United States
Environmental Protection
Agency
Office of
Toxic Substances
Washington, DC 20460
May 1980
EPA-560/11-80-009
Toxic Substances
&EPA
Environmental Sources of
Trichloroethylene Exposure:
Source Contribution Factors
-------
EPA-560/11-80-009
May 1980
ENVIRONMENTAL SOURCES OF TRICHLOROETHYLENE EXPOSURE:
SOURCE CONTRIBUTION FACTORS
by
M. Morse
The MITRE Corporation, Metrek Division
1820 Dolley Madison Boulevard
McLean, Virginia 22102
Contract No. 68-01-5863
Project Officer
Charles L. Trichilo, Ph.D.
Assessment Division
Office of Pesticides and Toxic Substances
U.S. Environmental Protection Agency
Washington, D.C. 20460
U.S. Environmental Protection Agency
Office of Pesticides and Toxic Substances
Washington, D.C. 20460
-------
ABSTRACT
This study is intended to assist the Assessment Division, Office
of Testing and Evaluation of the U.S. Environmental Protection
Agency, in the assessment of human health risks associated with tri-
chloroethylene exposure. The levels and frequency of occurrence of
trichloroethylene in the various environmental media (air, food, and
drinking water) have been identified. The relative contribution of
each of these sources to an individual's total daily trichloroethyl-
ene uptake is determined through an exposure/uptake approach. It is
anticipated that such an approach in combination with other exposure
information can be used in the support of regulatory decision making
under the Toxic Substances Control Act (TSCA). Available occurrence
data, although limited, indicate a greater persistence of trichloro-
ethylene in ground water than in the atmosphere or surface water.
Numerous instances of trichloroethylene occurrence in drinking water
(supplied by aquifers) were cited. The fetus, children and those
consuming ethyl alcohol were subunits of the general population
qualitatively identified as hypersensitive to trichloroethylene.
iii
-------
DISCLAIMER
This report has been reviewed by the Assessment Division, Office
of Pesticides and Toxic Substances, U.S. Environmental Protection
Agency, and approved for publication. Approval does not signify the
contents necessarily reflect the views and policies of the U.S.
Environmental Protection Agency, nor does mention of trade names or
commercial products constitute endorsement or recommendation for use.
The addition of any referenced data after December 1978 does not
indicate that a literature review was conducted after this date.
iv
-------
ACKNOWLEDGMENT
The author wishes to thank Dr. Charles L. Trichilo for his
continuous support and encouragement during the preparation of this
document.
Appreciation is expressed to the Criteria and Standards Division
of the Office of Drinking Water for initiating this work and to
Messrs. Roger Garrett and Blake Biles of the Premanufacture Review
Division for their support in its completion.
This document was reviewed in final draft form by Dr. James V.
Bruckner, Department of Pharmacology and Toxicology, University of
Texas, Health Science Center at Houston.
-------
TABLE OF CONTENTS
Page
LIST OF ILLUSTRATIONS viii
LIST OF TABLES viii
EXECUTIVE SUMMARY ix
1.0 INTRODUCTION 1
1.1 Background 1
1.2 Approach 2
2.0 PRODUCTION AND USE 5
3.0 ENVIRONMENTAL SOURCES OF TRICHLOROETHYLENE EXPOSURE 9
3.1 Trichloroethylene Concentrations in Ambient Air 10
3.2 Trichloroethylene Concentrations in the Diet 13
3.3 Trichloroethylene Concentrations in Drinking Water 17
4.0 ABSORPTION, METABOLISM, RETENTION, AND ELIMINATION 24
4.1 Absorption Characteristics 24
4.1.1 Pulmonary Absorption 25
4.1.2 Gastrointestinal Absorption 28
4.1.3 Dermal Absorption 29
4.2 Metabolism: Enzymatic Pathway and Intermediates 30
4.3 Retention Characteristics 35
4.4 Elimination Characteristics 37
5.0 SOURCE CONTRIBUTIONS TO DAILY TRICHLOROETHYLENE UPTAKE
IN HUMANS 42
5.1 Approach 42
5.2 Basic Assumptions 43
5.3 Estimated Daily Trichloroethylene Uptake From
All Sources 45
5.4 Identification of Critical Receptors 53
6.0 REFERENCES 57
vii
-------
LIST OF ILLUSTRATIONS
Figure
Number
2-1
4-1
4-2
Summary of 1974 Product Release Information
Proposed Metabolic Pathway for Trichloroethylene
Excretion Kinetics of Trichloroethylene and its
Metabolites in Humans
Page
8
31
39
LIST OF TABLES
Table
Number Page
2-1 Trichloroethylene Production—Individual Plants 6
3-1 Trichloroethylene Concentrations in Air 11
3-2 Trichloroethylene Content in Selected Foodstuffs 14
3-3 Daily Adult Dietary Intake of Trichloroethylene by
Food Class ' 16
3-4 Trichloroethylene Concentrations in Drinking Water 18
4-1 Summary of Reported Pulmonary Absorption for
Trichloroethylene in Humans 27
5-1 Basic Assumptions Employed in the Calculation of
Individual Source Contribution Factors 44
5-2 Representative Environmental Trichloroethylene
Exposure Levels 46
5-3 Calculation Sequence in Determining Source
Contribution Factors 47
5-4 Estimated Daily Trichloroethylene Uptake (Adults) 48
5-5 Estimated Daily Trichloroethylene Uptake (Child) 49
viii
-------
EXECUTIVE SUMMARY
The MITRE Corporation, Metrek Division has identified and
analyzed sources of trichloroethylene in air, food, and drinking
water. This report is an assessment of ambient environmental concen-
trations of trichloroethylene and their percent contribution to man1s
total daily uptake. It is intended to aid in the identification of
those environmental exposures to trichloroethylene posing the great-
est health risk.
Total 1978 trichloroethylene production in the United States was
135,903 metric tons. Approximately 80 percent of this was utilized
by industry as a degreasing solvent, 9 percent was exported while the
remaining 11 percent was used in minor processes (e.g., extraction
agent, chemical intermediate), and stored as inventory.
Trichloroethylene is found in all environmental media although,
due to its physical characteristics (i.e., high volatility, rapid
photodegradability, low solubility in water), it is not considered a
persistent contaminant in the atmosphere and surface waters. How-
ever, data on trichloroethylene in ground water aquifer systems
indicate a greater persistence. There is a constant flow of tri-
chloroethylene into the environment. About 95 percent of that pro-
duced in the United States is lost through fugitive emissions and
dispersive uses.
Reported ambient concentrations in air are variable, ranging
from less than 1 to greater than 100 |4,g/m . A representative
average nonindustrial urban air concentration is 1 |ag/m^- Maximum
air concentrations were noted downwind from chemical landfill sites.
Average dietary intake of trichloroethylene has been estimated
to be 10 ug/day. Individual dietary preference can be an important
factor in the variation of this value.
A wide range of trichloroethylene concentrations occurs in pub-
lic water supplies. The values reported vary from less than 1 to
greater than 22,000 (J.g/1. A value of 0.5 H-g/1 is representative of
an average urban concentration. Maximum trichloroethylene concentra-
tions are characteristically found within deep well aquifer systems.
Characterization (i.e., industrial, geographical) of trichloroethyl-
ene occurrence in drinking water systems is not well defined at this
time. Occurrence of trichloroethylene in ground water systems cor-
responds with residential and industrial use, and subsequent dis-
charge and leaching of products containing trichloroethylene.
ix
-------
Trichloroethylene can be absorbed into the body via pulmonary,
gastrointestinal and dermal routes. Pulmonary absorption rates have
been reported within a range of 35 to 77 percent, while gastroin-
testinal absorption rates are assumed to range between 80 and 100
percent of intake. Dermal exposure and absorption are considered
negligible.
Absorbed trichloroethylene is metabolized via enzymatic bio-
transformation. The transformation sequence involves enzymatic
oxidation, intramolecular rearrangement and hydrolytic reactions.
The major excreted metabolic products are trichloroethanol, tri-
chloroethanol glucuronide, and trichloroacetic acid. Trichloro-
ethanol is of concern due to neurologic effects, while trichloro-
acetic acid and certain intermediates may be of toxic significance
due to protein binding abilities and subsequent hepatorenal cytotoxic
effects.
Some accumulation of unmetabolized trichloroethylene has been
noted in fatty tissues and is assumed to be a result of its high
lipid solubility. Otherwise, a fairly uniform distribution pattern
is found within internal organs.
Trichloroethylene, absorbed through the respiratory and gastro-
intestinal tracts, may be excreted unchanged, or metabolized and ex-
creted as soluble metabolites. The half-life of unmetabolized tri-
chloroethylene ranges from 1 to 20 hours, while the half-life of its
metabolites may range from 12 to 58 hours.
Trichloroethylene is eliminated from the body via respired air
or the urine, and to a considerably lesser extent in the feces and
perspiration. Pulmonary elimination is virtually complete 24 to 48
hours after either pulmonary or gastrointestinal exposure, while
urinary excretion of metabolites may persist for 2 weeks.
Based on calculations performed in this document, total trichlo-
roethylene uptake from air, food, and water can range from 26 to
45,492* |a.g/day in adults and from 9 to 31,111* fig/day in chil-
dren. The contribution of drinking water to total daily trichloro-
ethylene uptake can range from <1 to 99 percent in both adults and
children. This wide range is due to the variability of ambient
trichloroethylene concentrations in air and water.
*It is noted that, at the highest trichloroethylene concentration
in water selected for these calculations, the taste of trichloroethy-
lene can be perceived. Therefore, drinking water volume consumed
per day would decrease, and a more likely total trichloroethylene
daily uptake would be 6992 |j.g/day in adults and 5811 (j.g/day in
children.
-------
Those subpopulations within the general population that are
qualitatively identified as hypersensitive to trichloroethylene are
the fetus, children, and those consuming ethyl alcohol. The primary
physiological reasons for hypersensitivity to trichloroethylene in
each group are the facility of placental permeability, the ease of
deposition due to immature organogenesis, and the competitive
inhibition or stimulation of the mixed function oxidase enzymes,
respectively.
The exposure/uptake approach in this report offers a means of
identifying human health risks and in combination with other exposure
information can be used in regulatory decision making.
xi
-------
1.0 INTRODUCTION
The Toxic Substances Control Act (TSCA) authorizes the Environ-
mental Protection Agency (EPA) to take various types of actions to
identify and mitigate unreasonable risks to health or the environment
posed by chemical substances and mixtures. In determining unreason-
able risks the agency will perform risk assessments to evaluate the
adverse effects on health or the environment that are expected to
result from exposure to a chemical.
The MITRE Corporation/Metrek Division has identified and ana-
lyzed sources of trichloroethylene uptake from air, food, and drink-
ing water. In this assessment, the contribution from each source to
total daily uptake is determined over a broad range of environmental
occurrence levels. The source contribution model presented in this
study identifies routes of environmental exposure. This model, as
well as the identification of sensitive segments of the population,
may be used to support regulatory decision making under TSCA.
1.1 Background
Trichloroethylene is widely distributed in the environment,
occurring in variable quantities in food, drinking water and the
atmosphere. Due to its high rate of atmospheric photodegradation,
low water solubility, and high vapor pressure trichloroethylene does
not persist in the atmosphere or surface water (Dilling et al. 1976;
Moolenar, 1980). It is considered to have greater persistence in
ground water than in the atmosphere or surface water (DeWalle, 1979).
-------
However, due to the high volume of trichloroethylene released into
the environment (about 80 percent of the production in the United
States) there exists a constant influx to the environmental media
(EPA, 1977a; Geomet, 1977). Trichloroethylene is thus widely
dispersed in food, air and water. Ambient concentrations are usually
low, but can show wide variation (Section 3.0).
Trichloroethylene can be absorbed from environmental sources in
significant amounts (via pulmonary and gastrointestinal exposure),
accumulate in fatty tissues (due to its high lipid solubility), and
can cross tissue membranes as well as the placenta (Laham, 1970).
Trichloroethylene and its metabolites exert neurologic and hepator-
enal toxic effects. Trichloroethylene has been implicated as a
carcinogen (NCI, 1976) in humans. The combination of these factors
yields a potential health risk to populations exposed to trichloro-
ethylene.
1.2 Approach
Trichloroethylene is a highly lipid soluble solvent. In order
to properly assess the health significance of the ingestion of
trichloroethylene-contaminated drinking water, it is necessary to
*It is noted that, although hepatorenal toxicity of metabolized
trichloroethylene has been demonstrated, neurotoxicity has not been
demonstrated per se, but is alluded to through acknowledgment of
acute, reversible CNS depression, and "psychoorganic syndrome"
(Ertle et al., 1972). Measurement of neurological dysfunction has
not exhibited, to date, the sensitivity necessary to determine the
occurrence of residual neurologic effects.
-------
define the contributions to an individual's trichloroethylene uptake
from each major source of exposure. These source contribution
factors can be defined in three successive steps, i.e.,
o define and quantify the major environmental sources of
trichloroethylene exposure,
o determine the absorption/metabolism/retention and elimination
characteristics of trichloroethylene in man via each exposure
route, and
o estimate total daily uptake of trichloroethylene in man,
based on ambient exposures and absorption/retention
characteristics.
By examining the percent contribution to the total uptake from each
route of exposure, one can calculate the source contribution factors
for each type of trichloroethylene exposure. In this way, the
significance of trichloroethylene exposure via drinking water can be
assessed in view of the other possible exposure routes.
In the process of defining source contribution factors, it often
becomes necessary to consider instances where endogenous (e.g., age,
physiological condition) or exogenous (e.g., geographical area, occu-
pation) factors can affect the percent contribution from each
environmental source. With this in mind, average values for environ-
mental occurrence and absorption are considered as well as maximum
reported values, because inclusion of only the average values in
calculating the source contribution factors may lead to erroneous
conclusions.
This report defines the percent contribution to the total tri-
chloroethylene uptake from all the major' environmental sources of
-------
exposure. The report does not, however, consider or evaluate the
toxicological implications of such trichloroethylene uptake. Those
instances when critical data were insufficient or lacking are pointed
out in the text.
-------
2.0 PRODUCTION AND USE
Commercial production of trichloroethylene in the United States
began in 1925, yielding only a few hundred tons per year for minor
extraction processes. Trichloroethylene was in high demand during
the 1930s for use in metal degreasing and dry cleaning (Hardie,
1964).
Production of trichloroethylene has been declining since its
peak production of 276,635 metric tons in 1970. Total U.S. produc-
tion in 1978 was 135,903 metric tons and estimated production in 1979
was 115,739 metric tons (Emanuel, 1980). The decline in production
from 1970 is thought to be due to the enforcement of air pollution
restrictions (SRI, 1978) since the classification in 1966 of trich-
loroethylene as a photochemical reactant in smog, and the voluntary
discontinuation of trichloroethylene use in food processing after an
NCI alert in 1975 of the possible carinogenicity of trichloroethylene
in mice (Buxton, 1978).
The two major industrial processes employed to produce trichloro-
ethylene have been (1) oxychlorination of ethylene dichloride and (2)
chlorination of acetylene (followed by dehydrochlorination). Prior
to 1967, 85 percent of trichloroethylene produced in the United
States was derived from acetylene chlorination. Presently, 85 per-
cent of trichloroethylene is produced via the oxychlorination of
ethylene dichloride (NIOSH, 1973).
-------
TABLE 2-1
TRICHLOROETHYLENE PRODUCTION* - INDIVIDUAL PLANTS
Annual
Company Location Capacity
(1000 metric tons)
Dow Chemical U.S.A. Freeport, Texas 68
Ethyl Corporation Baton Rouge, Louisiana 20
PPG Industries, Inc. Lake Charles, Louisiana 91
TOTAL 179
Note: The Diamond Shamrock Corporation has a 23 metric ton per year
facility which was placed on standby in early 1978.
*Process used by these companies for trichloroethylene production is
oxychlorination of ethylene dichloride.
Source: Adapted from SRI, 1979.
-------
There are currently three active producers of trichloroethylene
in the United States. Their locations, capacities, and production
processes are displayed in Table 2-1.
Trichloroethylene is utilized in a variety of processes in the
United States. Over 80 percent is used by industrial metal fabricat-
ing plants for vapor degreasing. Other agents such as tetrachloro-
ethylene and methylene chloride have been employed as degreasers
since 1960, but trichloroethylene is still used in over 50 percent of
this industry (NIOSH, 1973). Of the remaining 20 percent, about 9
percent is exported, less than 10 percent is used as a solvent, chem-
ical intermediate and terminator, while the remainder is stored in
inventory (SRI, 1978).
Trichloroethylene had been used until 1976 for the selective
extraction of foods, fish meal, meat meal, oil-containing seeds,
soya beans, and coffee beans (decaffination). Current applications
include use as a metal cleaning solvent; as a swelling agent in the
disperse dyeing of polyesters and in the removal of basting threads
by the textile industry; as the raw material for production of a
chemical intermediate in fungicide formulation (Difolatan®); and as a
chain termination in polyvinyl chloride production (SRI, 1978).
A flowchart of trichloroethylene production and consumption in
the United States for 1974 is presented in Figure 2-1.
*Actual use of trichloroethylene for extraction purposes in food
products was voluntarily discontinued by manufacturers in 1975-76
after an NCI carcinogenicity alert (Buxton, 1978).
-------
oo
Trichloroethylene
R - 1.95xlOs metric tons/vr.
Imports
2.72x10** metric tons/yr.
Exports
1.90x10** metric tons/yr.
Total U.S.
Production
(P) R
1. 93x10 5 metric toas/yr.
„
•I t
Total U.S.
Consumption
(C)
2. 02x10 5 metric tons/yr.
* \
Loss of compound Loss of by-product
2.9xl03 metric tons/yr. N.A.
FPL ' 0-015
1.77x10° met
FD - 0.95
Dispersive use
1.92xl05 metric tons/yr.
O.lSxlQ5 metj
:ric tons/yr.
•ic tons/yr.
Metal
Cleanej j
Other
extractant
in food proc . ,
solvent ,
chemical
intermediate,
anesthetic
Source: Chan et al., 1975.
R • production rate
F_ - fraction dispersal
F_. " fraction of production lost
FIGURE 2-1
SUMMARY OF 1974 PRODUCT RELEASE INFORMATION
-------
3.0 ENVIRONMENTAL SOURCES OF TRICHLOROETHYLENE EXPOSURE
Approximately 95 percent of the total trichloroethylene produced
in the United States is lost to the environment each year (EPA,
1977a; Geomet, 1977). The majority of this loss is due to vapor loss
and discharge in waste streams from industrial degreasing operations
(EPA, 1977a). The great potential for release to the atmosphere
during vapor degreasing due to the relatively high volatility of the
chemical (i.e., vapor pressure of 57.8 mm Hg at 20°C [Irish, 1967]),
has led to objections to the use of trichloroethylene as a solvent in
this process (Dale, 1972; Greve, 1971).
Once released to the atmosphere, aerial transport plays a major
role in the dissemination of trichloroethylene throughout the
environment. The compound transfers rapidly to all compartments of
the biosphere. Trichloroethylene is not considered a persistent
atmospheric or surface water contaminant (Billing et al., 1976;
Moolenar, 1980). It exhibits low water solubility (i.e., 0.11 g/lOOg
at 20°C) high vapor pressure, and rapid atmospheric photodegradabil-
ity (Moolenar, 1980; Waters et al., 1977). A transport model for
trichloroethylene prepared by Moolenar (1980) shows trichloroethylene
leaving the biosphere as rapidly as it is introduced and that it does
not accumulate. An estimated half-life of 5 to 12 hours for trich-
loroethylene (in air) under bright sunlight was reported by Billing
et al. (1976). It is hypothesized, however, that trichloroethylene
leaching into deep aquifer systems may be persistent (Fliescher,
1978).
-------
In the sections that followj trichloroethylene concentrations
that have been reported for air,* water,* and food are presented.
3.1 Trichloroethylene Concentrations in Ambient Air
It has been estimated that the average background ambient
atmospheric concentration of trichloroethylene is 0.011 [ig/nH
(Moolenar, 1980). Midwest Research Institute (1977) reported
atmospheric levels of trichloroethylene ranging from undetected to
4.94 fig/m^ for 27 sites in the United States. Of the sites having
trichloroethylene in detectable concentrations, 79 percent had levels
greater than 0.05 jjig/m^. Other monitoring studies have reported
trichloroethylene levels greater than 100 [xg/m^ in industrial areas
(Pearson and McConnell, 1975).
Classification of ambient trichloroethylene air concentrations
by regional, industrial, or topographical characteristics is some-
what tenuous due to limited monitoring data. It has been proposed
i
that the distribution of trichloroethylene throughout the atmosphere
is consistent with its usage (McConnell et al., 1975); however, mon-
itoring data do not consistently support this contention. The lack
of supporting monitoring data may be due to the isolated or short-
term nature of most trichloroethylene sampling to date. Table 3-1
presents a compilation of reported atmospheric concentrations of tri-
chloroethylene. Analysis of these data indicates increased tri-
chloroethylene air concentrations downwind of landfill sites. Air
*Excludes occupational and/or industrial data.
10
-------
Concentration
(yg/m3)
Location
Undetected-26.6 United States
Trace
0.011
0.94
-1.0
1-10
1.2
Edison, NJ
Texas
Torrance, CA
Patterson, NJ
TABLE 3-1
TRICHLOROETHYLENE CONCENTRATIONS IN AIR
Reference
1.99 - 27.95 Rural England
2.69-13.97 U.S. excluding La
Jolla, CA
2.69 - 29.02 La Jolla, CA
4.03 - 31.17 Europe
Remarks
Midwest Research Institute, Ambient air samples from 27 cities or
1977 areas in the United States; of the
sites for which trichloroethylene was
detectable, 79 percent had levels
> 0.05 ug/m3.
Research Triangle Institute, Sample taken in landfill area.
1977c.
Moolenar, 1980
Approximate ambient concentration.
Research Triangle Institute, Average of nine samples.
1977c.
Pellizzari, 1977
McConnell et al., 1975
Pellizzari, 1977
Murray and Riley, 1973
Su and Goldberg, 1976
Su and Goldberg, 1976
Su and Goldberg, 1976
Typical concentrations.
Only one quantifiable value from eight
samples.
5.37 - 107.49 Liverpool/Manchester, Pearson and McConnell, 1975
England, suburbs
Northeast Atlantic
and rural Britain
Murray and Riley, 1973
-------
TABLE 3-1 (CONCLUDED)
Concentration
(ug/m3)
9.2
11.0
40 - 258
Location
Dominquez, CA
Edison, NJ
Edison, NJ
Reference
Remarks
Research Triangle Institute,
1977a
Research Triangle Institute, Average concentration, taken upwind
1977c from landfill site for chemical waste.
Research Triangle Institute, Average concentration was 87.5 yg/m3.
1977c Samples were taken downwind from land-
fill site.
-------
(Research Triangle Institute, 1977a).
Many values reported in Table 3-1 may not be representative of
monthly or annual averages for each site since the duration of most
air monitoring has been brief, consisting of single spot checks or
1-day measurements. Daily fluctuations in meteorological conditions
can vary ambient air levels erratically. Only long-term sampling
programs will provide figures that accurately represent average
ambient air concentrations of trichloroethylene.
The household use of trichloroethylene-containing solvents,
degreasers, adhesives, etc., in poorly ventilated areas could result
in exposure to concentrations far exceeding the environmental levels
indicated in Table 3-1. Exposure concentrations from this extremely
variable source have been suggested to reach the hundreds to thou-
sands of parts per million range (Bruckner, 1979). There are no data
available, however, for further quantification of this exposure
source.
3.2 Trichloroethylene Concentrations in the Diet
Quantitative analyses of trichloroethylene content of foodstuffs
are extremely limited. Only one study covering a variety of food
items in both animal and vegetable categories has been identified in
the literature to date. The trichloroethylene concentrations of
specific foodstuffs categorized by food class as defined by the Food
and Drug Administration (FDA) are presented in Table 3-2.
13
-------
TABLE 3-2
TRICHLOROETHYLENE CONTENT IN SELECTED FOODSTUFFS
Trichloroethylene
Food Class3 Content (yig/kg)b
I. Dairy Products
Fresh Milk 0.3
Cheshire Cheese 3.0
English Butter 10.0
Hens' Eggs 0.6
II. Meat, Fish and Poultry
English Beef (Steak) 16
English Beef (Fat) 12
Pig's Liver 22
III. Grain and Cereal Products
Fresh Bread 7
IV. Potatoes 3
V. Leaf Vegetables 4.6d
VI. Legume Vegetables 4.6^
VII. Root Vegetables 4.6d
VIII. Garden Fruits
Tomatoes0 1.7
IX. Fruits
Pears 4
Apples 5
Black Grapes (Imported) 7
X. Oils and Fats
Margarine 6
Vegetable Oil 7
Olive Oil 9
Cod Liver Oil 19
XI. Sugar and Adjuncts
XII. Beverages
Canned Fruit Drink 5
Light Ale 0.7
Wine 0.02
Tea (Packet) 60.0
Instant Coffee 4.0
Decaffinated Coffee (packet) 60.0
Food group category according to FDA, 1977
McConnell et al., 1975
Grown on reclaimed lagoon
Averaged values from Groups III, IV, VIII, and IX (McConnell et al., 1975)
14
-------
Assuming that the concentrations reported by McConnell et al.
(1975) are representative of the range and distribution of tri-
chloroethylene in foods and beverages,* it is apparent that an
individual's food preferences will vary the total daily intake of
trichloroethylene. Estimation of total dietary intake of trichloro-
ethylene involves the utilization of FDA's total diet composition
(quantifying food group intake [g/day]) and known concentrations of
trichloroethylene in -each food group. Table 3-3 displays estimated
total trichloroethylene ingested per day by food group. The total
dietary intake of trichloroethylene estimated by this method is 13.6
jig/day.
The inclusion of certain beverages can raise the daily trichlo-
roethylene intake. The addition of 1 liter of decaffeinated coffee/
tea (assuming 1.6 g of coffee per cup and trichloroethylene concen-
tration @ 60 ppb) to the dietary intake presented in Table 3-3 yields
a total dietary trichloroethylene intake of 14.1 jig/day.
MITRE/Metrek assumes 10 fig/day to be representative of adult
dietary trichloroethylene intake. This intake rate is utilized in
daily uptake calculations in Section 5.
Due to present decreases in production of trichloroethylene,
these values may have decreased; however, documented evidence is
not presently available to support this.
**Although the FDA is still in the process of officially banning
the use of trichloroethylene in the preparation of decaffeinated
and instant coffee and tea, the actual use of trichloroethylene
in the decaffeination process was terminated by manufacturers in
1975-76 due to an NCI alert (Buxton, 1978) (see Section 5.3). The
intent of FDA to delist trichloroethylene from use in the food
industry has been announced (Federal Register, 1977).
15
-------
TABLE 3^3
DAILY ADULT DIETARY INTAKE OF TRICHLOROETHYLENE
BY FOOD CLASS
Food Class
Estimated Adult Dietary
Trichloroethylene Intake
Ug/day
I. Dairy
II. Meat, Fish and Poultry
III. Grains and Cereals
IV. Potatoes
V. Leafy Vegetables
VI. Legume Vegetables
VII. Root Vegetables
VIII. Garden Fruits
IX. Fruits
X. Oils and Fats
XI. Sugars and Adjuncts
TOTAL
2.7
4.5
3.0
0.5
0.3
0.3
0.2
0.2
1.2
0.7
13.6
Does not include beverages
Food group categories according to FDA, 1977.
Estimated using trichloroethylene concentrations as in
McConnell et al., 1975 and FDA diet composition (1977),
16
-------
3.3 Trichloroethylene Concentrations in Drinking Water
Trichloroethylene is not routinely monitored in surface water.
Analyses to date have involved isolated and short-term samples.
These random samplings of municipal water supplies, rivers, oceans,
and rainwater indicate that the compound is widely distributed at or
below the 1 |jLg/l level (McConnell et al., 1975). However, trichloro-
ethylene concentrations of up to 47 jj.g/1 in finished surface drinking
water (EPA, 1977b) have been recorded. The analytical results of
these limited samplings are summarized in Table 3-4.
The most extensive monitoring study of trichloroethylene in
surface drinking water supplies is that of the National Organics
Monitoring Survey (EPA, 1977b). Three phases of this study, each of
about 2 months duration, identified measurable concentrations of tri-
chloroethylene in 3, 25, and 18 percent of the 113 community water
supplies sampled in each of the three phases, respectively. The mean
trichloroethylene concentrations of those samples in which trichloro-
ethylene was identified in each phase were 12, 2.1 and 1.3 |o.g/l for
phases 1, 2, and 3, respectively. The range of detected concentra-
tions found for all three phases was 0.06 to 47.0 [J.g/1. Mean
trichloroethylene values, including those samples in which trichloro-
ethylene was not identified, fell below 1 ug/1 for each phase of this
study. This appears to be in agreement with the predictions of both
McConnell et al. (1975) and Moolenar (1980).
17
-------
TABLE 3-4
TRICHLOROETHYLENE CONCENTRATIONS IN DRINKING WATER
00
Concentration (yg/liter)
0.1 - 0.5
0.0006
0.01 - 1.0
<0.1 - 0.5
Undetected-47
<2 - 32
4* - 300
0.01-30.85
0.2 - 0.5
*
Limit of detection
Location
10-city survey
5-city survey
113 municipal water
supplies throughout the
United States
14 cities or areas in
the United States
Nassau County, New York
Dade County, Florida
Huntington, West
Virginia
Reference
EPA, 1975
Moolenar, 1980
McConnell et al., 1975
Coleman et al., 1975
EPA, 1977b
Midwest Research
Institute, 1977
Myott, 1977
Stilwell, 1977
Brass, 1979
Remarks
Found in 5 of 10 drinking waters sampled by the
National Orgahics Reconnaissance Survey (average
concentration 0.2 ug/1).
Approximation of the background concentration.
Typical concentrations expected.
Average concentration was <1 ^g/liter.
Twenty-two cities or areas were sampled.
Of 422 samples taken from 377 wells, 54 contained
trichloroethylene.
Highest level detected in preliminary sampling data
collected from 218 wells. Trichloroethylene detected
in 104 wells at an average concentration of 0.62 ug/
liter in the quantified samples.
Several hundred samples (wells)
January 1978 - January 1979 testing period
-------
Concentration (ug/llter)
2200-3500
22
18
22000
20-10000
4.5
5-3100
undetected - 2500
100
0.7 -1420
0.5 - 170
7 - 600
Location
Collegeville Trappe,
Pennsylvania
Smyna, Delaware
Reamstown, Pennsylvania
TABLE 3-4 (CONCLUDED)
Reference
Blankenship, 1978
Blankenship, 1978
Blankenship, 1978
West Ormrod, Pennsylvania Blankenship, 1978
Danville, Virginia
New Castle, Delaware
Blankenship, 1978
Blankenship, 1978
Bucks County, Pennsylvania Runowski, 1980
Montgomery County,
Pennsylvania
Chester County,
Pennsylvania
Long Island, New York
Bergen County, New Jersey
San Gabriel Valley, Calif.
Runowski, 1980
Runowski, 1980
Referente, 1980
Referente, 1980
Lowe, 1980
Remarks
Industrial source of contamination (Uniform Tube Co.)
As a result, these private wells were destroyed. (30
private and 7 public wells - serving a population of 4500).
Landfill source of contamination. Use of aeration
equipment and boiling water reduced TCE levels to 10 pg/1
Public wells serving a population of 12000.
Industrial source of contamination - public wells serving
a population of 5000.
Wells destroyed. Source of contamination identified as'
landfill. 5 public wells serving a population of 650
were contaminated.
Industrial contamination source (Diston, Inc.) Wells
were destroyed. 8 wells serving a population of 15000
were contaminated.
Industrial contamintion source. 1 public water supply;
7 wells serving a population of 5500.
Contamination source unidentified. 11 public water
supplies involved; 20 public wells; serving a population
of 75,000 (many areas could tap into other water supplies).
Industrial contamination. Tube and electronic companies
(wells). Mean concentration less than 5 pg/Jl.
100 wells contaminated by 2 spills. Sources not identified.
Over 75% of the private wells in this area were contaminated,
serving a population of 650.
Contamination sources unidentified (58 wells).
Industrial contamination (21 wells).
Industrial contamination of 17 municipal ground water
systems effecting a population of about 3400.
-------
Trichloroethylene is not routinely monitored in ground water
supplies. However, due to contamination findings, Pennsylvania now
monitors trichloroethylene in ground water on a regular basis
(Runowski, 1980). Trichloroethylene concentrations in contaminated
ground water are as high as 22000 (ig/1 while background concentra-
tions are reported at about 0.5 [xg/1 (Table 3-4).
Extremely high trichloroethylene levels of 3500, 10,000, and
22,000 [j.g/1 were reported in Collegeville Trappe, Pennsylvania, Dan-
ville, Virginia, and West Ormrod, Pennsylvania, respectively (mean
values were not available). Maximum values reported for Dade County,
Florida, and Nassau County, New York, were 30 jj.g/1 and 300 (o.g/1,
respectively, while the mean trichloroethylene concentrations were
less than 1 |ag/l and less than 10 |o.g/l, respectively (Table 3-4).
Infiltration of the ground water system has been extensive where
trichloroethylene contamination has occurred, effecting a large num-
ber of public and private wells. It is apparent that as a result of
spill contamination, trichloroethylene can permeate an entire aquifer
system. This is exemplified by such areas as Danville, Virginia,
Smyrna, Delaware, Collegeville Trappe, Pennsylvania, Reams town,
Pennsylvania, and West Ormrod, Pennsylvania, where in each case the
entire community ground water supply was contaminated. As a group,
these cases effected a total population of over 40,000 (Runowski,
1980).
20
-------
Classification of trichloroethylene concentrations in surface
water by regional or industrial characteristics is difficult. Ground
water supplies appear to have higher levels of trichloroethylene than
surface water supplies. Therefore, it may be hypothesized that a
population supplied by aquifers has a greater chance of consuming
larger amounts of trichloroethylene than one supplied by surface
water.
High trichloroethylene levels in ground water correspond with
the use and subsequent discharge and leaching of industrial solvents
and degreasers (Fliescher, 1978). Occurrences in Pennsylvania,
Delaware, Virginia, and California reinforce this point (Table 3-4).
However, other high concentration sites (e.g., Nassau County, Bucks
County) cannot be classified as industrial areas. Small degreasing
operations (e.g., service stations, trucking fleets) were also
absent. It is suggested that industrial activity may have contami-
nated the aquifers as many as ten years prior to the time of measure-
ment and, due to low ambient temperatures, lack of adsorption to
sand, and absence of appreciable vaporization the trichloroethylene
has remained as a contaminant (Fliescher, 1978). Trichloroethylene
is considered a persistent contaminant in deep aquifers with a range
in degradation of 1 to 5 years (DeWalle, 1979). In comparison,
trichloroethylene in surface water and in the atmosphere is con-
sidered to be nonpersistent to moderately persistent, with an esti-
mated degradation range of a few hours to 18 months (Abrahms, 1977;
Moolenar, 1980; Smith, 1966).
21
-------
Another source of trichloroethylene contamination of ground-
water supplies in non-industrial areas is the leaching of septic tank
cleaning products containing trichloroethylene. It is believed that
the use of these cleaners could have created a detectable background
concentration of trichloroethylene in ground-water supplies ( in ad-
dition to any industrial contamination) in areas such as Collegeville
Trappe and Bucks County, Pennsylvania (Runowskij 1980).
The EPA and state authorities have dealt with trichloroethylene
contamination of ground water supplies by destroying effected wells,
or by instituting home treatment of drinking water. Granulated acti-
vated carbon filtration units have been shown to reduce trichloro-
ethylene concentrations of 20,000 p.g/1 to 5 fig/1. The period of
effectiveness of the columns is regarded as variable (Runowski,
1980). Boiling water in situations of low level contamination also
decreased the contaminant concentrations (Runowski, 1980).
Improper disposal through industrial spills and dumping, public
use of septic tank cleaners containing trichloroethylene, improper
disposal of other products containing trichloroethylene by the gener-
al public, as well as leachate from landfills are identified sources
of trichloroethylene contamination of ground-water systems. Imple-
mentation of proper disposal practices in each of these cases could
obviate hazardous groundwater contamination.
Although there is presently no drinking water standard for tri-
chloroethylene, it has occurred in potable water at sufficient
22
-------
frequency for the EPA Office of Drinking Water to provide a "suggest-
ed no adverse response level" (SNARL) upon request to those needing
advice on its health effects as the result of drinking water contami-
nation. A one-day and ten-day SNARL for the child have been provided
at 2 mg/liter and 0.2 mg/liter, respectively, for emergency and spill
situations with drinking water as the sole or primary source of human
intake of trichloroethylene. A long term or chronic SNARL has been
provided at 75 [ig/1 for the child when drinking water is the primary
source of explosure and 15 |og/l when additional sources are involved.
A drinking water standard or a Maximum Contaminant Level for tri-
chloroethylene is now being developed by the EPA Office of Drinking
Water (EPA, 1979).
Based on the available data, MITRE/Metrek has chosen trichloro-
ethylene concentrations of 0.5, 30, 300 and 22,000 [o.g/1 as represen-
tative drinking water levels to be used in all uptake calculations
presented in Section 5. These values are assumed to be representa-
tive of average drinking water concentrations, two high ground water
and maximum extreme ground water concentrations, respectively.
23
-------
4.0 ABSORPTION, METABOLISM, RETENTION, AND ELIMINATION
Trichloroethylene is absorbed in the body after pulmonary, gas-
trointestinal, and dermal exposure. Approximately one-third of the
absorbed trichloroethylene is rapidly eliminated through the pulmon-
ary compartment as unchanged trichloroethylene, while a small amount
(less than 10 percent) is eliminated via the urinary tract. The re-
maining portion of absorbed trichloroethylene is distributed through-
out the body, with some accumulation occurring in the fatty tissues,
and a majority is metabolized in the liver. This enzymatic process
produces trichloroacetic acid, trichloroethanol and trichloroethanol
glucuronide as final metabolites which are subsquently eliminated,
primarily in the urine. The following sections describe the mecha-
nisms of trichloroethylene absorption, metabolism, retention, and
elimination.
4.1 Absorption Characteristics
Kinetic modeling of pulmonary absorption is extensive in the
literature since it is a primary route of exposure in occupational
settings. Trichloroethylene is absorbed readily through the respi-
ratory epithelium as well as through the gastrointestinal wall.
Cutaneous absorption of trichloroethylene is considered negligible
from environmental sources. The following sections elucidate the
physiological characteristics of each of the three routes of absorp-
tion.
24
-------
4.1.1 Pulmonary Absorption
The pulmonary tract is an entry route for most solvents and va-
pors. Trichloroethylene vapors are readily absorbed through the res-
piratory epithelium. Absorption by the pulmonary tract is dependent
upon the equilibrium ratio; the rate of pulmonary ventilation; the
diffusion through the alveolar capillary and tissue membranes; solu-
bility in blood and tissues; exposure concentrations; the duration
of exposure; and the metabolic rate.
The pulmonary absorption rate is greatest upon early exposure,
decreasing until an as yet unidentified equilibrium level is reached
between inspiratory vapor concentration and trichloroethylene levels
in the blood (Astrand and Gamberale, 1978). The percent of pulmonary
absorption has been reported to be inversely dependent upon the equi-
librium ratio, the quotient of the concentrations in alveolar air and
inspiratory air (i.e., the percent uptake decreases as the alveolar
concentration increases) (Astrand, 1975; Astrand and Gamberale,
1978). The percent of pulmonary absorption increases with decreasing
exposure concentrations (Astrand and Ovrum, 1976).
The quantity of trichloroethylene absorbed by the pulmonary com-
partment (represented by trichloroethylene concentration in arterial
blood) is directly related to alveolar air concentration (Astrand and
Ovrum, 1976). However, this relationship appears to be limited by
the solubility of trichloroethylene in blood (the partition coeffi-
cient) (Astrand and Ovrum, 1976).
25
-------
Total pulmonary absorption has been found to increase during
physical exertion due to an overall rise in respiratory and meta-
bolic rate (Astrand and Ovrum, 1976). Although total absorption of
trichloroethylene increased during four consecutive exercise periods,
the relative absorption in each of the four exercise periods was
found to decrease. It is hypothesized that at a higher work output,
the rate at which trichloroethylene is supplied to the alveoli is
faster than the rate of diffusion from the alveoli to the blood.
The low rate of diffusion to the blood is believed to be a result
of the low partition coefficient (from alveolar air to blood) of
trichloroethylene (Astrand and Ovrum, 1976). An increase in uptake
of trichloroethylene is believed to be a result of rapid clearing of
trichloroethylene from the blood due to rapid deposition in the tis-
sues (high lipid solubility) and rapid biotransformation by the liver
(Astrand and Ovrum, 1976).
A summary of reported absorption percentages for trichloroethy-
lene is presented in Table 4-1. These percentages range from 35 to
77 and are based on exposures ranging from 268 to 2044 mg/nr. The
expected inverse dependency of percent absorption to exposure con-
centrations is not clearly apparent in Table 4-1. This is probably
a result of variation in experimental procedures in addition to indi-
vidual physiological differences. The distribution of absorption
percentages resulting from variable fat content of tissues (Astrand
26
-------
TABLE 4-1
SUMMARY OF REPORTED PULMONARY ABSORPTION
FOR TRICHLOROETHYLENE IN HUMANS
Percent
Absorption
75
53
50
51-64
55
50
56-60
35-63
58-70
74
62.5
67-77
Concentration
(mg/m3 )
540
1080
1043
1355-2044
268
1076
Duration
of Exposure
30 minutes
30 minutes
30 minutes
5 hours
2.7 hours
7 hours
Reference
Astrand and Gamberale,
Astrand, 1975
Astrand, 1975
Bartonicek, 1962
Nomiyama and Nomiyama,
Ikeda, 1977
Soucek et al.} 1952
Stewart et al., 1970
1976
1974
Soucek and Vlachova, 1960
376
753
— _
4 hours
4 hours
___
Monster et al., 1976
Monster et al. , 1976
Monster et al. , 1976
27
-------
and Ovrum, 1976) may be the result of the small sample size used in
these experiments.
Ambient atmospheric trichloroethylene concentrations are signif-
icantly less than experimental exposure levels by a factor of 10*
(Tables 3-1 and 4-1). It is assumed that the percent absorption will
be somewhat greater at the lower ambient environmental concentrations
than that of the higher experimental concentrations. Therefore,
MITRE/Metrek has selected a rate of 65 percent as representative of
the reported range of pulmonary absorption. Succeeding chapters will
employ the use of this value in source contribution and uptake con-
siderations.
4.1.2 Gastrointestinal Absorption
Analysis of isolated poisoning cases (i.e., attempted suicide)
indicate that trichloroethylene passes across the gastrointestinal
wall into the blood (Gibitz and Plochl, 1973; Vignoli et al., 1970).
There is a paucity of gastrointestinal absorption values in the lit-
erature due to limited quantification of blood levels and excreted
trichloroethylene in accidental ingestion cases, and a lack of human
or animal ingestion studies.
Oral administration of radioactively labeled trichloroethylene
to rats resulted in the excretion of 72 to 85 percent of the labeled
unchanged trichloroethylene via the pulmonary compartment, while
urinary excretion of labeled metabolites represented 11 to 21 percent
of the initial exposure. Thus, an estimated 80 to 100 percent of
28
-------
ingested trichloroethylene was absorbed by the gastrointestinal tract
(Daniel, 1963).
Based on Daniel's study, it is assumed that 90 to 100 percent of
small amounts of ingested trichloroethylene will be absorbed. There-
fore, 100 percent will be utilized as a representative rate of gas-
trointestinal absorption for all uptake calculations in Section 5.
4.1.3 Dermal Absorption
Trichloroethylene absorbed through the skin travels via the
venous blood to the pulmonary compartment where a portion is elimi-
nated according to the blood:alveolar air concentration relationship
mentioned in Section 4.1.1. Due to this characteristic distribution
cycle, an appreciably large portion of dermally absorbed trichloro-
ethylene is eliminated unchanged through the lungs before reaching
other tissues (Sato and Nakajima, 1978). The remaining trichloro-
ethylene is distributed to the body tissues via arterial blood.
Dermal absorption of trichloroethylene is dependent upon dura-
tion of exposure, and extent of surface area exposed. Trichloroethy-
lene absorption through the skin, however, is regarded as negligible
under ambient environmental conditions (Malkinson, 1960; Stewart and
Dodd, 1964). Since the dermal absorption of toxic quantities of tri-
chloroethylene is considered rare in industrial situations (Sato and
Nakajima, 1978), it will not be considered in the calculations that
define daily environmental trichloroethylene uptake in Section 5.
29
-------
4.2 Metabolism: Enzymatic Pathway and Intermediates
The major portion of enzymatic biotransformation of trichloro-
ethylene to its water soluble metabolites occurs within the micro-
somal fraction of the liver. It has been reported that limited
trichloroethylene metabolism occurs within perfused lungs of rats
and guinea pigs (Dalbey and Bingham, 1978).
The transformation sequence involves enzymatic oxidation, in-
tramolecular rearrangement, and hydrolytic reactions (Butler, 1949;
Leibman, 1965). The hypothesized intermediates and known final
metabolites of toxic risk are trichloroethylene oxide and trichloro-
acetic acid, due to their protein binding tendencies, and trichloro-
ethanol, due to its neurologic effects.
The pathway of trichloroethylene metabolism (Figure 4-1) is
fairly well established on the basis of animal data and human blood
and urine analyses. The major intermediates and final metabolites
have been identified chromatographically and spectrophotometrically,
»
while the unstable, chemically reactive intermediates have been more
difficult to identify (Allemand et al., 1978). Although the exist-
ence of these unstable intermediates (e.g., chloral hydrate) has been
verified in an in vitro system (Leibman, 1965), there is no direct
evidence for their presence in humans. Therefore, the illustrated
pathway presented in Figure 4-1 must be considered hypothetical due
to the inclusion of the stepwi^e formation of these intermediates,
their enzymatic catalysts and the final reactive metabolites.
30
-------
Cl Cl
I I
Cl-C-C-H
I I
L OH OH J
TRICHLOROETHYLENE
GLYCOL
PINACOL
REARRANGEMENT
ri n
Civ. XC1
C=C .
"1^ M
LS JL n
TKICHLOROETHYLENE
MICROSOMAL MIXED FUNCTION OXIDASES
NADPH/0-
NONENZYMATIC
COVALENT BINDING
TO PROTEINS
-H2°
+H20
- Cl -
A
Cl-C-C-H
I I
Cl OH
r Cl Cl -i
I I
Cl-C-C-H
w
0
TRICHLOROETHYLENE
OXIDE
OH-
EPOXIDE
CARBONYL
REARRANGEMENT
NONENZYMATIC
COVALENT
BINDING
TO
GLUTATHIONE
INTRAMOLECULAR REARRANGEMENT PRODUCT
Cl-C-C.
Cl
H
ALCOHOL DEHYDROGENASE/NADH
Cl H
I I
Cl-C-C-OH
I I
Cl H
TRICHLOROETHANOL
I
UDP GLUCURONYL TRANSFERASE
Cl H
Cl-C -C-O-C HnO
II 696
Cl H
TRICHLOROACETALDEHYDE
HYDROLYSIS
Cl OH
Cl-C-C-H
I I
Cl OH
CHLORAL HYDRATE
MIXED FUNCTION
OXIDASES
EXCRETION
CHLORAL HYDRATE
DEHYDROGENASE/NAD
Cl
I
Cl-C-C
I
Cl
\
OH
TRICHLOROACETIC ACID
COVALENT
BINDING
TO
PROTEINS
TRICHLOROETHANOL
GLUCURONIDE
SOURCE: Adapted from Waters, et al., 1977
FIGURE 4-1
PROPOSED METABOLIC PATHWAY FOR TRICHLOROETHYLENE
(ADAPTED FROM WATERS, ET AL., 1977)
31
-------
The initial step of this metabolic sequence is the oxidation
of trichloroethylene. This reaction is catalyzed by the microsomal
mixed function oxidase system (considered a hydroxylating system) in
the presence of an NADPH-energy generating system (Leibman, 1965).
The intermediates produced from this reaction are suggested to be the
epoxide (trichloroethylene oxide) and the glycol (trichloroethylene
glycol) of trichloroethylene. Both glycols and epoxides have been
shown to be products of microsomal oxidation of olefinic compounds
(Byington and Leibman, 1965). The particular enzyme of the microso-
mal mixed function oxidase system responsible for metabolizing tri-
chloroethylene to its epoxide has not been identified but is believed
to be cytochrome P-450 dependent (Allemand et al., 1978). Recent re-
search suggests the formation of the trichloroethylene epoxide as the
initial intermediate, although not actually isolated, since reactions
were enhanced and inhibited by known epoxide hydrase enhancers and
inhibitors (Banerjee and Van Duufen, 1978; Van Duuren and Banerjee,
1976). This highly reactive electrophilic intermediate is thought to
covalently bind with hepatic proteins as well as hepatic glutathione.
Radioactively labeled trichloroethylene has shown metabolite binding
with hepatic proteins, nucleic acids, and glutathione (Allemand et
al., 1978; Banerjee and Van Duuren, 1978). (Protein binding, if
extensive, has been associated with necrotic effects on the liver.)
32
-------
The reactive epoxide may also easily undergo an epoxide carbonyl
rearrangement reaction yielding an unstable chloronium ion interme-
diate (Byington and Leibman, 1965). This is an intermediate step in
the migration of the chlorine atom. Evidence exists supporting a
preferred chlorine atom migration within this epoxide rearrangement
(McDonald and Schwab, 1963).
The glycol formed in the initial step would be prone to a rear-
rangement reaction due to the known instability of haloalcohols. The
theoretical rearrangement, analogous to the Pinacol rearrangement,
would yield the same unstable chloronium ion intermediate produced in
the epoxide rearrangement previously described. The common product
of these rearrangements indicates the possibility of interconversion
of the epoxide and the glycol by hydration and dehydration (Byington
and Leibman, 1965). The chloronium ion is unstable, and its asso-
ciation with a hydroxyl ion yields rapid dehydration and continued
rearrangement, producing trichloroacetaldehyde as a hypothesized
nonvolatile intermediate within the metabolic scheme of trichloro-
ethylene. The existence of chloral hydrate as an intermediate was
postulated by Butler in 1949, since the end products of the me-
tabolism of chloral hydrate and trichloroethylene were the same.
Chloral hydrate was isolated and identified in rats and dogs by
chromatographic, colorimetric and enzymatic techniques in 1965 by
Leibman and confirmed by Ikeda and Imamura (1973).
33
-------
The final stage of this biotransformation is formation of those
metabolites that are excreted or accumulated. Chloral hydrate is
rapidly metabolized via reduction by liver alcohol dehydrogenase
(with an NADH coenzyme) yielding trichloroethanol; and by oxidation
via chloral hydrate dehydrogenase (with an NAD coenzyme) producing
trichloroacetic acid (Leibman, 1965). It must be further noted that
the metabolite trichloroethanol can combine with hepatic glucuronic
acid, yielding trichloroethanol glucuronide.
Monochloroacetic acid and chloroform have been implicated as
two additional excreted metabolites of trichloroethylene (Soucek and
Vlachova, 1960). Their existence as metabolites is still in conten-
tion (Monster et al., 1976).
It has been shown that trichloroacetic acid binds with hepa-
tic* and plasma proteins as does trichloroethylene oxide, which can
cause displacement reactions with other drugs in the system (e.g.,
barbiturates), as well as initiate cytotoxic effects (Banerjee and
>
Van Duuren, 1978; Bolt and Filser, 1977; Ertle et al., 1972; Muller
et al., 1972; Muller et al., 1975; Soucek and Vlachova, 1960). The
final excreted metabolites of this biotransformation pathway are
trichloroacetic acid, trichloroethanol, and trichloroethanol glucuro-
nide.
rln vitro experimentation.
34
-------
4.3 Retention Characteristics
Immediately after absorption, trichloroethylene is carried in
the blood to the body organs and tissues. Powell (1947) concluded
that trichloroethylene was carried by the hemoglobin in the erythro-
cytes. Analysis of trichloroethylene distribution in rats revealed
41 percent of the total absorbed to be carried in the blood cellular
components and 2.5 percent within the plasma (the remaining portion
of absorbed trichloroethylene was expired) (Fabre and Truhaut, 1952).
It is hypothesized that trichloroethylene is absorbed and transported
by the lipids within the erythrocyte membrane (Fabre and Truhaut,
1952). Although this hypothesis has been disputed by other inves-
tigators, the precise nature of trichloroethylene transport has not
yet been determined (Bruckner, 1979). Trichloroethylene is rapidly
cleared from the blood via deposition, metabolic biotransformation
and excretion.
The high lipid solubility of trichloroethylene results in depo-
sition and accumulation of the compound within tissues according to
their lipid content. Human autopsy studies revealed the presence of
trichloroethylene inmost organs, with highest concentrations occur-
ring within the body fat and liver (McConnell et al., 1975).
Distribution of trichloroethylene and its metabolites in animal
tissues was shown to be dependent upon the duration of exposure.
Concentrations of trichloroethylene were reported after chronic
exposure in the body fat, adrenals, and ovaries while the spleen
35
-------
showed higher concentrations of trichloroacetic acid (Waters et al.,
1977). The lungs were found to retain the highest concentration of
trichloroacetic acid after chronic exposures, while the gonads and
the spleen retained the highest amounts after acute exposures (Smith,
1966).
The length of time that trichloroethylene is retained in the
fatty tissue has not yet been determined; however, the biological
half-life of the majority of trichloroethylene which is destined to
be metabolized has been determined to be 13 to 41 hours (Ikeda and
Imamura, 1973; Muller et al., 1975). (This range was determined by
occupational exposures to vapor for durations of 4 hours twice a
month [10 to 150 ppm] to daily intermittent exposures up to 200 ppm
8 hours/day 5 days a week.) The half-life of that portion of tri-
chloroethylene that is eliminated by the pulmonary compartment ranges
from 1 to 20 hours (Stewart et al., 1970); Ikeda (1977) calculated
this respiratory half-life to be 25 hours. The biological half-life
•»
for the two major metabolites as determined through urinary analysis
ranges from 36.1 to 57.6 hours for trichloroacetic acid and from 12
to 49.7 hours for trichloroethanol (Bartonicek, 1962; Ertle et al.,
1972; Ikeda and Imamura, 1973; Nomiyama and Nomiyama, 1971; Stewart
et al. , 1970). The longer half-life (or slower excretion rate) of
trichloroacetic acid is caused by its binding to plasma proteins
(Muller, 1975). The extent of binding was found to be approximately
90 percent (where trichloroacetic acid concentrations ranged from 10
36
-------
to 50 yg/ml) (Muller et al., 1975). The shorter half-life of tri-
chloroethanol is due to the ease of excretion of trichloroethanol and
its glucuronide (Muller et al., 1975). Due to the varied retention
rates of the trichloroethylene metabolites, their 24-hour urinary
excretion is not a representative indicator of prior trichloroethyl-
ene exposure (especially in an environment of fluctuating exposure)
(Muller et al., 1972).
4.4 Elimination Characteristics
Trichloroethylene and its metabolites are eliminated from the
body via respired air and urine and, to a considerably lesser extent,
through the feces and perspiration. The elimination kinetics of
trichloroethylene and its metabolites show varied excretion rates as
revealed by comparison of their half-lives (Section 4.3).
Respired air appears to be the major route of elimination for
unmetabolized trichloroethylene, with elimination beginning immedi-
ately after exposure. Trichloroethylene concentration decreases
rapidly in expired air, with detectable levels remaining as long as
88 hours after 7 hours exposure to 200 ppm (Stewart et al., 1970).
Trichloroethanol is excreted via the lungs in man for about four days
after exposure (Bartonicek, 1962). Elimination via this route be-
comes negligible 24 to 28 hours after exposure (Ahlmark and Forssmah,
1951; Powell, 1947). In one study, the highest concentrations of
trichloroethylene in expired air were noted after three hours of
exposure to 200 ppm atmospheric trichloroethylene (Stewart et al.,
37
-------
1970). An average of 10 percent (range of 7 to 17) of absorbed tri-
chloroethylene was eliminated via respiratory air after inhalation
exposures of 4 hours duration to 70 and 140 ppm trichloroethylene
(Monster et al., 1976).
The urinary tract is responsible for the elimination of the
major portion of trichloroethylene metabolites. Urinary excretion
of unmetabolized trichloroethylene is very slight (Fabre and Truhaut,
1952; Powell, 1947). Urinary excretion of trichloroethylene metab-
olites has been reported to account for 65 to 75 percent of the
trichloroethylene retained in the body after respiratory exposure
(Ogata et al., 1971; Soucek and Vlachova, 1960). Urinary excretion
accounted for 11 to 21 percent of an oral dose in rats (Daniel,
1963).* The concentration of metabolites in human urine range in
composition from 38 to 53.1 percent trichloroethanol and from 18.1
to 35.7 percent trichloroacetic acid (Bartonicek, 1962; Ogata et al.,
1971; Soucek and Vlachova, 1960).
"9
The urinary excretion kinetics of trichloroethylene metabolites
appear to be biphasic (Figure 4-2). It has been documented that the
*It is noted that very high doses of trichloroethylene were admin-
istered to these rats (1.8 to 3.9 g). The proportion of the dose
that is metabolized is expected to vary inversely with the magni-
tude of the dose. Therefore, it is presumed that, if relatively
small amounts of trichloroethylene were given, a majority of the
dose would be metabolized and a greater percentage of metabolic
products would be excreted in the urine (Bruckner, 1979; Daniel,
1963).
38
-------
DAYS POST EXPOSURE
TRICHLOROETHYLENE IN EXPIRED AIR
TRICHLOROETHANOL IN URINE
— • — TRICHLOROACETIC ACID IN URINE
SOURCE: Adapted from Piotrowski, 1977
FIGURE 4-2
EXCRETION KINETICS OF TRICHLOROETHYLENE AND
ITS METABOLITES IN HUMANS
39
-------
trichloroethanol/trichloroacetic acid elimination ratio increases
rapidly immediately after exposure (due to the shorter half-life of
trichloroethanol) while 24 to 48 hours after exposure the ratio is
reversed. The excretion of trichloroacetic acid in humans lasted
nearly 2 weeks (while trichloroethanol excretion was negligible for
the latter part of this period) (Muller et al., 1972). Trichloro-
ethanol was found to appear as a glucuronide in the urine within 2
hours of pulmonary exposure, reaching a maximum level roughly twice
that of trichloroacetic acid within 24 hours, after which excretion
declined exponentially, showing negligible levels for about 2 weeks
(Bartonicek, 1962).*
Monochloroacetic acid was found to appear in the urine a few
minutes after initiation of exposure to trichloroethylene with
maximal levels appearing after 5 hours. The estimated half-life
was 15 hours, with negligible levels found after 4 days (Soucek and
Vlachova, 1960). About 4 percent of absorbed trichloroethylene was
„>
IT
assumed to be excreted in this form.
Other elimination routes releasing lesser amounts of trichloro-
ethylene metabolites are those of fecal excretion and perspiration.
Fecal elimination of 8.4 percent of metabolized trichloroethylene
(in the form of trichloroethanol and trichloracetic acid) has been
*Figure 4-2 shows a decline of metabolite excretion to a negligible
level, but has only been extrapolated for 5 days.
40
-------
reported in humans (Bartonicek, 1962). Perspiration concentrations
were recorded as 0.1 to 1.9 mg/100 ml trichloroethanol and 0.15 to
0.35 mg/100 ml trichloroacetic acid, and were assumed to be negligi-
ble (Bartonicek, 1962).
41
-------
5.0 SOURCE CONTRIBUTIONS TO -DAILY TRICHLOROETHYLENE UPTAKE IN HUMANS
Due to the multimedia exposure to trichloroethylene, it is
necessary to employ a source contribution model to identify daily ex-
posure/uptake relationships. The utilization of ambient environ-
mental levels in the source contribution model will ascertain the
total daily intake of trichloroethylene for an individual and deter-
mine the relative magnitude of trichloroethylene contribution from
drinking water.
5.1 Approach
The method employed in this study to estimate the degree to
which each major environmental source of trichloroethylene exposure
contributes to an individual's total daily uptake is based on proba-
ble exposure conditions (i.e., ambient trichloroethylene levels) as
well as absorption rates for each exposure route. The method con-
sists of a five-step process:
• Definition of ambient concentrations of trichloroethylene
for the major exposure sources (i.e., air, food, and drinking
water). ;
• Determination of daily trichloroethylene intake according to
the relationship:
where l£ is the daily trichloroethylene intake from source
i (i.e., air, food, drinking water), C£ is the consumption
per day of each trichloroethylene source i and [TRI]^ is
the concentration of trichloroethylene in each source i.
Calculation of the amount of trichloroethylene absorbed from
each exposure source i:
42
-------
where U£ is trichloroethylene uptake for each exposure
source i, l£ is daily trichloroethylene intake from each
source i, and A£ is the percent absorption of tri-
chloroethylene, via the appropriate exposure route, for a
particular source.
• Calculation of the total trichloroethylene uptake
from all sources (Ut) :
Ut = S(li • A£) = 2U£
• Determination of the proportion (P^) of total daily uptake
(U|-) provided by each of the three exposure sources (i.e.,
source contribution factors):
ui
Pi = __ • 100
5.2 Basic Assumptions
Several assumptions were made in defining the amount of each
source material consumed each day. When possible, Reference Man
values were utilized for daily air and food consumption rates (see
Table 5-1). Daily consumption of drinking water is that value sug-
gested by NAS (1977) and Snyder et al. (1975), i.e., 2.0 I/day for
adults and 1.4 I/day for children.
Pulmonary and gastrointestinal absorption percentages utilized
in the calculations are also specified in Table 5-1. These figures
represent absorption values for inhaled or ingested trichloroethy-
lene, as reported in the scientific literature. Pulmonary and gas-
trointestinal absorption rates are assumed to be the same in the
*From the ICRP Reference Man Tables (Snyder et al., 1975).
43
-------
TABLE 5-1
BASIC ASSUMPTIONS EMPLOYED IN THE
CALCULATION OF INDIVIDUAL SOURCE CONTRIBUTION FACTORS
Basic Assumptions
• Reference Man:
Adult consumes:
Child consumes:
Absorption Characteristics:
Gastrointestinal
Adult
Pulmonary
Adult
Dermal
2.0A H20/day
(v-2200g food/day
22.8 m3 air/day
1.4A H20/day
M.000g food/day
4.7 m3 air/day
100%
65%
Insignificant
Remarks
- Daily intake as .suggested by NAS (1977).
- Approximate daily intake for 18 yr old in
FDA total diet studies; comparable to Reference
Man (Snyder et al., 1975); however, since
daily trichloroethylene intake from the
total diet will be assumed, this figure is
not used in the calculations.
- Assumes 8 hrs light work, 8 hrs nonoccupational,
and 8 hrs resting.
- Conservative estimate; <2 yr old child assumed
to obtain liquid from foods alone.
- Approximate daily intake for child-
- For 1 yr old; 0.8 m3/day for newborn.
Approximation based on limited data (see Section
4.1.2).
- Representative mid-range value in reported litera-
ture (see Section 4.1.1).
- Relatively unimportant, except in rare circumstances.
-------
child as in the adult, since there are no empirical data to suggest
otherwise.
5.3 Estimated Daily Trichloroethylene Uptake From All Sources
The relative contribution to an individual's daily trichloro-
ethylene uptake from each of the three exposure routes was determined
by using average environmental trichloroethylene occurrence data in
the calculation sequence previously described. Several concentra-
tions of trichloroethylene in air and drinking water and one value
for daily intake from food are utilized to represent the range of
values reported. Table 5-2 provides the exposure values used in the
calculations.
It should be noted that the assumed total daily dietary intake
of trichloroethylene reflects the inclusion of coffee and tea in the
diet. The maximum intake per day for a coffee/tea drinker would be
an additional 0.5 [jg trichloroethylene (assuming 1 liter of coffee/
tea per day). This addition proves to be negligible with respect to
percent contribution. Although the FDA is in the process of offi-
cially banning the use of trichloroethylene in the preparation of
decaffeinated and instant coffee and tea, the actual use of trichlo-
roethylene in the decaffeination process was terminated by manufac-
turers in 1975-1976 due to an NCI alert (Buxton, 1978).
Table 5-3 provides an example of the actual calculation sequence
employed. The source contribution factors for air, food and drinking
water for adults are summarized in Table 5-4, and for children in
Table 5-5.
45
-------
TABLE 5-2
REPRESENTATIVE ENVIRONMENTAL TRICHLOROETHYLENE EXPOSURE LEVELS
ON
Exposure -Routes
Diet
Adult
Child (2 yr old)
Ambient Air
Drinking Water
Exposure Level
10 yg/day
5 yg/day
1 yg/m3
•
-------
TABLE 5-3 ~
CALCULATION SEQUENCE IN DETERMINING SOURCE CONTRIBUTION FACTORS
Ambient Consumption Absorption Percent of
Source Concentrations x Rate x Rate = Daily Uptake Total Uptake
Air
.nking Water
d
0.5 yg/fc
10 yg/day
1 yg/m3
22
—
22.8 m3/day
1.0
1.0
0.65
1 yg/day
10 yg/day
15 yg/day
4
38
58
TOTAL 26 yg/day 100
-------
TABLE 5-4
ESTIMATED DAILY TRICHLOROETHYLENE UPTAKE (ADULTS)
Air @ 1 pg/m3
Air @ 10 ug/m3
Air 9 100 ug/m3
JS
00
Water
1? 0.5 ug/1
Water
9 30 pg/1
Water
9 300 pg/1
Water
@ 22000 pg/1
Source
Air
Food
Drinking
Water
Total
Air
Food
Drinking
Water
Total
Air
Food
Drinking
Water
Total
Air
Food
Drinkinr
Water
Total
Level
1 pg/m3
10 pg/day
0.5 pg/1
1 Pg/m3
10 ug/day
30 pg/1
1 Pg/m3
10 pg/day
300 pg/1
1 Pg/m3
10 pg/day
22000ug/day
Uptake
(pg/day)
15
10
1
26
15
10
60
85
15
10
600
625
15
10
44000*
44025
Percent
Contribution
58
38
4
18
12
70
-V
2
2
96
<1
<1
99
Source Level
Air 10 pg/m3
Food 10 pg/day
Drinking
Water 0.5 ug/1
Total
Air 10 pg/m3
Food 10 pg/day
Drinking
Water 30 pg/1
Total
Air 10 ug/m3
Food 10 ug/day
Drinking
Water 300 pg/1
Total
Air 10 ug/m3
Food 10 Pg/day
Uptake
(pg/day)
148
10
1
159
148
10
60
218
148
10
600
758
148
10
Drinking 22000ug/day 44000
Water
Total
44158
Percent
Contribution
93
6
<1
68
5
27
20
1
79
-------
TABLE 5-5
ESTIMATED DAILY TRICHLOROETHYLENE UPTAKE (CHILD)
VO
Water
@ 0.5 yg/1
•
Water
@ 30 vs/1
Water
@ 300 vg/1
Water
@ 22000 vg/1
f
Source
Air
Food
Drinking
Water
Total
Air
Food
Drinking
Water
Total
Air
Food
Drinking
Water
Total
Air
Food
Drinking
Water
Total
Air @ 1
Level
1 vg/m3
5 yg/day
0.5 yg/1
1 yg/m3
5 vg/day
30 vg/1
1 yg/m3
5 yg/day
300 yg/1
1 yg/m3
Vg/m3
Uptake Percent
(yg/day) Contribution
3 33
5 56
i. 11
9
3 6
5 10
42 84
50
3 <1
5 1
420 98
428
3 <1
5 yg/day 5
-------
The relative contribution of trichloroethylene in drinking water
to the estimated total daily uptake is variable, due to the extremely
broad range in ambient water and air concentrations (Tables 3-1 and
3-4). The percent contribution of trichloroethylene in drinking
water to total daily uptake in both children and adults ranges from
<1 to 99 depending on the ambient water and air exposure levels
(Table 5-4 and 5-5).
The predominant source of trichloroethylene uptake alternates
between water and air, depending on the ambient concentrations con-
sidered; however, given the most frequently occurring ambient concen-
trations, the atmosphere is the source of greater significance. At
these average ambient levels of trichloroethylene (1 (jig/m^ in air
and 0.5 \ig/l in drinking water), air contributes 58 percent to the
daily uptake, while drinking water contributes only 4 percent in
adults (Table 5-4).
Water is the predominant source of trichloroethylene absorption
..»
in children in situations characterised by drinking water levels of
30 |jg/l with concurrent air concentrations of 1 and 10 (jg/m , and
in all situations where drinking water trichloroethylene levels are
300 or 22,000 |JLg/l. Assuming the trichloroethylene concentration in
air is 1 (Ag/m^ (estimated urban average), drinking water contri-
butes 84, 98 and 99 percent of the total daily trichloroethylene
uptake at 30, 300 and 22,000 p.g/1, respectively.
50
-------
Quantitative characterization of the uptake situations shown
in Tables 5-4 and 5-5 is tentative due to limited monitoring data in
air, food, and surface water. From the representative concentrations
selected ambient levels for air and drinking water of 1 |o.g/m-* and
0.5 H-g/1, respectively, appear to occur most frequently and affect
the largest portion of the general population.
Trichloroethylene concentrations in drinking water ranging from
30 to 22,000 |o.g/l contribute significantly to the total daily uptake.
These levels have been found only in ground water aquifers (Table
3-4). The source of many of these high trichloroethylene concentra-
tions is considered to be a result of improper disposal of trichloro-
ethylene and products containing trichloroethylene by both industrial
and residential users.
If trichloroethylene air levels are presumed to be dependent
upon extent of industrial use, populations adjacent to industrialized
and landfill areas have the potential for increased uptake and cor-
responding risk. The worst case situations presented in Tables 5-4
and 5-5 (i.e., air levels of 100 (o.g/m^ and drinking water levels of
300 or 22,000 H-g/1) would be characteristic of an area downwind from
a landfill or industry and supplied with drinking water from a con-
taminated aquifer. It is not clear that this situation actually
exists. If it does, it would be expected to affect a limited portion
of the general population.
51
-------
Approximately 50 percent of the U.S. general population relies
on ground-water systems as a source of drinking water (Morton, 1976).
Since ground-water contamination has been identified with increasing
frequency, a larger portion of the general population will be exposed
to trichloroethylene.
Analysis of exposure levels of trichloroethylene for the child
(Table 5-5) reveals that the 1 day SNARL value is exceeded in all
scenarios where the trichloroethylene concentration in water is
22,000 (j.g/1.* The 10-day SNARL value is exceeded in all scenarios
where a drinking water concentration of 300 |J.g/l occurs. As previ-
ously indicated, these concentrations would apply to only a limited
portion of the population. However, it is noted that a larger por-
tion of the population exceeds the chronic SNARL value of 75 p.g/1.
In addition, the SNARL value drops to a concentration of 15 u.g/1 when
sources other than drinking water are prevalent. In this case a
larger portion of the population would be exposed to trichloroethyl-
,>
ene concentrations in drinking water exceeding the chronic SNARL
value (this would include all scenarios above the average drinking
water concentration in Table 5-5).
It has been estimated that the taste threshold value for tri-
chloroethylene in water is 500 fJig/1 (Blankenship, 1980). Therefore
populations ingesting trichloroethylene in drinking water above the
*It is noted that the 1- and 10-day SNARL values have been exceeded
in numerous instances in Table 3-3.
52
-------
chronic SNARL values (15 g/1 and 75 g/1) as well as those ingesting
water above the 10-day SNARL value, would not be aware of the
presence of trichloroethylene in the water.
Due to the increased number of children in the general popula-
tion that could be affected by trichloroethylene concentrations of 15
g/1 or greater in drinking water, regulatory action which would aid
in the limitation of trichloroethylene exposure should be considered.
5.4 Identification of Critical Receptors
In order to thoroughly elucidate the toxicological significance
of environmental trichloroethylene it is important to identify those
specific subunits of the population (subpopulations) that are inher-
ently more susceptible to the deleterious affects of the compound.
Due to a lack of laboratory, case, and epidemiclogical studies, ex-
trapolation of general physiological knowledge is utilized to identi-
fy these susceptible populations.
Three subpopulations within the general population (i.e., the
fetus; the infant or young child; and those under the influence of
ethyl alcohol) exhibit the capacity for enhanced sensitivity to
trichloroethylene. The use of trichloroethylene as an obstetrical
anesthetic has provided an excellent opportunity to determine whether
placental transfer took place. In one study, analysis of maternal
and fetal blood revealed that unmetabolized trichloroethylene easily
diffused through the placenta (Laham, 1970). The lack of development
of many enzyme systems, and the deficiency of a blood-brain barrier
53
-------
in the fetus readily promote accumulation of trichloroethylene and
its metabolites after placental transfer. Any accumulation could be
extremely dangerous to the fetus due to the suggested neurotoxic
effects of trichloroethylene metabolites and their ability to bind
and precipitate proteins. The lack of a blood-brain barrier renders
the fetal central nervous system particularly sensitive to any damag-
ing effects that may be characteristic of trichloroethylene metabo-
lites (Casarett and Doull, 1975), while the immature state of
organogenesis in the fetus provides additional easily damaged targets
for these chemicals.
In a study of ten pregnant women exposed (via inhalation) to
trichloroethylene as an obstetrical anesthetic, Laham (1970) found
that the ratios of trichloroethylene concentration in fetal to mater-
nal blood ranged from 0.52 to 1.9 with a mean of about 1. Placental
transfer of trichloroethylene appears to function in a 1:1 relation-
ship. The fetus is, therefore, vulnerable to approximately those
same concentrations absorbed by the pregnant female under various
exposure conditions.
For reasons of immature physiologic development paralleling
those for the fetus, the newborn infant and the young child can also
be identified as critical receptors within the population. Neurolo-
gical development proceeds at a rapid pace from the third trimester
of pregnancy until several years postpartum, and permanent neurologi-
cal damage may result if an individual is stressed (i.e., ingestion
54
-------
of toxic substances, starvation inducing nutritional deficiencies)
during this sensitive period of growth (NAS, 1976). It is assumed
that the neurotoxic and hepatorenal toxic effects of trichloroethyl-
ene would be amplified due to the child's inherent sensitivity during
the growth spurt. Slower or partial metabolic breakdown (due to
limited development of enzymatic systems) may lead to enhanced depo-
sition of trichloroethylene within the central nervous system.
Human sensitivity to trichloroethylene is increased after con-
sumption of even small amounts of ethyl alcohol and concurrent or
subsequent exposure to trichloroethylene. Ethyl alcohol is thought
to interact with trichloroethylene through competitive inhibition of
the mixed function oxidase enzymes required for the metabolism of
both chemicals. This competitive inhibition yields increased tri-
chloroethylene and ethanol levels in the blood due to the lower rate
of metabolism (Muller et al., 1975). The build-up of trichloroethy-
lene in the blood, along with its characteristic high lipid solubil-
ity, is believed to lead to its deposition and accumulation within
the central nervous system. Concentrations are believed to approach
subhypnotic levels, yielding early onset of intoxication symptoms
(Muller et al., 1975). Pre-exposure to ethanol, a microsomal enzyme-
inducing agent, can result in enhanced metabolism of trichloroethyl-
ene to its cytotoxic metabolites, thereby potentiating hepatorenal
toxicity (Priest and Horn, 1965). Similar accentuation of trichlor-
oethylene hepatotoxicity is noted after the ingestion of barbiturates
55
-------
(microsomal enzyme-indueing agents) (Moslen et al., 1977). Due to
data limitations, it is not possible to estimate the effect this
condition might have on the factors utilized in the source contribu-
tion model, and it is also not possible to quantify the size of this
population.
56
-------
6.0 REFERENCES
Abrahms, E., 1977. Identification of Organic Compounds in Effluents
from Industrial Sources. Versar, Inc., Springfield, Virginia.
Ahlmark, A. and S. Forssman, 1951. Archives of Industrial Hygiene
_3:386.
Allemand, H., D. Pessayre, V. Descatoire, C. Degott, 6. Feldman and J.
Benhamon, 1978. "Metabolic Activation of Trichloroethylene into
a Chemically Reactive Metabolite Toxic to the Liver." Journal of
Pharmacology and Experimental Therapeutics 204(3):714-723.
Astrand, I., 1975. "Uptake of Solvents in the Blood and Tissues of
Man. A Review." Scandinavian Journal of Work Environment and Health
J_:199-218.
Astrand, I. and F. Gamberale, 1978. "Effects on Humans of Solvents
in the Inspiratory Air: A Method for Estimation of Uptake." Envi-
ronmental Research 15:1-4.
Astrand, I. and P. Ovrum, 1976. "Exposure to Trichloroethylene. I.
Uptake and Distribution in Man." Scandinavian Journal of Work Envi-
ronment and Health 4_:199-211.
Banerjee, S. and B.L. Van Duuren, 1978. "Covalent Binding of the
Carcinogen Trichloroethylene to Hepatic Microsomal Proteins and to
Exogenous DNA In Vitro." Cancer Research 38:776-780.
Bartonicek, V., 1962. "Metabolism and Excretion of Trichloroethylene
after Inhalation by Human Subjects." British Journal of Industrial
Medicine JL£: 134-141.
Blankenship, W., 1978. "Trichloroethylene (TCE) Contamination of
Potable Water Wells." Memorandum to J.A. Cotruvo, Director, Criteria
and Standards Division, Office of Drinking Water, U.S. Environmental
Protection Agency, Washington, D.C., from Technical Advisor, Water
Supply Branch, U.S. Environmental Protection Agency, Philadelphia,
Pennsylvania, 7 November.
Blankenship, 1980. U.S. Environmental Protection Agency, Water Supply
Branch, Philadelphia, Pennsylvania. Personal communication, telephone
conversation, 20 February.
Bolt, H.M. and J.G. Filser, 1977. "Irreversible Binding of Chlori-
nated Ethylenes to Macromolecules." Environmental Health Perspectives
21:107-112.
57
-------
Brass, B., 1979. U.S. Environmental Protection Agency, Office of
Water Criteria, Cincinnati, Ohio. Personal communication, telephone
conversation, 17 January.
Bruckner, J., 1979. University of Texas, Health Science Center,
Department of Pharmacology and Toxicology, Houston, Texas. Personal
communication, telephone conversation, 31 July.
Butler, T., 1949. "Metabolic Transformations of Trichloroethylene."
Journal of Pharmacology Experimental Therapeutics 97:84-93.
Buxton, M., 1978. Food and Drug Administration, Office of Food
Technology. Personal communication, 25 September.
Byington, K. and K. Leibman, 1965. "Metabolism of Trichloroethylene
in Liver Microsomes. II. Identification of the Reaction Product as
Chlorolhydrate." Molecular Pharmacology 1:247-254.
Capurro, P.U., 1973. "Effects of Exposure to Solvents Caused by Air
Pollution with Special Reference to Carbon Tetrachloride and its
Distribution in Air." Clinical Toxicology 6(1):109-124.
Casarett, L. and J. Doull (editors), 1975. Toxicology: The Basic
Science of Poisons. Macmillan Publishing Co., Inc., New York.
Chann, S., J. Jones, D. Liu, K. McCaleb, U. Sopios and D. Schendel,
1975. Research Program on Hazard Priority Ranking of Manufactured
Chemicals. Stanford Research Institute, Menlo Park, California.
Coleman, W.E., R.D. Lingg, R.C. Melton and F.C. Kopfler, 1975. The
Analysis of Purgeable Organics in the Drinking Water of Five U.S.
Cities. U.S. Environmental Protection Agency, Cinncinnati, Ohio.
*»
Dalbey, W. and E. Bingham, 1978. "Metabolism of Trichloroethylene
by the Isolated Perfused Lung." Toxicology and Applied Pharmacology
43:267-277.
Dale, R.M., 1972. "The Control of Solvent Emission from Solvent
Vapor Cleaning Plants." Annals of Occupational Hygiene 15:85-90;
as cited in Sweeney, 1974.
Daniel, J., 1963. "The Metabolism of Cl36-labeled Trichloroethylene
and Tetrachloroethylene in the Rat." Biochemical Pharmacology 12(8):
795-802.
DeWalle, F., 1979. University of Washington, Seattle, Washington.
Personal communication, telephone conversation, 17 January.
58
-------
Dilling, W. , C. Bredeweg and N. Terfertiller, 1976. "Simulated
Atmospheric Photodecomposition Rates of Methylene Chloride, 1,1,1-
Trichloroethane, Trichloroethylene, Tetrachloroethylene, and Other
Compounds." Environmental Science and Technology 10(4) :35 1-356.
Emanuel, J. , 1980. U.S. International Trade Commission, Washington,
D.C. Personal communication, telephone conversation, 7 March.
Ertle, T., D. Henschler, G. Muller and M. Spassowski, 1972. "Metab-
olism of Trichloroethylene in Man. I. .The Significance of Trichloro-
ethanol in Long-term Exposure Conditions." Archives Toxikologie
_29_:171-188.
Fabre, R. and R. Truhaut, 1952. "Toxicology of Trichloroethylene.
II. Results of Experimental Animal Studies." British Journal
Industrial Medicine _9_: 39-43.
Federal Register, 1977. "Proposed Rule for the Removal of Provisions
for Trichloroethylene." Department of Health Education and Welfare,
Food and Drug Administration. Office of the Federal Register,
National Archives and Records Service, General Services Administra-
tion, Washington, D.C. September 27.
Fliescher, M. , 1978. Nassau County Health Department, Nassau County,
New York. Personal communication, 1 October.
Food and Drug Administration (FDA), 1977. Compliance Program Evalua-
tion FY 74 Total Diet Studies. Bureau of Foods, Washington, D.C.
Geomet, Inc., 1977. Assessment of the Contribution of Environmental
Carcinogens to Cancer Incidence in the General Population Volume 2:
Final Report Tasks 1 and 2. EPA Contract 68-03-2504.
Gibitz, H.J. and E. Plochl, 1973. "Oral Trichloroethylene Intoxica-
tion in a Four-and-one-half Year Old Boy." Archives Toxikologie
Greve, M.H. , 1971. "Solvent Losses in Vapor Degreasing." Werkstatt
Betr. 104(8) :559-561; as cited in Sweeney, 1974.
Hardie, D. , 1964. "Trichloroethylene." In Encyclopedia of Chemical
Technology^ Volume 5. Interscience Publishers, New York.
Ikeda, M. , 1977. "Metabolism of Trichloroethylene and Tetrachloro-
ethylene in Human Subjects." Environmental Health Perspectives
21:239-245.
Ikeda, M. and T. Imamura, 1973. "Biological Half-life of Trichloro-
ethylene and Tetrachloroethylene in Human Subjects." International
Archives Arbeitsmed. 3^:209-224.
59
-------
Irish, D.D., 1967. "Trichloroethylene." In Industrial Hygiene and
Toxicology, Second Revised Edition. F.A. Patty (editor). Volume"Tl_:_
Toxicology. D.W. Fassett and D.D. Irish (editors), Interscience
Publishers, New York, pp. 1309-1313.
Laham, S., 1970. "Studies on Placental Transfer—Trichloroethylene."
Industrial Medicine 39(l):22-25.
Leibman, K.C., 1965. "Metabolism of Trichloroethylene in Liver
Microsomes. I. Characteristics of the Reaction." Molecular Pharma-
cology 1:239-246.
Leibman, K. and W. McAllister, Jr., 1967. "Metabolism of TCE in Liver
Microsomes. III. Induction of the Enzymic Activity and Its Effect on
Excretion of Metabolites." Molecular Pharmacology 157(3):574-580.
Leibman, K. and E. Ortiz, 1977. "Metabolism of Halogenated Ethy-
lenes." Environmental Health Perspectives 21:91-97.
Lowe, N., 1980. U.S. Environmental Protection Agency, Office of
Water Criteria, San Francisco, California. Personal communication,
telephone conversation, 20 February.
Lowenheim, F. and M. Moran, 1975. Faith Neyes and Clark's Industrial
Chemicals, 4th edition. John Wiley, New York.
Malkinson, F.D., 1960. Archives of Industrial Health 21:87.
McConnell, G., D.M. Ferguson and C.R. Pearson, 1975. "Chlorinated
Hydrocarbons and the Environment." Endeavour 34:13-18.
McDonald, R. and P. Schwab, 1963. Journal of American Chemical
Society 85:4004.
••
Midwest Research Institute, 1977. An Assessment of the Need for
Limitations on Trichloroethylene, Methyl Chloroform and Perchloro-
ethylene. MRI Project No. 4276-L, EPA Contract No. 68-01-4121. U.S.
Environmental Protection Agency, Office of Toxic Substances,
Washington, D.C.
Monster, A., 1979. "Difference in Uptake, Elimination, and Metabolism
in Exposure to Trichloroethylene, 1,1,1-Trichloroethane and Tetra-
chloroethylene." International Archives of Occupational and Environ-
mental Health 42:311-317.
Monster, A., 6. Boersma and W. Duba, 1976. "Pharmacokinetics of
Trichloroethylene in Volunteers, Influence of Workload and Exposure
Concentration." International Archives of Occupational and Environ-
mental Health 38:87-1023.
60
-------
Moolenar, R., 1980. Dow Chemical Company, Division of Health and
Environmental Sciences, Midland, Michigan. Personal communication,
telephone conversation, 7 March.
Morton, S., 1976. Water Pollution-Causes and Cures. Mimir Publishers
Inc., Madison, Wisconsin.
Moslen, M., E. Reynolds and S. Szabo, 1977. "Enhancement of the
Metabolism and Hepatotoxicity of Trichloroethylene and Perchloro-
ethylene." Biochemical Pharmacology 26:369-375.
Muller, G., M. Spassovski and D. Henschler, 1972. "Trichloroethy-
lene Exposure and Trichloroethylene Metabolites in Urine and Blood."
Archives Toxikologie 29:335-340.
Muller, G., M. Spassovski and D. Henschler, 1975. "Metabolism of
Trichloroethylene in Man. III. Interaction of Trichloroethylene
and Ethanol." Archives of Toxicology 33:173-189.
Murray, A. and J. Riley, 1973. "Occurrence of Some Chlorinated
Aliphatic Hydrocarbons in the Environment." Nature 242:37-38; as
cited in Sweeney, 1974.
Myott, Mr., 1977. Nassau County Health Department, Nassau County,
New York. Personal communication, 12 December.
National Academy of Sciences (NAS), 1976. Recommendations for the
Prevention of Lead Poisoning in Children. Washington, D.C.
National Academy of Sciences (NAS), 1977. Drinking Water and Health.
Safe Drinking Water Committee, Washington, D.C.
National Cancer Institute (NCI), 1976. Carcinogenesis Bioassay for
Trichloroethylene. NCI-CG-TR-2. Washington, D.C.
National Institute for Occupational Safety and Health (NIOSH), 1973.
Criteria.for a Recommended Standard...Occupational Exposure to Tri-
chloroethylene. U.S. Department of Health, Education, and Welfare.
Public Health Service, Washington, D.C.
Nomiyama, K. and H. Nomiyama, 1974. "Metabolism of Trichloroethylene
in Humans. Sex Difference in Excretion of Trichloroacetic Acid and
Trichloroethanol." International Archives Arbeitsmed. 28:37.
Ogata, M., Y. Takatsuka and K. Tomokuni, 1971. "Excretion of Organic
Chlorine Compounds in the Urine of Persons Exposed to Vapours of
Trichloroethylene and Tetrachloroethylene." British Journal Indus-
trial Medicine 28:386-391.
61
-------
Pearson, C.R. and G. McConnell, 1975. "Chlorinated Cj and G£
Hydrocarbons in the Marine Environment." Proceedings of the Royal
Society of London B. 189(1096):305-332.
Pellizzari, E.D., 1976a. Development of Analytical Techniques for
Measuring Ambient Atmospheric Carcinogenic Vapors. EPA Contract
#68-02-1228.
Pellizzari, E.D., 1976b. Identification and Analysis of Ambient Air
Pollutants Using the Combined Techniques of Gas Chromatography and
Mass Spectrometry. EPA Contract #68-02-2262.
Pellizzari, E.D., 1977. The Measurement of Carcinogenic Vapors in
Ambient Atmospheres. EPA-600/7-77-055.
Piotrowski, J., 1977. Exposure Tests for Organic Compounds in In-
dustrial Toxicology. National Institute for Occupational Safety
and Health, Cincinnati, Ohio.
Powell, J., 1947. "The Solubility or Distribution Coefficient of
Trichloroethylene in Water, Whole Blood, and Plasma." British
Journal of Industrial Medicine 4^:233-236.
Priest, R. and R. Horn, 1965. "Trichloroethylene Intoxication."
Archives of Environmental Health 11;361-365.
Referente, H., 1980. U.S. Environmental Protection Agency, Water
Supply Branch, New York, New York. Personal communication, tele-
phone conversation, 20 February.
Research Triangle Institute, 1977a. Development of Analytical
Techniques for Measuring Ambient Atmospheric Carcinogenic Vapors.
Monthly Progress Report #8. Project;>#314-885.
Research Triangle Institute, 1977b. Development of Analytical
Techniques for Measuring Ambient Atmospheric Carcinogenic Vapors.
Monthly Progress Report #3. Project #314-885.
Research Triangle Institute, 1977c. Development of Analytical
Techniques for Measuring Ambient Atmospheric Carcinogenic Vapors.
Monthly Progress Report #9. Project #314-885.
Runowski, R., 1980. U.S. Environmental Protection Agency, Water
Supply Branch, Philadelphia, Pennsylvania. Personal communication,
telephone conversation, 20 February.
62
-------
Sato, A. and T. Nakajima, 1978. "Differences Following Skin or
Inhalation Exposure in the Absorption and Excretion Kinetics of Tri-
chloroethylene and Toluene." British Journal of Industrial Medicine
35_:43-49.
Skinner, P., 1978. Bureau of Environmental Protection, Office of the
Attorney General. Personal communication, 1 October.
Smith, G.F., 1966. "Trichloroethylene: A Review." British Journal
of Industrial Medicine 23:249-262.
Snyder, W., M. Coou, E. Nasset, L. Narhausen, G. Howells and I. Tip-
ton, 1975. Report of the Task Group on Reference Man, No. 23. In-
ternational Commission on Radiological Protection, Pergamon Press,
New York.
Soucek, B. and D. Vlachova, 1960. "Excretion of Trichloroethylene
Metabolites in Human Urine." British Journal of Industrial Medicine
r7:60-64.
Soucek, B., J. Teisinger and E. Pavelkova, 1952. Pracov. Lek. 4:31.
Stanford Research Institute (SRI), 1978. Chemical Economics Handbook.
Menlo Park, California.
Stanford Research Institute International (SRI), 1979. 1979 Directory
of Chemical Producers - United States. Chemical Information Services,
Menlo Park, California.
Stewart, R. and H. Dodd, 1964. "Absorption of Carbon Tetrachloride,
Trichloroethylene, Tetrachloroethylene, Methylene Chloride and
1,1,1-Trichloroethane through the Human Skin." American Industrial
Hygiene Association Journal ^5_(5) :439-446.
Stewart, R., H. Dodd, H. Gay and D. Erley, 1970. "Experimental Human
Exposure to Trichloroethylene." Archives Environmental Health 20:64.
Stillwell, J.T., 1977. Inspector, Dade County Environmental Resources
Management, Miami, Florida. Personal communication, letter dated 28
December.
Su, C. and E.D. Goldberg, 1976. "Environmental Concentrations and
Fluxes of Some Halocarbons." In Marine Pollutant Transfer, H.L.
Windom and R.A. Duce (editors), Lexington Books, D.C. Heath and
Company, Lexington, Massachusetts, pp. 353-374.
63
-------
Sweeney, S.C., 1974. A Study of Optical Brighteners, Methyl Chloro-
form, Trichloroethylene, Tetrachloroethylene, and Ion-Exchange Resins.
Science Information Services Department, Franklin Institute Research
Laboratories, Philadelphia, Pennsylvania.
U.S. Department of Health, Education, and Welfare (HEW), 1973.
Criteria for a Recommended Standard—Occupational Exposure to
Trichloroethylene.
U.S. Environmental Protection Agency (EPA), 1975. Preliminary Assess-
ment of Suspected Carcinogens in Drinking Water. Report to Congress.
U.S. Environmental Protection Agency (EPA), 1977a. Control of Vola-
tile Organic Emissions from Solvent Metal Cleaning. EPA-450/2-77-022.
Office of Air Quality Planning and Standards, Research Triangle Park,
North Carolina.
U.S. Environmental Protection Agency (EPA), 1977b. The National Or-
ganic Monitoring Survey (interim Report). Technical Support Division,
Office of Water Supply.
U.S. Environmental Protection Agency (EPA), 1979. "SNARL for
Trichloroethylene." Internal Memorandum - Health Effects Branch,
Criteria and Standards Division, Office of Drinking Water. November
26.
Van Duuren, B.L. and S. Banerjee, 1976. "Covalent Interaction of
Metabolites of the Carcinogen Trichloroethylene in Rat Hepatic Micro-
somes." Cancer Research 36:2419.
Vignoli, L., J. Jouglard, P. Vignoli and T. Terrasson, 1970. "Acute
Intoxication by Trichloroethylene, Metabolism of this Poison." Med.
Leg. Assicur. 18(3-4):789-798.
Waters, E.M., H.B. Gerstner and J.E. Huff, 1977. "Trichloroethylene.
I. An Overview." Journal of Toxicology and Environmental Health
2^:671-707.
Willard, J.J., 1972. "Textile Processing with Nonaqueous Solvents."
Text. Chem. Color 4(3):62-65; as cited in Sweeney, 1974.
64
-------
TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
2.
4. TITLE AND SUBTITLE
Environemental Sources of Trichloroethylene Exposure
Source Contribution Factors
3. RECIPIENT'S ACCESSIONED.
5. REPORT DATE
May 1980
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
Myles E. Morse
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
MITRE Corporation
Washington Center
1820 Dolley Madison Boulevard
McLean, Virginia 22102
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
68-01-5863
12. SPONSORING AGENCY JMAM.E AND AJ3DRESS
Assessment Division
Office of Pesticides and Toxic Substances
U.S. Environmental Protection Agency
UacVn'-norrm Tl C.
13. TYPE OF REPORT AND PERIOD COVERED
Final
14. SPONSORING AGENCY CODE
nor
N'T/
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This study is intened to assist the Assessment Division, Office of Testing and
Evaluation of the U.S. Environmental Protection Agency, in the assessment
of human health risks associated with trichloroethylene exposure. The levels
and frequency of occurrence of trichloroethylene in the various environmental
media (air, food, and drinking water) have been identified. The relative
contribution of each of these sources to an individual's total daily trichloro-
ethylene uptake is determined through an exposure/uptake approach. It is
anticipated that such an approach in combination with other exposure information
can be used in the support of regulatory decision making under the Toxic
Substances Control Act (TSCA). Available occurrence data, although limited,
indicate a greater persistence of trichloroethylene in ground water than in the
atmosphere or surface water. Numerous instances of trichloroethylene occurrence
in drinking water (supplied by aquifers) were cited. The suggested no adverse
response level was found to be exceeded in all situations considered above the
average value scenario. The fetus, children and those consuming ethyl alcohol
were subunits of the general population qualitatively identified as hypersensitive
to trichloroethylene.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COSATI Field/Group
8. DISTRIBUTION STATEMENT
19. SECURITY CLASS (This Report)
21. NO. OF PAGES
20. SECURITY CLASS (Thispage)
22. PRICE
EPA Form 2220-1 (9-73)
65
------- |