" SEP
Advisory Opinion for Trans-1,2-Dichloroethylene
Office of Drinking Water p^>«r* £*, f4
5012 U.S. Environmental Protection Agency |V;|^ *!J i:"4
Washington, D.C. 20460
AN OFFICE OF DRINKING WATER HEALTH EFFECTS ADVISORY
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 ad-
verse health effects would not be anticipated. A margin of
safety is factored in so as to protect the most sensitive
members of the general population. The advisories are
called Suggested No Adverse Response Levels (SNARLs).
SNARLs have been calculated by EPA and by the National
Academy of Sciences (NAS) for selected contaminants in
drinking water. An EPA-SNARL and a NAS-SNARL may well
differ due to the possible selection of different experimen-
tal studies for use as the basis for the calculations. Fur-
thermore, NAS-SNARLs are calculated for adults while the
EPA-SNARLs are established for a 10 kg body weight child.
Normally EPA-SNARLs are provided for one-day, ten-day and
longer-term exposure periods where available data exist. 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 where
contamination occurs. EPA-SNARLs are provided on a case-by-
case basis in emergency situations such as spills and acci-
dents.
In the absence of a formal drinking water standard for an
identified drinking water contaminant, the Office of Drink-
ing Water develops EPA-SNARLs following the state-of-the-art
concepts in toxicology for non-carcinogenic risk for short
and longer term exposures. In cases where a substance has
been identified as having carcinogenic potential, a range of
estimates for carcinogenic risk based upon lifetime exposure
as developed by the NAS (1977 or 1980)^ and/or EPA Carcinogen
Assessment Group (EPA, I980a) .is .presented. "However, the
EPA-SNARL calculations for—ail- exposures-• ig-nor-e-~the-possible.
carcinogenic risk that may result from these exposures. In
addition, EPA-SNARLs usually do not consider the health risk
resulting from possible synergistic effects of other
chemicals in drinking water, food, and air*
EPA-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 national standards or
Maximum Contaminant-Levels (MCLs).. The latter must take
into account occurrence, relative source contribution
factors, treatment technology, monitoring capability, and
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costs, in addition to health effects. It is quite conceiv-
able that the concentration set for EPA-SNARL purposes might
differ from an eventual MCL. The EPA-SNARLs may also change
as additional information becomes available. In short, EPA-
SNARLs are offered as advice to assist those such as Region-
al and State environmental and health officials, local pub-
lic officials, and water treatment facility personnel who
are responsible for the protection of public health when
dealing with specific contamination situations.
General Information and'Properties
Trans-l,2-dichloroethylene is one of three isomers of
dichloroethylene, all clear, colorless liquids with the
molecular formula of C2^2c^-2 and a molecular weight of
96.95 (Irish, 1963). It is moderately soluble in water
(6300 mg/1), but soluble in most organic solvents (Irish,
1963). Trans-l,2-dichloroethylene is volatile, but less so
than 1,1-dichloroethylene. The trans-isoraer has a vapor
pressure of 265 Torr ( mm Hg) at 20°C and a boiling point of
47°C. Its vapor density is 3.34, over three times that of
air, so that it will .settle in low places in a still atmos-
phere. Its specific gravity is 1.27 at 25°C. Thus, it also
would tend to sink in a still body of water.
Horsely (1947) lists a binary azeotrope with water (1.9%
water by weight, boiling at 45.3°C) and a ternary azeotrope
with water and ethanol (1.1% water, 94.5% trans-1,2-
dichloroethylene and 4.4% ethanol by weight. This isomer
also forms an azeotrope with ethanol alone.
In air, one (1) ppm is equivalent to 3.97 mg/m3 and one
(1) mg/1 is equivalent to 252 ppm (Irish, 1963).
The present threshold limit value (TLV) for the dichloro-
ethylenes in the United States is 200-ppm (794 mg/m3) -
(ACGIH, 1977).
1,2-Dichloroethylene, as a mixture of the cis- and trans-
isomers, is used as a solvent for such substances as fats,
rubber, phenol and camphor and for retarding fermentation
(Windholz et al., 1976). It is also used as a low tempera-
ture extraction solvent for heat sensitive substances and
has been employed as a coolant in refrigeration plants .
(Bardie, 1964).
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Sources of Exposure
Trans-l,2-dichloroethylene has been detected in a number of
raw and finished drinking waters, principally from ground
w ter sources. During the National Organics Reconnaissance
Survey (NORS), this isomer was detected in Miami drinking
water at 1.0 ug/1 (U.S. EPA, 1975).
Trans-3 ,2-dichloroethylene was detected at 0.1 ug/1 in one
of 105 raw surface waters examined (Coniglio, et al, 1980).
None was detected in 103 samples of finished water from
these surface water. supplies. Of ground water samples
collected in 13 cities during one or more of several surveys
(NORS, NOMS, or the. recent -SRI. .survey conducted -for-- EPA) , - --
15.4% of both raw and finished samples were positive for
trans-l,2-dichloroethylene. Mean concentrations were 1.75
and 1.05 ug/1 for raw and finished water, respectively
(ranges = 0.2-3.3 and 0.2-1.9 ug/1, respectively)*
Pellizzari (1978) found slightly higher levels of 1,2-
dichloroethylene (cis- and trans- isomers not distinguished)
than 1,1-dichloroethylene during his air sampling survey.
The greatest amount of 1,1-dichloroethylene measured was
2500 ng/m3 at Front Royal, Virginia. Maximum concentra-
tions of 1 ,2-dichloroethylene detected in various areas of —
the United States varied from a trace (detection limit « 260
ng/m3) near Magna, Utah, South Charleston, West Virginia,
and Grand Canyon, Arizona, to 5263 ng/—3 at the Kin-Buc
Disposal Site in Edison, New Jersey.
No data are available on the presence of either isomer of
1,2-dichloroethylene in foodstuffs.
frnarroacoklnefcics ___
Trans-1, 2-dichloroethyiene>: -as— at neutral r-iow nnolecuiar"^;
weight, lipid soluble material, should be systemically
absorbed following .any.-route of -administration..— — .~ — .........
No pharmacokine tic -data ..appear.- ta-exist which define -the — -
absorption rate of trans-l,2-dichloroethylene after oral
exposure. However, pharmacokine tic studies based on urinary
and biliary excretion data show that administration of a
single oral dose of 1,1-dichloroethylene (1.0 or 50 mg/kg)
results in rapid and complete absorption in rats and mice
(McKenna,- et al, 197-Sb^)^. Rap id -absorptlon..and^distri hut-ion
of 1,1-dichloroethylene after intraperitoneal administration
to rats also occurs (Jones and Hathway, 1978). For purposes
of SNARL development, then, we will assume that trans-1,2-
dichloroethylene is absorbed rapidly and completely after
oral exposure.
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The absorption of 'gases from the lung is highly dependent
upon the blood:gas partition coefficient. Sato and Nakajima
(1979) showed that trans-lf2-dichloroethylene has a blood:
gas partition_coefficient of 5.8 in the rat. While it has a
high blood solubility, this chemical in air reaches a
steady-state within the whole rat in about 1.5 hours (Pilser
and Bolt, 1979). v
Using relatively new pharmacokinetic procedures, a mixed
partition coefficient(S) of 10.9 was determined for the
trans-isomer (Andersen et al., 1980). A mixed partition
coefficient is defined as the concentration of a chemical in
the richly perfused tissues divided by its concentration in
the gas phase. This was over 2.5 times higher than that
determined for l^l-dichloroethylene. "Thus, a rat exposed to
trans-1,2-dichloroethylene would contain more chemical at
equilibrium tharuwould a-rat exposed—to-the--same-concentra*—
tion of 1,1-dichloroethylene.
Distribution data -on -tr-ans-lr2-diehloroethylene-are~not
available. However, if this isomer follows the same distri-
bution pattern as that observed for 1,1-dichloroethylene,
the highest concentration would be found in the liver and
kidney (McKenna, et al, 1978a). These studies were performed
in rats, exposed by—inhalation to concentrations-varying
from 10-2000 ppm (40-800& mg/m^-) for--2 or 6 hours. ~
Bonse, et al. (1975) observed that metabolism of trans-1,2-
dichloroethylene in perfused rat liver produced detectable
amounts of dichloroethanol and dichloroacetic acid, possi-
bly indicating the initial formation of dichloroacetalde-
hyde. Liebman and Ortiz (1977) have postulated the metabol-
ic pathways for trans-1,2-dichloroethylene. One proposed
pathway would be conversion to a reactive epoxide inter-
med i ate, . then-to- monochloroacfrtyl- chlor ide~-and--inonochioro*<—
acetic acid. The authors also suggested that the.production-~-
of dichloroacetal
glycol or the epoxide with migration of a chloride ion.
Their attempts to~identify a chromat©graphic peak as -
dichloroacetaldehyde were inconclusive.
An essential feature of the metabolic pathway*is-*that~the*' *
compound appears to be metabolized to an epoxide intermedi-
ate which is reactive and which may—form covalent bonds with
tissue macromolecules (Henschler, 1977; Henschler and Bonse,
1977). These authors have synthesized the epoxides for both
isomer a =of-«4-,2«^c^loroe±toyf'eT*erv^heY'~be£
epoxides are formed in vivo during the metabolic process.
Each was inactive when tested for mutagenic potential in a
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modified Ames system (Greim, et al, 1975). However, these
results only added support to the hypothesis of Henschler
and co-workers that the epoxides with symmetrical chlorines
are more stable and less likely to be mutagenic. This does
not exclude the possibility that these symmetrical epoxides
may still interact with other tissue macromolecules, a pro-
cess which may result in some form of damage other than
mutagenic or carcinogenic. /
There are apparently no published studies^which test the
interaction of the isomers of 1,2-dichloroethylene with DNA;
nor are there any which evaluate the interaction of these
two isomers with other tissue macromolecules. \
No data concerning the excretion of trans-l,2-dichloroethy-
lene are available. The rate of elimination of 1,1-dichloro-
ethylene is relatively rapid, with most of a dose being
eliminated in the first 24-72 hours after cessation of expo-
sure. One might assume that trans-l,2-dichloroethylene
would be eliminated at a similar rate.
Health'Effects
There are no published-reports .available-to us at this time
which describe non-fatal accidental, occupational or con-
trolled exposures to trans-1,2-dichloroethylene in humans by
any route or for any duration of exposure. Only through
secondary references do we know that at high concentrations
(> 9500 ppm or 38,000 mg/m3) central nervous system ef-
fects have been observed in humans as reported in the German
scientific literature (Villinger, 1907; Albrecht, 1927;
Lehmann and Flury, 1938). It would appear that the trans-
isomer was about twice as potent as the cis-isomer in
depressing the central nervous system.
Data on the acute toxicity of trans-1,2-dichloroethylene in
animals are limited. Freundt, et al. (1977) determined the
oral LD5g in the 200 g rat to be 1300 mg/kg. When given
intraperitoneally, the LD5Q increased six-fold to 7800
mg/kg. The 1*050 after intraperitoneal administration to
the mouse was 4160 mg/kg-
Jenkins, et al. (1972) tested the effects of single 400 or
1500 mg/kg oral doses of each isomer of 1,2-dichloroethylene
in corn oil given to adult femaie^oitamaTi~rats"W€rtgh;ing--~r
200-470 g. Liver and plasma enzyme activities were deter-
mined. The trans- isomer appeared to exert a less potent
effect at the higher dose than did the cis- isomer. The
trans- isomer caused changes in the level of only one
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enzyme, whereas the cis- isoroer caused significant changes
in the levels of three enzymes. No difference was observed
at the lower dose. Each was less potent than 1,1-dichloro-
ethylene at any dose level.
At 400 rag/kg, trans-1,2-dichloroethylene significantly
increased glucose-6-phosphate to a level 11% above control
(P < 0.05). At 1500 mg/kg, this isoraer significantly
decreased the level of liver tyrosine transarainase to about
80% of control (Jenkins, et al, 1972) (P < 0.05). Liver
alkaline phosphatase, plasma alkaline phosphatase and
alanine transarainase were not significantly affected at
either dose.
Preundt, et al (1977) reported on the effects of trans-1,2-
dichloroethylene after inhalation in mature female Wistar
rats (180-200 g) at 200 ppm (/xxSOO mg/ra3) (the currently-
established TLV/MAC in a number of countries) and at 1000
and 3000 ppm C^4,000 and 12,000 mg/m3, respectively). A
brief (8-hour) or prolonged exposure (8 hours/day, 5 days/
week for 1, 2, 8 or 16 weeks) at 200 ppm (/^800 mg/m3)
yielded an increased incidence of slight to severe fatty
degeneration of the hepatic lobule and lipid accumulation by
the Kupffer cells. Changes were observed in one of six rats
exposed once. Two of six rats showed slight changes after
one week of exposure; three of six rats exhibited slight
changes during the t wo-«weefc-v expose re r- -Damage -became more--
noticeable in a higher percentage of the animals as the
length of exposure increased to 8 or 16 weeks. At all
exposure levels, the appearance of pulmonary capillary
hyperemia and distention ofthe alveolar septum was increased
over that observed in controls. At 8 and 16 weeks of
exposure, severe pneumonic infiltration was observed in
three of the six treated rats; none occurred in the
controls.
At higher levels of exposure (1000 (4000 mg/m3) or 3000
(12,000 mg/m3) ppm. for.8 hours), liver- and pulmonary
effects similar to those observed at 200 ppm were seen in
two of six treated rats.- At these higher levels, fibrous ~
swelling and hyperemia of cardiac muscle also occurred in
four of six rats treated at each exposure level. This effect
persisted until at least 14 hours post-exposure, although
the liver effects appeared to be reversing somewhat at that
time.
At all doses and durations of exposure, there was no
evidence • of histopathoiogy: iinvoiving^the^^cidneys^r spi-een r*^*
brain, striated muscle (quadriceps) or peripheral nerve
(sciatic). In addition, there were no signs of central
nervous system depression (pre-narcotic signs or narcosis).
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A number of biochemical and hematological parameters in rat
blood were also tested in the Freundt/ et al (1977) study.
wo changes in serum cholesterol, albumin, uric acid, urea
nitrogen, glucose, alkaline phosphatase, SCOT or SGPT were
observed after 8 hours' exposure at 200 ppm (800 mg/m3).
Exposure at 1000 ppm (4000 mg/ra3) for 8 hours resulted in
significant reductions in serum albumin, urea nitrogen and
alkaline phosphatase (0.01 < P < 0.05). Eight hour expo-
sures to both 200 and 1000 ppm concentrations caused a
significant decrease in the number of leukocytes; 1000 ppm
also significantly decreased the number of erythrocytes
(0.01 < P < 0.05). Clinico-chemical parameters were not
studied at the 3000 ppm exposure level.
A later study by Freundt and Macholz (1978) showed that a
single 8-hour inhalation exposure to trans-1,2-dichloro-
ethylene at 200 ppm (800 mg/m3) resulted in significant
increases in hexobarbital sleeping time, the zoxazolamine
paralysis time and the metabolic formation of 4-aminoanti-
pyrine from aminopyrine in adult female Wistar rats. The
effects were less severe after trans-l,2-dichloroethylene
than after cis-isomer. In addition, trans-1,2-dichloro-
ethylene competitively inhibited the oxidative N-demethy-
lation of aminopyrine, and the O-methylation of p-nitro-
anisole in rat liver iriicrosomes. The investigators
concluded that the inhibition of hepatic drug metabolism was
caused by a competitive,0reversible interaction of the
chemical with the mixed function oxidase system.
Teratooenicity •
No reports on the terstcgsnic potential of trans-1,2-
dichloroethylene are available at the present time.
Mutagenicity
Both cis- and trans-1,2-dichloroethylene were non-mutagenic
when assayed with E. coli K12 at similar concentrations used
for 1,1-dichloroetlTylene at which the latter was found to be
mutagenic (Greim, et al, 1975). The mediQjqj concentration of.
the trans-isoraer was 2.3 mM, that of cis-1,2-dichloroethy-
lene 2.9 mM, and that of 1,1-dichloroethylene 2.5 mM.
Trans-1,2-dichloroethylene was found to be non-mutagenic in
the host-mediated assay using Salmonella tester strains in
mice (Cerna and Kypenova, 1977). In contrast, both cis-1,2-
and 1,1-dichloroethylene were mutagenic in this system. In
addition,, -trans-l^rdlchloroeth-ylgne..did--aot. .produce,.-cJiromo-.
somal aberrations in bone marrow cells following repeated
intraperitoneal injections in mice.
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8
Carcihogehicity
No studies have been completed which test the carcinogenic
potential of trans-1,2-dichloroethylene. It is currently
under consideration for testing by the National Toxicology
—Program. •_- - .-
SNARL-'&eveloproenfc
Oneway'SNARL
Although there are no published animal studies on trans-1,2-
dichloroethylene which define a no-effect level, there are
two studies which describe a minimal effect level as well as
a dose response (Jenkins, et al, 1972; Freundt, et al,
1977). The results of the Freundt et al. study appear to be
the best to use since more parameters were measured, a sig-
nificant number of which showed no change from control after
a single 8-hour exposure to 200 ppro. Also, this study bet-
ter describes the dose-response relationship over several
durations and concentrations.
The study by Freundt, et al. (1977) identified a minimal
effect level of 200 ppra inhaled over a single 8-hour expo-
sure period. This exposure.resulted in slight-liver effects
in one of six animals, as observed histologically. In addi-
tion, no changes were observed in any of several serum bio-
chemical parameters.
A one-day SNARL developed from the Freundt, et al study
would be derived thusly:
Step'I;
{200."x'3,'97)"mg7m3 x'8'x' l'x'0;3 . 27.2 mgAg (total
70 dose)
Where: (200 x 3.97) mg/m3 -dose converted from ppm to
mg/m3
8 « duration of exposure in hours
1 • ratio of lung/body weight ratios between adult
man and rat, as per Olsen and Gehring (1976)
0.3 » assumed-rartib' of "dase^ta'keTT up/dose e'x'posed to
70 - weight in kg of adult exposed to 200 ppm dose
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Sfcep'2;
x~l(Tfcg « 2.72 mg/1
~
OO x
Where: 27.4 = total dose in ing/kg
10 kg = weight of child
100 =~ safety factor
11= volume of drinking water imbibed/day by 10 kg
child
ten-day" SNARL
A ten-day SNARL can be derived from the one-day- SNARL which
should adequately protect the sensitive individual from
adverse health effects over that duration of exposure.
A ten-day SNARL would be derived simply by dividing the
one-day SNARL by 10 to get 0.27 ing/1.
Analysis
Cis-1, 2-dichloroethylene and trans-l,2-dichloroethylene can
be analyzed by the purge-and-trap gas chromatographic proce-
dure used for the determination of volatile organohalides in
drinking waters (U.S. EPA, 1980b; Be liar and Lichtenberg,
1979). In this procedure, volatile components are extracted
by an inert gas which is bubbled through the aqueous sample.
The compounds are swept from the purging device into- a~ short
sorbent trap. After a predetermined period of time, the
trapped components are thermally desorbed and backflushed
onto the head of a gas chroma tog raphic ^column -vheresepara--
tion takes place.
The recommended primary columns for organohalide analysis do
not adequately resolve the cis- and -trans-1^2--dichloroethy-
lene isomers. Therefore, it is suggested that the column
recommended for confirmatory analysis be used when these two
chemicals are being determined. The recommended chromato-
graphic conditions for the analysis are given below:
Column: Six^ feet. -long- -x-~0-^L; inch— IIX^s.tainl ess. ^stee
glass.
Packing; n - octane on Porisil - C (100/120 mesh).
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10
Temperature; 50°C isothermal for 3 minutes, then program at
6°/minute to 170°C.
Carrier gas; Helium at 40 ml/minute.
Detection; Hall model electrolytic conductivity or other
halogen specific detector.
Sample volume; 5 ml.
The retention time for the cis- isomer is 726 seconds and
for the trans- isomer is 563 seconds under the conditions
specified above. Confirmatory analysis of each isomer by a
second column or by GC-MS techniques is recommended. Al-
though the MS itself will not distinguish between cis- and
trans- dichloroethylene, the difference in GC retention
times will allow for proper identification.
The purge-and-trap •-procedti*ke-™i-s~appl«icabbie- -to- the- -me-a-s-are-~
ment of most organohal-ides- over- a. .concentr a t ion, .range o_£ ..0-. L
to 1500 ug/1 when the Hall model electrolytic conductivity
detector is used. -Other hadogen- specific--detectors-are—- -—
generally limited to measurements of 1.0 ug/1 or above.
Treatment
Very few data are available concerning the removal of trans-
1,2-d ich 1orou :
suggest—that"bothr aeration and""adsorptirOTr"by •grarrnrar~'a-ct'i~
vated carbon will be somewhat effective in reducing the
levels of this chemical.
Dobbs and Cohen (1980) developed adsorption isotherms for a
number of organic chemicals, including trans-l,2-dichloro-
ethylene. Their data show that, .at_,an-.equilibrium con.cen=-
tration of 100 ug/1, the activated carbon had an adsorptive
capacity of 0; 9^ mg' -o f "tr an-s-l:7-2-*di^hiro r oe* Lhyl en-e—pe r g t- am o £
cstirboft • ~ Trisx r- oft t2^~* fp^iff^tflrQr^^stiow^ -t'fa^^r'^~^^-*iT:Sj>jjC?nj&pm~cri^^f ^^'Sfio^i^ ~^*j^^-^- -TF-V^'H* •
be adsorbed—with-greater- eff icrency than—methyl ene—chlorlde>
but with far less efficiency than either tetrachloroethylene
or chlorobenzene.
Theoretical considerations indicate that aeration may have
some effectiveness in reducing" the levels of- trans-1,2-
dichloroethylene. -Love and. EiLers...419.8.1). found that the. . .. .
Henry's Law constant for a substance is a good predictive
tool for forecasting-the-relative amenabirl-ity of -that-stib--
stance _to- Aeration* Lov£ _tia8J..)... f nr t her—repdrJbad^Jthe- ^..... ,-.....
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11
Henry's Law constant for trans-1,2-dichloroethylene as 0.27.
This suggests that this chemical will be somewhat amenable
to air stripping, being somewhat more easily removed than
chlorobenzene (a chemical known to be relatively poorly
removed by aeration with a Henry's Law constant of 0.19),
but much less easily removed than tetrachloroethylene (a
chemical known to be amenable to aeration with a Henry's Law
constant of 1.2).
In summary, the levels of trans-1,2-dichloroethylene in
drinking water can be reduced by either aeration or"adsorp-
tion onto activated carbon. However, no full-scale field
data are currently available to support this conclusion.
All approaches should be considered since the preferred
approach will undoubtedly be determined on a case-by-case
basis. In addition, once a possible long-term treatment
technique has been identified, pilot-scale studies should be
conducted, not only to verify initial conclusions, but also
to estimate technical and economic considerations which such
a system will entail.
Conclusions and Recommendations
One-day and ten-day SNARLs of 2.7 mg/1 and 0.27 mg/1, re-
spectively, have been developed for trans-1,2-dichloroethy-
lene. At this time, no satisfactory dose-response no-effect
level data exist from which a longer-term SNARL can be de-
rived. In addition, it would be preferable to have dose-
response, no-effect data for the one-day and ten-day SNARLs
as well. A grant has been awarded under the EPA Competitive
Grants program to study the toxicity of all three dichloro-
ethylenes and compare the percentage absorption via inges-
tion and inhalation. Data from this study, which will
include no-effect, dose-response data, should be available
in 1982. At that time, the data will be reviewed and, if
found suitable, will form the basis for the revision of the
existent SNARLs. If the data are found lacking, further
research will be requested.
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12
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Anderson, M.E., N.L. Gargas, R.A. Jones, L.B. Jenkins, Jr.
1980. Determination of the kinetic constants for meta-
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Bellar, T. and J.J. Lichtenberg. 1979. Semiautomated
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13
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DISCLAIMER
This health advisory is a preliminary draft. It has
not been released formally by the Office of Drinking
Water, U.S. Environmental Protection Agency, and .should
not at this stage be construed to represent the position
of the Office of Drinking Water. It is being circulated
for comments on its technical merit.
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