DATt:
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
2 8 1S8Q
SUBJECT. SurgesjLed^o A^^erse Response Level (SNARL) for Tetrachloroethylene
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Victor J-^Kimin, Deputy Assistant
FROM: Administrator for Drinking Water (WH-550)
Regional Administrators
TO:
The Office of Drinking Water (ODW), has completed a SNARL
for tetrachloroethylene. We develop SNARLs upon request and
when sufficient toxicological data are available for
contaminants found in drinking water where no standard
exists. SNARLs are not regulations, but are advisory guidance
which should be interpreted on a case-by-case basis as
applied.
In developing this SNARL,, the Criteria and Standards Division,
ODW, reviewed the current literature on the health effects
of tetrachloroethylene. Both data from animal tests and
some studies from high level exposure in humans were used as
basis for extrapolating to levels in drinking water that
would result in negligible risks to the general human population.
When considering toxicity that does not include the risk of
cancer, we generally use a child weighing 10 kg (22 pounds)
and drinking one liter of water per day as the basis for
calculations of short exposure (acute) toxicity and longer
exposure (chronic) toxicity. These levels are derived using
safety factors from classical toxicology and a logic similar
to that used by the National Academy of Sciences in "Drinking
Water and Health." When considering the possible cancer
risk, where it is assumed that there is some risk at any
level of exposure, and that the risk increases as the lifetime
exposure increases, we use the 70 kg (154 pounds) adult
living 70 years who drinks two liters of water as the base,
and calculate the excess cancer risk above the normal background
according to a mathematical model developed by the National
Academy of Sciences in "Drinking Water and Health," and
based on animal tests conducted by the National Cancer
Institute.
The drinking water levels that we have calculated providing
a margin of safety from likely toxic effects in humans
{assuming that 100% of the exposure is from drinking water)
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were related to the length of time that water is being
consumed, and range from short-term emergency levels to
long-term chronic exposure. We have separately computed the
potential additional cancer risk.
The computed drinking water guidance levels for effects
excluding cancer risks are as follows:
Time Concentration
1 day 2.3 mg/1
10 days 175 ug/1
Chronic (long-term) 20 ug/1
The computed excess lifetime cancer risks from the HAS model
at various exposures assuming the 70 kg adult drinking •two
liters of water per day for 70 years at the indicated concen-
tration are as follows:
Concentration Excess Risk
3.5 ug/1 one in 1,000,000
35 ug/1 one in 100,000
20 ug/1 approximately six in 1,000,000
The development of a SNARL for tetrachloroethylene does not
condone its presence in drinking water, but rather provides
useful information to assist in setting control priorities
in cases where it is found as a contaminant. The applicable
treatment technologies include aeration and granular activated
carbon. Human exposure to contaminants in drinking water
such as tetrachloroethylene should be reduced to the extent
feasible, to avoid the unnecessary risks from their presence
as adulterants.
Attachments
cc: Regional Water Supply Representatives
Lowell Van Den Berg
Alan Levin
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FEB c 1980
SNARL for Tetrachloroethylene
Office of Drinking Water —
U.S. Environmental Protection Agency
Washington, D.C. 20460
THE OFFICE OF DRINKING WATER "SNARLS" PROGRAM
The Office of Drinking Water provides advice on health
effects upon request, concerning unregulated contaminants
found in drinking' water supplies. This information suggests
the level of a contaminant in drinking water at which adverse
health effects would not be anticipated with a margin of
safety; it is called a ""SNARL (suggested no adverse response
level). Normally values are provided for one-day, 10-day
and longer-term exposure periods where available data exists.
A SNARL does not condone the presence of a contaminant in
drinking water, but rather provides useful information to
assist in the setting of control priorities in cases when
they have been found.
In the absence of a formal drinking water standard .for
tetrachloroethylene, the Office of Drinking Water has estimated
a suggested no adverse response level (SNARL) following the
state-of-the-art concepts in toxicology for non-carcinogenic
risk for short and long term exposures. For carcinogenic
risk, a range of risk estimates is p-rovided for life-time
exposures using a model and computations from the NAS Report
(1979) entitled "Toxicity of selected drinking water contami-
nants." However, SNARLS are given on a case-by-case basis
in emergency situations such as spills and accidents. The
SNARL calculations for short-term and chronic exposures
ignore the possible carcinogenic risk that may result from
those exposures. In addition, SNARLS usually do not consider
the health risk resulting from possible synergistic effect
of other chemicals in drinking water, food and air.
SNARLs are not legally enforceable standards; they are not
issued as an official regulation, and they may or may not
lead ultimately to the issuance of a national standard or
Maximum Contamination Level (MCL). The- latter must take
into account occurrence, relative source contribution factors,
treatment technology, monitoring capability, and costs, in
addition to health effects. It is quite conceivable that
the concentration set for SNARL purposes might differ from
an eventual MCL. The SNARLs raay also change as additional
information becomes available. In short SNARLs are offered
as advice to assist those that are dealing with specific
contamination situations to protect public health.
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General Information a_n_jd He a 1th Effects
Substantial quantities of tetrachloroethy 1ene are
produced (7CC million pounds in the U.S. in 1973). Tetra-
chloroethylene (perchloroethylene) is used as a dry cleaning
and degreasing solvent, heat-transfer medium, and in the
manufacture of fluorocarbons. This chemical is sliohtly
soluble in water (0.01% by volume).
Little work has been done to delineate the uptake, distri-
bution, metabolis-tn and excretion patterns following oral
exposures to tetrachloroethylene. For our purposes, an
assumption is being made that 30% is absorbed via respi-
ration and almost 100% via the gastrointestinal tract, as
has been shown for trichloroethylene. Only a small fraction
of tetrachloroethylene is metabolized to trichloroacetic
acid and/or trichloroethanol. The urinary half-life of
tetrachloroethylene is markedly longer (144 hours) than that
of trichloroethylene indicating some level of bioaccuraulation.
Tetrachloroethylene, like other halogenated hydrocarbons at
high doses, has been reported to produce liver and .kidney
.damage and central nervous system disturbances in mammals,
including humans. In addition, tetrachloroethylene has been
demonstrated to lower the DNA and RNA content of several
organ systems of rats. High concentrations of this chemical
result in growth inhibition and mortality as demonstrated in
animal inhalation studies.
Investigations of chronic toxicity of tetrachloroethylene in
animals have all involve-.l inhalation exposure, with the
exception of an assessment of carcinogenesis which involved
oral dosing (NCI, 1977). The National Cancer Institute has
reported tetrachloroethy1ene-induced hepatoce1lular carcinomas
in male and female mice, but not in male or female rats.
Schwetz e_t a_l. (1975) reported that tetrachloroethylene was
not teratogenic to rats and Swiss Webster mice after in-
halation exposures of 300 ppm for seven hours per day on
days six-15 of gestation. Careful examination of their
data, however, indicate that there were a number of modest
but statistically significant deviations of adverse health
effect parameters from control animals, including increased
body maternal weights, decreased body weight of mouse fetuses,
increased fetal resorptions and increased incidence of split
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sternebrae, subcutaneous edema and delayed ossification of
skull bones in mouse fetuses. Shuraacher et al. (1962)
exposed three week old mice for eight hours/day, three days
each to 200, 400, 800 and 1600 ppm perchloroethylene. The
exposures produced significant mortality and growth inhibition
i n survivors•
Tetrachlorgethy'qne SNARL
Tetrachloroethylene is a carcinogen in mice, and also causes
non-carcinogenic bioeffects at high doses. One-day, 10-day
and chronic SNARL values based on non-carcinogenic bioeffects
are computed incorporating appropriate factors of safety.
Estimates of concentrations projected to increase the lifetime
cancer risk by one in 100,000 and one in a 1,000,000 are
also provided using the HAS model. The non-carcinogenic
SNARL recommendations are made considering the child and
other sensitive members of the population.
A one-day SNARL of 2.3 mg/1 can be calculated using a study
by Kylin (1963). In this study mice were exposed to 200 ppta
tetrachloroethylene in air for a period of four hours.
Histological examinations of the liver demonstrated fatty
infiltration but not cellular necrosis. Even though the
exposure levels ranged from 200 to 1600 ppm tetrachloro-
ethylene, the no-adverse-effect level was not established.
Using the method by Olsen and Gehring (1976) whereby the
lung/whole body ratios for humans and animals are assuned to
be roughly equivalent, the total exposure of 200 ppni (1358
mg/m ) for four hours via inhalation, could be used to
determine the one-day SNARL:
.(1358 rag/m )(4 m3/day) (0.30 ) (J__)_ « 2.3 mg/1
(1 l/day)(100 uncertainty factor)(7)
Where: 1/7 = child/adult body weight ratio
0.30 - absorption factor
1 I/day • child's daily water consumption
100 uncertainty factor because of animal experiment
1358 mg/m = (200 ppm)(6.79 conversion factor)
4m « according -to Olsen and Gehring whereby the
lung-whole body ratios for humans (adults) and
rats (adults) are assigned to be roughly
equivalent
An uncertainty factor of 100 was chosen rather than 1,000
even though the SNARL is based upon an animal experiment in
which the no-observed-effect level was not identified. It
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was felt that the i.-.dex of toxicity, namely fatty infil-
tration of the liver, is a delicate disorder in itself which
is reversible and not life-threatening after a short exposure/
therefore an additional margin of safety was not warranted.
The National Academy of Sciences (NAS, ,1979) has computed a
one-day SNARL of 172 mg/1 and 24.5 mg/]j for the seven-day
SNARL. Calculations used by the NAS to determine a one-day
SNARL were based on hepatotoxicity at a dose level of 490
rag/kg body weight given intraperitoneally to the animals.
The calculations were made for a 70 kg man and the drinking
water was considered to be the sole source of exposure. The
seven-day NAS SNARL was calculated by dividing the one-day
SNARL value by the appropriate number of days.
The NAS chose to work with data in animals given intra-
peritoneal injections. The Office of Drinking Water selected
an inhalation study in animals for extrapolation of its
SNARL and calculated the SNARL for the 10 kg child. Animal
studies and a human case history suggest that, in this case,
children appear to be a sensitive population which needs
to be protected from the adverse health effects.
The Office of Drinking Water 10-day SNARL was calculated
using an inhalation study by Savolainen, et al. (1977) in
which inhalation exposures of adult male rats to 200 ppn of
tetrachloroethylene six hours daily for five days caused
diminished brain RNA content. The 10-day SNARL of 175 ug/1
was thus determined:
(1353 mg/m ) (6 m3)(0.30)(1)(1) « 175 4ig/l
(1 l/day)(1000) (7)(2)
Where: 1358 mg/m = (200 ppm)(6.79 conversion factor)
6m = according to Olsen and Gehring whereby the
lung-whole body ratio for humans (adults) and rats
(adults) are assumed to be roughly equivalent
0.30 * absorption factor
1 I/day « Child's daily consumption of drinking
water
1000 = uncertainty factor due to animal experi-
ment with no-observed-effect level identified
1/7 .» child/adult body weight ratio
1/2 = factor to provide for equivalent toxicity on
day 10 as noted on day five
As a matter of interest "Medical World News" contained a
report of a six week old baby with jaundice and an enlarged
liver; the baby was breast fed by a mother who was frequently
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exposed tr t e t r £ ch Icr ce thy le ne in a dry clear.ing establishment
(Anonymous, 1978). The mother's milk contained -perchloroethylene
levels up to one mg %. The child's symptoms vanished when
breast feeding was discontinued.
Lon ge r-Term SNARL:
A longer-term SNARL of 20 ug/1 (rounded from the compu-
tation) can be estimated from a study by Navrotskii et a 1.
(1971). The authors reported increased urinary urobilinogen
and pathological changes in the parenchyma of the liver and
kidneys of rabbits after inhalation exposure to 100 mg/m
perchloroethylene for three to four hours/day for seven to
11 months. The calculations for a longer-term SNARL are:
(100 mg/m3)(4 m3/day ) ( 0 . 30 ) ( 1 ) - 0.017 mg/1
(1 I/day) (1000 uncertainty factor)(7)
Where: 100 mg/m « observed effect level
4m = according to Olsen and Gehring whereby the
lung-whole body ratio for humans (adults)
and rats (adults) are assumed to be roughly equivalent
0.30 = absorption factor
1 I/day = child's consumption of drinking water
1/7 = child/adult body weight ratio
1000 « uncertainty factor due to animal study
where health effect was observed
Since tetrachloroethylene is considered a carcinogen, at
least for mice, and using the risk etimates generated by the
National Academy of Sciences (NAS), it is possible to identify
that range of tetrachloroethylene concentrations that would
increase fhe risk of one excess cancer per 10 or 10 people
exposed over a lifetime. From the NAS model it is estimated
that consuming 2 I/day over a lifetime having a tetra ch l.or oethy lene
concentration of 3.5 ug/1 or 35 ug/1 would increase the risk
by one excess cancer/million exposed or one excess cancer/100,000
exposed, respectively. This is the range of risks where
raany EPA regulatory values for other carcinogens have been.
These risk extrapolations were based on an assumption that
there is no threshold effect level for carcinogens. The
state-of-the-art at the present time is such that no experimental
tools can accurately define the absolute numbers of excess
cancer deaths attributable to tetrachloroethylene in drinking
water. Due to biological variability and the number of
assumptions required, each of the risk estimating procedures
leads to a different value. There is wide variation between
these estimates and also in their interpretation. For this
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reason we report the results of the NAS risk computations,
which is a conservative approach, as a range of values from
one in 100,000 to one in 1,000,000 incremental risk (risk
above background) for a carcinogen. The NAS risk estimates
are based on the multistage model concept. "At low dose,
the raultistage model is often mathematically equivalent to
•the linear or single hit model. Therefore, its use for
extrapolation is consistent with the conservative linear
risk estimation. If the precj.se mechanism of carcinogenesis
is represented by a threshold or log-normal dose response
relationship, the multistage model may considerably over
estimate the risk at low dose levels. However, this possibility
cannot be reasonably quantified" (NAS-1979).
In summary, the one-day, ten-day and longer-term SNARL
values for tetrachloroethylene are 2300 ug/1, 175 ug/1 and
20 ug/1, respectively, if drinking water is the only source
of exposure. The concentrations resulting in a lifetime
risk of 10 and 10 are 3.5 ug/1 and 35 ug/1, respectively,
if the contaminated drinking water was consumed over a
lifetime. The longer-term SNARL of 20 ug/1 tetrachloro-
ethylene in drinking water may result in excess cancer risk
of approximately six in one million, if the exposure was for
a lifetime (70 years).
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