United States
Environmental Protection
Agency
Environmental Criteria and
Assessment Office
Research Triangle Park NC 27711
Research and Development
EPA/600/S8-82/003F  Sept. 1985
Project  Summary
Health  Assessment
Document  for
1,1,1 -Trichloroethane
(Methyl  Chloroform)
  Methyl chloroform (MC) is a volatile
chlorinated  hydrocarbon used  exten-
sively as an industrial solvent  and in
consumer products. It has been detect-
ed in the ambient air of a variety of
urban and non-urban areas of the Unit-
ed States. Normally, background levels
are in the range of 0.1 to 0.2 ppb (0.54 x
10'3 to 1.08 x 10"3 mg/m3). Levels in
some urban areas have ranged up to 20
ppb (0.11 mg/m3). MC has been less
frequently detected in water, generally
at levels of 1  ppb or less. In certain
instances involving contamination of
groundwater, much higher levels have
been reported.
  The weight of  available evidence
obtained from both human and animal
data suggests that long-term exposure
to environmental levels of MC poses no
serious health concern to  the general
population. However, the available data
are inadequate for classifying the mut-
agenic and carcinogenic potential for
MC.
  The no-observed-effect level (NOEL*)
for short-term exposure of humans is in
the range of 350 to 500 ppm (1,890 to
2,700 mg/m3).
  This Project Summary was developed
by EPA's Office of Health and Environ-
mental A ssessment. En vironmental Cri-
teria and Assessment Office, Research
Triangle  Park, NC, to announce key
findings  of the research project  that is
fully documented in a separate report of
the same title (see Project Report order-
ing information at back).
"NOEL (no-observed-effect level) the lowest expo-
 sure level at which there are no statistically signif-
 icant increases in frequency or seventy of effects
 between the exposed population and its appropriate
 control
Introduction

  1,1,1-Trichloroethane (methyl chloro-
form, MC) is a volatile chlorinated hydro-
carbon. Since its commercial introduc-
tion, MC has been used increasingly as
an industrial solvent and in consumer
products such as spot removers. Produc-
tion of MC in the United States is esti-
mated to have increased from 121,000
metric tons in 1970 to 315,000 in 1980.
About 88 percent of annual production in
the United States is released largely to
the atmosphere through dispersive use.
There are no known natural sources of
emissions of MC.
  Methyl chloroform has been detected
in the ambient (natural environment) air
of a variety of urban and non-urban areas
of the United States and other regions of
the world. Levels range from trace
amounts in rural areas to about 20 parts
per billion (ppb) or 0.108 mg/m3 in some
large urban centers. Normally, back-
ground levels of MC are in the range of
0.1 to 0.2 ppb (0.54 x 10'3 to 1.08 x 10"3
mg/m3).  Less frequently has MC been
detected  in water. It is not soluble to any
appreciable extent but in some surface
and drinking waters has been monitored
at levels of 1 ppb or less. In certain instan-
ces involving contamination of ground-
water, much higher  levels have been
reported.
  In the  troposphere,  a region  of the
atmosphere extending from ground level
to as  high as 15 kilometers, MC is
removed  to a substantial extent through
reaction with hydroxyl radicals. Based on
current knowledge of its reaction kinet-
ics, the lifetime of MC in the troposphere
is in the range of 5 to 10 years. This time
period permits a portion of the MC to be

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conveyed to the stratosphere where,
along with other compounds, it may par-
ticipate in ozone (Os) destruction path-
ways. MC and other compounds that add
to the chlorine burden in the stratosphere
may contribute to the effects of global Oa
depletion. Occurrence of such  depletion
could result in an increased incidence of
non-malignant forms of skin cancer due
to increases in the amount of biologically
damaging radiation  reaching the earth's
surface.The extent to which past, current,
and future emissions of MC contribute to
O3 depletion can be realistically estimated
only by assessing the interrelationships
between all the principal reactions in-
volved in both the formation and destruc-
tion of atmospheric Oa. The extent and
direction to which actual global Os levels
have changed over the years can not be
estimated with available measurement
methods.

Exposure and Effects
  Because MC is primarily an air contam-
inant, inhalation is the principal and most
rapid route of exposure. An 8-hour expo-
sure to theTWA** of 350 parts per million
(ppm) or 1,890  mg/m3 is estimated to
result in about two grams of MC absorbed
into the body of an average-sized  70 kg
man. The total amount absorbed increas-
es in direct proportion to inspired air con-
centrations and to the length of exposure
and physical activity. Once body equilib-
rium or steady-state has been attained,
no  further uptake is possible. There is
strong evidence that MC will partition
selectively into lipid-tissues upon chronic
or long-term exposure to even low ambi-
ent air concentrations, until steady-state
is attained. Because  of its lipophilic
nature, MC  is expected to cross  mem-
brane barriers in the body and diffuse into
the brain  and the colostrum of nursing
mothers, as  well as into the fetus during
pregnancy. Unlike other chlorinated sol-
vents such  as trichloro-  and tetrachlo-
roethylene,  MC  is only metabolized  in
humans toa limited extent, about six per-
cent or less of  the  total retained dose.
Although metabolism of MC is affected by
other chemicals and drugs, there is no
evidence that it enhances its own metab-
olism. The primary route of elimination
from the body is via the lungs, through
which MC is exhaled in unchanged form
along with a metabolite, carbon dioxide.
The only identified urinary metabolites
are trichloroethanol and trichloroacetic
acid.
  Based on presently available data, the
likelihood of adverse health effects result-
ing from chronic exposure to the ambient
air levels commonly encountered appears
to be extremely low. Although the availa-
ble health data are inadequate to classify
MC's mutagenic and carcinogenic poten-
tial, if any, the NOEL for short-term expo-
sure of humans to MC is estimated to be
in the range of approximately 350 to 500
ppm (1,890 to 2,700 mg/m3). This NOEL
is many orders of magnitude higher than
the highest levels of MC (20 ppb; 0.108
mg/3) measured  in the ambient  air of
urban areas. Based upon available human
data, the estimated relationship between
acute effects and single short-time expo-
sures is as follows:
       Exposure


       100 ppm
      (540 mg/m')
     350 - 500 ppm
  (1,890-2,700 mg/m3)


       1,000 ppm
     (5,400 mg/m3)
    1,900-2,650 ppm
 (10,260-14,310 mg/m3)


      > 5,000 ppm
     (27,000 mg/m3)
   Acute Effect

Apparent odor
 threshold
Obvious odor, slight
 changes in
 perception
Disturbance of
 equilibrium
Lightheadedness,
 irritation of the
 throat
Onset of narcosis
"TWA (Time Weighted Average)'the time-weighted
  average concentration for a normal 8-hour work-
  day and a 40-hour workweek to which nearly all
  workers may be exposed repeatedly, day after day,
  without adverse effect
  In the range of the NOEL, no significant
abnormal blood chemistry or organ func-
tion decrements have been noted. Symp-
toms  of  neurological  dysfunction were
observed at higher exposure levels. These
symptoms were qualitatively diagnosed
by the subjects' impaired performance of
clinical-level cognitive and manual tasks.
More  extensive human and laboratory
animal data are needed before firm con-
clusions about adverse health responses
to low-level exposures  to  MC  can be
drawn.
  Similarly,  MC has not demonstrated
any teratogenic potential in the studies
conducted to  date in rodent  species.
Commercially  available samples of MC
are genotoxic to mouse hepatocytes and
are weakly  mutagenic in Salmonella
under treatment conditions where suffi-
cient exposure is ensured. The available
data are inadequate, however, for reach-
ing  firm conclusions regarding the ability
of MC to cause gene mutations  in other
organisms; however, the possibility that
this substance, its associated stabilizing
materials, or its metabolites may  have
mutagenic effects in humans  has not
been eliminated.
  On the basis of animal bioassays per-
formed  to date and in  the  absence of
epidemiological information,  it is not pos-
sible to classify MC as to its carcinogenic
potential in humans.

Recommendations for  Further
Studies
  Although the available human and tox-
icity data indicate that ambient exposure
to MC is not currently a human health
concern, it is apparent that further invest-
igation is needed in several areas. Areas
in which incomplete information is avail-
able, and that should be considered when
formulating research needs, are present-
ed  below,  not necessarily  in order of
priority.

  1.  Neurobehavioral Toxicity. Few an-
     imal studies have been  made of the
     effects of MC on the nervous sys-
     tem and behavior. Most endpoints
     studied have been relatively insen-
     sitive. Further studies on more sen-
     sitive endpoints are needed.
  2.  Teratogenicity and Reproductive
     Effects. Published data on three-
     generation animal studies via  inha-
     lation do not adequately assess the
     teratogenic and reproductive effects
     potential of MC.
  3.  Mutagenicity. In order to determine
     conclusively the mutagenic poten-
     tial  of  MC, pure  MC should  be
     tested in studies appropriately de-
     signed to ensure exposure of the
     indicator organism.
  4.  Carcinogen/city. In  order to deter-
     mine more  effectively  the human
     carcinogenic potential  of MC, life-
     time inhalation studies in appro-
     priate rodent species should  be
     undertaken.

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     This Project Summary was prepared by staff of Environmental Criteria and
       Assessment Office, U.S. Environmental Protection Agency. Research Triangle
       Park. NC 27711.
     Mark Greenberg is the EPA Project Officer (see below).
     The complete report, entitled "Health Assessment Document for 1,1,1-Trichloro-
       ethanefMethylChloroform),"(OrderNo. PB84-183565; Cost: $17.50, subject
       to change) will be available only from:
            National Technical Information Service
            5285 Port Royal Road
            Springfield, VA22161
            Telephone: 703-487-4650
     The EPA Project Officer can be contacted at:
            Environmental Criteria and Assessment Office
            U.S. Environmental Protection Agency
            Research Triangle Park, NC 27711
United States
Environmental Protection
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
Official Business
Penalty for Private Use $300
       0000329   PS
       U  S  ENVIR  PROTECTION  AGENCY
       CHICAGO

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