SNARL for Tetrachloroethylene
                   Office of  Drinking Water
             U.S.  Environmental Protection Agency
                   Washington,  D.C.  20460


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 provided 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 d,o 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 may 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  protec^, (g

                     ancl Hea 1th Ef
Substantial  quantities of t etrachloroethylene  are being
produced  (700  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 f luorocarbons .   This chemical  is slightly
soluble in water  (0.01%  by volume).

Little work  has  been done to delineate  the uptake, distri-
bution, metabolism  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  tr ichloroethylene.   Only  a  small fraction
of tetrachloroethylene is metabolized to  trichloroacetic
acid and/or  tr ichloroethanol .   The urinary half-life of
tetrachloroethylene is markedly longer  (144  hours) than that
of tr ichloroethylene indicating some level of  bioaccumulation .

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  involved inhalation exposure, with the
exception of an  assessment of carcinogenesis  which involved
oral dosing  (NCI,  1977).  The National  Cancer  Institute has
reported  tetrachloroethylene-induced hepatocel lular carcinomas
in male and  female  mice, but not in male  or  female rats.

Schwetz e__t a^.  (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 statisticallysignificant 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


was  felt  that the index  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 (HAS,  1979) has computed a
one-day SNARL of 172 mg/1 and 24.5 mg/1  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
mg/kg body  weight given  intraperitoneally to the animals.
The  calculations were  made  for a 70 kg  man and the drinking
waiter 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 ppm  of
tetrachloroethylene six  hours daily for  five days caused
diminished  brain RNA content.  The 10-day SNARL of 175  ug/1
was  thus  determined:

                f.lii_Elll£±.l£IillIlI      =    175 ug/1
      (1  I/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
           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

sternebrae,  subcutaneous edema  and delayed ossification of
skull bones  in mouse fetuses.   Shumacher 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
in survivors.

Tet rach lorethylei e SN ARL '
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 NAS  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 ppm
t e tr achloroe thylene 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 assumed to
be roughly equivalent, the total exposure of 200  ppm  (1358
mg/m ) for four hours via inhalation, could be  used to
determine  the one-day SNARL:

                              ilO.l _____ ill    =     2.3 rag/ 1
      (1 I/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. 7 9 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

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

exposed  to tetrachloroethy lene in  a  dry cleaning  establishment
(Anonymous,  1978).  The  mother's milk contained perchloroethy lene
levels up  to one mg %.   The child's  symptoms vanished when
breast feeding was discontinued.

Lo n_c[e_£^T_e_r m SNARL :

A longer-term SNARL of  20 ug/1 (rounded from the  compu-
tation)  can be estimated from a study by Navrotskii e_t a 1 .
(1971).  The authors  reported increased urinary urobilinogen
and" pathologica 1 changes in the parenchyma of  the liver and
kidneys  of rabbits after inhalation  exposure to  100 mg/rti
perchloroethy lene for three to four  hours/day  for seven to
11 months.  The calculations for a longer-term SNARL are:

                             Li.L3_.Oi ______ 111   =    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 tetrachloroethy lene is considered a carcinogen, at
least for  mice,  and  using the risk  etimates generated by the
National  Academy of  Sciences (HAS), it is possible to identify
that  range of tetrachloroethy lene  concentrations that would
                                                 o       j
increase  the 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 tetrachloroethy 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/ 1 00 , 0 0 0
exposed,  respectively.  This is  the range of  risks where
many  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 tetrachloroethy lene 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 estimate-s and  also in their  interpretation.  For this

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 multistage  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 precise 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).