 and 400 ppm (rats) and 0, 100 and 200 ppm
(mice) tetrachloroethylene. Male rats exhibited a significantly
increased incidence of mononuclear cell leukemia, and an increased
incidence of renal tubular adenomas/carcinomas (combined). PCE
induced hepatocellular carcinomas in male and female mice at both
doses. Classification of PCE as carcinogenic in the rat is contro-
versial. The Science Advisory Board's Halogenated Organics Subcommittee
(U.S. EPA, 1987) has questioned the relevance of mononuclear leukemia
to man, a species not susceptible to this type of leukemia, and the
validity of combining renal adenomas/carcinomas to achieve statistical
significance to the results.
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS
Health Advisories (HAs) are generally determined for One-day, Ten-day,
Longer-term (approximately 7 years) and Lifetime exposures if adequate data
are available that identify a sensitive noncarcinogenic end point of toxicity.
The HAs for noncarcinogenic toxicants are derived using the following formula:
HA = (NOAEL or LOAEL) x (BW) = /L ( /L)
(UF) x ( L/day)
where:
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
in mg/kg bw/day.
BW = assumed body weight of a child (10 kg) or
an adult (70 kg).
UF = uncertainty factor (10, 100 or 1,000), in
accordance with NAS/ODW guidelines.
L/day * assumed daily water consumption of a child
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One-day Health Advisory
The available studies were not considered sufficient for derivation of a
One-day HA. It is recommended that the value for the Ten-Day HA, 2 mg/1, be
used at this time as a conservative estimate for the One-Day HA.
Ten-day Health Advisory
Hepatotoxicity in mice exposed to tetrachloroethylene was selected as the
basis for calculating the Ten-day HA value. Schumann et al. (1980) administered
PCE in corn oil to rats and mice via gavage for 11 consecutive days at doses
of 0, 100, 250, 500 and 1000 mg/kg. For mice, histopathological changes
(centrilobular hepatocellular swelling) were observed in all treated animals,
and increased liver weight/body weight ratios were observed in animals exposed
to doses of 250 mg/kg and higher. The lowest dose, 100 mg/kg/day, represents
the LOAEL for the study. This value is consistent with the estimated LOAEL
(based on altered hepatic lipid and triglyceride content) of 160 mg/kg/day
for mice exposed to 200 ppm for 4 hours (Kylin et al, 1963; see appendix),
and could be used as the basis for the Ten-Day Health Advisory with the
application of an uncertainty factor of 1000. This uncertainty factor is in
accordance with NAS/ODW guidelines for derivation of the HA based on a LOAEL
from an animal study. Data from longer-term studies indicates that an uncer-
tainty factor of 1000 may be overly conservative in this case.
Buben and 0"Flaherty (1985) treated mice with doses ranging from 20 to
2000 mg/kg, 5 days/week for 6 weeks and observed a slight increase in liver
weight in mice treated with 20 mg/kg; at 100 mg/kg, increases were significantly
different from controls. From this study, a dose of 20 mg/kg was identified as
a NOAEL and 100 mg/kg was identified as a LOAEL. Basing the Ten-day HA on the
NOAEL of 20 mg/kg with an uncertainty factor of 100 is consistent with the
protection of humans from the CNS effects observed by Stewart et al. (1980)
at 100 ppm for 7 hours (approximately 20 mg/kg, see appendix).
The value was calculated as follows:
Ten-day HA = (20 mgAg/day) (10 kg) = 2.0 mg/L = 2,000 ug/L
y (100) (1 L/day)
where:
20 mgAg/day = NOAEL based on the absence of effects on liver weight
of mice exposed to tetrachloroethylene via gavage.
10 kg = assumed body weight of child.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use of a NOAEL from an animal study.
1 L/day = assumed daily water consumption for a child.
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Tetrachloroethylene March 31, 1987
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Longer-term Health Advisory
The study by Buben and 0'Flaherty was also selected as the basis for the
longer-term HA. Lifetime carcinogenicity bioassays did not provide an indication
of toxicity at the low dose range (NCI, 1977; NTP, 1985). The NOAEL of
20 mg/kg/day and the LOAEL of 100 mg/kg/day identified in the study by Buben
and O'Flaherty are consistent with estimates of LOAELs from inhalation studies.
A LOAEL of 63 mg/kg/day (based on increased liver weight and fatty infiltration
of the liver) was estimated from chronic exposure of guinea pigs to 100 ppm
for 7 hours/day (Rowe et al., 1952; see appendix), and a LOAEL of 160 mg/kg/day
(based on fatty infiltration of the liver) from mice exposed to 200 ppm for 4
hours (Kylin et al, 1965). The Longer-term HA value for a 10-kg child was
calculated as follows:
Longer-term HA = (20 mg/kg/day)(5/7)(10 kg) = , >4 /L = ,,400 /L
(100) (1 L/day)
where:
20 mg/kg/day = NOAEL based on the absence of effects on liver weight
for mice exposed to tetrachloroethylene via gavage.
5/7 = factor to convert 5 day/week exposure to daily exposure.
10 kg = assumed weight of child.
100 = uncertainty factor chosen in accordance with NAS/ODW
guidelines for used of a NOAEL from an animal study.
1 L/day = assumed water consumption for a 10 kg child.
The Longer-term HA value for a 70-kg adult was calculated as follows:
Longer-term = (20 mg/kg/day)(5/7)(70 kg) = 5>0 /L = 5 000 /L
(100) (2 L/day) y
where:
20 mg/kg/day = NOAEL based on the absence of effects on liver weight
for mice exposed to tetrachloroethylene via gavage.
5/7 = factor to convert 5 day/week exposure to daily exposure.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use of a NOAEL from an animal study.
70 kg = assumed weight of adult.
2 L/day = assumed water consumption for 70 kg adult.
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Tetrachloroethylene March 31, 1987
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Lifetime Health Advisory
The Lifetime HA represents that portion of an individual's total exposure
that is attributed to drinking water and is considered protective of noncar-
cinogenic adverse health effects over a lifetime exposure. The Lifetime HA
is derived in a three step process. Step 1 determines the Reference Dose
(RfD), formerly called the Acceptable Daily Intake (ADI). The RfD is an esti-
uidLe of d daily exposure to the human population that is likely to be without
appreciable risk of deleterious effects over a lifetime, and is derived from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor(s). From the RfD, a Drinking Water Equivalent Level
(DWEL) can be determined (Step 2). A DWEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
adult. The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC). The RSC from drinking
water is based on actual exposure data or, if data are not available, a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals. If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential (U.S. EPA, 1986), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.
No suitable chronic oral or lifetime oral studies were located in the
literature to serve as the basis for the Lifetime HA value. NOAELs were not
identified in the NCI (1977) study in which LOAELs were identified at high
doses (386 ragAg/day, mice, 471 mgAg/day, rats). The NTP (1983) study in
which lower doses were tested has not been validated.
Approximate NOAELs and LOAELs calculated from chronic and lifetime inhalation
studies give less conservative estimates of toxic doses than the six-week
oral study of Buben and O'Flaherty (1985). LOAEL estimates of 63 mgAg/day
for guinea pigs exposed to 100 ppm, 7 hrs/day (Rowe et al., 1952), 400 mgAg/day
for rats exposed to 475 ppm for 7 hr/day (Carpenter, 1937) and 160 mgAg/day
for mice exposed to 100 ppm for 6 hr/day (NTP, 1985) are consistent with the
NOAEL of 20 mgAg/day and LOAEL of 100 mgAg/day identified in the study by
Buben and O'Flaherty. In this study, mice were treated with doses of 20 to
2000 mgAg/day, 5 days/week for 6 weeks. A slight increase in liver weight
was observed at 20 mgAg» at 100 mgAgr liver weight and hepatic triglyceride
levels were significantly increased over controls. Using the NOAEL of 20
mgAg/day and an uncertainty factor of 1000 consistent with the use of data
from less than lifetime studies, the Reference dose and DWEL were calculated
as follows:
Step 1: Determination of the Reference Dose (RfD)
Reference Dose = (20 mgAg/day) (5/7) = Q.0143
1000
where:
20 mgAg/day = NOAEL based on the absence of effects in liver weight
for mice exposed to tetrachloroethylene via gavage.
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Tetrachloroethylene March 31, 1987
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S/7 = factor to convert 5 day/week exposure to daily exposure.
1000 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study of
less-than-lifetime duration.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0.0143 mg/kg/day) (70 kg) = 0>5 mg/L = 500 ug/L
(2 L/day)
where:
0.0143 mg/kg/day = RfD.
70 kg = assumed body weight of an adult.
2 L/day = assumed daily water consumption of an adult.
Step 3: Determination of the Lifetime Health Advisory
A lifetime HA is not recommended for PCE because of its classification as
group B2: probable human carcinogen (US EPA, 1986). The estimated excess
cancer risk associated with lifetime exposure to drinking water containing
tetrachloroethylene at 500 ug/L is approximately 1 x 10~^. This estimate
represents the upper 95% confidence limit from extrapolations prepared by
EPA's Carcinogen Assessment Group using the linearized, multistage model.
The actual risk is unlikely to exceed this value, but there is considerable
uncertainty as to the accuracy of risks calculated by this methodology.
Controversy surrounds the classification of PCE. The Science Advisory
Board, Halogenated Organics Subcommittee has recommended a classification of
Group C: possible human carcinogen (U.S. EPA, 1987). This committee
concluded that the animal evidence of carcinogenicity was limited and
questioned grouping rat renal adenomas/carcinomas for statistical analysis
and extrapolating mouse mononuclear cell leukemia to man, a species which is
not susceptible to this type of leukemia. In contrast to group B2 carcinogens
for which no lifetime HA values are recommended, lifetime HA values are
calculated for group C carcinogens as follows:
Lifetime HA = 500 ug/L x 20% = 10 ug/L
10
where:
500 ug/L = DWEL.
20% = assumed relative source contribution from water.
10 = additional uncertainty factor per ODW policy to
account for possible carcinogenicity.
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Tetrachloroethylene March 31, 1987
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Evaluation of Carcinogenic Potential
0 The National Academy of Sciences (NAS, 1977, 1980) and EPA's Carcinogen
Assessment Group (Anderson, 1983) have calculated drinking water con-
centrations that would be estimated to increase the risk by one excess
cancer per million (10~®) and per one hundred thousand (10~5). Assuming
consumption of 2 liters of water/day by a 70 kg adult over a 70 year
lifetime, NAS calculated drinking water concentrations of 3.5 ug/L and
35 ug/L for 10~6 and 10~5 risks, respectively. CAG calculated concen-
trations of 66, 6.6 and 0.7 ug/L for 10~4, 10~5 and 10~6 risks, respec-
tively. Each group employed the linearized, non-threshold multistage
model, extrapolating from data obtained in the 1977 NCI bioassay in
mice.
0 The linear multistage model is only one method of estimating carcino-
genic risk. It is possible to estimate carcinogenic risk with the
probit, logit or Weibull models, but for PCE the data are inadequate
for calculating reasonable risk estimates using these techniques.
While recognized as statistically alternative approaches, the range of
risks described by using any of these modelling approaches has little
biological significance unless data can be used to support the selection
of one model over another. In the interest of consistency of approach
and in providing an upper bound on the potential cancer risk, the
Agency has recommended use of the linearized multistage approach.
0 IARC (1979) stated that there is limited evidence to conclude that it
is a carcinogen in mice, and placed it in Group 3.
0 The US EPA Carcinogen Assessment Group (CAG) classified tetrachloroethylene
in Group B2: Probable human carcinogen (U.S. EPA, 1986). This classifica-
tion has been questioned by the Science Advisory Board, Halogenated Orgar) < < •
Subcommittee, which has recommended a classification of Group C:
Possible human carcinogen (U.S. EPA, 1987).
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 The World Health Organization has recommended a tentative guideline
value of 10 ug/L for PCE in drinking water, based on carcinogenic
properties (WHO, 1984).
0 The National Academy of Sciences (NAS, 1980) calculated 24-hour and
7-day SNARLS. The 24-hour SNARL was 172 mg/L, based on a 490 mg/kg
LOAEL following i.p. administration, a 100-fold uncertainty factor,
and a 70 kg adult drinking 2 L/day of drinking water. A 7-day SNARL
of 24.5 mg/liter was calculated by dividing the 24-hour SNARL by seven*
VII. ANALYTICAL METHODS
0 Analysis of tetrachloroethylene is by a purge-and-trap gas chromato-
graphic procedure used for the determination of volatile organohalides
in drinking water (U.S. EPA, 1985b). This method calls for the
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Tetrachloroethylene
March 31, 1987
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bubbling of an inert gas through the sample and trapping tetrachloro-
ethylene on an adsorbant material. The adsorbant material is heated
to drive off the tetrachloroethylene onto a gas chromatographic
column. This method is applicable to the measurement of tetrachloro-
ethylene over a concentration range of 0.03 to 1500 ug/L. Confirmatory
analysis for tetrachloroethylene is by mass spectrometry (U.S. EPA,
1985c). The detection limit for confirmation by mass spectrometry is
0.3 ug/L.
VIII. TREATMENT TECHNOLOGIES
Treatment technologies which will remove tetrachloroethylene from
water include granular activated carbon adsorption (GAG), aeration
and boiling.
Dobbs and Cohen (1980) developed adsorption curves for several organic
chemicals including PCE. It was reported' that Filtrasorb® 300 carbon
exhibited adsorptive capacities of 51 mg, 14 mg, 3.9 mg and 1.1 mg
PCE/gm carbon at equilibrium concentration of 1,000, 100, 10 and 1
mg/L respectively. USEPA-DV7RD installed pilot-scale adsorptiion
columns in New Jersey and Rhode Island. In Rhode Island, a Filtrasorb®
400 GAC column maintained a concentration of PCE below 0.1 mg/L for
11 weeks of operation and below for 20 weeks of operation in the
effluent, given an influent concentration that ranged from 600 to
2,500 mg/L (Love and Eilers, 1982). In New Jersey, PCE concentration
ranging from 60 to 205 mg/L were reduced to less than 0.1 mg/L by
GAC over a 58-week study period (Love and Eilers, 1982).
PCE is amenable to aeration on the basis of its Henry's Law Constant
of 1,100 atm (Kavanaugh and Trussell, 1980). In a pilot-scale packed
tower aeration study, removal efficiencies of 72 to 99.8% for PCE
were achieved using air-to-water ratios of 5-80, respectively (ESE,
1985).
In diffused-air aeration pilot-scale studies using either spiked
Cincinnati tap water (17-1,025 mg/L PCE) or actual PCE contaminated
New Jersey groundwater (94 mg/L PCE), diffused aeration removed 90%
of PCE at an air-to-water ratio of 4 for the latter and 98+% for the
Cincinnati water at air-to-water ratios of 8, 16 and 20 (Love and
Eilers, 1982).
Air stripping is an effective, simple and relatively inexpensive
process for removing PCE and other volatile organics from water.
However, use of this process then transfers the contaminant directly
to the air stream. When considering use of air stripping as a treat-
ment process, it is suggested that careful consideration be given to
the overall environmental occurrence, fate, route of exposure and
various other hazards associated with the chemical.
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Tetrachloroethylene March 31, 1987
-14-
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March 31, 1987
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Appendix
Estimation of absorbed dose based on inhalation exposure
Species
Human
Guinea
pig
Rat
Mouse
Approx .
weight
(kg)
70.0
0.50
0.25
0.025
Approximate
minute vol.
(liter/min)
10.0
0.222
0.132
0.024
[PCE]
(ppm)
100
100
200
400
230
470
100
200
200
Time of
Exposure
(hr/day)
7
7
6
6
8
8
6
6
. 4
Approximate
dose
(mg/kg/day)a
20
63
130
260
200
400
120
230
160
Reference
Stewart et al, 1977
Rowe et al, 1952
Savolainen et al, 1977
Savolainen et al, 1977
Carpenter, 1937
Carpenter, 1937
NTP, 1985
NTP, 1985
Kylin, 1963, 1965
aDose = [PCE(mg/D] [min. vol. (L/hr) ] [Time (hr/day) ] [50% absorption]/[bw(kg)]
where:
[PCE(mg/L] = [PCE(ppm)] x (6.78 mg/m3 - ppm) x (1 L/1000 m3)
[min. vol.(L/hr)] = [min. vol.(L/min)] x (60 min/hr)
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