DRAFT DO NOT CITE OR QUOTE

Page 1 

United States Office of Chemical 

Environmental Protection Safety and Pollution 

Agency Prevention 

TSCA Workplan Chemical Risk Assessment for 

Trichloroethylene:

Degreaser and Arts/Crafts Uses

CASRN: 79-01-6 

Ethene, 1,1,2-trichloroDecember 2012

NOTICE

This document is an External Review Draft. This information is distributed solely for the 

purpose of pre-dissemination peer review under applicable information quality guidelines. It 

has not been formally disseminated by EPA. It does not represent and should not be construed 

to represent any Agency determination or policy. It is being circulated for review of its 

technical accuracy and science policy implications.

Cl

Cl H

Cl
DRAFT DO NOT CITE OR QUOTE

Page 2 

Table of Contents

AUTHORS / CONTRIBUTORS / ACKNOWLEDGEMENTS / REVIEWERS....................................................6

GLOSSARY OF TERMS AND ABBREVIATIONS .......................................................................................7

EXECUTIVE SUMMARY .....................................................................................................................10

CHAPTER 1: BACKGROUND AND SCOPE ...........................................................................................13

BACKGROUND ..............................................................................................................................................................13

SCOPE OF ASSESSMENT FOR TCE .....................................................................................................................................14

CHAPTER 2: SOURCES AND ENVIRONMENTAL FATE OF TCE ..............................................................16

A. PHYSICAL AND CHEMICAL PROPERTIES OF TCE...............................................................................................................16

B. ENVIRONMENTAL FATE..............................................................................................................................................17

C. PRODUCTION VOLUME AND GENERAL INFORMATION ON USES..........................................................................................21

CHAPTER 3: HUMAN HEALTH RISK ASSESSMENT ..............................................................................22

A. ENVIRONMENTAL RELEASES AND EXPOSURE SUMMARY ...................................................................................................22

ENVIRONMENTAL RELEASES OF TCE...................................................................................................................22

Calculating Exposures used in this Risk Assessment ...........................................................................................29

Consumer Exposures – Degreaser and Arts/Crafts Uses of TCE..........................................................................30

B. HAZARD SUMMARY ..................................................................................................................................................33

Toxicokinetics (Absorption, Distribution, Metabolism, and Excretion) ...............................................................34

Summary of Toxicity Information on TCE............................................................................................................38

Hazard Data to be used in Risk Assessment for TCE ...........................................................................................55

C. HUMAN HEALTH RISK CHARACTERIZATION ....................................................................................................................57

Risk Estimation Approach for Acute and Repeated Exposures ...........................................................................57

Risk Estimates for Acute (Short-Term) and Chronic (Repeated) Exposures to TCE .............................................60

Summary.............................................................................................................................................................65

D. DISCUSSION OF KEY SOURCES OF UNCERTAINTY AND DATA LIMITATIONS ............................................................................69

Uncertainties in the Exposure Assessment..........................................................................................................69

Uncertainties in the Hazard Assessment.............................................................................................................70

Uncertainties in the Risk Assessment..................................................................................................................71

CONCLUSIONS ..............................................................................................................................................................72

REFERENCES ....................................................................................................................................73

APPENDIX A: REGULATORY HISTORY OF TCE AT THE US EPA.............................................................86

APPENDIX B: 2006 INVENTORY UPDATE RULE DATA FOR TCE ...........................................................88

APPENDIX C: NAICS CODES FOR TCE DEGREASING............................................................................91

APPENDIX D: CALCULATIONS FOR SMALL COMMERCIAL WORKER DEGREASER EXPOSURES ..............93

APPENDIX E: CONVERTING E-FAST ADRS TO CONCENTRATION IN AIR...............................................97

APPENDIX F: HAZARD VALUES IDENTIFIED FOR USE IN THIS RISK ASSESSMENT................................. 99
DRAFT DO NOT CITE OR QUOTE

Page 3 

List of Tables

Table 1-1. Primary Uses of TCE and Determination of Inclusion in this Risk Assessment.........................15

Table 2-1. Physical-Chemical Properties of TCEa

. .......................................................................................16

Table 2-2. Environmental Fate Characteristics of TCEa

. .............................................................................20

Table 3-1. TCE Ambient Air Monitoring Data (μg/m3

)

a

. .............................................................................23

Table 3-2. The Number of TCE-Emitting Emission Points and Corresponding Total Annual Air Emissions 

of TCE as reported in the 2008 NEI (US EPA, 2008b). ............................................................25

Table 3-3. Total Annual Air Emissions of TCE as Reported in the 2008 TRI (TRI, 2012b)...........................25

Table 3-4. Relevant TCE Releases from Solvent Cleaning in 2010. ............................................................26

Table 3-5. Breakdown of Degreasing Cleaning Machine Type for Point Source TCE Emissions................27

Table 3-6. Estimate of 2010 TCE Releases for Small Industrial/Commercial Facilities (n = 1,483)............28

Table 3-7. Potential Operating TCE Emission Factors from Degreasing (Calculated and Reported Values).

................................................................................................................................................29

Table 3-8. Summary of Potential Workplace TCE Inhalation Exposures: Small Commercial Degreaser. ..30

Table 3-9. TCE Products in Household Products Database Retrieval.........................................................31

Table 3-10. Estimated TCE Potential Acute Dose Rates from Use of Two Hobbyist Products Indoors at 

Residences as Determined by E-FAST. ...................................................................................32

Table 3-11. Estimated TCE Inhalation Calculated Concentration in Air (Over the Course of a Daya

) from 

Use of Two Hobbyist Products Indoors at Residences...........................................................33

Table 3-12. Hazard/Risk Assessment Documents Consulted for this Report. ...........................................33

Table 3-13. Common Metabolites of TCE and Related Compoundsa ........................................................35

Table 3-14. TCE Metabolites Identified by Pathwaya

. ................................................................................36

Table 3-15: Half-Life Data For TCE in Rats and Humansa

. ..........................................................................38

Table 3-16. Proposed AEGL Values for TCE (in ppm)a

. ...............................................................................40

Table 3-17. Inhalation Studies Identified In US EPA (2011c) For Use In OPPT TCE Risk Assessment. .......53

Table 3-18. U.S. EPA IRIS PBPK-Modeled Dose Metrics for TCE Dose-Response Assessment................... 56
DRAFT DO NOT CITE OR QUOTE

Page 4 

Table 3-19. Range of TCE Candidate POD/HEC Values Derived by US EPA (2011c). ................................. 57

Table 3-20. Use Scenarios, Population of Concern, and Health Effects of Concern.................................. 59

Table 3-21. TCE Noncancer Risk Estimates for Small Commercial Degreasers and Non-users: Using the 

Lowest 99th Percentile HECs (Numbers are MOEs)1,2 ...........................................................62

Table 3-22. TCE Cancer Risk Estimates for Small Commercial Degreasers and Non-users (Numbers are 

Extra Lifetime Cancer Risk and Bolded Vales Represent Concern ........................................63

Table 3-23. TCE Non-cancer Risk Estimates for Use of Two Hobbyist Products Indoors at Residences: 

Neurotoxicity as Endpoint of Concern and Using the Lowest 99th Percentile HECs and 24-

Hour Average Exposure Concentrations (Numbers are MOEs])1

. ..........................................64

Table 3-24. TCE Non-cancer Risk Estimates for Use of Two Hobbyist Products Indoors at Residences: 

Developmental Toxicity as Endpoint of Concern Using the Lowest 99th Percentile HECs and 

24-Hour Average Exposure Concentrations (Numbers are MOEs)1

.......................................65

Table 3-25. Summary of Overall Risk Assessment for TCE Using the Lowest 99th Percentile HECs...........66

Table 3-26. Changes in the Non-Cancer MOEs If Different HECs are Used a .............................................68

Table B-1. US EPA 2006 IUR Data for TCE. ................................................................................................. 88

Table B-2. National Chemical Information.................................................................................................89

Table B-3. Summary of TCE Uses. ..............................................................................................................89

Table B-4. TCE Use Category Summary......................................................................................................90

Table C-1. TCE Used as a Degreaser Primarily in These Industries (US Census, 2008). .............................91

Table D-1. Near-Field/Far-Field Model Inputs. ..........................................................................................95

Table D-2. Potential Workplace TCE Inhalation Exposures and Number of Workers Exposed; No LEV....95

Table D-3. Potential Workplace TCE Inhalation Exposures and Number of Workers Exposed; With LEV.96

Table E-1. Estimated TCE Inhalation Calculated Concentration in Air (Over Course of Day) from Use of 

Two Hobbyist Products Indoors at Residences......................................................................98

Table F-1. Studies Identified In US EPA (2011c) For Use In Dose-Response Assessment For TCE.............99
DRAFT DO NOT CITE OR QUOTE

Page 5 

List of Figures

Figure D-1. An Illustration of an Imperfectly Mixed Room; Near-Field/Far-Field Approximation of a 

Solvent Cleaning Facility; Potential Worker Exposures Depend on How Close a Worker is to

the Emission (Volatile) Source. ..............................................................................................93
DRAFT DO NOT CITE OR QUOTE

Page 6 

Authors / Contributors / Acknowledgements / Reviewers

This report was developed by the Office of Pollution Prevention and Toxics (OPPT), Office of 

Chemical Safety and Pollution Prevention (OCSPP). The 2012 workplan risk assessments were 

prepared based on existing data and any additional information received up to June 15, 2012.

Mention of trade names does not constitute endorsement by the US EPA.

EPA Assessment Team

Lead: Louis Scarano, OPPT/RAD

Team: David Lynch, OPPT/EETD Lead

Marcus Aguilar, OPPT/CCD

Rehan Choudhary, OPPT/EETD

Lynn Delpire, OPPT/EETD (retired)

Cathy Fehrenbacher, OPPT/EETD

Kathy Hart, OPPT/EETD

Laura Nielsen, OPPT/EETD

Nhan Nguyen, OPPT/EETD

Justin Roberts, OPPT/EETD 

Yvette M. Selby – Mohamadu, OPPT/EETD

David Tobias, OPPT/EETD

Acknowledgements

Weihsueh Chiu, ORD/NCEA for consultations on TCE IRIS assessment and PBPK modeling

Acknowledgements

Portions of this document were developed with support from:

Contractor name (contract number) Task 

SRC, Inc. (EP-W-12-003) Environmental Fate

Internal Peer Reviewers 

H. Kay Austin, OPPT/EETD 

Stan Barone Jr., OPPT/RAD

Todd Stedeford, OPPT/RAD

External Peer Review - A peer review panel is being arranged for this influential workplan 

assessment product based upon need and following Agency peer review guidance. The format 

will be a teleconference of an ad hoc panel meeting consisting of independent experts. 
DRAFT DO NOT CITE OR QUOTE

 Page 7 

Glossary of Terms and Abbreviations

μg/m3 Microgram(s) per cubic meter

ACGIH American Conference of Governmental Industrial Hygienists

ADR Acute dose rate 

AEGL Acute Exposure Guideline Level

ATSDR Agency for Toxic Substances and Disease Registry

BAF Bioaccumulation factor

BCF Bioconcentration factor

BMD Benchmark dose

BMDL Benchmark dose, lower confidence limit(s)

BOD Biochemical oxygen demand

CalEPA California Environmental Protection Agency

CASRN Chemical Abstracts Service Registry Number

CCD Chemical Control Division

CEM Consumer Exposure Module

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act

CI Confidence interval

CNS Central nervous system

cRfC Candidate reference concentration

CYP Cytochrome P450

DCA Dichloroacetic acid

DCAC Dichloroacetyl chloride

DCVC S-Dichlorovinyl-L-cysteine (collectively, the 1,2- and 2,2- isomers)

DCVG S-Dichlorovinyl-glutathione

DCVT Dichlorovinyl thiol

DIY Do-it-yourself

DNA Deoxyribonucleic acid

ECA Enforceable consent agreement

EEG Electroencephalogram

EETD Economics, Exposure and Technology Division

E-FAST Exposure and Fate Assessment Screening Tool

EFH Exposure Factors Handbook

EIS Emissions Inventory System

EU European Union

g Gram(s)

GGTP Gamma glutamyl transpeptidase

GSH Glutathione (reduced)

HAP Hazardous air pollutant

HCV Human cancer value

HEC Human equivalent concentration

HEC50 “Typical” human equivalent concentration

HEC99 “Sensitive” human equivalent concentration
DRAFT DO NOT CITE OR QUOTE

 Page 8 

HSIA Halogenated Solvents Industry Alliance, Inc. 

lb Pound(s)

IARC International Agency for Research on Cancer

IRIS Integrated Risk Information System

IUR Inhalation unit risk

kg Kilogram(s)

LADC Lifetime average daily concentration 

LADD Lifetime average daily dose 

LEV Local exhaust ventilation

LOAEL Lowest-observed-adverse-effect level

MCL Maximum contaminant level

MCLG Maximum contaminant level goal

mg/kg-bw/day Milligram(s) per kilogram body weight per day

mg/L Milligram(s) per liter

mg/m3

 Milligram(s) per cubic meter

mg/mL Milligram(s) per milliliter

MITI Ministry of International Trade and Industry

MOE Margin of Exposure

MOEacute Margin of Exposure (for acute exposure/hazard concerns)

MOEchronic Margin of Exposure (for chronic exposure/hazard concerns)

MOU Memorandum of understanding

NAcDCVC N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine

NAICS North American Industry Classification System

NAS National Academy of Sciences

NCI National Cancer Institute

NEI National Emissions Inventory

NHL Non-Hodgkins lymphoma

NIH National Institutes of Health

NOAEL No-observed-adverse-effect level

NOES National Occupational Exposure Survey

NIOSH National Institute for Occupational Safety and Health

NPL National Priority List

NTP National Toxicology Program

OAR Office of Air and Radiation

OCSPP Office of Chemical Safety and Pollution Prevention

OECD Organisation for Economic Co-operation and Development

OPPT Office of Pollution Prevention and Toxics 

OR Odds ratio

OSHA Occupational Safety and Health Administration

OSWER Office of Solid Waste and Emergency Response

OW Office of Water

PBPK Physiologically-based pharmacokinetic

p-cRFCs PBPK model-based candidate RfCs

PFC Plaque-forming cell
DRAFT DO NOT CITE OR QUOTE

 Page 9 

PND Postnatal day

POD Point of departure

POTW Publicly owned treatment works

ppb Parts per billion

ppm Parts per million

PVC Polyvinyl chloride

RAD Risk Assessment Division

RCC Renal cell carcinoma

RCRA Resource Conservation and Recovery Act

RfC Reference concentration

RfD Reference dose

RR Rate ratio

RRm Summary relative risk

SAB Science Advisory Board

SARA Superfund Amendments and Reauthorization Act

SCC Source Classification Code

TCA Trichloroacetic acid

TCE Trichloroethylene

TCOG Trichloroethanol, glucuronide conjugate

TCOH Trichloroethanol

TRI Toxics Release Inventory

TTC Total trichloro compounds

TSCA Toxic Substances Control Act

TWA Time-weighted average

UF Uncertainty factor 

US United States

US EPA United States Environmental Protection Agency

VCCEP Voluntary Children’s Chemical Evaluation Program

VOC Volatile organic compound
DRAFT DO NOT CITE OR QUOTE

 Page 10

Executive Summary

Trichloroethylene (TCE) was identified for risk assessment as part of the United States (US) 

Environmental Protection Agency’s (EPA)’s Existing Chemicals Management Program. The US 

EPA reviewed readily available information on TCE including uses, physical and chemistry

properties, fate, exposure potential, and associated hazards to humans and the environment. 

TCE was selected based on concerns for its human health hazard (e.g., probable human 

carcinogen), and its exposure profile (i.e., widely used in consumer products and detected in 

drinking water, indoor environments, surface water, ambient air, groundwater, and soil) using 

the recently adopted Office of Pollution Prevention and Toxics (OPPT) screening methodology 

(US EPA, 2012c). TCE also was determined to have moderate persistence and low 

bioaccumulation potential. The potential for environmental effects was judged to be low 

because of TCE’s moderate persistence, low bioaccumulation, and low hazard for aquatic 

toxicity. This risk assessment does not include an assessment of environmental effects. 

TCE is a volatile organic compound (VOC) that is produced or imported into the US in large 

quantities (>250 million lbs (lbs) per year) and has multiple uses. The majority, roughly 84 

percent, of TCE is used as an intermediate chemical for manufacturing refrigerant chemicals, 

but no emission information was available because it is processed in a closed system. Much of 

the remaining ~15 percent is used as a solvent for metals degreasing, leaving a relatively small 

percentage to account for all other uses, including its use in consumer products. 

This assessment is focused on TCE’s use as a degreaser in small commercial settings1 and by 

consumers in residential settings and its use as a clear protective coating spray by arts and 

crafts hobbyists. Due to TCE’s high volatility, all exposures were evaluated for the inhalation 

exposure pathway only. The US EPA recognizes that dermal exposure can occur, but this 

exposure pathway is considered less significant and was not considered within the scope of this 

risk assessment.

For the exposure assessment, OPPT reviewed available data from three separate sources (i.e., 

National Emissions Inventory [NEI], Toxics Release Inventory [TRI], and the North American 

Industry Classification System [NAICS]) and developed estimates for exposures for the small 

commercial degreaser use. There were no reliable data regarding the hobbyist scenarios, so 

OPPT estimated hobbyist exposures using a standard exposure assessment modeling approach 

(i.e., EPA’s Exposure and Fate Assessment Screening Tool [E-FAST], Consumer Exposure Module 

[CEM]).

Modeling and evaluation were used to develop exposure estimates for the following exposure 

scenarios: small commercial degreaser worker; consumer/hobbyist degreaser user; and 

consumer/hobbyist clear protective coating spray user. For all three scenarios, exposure 

estimates also were developed for bystanders (i.e., non-users) defined as individuals not 

actually using the TCE product, but who are physically nearby and thus, possibly exposed. 

 1 Small commercial settings represent small businesses that use degreaser products/equipment regularly, but not 

all day during the course of their job. An example would be a garage/car mechanic business.
DRAFT DO NOT CITE OR QUOTE

 Page 11

For the hazard information, the US EPA relied on the Integrated Risk Information System’s (IRIS) 

published toxicological review of TCE (US EPA, 2011c). This information was used to identify 

non-cancer hazard values for acute (i.e., single or short-term) and chronic (i.e., repeated) 

exposure conditions. There were 27 different candidate studies identified that evaluated 32 

endpoints, which encompassed a variety of effects following both acute (i.e., developmental 

toxicity and neurotoxicity) and chronic (i.e., liver, kidney, immunotoxicity, and male 

reproductive toxicity) exposures. From this pool of studies, OPPT chose 12 studies that used 

inhalation as the route of exposure. These 12 studies evaluated 17 different endpoints. Hazard 

values were chosen to represent effects in each of the major target organs. By not limiting the 

analysis to a single, sensitive endpoint or effect, this assessment allows both the exposure 

duration and the population exposed to help determine which hazard value may be the most 

appropriate or important. 

The IRIS inhalation unit risk (IUR) value, based on concerns for human cancers of the kidney, 

liver, and non-Hodgkin’s lymphoma (NHL), was used for OPPT’s TCE cancer risk assessment.

Adult male and female workers and bystanders in small commercial facilities were identified as 

a population or life stage targeted for chronic or daily exposure scenarios in this assessment. 

Because acute exposures also can occur during daily exposures, there may be a potential 

hazard for both neurotoxicity and developmental toxicity; thus, given the latter, women of 

child-bearing age were included as a life stage or population. 

For both the residential consumer and hobbyist user scenarios, the same populations identified 

for the small commercial worker and bystander scenarios (i.e., males and females, including 

women of child-bearing age) were used. However, the non-cancer evaluation was limited to 

acute exposures and to neurological effects to males and females, and developmental effects to

women of child-bearing age. For the consumer, non-user population, the US EPA identified all 

ages for evaluation because all-age members of a household could be in the home during the 

use of the consumer product. 

For all non-cancer risk calculations, the Margin of Exposure (MOE) approach was used. In this 

approach, the hazard value is divided by the exposure value to derive a number that is 

compared to conventional benchmark values used to estimate or quantify risk. In this risk 

assessment, all of the hazard values were derived using a special mathematical model as 

determined by US EPA (2011c). The modeling exercise used test data from both animals and 

humans to derive values called Human Equivalent Concentrations (HEC). Although many HEC 

values were calculated by the IRIS program, in this assessment a more conservative value was 

used (i.e., the lower bound 99th percentile HEC value) for each of the non-cancer adverse effect 

outcomes evaluated. 

When the hazard value (HEC) is divided by the exposure value, the resulting number is called 

the “Margin of Exposure” or MOE. In this risk assessment, if the value is determined as less 

than 30, there is a potential risk concern; if the value is found as greater than 30, there is no risk 

concern. 

 

For the cancer risk assessment, a different metric was used to quantify risk. The method EPA 

used calculated extra cancer risk from benchmarks of concern based on no more than one 
DRAFT DO NOT CITE OR QUOTE

 Page 12 

excess cancer in a population of 100,000 workers (i.e., 1 x 10-5) or one excess cancer in a 

population of one million nonworkers (i.e., 1 x 10-6). 

EPA relied on physiologically-based pharmacokinetic (PBPK) modeling performed by the US 

EPA’s IRIS program, which resulted in a variety of hazard values to represent HECs. In choosing 

the values used, assumptions were made that could introduce some uncertainty into the risk 

assessment. However, using conservative measures (i.e., the lower bound 99th percentile HEC) 

and values from inhalation-only studies for each of the six major target organs or adverse 

effects associated with TCE, strengthens the degree of confidence that the risks were not 

under-estimated for the scenarios evaluated in this report. 

As with any risk assessment, there are uncertainties that need to be considered when 

interpreting the results. Assumptions were used in estimating the exposure scenarios covered 

in this assessment. Examples include assumptions about the number and duration of use events 

(i.e., how often a consumer may use a degreaser or clear protective coating spray product) and 

the assumptions used to estimate inhalation exposures to small shop commercial degreaser 

workers. OPPT did not quantify these uncertainties and recognizes that they may under- or 

over-estimate actual exposure.

Finally, by focusing on six different target organs or effects for chronic and acute exposure 

durations, rather than on a single, sensitive value or endpoint, the robust hazard database on 

TCE is fully utilized. This provides important context that is both useful and informative to those 

interested in understanding the potential risks of concern from TCE exposures for the scenarios 

evaluated in this risk assessment.

The results of the risk assessment show: 

• For the commercial degreaser user and non-user, non-cancer MOEs were less than 30 

for acute toxicity for developmental toxicity and neurotoxicity effects, and chronic 

effects for liver, kidney, and immune system effects. This indicates potential risks of 

concern.

• For the commercial degreaser user and non-user, using the IRIS IUR the cancer risks 

were all below the benchmark values. This indicates potential risks of concern. 

• For the hobbyist degreaser user and non-user and for the hobbyist clear protective 

spray users, the acute non-cancer MOEs for developmental toxicity were less than 30. 

This indicates potential risks of concern.

• The hobbyist clear protective spray non-user scenario resulted in an MOE of greater 

than 30 for both developmental toxicity and neurotoxicity. This indicates no potential 

risks of concern.
DRAFT DO NOT CITE OR QUOTE

 Page 13

Chapter 1: Background and Scope

Trichloroethylene (TCE) has been identified for assessment as part of the United States (US) 

Environmental Protection Agency’s (EPA) Existing Chemicals Management Program. TCE was 

selected based on EPA’s concerns for human health hazard (i.e., probable human carcinogen), 

and its exposure profile (i.e., widely used in consumer products and detected in drinking water, 

indoor environments, surface water, ambient air, groundwater, and soil) using the recently 

adopted Office of Pollution Prevention and Toxics (OPPT) screening methodology (US EPA, 

2012c). 

In this chapter, a brief discussion is presented on the steps that EPA has taken to determine the 

focus and scope of this risk assessment.

BACKGROUND

TCE is a liquid, volatile organic compound with high vapor pressure, moderate water solubility, 

and high mobility in soil. The biodegradation of TCE in the environment is dependent on a 

variety of factors (e.g., pH, resident microorganisms, moisture, etc.) and so a wide range of 

degradation rates are possible, ranging from days to years. TCE also has moderate persistence 

and low bioaccumulation potential.

This substance is produced or imported into the US in large quantities (i.e., >250 million lbs/ yr) 

and has many uses. The majority, almost 84 percent, of TCE is used as an intermediate 

chemical for manufacturing refrigerant chemicals. Much of the remaining roughly 15 percent is 

used as a solvent for metals degreasing, leaving a relatively small percentage to account for all 

other uses, including, its use in some consumer products. TCE can be found in consumer 

products including but not limited to those “do-it-yourself” [DIY] consumer uses such as a 

solvent for metal degreasing for use on cars, bikes, etc., or as an ingredient in hobbyist 

products, including a clear protective coating spray for artwork, a film cleaner, a toner aide, and 

a mirror edge sealant. 

Most reported environmental releases of TCE are to air with much fewer releases to landfills 

and very little releases to water (see Chapter 3, Section A, Environmental Release and Exposure 

Summary). 

Due to its high production volume, physical-chemical properties, uses, and environmental 

releases, TCE has been the subject of various regulations across many offices within the US EPA: 

the Office of Air and Radiation (OAR), the Office of Solid Waste and Emergency Response 

(OSWER), the Office of Water (OW), and OPPT. Appendix A provides a review of the US EPAwide regulatory history of TCE. 

The US EPA’s assessment of the human health hazard of TCE is largely based on the US EPA’s 

toxicological review of TCE (US EPA, 2011c). This comprehensive review compiled hazard 
DRAFT DO NOT CITE OR QUOTE

 Page 14

information and was reviewed by the US EPA’s Science Advisory Board (SAB) (US EPA, 2011a). 

In addition, a literature search was conducted in March, 2012 for new information. 

SCOPE OF ASSESSMENT FOR TCE

Given that the majority of TCE produced and used in the US is as a chemical intermediate that 

would not likely result in exposures to the general population, the US EPA assumed that 

virtually all of the TCE that is used as an intermediate for manufacturing refrigerant chemical is 

consumed in this process or released as fugitive air emissions. Large-scale manufacturing 

occupational exposure scenarios were not addressed in this risk assessment. In general, 

exposures that result from large-scale industrial operations are likely to be better controlled 

and monitored than those exposures from small commercial settings and consumer uses. 

The US EPA focused the assessment on uses of TCE as a degreaser (i.e., both in small 

commercial settings and by consumers or hobbyists) and on consumer use of TCE in products 

used by individuals in the arts and crafts field. Bystanders, those who are in the vicinity of the 

product use, also were addressed. Because of TCE’s high volatility, all exposures were 

evaluated only for the inhalation exposure pathway. The US EPA recognizes that dermal 

exposure can occur for both of these scenarios, but this exposure pathway is considered less 

significant and is not considered in this risk assessment.

Information from EPA’s toxicological review of TCE (US EPA, 2011c) was used as the basis for 

developing an assessment of the human health hazard of TCE in targeted use by workers in 

small commercial degreasing applications and by consumer/hobbyists using TCE as a degreaser 

and an art spray fixative. EPA identified non-cancer hazard values for acute (i.e., single or shortterm) and chronic (i.e., repeated) exposure conditions for a variety of effects including both 

acute (i.e., developmental toxicity and neurotoxicity) and chronic (i.e., liver, kidney, 

immunotoxicity, and neurotoxicity) endpoints. 

EPA did not evaluate environmental effects in this risk assessment from the manufacture and 

use of TCE. Available information reviewed in the European Union (EU) risk assessment for TCE 

(EC, 2004) concluded there were no concerns for environmental effects on aquatic organisms, 

including benthic organisms, terrestrial organisms, and the atmosphere. The EU risk

conclusions were based on the production and use of TCE (i.e., including releases to wastewater 

treatment plants, to air from all uses, and from dichloroacetic acid [DCA; photodegradation 

product of TCE]). The hazard information EPA reviewed, particularly the aquatic toxicity data, 

suggest there is no immediate concern for potential environmental effects. 

Table 1-1 shows the use and exposure scenarios considered and the rationale for inclusion or 

exclusion in this assessment. The primary criteria for inclusion were whether there was a high 

TCE concentration in the product and the frequency of use of the product. EPA focused its 

assessment on small commercial operators where workers such as garage mechanics may use a 

solvent degreaser at some point as a part of their daily activities. It is assumed that these 

individuals are all adults (>16 and older). Furthermore, exposures were estimated and risks 
DRAFT DO NOT CITE OR QUOTE

 Page 15

were calculated for workers in the vicinity of the degreasing use, but not actually performing 

the operation (i.e., bystanders).

Table 1-1. Primary Uses of TCE and Determination of Inclusion in this Risk Assessment. 

Use Category

Typical 

Percent 

TCE 

Content

Population Exposed To Be Considered in this Assessment?

Intermediate in 

the 

manufacturing of 

refrigerant 

>99 Workers in the 

refrigerant 

manufacturing 

process

No – US EPA is assuming that most of the 

TCE is consumed in producing the 

refrigerant

Solvent 

degreaser

>90 Large commercial/

industrial settings 

(adults)

No – Such exposure scenarios are more 

likely to be monitored/controlled in the 

workplace and by OSHA

Solvent 

degreaser

>90 Small commercial 

shop employees and 

non-users (all 

adults) 

Yes – high content, possible frequent use 

(i.e., chronic exposures) 

Solvent 

degreaser

>90 Consumer users 

(adults >16 years 

old), non-users (all 

ages)

Yes – high content, assumed low frequent 

use (i.e., acute exposures)

Plastic clear 

protective 

coating spray

(hobbyists; 

arts/crafts)

20-30 Yes – low content, but likely most frequent 

use of consumer products evaluated (i.e., 

acute exposures)

Film cleaner 

(hobbyists)

>90 No – although high content, use of 

negatives/cameras with film is thought to be 

low and so frequency of use is assumed to 

be negligible; there is the potential for 

frequent use by small population (i.e., film 

developers)

Toner aide

(home office)

15-20 No – low content, assumed less frequent use

Mirror edge 

sealant 

(hobbyist/home 

maintenance)

20-30 No – low content, assumed less frequent use

Consumers are individuals using the products listed in Table 1-1 in and around their home. 

Non-users are individuals physically close to the use activity as it occurs and/or living in the 

user’s residence. The consumer/hobbyist users are assumed to be adults (16 years or older), 

and the non-users could be any age.
DRAFT DO NOT CITE OR QUOTE

 Page 16

Chapter 2: Sources and Environmental Fate of TCE

In this chapter, information on the physical and chemical properties and environmental fate of 

TCE is presented. There also is a brief summary of the production volume and general 

information on the uses of TCE in the US. All of these factors are important to understanding 

the potential risks of TCE to workers in this assessment.

A. PHYSICAL AND CHEMICAL PROPERTIES OF TCE

TCE is a colorless liquid with a pleasant, sweet odor resembling that of chloroform. It is 

considered a VOC because of its moderate boiling point, 87.2 °C, and high vapor pressure, 73.46 

mm Hg at 25 °C. TCE is moderately water soluble (1.280 g/L at 25 °C), and has a log 

octanol:water partition coefficient (Kow) of 2.42. The density of TCE, 1.46 g/cm3 at 20 °C, is 

greater than that of water. Table 2-1 lists the chemical/physical properties of TCE.

Table 2-1. Physical-Chemical Properties of TCEa

.

Property Value

CASRN 79-01-6 

Molecular weight 131.39

Molecular formula C2HCl3

Physical state Colorless liquid

Odor Sweet, pleasant, resembles chloroform

Density 1.46 g/cm3 @ 20 °Cb

Flash point 90 °C (closed cup)b

Auto flammability 410 °Ca

Viscosity 0.53 mPa·s @ 25 °Cc

Refractive index 1.4775e

Dielectric constant 3.4 ε0 @ 16 °Cc

Melting point -84.7 °C (measured)

Boiling point 87.2 °C (measured)

Vapor pressure 73.46 mm Hg at 25 °C (measured)d

Dissociation constant (pKa) Not applicable

Henry’s law constant 9.85×10-3 atm-m3/mole (measured)

Water solubility 1,280 mg/L at 25 °C (measured)

Log Kow 2.42 (measured)

a

SRC (2012). b

EC (2000). c

Weast and Selby (1966). 

d

Daubert and Danner (1989). e

O'Neil et al. (2001).
DRAFT DO NOT CITE OR QUOTE

 Page 17

B. ENVIRONMENTAL FATE

The environmental fate of a compound is important to understanding potential exposures to its 

impact on specific environmental media (e.g., water, sediment, soil, and plants) and target 

organisms of concern. TCE is a volatile liquid with high vapor pressure, moderate water 

solubility, and high mobility in soil. Most reported environmental releases of TCE are to air with 

much fewer releases to landfills and very little released to water (see Chapter 3, Section A, 

Environmental Release and Exposure Summary). If released to air, degradation by sunlight and 

reactants in the atmosphere is slow. If released to water, sediment, or soil, the fate of TCE is 

influenced by volatilization from the water surface or from moist soil and by microbial 

biodegradation under some conditions. The biodegradation of TCE in the environment is 

dependent on a variety of factors and so a wide range of degradation rates are possible (i.e., 

ranging from days to years). Finally, TCE is not expected to bioconcentrate in aquatic 

organisms. 

Fate in Air 

TCE does not absorb light greater than 290 nm very well; therefore, degradation of TCE by 

direct exposure to light, if it is released to the atmosphere, is not expected to be an important 

fate process (US EPA, 1979a). TCE is expected to undergo relatively slow atmospheric hydroxy 

radical oxidation with an estimated atmospheric half-life of about 13 days (using Version 4.10 of

EpiSuite,US EPA 2012a). Phosgene, dichloroacetyl chloride (DCAC), chloroform, and formyl 

chloride can be formed from the reaction of TCE with hydroxyl radicals (Kao, 1994; Gay et al., 

1976; US EPA, 1980). 

Fate in Water

Volatilization from water surfaces will be an important fate process based upon TCE’s measured 

Henry's law constant. However, its density may cause it to sink in the water column, potentially 

increasing the aquatic residence time of TCE. Volatilization half-lives in an experimental field 

mesocosm consisting of seawater, planktonic, and microbial communities ranged from 10.7 to 

28 days (Wakeham et al., 1983). TCE achieved only 19 percent of its theoretical biochemical 

oxygen demand (BOD) over the course of a 28-day incubation period using the closed bottle 

(Organisation for Economic Co-operation and Development [OECD] 301D) test, and thus is not 

considered readily biodegradable. It achieved 2.4 percent of its theoretical BOD using an 

activated sludge inoculum in the modified Ministry of International Trade and Industry (MITI, 

OECD 301C) test over the course of a 14-day incubation period. It was not inherently 

biodegradable in a Zahn-Wellens (OECD 302B) test. These studies suggest that TCE will 

biodegrade slowly in surface waters. However, slow photooxidation in water has been reported 

(half-life of 10.7 months) (Dilling et al., 1975). Based on these studies, biodegradation and 

hydrolysis in surface waters are not expected to be important environmental fate processes. 
DRAFT DO NOT CITE OR QUOTE

 Page 18

Fate in Soil, Sediment, and Groundwater

TCE is expected to have high mobility in soil based on measured soil organic carbon partition 

coefficients ranging from 72 to 148. Volatilization of TCE from moist soil surfaces is expected to 

be an important fate process given its relatively high Henry's law constant. TCE is expected to 

volatilize from dry soil surfaces based upon its high vapor pressure. 

Both laboratory tests and field studies in the environment show wide variation in TCE 

biodegradation rates. In some cases, laboratory studies have shown rapid biodegradation. TCE 

has been shown to biodegrade under aerobic conditions by methanotrophic microbes in the 

presence of other substrates and under anaerobic conditions (in suitable reducing 

environments) in the presence of other organic matter. Without competent microorganisms 

that can degrade TCE and favorable environmental conditions, TCE can persist in the 

environment on the order of years.

Aerobic biodegradation of TCE by specialized communities of microorganisms has been 

reported (Wackett et al., 1989). Biodegradation of TCE has also been shown to occur under 

conditions where additional substrates have been added to the medium (Mu and Scow, 1994; 

Kao and Prosser, 1999; Wilson and Wilson, 1985). Mixed microbial cultures of methaneutilizing bacteria have been shown to degrade TCE in two days under aerobic conditions (Fogel

et al., 1986). However, there are several factors that can limit the aerobic biodegradation of 

TCE, including TCE concentration, pH, and temperature. Toxicity of the degradation products 

(e.g., dichloroethylene, vinyl chloride, chloromethane) to the degrading microorganisms may 

also reduce the rates of biodegradation of TCE in aerobic soils. 

Biodegradation of TCE also occurs under anaerobic conditions. Under these conditions, as 

might be seen in flooded soils, sediment, or aquifer environments, TCE is biodegraded via

reductive dechlorination; the extent and rate of degradation are dependent upon the strength 

of the reducing environment and other factors (McCarty, 1996). TCE half-lives in the field for 

aquifer studies range from 35 days to over six years. Major products of biodegradation of TCE 

in groundwater include dichloroethylene, chloromethane, and vinyl chloride (HSDB, 2012). 

TCE contamination exists in the subsurface environment as a result of spills and leaking transfer 

lines/storage tanks. Because of its density and low Koc, TCE will ultimately move downward in 

the soil until an impermeable barrier is reached. This may occur when a TCE spill is of sufficient 

magnitude or deep enough in soil for volatilization to be restricted. Once in soil, TCE can 

become associated with soil pore water, enter the gas phase because of its Henry’s Law 

constant, or exist as a nonaqueous phase liquid (NAPL). It is possible that upward or downward 

movement of TCE can occur in each of these three phases, thereby increasing the areal extent 

of the original spill. Nonaqueous phase concentrations of TCE which are large enough to 

overcome capillary forces will move downward into the aquifer. Once the water table is 

penetrated, lateral flow may be mediated by the regional ground-water flow. Due to its high 

density, the movement of free-phase TCE is still directed vertically until lower permeability 

features are encountered. Once an impermeable layer is encountered, horizontal movement 
DRAFT DO NOT CITE OR QUOTE

 Page 19

will occur. Such movement may even be directed against the natural ground-water flow by the 

effects of gravity. Since permeability is a function of the liquid as well as the medium, the 

vertical movement of TCE through an aquifer is determined by geological properties of the 

aquifer material; i.e., granular size of sand or clay lenses. TCE will tend to pool near these 

impermeable features. Water passing over and around these pools may solubilize TCE so that it

can be spread throughout the aquifer. This pattern of release and distribution in aquifers and 

TCE persistence have led to the widespread detection of TCE in groundwater and drinking water 

supplies derived from the contaminated groundwater (US EPA, 1992). 

Bioconcentration

TCE is not expected to bioconcentrate in fish, with measured bioconcentration factors (BCFs) in 

carp ranging from four to 17. TCE’s low measured BCF value suggests that bioconcentration in 

aquatic organisms is low (NITE, 2012). The estimated upper trophic level bioaccumulation 

factor (BAF) for TCE is 24 (using Version 4.10 of EpiSuite,US EPA, 2012a). 

Table 2-2 provides a summary of the environmental fate information for TCE. 

Conclusions on Environmental Fate

TCE is a volatile liquid and if released to air, will be slowly degraded by atmospheric hydroxy 

radicals. If released to water, volatilization to the atmosphere will be an important fate process 

and biodegradation will be slow. In soil, TCE does not bind strongly to soil organic matter and if 

not biodegraded at an appreciable rate, TCE can migrate through soil to groundwater. Based 

on the experimental evidence and environmental fate data available, TCE is expected to have 

low bioaccumulation potential and moderate persistence.
DRAFT DO NOT CITE OR QUOTE

 Page 20

Table 2-2. Environmental Fate Characteristics of TCEa. 

Property Value

CASRN 79-01-6

Photodegradation half-life 13.2 days (estimated)

Hydrolysis half-life Does not hydrolyze under environmental conditionsb

Biodegradation 19% after 28 days (not readily biodegradable)b; 

4% after 28 days (not inherently biodegradable)b

; 

100% after 2 days (anaerobic conditions using mixed march cultures)b

;

2.4% after 14 days (not readily biodegradable)c 

Bioconcentration BCF = 4.3-17 (measured in carp at 0.070 mg/L)c; 

BCF = 4-16 (measured in carp at 0.007 mg/L)c

; 

BCF = 17 (measured in freshwater fish at 0.0087 mg/L)c

;

BAF = 23.7 (estimated)a 

Log Koc 2.17 (measured in silty clay Nebraska loam)c; 

1.94 (measured in silty clay Nevada loam)c

; 

1.86 (measured in a forest soil)c

; 

1.8 (estimated)

Fugacity (Level III Model)b

Air (%)

Water (%)

Soil (%)

Sediment (%)

35.4

54.2

10.1

0.3

Persistenced P2 (moderate)

Bioaccumulationd B1 (low)

a

US EPA (2012a). b

EC (2000). c

NITE (2012). c

US EPA (1999).
DRAFT DO NOT CITE OR QUOTE

 Page 21

C. PRODUCTION VOLUME AND GENERAL INFORMATION ON USES

In 2011, global consumption of TCE was 945 million lbs with expected growth at about 1.5

percent annually over the next five years. The corresponding US consumption was 255 million 

lbs (Glauser and Funda, 2012). There were two US producers for TCE as of 2011: The Dow 

Chemical Company in Freeport, TX and PPG Industries, Inc. in Lake Charles, LA (Glauser and 

Funda, 2012)

2

. 

TCE production volumes of 100 to 500 million lbs were reported to EPA in 2006 under the 

Inventory Update Rule (IUR). In 2005, there were four known importers of TCE (Chemcentral

Corporation; Ineos Chlor Americas, Inc.; JSL Chemical Corporation; and TR International, Inc.) 

reported in the IUR (US EPA, 2006b). Exports of TCE from the US have increased along with 

similar increases for all chlorinated solvents (80 percent in 2011, 72 percent in 2010) (ICIS, 

2010, 2012). More information can be found in Appendix B.

TCE has historically had a wide range of uses drawn from various markets, including 

intermediate chemicals (for refrigerant and polyvinyl chloride [PVC] manufacture), industrial 

and commercial solvents, pharmaceuticals, insecticides, fumigant, textiles (processing and 

flame retardants), adhesives, and paints (as diluent) (Ash and Ash, 2009). However, as of 2011, 

most US consumption is attributable to two specific uses: 83.6 percent of total TCE production 

volume is used as an intermediate for manufacturing the refrigerant, HFC-134a (a major 

alternative to CFC-12), and 14.7 percent is used as a solvent for metals degreasing, with 1.7

percent attributed to “other uses” (Glauser and Funda, 2012)

3

. 

 2 This material includes data or information derived from IHS Products provided to the US EPA. IHS products have 

been provided to the US EPA for its internal use and in the context of a license agreement. By receiving and 

accessing this material, you agree that IHS is not liable to you or any third party for your use of and/or reliance on 

the IHS data and information contained in this document, and any such use shall be at your own risk.

3 Ibid. 
DRAFT DO NOT CITE OR QUOTE

 Page 22

Chapter 3: Human Health Risk Assessment 

This chapter has five major sections: (1) Environmental Releases and Exposure Summary; 

(2) Hazard Summary; (3) Risk Characterization; (4) Discussion of Uncertainties and Data Gaps; 

and (5) Conclusions.

A. ENVIRONMENTAL RELEASES AND EXPOSURE SUMMARY 

TCE has been detected in air, water, and humans (US EPA, 2011c). In identifying exposure 

pathways for TCE, its volatility plays a major role, and the inhalation route of exposure is of 

primary importance and concern. This section characterizes the environmental releases of, and 

workplace and consumer/hobbyist exposures to, TCE. 

ENVIRONMENTAL RELEASES OF TCE

General 

There is potential for release of TCE to air, water, sediment, and soil from manufacture, 

processing, and use. As noted previously, the largest percentage of TCE production and

importation is used as an intermediate in the manufacture of refrigerants (~84 percent). 

Because most of the TCE associated with this use is expected to be reacted to form another 

chemical, potential releases to the environment from the refrigerant use is unlikely to 

contribute to the TCE found in ambient air/water/human biomonitoring as described below. It 

is expected that a small percentage of TCE may be released as fugitive air emissions (i.e., 

material lost during use). This consistent with the Toxics Release Inventory (TRI) data which 

indicates some of the highest fugitive and point source air releases reported for TCE come from 

the degreaser use (i.e., roughly 15 percent of the production/importation volume in the US). 

Thus, while there is some potential for fugitive emissions, fugitive TCE releases from 

manufacture of refrigerants will not be considered in this risk assessment.

The US EPA developed a summary of ambient air monitoring (i.e., measured) data for TCE in the 

US from 1999 to 2006 (as reported in US EPA, 2011c) that is provided in Table 3-1. These data 

suggest that TCE levels have remained fairly constant in the US since 1999, with an approximate

mean value of 0.3 μg/m3

 (i.e., which is equivalent to 5.6 x 10-5 ppm). 
DRAFT DO NOT CITE OR QUOTE

 Page 23

Table 3-1. TCE Ambient Air Monitoring Data (μg/m3)

a

. 

Year 

Number of 

Monitors

Number of 

States Mean

Standard 

Deviation Median Range

1999 162 20 0.30 0.53 0.16 0.01-4.38

2000 187 28 0.34 0.75 0.16 0.01-7.39

2001 204 31 0.25 0.92 0.13 0.01-12.90

2002 259 41 0.37 1.26 0.13 0.01-18.44

2003 248 41 0.35 0.64 0.16 0.02-6.92

2004 256 37 0.32 0.75 0.13 0.00-5.78

2005 313 38 0.43 1.05 0.14 0.00-6.64

2006 258 37 0.23 0.55 0.13 0.03-7.73

a The US EPA’s Air Quality System database at the AirData Web site: http://www.epa.gov/airdata/ (as 

summarized in US EPA, 2011c). Note that the data are not from a statistically based survey and cannot be 

assumed to provide nationally representative values.

Other releases of TCE may occur, such as TCE entering publicly owned treatment works 

(POTWs), which will likely result in releases to surface waters and air. Disposal of TCE wastes to 

Resource Conservation and Recovery Act (RCRA) Subtitle C landfills also occurs and is of 

potential concern because TCE has moderate persistence under certain environmental 

conditions, and it is volatile, water soluble, mobile in soil and groundwater, and present in 

landfills. Under the Comprehensive Environmental Response, Compensation, and Liability Act 

(CERCLA) and the Superfund Amendments and Reauthorization Act (SARA), the US EPA and the 

Agency for Toxic Substances and Disease Registry (ATSDR) have established a prioritized list of 

substances most commonly found at facilities on the National Priority List (NPL) (ATSDR, 2011). 

The listing is based on the frequency of occurrence, toxicity, and potential for human exposure. 

TCE was ranked 16th out of 847 candidate substances for the 2011 ranking; only the top 275 are 

considered to be on the list. 

Releases of TCE from Consumer Uses

TCE can be released to indoor air from the use of consumer products that contain it, as well as 

from vapor intrusion and volatilization from contaminated water supplies (US EPA, 2011c). 

Where indoor air sources are present, it is likely that indoor levels will be higher than outdoor 

levels (US EPA, 2011c). US EPA (2011c) discussed several studies that measured indoor levels of 

TCE, but did not include any monitoring data for use of consumer products containing TCE. 

Recent literature sources report a few TCE air and personal monitoring studies that were not 

included in US EPA (2011c); however, no monitoring data for use of consumer products 

containing TCE were found. Specifically, the literature search did not find any studies that 

measured emissions of TCE from the six consumer products identified for consideration in this 

risk assessment (see below).
DRAFT DO NOT CITE OR QUOTE

 Page 24

Releases of TCE from Small Commercial Degreasing Operations

Halogenated solvent cleaning (degreasing) is widely used to remove grease, oils, waxes, carbon 

deposits, fluxes, and tars from metal, glass, or plastic surfaces (US EPA, 2006a, 2007b). The 

degreasing process is used in many industries, both large and small. An analysis of the North 

American Industry Classification System (NAICS) identified 78 different industries (NAICS codes 

are listed in Appendix C; data not shown, but available in US EPA (2008b). 

There are two general types of degreasing machines: batch and in-line. Batch cleaning 

machines are the most common type, while in-line cleaners are typically used in large-scale 

industrial operations (US EPA, 2006a). The size of a degreasing machine is defined by the area 

of its solvent-to-air interface. Emissions from degreasing machines typically result from: (1) 

evaporation of the solvent from the solvent-to-air interface; (2) “carry out” of excess solvent on 

cleaned parts; and (3) evaporative losses of the solvent during filling and draining of the 

degreasing machine (US EPA, 2006a).

Use of TCE as a degreaser in an occupational/commercial setting will result in its releases 

primarily to air due to its volatility. The US EPA has developed an analysis of available 

information from the 2008 National Emissions Inventory (NEI), the 2010 TRI, and the NAICS to 

estimate TCE releases and occupational exposures from this use. These release estimates were 

used to estimate TCE exposures to workers in small commercial degreaser operations. Though 

these releases also could result in TCE exposure to the general population, such an analysis is 

outside the scope of this risk assessment. 

The NEI is a comprehensive and detailed estimate of air emissions of both criteria and 

hazardous air pollutants (HAPs) from all air emissions sources; the NEI is prepared every three 

years by the US EPA (2008b)

4

. As background, point sources are stationary sources (i.e., 

sources that remain in one place); a large facility that houses an industrial process is an 

example of a point source (US EPA, 2004a). Nonpoint sources refer to smaller, more diffuse 

sources; a variety of sources are categorized as nonpoint sources, including small 

industrial/commercial operations (US EPA, 2004a). 

Data from the most recent NEI (US EPA, 2008b) were considered. Based on the 78 NAICS codes 

(identified in Appendix C), and in conjunction with Source Classification Codes (SCC), the 

Pollutant Name, and Unit Type descriptions from the NEI, it is possible to identify the reported 

number of TCE emission points from 2008 (see Table 3-2); 66 percent of TCE emissions in 2008

 4 For those interested, here are the specific data sources/files used: 

ftp://ftp.epa.gov/EmisInventory/2008v2/nei2008v2_national_county_level_sector.zip; 

ftp://ftp.epa.gov/EmisInventory/2008v2/2008neiv2_facility.zip; 

http://www.epa.gov/ttn/chief/net/neip/appendix_6.mdb

At the following website: http://www.epa.gov/ttn/chief/net/2008inventory.html, under “SCC Data Files”, there is 

an option to download data by pressing the “Download” button. The following data sets are relevant: 1) Point and 

2) Nonpoint. 
DRAFT DO NOT CITE OR QUOTE

 Page 25

were from nonpoint sources (NPS), while approximately 34 percent were from point sources

PS). Thus, approximately two-thirds of the estimated emission points for TCE come from 

nonpoint sources.

Table 3-2. The Number of TCE-Emitting Emission Points and Corresponding Total Annual Air 

Emissions of TCE as reported in the 2008 NEI (US EPA, 2008b).

Type of Emission Point Reported Number of Emission 

Points

Total Annual Air Emissions 

(Lbs/Yr) 

Point source (PS) 186 1,480,000

Nonpoint source (NPS) 1,779 2,860,000

The US EPA’s TRI is a database that contains detailed information on environmental releases 

and transfers of certain listed toxic chemicals from industrial facilities; the TRI is maintained by 

the US EPA and is updated annually (TRI, 2012a). Based on the NAICS codes, the 2008 TRI can 

be queried to identify stack and fugitive air emissions of TCE (see Table 3-3). Thus, the NEI and 

TRI data from the same year (2008) can be compared.

 

Table 3-3. Total Annual Air Emissions of TCE as Reported in the 2008 TRI (TRI, 2012b). 

Type of Emission Total Annual Air Emissions (Lbs/Yr)

Stack air emissions 1,320,000

Fugitive air emissions 1,230,000

 

In 2008, based on the NAICS codes listed in Appendix C, total NEI TCE air emissions were 

approximately 1.7 times greater than those reported in the 2008 TRI5

. Whereas the NEI is the 

US EPA’s primary emissions inventory for HAPs and criteria pollutants, the TRI is another 

inventory that may be considered. The TRI provides releases to other environmental media 

(e.g., land and water) besides air; however, the TRI may exclude releases from small-scale 

operations, the intended focus of this risk assessment (US EPA, 2004a, 2011e). In light of this, 

release values from the 2010 TRI will be referenced, but the TCE air emissions will be 

estimated/adjusted based on the comparison between the 2008 NEI and TRI data (1.7 times the 

TRI reported value). 

Point sources include large industrial facilities; they can also include small industrial/ 

commercial facilities, which have traditionally been classified as nonpoint sources (US EPA,

2008b). However, the choice of whether small industrial/commercial facilities are classified as 

point or nonpoint sources is determined by the appropriate State, Local, or Tribal air agency (US 

EPA, 2008b). Thus, EPA assumed that point sources are representative of large industrial 

facilities, while nonpoint sources are assumed to be representative of small/commercial 

facilities.

 5 Derived by adding the total 2008 NEI emissions (1,480,000 + 2,860,000 = 4,340,000) and dividing this by the total 

2008 TRI emissions (1,320,000 + 1,230,000 = 2,550,000), which results in 4,340,000/2,550,000 = 1.7.
DRAFT DO NOT CITE OR QUOTE

 Page 26

For point source emissions, based on the Emissions Inventory System (EIS) Identifier and EIS 

Unit Identifier from NEI, it is possible to identify the number of unique facilities (154) and 

degreasing units (machines; 180) reporting TCE emissions in 2008 (or about 1.2 degreasing 

units/facility). These 154 facilities would be considered large industrial facilities rather than 

small commercial operations. 

Assuming each reported nonpoint source represents a unique facility, and by applying the 

estimate of 1.2 degreasing units per facility to nonpoint sources, the number of facilities 

corresponding to the nonpoint sources in Table 3-2 can be approximated to be 1,483 (i.e., 

1,779 divided by 1.2 degreasing unit per facility), making the total number of degreasing 

facilities 1,637 (i.e., 154 unique, large Industrial facilities, plus the 1,483 small 

industrial/commercial facilities).

Based on the NAICS codes listed in Appendix C and information reported in the 2010 TRI, EPA 

identified relevant releases of TCE from solvent cleaning/degreasing operations (see Table 3-4).

Table 3-4. Relevant TCE Releases from Solvent Cleaning in 2010.

Release Type Total Annual Release

(lbs/Yr) 

Percentage of Air-Emitting Facilities also 

Reporting this Type of Release (Percent)

Fugitive air emissions 780,000 100

Stack air emissions 750,000 100

Surface water releases 70 5.5

Release to RCRA Subtitle C landfill 1,711 1.1

Release to other landfill 8,308 2.2

Source: US EPA (2011e). 

By examining the SCC from the NEI, the cleaning machine type could be identified (see Table 3-

5). Large industrial facilities are not typically classified as nonpoint sources (US EPA, 2008b). 

Based on this, in-line degreasing units also are not classified as nonpoint sources. For this 

assessment, EPA classified nonpoint sources as either batch vapor or batch cold units. Table 3-

5 shows a total of 129 (i.e., 116 batch vapor plus 13 batch cold units) of this 

cleaning/degreasing machine type. Thus, EPA determined that approximately 90 percent (i.e., 

116 out of 129) of the 1,779 nonpoint sources would be expected to be batch vapor degreasing 

units, while 10 percent would be expected to be batch cold degreasing units. General 

degreasing units were ignored in this calculation because they cannot be categorized; their type 

is unknown.
DRAFT DO NOT CITE OR QUOTE

 Page 27

Table 3-5. Breakdown of Degreasing Cleaning Machine Type for Point Source TCE Emissions 

Cleaning Machine Type Number of 

Units

Percentage of 

Units

Total Annual Air Emissions

(lbs/Yr)

a 

Open top vapor degreasing (batch vapor) 116 64 890,000

Conveyorized vapor degreasing (in-line) 11 6 120,000

Cold solvent cleaning (batch cold) 13 7 140,000

General degreasing units (unknown) 40 22 330,000

a

The total is equal to 1,480,000 lbs as reported for point sources in Table 3-2.

Source: US EPA (2008c). 

All the information described above and presented in Tables 3-2 through 3-5 was used to 

develop an estimate of TCE releases to air from small commercial degreasing operations (Table 

3-6). An explanation of how these estimates were derived follows:

Air Releases

As indicated earlier, TCE air emissions from degreasing were estimated to be 1.7 times the 2010

TRI reported value. Also, based on the 2008 NEI, point sources (large industrial facilities) 

accounted for 34 percent of all air releases, while nonpoint sources (small industrial/

commercial facilities) accounted for a higher number, 66 percent. Thus, for small industrial/

commercial facilities, the “Annual Release” was calculated as follows: 1.7 × 0.66 × “Total 2010

TRI TCE Air Releases”; or 780,000 + 750,000 = 1,530,000. Thus, the final estimate for small 

commercial degreasing facilities emissions to air is: 

1.7 × 0.66 × 1,530,000 = 1,720,000 lbs 

All Other Releases

The percentage values from Table 3-4 were applied to the number of facilities (1,483 small 

industrial/commercial facilities) to develop estimates for TCE release to other environmental 

media as presented in Table 3-66. 

 6 Thus, as an example, the value for “Release per Facility” in Table 3-6 for releases to surface water was calculated 

as follows: “Annual release” (3,426 lbs) divided by the product of “Number of Facilities” (1,483 small commercial 

degreaser operations) x “Percentage of Air-Emitting Facilities Expected to also have this Type of Release” (0.055) = 

3,426/82 = 42 lbs released to surface water per facility.
DRAFT DO NOT CITE OR QUOTE

 Page 28

Table 3-6. Estimate of 2010 TCE Releases for Small Industrial/Commercial Facilities (n = 1,483).

Media of Release Annual Release

(Lbs/Yr) 

Release per Facility

(Lbs/Yr) 

Percentage of Air-Emitting 

Facilities Expected to also have 

this Type of Release

(Percent) 

Air 1,720,000 1,160 100

Surface water 3,426 42 5.5

RCRA Subtitle C landfill 150,000 8,308 1.2

Other landfill 55,823 1,711 2.2

POTWs 245 5 3.3

To estimate worker exposure in small degreaser operations using environmental release data 

required some additional assumptions about working operations in small commercial 

degreasing operation. For the purposes of this assessment, small industrial / commercial 

degreasing processes are expected to operate 260 days per year for 2 hours per day (US EPA, 

2001a). Thus, combining the information from environmental releases and assumptions for 

operations, the potential operating emission factors (amount of TCE released) were calculated 

as follows:

“Annual Air Release per Facility” × “1 / Number of operating days per year” × “1 / 

Operating hours per day” × “1 hour / 60 minutes”, OR (providing all units and 

conversion values)

1,160 lbs/yr × 454 grams/lb. × 1/260 days × 1 / 2 hours × 1 hour/60 minutes = 16.8 

grams of TCE/minute

Depending on workplace controls (e.g., local exhaust ventilation), average TCE emissions 

escaping into the workplace from Open Top degreasers (i.e., the kind noted above in Table 3-5 

as representative of nonpoint, or small commercial operations) can range from 2.57 to 27.29 

grams of TCE per minute (Wadden et al., 1989). For this assessment, EPA assumed that TCE 

emissions occur only during the hours of operation, and that the calculated and reported 

potential operating emission factors are of the same order of magnitude (see Table 3-7).
DRAFT DO NOT CITE OR QUOTE

 Page 29

Table 3-7. Potential Operating TCE Emission Factors from Degreasing (Calculated and Reported 

Values).

Type of Facility

Calculated Potential Operating TCE 

Emissions Escaping into the Workplace

(g TCE/Minute)

Reported Potential Operating TCE 

Emissions Escaping into the 

Workplace (g TCE/Minute)

Large industrial 27.471 27.29 (Wadden et al., 1989) 

24.9 (US EPA, 2001a) 

Small industrial/commercial 16.73 27.29 (Wadden et al., 1989) 

9.72 (US EPA, 2001a) 

1 Data/calculation not shown; information provided because it represents an 8-hour work shift and so is most 

comparable to the Wadden et al. data.

Calculating Exposures used in this Risk Assessment

This section characterizes exposures for the two scenarios that are the focus of this assessment: 

small industrial/commercial facilities, where TCE is used as a cleaning solvent (degreaser), and 

the hobbyist at home who may use TCE either as a degreaser or in an arts and crafts use 

scenario. For these scenarios, EPA also provided estimates for individuals who may be in the 

same building as the user, but are not physically near the user or use of the TCE product. These 

individuals are called bystanders or non-users.

Calculating Occupational/Worker Exposures to TCE from Degreasing

The National Occupational Exposure Survey (NOES), conducted by the National Institute for 

Occupational Safety and Health (NIOSH) from 1981 to 1983, estimated that 401,000 workers

employed at 23,225 plant sites were potentially exposed to TCE in the US; about 17 workers 

were estimated per facility (ATSDR, 1997). This estimate is understood to include both workers 

who are and are not (occupational non-users) directly involved with solvent cleaning 

operations. EPA estimated the average number of workers directly involved with solvent 

cleaning operations as five workers per facility (US EPA, 2001a). 

Appendix D presents the rationale and calculations for estimating inhalation exposures for 

workers and bystanders in small commercial/industrial degreasing facilities. Exposure 

estimates were calculated for bystanders (i.e., those non-users, likely all adults, who may be in 

the building/room, but not physically close to the degreasing operation). Typical and worst-case 

values represent the range of room ventilation volumes (i.e., 3,000 cubic feet per minute (min-1

)

and 500 cubic feet per min-1, respectively). Finally, the use of local exhaust ventilation (LEV) is 

important because it offers some control of TCE emissions and exposures. Results are shown in 

Table 3-8. These values were used to determine the range of exposures for the small 

commercial degreaser scenario in the risk assessment. 
DRAFT DO NOT CITE OR QUOTE

 Page 30

Table 3-8. Summary of Potential Workplace TCE Inhalation Exposures: Small Commercial Degreaser. 

Typical Worst-Case Number 

of 

Workers

With 

LEV4

No 

LEV

With 

LEV

No 

LEV

Worker1 Inhalation exposure (8-hour TWA3, ppm) 2 17 6 63 7,415

Occupational 

bystander/non-user2

Inhalation exposure (8-hour TWA, ppm) 1 9 5 55 17,796

1 Workers are directly involved with degreasing operations.

2 Occupational Bystanders have the potential to be exposed to TCE but they are not directly involved with 

degreasing operations

3 TWA = Time Weighted Average

4 LEV = local exhaust ventilation

Consumer Exposures – Degreaser and Arts/Crafts Uses of TCE 

TCE has been used in many different formulations and in many commercial and consumer 

products over the years. In March 2012, 12 consumer products from three manufacturers were 

found in the National Institutes of Health’s (NIH)’ Household Products Database that contained 

TCE. Further research confirmed that six of these products contained TCE (Table 3-9)7. The 

other six products were absent from the former product manufacturer’s website or were 

determined not to contain TCE. Three of the six non-TCE containing products were 

reformulated (i.e., using tetrachloroethylene, hydrotreated light distillate, dipropylene glycol npropyl ether, dipropylene glycol methyl ether acetate, aliphatic petroleum solvent, or acetone 

instead of TCE); the other three products were discontinued. There may be other consumer and 

hobbyist products that contain TCE that EPA did not identify8

. 

The six products highlighted in bold in Table 3-9 are auto products and arts and crafts aerosol 

spray products that may be used at home by hobbyists, as well as in commercial settings. Use 

of these products by hobbyists indoors, at home, may lead to inhalation exposure to users and 

other residents of the home. Dermal exposure to users may also occur, although there is a low 

concern for this exposure due to TCE’s high vapor pressure. Ingestion exposure from the use of 

these products appears to be unlikely given the way they are used (i.e., sprayed onto artwork).

 7 See attached document entitled: “Supplemental Product Information for the TSCA Workplan Chemical Risk 

Assessment of TCE (External Review Draft).pdf” for further details on the results of the Household Products Database 

retrieval and for the Material Safety Data Sheets and other information retrieved from company websites. 8 Though the search was not exhaustive, there were several spot cleaners for fabrics marketed to consumers, but

none contained TCE; lists of ingredients were not available for a few of the spot cleaners.
DRAFT DO NOT CITE OR QUOTE

 Page 31

Table 3-9. TCE Products in Household Products Database Retrieval. 

Product Percent TCE (as of March 2012)

a

Lectra Clean 02018 heavy duty electrical parts 

degreaser

None

Lectra Clean 02120 Lectra Clean II non-chlorinated 

heavy duty electrical parts degreaser

None

Sprayway C-60 063 solvent degreaser >90

Sprayway C-60 064 solvent degreaser >90

Sprayway 073 brake parts cleaner None

Sprayway 201 clear protective coating spray 20-30

Sprayway 205 film cleaner >90

Sprayway 208 toner aide 15-20

Sprayway 209 mirror edge sealant 20-30

Sprayway 669 gravel guard Product not found on manufacturer product list

Sprayway 732 industrial cleanup dry cleaner Product not found on manufacturer product list

TrakAuto Trouble Free Rust Buster Company no longer in business

a

Percent TCE according to Material Safety Data Sheets retrieved from company websites in March, 2012 (See 

attached document titled “Supplemental Product Information for the TSCA Workplan Chemical Risk Assessment of 

TCE (External Review Draft).pdf”).

In the absence of available emissions and monitoring data for use of consumer products 

containing TCE, EPA used a screening level modeling approach to assess consumer exposure. 

Of the six products confirmed (Table 3-9) to contain TCE, two hobbyist products, a clear 

protective coating spray and an aerosol solvent degreaser, were selected for exposure 

modeling. 

The Exposure and Fate Assessment Screening Tool Version 2 (E-FAST2) Consumer Exposure 

Module (CEM)9 was selected for the consumer/hobbyist exposure modeling because it 

generates inhalation exposure estimates for aerosol spray products such as the two TCEcontaining products identified above. E-FAST2/CEM requires fewer inputs than do higher tier 

(more complex) indoor air models. For example, higher tier indoor air models require inputs 

for measured emission values (generally based on chamber studies), which usually are not 

available for the consumer products that are the subject of this exposure assessment. 

The E-FAST2/CEM modeling for TCE included a combination of upper percentile, mean, and 

assumed (hypothetical) input values in the calculation of potential exposures. The resulting 

exposure estimates are characterized as hypothetical exposures. As explained more fully in the 

 9 For further information on the E-FAST/CEM defaults or underlying equations, see the E-FAST documentation 

manual (US EPA, 2007a). 
DRAFT DO NOT CITE OR QUOTE

 Page 32

Supplemental Information,

10,11 these hypothetical exposures are more likely to be high-end 

exposures than they are to be central tendency exposures; thus they represent conservative 

exposure values12. 

OPPT did not locate consumer product survey data for hobbyist use patterns for the two 

hobbyist products, including mass of product used per event, duration of event, and events per 

year, so these values are hypothetical. Specific information and assumptions are provided in

the Supplemental Information (notes 10 and 11); however, the general assumptions were:

• For the consumer degreaser scenario: 1 hour/event, two events/month

• For the consumer clear protective coating spray scenario: 0.5 hour/event, one event per 

week

It was assumed that these exposures represent unique and separate acute exposure events for 

both users and non-users. This was based primarily on the information mentioned in the Hazard 

section below in which a high end estimate for the half-life in humans is 51 hours. This suggests 

that from week to week there would be some residual TCE (or metabolite[s]) left over from the 

previous week, but EPA did not assume that the residual would be substantial or build up.

 

Exposure factors for age groupings, inhalation rates, body weights, and life expectancy are 

derived from the 2011 Exposure Factors Handbook (EFH; US EPA, 2011d) and replace the EFAST2 defaults derived from the 1997 EFH (US EPA, 1997). The E-FAST2/CEM exposure 

estimates are potential dose rates that do not include any assumptions about absorption 

through the lung. Selected modeling results appear in Table 3-10. Details on modeling results 

appear in the attached Supplemental Information (notes 10 and 11). 

Table 3-10. Estimated TCE Potential Acute Dose Rates from Use of Two Hobbyist Products Indoors at 

Residences as Determined by E-FAST.

Age 

(Yrs)

Clear Protective Coating 

Spray User ADRpot

(mg/kg-bw/day)

Clear Protective Coating 

Spray Non-user ADRpot

(mg/kg-bw/day)

Solvent Degreaser 

User ADRpot (mg/kgbw/day)

Solvent Degreaser 

Non-user ADRpot

(mg/kg-bw/day)

<1 NA 0.5 NA 3

1-2 NA 0.4 NA 3

3-5 NA 0.4 NA 2 

6-10 NA 0.3 NA 2 

11-15 NA 0.2 NA 1 

 10 See attached document titled “Supplemental Information on E-FAST2 CEM Outputs (Degreaser Use) TSCA 

Workplan Chemical Risk Assessment of TCE (External Review Draft).pdf”). 11 See attached document titled “Supplemental Information on E-FAST2 CEM Outputs (Clear Protective Coating 

Spray) TSCA Workplan Chemical Risk Assessment of TCE (External Review Draft).pdf” 12 High-end exposures represent values above a mean or median and may include the high end of an exposure 

distribution. A central tendency value represents some measure of the center of a distribution, such as an average 

or mean or median.
DRAFT DO NOT CITE OR QUOTE

 Page 33

16-20 0.5 0.2 3 1 

21-78 0.4 0.1 3 0.8

ADRpot = potential acute dose rate; NA = not applicable

These values were converted to concentrations in air in ppm following the methodology 

presented in Appendix E. Table 3-11 presents the hobbyist exposure values that will be used in 

the risk assessment.

Table 3-11. Estimated TCE Inhalation Calculated Concentration in Air (Over the Course of a Daya) 

from Use of Two Hobbyist Products Indoors at Residences. 

Age

(yrs) 

Clear Protective 

Coating Spray User 

ADRpot (ppm)

Clear Protective Coating 

Spray Non-user ADRpot

(ppm)

Solvent Degreaser 

User ADRpot

(ppm)

Solvent Degreaser 

Non-user ADRpot

(ppm)

<1 NA 0.1 NA 0.8

1-2 NA 0.1 NA 0.8

3-5 NA 0.1 NA 0.8

6-10 NA 0.1 NA 0.8

11-15 NA 0.1 NA 0.8

16-20 0.4 0.1 2 0.8

>21 0.4 0.1 2 0.8

a

See Appendix E for method.

B. HAZARD SUMMARY

In this section, a brief summary of the hazard information on TCE is presented and is followed 

by a discussion of the hazard data that were used in this risk assessment.

EPA identified a number of published hazard and/or risk assessments on TCE that have been 

conducted by numerous governmental bodies, review panels and others. Table 3-12 shows 

some of the major documents reviewed and used in this assessment. 

Table 3-12. Hazard/Risk Assessment Documents Consulted for this Report. 

US Government Reports US NRC Reports International Reports

US EPA IRIS Toxicological Review 

and RfD/RfC summary for TCE (US 

EPA, 2011c) 

Gulf War and health, Vol. 2: Insecticides and 

solvents (IOM, 2003) 

EU Risk Assessment (EC, 

2004) 

OPPT/AEGL for TCE (US EPA, 

2008a) 

Human health risks of TCE: Key scientific issues 

(NAS, 2006) 

Australia (NICNAS, 2000) 

ATSDR Toxicological Profile for 

TCE (ATSDR, 1997) 

Contaminated water supplies at Camp Lejeune: 

Assessing potential health effects (NAS, 2009) 

OECD/SIDS (1996) 
DRAFT DO NOT CITE OR QUOTE

 Page 34

Review of studies of possible toxic effects from 

past environmental contamination at Fort 

Detrick: A letter Report (NAS, 2010) 

AEGL = Acute Exposure Guideline Level; RfC = reference concentration; RfD = reference dose

Toxicokinetics (Absorption, Distribution, Metabolism, and Excretion)

Absorption 

TCE is fat soluble (lipophilic) and easily crosses biological membranes. Though there are 

quantitative differences across species and routes, TCE is readily absorbed into the body 

following oral, dermal, or inhalation exposure. Because of its lipophilicity, TCE can cross the 

placenta and also passes into breast milk.

Absorption following inhalation of TCE is rapid and depends upon exposure concentration, 

duration of exposure, and lung ventilation rate. Mammalian lungs have the capacity to 

metabolize TCE, but uptake and distribution is based largely on the blood:air partition 

coefficient, which ranges between 8.1 and 11.7 in humans and between 13.3 and 25.8 in 

rodents (US EPA, 2011c)

13. 

Although this assessment focuses on inhalation exposure only, it is worth noting that following 

oral ingestion, TCE is rapidly absorbed from the gastrointestinal tract into the systemic 

circulation (i.e., blood). Absorbed TCE is first transported to the liver where it is metabolized 

for eventual elimination (i.e., “first-pass effect”). Also, US EPA (2011c) summarized several 

volunteer studies in which both TCE liquid and vapors were shown to be absorbed in humans

via the dermal route. Following exposures of between 20 and 30 minutes, absorption was 

rapid, with peak TCE levels in expired air occurring within 15 minutes (liquid) and 30 minutes 

(vapor).

Distribution

Regardless of the route of exposure, TCE is widely distributed throughout the body. The major 

determining factor in its distribution is the blood: tissue partition coefficient14. Other 

important factors include age-dependencies (i.e., largely based on anatomical and physiological 

parameters such as metabolic and ventilation rates) and TCE binding to tissues/cellular 

components. Human data and data from animals indicate TCE levels can be found in many 

different tissues including: brain, muscle, heart, kidney, lung, liver, and adipose tissues. Human 

data also document levels of TCE in maternal and fetal blood and in the breast milk of lactating 

women. It is difficult to interpret the available human data given the lack of accurate 

information on source and extent of exposures.

US EPA (2011c) summarized many experiments in animals that quantify TCE levels in various 

tissues in rodents following oral and inhalation exposures, some of which provide key 

 13 For ease in reading, “the IRIS program” will be used often to refer to this reference. 14 This represents the ratio of the concentration of TCE in blood to the concentration of TCE in tissue. When the 

ratio is much less than 1, more TCE would be found in tissue rather than in the circulating blood.
DRAFT DO NOT CITE OR QUOTE

 Page 35

data/parameters for the physiologically-based pharmacokinetic (PBPK) model used to derive 

the EPA’s reference concentration (RfC) and reference dose (RfD)15. 

Metabolism 

The metabolism of TCE has been extensively studied; the resulting metabolites play a key role 

in the toxicity of TCE. Of additional importance are the many TCE metabolites that also are 

known metabolites of other, similar compounds to which people may be exposed (see Table 3-

13). This may be important in determining exposures because people may be co-exposed to 

many of these solvents at the same time (e.g., DCA as disinfection by-products of chlorination 

of drinking water supplies) (Johnson et al., 1998).

 

Table 3-13. Common Metabolites of TCE and Related Compoundsa

 Parent →

Metabolites

↓

Tetrachloroethylene

1,1,2,2,-

Tetrachloroethane TCE

1,1,1-

Trichloroethane

1,2,-

Dichloroethylene

1,1-

Dichloroethane

Oxalic acid X X X 

Chloral X X 

Chloral hydrate X X 

Monochloroacetic acid X X X X X X 

Dichloroacetic acid (DCA) X X X X 

Trichloroacetic acid X X X X 

Trichloroethanol X X X X 

Trichloroethanol-glucuronide X X X X 

a

Adapted from Table 2-1 in US EPA (2011c). 

A comprehensive review of the metabolism of TCE in humans and rodents was provided in the 

IRIS document (US EPA 2011c). Animals and humans extensively metabolize TCE. The two 

major metabolic pathways are oxidative metabolism via the cytochrome P450 (CYP) mixed 

function oxidase system and glutathione (GSH) conjugation, the latter followed by further 

transformations with other enzymes. Both pathways are saturable, and above the saturable 

concentration/dose, TCE is excreted unchanged in expired air. According to US EPA (2011c), 

there was no metabolic saturation achieved in the human studies reviewed. However, in 

animal studies when metabolic saturation was achieved, 43 to 78 percent of TCE was exhaled as

unchanged TCE in rats with a lower amount (from 10 to 18 percent) observed in mice.

 15 The RfC/RfD as defined by the IRIS program (http://www.epa.gov/iris/help_ques.htm#rfd ): “RfD (expressed in 

units of mg of substance/kg body weight-day) is defined as an estimate (with uncertainty spanning perhaps an 

order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be 

without an appreciable risk of deleterious effects during a lifetime. An RfD can be derived from a no-observedadverse-effect level (NOAEL), lowest-observed-adverse-effect level (LOAEL), or benchmark dose, with uncertainty

factors generally applied to reflect limitations of the data used. The inhalation RfC (expressed in units of mg of 

substance/m3 air) is analogous to the oral RfD but provides a continuous inhalation exposure estimate.”
DRAFT DO NOT CITE OR QUOTE

 Page 36

Table 3-14 presents the important metabolites formed following both the CYP (oxidation) and 

GSH (conjugation) pathways. The amount and types of metabolites formed are important for 

understanding the toxicity of TCE in both animals and humans.

Table 3-14. TCE Metabolites Identified by Pathwaya

. 

Oxidative Metabolitesb GSH Conjugation Metabolitesc

Chloral; metabolized to TCOH DCVG; metabolized to DCVC isomers (there are 

different theories as to how the presumed toxic 

metabolite intermediate [DCVT] is formed; see text) TCE oxide; re-arranged to DCAC

TCOH; metabolized to TCOG

TCA; may lead to DCA a

In humans and animals.

b

In vitro data suggest that rodents have a greater capacity to metabolize TCE via this pathway. c

There are sex and species differences in this metabolic pathway (see text).

DCVC = either S-(1,2-dichlorovinyl cysteine) [1,2-DCVC] or S-(2,2-dichlorovinyl cysteine) [2,2-DCVC]; 

DCVG = S-dichlorovinyl-glutathione; DCVT = dichlorovinyl thiol; TCOG = trichloroethanol, glucuronide conjugate; 

TCOH = trichloroethanol

A review of in vitro data suggests that rodents (i.e., especially mice) have greater capacity to 

metabolize TCE via the oxidation pathway (US EPA, 2011c). In addition, although there doesn’t 

appear to be large sex- or age-dependent differences in TCE oxidative metabolism, there may 

be substantial differences in humans based on the existence of CYP isoforms and/or genetic 

polymorphisms.

Normally, conjugation is a process that leads to detoxification; however, this is not the case for 

many halogenated alkanes and alkenes, including TCE. For TCE, the eventual metabolite(s) of 

concern are formed several steps from the initial GSH conjugate formed in the liver, which

ultimately results in toxicity or carcinogenicity in the kidney. The key GSH metabolite is one of 

two cysteine conjugate isomers; either S-(1,2-dichlorovinyl cysteine) [1,2-DCVC] or S-(2,2-

dichlorovinyl cysteine) [2,2-DCVC], which can be further metabolized via N-acetylation to Nacetyl-S-(1,2-dichlrovinyl)-L-cysteine (or the 2,2-dichlorovinyl one)—NAcDCVC. 

There are various theories about how DCVC is toxic to the kidney and, to a lesser extent, the 

liver. One theory states that a β-lyase enzyme catalyzes the breakdown of 1,2-DCVC to 

S-dichlorovinyl thiol (DCVT), an unstable intermediate that rearranges to other metabolites 

(enethiols) that form covalent bonds with cellular nucleophiles and results in toxicity. Another 

theory is that there is a kidney enzyme (L-alpha-hydroxy [L-amino] acid oxidase) that can form 

intermediates and keto acid analogues that decompose to DCVT. In rat kidney homogenates, 

this enzyme appeared to be responsible for up to 35 percent of the GSH pathway. However, 

this enzyme is not found in humans. A third theory suggests involvement of sulfoxidation of 

either the cysteine (DCVC) or mercapturic acid (NAcDCVC) conjugates by flavin-containing

monooxygenase and CYP3A enzymes, respectively.
DRAFT DO NOT CITE OR QUOTE

 Page 37

In contrast to the CYP oxidation pathway, there appear to be sex and species differences in TCE 

metabolism via the GSH pathway (US EPA, 2011c). Animal data show that rates of TCE GSH 

conjugation in male rats/mice are higher than females. According to some in vitro data, the 

rates of DCVG production in liver/kidney cytosol are highest in humans, followed by mice, and 

then rats. In vitro data also suggest that γ-glutamyl transpeptidase (i.e., GGTP, an enzyme 

involved in DCVC production) activity in kidneys seems to be highest in rats, then humans, and

then mice.

Thus, the key in evaluating the TCE metabolism data is to determine the relative roles of CYP 

and GSH pathways. It appears that, in rodents, the oxidation pathway is clearly more dominant 

than the GSH pathway. US EPA (2011c) suggests that the GSH pathway may play a larger role in 

humans than it does in rodents, but there is substantial uncertainty about this given the 

available data. In fact, Jollow et al. (2009), using essentially the same data, suggested that 

rodents have a higher capacity to conjugate TCE with GSH and are thus more susceptible to 

kidney toxicity/cancer compared with humans.

US EPA (2011c) concluded the following regarding the metabolism of TCE:

“In summary, TCE oxidation is likely to be greater quantitatively than conjugation with 

GSH in mice, rats, and humans. Some evidence suggests that the flux through the GSH 

pathway, particularly in humans, may be greater by an order of magnitude or more than 

the <0.1% typically excreted of NAcDCVC in urine...However, these data are not 

consistent with studies in other laboratories using different analytical methods, which 

report 2-5 orders of magnitude lower estimates of GSH conjugation. Because the 

reasons for these differences have not been fully determined, substantial uncertainty 

remains in the degree of GSH conjugation, particularly in humans.” (US EPA, 2011c, p. 3-

51). 

Excretion

As noted earlier, the major routes of excretion are urinary (i.e., predominantly with oxidative 

metabolites such as TCA and TCOH, with minor GSH metabolites), followed by exhalation of 

unchanged TCE; elimination (i.e., as metabolized TCE) via feces and via exhalation are minor 

pathways. Table 3-15 provides elimination half-life values in humans and rodents from 

different conditions for total trichloro compounds (TTC) following TCE exposures. 

Half-lives are useful indicators for bioaccumulation potential. Assuming first-order kinetics, 

>90 percent is eliminated after four half-lives and about 99 percent after seven half-lives (Shen, 

2008). Thus, assuming a half-life of about 51 hours (e.g., the longest value listed in Table 3-15), 

TCE would be mostly cleared by approximately 200 hours (i.e., about eight days) with nearly 

complete clearance by approximately 350 hours (i.e., a little over two weeks).
DRAFT DO NOT CITE OR QUOTE

 Page 38

Table 3-15: Half-Life Data For TCE in Rats and Humansa. 

Elimination 

Route

Rats Humans

Exposure 

Conditions Elimination Half-life Exposure Conditions Elimination Half-life

Exhaled air – – Inhalation: 

100 ppm/4 hoursb 

6-38 ppm/0.5-1 hour

c

1 ppm/6 hoursd

0.04, 0.67, 5.6 hours

 8-44 hours

14-23 hours

Urine Inhalation:

50, 100, and 

200 ppm/

8 hours4

Oral (gavage)

Dose not 

givenf

14.3-15.6 hours 

(females); 

15.5-16.6 hours 

(males) 

“complete” within 

1-2 days

Assumed Inhalation:

Measured various metabolites

for three post-exposure days 

in four exposure groups (no 

concentrations provided)e

Experimental exposures in 

groups of two to five adults 

(no concentrations provided)g 

Inhalation:

Occupational setting, six males 

and six females; males 

exposed to 200 ppm, females 

exposed to 50 ppm (duration 

not reported)h

Males:

TTC (50.7 hours)

Females:

TTC (26-48.8 hours)

TTC (31-50 hours)

Males:

TTC (26.1 hours)

Females:

TTC (50.7 hours)

a

All data taken from information presented in pp. 3-53 to 3-56 in US EPA (2011c). 

b

Sato et al. (1977) . c

Opdam (1989). 

d

Chiu et al. (2007) . e

Ikeda and Imamura (1973) . 

f

Green and Prout (1985); Prout et al. (1985); Dekant et al. (1984) . 

g

Nomiyama and Nomiyama (1971); Ogata et al. (1971); Stewart et al. (1970); Bartonicek (1962) . 

h

Ikeda (1977) . 

Summary of Toxicity Information on TCE

A very brief overview of the TCE hazard database is presented. Based primarily on the IRIS 

Toxicological Review (US EPA, 2011c), the multiple studies identified for evaluation as points of 

departure (PODs)16 for candidate RfCs (i.e., specifically p-cRfCs values derived using PBPK 

modeling instead of an applied dose/concentration) for non-cancer endpoints are specifically 

identified below as they are used in evaluating the hazard for this risk assessment. These 

include three studies for liver toxicity; four studies on immunotoxicity; five studies each for the 

 16 POD represents the derived value from the animal or human study. It can be the actual dose or concentration at 

which an effect was observed or a benchmark dose (BMD) calculated for a pre-defined response rate for that 

effect.
DRAFT DO NOT CITE OR QUOTE

 Page 39

kidney and the nervous system; seven studies for developmental toxicity; and nine studies for 

reproductive toxicity. Because there was some overlap (i.e., one study may be used for several 

endpoints), the total of number of different studies is 29. PODs were identified for each of the 

studies and are based on the identified route of exposure/units. All values were converted to 

concentrations in air by the US EPA (2011c) and are presented in later sections of this report. 

TOXICITY FOLLOWING ACUTE (SHORT-TERM) EXPOSURE

This summary is taken from the Interim Acute Exposure Guideline Level (AEGL) document (US 

EPA, 2008a). AEGLs represent threshold exposure limits to which the general public may be 

exposed under emergency conditions (e.g., an evacuation) for a short time (i.e., acute) period

from 10 minutes to eight hours (i.e., five values for each AEGL level are established at 10 

minutes, 30 minutes, and one, four, and eight hours). The development of these values 

involved a rigorous scientific review of acute toxicity data, first by a Federal Advisory 

Committee and then by a National Academy of Sciences (NAS) panel (see US EPA, 2012b for 

more information). 

In humans, TCE odors can be detected at concentrations of ≥50 ppm, although the Level of 

Distinct Odor Awareness determined by the AEGL program is 337 ppm. Information on the 

toxicity of TCE in humans comes from either volunteer studies or case reports in the medical/

occupational literature. As mentioned previously, in the early part of the 20th century, TCE was 

used as a medical anesthetic. According to the AEGL program, the concentrations applied for 

this particular use ranged from 5,000 to 15,000 ppm for anesthetic use and from 3,500 to 5,000 

ppm for use as an analgesic. 

Volunteer studies have shown that acute exposure to TCE results in central nervous system 

(CNS) effects and irritation in humans. The AEGL document summarizes 14 different human 

volunteer studies conducted between 1969 and 1982. Most of these studies had limitations 

(i.e., no control group, reporting of effects were subjective). However, EPA used two of the 

studies as the basis for the AEGL values reported below. Researchers (Vernon and Ferguson, 

1969; Ferguson and Vernon, 1970; as reported in US EPA, 2008a) exposed eight male 

volunteers to 0, 100, 300, or 1,000 ppm TCE for a two-hour period (via a breathing tube) in two 

separate studies. In both cases, subjects performed six different tests to assess visual-motor 

function. The 1,000 ppm concentration in this study was the highest concentration used in any 

of the 14 volunteer studies. There were clear effects at that concentration in both studies (i.e., 

subjective symptoms such as CNS-depression, dizziness, and lethargy as well as reductions in 

performance of visual perception, steadiness, and a pegboard test17). Some subjects had 

similar effects at the middle concentration (300 ppm), with no such effects observed at the 100 

ppm concentration.

 17 A pegboard test evaluates the ability of the subject to place pegs into holes. It is an indicator of hand eye 

coordination and motor effects.
DRAFT DO NOT CITE OR QUOTE

 Page 40

The AEGL process proposed the values shown in Table 3-16. These values are considered 

interim and not yet final. Only three of the five AEGL values are presented because these 

coincide with the time frames of interest for this risk assessment18. 

Table 3-16. Proposed AEGL Values for TCE (in ppm)a

. 

Classification 30-Minute 

Value

1-Hour 

Value

8-Hour Value Endpoint

AEGL-1 (non-disabling 

effects)

180 130 77 CNS (humans)

Marginal CNS effects (not specified 

in original study, according to US 

EPA, 2008a), in 1/8 volunteers 

exposed to 300 ppm for 2 hours

AEGL-2 (disabling 

effects)

620 450 240 CNS (humans)

Light-headedness, dizziness, or 

lethargy in combination with

reduced performance in 

neurobehavioral test in volunteers 

exposed to 1000 ppm for 2 hours

AEGL-3 (lethal) 6,100 3,800 970 Mortality in mice (4600 ppm for 4 

hours)

a

Only the 30-minute, 1-hour, and 8-hour values are presented (representing the three time frames of interest in 

this assessment).

TOXICITY FOLLOWING REPEATED EXPOSURES (INCLUDING CANCER)

There are many studies in animals and humans that report effects in a variety of organ systems 

following exposure to TCE. The summary presented below is very brief and touches on the 

major points for each type of toxicity/cancer. For the purposes of this risk assessment, there 

was no attempt to re-review the majority of the original studies/literature, because a very 

thorough review was most recently published by the US EPA (2011c). A number of key studies 

were reviewed, and other assessment/reviews are referenced where appropriate.

Liver Toxicity (Including Cancer)

Animals and humans exposed to TCE consistently experience liver toxicity. Specific effects 

include the following structural changes: increased liver weight, increase in deoxyribonucleic 

acid (DNA) synthesis (transient), enlarged hepatocytes, enlarged nuclei, and peroxisome 

proliferation. In addition, US EPA concluded that TCE exposure causes liver tumors in mice but 

not rats and there is “...minimal support for association between TCE exposure and liver and 

gallbladder/biliary cancer” (US EPA, 2011c, p. 4-238). 

 18 The clear protective coating spray use assumes a 30-minute exposure, the hobbyist degreaser use assumes one 

hour and the small commercial degreaser, although assuming only two hours of degreaser use, is reported as an 

eight-hour TWA.
DRAFT DO NOT CITE OR QUOTE

 Page 41

Human Data

The US EPA (2011c) reviewed 21 non-cancer and 24 cancer studies in humans that evaluated 

effects on the liver. In the non-cancer studies, 13 were epidemiology studies evaluating the 

role of TCE exposure and liver cirrhosis. The US EPA concluded that the role of TCE exposure on 

liver cirrhosis could not be ruled out.

Five of the 21 human non-cancer reports were occupational studies, four of which were 

specifically TCE degreaser operations (Nagaya et al., 1993; Rasmussen et al., 1993; Xu et al., 

2009; Neghab et al., 1997; as cited in US EPA, 2011c). Overall, the US EPA (2011c) concluded 

that “...these observations are suggestive of liver disorders as associated with potential TCE 

exposure, but whether TCE caused these conditions is not possible to determine given the 

study’s limitations” (US EPA, 2011c, p. 4-221). 

The human cancer studies evaluated included cohort, case-control, and community 

(geographic) studies that evaluated the following cancer types in humans: liver and biliary tract 

cancer, primary liver cancer, and gallbladder and extra-hepatic bile duct cancer (see Table 4-57 

in US EPA, 2011c, for a summary of the 24 studies). Not all studies were used in the US EPA’s

meta-analysis, but the overall conclusions suggested a small, statistically significant summary 

relative risk (RRm) for liver and gallbladder/biliary cancer and TCE exposure. 

Animal Data

The IRIS program devotes Appendix E, of its document, to evaluation of liver toxicity (primarily) 

to animals. The discussion revolves around two main issues: (1) understanding the events 

leading to liver tumors in rodents, and (2) determining the role of the various metabolites in 

that process (termed “co-exposure” by the IRIS program). In terms of the latter, many 

investigators have dosed animals with TCE, as well as with many of its metabolites to determine 

the role and potency of each in terms of target organ toxicity. It appears that the oxidation 

pathway is important for the development of liver toxicity, but the specific role of each 

metabolite (i.e.,that of TCA, DCA, and chloral hydrate), as well as the parent TCE, is unclear. 

For non-cancer effects, many oral/inhalation studies in rats and mice were reviewed; US EPA 

(2011c) concluded that TCE exposure in animal studies does result in increased liver weight, a 

small, transient increase in DNA synthesis, enlarged hepatocytes, increased size of nuclei of 

liver cells, and proliferation of peroxisomes. 

Liver effects (increase in liver/body weight ratio) observed in three animal studies (Kjellstrand

et al., 1983; Woolhiser et al., 2006; Buben and O'Flaherty, 1985; as cited in US EPA, 2011c) were 

chosen by the IRIS program for use in the non-cancer dose-response assessment. NMRI mice 

were exposed to up to nine different TCE concentrations (ranging from 37 to 3,600 ppm) for 

various durations (1, 2, 4, 8, 16, or 24 hours/day) and for different time frames (from 30 to 120 

days) (Kjellstrand et al., 1983; as cited in US EPA, 2011c). The IRIS program calculated a 

benchmark dose, lower confidence limit (BMDL) of 21.6 ppm as a POD for an increase in the 

liver/body weight ratio from this experiment. In Woolhiser et al. (2006) (as cited in US EPA, 

2011c), Sprague-Dawley rats were exposed to TCE via inhalation at concentrations of 0, 100, 
DRAFT DO NOT CITE OR QUOTE

 Page 42

300, or 1,000 ppm for six hours/day, five days/week for four weeks. As with the Kjellstrand et 

al. (1983) data, a BMDL of 25.2 ppm for increased liver/body weight ratio. Finally, the Buben 

and O'Flaherty (1985) data came from an oral study with Swiss-Cox mice (gavage, seven doses 

ranging from 100 to 3,200 mg/kg-bw/day plus control, five days/week for six weeks) and a 

BMDL of 81.5 mg/kg-bw/day was calculated as a POD for increased liver/body weight ratio. 

In the cancer bioassays, B6C3F1 mice (via inhalation and gavage routes) and Swiss mice (via

inhalation) have consistently shown to have increased liver tumors following exposure to TCE. 

Gene marker studies cited by the IRIS program have shown specific mutation frequencies 

associated with tumors following exposure to TCE, TCA, DCA, and chloral hydrate. There is 

some overlap among the groups, but it is not clear what may be the predominant metabolite. 

Studies with rats do not report statistically significant increases in liver tumors.

Summary for Liver Toxicity/Cancer

For both cancer and non-cancer effects on the liver, the role of metabolites is important but not 

well understood. The oxidation pathway seems necessary for TCE-induced liver toxicity. Thus, 

IRIS concluded that multiple TCE metabolites (i.e., and thus pathways) likely contribute to TCEinduced liver tumors. 

Kidney Toxicity (Including Cancer)

Studies in both humans and animals have shown changes in the proximate tubules of the 

kidney following exposure to TCE. As with liver toxicity, TCE metabolites appear to be the 

causative agents that induce renal toxicity, including cancer. DCVC formation appears critical, 

because animals treated with DCVC alone show the same type of kidney damage as those 

treated with TCE. 

Human Data

Eight human studies were reviewed by the IRIS program that evaluated kidney toxicity and over 

35 epidemiological studies examining the possible relationship of kidney cancer and TCE 

exposure in humans. 

All eight non-cancer studies evaluated workers (i.e., for all degreasing operations) exposed to 

some level of TCE, and several followed renal cell carcinoma (RCC; or kidney cancer) or end 

stage renal disease cases. These studies showed increased levels of kidney damage (proximal 

tubules) exposed to “high” levels of TCE. Determining the level of TCE exposure was somewhat 

complicated and was expressed as one or more of the following descriptors: “intensity” × 

duration; job title; “ever exposed;” “high;” and “very high”. 

The more than 30 cancer studies with humans include evaluation of possible association of TCE 

exposure with cancer of the kidney and renal pelvis as well as RCC (the most common type of 

kidney cancer). US EPA (2011c) performed a meta-analysis of 15 cohort and case-control 

studies to evaluate the relationship between kidney cancer and TCE exposure, resulting in a 

summary relative risk (RRm) of 1.27 (95 percent confidence interval [CI] of 1.13 to 1.43). A 
DRAFT DO NOT CITE OR QUOTE

 Page 43

similar metric was determined for the 13 studies with higher TCE exposures (RRm of 1.64; 

95 percent CI of 1.31 to 2.04). 

There appears to be greater susceptibility to TCE exposure/kidney cancer in individuals with an 

active polymorphism in a gene associated with the GST metabolic pathway, which is associated 

with the β-lyase gene region (i.e., which is responsible for converting DCVC to the presumed 

unstable intermediate DCVT). Also, there are some human studies suggesting a role for 

mutations to the tumor suppressor gene, von Hippel Lindau. US EPA (2011c) suggests that this 

tumor suppressor gene is inactivated in certain TCE-induced kidney cancers. 

The US EPA concluded that TCE is “carcinogenic to humans” based on convincing evidence of a 

causal relationship between TCE exposure in humans and kidney cancer. 

Animal Data

In the animal studies, renal toxicity was evident in both rats and mice following either 

inhalation or gavage exposures. The toxicity includes damage to the renal tubules (e.g., both 

cytomegaly and karyomegaly). Under chronic gavage exposure scenarios, rodents exhibit 

almost 100 percent kidney toxicity induction. Under inhalation exposure scenarios, male rats 

are more susceptible than female rats or mice to kidney toxicity. As noted earlier, this toxicity 

is likely caused by DCVC formation, with possible roles for TCOH and TCA. Kidney effects 

observed in five animal studies were chosen by the IRIS program for use in the non-cancer 

dose-response assessment: three studies for histological changes in the kidney (Maltoni and 

Cotti, 1986; (NCI, 1976; NTP, 1988; as cited in US EPA, 2011c) and two studies for increases in 

the kidney/body weight ratio (Kjellstrand et al., 1983; Woolhiser et al., 2006; as cited in US EPA, 

2011c). 

The three studies that reported histological changes in the kidney of exposed animals included 

one inhalation and two oral exposure studies. The Maltoni and Cotti (1986) study (as cited in 

US EPA, 2011c) exposed Sprague-Dawley rats to TCE via inhalation (0, 100, 300, or 600 ppm) 

seven hours/day, five days/week for 104 weeks (and allowed all rats to continue unexposed 

until they died). A BMDL of 40.2 ppm was derived for renal tubular pathological changes 

(meganucleocytosis). The National Cancer Institute (NCI, 1976; as cited in US EPA, 2011c) 

reported an oral (gavage) 90-week study with B6C3F1 mice (i.e., dosed five days/week for 78 

weeks, the final 12 weeks with no exposure) at doses ranging from 0 to 2,339 mg/kg-bw/day; a 

lowest-observed-adverse-effect level (LOAEL) was identified as the POD for toxic nephrosis. 

The National Toxicology Program (NTP, 1988) study (as cited in US EPA, 2011c) reported toxic 

nephropathy in Marshall rats exposed to TCE via gavage at doses of 0, 500, or 1,000 mg/kgbw/day, five days/week for 104 weeks. The derived POD for this study was a BMDL of 9.45 

mg/kg-bw/day. 

The two studies that reported increases in kidney/body weight ratio that were used to develop 

PODs/p-cRfCs were both inhalation studies and were also used for the observed effects in the 

liver (Kjellstrand et al., 1983; Woolhiser et al., 2006; as cited in US EPA, 2011c). The PODs 
DRAFT DO NOT CITE OR QUOTE

 Page 44

developed were BMDL values for 34.7 ppm (Kjellstrand et al., 1983) and 15.7 ppm (Woolhiser

et al., 2006). 

Cancer bioassays with TCE in animals (i.e., both gavage and inhalation exposure routes) did not 

show increased kidney tumors in mice, hamsters, or female rats, but did show a slight increase 

in male rats. Kidney tumors in rats are relatively rare (US EPA, 2011c). 

Summary of Kidney Toxicity/Cancer

From a mechanistic standpoint, it is suggested that DCVC (and to a lesser extent other 

metabolites) is responsible for kidney damage and kidney cancer following TCE exposure (US 

EPA, 2011c). There are data that demonstrate that DCVC is delivered to the kidney following 

TCE exposure. Also, the genotoxicity of DCVC (see genotoxicity section below) further suggests 

that a mutagenic mode of action is involved, although cytotoxicity followed by compensatory 

cellular proliferation cannot be ruled out. There are possible roles for both genetic 

polymorphism (GST pathway) and mutations to tumor suppressor genes in the development of 

kidney cancers in humans following exposure to TCE.

Neurotoxicity

Neurotoxicity has been demonstrated in animal studies under both acute and chronic exposure 

conditions, and has been observed in human studies under acute conditions (chamber studies), 

as well as under chronic, occupational exposure conditions. The effects observed include 

alterations in nerve function, cognitive effects, sensory effects, and changes in psychomotor 

function, mood, and sleep behaviors. As already noted, due to these effects on the nervous 

system, TCE was initially synthesized for use as an anesthetic in humans in the early part of the 

20th century. 

Human Data

The available human studies that evaluated neurotoxicity fall into three general categories: 

(1) evaluation of residents exposed to TCE (and sometimes other solvents) near Superfund 

sites; (2) occupationally exposed individuals (generally degreasers and generally studies already 

discussed above under either liver or kidney toxicity); and (3) short-term controlled 

experiments/studies with volunteers. Many different endpoints have been evaluated, and a 

brief review is presented below.

Thirteen studies were reviewed by the IRIS program, which concluded there was evidence of 

changes in trigeminal nerve function/morphology in humans following exposure to TCE. One of 

these studies was used in the dose-response assessment for neurotoxicity (i.e., increased 

latency in the jaw muscle reflex [masseter reflex]) (Ruijten et al., 1991; as cited in US EPA, 

2011c). In that study, human mail printing workers (31 exposed and 28 controls) were 

evaluated for possible health effects from TCE exposure, defined as “cumulative exposure” 

(concentration × time). Using historical monitoring data mean exposures were calculated as 

704 ppm × number of years worked, where the mean number of years was 16. The POD 

derived from the dataset was a LOAEL of 14 ppm (US EPA, 2011c). 
DRAFT DO NOT CITE OR QUOTE

 Page 45

Four studies evaluated effects on auditory function in humans; all reported effects from TCE 

exposure. All five studies that evaluated effects of TCE exposure on vision reported effects, one 

of which was the basis for one of the AEGL values discussed above (Ferguson and Vernon, 1970; 

Vernon and Ferguson, 1969; as reported in US EPA, 2008a). Ten studies evaluated cognitive 

functions such as learning and memory; the US EPA concluded that these studies “...collectively 

suggest cognitive function impairment” (US EPA, 2011c, p. 4-110). 

There were nine human studies that specifically evaluated developmental neurotoxicity and 

exposure to TCE; four looked at birth defects (CNS defects and neural tube defects) and the 

remainder evaluated postnatal effects (delayed newborn reflex, impaired learning and memory, 

aggressive behavior, speech and hearing impairments, encephalopathy, impaired executive 

function, impaired motor function, attention deficits, and autism spectrum disorder). US EPA

concluded that “... (W)hile there are broad developmental neurotoxic effects that have been 

associated with the TCE exposure, there are many limitations in the studies” (US EPA, 2011c, p. 

4-568). 

Animal Data

Dozens of animal studies were reviewed in US EPA (2011c) that evaluated many endpoints 

under a variety of exposure conditions; however, only the following four studies were used in 

the dose-response assessment to evaluate neurotoxicity.

Isaacson et al. (1990) (as cited in US EPA, 2011c) dosed weanling Sprague-Dawley rats via the 

oral route (drinking water) in an experimental protocol for an eight-week period. Animals were 

given no TCE for eight weeks (control group), 47 mg/kg-bw/day TCE for four weeks and then no 

TCE for four weeks (“5.5 mg/kg-bw/day group”), or 47 mg/kg-bw/day TCE for four weeks, no 

TCE for two weeks, and then 24 mg/kg-bw/day TCE for two weeks (“8.5 mg/kg-bw/day group”). 

From this study, a LOAEL of 47 mg/kg-bw/day for demyelination in the hippocampus was 

identified as the POD. 

Male Wistar rats were exposed to TCE via inhalation to concentrations of 0, 50, 100, or 

300 ppm for eight hours/day, five days/week for six weeks (Arito et al., 1994; as cited in US 

EPA, 2011c). Electroencephalogram (EEG) responses were used to measure the number of 

wakeful hours versus sleep hours. A significant decrease in wakefulness was identified as the 

neurological effect; a POD of 14 ppm (i.e., LOAEL, adjusted for continuous exposure) was 

identified.

Gash et al. (2008) (as cited in US EPA, 2011c) evaluated the effects of TCE (i.e., oral gavage 

experiments with F344 male rats at doses of 0 or 1,000 mg/kg-bw/day, five days/week for six 

weeks) on dopamine-containing neurons in the CNS. The POD of 710 mg/kg-bw/day represents 

a LOAEL (adjusted for time) for loss of dopamine containing neurons.

The final animal neurotoxicity study used in the dose-response assessment for this endpoint is 

Kjellstrand et al. (1987) (as cited in US EPA, 2011c). In this study, the effect of TCE on 

regeneration of the sciatic nerve after a crush lesion was evaluated in mice (NMRI strain, males 
DRAFT DO NOT CITE OR QUOTE

 Page 46

only) and rats (Sprague-Dawley, females only). Animals were pre-exposed to TCE (0 or 300 ppm 

in rats and 0, 150, or 300 ppm in mice, both via inhalation and for 24 hours/day) for 20 days, 

the lesion was induced, and exposure continued for an additional four days prior to evaluation. 

The POD for this effect was a LOAEL of 300 ppm (rats) and 150 ppm (mice).

Summary of Neurotoxicity

Like kidney and liver toxicity, neurotoxicity is a well-documented effect in both humans and 

animals following exposure to TCE. The following effects were concluded to be a result of 

exposure to TCE by US EPA (2011c): alterations in trigeminal nerve function (humans); auditory 

effects (humans and animals); alterations in nystagmus (humans and animals); changes in vision 

(humans and animals); changes in cognitive function (humans and animals); changes in 

psychomotor effects (humans and animals); mood disturbance (humans and animals); sleep 

disturbance (animals); and developmental neurotoxicity (primarily animals).

Immunotoxicity (Including Cancer)

Immune-related effects following TCE exposures have been observed in both animal and 

human studies. In general, these effects were associated with inducing enhanced immune 

responses as opposed to immunosuppressive effects. Of concern are the indirect effects of 

immune hypersensitivity (i.e., development of cancer via faulty tumor surveillance by a 

compromised immune system, and atherosclerosis). 

Two of the three key studies used to derive the US EPA’s RfD, one of which was also used to 

derive the RfC, were immunotoxicity studies in mice (Keil et al., 2009; Peden-Adams et al., 

2006); because the latter is a developmental study, it is discussed in the Developmental Toxicity

section below). In all, four animal studies evaluating immunotoxicity were used in the noncancer IRIS dose-response assessment. Also, one of the three cancers for which the US EPA 

(2011c) based its cancer findings was non-Hodgkin’s lymphoma (NHL) (the other two being 

kidney and liver cancer). 

Human Studies

US EPA (2011c) found only limited evidence of immunosuppression, asthma, and allergies in the

three studies reviewed. However, Arif and Shah (2007) did not find an association between 

TCE19 exposure (as measured with passive monitors in NHANES participants over a 48- to 

72-hour period; geometric mean reported levels were 0.03 μg/m3 [95 percent CI of 0.02 to 

0.04]) and asthma in 550 individuals in that study. 

There is evidence for high TCE exposures in the workplace leading to a generalized 

hypersensitivity skin disease. As summarized in US EPA (2011c), a number of studies published 

since 1995—largely from Asian countries reflecting recent industrialization in those areas—

report a skin disorder (not contact dermatitis) that includes systemic effects (hepatitis, lymph 

 19 In their paper, Arif and Shah (2007) use the abbreviation TCE for perchloroethylene and trichloroethylene is 

identified as trichloroethene. In this assessment, the acronym TCE means the trichloroethene results from the Arif 

and Shah (2007) paper. 
DRAFT DO NOT CITE OR QUOTE

 Page 47

nodes, and other organs). These were seen in workers exposed to high levels of TCE in air (from 

~9 to >700 ppm). The US EPA (2011c) performed a meta-analysis of a number of human studies 

evaluating a possible connection between scleroderma i.e., (an autoimmune disease) and TCE 

exposure. Results indicated a significant odds ratio (OR) in men with a lower (not significant) 

increase in women. These results may not reflect a true gender difference in response because 

the incidence of this disease is very low in men (approximately one per 100,000 per yr) and 

somewhat higher in women (approximately one per 10,000 per yr).

Finally, in a study of degreasers, there was an increase in human inflammatory cytokine levels 

following TCE exposure (Iavicoli et al., 2005; as cited in US EPA, 2011c). These findings are 

supported by studies in auto-immune prone mice (described below) in which short exposures 

to TCE result in increased levels of inflammatory cytokines. What does this mean then?

Animal Data

The following is a short description and identification of the PODs for the four immunotoxicity 

studies identified for consideration in the dose-response analysis for immunotoxicity.

Keil et al. (2009) exposed two strains of mice (NZBWF1 mice, genetically prone to develop 

autoimmune disease, and B6C3F1 mice, a standard test strain not genetically prone to develop 

autoimmune disease) to TCE via drinking water for 27 or 30 weeks at concentrations in water of 

0, 1.4, or 14 ppm. A variety of immune system markers were measured. TCE did not affect 

some markers (natural killer cell activity or T- and B-cell proliferation) in either strain. However, 

other findings showed an increase in renal pathology scores (low concentration only; not 

observed at the high concentration), a significant decrease in thymus weight concentrations 

(both concentrations), and increased anti-dsDNA (at several time points, at both 

concentrations) in the B6C3F1 strain. Two PODs were identified in this study, both at the same 

level (LOAEL of 0.35 mg/kg-bw/day for two different effects: decreased thymus weight and an 

increase in anti-dsDNA). 

In an inhalation study, Kaneko et al. (2000) (as cited in US EPA, 2011c) exposed auto-immune 

prone mice to TCE at concentrations of 0, 500, 1,000, or 2,000 ppm for four hours/day, six

days/week, for eight weeks. There were changes in organs associated with immune response 

(liver inflammation, splenomegaly, and hyperplasia of lymphatic follicles); a LOAEL of 70 ppm 

was used as the POD for these effects.

There were two studies that evaluated immunosuppression in rodents. In Sanders et al. (1982) 

(as cited in US EPA, 2011c), male and female CD-1 mice were given TCE in drinking water 

concentrations of 0, 0.1, 1.0, 2.5, or 5.0 mg/mL for four or six months. Immunity was 

suppressed in females only; a POD of 18 mg/kg-bw/day was identified as a LOAEL for inhibition 

of cell-mediated immunity and bone marrow stem cell activity. Another study that has already 

been discussed for evaluating both liver and kidney effects (Woolhiser et al., 2006; as cited in 

US EPA, 2011c) also reported immunosuppressive effects (decreased plaque-forming cell [PFC]

assay response) in rats exposed to TCE via inhalation for four weeks. In that study, a BMDL of 

24.9 ppm was identified as a POD for this immunosuppressive effect.
DRAFT DO NOT CITE OR QUOTE

 Page 48

Summary of Immunotoxicity

US EPA (2011c) concludes that “...the human and animal studies of TCE and immune-related 

effects provide strong evidence for a role of TCE in autoimmune disease and in a specific type of 

generalized hypersensitivity syndrome, while there are less data pertaining to 

immunosuppressive effects” (US EPA, 2011c, p. 4-627). 

Reproductive Toxicity

Available human and animal data suggest possible reproductive effects in males, but not in 

females following exposure to TCE. Nine reproductive studies were used by the IRIS program in 

their dose-response assessment for this endpoint, including one human study. 

Human Studies

Twelve human studies were evaluated; and most looked at potential effects in both males and 

females. One of the 12 studies was carried forward in US EPA (2011c) for the dose-response 

assessment. In that study (Chia et al., 1996; as cited in US EPA, 2011c), a cohort of 85 workers 

in an electronics factory was selected, and 12/85 were monitored to assess exposure. The 

mean TCE exposure (via inhalation) after an eight-hour shift of these 12 workers was 29.6 ppm 

(range of nine to 131 ppm). There were no controls in the study. Males experienced decreased 

normal sperm morphology and other sperm effects (hyperzoospermia); a BMDL of 1.4 ppm was 

identified as the POD for these effects.

Overall, US EPA concluded that the TCE studies in humans showed a decreased incidence of 

fecundability (time-to-pregnancy) and menstrual cycle disturbances in women and the 

following effects in males: altered sperm morphology, hyperzoospermia, altered endocrine 

function, decreased sexual drive and function, and altered fertility.

Animal Data

Seven inhalation (all with males only) and eleven oral (both males and females evaluated) 

studies were evaluated to assessed reproductive effects in animal studies. Eight of these 

studies were carried into the dose-response evaluation and are briefly described below. 

Overall, the data support findings seen in humans in that females appear to be less affected 

than males.

There were five inhalation animal studies that evaluated reproductive toxicity and were used in 

the IRIS dose-response assessment; all of these studies focused on effects on the male. Xu et 

al. (2004) (as cited in US EPA, 2011c) exposed male CD-1 mice to TCE at concentration of 0 or 

1,000 ppm for six hours/day, five days/week for six weeks. Sperm from treated animals 

resulted in decreased in vitro sperm-oocyte binding and in vivo fertilization; a POD of 180 ppm 

(LOAEL) was identified for this effect. In two separate experiments (Kumar et al., 2000; Kumar

et al., 2001; as cited in US EPA, 2011c), male Wistar rats were exposed to TCE via inhalation at 

concentrations of 0 or 376 ppm. Both study protocols reported exposures of four hours/day, 

five days/week, but in the 2000 report, exposures were from two to 10 weeks, followed by an 

unexposed time frame of between two and eight weeks. In the 2001 report, exposures were 
DRAFT DO NOT CITE OR QUOTE

 Page 49

for either 12 or 24 weeks. Effects on sperm and reproductive tract effects (decreased testes 

weight, smaller, necrotic spermatogenic tubules, and other effects) were observed and PODs 

for these two types of effects were derived; LOAELs of 45 ppm. 

Importantly, there was an increase severity in the effects when exposure duration went from 

12 to 24 weeks. The final two inhalation studies evaluated effects on the male reproductive 

tract of CD-1 male mice exposed to 0 or 1,000 ppm TCE for six hours/day, five days/week for 

either 19 days over a four-week period (Forkert et al., 2002; as cited in US EPA, 2011c) or for 

one to four weeks (Kan et al., 2007; as cited in US EPA, 2011c). Sloughing of epididymal 

epithelial cells were observed in treated mice, and increased in severity with duration of 

exposures. A LOAEL of 180 ppm was identified as a POD for this effect.

The three oral animal studies selected for dose-response assessment for reproductive toxicity 

evaluated effects on males (DuTeaux et al., 2004; as cited in US EPA, 2011c), female 

reproductive outcomes (Narotsky et al., 1995; as cited in US EPA, 2011c), and reproductive 

behavior in both genders (NTP, 1986; as cited in US EPA, 2011c). 

DuTeaux et al. (2004) (as cited in US EPA, 2011c) treated two strains of male rats (SpragueDawley or Simonson albino) by TCE exposure via the drinking water (0, 0.2, or 0.4 percent, 

resulting in doses of 0, 143, or 270 mg/kg-bw/day for 14 days). Results showed decreased 

fertilization (as measured by in vitro fertilization of oocytes from untreated female rats) at both 

concentrations in both rats strains, with a LOAEL of 141 mg/kg-bw/day identified as a POD. 

Narotsky et al. (1995) (as cited in US EPA, 2011c) treated F344 rats via gavage during gestation 

(nine days) to TCE at doses of 0, 475, 633, 844, or 1,125 mg/kg-bw/day. The study was a 

prequel to a complicated protocol with other chemicals in a mixture study; however, delayed 

parturition was seen at all dose levels and was used as a POD (LOAEL = 475 mg/kg-bw/day). In 

an NTP (1986) study (as cited in US EPA, 2011c), F344 rats were exposed to TCE via the diet (TCE 

placed in microcapsules and incorporated into feed) at estimated internal doses of 0, 72, 186, 

or 389 mg/kg-bw/day. Male and female animals were treated for one week pre-mating, then 

for 13 weeks, and then pregnant females were continued on treated diet throughout gestation. 

Results showed a decrease in mating and the LOAEL of 389 mg/kg-bw/day was used as the POD 

for consideration in the dose-response assessment.

Summary of Reproductive Toxicity

Overall, the US EPA concluded: “...the human and laboratory animal data together support the 

conclusion that TCE exposure poses a potential hazard to the male reproductive system” (US 

EPA, 2011c, p. 4-629). 

Developmental Toxicity

Because the US EPA RfC is based primarily on a developmental endpoint (I.e., congenital cardiac 

defects or heart malformations), considerable attention has been given to this issue in the 

literature. US EPA (2011c) evaluated many different developmental outcomes in both human 

and animal studies, including prenatal (i.e., death, decreased growth, and congenital 

malformations) and postnatal (i.e., growth, survival, developmental neurotoxicity, 
DRAFT DO NOT CITE OR QUOTE

 Page 50

developmental immunotoxicity, and childhood cancers) effects. There are seven animal studies 

used to develop PODs for eight different endpoints; all briefly described below.

Human Studies

The US EPA evaluated numerous studies—both occupational and geographically-based—in 

humans to examine the possible association of TCE with various developmental outcomes. 

Most of these studies have been mentioned earlier and represent workplace exposures (Finnish 

studies of Taskinen et al., 1989; Taskinen et al., 1994; both as cited in US EPA, 2011c); the 

geographic studies in Arizona, CO (Rocky Mountain Arsenal) and Woburn, MA. Some have 

focused on reproductive/developmental outcomes (ATSDR studies in Endicott, NY and the 

Camp Lejeune studies, the latter of which was the subject of an NAS investigation) (NAS, 2009). 

US EPA (2011c) concluded that there are positive associations between TCE exposures and the 

following developmental effects in humans: spontaneous abortions, miscarriage, pre- and/or 

post-implantation loss, perinatal death, reduction in live births, decreased birth weight, small 

for gestational age, postnatal growth, cardiac defects, eye/ear birth anomalies, oral cleft 

defects, kidney/urinary tract disorders, musculoskeletal birth anomalies, anemia/blood

disorders, and lung/respiratory tract disorders.

Since the publication of the IRIS Toxicological Review in 2011, one recent update for the 

Endicott, NY community was published by the NY State Health Department that evaluated 

maternal exposure to TCE and other VOCs and pregnancy outcome (Forand et al., 2012). The 

study evaluated all births recorded in Endicott, NY from either 1978 to 2002 (to assess low birth 

weight, pre-term and fetal growth) or from 1983 to 2000 (birth defects). The comparison group 

was the rest of NY State except for the city of New York. A large chemical spill occurred in the 

town in 1979, and monitoring of the contaminant plume occurred for years. Residents obtain 

their drinking water from an uncontaminated water source; however, TCE and other VOCs have 

been measured in groundwater, soil, and inside buildings, the latter due largely to vapor 

intrusion. The study authors reported significant adjusted rate ratios (RRs) for the TCEcontaminated area for, among others, the following endpoints: low birth weight (RR of 1.36; 

95 percent CI of 1.07 to 1.73), small for gestational age (RR of 1.23; 95 percent CI of 1.03 to 

1.48), and cardiac defects (RR of 2.15; 95 percent CI of 1.27 to 3.62). 

 

Animal Data

There were five inhalation and 17 oral developmental toxicity studies with TCE in animals 

reviewed in US EPA (2011c); however, only five were considered in the dose-response 

assessment and only one was an inhalation study (Healy et al., 1982; as cited in US EPA, 2011c) 

and the other four were oral studies.

Two developmental studies reported mortality (pre- and postnatal mortalities as resorptions). 

Healy et al. (1982) (as cited in US EPA, 2011c) exposed female Wistar rats to TCE via inhalation 

at concentrations of 0 or 100 ppm for four hours/day, for 13 days (gestation days eight to 21). 

There was an increase in resorptions at the only concentration tested and a LOAEL of 17 ppm 

was identified as a POD. The other study in which a POD was identified for mortality in the 
DRAFT DO NOT CITE OR QUOTE

 Page 51

developing fetus was the Narotsky et al. (1995) study (as cited in US EPA, 2011c) mentioned 

above in the reproductive toxicity section (gavage study with rats treated during gestation); 

resulting in a BMDL of 32.2 mg/kg-bw/day for resorptions as a POD. The Healy et al. (1982) 

study (as cited in US EPA, 2011c) was also used to derive a POD for reduced fetal weight (as a 

LOAEL of 17 ppm).

Johnson et al. (2003) reported data from different experiments over a several-year period in 

which pregnant Sprague-Dawley rats were exposed (via drinking water) to TCE at four different 

concentrations (0, 0.0025 ppm, 0.250 ppm, 1.5 ppm, and 1,100 ppm) for the duration of their 

pregnancies (22 days). The authors concluded that there was a statistically and biologically 

significant increase in the formation of heart defects at the 0.250 ppm dose level at both the 

individual fetus level and the litter level. There was no statistical increase at the 1.5 ppm dose 

level (at either the individual fetus or litter level), but there was an increase at the highest 

concentration (1,100 ppm).20 A BMDL of 0.0207 mg/kg-bw/day as a POD for heart 

malformations was identified (US EPA, 2011c). 

There were two oral studies that evaluated developmental neurotoxicity and were used in the 

dose-response evaluation for developmental toxicity. Fredriksson et al. (1993) (as cited in US 

EPA, 2011c) treated male NMRI mouse pups with TCE via gavage (0, 50, or 290 mg/kg-bw/day) 

for six days (postnatal days [PNDs] 10 to 16) and then measured spontaneous activity in several 

ways on PNDs 17 and 60. Treated animals showed decreased rearing activity at both dose 

levels on PND 60 (but not PND 17), resulting in a LOAEL of 50 mg/kg-bw/day as a POD. In a rat 

study (Taylor et al., 1985; as cited in US EPA, 2011c), pregnant female Sprague-Dawley rats 

were given TCE in their in their drinking water until 21 days post partum at concentrations of 0, 

312, 625, or 1,250 mg/L. Male offspring from treated animals in the mid and high exposure 

groups showed increased exploratory behavior on PNDs 60 and 90, resulting in a derived LOAEL 

of 45 mg/kg-bw/day as a POD. 

Finally, there was a developmental immunotoxicity study that was used as a critical study for 

developing the RfD (for oral exposure). Although not used for the RfC, it is described here 

because it is the only other critical study not otherwise mentioned. Peden-Adams et al. (2006) 

also exposed B6C3F1 mice to TCE via drinking water. Mice were exposed during mating and 

through gestation to TCE levels of 0, 1.4, or 14 ppm in drinking water. After delivery, pups were 

further exposed for either three or eight more weeks at the same concentration levels in 

drinking water. Suppressed PFC response was seen in male pups (after three and eight weeks 

of exposure) and female pups (only at eight weeks) at 1.4 ppm. Delayed hypersensitivity 

response was increased in the females exposed for eight weeks at this concentration. At the 

higher concentration (14 ppm), both of these effects were observed again, but were seen in 

both males and females at both time points (suppressed PFC response) or in both males and 

females only at eight weeks (increase in delayed hypersensitivity response). A LOAEL of 0.37 

 20 The EPA Science Advisory Board (US EPA, 2011a) reviewed these data and suggested that the IRIS program use 

the Johnson et al. (2003) study as one of the critical/principal studies for RfD/RfC derivation.
DRAFT DO NOT CITE OR QUOTE

 Page 52

mg/kg-bw/day served as a POD for the decreased PFC and increased delayed hypersensitivity 

responses (US EPA, 2011c). 

Summary of Developmental Toxicity

The US EPA (2011c) concluded the following regarding developmental toxicity and TCE 

exposure:

“Overall, based on weakly suggestive epidemiologic data and fairly consistent laboratory 

animal data, it can be concluded that TCE exposure poses a potential hazard for prenatal 

losses and decreased growth or birth weight of offspring... Epidemiological data provide 

some support for the possible relationship between maternal TCE exposure and birth 

defects in offspring, particularly cardiac defects” (US EPA, 2011c, p. 4-629). 

Regarding studies of birth defects in animals, the US EPA concluded that there is potential for 

disruption of the development of the eye (from exposure to TCE and its oxidative metabolites) 

(US EPA, 2011c, p. 4-630), and although the cardiac defect studies have some limitations, their 

findings cannot be dismissed and are based on some mechanistic grounds (predominantly 

findings in developmental studies with chick embryo, and concordance in the stages of heart 

formation between mammals and birds) (US EPA, 2011c, p. 4-631). 

Genetic Toxicity

TCE, and many of its metabolites, have been shown to be genotoxic. TCE, however, does not 

appear to be a direct-acting mutagen, but it does affect both DNA and chromosomes. In 

bacterial test systems, TCE does not induce mutations unless there is metabolic activation (i.e., 

the presence of metabolizing enzymes). TCA, an oxidative metabolite of TCE, also does not 

induce mutations in bacterial test systems unless metabolic activation systems are present. 

However, other TCE metabolites (DCA, chloral hydrate, DCVG, and DCVC) all induce mutations 

without metabolic activation. 

US EPA (2011c) evaluated data on TCE and the aforementioned metabolites in a variety of in 

vitro and in vivo test systems. Though it is thought that these metabolites may be responsible 

for TCE genotoxicity, US EPA (2011c) did not draw any conclusions on this matter, largely 

because there were not sufficient genotoxicity data with standard tests for all of the 

metabolites. However, the IRIS program did state that DCVC appears to have “predominantly 

resulted in positive data,” supporting the conclusion that it is genotoxic (particularly in the 

kidney).

Hazard Summary

Table 3-17 provides a list of the 12 inhalation studies from which hazard values will be used in 

this risk assessment. There are at least two studies for each major target organ. Multiple 

species have been evaluated (i.e., humans, mice, rats). Because some of the studies report 

more than one adverse outcome, 17 PODs (and therefore modeled human equivalent

concentrations; explained more fully in the next section) were identified.
DRAFT DO NOT CITE OR QUOTE

 Page 53

Table 3-17. Inhalation Studies Identified In US EPA (2011c) For Use In OPPT TCE Risk Assessment.

Target Organ Species Range of Doses or 

Concentrationsa Duration POD Typeb Effect HEC50

(ppm)

HEC99

(ppm) Reference

Liver Mouse 37-3,600 ppm 30-120 days BMDL = 21.6 ppm Increased liver 

weight/body weight 

ratio

25 9.1 1 

Rat 100-1,000 ppm 28 days BMDL = 25 ppm 53 19 2 

Kidney Rat 100-600 ppm 104 weeks BMDL = 40.2 ppm Pathology changes in

renal tubule

0.28 0.038 3 

Mouse 37-3,600 ppm 30-120 days BMDL = 34.7 ppm Increased kidney 

weight/body weight 

ratio

0.88 0.12 1 

Rat 100-1,000 ppm 28 days BMDL = 15.7 ppm 0.099 0.013 2 

NeurotoxicityHuman Mean exposure of 

CxT

Mean of 16 years LOAEL = 14 ppm Trigeminal nerve 

effects

14 5.3 4

Rat 50-300 ppm 6 weeks LOAEL = 12 ppm Changes in 

wakefulness

13 4.8 5 

Rat 300 ppm 24 days LOAEL = 300 ppm Decreased 

regeneration of sciatic 

nerve

274 93 6 

Mouse 150-300 ppm 24 days LOAEL = 150 ppm 378 120

ImmunotoxicityMouse

(autoimmune 

prone 

strain)

500-2,000 ppm 8 weeks LOAEL = 70 ppm Changes in 

immunoreactive 

organs

97 37 7 

Rat 100-1,000 ppm 28 days BMDL = 24.9 ppm Immunosuppression 29 11 2 

Reproductive toxicityHuman

(male)

Mean exposure = 

29.6 ppm

Measured values after an 

8-hour work shift; mean 

years on job was 5.1

BMDL = 1.4 ppm Sperm effects 1.4 0.5 8 

Mouse 

(male)

1,000 ppm 6 weeks LOAEL = 180 ppm Sperm effects 190 67 9 

Rat (male) 376 ppm 2-10 weeks,

12 weeks, 24 weeks

LOAEL = 45 ppm Sperm effects and 

male reproductive 

tract effects

32 13 10
DRAFT DO NOT CITE OR QUOTE

 Page 54

Table 3-17. Inhalation Studies Identified In US EPA (2011c) For Use In OPPT TCE Risk Assessment.

Target Organ Species Range of Doses or 

Concentrationsa Duration POD Typeb Effect HEC50

(ppm)

HEC99

(ppm) Reference

Mouse 

(male)

1,000 ppm 19 days over 4 weeks, 

1-4 weeks

LOAEL = 180 ppm Effects on epididymis 

epithelium

190 67 11

Developmental 

toxicity

Rat

(female)

100 ppm 13 days (during 

gestation)

LOAEL =17 ppm Increased resorptions 16 6.2 12

Rat

(female)

100 ppm 13 days (during 

gestation)

LOAEL = 17 ppm Decreased fetal 

weight

16 6.2 12

a

Controls (or zero dose/concentration) are not presented, so a sense of the lowest and highest values is understood.

b

POD type can be NOAEL, LOAEL, or BMDL; the IRIS program adjusted all values to continuous exposure. 

Reference List (all as cited in US EPA, 2011c): 

1 = Kjellstrand et al. (1983) 

2 = Woolhiser et al. (2006) 

3 = Maltoni and Cotti (1986)

4 = Ruijten et al. (1991) 

5 = Arito et al. (1994) 

6 = Kjellstrand et al. (1987) 

7 = Kaneko et al. (2000) 

8 = Chia et al. (1996) 

9 = Xu et al. (2004) 

10 = Kumar et al. (2000); Kumar et al. (2001) 

11 = Forkert et al. (2002); Kan et al. (2007) 

12 = Healy et al. (1982) 
DRAFT DO NOT CITE OR QUOTE

 Page 55

Hazard Data to be used in Risk Assessment for TCE

The US EPA’s IRIS program evaluates hazard and dose-response information on effects that may 

result from exposure to environmental contaminants. The results of their analyses are hazard 

values; an RfD or RfC to be used for non-cancer risk estimates and an oral slope factor or 

inhalation unit risk (IUR) factor for cancer risk estimates. In this risk assessment, the inhalation 

route of exposure was evaluated; therefore, cancer risks were assessed based on the IUR, and 

non-cancer risks were assessed based on the identified PODs from studies used to develop the 

US EPA’s RfC. 

Rather than use a single, point estimate value for the non-cancer risk assessment, a range of 

risk estimates are presented, thereby providing a range of data. This allows flexibility in 

evaluating or estimating risk based on exposure duration. Given the different exposure 

scenarios considered (both acute and chronic for small commercial degreasers, and just acute 

for the two consumer exposure scenarios), different endpoints were used based on the 

expected exposure durations. For non-cancer effects, both neurotoxicity and developmental 

toxicity could occur following acute (short-term) exposures, whereas other effects (toxicity to 

the liver, kidney, immune system, and the reproductive system) could occur following repeated 

exposure to TCE. Cancer risk estimates were only derived for chronic exposure scenarios. 

The US EPA (2011c) non-cancer hazard PODs were derived using PBPK modeling. This model 

was reviewed by the SAB (US EPA, 2011a) and found to be both useful and sophisticated. The 

PODs for each endpoint to be used in this risk assessment are those for which a human 

equivalent concentration (HEC) was derived using this model developed by IRIS for TCE.

PBPK Modeling of TCE and its Metabolites

Given the complicated metabolic profile of TCE, understanding the relationship between the 

external dose/concentration (i.e., exposure) and internal dose at the target organ of interest is 

critical to quantifying potential risk(s). US EPA (US EPA, 2011c) developed a detailed PBPK 

model for TCE and its metabolites designed to make such predictions of PODs. As part of 

building the model, the IRIS Toxicological Review provides a detailed summary of the history of 

TCE PBPK models that have been built over the years, resulting in an updated model reported in 

both Evans et al. (2009) and Chiu et al. (2009). This model was used to predict 14 different 

dose-metrics as measures of potential TCE toxicity (each dose-metric was developed to 

evaluate a different metabolic pathway/target organ effect based on the dose-response 

analysis and understanding of metabolism) (Table 3-18).
DRAFT DO NOT CITE OR QUOTE

 Page 56

Table 3-18. U.S. EPA IRIS PBPK-Modeled Dose Metrics for TCE Dose-Response Assessment.

Dose-Metric Identifier Explanation of What the Dose-Metric Identifier Represents

ABioactDCVCBW3/4 Amount of DCVC bioactivated in the kidney per unit body weighta

ABioactDCVCKid Amount of DCVC bioactivated in the kidney per unit kidney mass

AMetGSHBBW3/4 Amount of TCE conjugated with GSHb

AMetLiv1BW3/4 Amount of TCE oxidized in liverc

AMetLivOtherBW3/4 Amount of TCE oxidized to metabolites other than TCA or TCOH 

(per unit body weight)

AMetLivOtherLiv Amount of TCE oxidized to metabolites other than TCA or TCOH 

(per unit liver weight)

AMetLngBW3/4 Amount of TCE oxidized in respiratory tract (per unit body weight)

AMetLngResp Amount of TCE oxidized in respiratory tract (per unit respiratory 

tract tissue)

AUCCBld Area under the curve of venous blood concentration of TCEd

AUCCTCOH Area under the curve of blood concentration of TCOH

AUCLivTCA Area under the curve of the liver concentration of TCA

TotMetabBW3/4 Total amount of TCE metabolized (per unit body weight)e

TotOxMetabBW3/4 Total amount of TCE oxidized (per unit body weight)f

TotTCAInBW Total amount of TCA produced a This was the dose-metric used to derive the IUR for kidney cancer and some non-cancer kidney effects.

b This was the dose-metric used for some non-cancer kidney effects. c This was the dose-metric used to derive the IUR for liver cancer and the non-cancer liver effects.

d This was the dose-metric used to derive a reproductive toxicity endpoint (effects on male reproductive outcomes 

from one study; DuTeaux et al., 2004; as cited in US EPA, 2011c). e This was the dose-metric used to derive the cRfC for the immunological effect endpoint, some reproductive 

toxicity endpoints, some developmental toxicity endpoints, and neurotoxicity. It was also used to derive the IUR 

for NHL.

f

This is the dose-metric used to derive the cRfC for the cardiac malformations (developmental) endpoint.

These dose-metrics were converted to daily or weekly average concentrations based on 

simulations lasting 10 weeks for rats/mice and 100 weeks for humans. The predicted values 

were compared across species, compared to in vivo data, and were also subjected to sensitivity 

analyses (all summarized in Section 3.5.6 in US EPA, 2011c). 

The 32 different candidate PODs/HECs that were identified and developed by the IRIS program 

to inform the development of the RfC (primarily) were used to identify the range of hazard 

values that could be used in the current risk assessment. Appendix F contains a detailed table 

that presents all of the values. Table 3-19 provides a list of the values that will be used in this 

risk assessment by endpoint and exposure duration.

The data in Table 3-19 are from the 12 inhalation studies summarized in Appendix F. In this risk 

assessment, the lower-end of the range of hazard values for the “sensitive” human (the 99th

percentile, or HEC99) for each target organ/endpoint was used. These values are bolded in 

Table 3-19. To provide an indication of the variability in the HEC predictions, the range of 
DRAFT DO NOT CITE OR QUOTE

 Page 57

hazard values for the “typical” human (the 50th percentile or HEC50) is also presented. In both 

instances, the terms “low-end” and “high-end” represent the minimum and maximum values 

within the data presented in Table 3-17 for the 12 inhalation studies used herein. Also, the 

third column in the table presents the original POD (i.e., a benchmark dose value or LOAEL) 

prior to the use of the PBPK model to develop the HEC. Importantly, for five of the six target 

organs, the HEC value is reasonably close to the original POD (within a factor of ~2). The 

exception is the kidney, for which the HEC is between 100- and 1000-fold lower than the 

original POD. 

Table 3-19. Range of TCE Candidate POD/HEC Values Derived by US EPA (2011c).

Exposure 

Duration Target Organ

Original 

POD (Prior 

to PBPK 

Model) 

Range (Minimum and Maximum) of HEC values

(All Values in ppm)

By Target 

Organ 

(HEC50)

a

By Target 

Organ 

(HEC99)

b

By Exposure 

Duration 

(HEC50) 

By Exposure 

Duration 

(HEC99) 

Chronic Liver 21.6c – 25c 25-53 9.1-19

0.28 – 190 0.013 - 67 Kidney 40.2c

 – 34.7c 0.28 – 0.88 0.013 – 0.12

Immune system 24.9c – 70d 29 - 97 11-37

Reproductive system 1.4c – 180d 1.4-190 0.5-67

Acute Nervous system 12d – 150d 13-378 4.8-120 16-378 4.8-120

Developing organism 17d 16 6.2 a

HEC50 is the 50th percentile for the continuous concentration that leads to an internal dose in a human equivalent 

to the rodent internal dose POD. 

b

HEC99 is the lower 99th percentile for the continuous concentration that leads to an internal dose in humans 

equivalent to the rodent internal dose POD. c

BMDL, in ppm.

d

LOAEL, in ppm.

Bolded values will be used in the risk assessment

C. HUMAN HEALTH RISK CHARACTERIZATION

Risk Estimation Approach for Acute and Repeated Exposures

For the current risk assessment (i.e., targeted at the use of TCE as a degreaser in a small 

commercial shop and by a consumer and the spray fixative use by a hobbyist), a range of PODs

identified in the US EPA (2011c) for TCE were used for non-cancer endpoints (Table 3-19). The 

IRIS IUR value for cancer also developed by US EPA (2011c) was used for cancer risk estimates 

for the chronic exposure scenarios. 

The exposure scenarios evaluated in this risk assessment are shown in Table 3-20. For the 

worker scenario, non-cancer (acute and chronic) and cancer effects was evaluated. EPA 

assumed that chronic (i.e., working lifetime) conditions apply. It is further assumed that only 
DRAFT DO NOT CITE OR QUOTE

 Page 58

adults (i.e., greater than 16 years old) would be working with the degreaser, and adults (i.e., 

greater than 16 years old) would be in the vicinity as bystanders or non-users in the workplace. 

Because there are both acute and chronic effects following exposure to TCE, endpoints 

encompassing both exposure durations were evaluated for the non-cancer risk assessment. 

The acute endpoints include two that are known to occur following short exposures, including

neurotoxicity and developmental effects. Neurotoxicity is the basis for the identified AEGL and 

also is the basis for the development of occupational guidelines by OSHA and the American 

Conference of Governmental Industrial Hygienists (ACGIH)21. The developmental endpoints of 

concern in the inhalation studies are both increased resorptions and decreased fetal body 

weight. Thus, the populations of concern include both adult male (neurotoxicity) and females 

(neurotoxicity for non-pregnant women and developmental toxicity for women of child-bearing 

age). For chronic exposure concerns, the following target organs/systems have been shown to 

be affected in animals and/or humans following exposure to TCE: liver, kidney, immune system, 

male reproductive system, and cancer (i.e., primarily kidney and liver, but also NHL). 

For the two consumer exposure scenarios, acute exposure/effects were identified as concerns 

because the half-life data for TCE in humans (i.e., range of values for elimination in urine after 

inhalation exposures is ~15 to 51 hours; see Table 3-15 and associated text) suggests that the 

residual TCE/metabolites from week to week for the clear protective coating spray use or for 

the degreaser use over two events/month, would be relatively small. Furthermore, based on 

the hazard endpoint, the population of concern for users of the two consumer products are 

adults (i.e., >16 years old) and include females who are, or could possibly be, pregnant, or are 

of child-bearing age, and both males and females for possible neurotoxicity effects. This also 

means that the populations of concern for the non-user scenario also would have to be women 

of child-bearing age (developmental effects) and all gender/ages (neurotoxicity). 

 

21 The current OSHA PEL is 100 ppm and the ACGIH TLV is 25 ppm for TCE.
DRAFT DO NOT CITE OR QUOTE

 Page 59

Table 3-20. Use Scenarios, Population of Concern, and Health Effects of Concern.

Use Scenario Assumptions For 

Exposure Duration

Population of 

Interest

Hazard Value 

Used Comments

Small commercial 

degreaser

Chronic exposure 

(2 hours per 8-hour 

workday, 5 days/week)

Adults (>16 years 

old), including 

women of childbearing age

Non-cancer:

range of hazard 

values for both 

acute and 

chronic effects

Cancer: IRIS IUR 

Footnotes a, b, c

Bystander to small 

commercial 

degreaser

In the same building, no 

direct exposure

Hobbyist – clear 

protective coating 

spray

Acute exposure 

(0.5 hour/event, one 

event per week)

Adults (> 16 years 

old), including 

women of childbearing age

Non-cancer: 

range of hazard 

values for acute 

effects only

Footnotes a,d 

Bystander to 

hobbyist – clear 

protective coating 

spray

In the same building, no 

direct exposure

All ages Footnotes a,d,e

Hobbyist – 

degreaser use

Acute (1 hour/event, 

two events/month)

Adults (> 16 years 

old), including 

women of childbearing age

Footnotes a,d 

Bystander to 

hobbyist – 

degreaser use

In the same building, no 

direct exposure

All ages Footnotes a,d,e

a

Acute exposure concern is for women of child-bearing age (possible developmental effects) as well as all adults 

for possible neurotoxicity. b

Possible chronic exposure concern due to effects on the liver, kidney, immune system and reproductive (male) 

effects. c

Possible cancer concern from chronic exposure (kidney, liver, NHL).

d

Half-life in humans suggests that there would be minimal carryover exposure from week to week; thus, there is 

no chronic exposure concern.

e

Acute exposure concern is for women of child-bearing age (possible developmental effects) as well as all ages for 

possible neurotoxicity. The neurotoxicity endpoints used were based on adult animals or humans; thus, there is 

some uncertainty about their applicability to younger ages which are included in the consumer bystander 

scenario.

Acute or chronic MOEs (MOEacute or MOEchronic) are used in this assessment to estimate noncancer risks:

 MOE acute or chronic = Hazard value (POD)

 Exposure value

 MOE = margin of exposure (unitless) 

 Hazard value (POD) = point of departure for hazard endpoint (ppm) 
DRAFT DO NOT CITE OR QUOTE

 Page 60

 Exposure value = Exposure (in ppm)

Benchmark MOE values generally range between 10 and 100, depending on the endpoint, the 

population being evaluated, and a number of other factors generally associated with 

uncertainty. Generally, each order of magnitude (i.e., factor of 10) is used to represent some 

uncertainty, such as in extrapolating data from animal studies to humans, from one route of 

exposure to another, for intraspecies differences within the human population, or extrapolation 

based on exposure duration of the study (i.e., from short- to longer-term). In this case, all of 

the PODs were derived using a PBPK model to extrapolate an internal dose in the animal to an 

internal dose in humans (HEC). In addition, the HECs derived were presented both in terms of 

median (HEC50) and 99th percentile (HEC99) predictions. 

If MOEs are less than the benchmark MOE value, there could be a cause for concern, depending 

upon the frequency of such exposures and their magnitude. Thus, in this assessment, because 

the HEC99 is more conservative, a benchmark MOE will be 30 (i.e., based on a factor of 10 for 

intraspecies variability and uncertainty and a factor of 3 for the pharmacodynamic portion of 

the interspecies extrapolation factor; the latter being reduced based on the kinetic modeling 

performed to arrive at an HEC). 

The equation for cancer risk estimation is presented below. Estimates of cancer risks should be 

interpreted as the incremental probability of an individual developing cancer over a lifetime as 

a result of exposure to the potential carcinogen (i.e., incremental or excess individual lifetime 

cancer risk).

 Risk = Human Exposure × IUR 

 Risk = cancer risk (unitless) 

 Human exposure = human exposure estimate (μg/m3) 

 IUR = inhalation unit risk (4.1 × 10-6 per μg/m3

) 22

Risk Estimates for Acute (Short-Term) and Chronic (Repeated) Exposures to TCE

Small Commercial Degreaser Scenario

Table 3-21 presents the results of calculating the non-cancer risk estimate for the small 

commercial degreaser exposed to TCE using the MOE method. Calculations were made for 

different exposure scenarios (i.e., acute and chronic, user and bystander, with and without 

LEV). Six different hazard endpoints were evaluated and for each one the lowest HEC99 was 

used from among the available inhalation studies (see Table 3-17). 

 22 The IUR is 4.1 × 10-6 per μg/m3

; which converts to 4.1 × 10-6 per 0.2 ppb (or 0.0002 ppm), which in turn is 

(4.1 × 10-6)(5,000) [conversion factor to make the unit risk per ppm for ease in calculation) = 2 × 10-2 

per ppm. 
DRAFT DO NOT CITE OR QUOTE

 Page 61

The results show that there are potential non-cancer risk concerns for all endpoints and for 

both acute and chronic exposure conditions when the lowest HEC99 POD is used. Table 3-19 

also presents a higher HEC99 POD value as well as a range of HEC50 values. If these values are 

used, there would be changes in some scenarios (i.e., see summary at the end of this section 

and Table 3-26). Though there is a wide range of POD values for different inhalation endpoints, 

the results suggest an important point about the relative sensitivity of different organ systems. 

For TCE, the most sensitive endpoints appear to be developmental toxicity and toxicity to the 

kidney and immune system; neurotoxicity and reproductive toxicity are estimated to be 10 

times less sensitive, whereas liver toxicity is approximately 100 times less sensitive than those 

endpoints. 

Table 3-22 presents the excess lifetime cancer risk to TCE using the exposure assumptions 

identified previously and the US EPA (2011c) IRIS IUR value for cancer potency for the small 

commercial degreaser/bystander exposure scenarios. The values indicate that all estimated 

cancer risks are above concern levels for either the occupational setting (1 × 10-5) or the general 

population (1 × 10-6). Again, the non-users represent individuals who are nearby where the 

actual work is being done, but are not directly involved in use of product. 
DRAFT DO NOT CITE OR QUOTE

 Page 62

Table 3-21. TCE Noncancer Risk Estimates for Small Commercial Degreasers and Non-users: Using the Lowest 99th Percentile HECs 

(Numbers are MOEs)1,2

Exposure 

Duration

Hazard 

Value2 

Degreaser Worker Degreaser Bystander

With LEV3 Without LEV With LEV Without LEV

Typical Worst-Case Typical Worst-Case Typcial Worst-Case Typical Worst-Case

Exposure

Values4

↓ 

→ 

Endpoint of

Concern

2 ppm 6 ppm 17 ppm 63 ppm 1 ppm 5 ppm 9 ppm 55 ppm

Acute

4.8 Neurotoxicity 2.4 0.8 0.3 0.08 4.8 1.0 0.5 0.09

6.2 Developmental 

Toxicity

3.1 1.0 0.4 0.1 6.2 1.2 0.7 0.1

Chronic

9.1 Liver 4.6 1.5 0.5 0.1 9.1 1.8 1.0 0.2

0.013 Kidney 0.007 0.002 0.0008 0.0002 0.013 0.003 0.001 0.0002

11 Immune System 5.5 1.8 0.6 0.2 11 2.2 1.2 0.2

0.5 Male 

Reproductive 

System

0.3 0.08 0.03 0.008 0.5 0.1 0.06 0.009

1 All values are rounded for simplicity. See text for further explanation about MOEs; all bolded values are considered to represent potential risk concern. 

2 All values are in ppm and represent the lowest HEC99 from an inhalation study for the endpoint listed.

3 LEV = local exhaust ventilation

4 The two numbers represent typical and worst case as 8 hour TWA in ppm. See text under Exposure Assessment for details
DRAFT DO NOT CITE OR QUOTE

 Page 63

Table 3-22. TCE Cancer Risk Estimates for Small Commercial Degreasers and Non-users (Numbers are 

Extra Lifetime Cancer Risk and Bolded Vales Represent Concern

Typical Exposure Valuesa Worst-Case Exposure Valuesa

Degreaser

(Inhalation) 

Degreaser Bystander 

(Inhalation) 

Degreaser

(Inhalation) 

Degreaser Bystander 

(Inhalation) 

With LEV Without 

LEV With LEV Without LEV With LEV Without LEV With LEV Without LEV

Estimated 

exposure levels 

(concentration 

in air in ppm)

2 17 1 9 6 63 5 55

Cancer riskb 1.3 × 10-3 >10-2 6.6 × 10-4 5.9 × 10-3 4.0 × 10-3 >10-2 3.3 × 10-3 >10-2

a

The two numbers represent typical and worst case as 8-hour TWA in ppm. See text under Exposure Assessment

for details.

b

Excess lifetime cancer risk calculated as follows using California Environmental Protection Agency methodology

(CalEPA, 2007): 

Excess Lifetime Risk = (concentration in μg/m3

)(2 hours/24 hours)(5 days/7 days)(50 weeks/52 weeks)(40 years/

70 years)(IUR per μg/m3

). The IUR value from US EPA (2011c) IRIS is 4.1 × 10P

-6P per μg/mP3

P, which converts to 

4.1 × 10P

-6P per 0.2 ppb (or 0.0002 ppm) and in turn is (4.1 × 10P-6P)(5,000) (conversion factor to make the unit risk per 

ppm for ease in calculation) = 2 × 10P

-2 

Pper ppm. Thus, for each exposure value above, the excess lifetime cancer 

risk = (exposure concentration in ppm)(0.033)(2 × 10P

-2P per ppm), where the 0.033 is the product of (2 hours/

24 hours)(5 days/7days) (50 weeks/52 week) (40 years/70 years). A cell’s notation that the excess lifetime cancer 

risk is “>10P

-2P” indicates that the average daily lifetime exposure is larger than the value at which the linear 

approximation ceases to apply (the threshold value is 15.2 ppm, which is (1 × 10P

-2P)(IUR)).

Consumer (Hobbyist Degreaser and Arts and Crafts Clear Protective Coating Spray User)

No chronic risk concerns were identified for these scenarios, based on the following

assumptions: 1) the half-life data in humans, and 2) the duration of 0.5 or one hour per event, 

which occurs once per week for the arts/crafts user two times per month for the consumer 

hobbyist degreaser use. Because only acute exposure scenarios are expected, the two 

endpoints of concern are neurotoxicity (both genders and all ages) and developmental toxicity 

(women of child-bearing age). 

Table 3-23 presents the results of calculating the acute, non-cancer risk estimate for the 

hobbyist degreaser, arts/crafts user, and non-users exposed to TCE using the MOE method and 

neurotoxicity as an endpoint of concern. Results show no risk concern for non-users of the clear 

protective coating spray; all other scenarios show risk concerns (clear protective spray users 

and degreaser user and non-user).

Because the neurotoxicity endpoint of concern used to derive the POD was observed in adult 

animals (change in wakefulness), it is likely that the younger ages in Table 3-23 may respond 

differently (in terms of dose, magnitude or response, or different response). Thus, the MOEs 

presented in Table 3-23 may under-estimate risk to these age groups for this endpoint. 
DRAFT DO NOT CITE OR QUOTE

 Page 64

Table 3-23. TCE Non-cancer Risk Estimates for Use of Two Hobbyist Products Indoors at 

Residences: Neurotoxicity as Endpoint of Concern and Using the Lowest 99th Percentile 

HECs and 24-Hour Average Exposure Concentrations (Numbers are MOEs])1

.

Ages 

of Ind. 

(yrs)

Clear protective 

coating spray

User 

Clear protective 

coating spray nonuser 

Solvent degreaser 

user 

Solvent degreaser 

non-user

4.82 4.8 4.8 4.8

<1 NA3 485 NA 67

1-2 NA 48 NA 6 

3-5 NA 48 NA 6 

6-10 NA 48 NA 6 

11-15 NA 48 NA 6 

16-20 124 48 26 6 

> 21 12 48 2 6 

1

All values are rounded for simplicity. See text for further explanation about acceptable MOEs; all 

bolded values are considered to represent risk concerns. 2

The lowest HEC99 for neurotoxicity from an inhalation study is presented (in ppm). 3

NA = not applicable. Individuals less than 16 years old are assumed to not use either TCE-containing 

product.

4

The exposure value used was 0.4 ppm

5 The exposure value used was 0.1 ppm

6

The exposure value used was 2 ppm

7

The exposure value used was 0.8 ppm

 

Table 3-24 presents the results of calculating the acute, non-cancer risk estimate for the 

hobbyist degreaser, arts/crafts user, and non-users exposed to TCE using the MOE method and 

developmental toxicity as an endpoint of concern. For these scenarios, only women of childbearing age are considered the population of concern. As with the neurotoxicity endpoint, 

results show no risk concern for non-users of the clear protective coating spray; all other 

scenarios show risk concerns (clear protective spray users and degreaser user and non-user.
DRAFT DO NOT CITE OR QUOTE

 Page 65

Table 3-24. TCE Non-cancer Risk Estimates for Use of Two Hobbyist Products Indoors at 

Residences: Developmental Toxicity as Endpoint of Concern Using the Lowest 99th Percentile HECs 

and 24-Hour Average Exposure Concentrations (Numbers are MOEs)1

Population of 

Concern

Clear Protective 

Coating Spray

User

Clear Protective 

Coating Spray Nonuser

Solvent Degreaser 

User

Solvent Degreaser 

Non-user

6.22 6.2 6.2 6.2

Women of childbearing age163 624 25 86

1

All values are rounded for simplicity. See text for further explanation about acceptable MOEs; all bolded 

values are considered to represent risk concerns. 2

The lowest HEC99 for developmental toxicity from an inhalation study is presented (in ppm). 3

The exposure value used was 0.4 ppm

4 The exposure value used was 0.1 ppm

5

The exposure value used was 2 ppm

6

The exposure value used was 0.8 ppm

Summary 

This risk assessment focused on three exposure scenarios for TCE: small commercial degreasing 

operations; consumer use of an aerosol degreaser; and the consumer use of a clear protective 

coating spray in an arts/crafts home setting. Assumptions and estimations on the exposure 

values used have been presented, and the associated uncertainties are described below. Only 

the inhalation route of exposure was considered in this risk assessment.

On the hazard side of the risk equation, OPPT used the literature review and analyses 

performed by the US EPA’s IRIS program to identify 12 inhalation studies considered relevant 

for this particular assessment. Relevancy was primarily based on the route of exposure 

(inhalation). In addition, the TCE database is robust, and there is evidence for a variety of 

adverse effects in animals, and potentially, humans. For inhalation studies, these include effects 

that may be elicited following a single, or short-term exposure (e.g., neurotoxicity and 

developmental toxicity), as well as effects associated with long-term or chronic exposures (e.g., 

immunotoxicity, kidney toxicity, liver toxicity, reproductive effects in males and cancer [kidney, 

liver, and NHL).

This risk assessment, using MOEs for all non-cancer effects and the IRIS IUR for cancer effects, 

identified risks for virtually all scenarios (see Table 3-25). 
DRAFT DO NOT CITE OR QUOTE

 Page 66

Table 3-25. Summary of Overall Risk Assessment for TCE Using the 

Lowest 99th Percentile HECs

Exposure Category Chronic NonCancer Risk?

Acute NonCancer Risk? Cancer Risk?

Small Commercial Degreaser operator 

(user)

YES YES YES

Small Commercial Degreaser operator 

(non-user) 

YES YES YES

Consumer Degreaser (user) Not Applicable YES Not Applicable

Consumer Degreaser (non-user) Not Applicable YES Not Applicable

Consumer Clear Protective Coating Spray 

(user)

Not Applicable YES Not Applicable

Consumer Clear Protective Coating Spray 

(non-user)

Not Applicable NO Not Applicable

The range of estimated exposure values for the worker and consumer scenarios are:

• Small commercial degreaser worker user: from 2-63 ppm (30× difference)

• Small commercial degreaser non-user: from 1-55 ppm (55× difference)

• Consumer degreaser user/non-user: from 0.8 - 2 ppm (~2× difference)

• Consumer clear protective coating spray user/non-user: from 0.1 - 0.4 ppm (4× 

difference) 

The range of hazard values used in the risk assessment (using the lowest HEC99 value in the 

range reported for each major target organ/endpoint) was < 2 for the acute toxicity endpoints 

and almost 1,000 for the chronic toxicity endpoints:

• Acute toxicity: 4.8 – 6.2 ppm (neurotoxicity and developmental toxicity, respectively)

• Chronic toxicity: 0.013 – 9.1 ppm (for kidney and liver toxicity, respectively).

Although there may be some differences in the risk outcome if alternate exposure values were 

available, given the ranges seen (i.e., 55x being the highest), this difference is only slightly 

higher than an order of magnitude. However, there are many different hazard values that could 

also be used and, if used, would likely present a different risk profile for the scenarios that are 

the focus of this assessment. 

Although not presented quantitatively, Table 3-26 presents the results of the risk assessment if 

different HEC values were used. In Table 3-19, in order to provide an indication of the variability 

in the HEC predictions, the range of hazard values for the “typical” human (the 50th percentile 

or HEC50) is also presented. As explained earlier, the terms “low-end” and “high-end” represent 

the minimum and maximum values for the data sets within each major target organ/endpoint. 

Thus, if one were to take three other sets of hazard values (the high-end HEC99, the low-end 
DRAFT DO NOT CITE OR QUOTE

 Page 67

HEC50, and the high-end HEC50), the qualitative results are presented in Table 3-26. Examples 

for each “alternate” hazard value used are presented below: 

• The high-end HEC99 value in the range reported in Table 3-19 for each target 

organ/endpoint (i.e., the 99th percentile represents a “sensitive” human HEC; an 

example value is 19 ppm for the liver [the low-end HEC99 used in Tables 3-20 was 9.1 

ppm]).

• The low-end HEC50 value in the range reported in Table 3-19 for each target 

organ/endpoint (i.e., the 50th percentile represents a “typical” human HEC; an example 

value is 25 ppm for the liver).

• The high-end HEC50 value in the range reported in Table 3-19 for each target 

organ/endpoint (i.e., the 50th percentile represents a “typical” human HEC; an example 

value is 53 ppm for the liver).

Though complicated given all the permutations23, EPA draws some generalizations, including: 

• If evaluated by “typical” or “sensitive” HEC:

o The lower-end HEC50 shows risk for all scenarios/endpoints except for the acute 

clear protective coating spray user and non-user scenarios;

o The higher-end HEC50 and higher-end HEC99 values show no risk concern for 

some scenarios (see Table 3-26) and some endpoints (reproductive toxicity, 

immunotoxicity, and liver toxicity)

• If evaluated by user/non-user scenario:

o If any of the three alternate HEC values listed above is used (except for 

developmental toxicity for the higher-end HEC99 value) for the clear protective 

coating spray user/non-user scenario, there is no risk concern

• If evaluated by acute effect endpoint:

o Risk concern for neurotoxicity does change from “risk” to “no risk” for all 

scenarios except for the worker and consumer degreaser when the lower-end 

HEC50 is used

• If evaluated by chronic effect endpoint:

o There is no change in risk estimates for kidney effects regardless of the HEC 

value used

o Some risk concerns are alleviated depending on the HEC value used for 

reproductive toxicity and immunotoxicity, and, to a lesser extent, liver toxicity

Even with these alternative analyses, the results suggest concern for most scenarios that were 

the focus of this risk assessment except perhaps for the clear protective coating spray in the 

case of non-users. In terms of acute effects, neurotoxicity seems less of a concern than 

 23 Four different hazard values (the lowest HEC99; the primary value used in this risk assessment) plus three other

measures as shown in Table 3-19. Especially for the worker scenario: typical vs. worst-case, with and without LEV, 

user and non-user, two acute endpoints and four chronic endpoints. For the consumer scenarios it is less 

complicated (user and non-user).
DRAFT DO NOT CITE OR QUOTE

 Page 68

developmental toxicity. For the chronic effect endpoints, the kidney hazard value appears to be 

the predominant concern regardless of HEC value chosen (i.e., kidney toxicity seems to be the 

most sensitive chronic endpoint).

In terms of cancer risk assessment, use of the IRIS IUR suggests risk to workers/non-users 

regardless of their potential exposure (i.e., from a low of 1 ppm up to the highest exposure 

estimate of 63 ppm).

Table 3-26. Changes in the Non-Cancer MOEs If Different HECs are Used a

Exposure Category

Change in Chronic Risk With... Change in Acute Risk With...

Higher-End

HEC99

Lower-End

HEC50

Higher-End

HEC50

Higher-End

HEC99

Lower-End 

HEC50

Higher-End 

HEC50

Small Commercial 

Degreaser operator 

(user)

YESb NOb YES - YES NO YES 

Small Commercial 

Degreaser operator 

(non-user) 

YES NO YES YES NO YES 

Consumer Degreaser 

(user)

Not Applicable

(N/A)

YES NO YES 

Consumer Degreaser 

(non-user)

YES NO YES 

Consumer Clear 

Protective Coating Spray 

(user)

YES YES YES 

Consumer Clear 

Protective Coating Spray 

(non-user)

NO NO NO

a

HEC50 represents the typical human HEC; HEC99 represents the sensitive human HEC. the terms “low-end” and 

“high-end” represent the minimum and maximum values for the data presented in Table 3-19. Changes are meant to 

be from the non-cancer MOEs listed in Tables 3-21, 3-23 and 3-24. b In general, a “YES” means a change in one or more risk values from “potential risk” to “no risk”. A “NO” means 

there were no changes from the risk assessment as presented in the main body of this risk assessment.
DRAFT DO NOT CITE OR QUOTE

 Page 69

D. DISCUSSION OF KEY SOURCES OF UNCERTAINTY AND DATA LIMITATIONS

Uncertainties in the Exposure Assessment

The production volume and release information on TCE are estimates, actual TCE production or 

import into the US may differ from these estimates. The 2011 production volume and use data 

reported here (Glauser and Funda, 2012) are recent and considered reliable. It seems clear that 

the vast majority of the TCE used in the US is as an intermediate for the production of a 

refrigerant and the second highest use (in terms of production volume) is as a degreaser. 

Confidence in the remaining uses (i.e., <2 percent of the production volume) is less certain.

For small commercial/industrial degreasing facilities, environmental releases of and workplace 

exposures to TCE were estimated based on several data sources (i.e., NAICS, NEI, and TRI). 

Further, certain assumptions were made in developing these estimates (e.g., effectiveness of 

workplace controls, operating hours, number of workers per facility, the number of small 

commercial/industrial facilities) and various “what-if” scenarios were evaluated to quantify 

“typical” and “worst-case” workplace exposure estimates. Though the uncertainty in these 

assumptions was not extensively evaluated, EPA did compare its release and exposure 

estimates to values in the literature; EPA estimates and literature values were of the same 

order of magnitude. For the purposes of this assessment, “typical” and “worst-case” estimates 

represent exposure values to which workers are likely exposed to during (1) routine working 

conditions, and (2) non-routine (episodic) working conditions, respectively.

Although TCE products intended for use by consumers were found by EPA, there is some 

uncertainty in terms of the nature and extent of the consumer use of TCE in general. 

Furthermore, for the exposure estimations in this risk assessment, the use patterns assumed 

for the two hobbyist products, including mass of product used per event, duration of event, and 

events per year, are hypothetical and are not based on consumer product survey data. 

Therefore, they are likely the source of the greatest uncertainties/data gaps in the exposure 

estimates for the two hobbyist products. However, there is a high degree of confidence in the 

consumer product weight fractions identified for the two hobbyist products evaluated in this 

assessment. Also, there is a medium to high degree of confidence in certain modeling inputs to 

the E-FAST/CEM model, including vapor pressure, molecular weight, room volumes, whole 

house volume, air exchange rate, body weight, and inhalation rate.

Because the E-FAST2/CEM model outputs for exposure to the user and non-user hobbyist 

scenarios are reported in mg/kg-bw/day, it was necessary to convert these values to air 

concentrations (ppm) in order to perform the non-cancer and cancer risk assessment. This 

conversion introduces some uncertainty, but it is not apparent whether it may over- or underestimate exposures. 

Finally, although it was assumed that dermal exposure to the TCE use scenarios was less 

significant compared with the inhalation exposure, EPA expects dermal exposures under some 
DRAFT DO NOT CITE OR QUOTE

 Page 70

conditions. Thus, total exposure may be underestimated because combining dermal and 

inhalation exposures was not done in this risk assessment. This would likely be an issue of 

concern in those exposure scenarios which resulted in a “no-risk” finding. Additional exposure 

via the dermal route could lead to an alternative risk finding. However, use of the lower-end 

HEC99 value for hazard – which represents a sensitive human HEC – does provide a certain 

amount of conservatism that can provide a counterweight to not considering dermal exposure. 

Uncertainties in the Hazard Assessment

The hazard information available on TCE is quite large and includes many studies with both 

humans and animals. Virtually all of the information on TCE hazard for this risk assessment was 

taken from the recent IRIS publication (US EPA, 2011c), in which dozens of pages are devoted to 

discussions of uncertainty throughout the document24. Only the uncertainties germane to the 

specifics of this risk assessment are discussed. 

In developing an RfC or RfD, uncertainty is captured by the use of uncertainty factors (UFs). 

Depending on the POD, UFs of between 10 and 1,000 were used to derive candidate RfD/RfCs. 

In this risk assessment, rather than using a single value (i.e., the RfC) to evaluate inhalation 

exposures for the scenarios identified, it was decided to evaluate the range of data evaluated 

by the IRIS program to derive the RfC. This resulted in the identification of 32 PODs from 27 

studies for use in the non-cancer risk assessment; of which 17 PODs from 12 inhalation studies 

were chosen and from which six hazard values were identified for use in this risk assessment. 

The PODs covered both acute (i.e., neurotoxicity and developmental toxicity) and chronic (i.e., 

liver, kidney, immunotoxicity, reproductive toxicity) endpoints. For the cancer risk assessment, 

the IRIS IUR was used. 

The use of PODs for each major adverse effect, adds a level of confidence to the hazard and risk 

assessment. Because the database for TCE exposures to animals and humans is very robust, 

using specific adverse effects with the appropriate exposure scenarios raises the confidence 

that the risk estimations are relevant for real world exposures. 

As pointed out in the IRIS Toxicological Review (US EPA, 2011c), there is uncertainty associated 

with each POD.

25 In this risk assessment, these individual UFs may be minimized given that EPA

used a maximum value for each endpoint type for the inhalation studies used in our analysis. 

By focusing only on inhalation studies and using lower-end HEC99 values, OPPT has increased 

 24For example, the confidence pertaining to the knowledge of the metabolism of TCE in both animals and humans

will not be discussed here. The PBPK model developed for TCE tries to take this into account. Associated with the 

metabolism issue is the uncertainty of extrapolating from one route of exposure to another; which is one reason 

why OPPT chose to use only the inhalation studies identified by IRIS.

25 UFs = uncertainty factors; UFL = uncertainty in extrapolating from a LOAEL to a NOAEL; UFA = uncertainty in 

extrapolating from animals to humans (“interspecies UF”); UFH = uncertainty to address variation in human 

susceptibility (“intraspecies UF”); UFs = uncertainty in extrapolating data from less-than lifetime studies; 

UFD = uncertainty due to incomplete database.
DRAFT DO NOT CITE OR QUOTE

 Page 71

the likelihood that risks are not under-estimated. Furthermore, use of the lower-end HEC for 

the 99th percentile, although conservative, presents an interesting picture of the likely hazard of 

TCE. As seen below, there is an approximate1000-fold difference between the lowest (0.013 

ppm) and highest (11 ppm) lower-end HEC99: 

• Neurotoxicity = 4.8 ppm 

• Developmental Toxicity = 6.2 ppm

• Liver toxicity = 9.1 ppm 

• Kidney toxicity = 0.013 ppm 

• Immune system =11 ppm 

• Male reproductive toxicity = 0.5 ppm 

By choosing only one of these values (e.g., the lowest), the risk picture would be quite different 

than if another (e.g., the highest) single value is used; there is a 1000-fold difference between 

these two values. However, by presenting all six endpoints in the context of the exposure 

duration of concern, a “full” hazard/risk picture is observed.

As shown in Table 3-26, using different HEC50 and HEC99 values does change the risk picture 

somewhat for some exposure scenarios; primarily eliminating acute effect risk concerns for 

neurotoxicity for consumer users and non-users of both the degreaser and clear protective 

coating spray scenarios. However, regardless of the hazard value used within the bounds 

identified in this assessment, chronic effects concerns continue to exist for the small 

commercial worker for most scenarios, and for all scenarios with kidney toxicity as the endpoint 

of concern.

Uncertainties in the Risk Assessment

The uncertainties discussed above for both the exposure and hazard portions of this risk 

assessment can be discussed in a qualitative manner. First, the range of values in the exposure 

estimations for the worker and consumer scenarios is not large. Including all scenarios for users

and non-users, the range in exposure values for the worker (1 to 63 ppm), and the two 

consumer uses (0.1 to 2 ppm) is between 60 and 20 fold, respectively. The hazard values (i.e., 

using the lowest HEC99 values) ranged from <2 to almost 1,000 for the acute toxicity endpoints 

and for the chronic toxicity endpoints, respectively: 

• Acute toxicity: 4.8 to 6.2 ppm (neurotoxicity and developmental toxicity, respectively)

• Chronic toxicity: 0.013 to 9.1 ppm (for kidney and liver toxicity, respectively).

Thus, understanding that the exposure estimates may be an over- or under-estimation, the 

choice in the hazard value used will likely have a greater influence on the outcome of the risk 

assessment for the uses discussed in this risk assessment.
DRAFT DO NOT CITE OR QUOTE

 Page 72

CONCLUSIONS

TCE is a volatile organic compound that is produced/imported into the US in large quantities 

(i.e., >250 million lbs per year), the majority (~85 percent) of which is used as an intermediate 

chemical for manufacturing refrigerant chemicals. Much of the remainder (i.e., ~15 percent) is 

used as a solvent for metals degreasing. A relatively small percentage (i.e., ~2 percent) is used 

in a variety of applications, including as a solvent for metal degreasing by consumers who work 

on their own cars, bikes, etc. (i.e., DIY hobbyists) and as an ingredient in other hobbyist 

products, including a clear protective coating spray used in the arts/crafts field, a film cleaner, a 

toner aide, and a mirror edge sealant. EPA’s assessment focused on uses of TCE as a degreaser 

both in small commercial settings and consumers, and the consumer use of TCE in a clear 

protective coating spray by individuals in the arts/crafts field. 

The results of this risk assessment indicate possible acute and chronic non-cancer risk concerns 

for occupational (i.e., small commercial settings) degreasers and bystanders (non-users). There 

are also cancer risk concerns for this population:

 

• For the commercial degreaser user and non-user, non-cancer MOEs were less than 30 

(potential risk concern) for acute toxicity effects (i.e., developmental toxicity and 

neurotoxicity) and chronic effects (i.e., liver, kidney, and immune system effects). 

• For the commercial degreaser user and non-user, using the IRIS IUR, the cancer risks 

were all below the benchmark value (i.e., potential risk concern). 

Results of evaluating the two consumer use products suggest acute, non-cancer risks to users of 

both types of products for both developmental toxicity and neurotoxicity. For non-users, EPA’s 

analysis suggests there is potential concern for the degreaser exposure scenario (for both 

developmental toxicity and neurotoxicity); whereas no concern was identified for either effect 

for the clear protective spray non-user scenario:

• For the hobbyist degreaser user and non-user and for the hobbyist clear protective 

spray users, the acute, non-cancer MOEs for developmental toxicity were less than 30 

(potential risk concern).

• The hobbyist clear protective spray non-user scenario resulted in an MOE of greater 

than 30 (no risk concern) for both developmental toxicity and neurotoxicity 

The use of the consumer products is infrequent, and thus, EPA did not conduct either a chronic 

non-cancer or cancer risk assessment for these use scenarios.
DRAFT DO NOT CITE OR QUOTE

 Page 73

References

Arif, A., and Shah, S. (2007). Association between personal exposure to volatile organic compounds and 

asthma among US adult population. Int. Arch. Occup. Environ. Health 80, 711-719. 

Arito, H., Takahashi, M., and Ishikawa, T. (1994). Effect of subchronic inhalation exposure to low-level 

trichloroethylene on heart rate and wakefulness-sleep in freely moving rats. J. Occup. Health 36, 1-8. (as 

cited in US EPA, 2011c).

Arkema (2011). Material Safety Data Sheet. Trichloroethylene. Arkema Inc. http://www.arkemainc.com/msds.cfm. Accessed August 17, 2012. 

Ash, M., and Ash, I. (2009). 1,1,2-Trichloroethylene. In Handbook of Industrial Chemical Additives. 

Second edition, Volume II. Synapse Information Resources.

ATSDR (1997). Toxicological profile for trichloroethylene. Agency for Toxic Substances and Disease 

Registry. http://www.atsdr.cdc.gov/toxprofiles/tp19.pdf. Accessed September 6, 2012. 

ATSDR (1999). Update on the status of the Superfund Substance-specific Applied Research Program. 

Agency for Toxic Substances and Disease Registry. Fed. Regist. 64(10), 2760-2790. 

http://www.gpo.gov/fdsys/pkg/FR-1999-01-15/pdf/99-971.pdf. Accessed August 17, 2012. 

ATSDR (2011). Priority list of hazardous substances. Agency for Toxic Substances and Disease Registry, 

Atlanta, GA. http://www.atsdr.cdc.gov/SPL/. Accessed November 6, 2012. 

Baldwin, P. E., and Maynard, A. D. (1998). A survey of wind speeds in indoor workplaces. Ann. Occup. 

Hyg. 42(5), 303-313. 

Bartonicek, V. (1962). Metabolism and excretion of trichloroethylene after inhalation by human 

subjects. Occup. Environ. Med. 19, 134-141. (as cited in US EPA, 2011c).

Buben, J., and O'Flaherty, E. (1985). Delineation of the role of metabolism in the hepatotoxicity of 

trichloroethylene and perchloroethylene: A dose-effect study. Toxicol. Appl. Pharmacol. 78, 105-122. (as 

cited in US EPA, 2011c).

CalEPA (2007). Occupational health hazard risk assessment: Project for California: Identification of 

chemicals of concern, possible risk assessment methods, and examples of health protective 

occupational air concentrations. California Environmental Protection Agency. 

www.cdph.ca.gov/programs/hesis/Documents/riskreport.pdf. Accessed November 6, 2012. 

Chia, S., Ong, C., Tsakok, M., and Ho, A. (1996). Semen parameters in workers exposed to 

trichloroethylene. Reprod. Toxicol. 10, 295-299. (as cited in US EPA, 2011c).

Chiu, W., Micallef, S., Monster, A., and Bois, F. (2007). Toxicokinetics of inhaled trichloroethylene and 

tetrachloroethylene in humans at 1 ppm: Empirical results and comparisons with previous studies. 

Toxicol. Sci. 95, 23-36. 
DRAFT DO NOT CITE OR QUOTE

 Page 74

Chiu, W. A., Okino, M. S., and Evans, M. V. (2009). Characterizing uncertainty and population variability 

in the toxicokinetics of trichloroethylene and metabolites in mice, rats, and humans using an updated 

database, physiologically based pharmacokinetic (PBPK) model, and Bayesian approach. Toxicol. Appl. 

Pharmacol. 241(1), 36-60. 

Daubert, T. E., and Danner, R. P. (1989). Physical and thermodynamic properties of pure chemicals: Data 

compilation. Design Institute for Physical Property Data, American Institute of Chemical Engineers. 

Hemisphere Pub. Corp., New York.

Dekant, W., Metzler, M., and Henschler, D. (1984). Novel metabolites of trichloroethylene through 

dechlorination reactions in rats, mice and humans. Biochem. Pharmacol. 33, 2021-2027. (as cited in US 

EPA, 2011c).

Dilling, W. L., Tefertiller, N. B., and Kallos, G. J. (1975). Evaporation rates and reactivities of methylene 

chloride, chloroform, 1,1,1-trichloroethane, trichloroethylene, tetrachloroethylene, and other 

chlorinated compounds in dilute aqueous solutions. Environ. Sci. Technol. 9(9), 833-838. 

DuTeaux, S., Berger, T., Hess, R., Sartini, B., and Miller, M. (2004). Male reproductive toxicity of 

trichloroethylene: Sperm protein oxidation and decreased fertilizing ability. Biol. Reprod. 70, 1518-1526. 

(as cited in US EPA, 2011c).

EC (2000). IUCLID Dataset for trichloroethylene. European Chemical Substances Information System 

(ESIS). European Commission, Joint Research Centre. Institute for Health and Consumer Protection 

(IHCP), European Chemicals Bureau. http://esis.jrc.ec.europa.eu/doc/IUCLID/data_sheets/79016.pdf. 

Accessed November 7, 2012. 

EC (2004). European Union Risk Assessment Report: Trichloroethylene. Cas No: 79-01-6. EINECS No: 

201-167-4. 1st Priority List, Vol. 31 European Commission, Joint Research Center. Institute for Health 

and Consumer Protection, European Chemicals Bureau. . EUR 21057 EN.

Evans, M. V., Chiu, W. A., Okino, M. S., and Caldwell, J. C. (2009). Development of an updated PBPK 

model for trichloroethylene and metabolites in mice, and its application to discern the role of oxidative 

metabolism in TCE-induced hepatomegaly. Toxicol. Appl. Pharmacol. 236(3), 329-340. 

Ferguson, R. K., and Vernon, R. J. (1970). Trichloroethylene in combination with CNS drugs. Effects on 

visual-motor tests. Arch. Environ. Health 20, 462-467. (as cited in US EPA, 2008a).

Fogel, M. M., Taddeo, A. R., and Fogel, S. (1986). Biodegradation of chlorinated ethenes by a methaneutilizing mixed culture. Appl. Environ. Microbiol. 51(4), 720-724. 

Forand, S.P., Lewis-Michi, E.L., and Gomez, M.I., (2012). Adverse birth outcomes and maternal exposure 

to trichloroethlene and tetracholorethylene throuh soil vapor intrusion in New York state.

Environmental Health Perspectives 120 (4), 616-621

Forkert, P., Lash, L., Nadeua, V., Tardif, R., and Simmonds, A. (2002). Metabolism and toxicity of 

trichloroethylene in epididymis and testis. Toxicol. Appl. Pharmacol. 182, 244-254. (as cited in US EPA, 

2011c).
DRAFT DO NOT CITE OR QUOTE

 Page 75

Fredriksson, A., Danielsson, B., and Eriksson, P. (1993). Altered behaviour in adult mice orally exposed to 

tri- and tetrachloroethylene as neonates. Toxicol. Lett. 66, 13-19. (as cited in US EPA, 2011c).

Gash, D., Rutland, K., Hudson, N., Sullivan, P., Bing, G., Cass, W., Pandya, J., Liu, M., Choi, D., Hunter, R., 

Gerhardt, G., Smith, C., Slevin, J., and Prince, T. (2008). Trichloroethylene: Parkinsonism and complex 1 

mitochondrial neurotoxicity. Ann. Neurol. 63, 184-192. (as cited in US EPA, 2011c).

Gay, B. W., Hanst, P. L., Bufalini, J. J., and Noonan, R. C. (1976). Atmospheric oxidation of chlorinated 

ethylenes. Environ. Sci. Technol. 10(1), 58-67. 

Glauser, J., and Funda, C. (2012). CEH marketing research report: C2 chlorinated solvents. In Chemical 

Economics Handbook.

Green, T., and Prout, M. (1985). Species differences in response to trichloroethylene: II. 

Biotransformation in rats and mice. Toxicol. Appl. Pharmacol. 79, 401-411. (as cited in US EPA, 2011c).

Healy, T., Poole, T., and Hopper, A. (1982). Rat fetal development and maternal exposure to 

trichloroethylene 100 ppm. Br. J. Anaesth. 54, 337-341. (as cited in US EPA, 2011c).

HSDB (2012). Trichloroethylene. Hazardous Substances Data Bank. National Library of Medicine.

http://toxnet.nlm.nih.gov/. Accessed August 15, 2012. 

Iavicoli, I., Marinaccio, A., and Carelli, G. (2005). Effects of occupational trichloroethylene exposure on 

cytokine levels in workers. J. Occup. Environ. Hyg 47, 453-457. (as cited in US EPA, 2011c).

ICIS (2010). Inorganics news in brief, October 25, 2010. ICIS Chemical Business Magazine. Reed Business 

Information Limited. http://www.icis.com/Articles/2010/10/25/9403851/inorganics-news-in-brief.html. 

Accessed November 6, 2012. 

ICIS (2012). Inorganics news in brief, January 23, 2012. ICIS Chemical Business Magazine. Reed Business 

Information Limited. 

Ikeda, M. (1977). Metabolism of trichloroethylene and tetrachloroethylene in human subjects. Environ. 

Health. Perspect. 21, 239-245. (as cited in US EPA, 2011c).

Ikeda, M., and Imamura, T. (1973). Biological half-life of trichloroethylene and tetrachloroethylene in 

human subjects. Int. Arch. Occup. Environ. Health 31, 209-224. (as cited in US EPA, 2011c).

IOM (2003). Gulf War and health: Volume 2. Insecticides and solvents. Committee on Gulf War and 

health: Literature review of pesticides and solvents. Institute of Medicine of the National Academies, 

National Academy of Sciences. National Academies Press, Washington, DC. 

http://www.nap.edu/catalog.php?record_id=10628. Accessed September 6, 2012. 

Isaacson, L., Spohler, S., and Taylor, D. (1990). Trichloroethylene affects learning and decreases myelin in 

the rat hippocampus. Neurotoxicol. Teratol. 12, 375-381. (as cited in US EPA, 2011c).

Johnson, P. D., Dawson, B. V., and Goldberg, S. J. (1998). A review: Trichloroethylene metabolites: 

Potential cardiac teratogens. Environ. Health. Perspect. 106 (Suppl 4), 995-999.
DRAFT DO NOT CITE OR QUOTE

 Page 76

Johnson, P. D., Goldberg, S. J., Mays, M. Z., and Dawson, B. V. (2003). Threshold of trichloroethylene 

contamination in maternal drinking waters affecting fetal heart development in the rat. Environ. Health. 

Perspect. 111(3), 289-292. (as cited in US EPA, 2011c).

Jollow, D. J., Bruckner, J. V., McMillan, D. C., Fisher, J. W., Hoel, D. G., and Mohr, L. C. (2009). 

Trichloroethylene risk assessment: a review and commentary. Crit. Rev. Toxicol. 39(9), 782-797. 

Kan, F., Forkert, P., and Wade, M. (2007). Trichloroethylene exposure elicits damage in epididymal 

epithelium and spermatozoa in mice. Histol. Histopathol. 22, 977-988. (as cited in US EPA, 2011c).

Kaneko, T., Saegusa, M., Tasaka, K., and Sato, A. (2000). Immunotoxicity of trichloroethylene: A study 

with MRL-lpr/lpr mice. J. Appl. Toxicol. 20, 471-475. (as cited in US EPA, 2011c).

Kao, A. S. (1994). Formation and removal reactions of hazardous air pollutants. J. Air Waste Manage. 

Assoc. 44, 683-696. 

Kao, C. M., and Prosser, J. (1999). Intrinsic bioremediation of trichloroethylene and chlorobenzene: field 

and laboratory studies. J. Hazard. Mater. 69(1), 67-79. 

Keil, D. E., Peden-Adams, M. M., Wallace, S., Ruiz, P., and Gilkeson, G. S. (2009). Assessment of 

trichloroethylene (TCE) exposure in murine strains genetically-prone and non-prone to develop 

autoimmune disease. J. Environ. Sci. Health A Tox Hazard Subst Environ. Eng 44(5), 443-453. (as cited in 

US EPA, 2011c).

Kjellstrand, P., Holmquist, B., Alm, P., Kanje, M., Romare, S., Jonsson, I., Mansson, L., and Bjerkemo, M. 

(1983). Trichloroethylene: Further studies of the effects on body and organ weights and plasma 

butyrylcholinesterase activity in mice. Acta Pharmacol. Toxicol. (Copenh) 53, 375-384. (as cited in US 

EPA, 2011c).

Kjellstrand, P., Kanje, M., and Bjerkemo, M. (1987). Regeneration of the sciatic nerve in mice and rats 

exposed to trichloroethylene. Toxicol. Lett. 38, 187-191. (as cited in US EPA, 2011c).

Kumar, P., Prasad, A., Maji, B., Mani, U., and Dutta, K. (2001). Trichloroethylene induced testicular 

toxicity in rats exposed by inhalation. Biomed. Environ. Sci. 14, 325-332. (as cited in US EPA, 2011c).

Kumar, P., Prasad, A., Saxena, D., Manu, U., Maji, B., and Dutta, K. (2000). Fertility and general 

reproduction studies in trichloroethylene exposed rats. Indian J. Occup. Health 43, 117-126. (as cited in 

US EPA, 2011c).

Maltoni, C and Cotti, G. (1986). Results of long-term carcinogenicity bioassays of tetrachloroethylene on 

Sprague-Dawley rats administered by ingestion. Acta Oncol 7: 11-26 (as cited in US EPA, 2011c). 

McCarty, P. L. (1996). Biotic and abiotic transformations of chlorinated solvents in ground water. In 

Symposium on natural attenuation of chlorinated organics in ground water. EPA/540/R-96/509. p. 5-9. 

US Environmental Protection Agency, Office of Research and Development, Washington, DC.
DRAFT DO NOT CITE OR QUOTE

 Page 77

Mu, D. Y., and Scow, K. M. (1994). Effect of trichloroethylene (TCE) and toluene concentrations on TCE 

and toluene biodegradation and the population density of TCE and toluene degraders in soil. Appl. 

Environ. Microbiol. 60(7), 2661-2665. 

Nagaya, T., Ishikawa, N., Hata, H., and Otobe, T. (1993). Subclinical and reversible hepatic effects of 

occupational exposure to trichloroethylene. Int. Arch. Occup. Environ. Health 64, 561-563. (as cited in US 

EPA, 2011c).

Narotsky, M., Weller, E., Chinchilli, V., and Kavlock, R. (1995). Nonadditive developmental toxicity in 

mixtures of trichloroethylene, di(2-ethylhexyl) phthalate, and heptachlor in a 5 x 5 x 5 design. Toxicol. 

Sci. 27, 203-216. (as cited in US EPA, 2011c).

NAS (2006). Assessing the human health risks of trichloroethylene: Key scientific issues. National 

Academy of Sciences. http://www.nap.edu/openbook.php?record_id=11707&page=R1. Accessed 

September 6, 2012. 

NAS (2009). Contaminated water supplies at Camp Lejeune: Assessing potential health effects. National 

Academy of Sciences. http://www.nap.edu/catalog.php?record_id=12618. Accessed August 31, 2012. 

NAS (2010). Review of studies of possible toxic effects from past environmental contamination at Fort 

Detrick: A letter report. National Academy of Sciences, National Research Council, Washington, DC. 

http://www.nap.edu/catalog.php?record_id=13375. Accessed September 6, 2012. 

NCI (1976). Carcinogenesis bioassay of trichloroethylene (NCI-CG-TR-2). National Cancer Institute, 

National Institutes of Health. US Department of Health, Education, and Welfare, Public Health Service, 

National Institutes of Health, Bethesda, MD. (as cited in US EPA, 2011c).

Neghab, M., Qu, S., Bai, C., Caples, J., and Stacey, N. (1997). Raised concentration of serum bile acids 

following occupational exposure to halogenated solvents, 1,1,2-trichloro-1,2,2-trifluoroethane and 

trichloroethylene. Int. Arch. Occup. Environ. Health 70, 187-194. (as cited in US EPA, 2011c).

NICNAS (2000). Trichloroethylene. Priority existing chemical assessment report. No. 8. National 

Industrial Chemicals Notification and Assessment Scheme, Australia. 

http://www.nicnas.gov.au/publications/car/PEC/PEC8.asp. Accessed September 6, 2012. 

NITE (2012). 1,1,2-Trichloroethene. CAS No. 79-01-6. Biodegradation and bioconcentration of the 

existing chemical substances under the Chemical Substances Control Law. National Institute of 

Technology and Evaluation, Incorporated Administrative Agency. Chemical Risk Information Platform 

(CHRIP). http://www.safe.nite.go.jp/english/sougou/view/ComprehensiveInfoDisplay_en.faces. 

Accessed November 7, 2012. 

Nomiyama, K., and Nomiyama, H. (1971). Metabolism of trichloroethylene in human: Sex difference in 

urinary excretion of trichloroacetic acid and trichloroethanol. Int. Arch. Occup. Environ. Health 28, 37-48. 

(as cited in US EPA, 2011c).

NTP (1986). Trichloroethylene: Reproduction and fertility assessment in F344 rats when administered in 

the feed. (NTP-86-085). National Toxicology Program, National Institute of Environmental Health 

Sciences Research Triangle Park, NC. (as cited in US EPA, 2011c).
DRAFT DO NOT CITE OR QUOTE

 Page 78

NTP (1988). Toxicology and carcinogenesis studies of trichloroethylene (CAS No. 79-01-6) in four strains 

of rats (ACI, August, Marshall, Osborne-Mendel) (gavage studies). National Toxicology Program. US 

Department of Health and Human Services, Public Health Service, National Institutes of Health, Research 

Triangle Park, NC. (as cited in US EPA, 2011c).

O'Neil, M. J., Smith, A., and Heckelman, P. E. (2001). Trichloroethylene. In Merck Index. 13th ed., p. 

1718. Merck & Co., Inc, Whitehouse Station, NJ.

OECD/SIDS (1996). SIDS initial assessment profile. Trichloroethylene (CAS No. 79-01-6). SIAM 4, 20-22 

May 1996. Organisation for Economic Co-operation and Development, Screening Information Data Sets. 

United Kingdom. http://webnet.oecd.org/hpv/ui/handler.axd?id=0bd4d332-9404-4bf6-8c31-

3b7aab3910bf. Accessed November 7, 2012. 

Ogata, M., Takatsuka, Y., and Tomokuni, K. (1971). Excretion of organic chlorine compounds in the urine 

of persons exposed to vapours of trichloroethylene and tetrachloroethylene. Occup. Environ. Med. 28, 

386-391. (as cited in US EPA, 2011c).

Opdam, J. (1989). Intra and interindividual variability in the kinetics of a poorly and highly metabolising 

solvent. Br. J. Ind. Med 46, 831-845. (as cited in US EPA, 2011c).

Peden-Adams, M. M., Eudaly, J. G., Heesemann, L. M., Smythe, J., Miller, J., Gilkeson, G. S., and Keil, D. E. 

(2006). Developmental immunotoxicity of trichloroethylene (TCE): studies in B6C3F1 mice. J. Environ. 

Sci. Health A Tox Hazard Subst Environ. Eng 41(3), 249-271. 

Prout, M., Provan, W., and Green, T. (1985). Species differences in response to trichloroethylene: I 

pharmacokinetics in rats and mice. Toxicol. Appl. Pharmacol. 79, 389-400. (as cited in US EPA, 2011c).

Rasmussen, K., Brogren, C., and Sabroe, S. (1993). Subclinical affection of liver and kidney function and 

solvent exposure. Int. Arch. Occup. Environ. Health 64, 445-448. (as cited in US EPA, 2011c).

Ruijten, M., Verberk, M., and Salle, H. (1991). Nerve function in workers with long term exposure to 

trichloroethene. Br. J. Ind. Med 48, 87-92. (as cited in US EPA, 2011c).

Sanders, V., Tucker, A., White, K., Kauffman, B., Hallett, P., Carchman, R., Borzelleca, J., and Munson, A. 

(1982). Humoral and cell-mediated immune status in mice exposed to trichloroethylene in the drinking 

water. Toxicol. Appl. Pharmacol. 62, 358-368. (as cited in US EPA, 2011c).

Sato, A., Nakajima, T., Fujiwara, Y., and Murayama, N. (1977). A pharmacokinetic model to study the 

excretion of trichloroethylene and its metabolites after an inhalation exposure. Br. J. Ind. Med 34, 56-63. 

(as cited in US EPA, 2011c).

Shen, D. D. (2008). Toxicokinetics. In Cassarett and Doull's toxicology: the basic science of poisons, 

seventh edition. p. 305-327. McGraw Hill Medical Publishers, New York.

SRC (2012). The physical properties database (PHYSPROP). Syracuse Research Corporation, Syracuse, NY. 

http://www.srcinc.com/what-we-do/product.aspx?id=133; accessed on February 24, 2012.
DRAFT DO NOT CITE OR QUOTE

 Page 79

Stewart, R., Dodd, H., Gay, H., and Erley, D. (1970). Experimental human exposure to trichloroethylene. 

Arch. Environ. Health 20, 64-71. (as cited in US EPA, 2011c).

Taskinen, H., Anttila, A., Lindbohm, M., Sallmén, M., and Hemminki, K. (1989). Spontaneous abortions 

and congenital malformations among the wives of men occupationally exposed to organic solvents. 

Scand. J. Work Environ. Health 15, 345-352. (as cited in US EPA, 2011c).

Taskinen, H., Kyyronen, P., and Hemminki, K. (1994). Laboratory work and pregnancy outcome. J. Occup. 

Med. 36, 311-319. (as cited in US EPA, 2011c).

Taylor, D., Lagory, K., Zaccaro, D., Pfohl, R., and Laurie, R. (1985). Effect of trichloroethylene on the 

exploratory and locomotor activity of rats exposed during development. Sci. Total Environ. 47, 415-420. 

(as cited in US EPA, 2011c).

TRI (2012a). Toxic Release Inventory (TRI) program. US Environmental Protection Agency, Washington, 

DC.http://www.epa.gov/tri/index.htm . Accessed April 30, 2012. 

RI (2012b). Toxic Release Inventory (TRI) program. US Environmental Protection Agency, Washington, 

DC..http://www.epa.gov/tri/tridata/data/basicplus/index.html Accessed April 30, 2012.

US Census (2008). North American Industry Classification System. Introduction to NAICS. US Census. 

http://www.census.gov/eos/www/naics/. Accessed November 9, 2012. 

US EPA (1979a). Water-related environmental fate of 129 priority pollutants. Volume II. Halogenated 

aliphatic hydrocarbons, halogenated ethers, monocyclic aromatics, phthalate esters, polycyclic aromatic 

hydrocarbons, nitrosamines, miscellaneous compounds. US Environmental Protection Agency, 

Washington, DC. EPA-440/4-79-029B.

US EPA (1979b). Identification of conventional pollutants, final rule. Fed. Regist. 44, 44501. 

US EPA (1980). Fate of toxic and hazardous materials in the air environment. US Environmental 

Protection Agency, Office of Research and Development, Research Triangle Park, NC. EPA-600/3-80-084.

US EPA (1982). Steam electric power generating point source category. Effluent limitations guidelines, 

pretreatment standards and new source performance standards. Final rule. Fed. Regist. 47, 52290. 

US EPA (1985a). Assessment of trichloroethylene as a potentially toxic air pollutant, proposed rule. Fed. 

Regist. 50, 52422. 

US EPA (1985b). National primary drinking water regulations. Volatile synthetic organic chemicals. Final 

rule. Fed. Regist. 50, 46880. 

US EPA (1986). Clarification and correction of previously published notice on the assessment of 

trichloroethylene as a potentially toxic air pollutant. Clarification and correction of previously published 

FR notice on trichloroethylene. Fed. Regist. 51, 7714. 

US EPA (1987a). National primary drinking water regulations. Synthetic organic chemicals. Monitoring 

for unregulated contaminants. Final rule. Fed. Regist. 52, 25690. 
DRAFT DO NOT CITE OR QUOTE

 Page 80

US EPA (1987b). Organic chemicals and plastics and synthetic fibers category effluent limitations 

guidelines, pretreatment standards, and new source performance standards. Final rule. Fed. Regist. 52, 

42522. 

US EPA (1988). Underground injection control program: hazardous waste disposal injection restrictions. 

Amendments to technical requirements for Class I hazardous waste injection wells. Additional 

monitoring requirements applicable to all Class I wells. Final rule. Fed. Regist. 53, 28118. 

US EPA (1989). Reportable quantity adjustments. Delisting of ammonium thiosulfate. Final rule. Fed. 

Regist. 54, 33426. 

US EPA (1991). Chemical engineering branch manual for the preparation of engineering assessments. US 

Environmental Protection Agency, Office of Toxic Substances, Cincinnati, OH. 

US EPA (1992) TCE removal from contaminated soil and groundwater. EPA Groundwater Issue January 

1992. EPA/540/S-92-002

US EPA (1994a). National emission standards for hazardous air pollutants for source categories. Organic 

hazardous air pollutants from the synthetic organic chemical manufacturing industry and other 

proccesses subject to the negotiated regulation for equipment leaks. Final rule. Fed. Regist. 59, 19402. 

US EPA (1994b). National emission standards for hazardous air pollutants: halogenated solvent cleaning. 

Final rule. Fed. Regist. 59, 61801. 

US EPA (1994c). Notice of opportunity to initiate negotiations for TSCA-Section 4. Enforceable consent 

agreements; solicitation of testing proposals for ATSDR chemicals. US Environmental Protection Agency. 

Fed. Regist. 59(189). http://www.gpo.gov/fdsys/pkg/FR-1994-09-30/html/94-24250.htm. Accessed 

August 17, 2012. 

US EPA (1995). Final water quality guidance for the Great Lakes System. Final rule. Fed. Regist. 60(56), 

15366-15425. 

US EPA (1997). Exposure factors handbook. US Environmental Protection Agency. 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=12464. Accessed November 

US EPA (1998a). Methods for exposure-response analysis for acute inhalation exposure to chemicals 

(external review draft). US Environmental Protection Agency, Washington, DC. EPA/600/R-98/051.

US EPA (1998b). Hazardous waste combustors; revised standards; final rule- Part 1: RCRA-comparable 

fuel exclusion; permit modifications for hazardous waste combustion units; notification of intent to 

comply; waste minimization and pollution prevention criteria for compliance extensions. US 

Environmental Protection Agency. Fed. Regist. 63(118), 33782-33829. 

http://www.gpo.gov/fdsys/pkg/FR-1998-06-19/pdf/98-15843.pdf. Accessed August 17, 2012. 

US EPA (1998c). National emission standards for hazardous air pollutants: wood furniture manufacturing 

operations. Final rule. Fed. Regist. 63(248), 71376-71385. 
DRAFT DO NOT CITE OR QUOTE

 Page 81

US EPA (1998d). National primary drinking water regulations. Consumer confidence reports. Final rule. 

Fed. Regist. 63, 44512-44536. 

US EPA (1999). Category for persistent, bioaccumulative, and toxic new chemical substances. Fed. 

Regist. 64(213), 60194-60204. 

US EPA (2000). Voluntary Children's Chemical Evaluation Program. US Environmental Protection Agency. 

Fed. Regist. 65(248), 81700-81718. http://www.gpo.gov/fdsys/pkg/FR-2000-12-26/pdf/00-32767.pdf. 

Accessed August 17, 2012. 

US EPA (2001a). Draft generic scenario- use of vapor degreasers. US Environmental Protection Agency, 

Office of Pollution Prevention and Toxics, Chemical Engineering Branch. 

US EPA (2001b). National emission standards for pharmaceuticals production. Final rule. Fed. Regist.

66(149), 40121-40137. 

US EPA (2002). National emission standards for hazardous air pollutants for friction materials 

manufacutring facilities. US Environmental Protection Agency. Fed. Regist. 67(202), 64498-64512. 

http://www.gpo.gov/fdsys/pkg/FR-2002-10-18/pdf/02-26309.pdf. Accessed August 17, 2012. 

US EPA (2003). National emission standards for hazardous pollutants; printing, coating, and dyeing of 

fabrics and other textiles; Final rule. US Environmental Protection Agency. Fed. Regist. 68(103), 32172-

32229. http://www.gpo.gov/fdsys/pkg/FR-2003-05-29/pdf/03-5738.pdf. Accessed August 17, 2012. 

US EPA (2004). National emission standards for hazardous air pollutants: Organic liquids distribution 

(non-gasoline). US Environmental Protection Agency. Fed. Regist. 69(22), 5038-5087. 

http://www.gpo.gov/fdsys/pkg/FR-2004-02-03/pdf/04-2227.pdf. Accessed August 17, 2012. 

US EPA (2004a). Air toxics risk assessment reference library. Volume 1. Technical resource manual. US 

Environmental Protection Agency, Research Triangle Park. www.epa.gov/ttn/fera/risk_atra_vol1.html. 

Accessed September 5, 2012. EPA453K04001a.

US EPA (2006a). Risk assessment for the halogenated solvent cleaning source category. US 

Environmental Protection Agency. 

http://yosemite.epa.gov/ee/epa/ria.nsf/vwRef/A.2006.10?OpenDocument. Accessed November 8, 

2012. 

US EPA (2006b). Non-confidential 2006 IUR records by chemical, including manufacturing, processing 

and use information. US Environmental Protection Agency. http://cfpub.epa.gov/iursearch/. Accessed 

November 9, 2012. 

US EPA (2007a). Exposure and fate assessment screening tool (E-FAST). Version 2.0. Documentation 

manual. US Environmental Protection Agency, Office of Pollution Prevention and Toxics Exposure 

Assessment Branch. www.epa.gov/oppt/exposure/pubs/efast2man.pdf. Accessed September 5, 2012. 

US EPA (2007b). Economic impact analysis of the halogenated solvent cleaners residual risk standard. US 

Environmental Protection Agency, Research Triangle Park, NC. 
DRAFT DO NOT CITE OR QUOTE

 Page 82

http://www.epa.gov/ttnecas1/regdata/EIAs/hsceconanalysisreportfinaldraft60000.pdf. Accessed 

November 8, 2012. EPA452R07005.

US EPA (2007c). National air emission standards for hazardous air pollutants: Halogenated solvent 

cleaning. US Environmental Protection Agency. Fed. Regist. 72(85), 25138-25159. 

http://www.gpo.gov/fdsys/pkg/FR-2007-05-03/pdf/E7-7668.pdf. Accessed August 17, 2012. 

US EPA (2007d). Protection of stratospheric ozone: Listing of substitutes for ozone-depleting substancesn-propyl bromide in solvent cleaning. US Environmental Protection Agency. Fed. Regist. 72(103), 30142-

30167. http://www.gpo.gov/fdsys/pkg/FR-2007-05-30/pdf/E7-9707.pdf. Accessed August 20, 2012. 

US EPA (2008a). Trichloroethylene (CAS Reg. No. 70-01-6). Interim acute exposure guideline levels 

(AEGLS). US Environmental Protection Agency. 

http://www.epa.gov/oppt/aegl/pubs/trichloroethylene_interim_dec_2008_v1.pdf. Accessed August 20, 

2012. 

US EPA (2008b). National emissions inventory data and documentation. US Environmental Protection 

Agency, Washington, DC. http://www.epa.gov/ttn/chief/net/2008inventory.html. Accessed August 16, 

2012. 

U.S. EPA. 2008c. 2008 National Emissions Inventory Data & Documentation. [Online] 2008 NEI v2, U.S. 

Environmental Protection Agency, 2008. [Cited: May 10, 2012.] 

http://www.epa.gov/ttn/chief/net/2008inventory.html.

US EPA (2009). National emission standards for hazardous air pollutants for chemical manufacturing 

area sources; Final rule. US Environmental Protection Agency. Fed. Regist. 74(208), 56008-56056. 

http://www.gpo.gov/fdsys/pkg/FR-2009-10-29/pdf/E9-25576.pdf. Accessed August 20, 2012. 

US EPA (2010). National primary drinking water regulations. Announcement of the results of EPA's 

review of existing drinking water standards and request for public comment and/or information on 

related issues. Notice, request for comments. Fed. Regist. 75(59), 15500-15572. 

US EPA (2011a). Letter to Lisa P. Jackon, EPA Administrator, Re: Review of EPA's draft assessment 

entitled "Toxicological Review of Trichloroethylene" (October 2009). US Environmental Protection 

Agency Science Advisory Board, Office of the Administrator, Washington, DC. EPA-SAB-11-002.

US EPA (2011b). Vocabulary catalog list detail - Integrated Risk Information System (IRIS) glossary. US 

Environmental Protection Agency, Office of Research and Development, National Center for 

Environmental Assessment, Washington, DC. 

http://ofmpub.epa.gov/sor_internet/registry/termreg/searchandretrieve/glossariesandkeywordlists/sea

rch.do?details=&glossaryName=IRIS%20Glossary. Accessed November 4, 2012. 

US EPA (2011c). Toxicological review of trichloroethylene (CAS No. 79-01-6). In support of summary 

information on the Integrated Risk Information System (IRIS). US Environmental Protection Agency, 

Integrated Risk Information System, Washington, DC. http://www.epa.gov/iris/supdocs/0199index.html. 

Accessed November 7, 2012. EPA/635/R-09/011F.
DRAFT DO NOT CITE OR QUOTE

 Page 83

US EPA (2011d). Expsoure factors handbook. Final. US Environmental Protection Agency, Washington, 

DC. http://cfpub.epa.gov/ncea/risk/recordisplay.cfm?deid=236252. Accessed September 5, 2012. 

EPA/600R-090052F.

US EPA (2011e). Toxic chemical release inventory reporting forms and instructions. Revised 2011 

version. US Environmental Protections Agency. EPA260R10001.

US EPA (2012a). Estimation Programs Interface Suite for Microsoft Windows, v4.10. US Environmental 

Protection Agency, Washington, DC. http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm. 

Accessed November 7, 2012. 

US EPA (2012b). AEGL program. US Environmental Protection Agency, Office of Pollution Prevention and 

Toxics, Washington, DC. http://www.epa.gov/oppt/aegl/. Accessed October 30, 2012. 

US EPA (2012c). TSCA work plan chemicals. US Environmental Protection Agency. 

http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html. Accessed November 9, 2012. 

Vernon, R. J., and Ferguson, R. K. (1969). Effects of trichloroethylene on visual motor performance. Arch. 

Environ. Health 18, 894-900. (as cited in US EPA, 2008a).

Wackett, L. P., Brusseau, G. A., Householder, S. R., and Hanson, R. S. (1989). Survey of microbial 

oxygenases: trichloroethylene degradation by propane-oxidizing bacteria. Appl. Environ. Microbiol.

55(11), 2960-2964. 

Wadden, R. A., Scheff, P. A., and Franke, J. E. (1989). Emission factors for trichloroethylene vapor 

degreasers. Am. Ind. Hyg. Assoc. J. 50(9), 496-500. 

Wakeham, S. G., Davis, A. C., and Karas, J. A. (1983). Mesocosm experiments to determine the fate and 

persistence of volatile organic compounds in coastal seawater. Environ. Sci. Technol. 17(10), 611-617. 

Weast, R. C., and Selby, S. M. (1966). Ethene, trichloro-. In CRC Handb. Chem. Phys. 47th ed., p. C-314. 

The Chemical Rubber Co, Cleaveland, OH.

Wilson, J. T., and Wilson, B. H. (1985). Biotransformation of trichloroethylene in soil. Appl. Environ. 

Microbiol. 49(1), 242-243. 

Woolhiser, M., Krieger, S., Thomas, J., and Hotchkiss, J. (2006). Trichloroethylene (TCE): Immunotoxicity 

potential in CD rats following a 4-week vapor inhalation exposure. Unpublished report, Midland, MI. (as 

cited in US EPA, 2011c).

Xu, H., Tanphaichitr, N., Forkert, P., Anupriwan, A., Weerachatyanukul, W., Vincent, R., Leader, A., and 

Wade, M. (2004). Exposure to trichloroethylene and its metabolites causes impairment of sperm 

fertilizing ability in mice. Toxicol. Sci. 82, 590-597. (as cited in US EPA, 2011c).

Xu, J. Q., Kochanek, K. D., Murphy, S. L., and Tejada-Vera, B. (2010). Deaths: Final Data for 2007. National 

Center for Health Statistics, Hyattsville, MD. http://www.cdc.gov/nchs/data/nvsr/nvsr58/nvsr58_19.pdf. 

Accessed November 9, 2012. 
DRAFT DO NOT CITE OR QUOTE

 Page 84

Xu, X., Yang, R., Wu, N., Zhong, P., Ke, Y., Zhou, L., Yuan, J., Li, G., Huang, H., and Wu, B. (2009). Severe 

hypersensitivity dermatitis and liver dysfunction induced by occupational exposure to trichloroethylene. 

Ind. Health 47, 107-112. (as cited in US EPA, 2011c).

 
DRAFT DO NOT CITE OR QUOTE

 Page 85

Appendices
DRAFT DO NOT CITE OR QUOTE

 Page 86

Appendix A: Regulatory History of TCE at the US EPA

The purpose of this section is to provide a brief regulatory history of TCE from the perspective 

of the EPA. TCE has been subject to 25 final rules and notices issued by the Agency from 1979

to 2009 that were relevant or significant with regard to TCE. These 25 rules and notices were 

promulgated by EPA’s OAR, OPPT, OSWER, and OW. 

OW initially identified TCE as a “toxic pollutant” in 1979 (US EPA, 1979b). TCE was classified as 

a “priority pollutant” in 1982 and no discharges of TCE were allowed from steam electric power 

generating point sources (US EPA, 1982). OW then established a non-enforceable maximum 

contaminant level goal (MCLG) of 0 mg/L for TCE in 1985 (US EPA, 1985b). Two years later, OW 

set a maximum contaminant level (MCL) of 0.005 mg/L for drinking water (US EPA, 1987a) and 

set an effluent limitation of 69 μg/L maximum per day and 26 μg/L maximum per month 

average for new and existing sources discharging to POTWs from the organic chemicals, 

plastics, and synthetic fibers industrial category (US EPA, 1987b). The following year, 1988, OW 

prohibited injection of TCE into class I underground injection wells (US EPA, 1988). TCE was 

identified by OW as a bioaccumulative chemical of concern pollutant in 1995 for a final water 

quality guidance for the great lakes system. This established water quality criteria for 

protection of human health by setting a human cancer value (HCV) of 29 μg/L for drinking 

water and 370 μg/L for non-drinking water for the Great Lakes system (US EPA, 1995). Then, in 

1998, OW identified TCE as a possible human carcinogen by establishing a national primary 

drinking water regulation that specified the following consumer confidence report health effect 

language: “some people who drink water containing trichloroethylene in excess of the MCL 

[0.005 mg/L] over many years could experience problems with their liver and may have an 

increased risk of getting cancer” (US EPA, 1998d). OW identified TCE’s major sources in drinking 

water originating from “discharge from metal degreasing sites and other factories (US EPA, 

1998d).” OW is currently evaluating and revising TCE’s MCL based upon analytical feasibility 

(US EPA, 2010). 

OAR has listed TCE as a HAP from several different industrial emission sources in multiple rules 

(US EPA, 1985a, 1986, 1994b, 1998c, 2001b, 2002, 2003, 2004, 2007c, 2009) as well as a 

“probable or possible human carcinogen” from operations including printing, coating, and 

dyeing of fabrics and other textiles (US EPA, 2003). OAR classified TCE as a group I chemical for 

emission standards for equipment leaks in the synthetic organic chemical manufacturing 

industry (US EPA, 1994a). In addition, OAR identified TCE as a substitute for two ozone 

depleting chemicals, methyl chloroform and CFC–113, for metals, electronics, and precision 

cleaning, in 2007 (US EPA, 2007d). 

OSWER set a reportable quantity of 100 lbs (45.4 kg) for releases of TCE from vessels or 

facilities in 1989 (US EPA, 1989). OSWER also set a minimum required detection limit for TCE of 

37 mg/kg for hazardous waste combustors in 1998 (US EPA, 1998b). 
DRAFT DO NOT CITE OR QUOTE

 Page 87

Although OPPT has only issued two notices relevant to TCE (US EPA, 1994c, 2000), other 

voluntary information collection activities for TCE have occurred in the past. These activities 

were primarily the result of two separate but related voluntary information collection activities: 

data gaps identified by ATSDR (US EPA, 1994c) and data gaps identified for pilot chemicals for 

EPA’s Voluntary Children’s Chemical Evaluation Program (VCCEP) (US EPA, 2000). 

EPA published a notice for voluntary solicitation of testing proposals in order to be considered 

for an enforceable consent agreement (ECA) negotiation in 1994 for 12 substances, including 

TCE (US EPA, 1994c). This notice was based on data gaps identified by ATSDR in coordination 

with EPA. After ATSDR updated its data needs for TCE in 1999 (ATSDR, 1999), the Halogenated 

Solvents Industry Alliance, Inc. (HSIA) responded with its intent to fulfill four of seven identified 

data needs. These four data needs included developmental neurotoxicity, developmental 

toxicity, immunotoxicity, and neurotoxicity via the oral route. HSIA entered into a 

memorandum of understanding (MOU) with ATSDR in June of 2001 to fulfill these four data 

needs. 

Over the course of the next several years, from 2001 to 2007, HSIA completed and submitted 

two studies to the Agency: a developmental toxicity and an immunotoxicity study via the 

inhalation route in rats. These two studies had been planned to be extrapolated to the human 

oral route using PBPK modeling. In addition, HSIA had planned to fulfill the data need for 

neurotoxicity via the oral route using PBPK modeling of existing published data from the 

inhalation route. Also, HSIA had planned to conduct a developmental neurotoxicity study in 

rats via the oral route. HSIA did not fulfill its MOU for these four planned studies due to several 

factors, including problems securing an appropriate lab, discontinuation of a strain of rat 

previously used in their completed studies, and discrepancies with ATSDR regarding the 

completeness of the three aforementioned studies using PBPK modeling. 

Since 2008, no further action has been taken by OPPT with regards to TCE and its existing data 

gaps identified by ATSDR.
DRAFT DO NOT CITE OR QUOTE

 Page 88

Appendix B: 2006 Inventory Update Rule Data for TCE 

The 2006 Chemical Data Reporting, or CDR, records indicate TCE production volume (PV) to be 

100 to 500 Mlbs. Since all importers and manufacturers are not required to report, CDR data 

likely underestimates actual TCE PV. For the purposes of this draft assessment, the low end of 

TCE PV was taken to be 100 Mlbs/yr while the high end was taken to be 500 Mlbs/yr.

The data tables below were taken from (US EPA, 2006b). 

Table B-1. US EPA 2006 IUR Data for TCE.

Company and Site Information

Company Site City State Zip Code Manufacture Import Site 

Limited

Basic 

Chemicals 

Company, LLC

Basic Chemicals 

Co – Wichita 

Plant

Wichita KS 67215 Yes No No

Chemcentral 

Corporation

Chemcentral 

International

Pompano 

Beach

FL 33069 No Yes N/A

Ineos Chlor 

Americas, Inc.

Ineos Chlor 

Americas, Inc.

Wilmington DE 19810 No Yes N/A

JSL Chemical 

Corporation

JSL Chemical 

Corporation

Palm Beach FL 33480 No Yes N/A

Oxy Vinyl, LP Oxy Vinyls – 

LaPorte

La Porte TX 77571 Yes No Yes

PPG Industries, 

Inc.

PPG Industries 

– Lake Charles

Lake Charles LA 70602 Yes No No

TR 

International, 

Incorporated

TR International 

Inc – Seattle

Seattle WA 98101 No Yes N/A

The Dow 

Chemical 

Company

Dow Chemical –

Freeport, TX

Freeport TX 77541 Yes No No
DRAFT DO NOT CITE OR QUOTE

 Page 89

Table B-2. National Chemical Information. 

Production volume (aggregated) 100-<500 million lbs

Maximum concentration (at manufacture or import site) >90%

Physical forms(s) Liquid

Number of manufacturing, processing, and use sites (aggregated) ≥1,000 

Number of reasonably likely to be exposed industrial manufacturing, 

processing, and use workers (aggregated)

≥1,000 

Was industrial processing or use information reported? Yes

Was commercial or consumer use information reported? Yes

Table B-3. Summary of TCE Uses.

Type of Processing Industrial Sector (Based on 

NAICS) Industrial Function

Not readily obtainable (NRO) NRO NRO

Processing as a reactant CBI Intermediates

Processing as a reactant Industrial gas manufacturing Intermediates

Processing as a reactant Other basic organic chemical 

manufacturing

Intermediates

Processing as a reactant Other basic organic chemical 

manufacturing

Other

Processing; incorporation into 

formulation, mixture, or reaction 

product

All other chemical product and 

preparation manufacturing

Solvents (that become part of 

product formulation or mixture)

Processing; incorporation into 

formulation, mixture, or reaction 

product

Invalid data provided Adhesives and binding agents

Processing; incorporation into 

formulation, mixture, or reaction 

product

Machine shops Solvents (for cleaning or 

degreasing)

Processing; incorporation into 

formulation, mixture, or reaction 

product

Paint and coating manufacturing Solvents (that become part of 

product formulation or mixture)

Processing; repackaging Other basic organic chemical 

manufacturing

Other

Processing; repackaging Other chemical and allied 

products merchant wholesalers

Solvents (for cleaning or 

degreasing)
DRAFT DO NOT CITE OR QUOTE

 Page 90

Table B-4. TCE Use Category Summary.

Commercial/Consumer 

Product Category

Maximum Concentration in 

Related Consumer/Commercial 

Product Category

Intended for Use in 

Children’s Products in Related 

Product Category

Adhesives and sealants >90% No

Lubricants, greases, and fuel 

additives >90% No

Paints and coatings 1-30% No

Other >90% No

NRO NRO NRO
DRAFT DO NOT CITE OR QUOTE

 Page 91

Appendix C: NAICS Codes for TCE Degreasing 

An analysis of the North American Industry Classification System (NAICS) identified 78 different 

industries (NAICS codes are listed in Table C-1). 

Table C-1. TCE Used as a Degreaser Primarily in These Industries (US Census, 2008). 

NAICS Codes

33121 331210 332811 334413 336411

33272 331419 332812 334414 336413

33341 331421 332813 334417 336414

33422 332111 332912 334419 336510

33512 332112 332913 334513 337125

33531 332116 332919 334515 337127

33634 332117 332994 335121 339114

33641 332211 332996 335211 339992

33999 332212 332999 335312 339995

314999 332311 333132 335313 339999

321113 332313 333298 335911 488111

323116 332431 333311 335921 493110

325188 332510 333415 335929 811310 

325998 332618 333921 335999 928110

326299 332721 333994 336321

331111 332722 333999 336340

Each number listed is a different industry that may be associated with TCE/degreasing 

operations. Those interested may go to the following URL and type in a code - 

http://www.census.gov/eos/www/naics/ (US Census, 2008) ). For example, the following results 

are seen when the listed numbers are searched:

33121:

33121 Iron and Steel Pipe and Tube Manufacturing from Purchased SteelT

331210 Iron and Steel Pipe and Tube Manufacturing from Purchased Steel 

332811 (results below slightly edited for simplicity)
DRAFT DO NOT CITE OR QUOTE

 Page 92

Metal Heat Treating - This U.S. industry comprises establishments primarily engaged in heat

treating, such as annealing, tempering, and brazing, and cryogenically treating metals and 

metal products for the trade.

Establishments primarily engaged in both fabricating and heat treating metal products are 

classified in the Manufacturing sector according to the product made.

Annealing metals and metal products for the trade

Brazing (i.e., hardening) metals and metal products for the trade

Burning metals and metal products for the trade

Cold treating metals for the trade

Cryogenic treating metals for the trade

Hardening (i.e., heat treating) metals and metal products for the trade

Heat treating metals and metal products for the trade

Shot peening metal and metal products for the trade

Tempering metals and metal products for the trade
DRAFT DO NOT CITE OR QUOTE

 

Appendix D: Calculations for Small Commercial Worker 

Degreaser Exposures 

In Figure E-1, a solvent degreasing facility is partitioned into two zones: the near-field and the 

far-field (Keil et al., 2009). This is done because in occupational settings, contaminant levels in 

the near-field are considered to provide a better representation of a worker’s personal 

breathing zone than those in the far-field; potential worker exposures depend on how close a 

worker is to the emission source. Also, for this risk assessment, the far-field exposures will 

represent bystanders, or non-users. In other words, those individuals who are in the building 

(and perhaps even the room), but are not physically close to the volatile source as shown in 

Figure D-1.

Figure D-1. An Illustration of an Imperfectly Mixed Room; Near-Field/Far-Field Approximation of a 

Solvent Cleaning Facility; Potential Worker Exposures Depend on How Close a Worker is to the 

Emission (Volatile) Source.
DRAFT DO NOT CITE OR QUOTE

 

For the purposes of mass transfer from and to the near-field, the free surface area, is 

defined to be the surface area that is available for mass transfer; the , will not necessarily be 

equal to the surface area of the near-field. For instance, if the near-field is defined to be a 

rectangular region, as illustrated in Figure D-1, the near-field floor will not be available for mass 

transfer; thus, the , will be less than the actual surface area of the near-field:
DRAFT DO NOT CITE OR QUOTE

 

Based on the model inputs in Table D-1, potential workplace TCE inhalation exposure values can 

be estimated for workers in the near-field and for non-users in the far-field (see Table D-2). The 

majority of data regarding worker exposure to TCE was obtained from degreasing operations; 

the data indicated that exposure is likely to vary, although mean TWA concentrations were 

generally consistent and usually ranged from ≤50 to 100 ppm (ATSDR, 1997). This is similar to 

the exposure values presented in the EU Risk Assessment for TCE (EC, 2004). The “typical” 

exposure values in Table D-2 are also similar, being of the same order of magnitude.

Table D-1. Near-Field/Far-Field Model Inputs.

Parameter Units

Parameter Values

Comments

Small Industrial/

Commercial Facilities

QFF

ft3/minute 500 (worst case)

3,000 (typical)

US EPA (1991) 

VNF cm/second 10 ~50th percentile; Baldwin and Maynard (1998) 

LNF ft 10 Assumes volatile source is centered in the fearfield and worker activities are within 5 feet of 

WNF the emitting source ft 10

HNF

ft 6 Adequate height to capture a typical worker’s 

breathing zone

FSA ft2 180 Equation (5)

G g/minute 16.73 No local exhaust ventilation (LEV); see Table 3-7 

in main body of this report.

G g/minute 1.67 With LEV; potential operating TCE emissions 

reduced by 90%; Wadden et al. (1989) 

Results of the calculations are shown below in Table E-2. 

Table D-2. Potential Workplace TCE Inhalation Exposures and Number of Workers Exposed; No LEV.

Type of Facility

Potential Workplace TCE Inhalation Exposures

(8-hour TWA)

Near-Field Far-Field

Typical

(ppm)

Worst Case

(ppm)

Number of 

Workers

Typical

(ppm)

Worst Case

(ppm)

Number of 

Workers

Small industrial/

commercial

17 63 7,415 9 55 17,796 

The potential workplace inhalation exposures in Table D-2 do not take LEV into account. 

Engineering controls, such as LEV, are recommended if practical (Arkema, 2011). The use of 

LEV can reduce potential operating TCE emissions into the workplace by approximately 
DRAFT DO NOT CITE OR QUOTE

 

90 percent (Wadden et al., 1989). Based on the model inputs in Table D-1, potential workplace 

TCE exposures in the presence of LEV are presented in Table D-3.

Table D-3. Potential Workplace TCE Inhalation Exposures and Number of Workers Exposed; With LEV.

Type of Facility

Potential Workplace TCE Inhalation Exposures

(8-hour TWA)

Near-Field Far-Field

Typical

(ppm)

Worst Case

(ppm)

Number of 

Workers

Typical

(ppm)

Worst Case

(ppm)

Number of 

Workers

Small industrial/ 

commercial

2 6 7,415 1 5 17,796
DRAFT DO NOT CITE OR QUOTE

 

Appendix E: Converting E-FAST ADRs to Concentration in Air

The exposure values generated using the E-FAST/CEM models are in mg/kg-bw/day (notes 10 

and 11). The only output in the acute exposure scenario expressed as a concentration is the 

peak concentration, which represents the maximum concentration in air calculated by the 

model during any 10-second time step during (in this case) 24 hours. This value is not a realistic 

one to use, even as a worst-case scenario (all peak concentrations can be found in documents 

cited in notes 10 and 11). 

Thus, to convert the E-FAST CEM outputs from mg/kg-bw/day to ppm, the following 

methodology was used: using the equation from the E-FAST manual to calculate the ADR 

(acute dose rate). 

The general expression for the potential acute dose rate (ADRpot) is as follows:

where:

ADRpot = potential acute dose rate (mg/kg-bw/day)

Cair = exposure concentration (mg/m3) 

InhR = inhalation rate (m3

/hour)

FQ = frequency of product use (events/year)

DEv = duration of an event (hour/event)

ED = exposure duration (years of product usage) 

BW = body weight (kg)

AT = averaging time (days)

Rearranging and simplifying this equation to calculate an approximation for Cair over the 

24-hour averaging time for the ADRPOT results in the following equation:

This simplification is reasonable since the averaging time for acute exposure is one day 

(24 hours). In both scenarios, the frequency is just once per day. Although the duration of the 

event for the two consumer scenarios is either one hour (degreaser) or 0.5 hours (clear 

protective coating spray)26, for the purposes of this exercise and to convert the model output to 

 26 However, for the user in both scenarios, the inhalation rates were slightly higher during use of the product, as 

stipulated in the model outputs. Thus, for the degreaser use, an inhalation rate of 0.74 m3

/hour (for 21 to 78 year 

olds, 0.72 m3

/hour for the 16 to 20 year olds) was used for one hour, and 0.611 m3/hour (for 21 to 78 yr olds, 

0.679 m3

/hour for the 16 to 20 yr olds) for the remaining 23 hours. For the clear protective coating spray use, the 
DRAFT DO NOT CITE OR QUOTE

 

a more useable exposure value to compare to the hazard value, there is no correction for this 

difference. This assumption is still conservative since the values generated are reasonably high 

exposures that probably overestimate the actual exposures. 

This is borne out by comparing the values calculated for the hobbyist degreaser scenarios (2 

ppm for the 16 to 20 year olds and the 21 to 78 year olds) to the estimate for the small 

commercial operators in which the typical and worst-case values of 2 and 6 ppm, respectively, 

were estimated for the local exhaust ventilation (LEV) scenario (the same values without LEV 

were 17 and 63 ppm, respectively). 

An example calculation is presented below, since the final value is in mg/m3 and the desired 

units will be in ppm. All calculated values are presented in Table E-1.

For the clear protective coating spray use, 21- to 78-yr-old user:

ADRpot = 0.45 mg/kg-bw/day

InhR (during use; 0.5 hours) = 0.74 m3

/hour 

InhR (other times; 23.5 hours) = 0.611 m3/hour 

BW = 80 kg (using 2011 Exposure Factors Handbook, US EPA, 2011d) 

Cair = (0.45)(80)/[0.74 x 0.5) + [0.611 x 23.5) = 2.4 mg/m3; converting to ppm27 = 0.446 ppm 

(converted to 0.4 ppm to use a single significant figure given the assumptions in the backcalculation).

Table E-1. Estimated TCE Inhalation Calculated Concentration in Air (Over Course of Day) from Use of 

Two Hobbyist Products Indoors at Residences.

Ages

Clear Protective 

Coating Spray User 

ADRpot (ppm)

Clear Protective Coating 

Spray Non-user ADRpot

(ppm)

Solvent Degreaser 

User ADRpot (ppm)

Solvent Degreaser 

Non-user ADRpot

(ppm)

<1 NA 0.1 NA 0.8

1-2 NA 0.1 NA 0.8

3-5 NA 0.1 NA 0.8

6-10 NA 0.1 NA 0.8

11-15 NA 0.1 NA 0.8

16-20 0.4 0.1 2 0.8

>21 0.4 0.1 2 0.8

 

higher, user inhalation rate was used for 0.5 hours, with the “normal” rate used for 23.5 hours. This correction 

was not done for any bystander (non-user) scenario. 27 ppm = mg/m3

/5.374.
DRAFT DO NOT CITE OR QUOTE

Page 99

Appendix F: Hazard Values Identified for use in this Risk Assessment

Table F-1. Studies Identified In US EPA (2011c) For Use In Dose-Response Assessment For TCE.

Target Organ Species Route of 

Exposurea

Range of Doses or 

Concentrationsb Duration POD Typec Effect HEC50

(ppm)

HEC99

(ppm) Reference

Liver Mouse Inhalation 37-3,600 ppm 30-120 days BMDL = 21.6 ppm Increased liver 

weight/body weight 

ratio

25 9.1 1 

Rat Inhalation 100-1,000 ppm 28 days BMDL = 25 ppm 53 19 2 

Mouse Oral (g) 100-3,200 mg/kgbw/day6 weeks BMDL = 82 mg/kgbw/day32 11 3 

Kidney Rat Inhalation 100-600 ppm 104 weeks BMDL = 40.2 ppm Pathology changes in 

renal tubule

0.28 0.038 4 

Mouse Oral (g) 869-2,339d mg/kgbw/day90 weeks LOAEL = 620 mg/kgbw/day3.9 0.5 5 

Rat Oral (g) 500-1,000 mg/kgbw/day104 weeks BMDL = 9.45 mg/kgbw/day0.042 0.0056 6 

Mouse Inhalation 37-3,600 ppm 30-120 days BMDL = 34.7 ppm Increased kidney 

weight/body weight 

ratio

0.88 0.12 1 

Rat Inhalation 100-1,000 ppm 28 days BMDL = 15.7 ppm 0.099 0.013 2 

NeurotoxicityHuman Inhalation Mean exposure of 

CxT

Mean of 16 years LOAEL = 14 ppm Trigeminal nerve 

effects

14 5.3 7 

Rat Oral (drw) 25-47 mg/kgbw/day8 weeks LOAEL = 47 mg/kgbw/dayDemyelination of 

hippocampus

18 7.1 8 

Rat Inhalation 50-300 ppm 6 weeks LOAEL = 12 ppm Changes in 

wakefulness

13 4.8 9 

Rat Oral (g) 1,000 mg/kgbw/day6 weeks LOAEL = 710 mg/kgbw/dayLoss of neurons 126 47 10

Rat Inhalation 300 ppm 24 days LOAEL = 300 ppm Decreased 

regeneration of sciatic 

nerve

274 93 11

Mouse Inhalation 150-300 ppm 24 days LOAEL = 150 ppm 378 120
DRAFT DO NOT CITE OR QUOTE

Page 100

Table F-1. Studies Identified In US EPA (2011c) For Use In Dose-Response Assessment For TCE.

Target Organ Species Route of 

Exposurea

Range of Doses or 

Concentrationsb Duration POD Typec Effect HEC50

(ppm)

HEC99

(ppm) Reference

ImmunotoxicityMouse Oral (drw) 1.4-14 ppm 27-30 weeks LOAEL = 0.35 mg/kgbw/dayDecreased thymus 

weight

0.092 0.033 12

Mouse Oral (drw) 1.4-14 ppm 27-30 weeks LOAEL = 0.35 mg/kgbw/dayIncreased anti-dsDNA 0.092 0.033 12

Mouse

(autoimmune 

prone 

strain)

Inhalation 500-2,000 ppm 8 weeks LOAEL = 70 ppm Changes in 

immunoreactive 

organs

97 37 13

Mouse Oral (drw) 0.1-5.0 mg/mL 4 or 6 months LOAEL = 18 mg/kgbw/dayImmunosuppression 4.8 1.7 14

Rat Inhalation 100-1,000 ppm 28 days BMDL = 24.9 ppm Immunosuppression 29 11 2 

Reproductive toxicityHuman

(male)

Inhalation Mean exposure = 

29.6 ppm

Measured values after an 

8-hour work shift; mean 

years on job was 5.1

BMDL = 1.4 ppm Sperm effects 1.4 0.5 15

Mouse 

(male)

Inhalation 1,000 ppm 6 weeks LOAEL = 180 ppm Sperm effects 190 67 16

Rat (male) Inhalation 376 ppm 2-10 weeks,

12 weeks, 24 weeks

LOAEL = 45 ppm Sperm effects and 

male reproductive 

tract effects

32 13 17

Mouse 

(male)

Inhalation 1,000 ppm 19 days over 4 weeks, 

1-4 weeks

LOAEL = 180 ppm Effects on epididymis 

epithelium

190 67 18

Rat (male) Oral (drw) 143-270 mg/kgbw/day14 days LOAEL = 141 mg/kgbw/dayDecreased in vitro

fertilization

16 9.3 19

Rat

(fem)

Oral (g) 475-1,125 mg/kgbw/day9 days (during gestation) LOAEL = 475 mg/kgbw/dayDelayed parturition 98 37 20

Rat

(both sexes)

Oral (f) 72-389 mg/kgbw/day18 weeks LOAEL = 389 mg/kgbw/dayDecreased mating 

(both sexes exposed)

204 71 21
DRAFT DO NOT CITE OR QUOTE

Page 101

Table F-1. Studies Identified In US EPA (2011c) For Use In Dose-Response Assessment For TCE.

Target Organ Species Route of 

Exposurea

Range of Doses or 

Concentrationsb Duration POD Typec Effect HEC50

(ppm)

HEC99

(ppm) Reference

Developmental 

toxicity

Rat

(female)

Inhalation 100 ppm 13 days (during 

gestation)

LOAEL =17 ppm Increased resorptions 16 6.2 22

Rat

(female)

Oral (g) 475-1,125 mg/kgbw/day9 days (during gestation) BMDL = 32.2 mg/kgbw/dayIncreased resorptions 29 28 20

Rat

(female)

Inhalation 100 ppm 13 days (during 

gestation)

LOAEL = 17 ppm Decreased fetal 

weight

16 6.2 22

Rat

(female)

Oral (drw) 0.0025-1,100 ppm 22 days (throughout 

gestation)

BMDL = 0.0207 

mg/kg-bw/day

Heart malformations 0.012 0.0037 23

Rat

(male pups)

Oral (g) 50 and 290 mg/kgbw/dayPNDs 10-16 LOAEL = 50 mg/kgbw/dayDecreased rearing 

activity 

8 3 24

Rat

(female)

Oral (drw) 312-1,250 mg/L From gestation through 

21 days post-partum

LOAEL = 45 mg/kgbw/dayIncreased exploratory 

behavior in male pups

22 8.4 25

a

g = gavage, drw = drinking water, f = feed

b

Controls (or zero dose/concentration) are not presented, so a sense of the lowest and 

highest values is understood.

c

POD type can be NOAEL, LOAEL, or BMDL; the IRIS program adjusted all values to 

continuous exposure. 

d

Reported doses were TWAs on the days in which animals received a dose (66 weeks 

over the 90-week period).

Reference List (all as cited in US EPA, 2011c): 

1 = Kjellstrand et al. (1983) 

2 = Woolhiser et al. (2006) 

3 = Buben and O'Flaherty (1985) 

4 = Maltoni and Cotti (1986)

5 = NCI (1976) 

6 = NTP (1988) 

7 = Ruijten et al. (1991) 

8 = Isaacson et al. (1990) 

9 = Arito et al. (1994) 

10 = Gash et al. (2008) 

11 = Kjellstrand et al. (1987) 

12 = Keil et al. (2009) 

13 = Kaneko et al. (2000) 

14 = Sanders et al. (1982) 

15 = Chia et al. (1996) 

16 = Xu et al. (2004) 

17 = Kumar et al. (2000); Kumar et al. (2001) 

18 = Forkert et al. (2002); Kan et al. (2007) 

19 = DuTeaux et al. (2004) 

20 = Narotsky et al. (1995) 

21 = NTP (1986) 

22 = Healy et al. (1982) 

23 = Johnson et al. (2003) 

24 = Fredriksson et al. (1993) 

25 = Taylor et al. (1985)