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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