Page 1 of 3

OPPT Charge to External Peer Reviewers for the review of the TSCA

Workplan Chemical Risk Assessment of TCE

June 2013

OPPT focused its risk assessment on three specific uses of TCE: as a spray degreaser by workers

in small commercial facilities, as a spray degreaser by consumers (hobbyists), and as a clear

protective coating spray (an art/crafts use) by consumers (hobbyists). For all uses, only the

inhalation route of exposure was evaluated, and risk estimates for individuals physically near the

user of the TCE product (but not using it; called either bystanders or non-users) were also

calculated.

General Question on the Risk Assessment Document

Issue 1. This risk assessment is divided into three chapters with six appendices and

three supplemental documents. The first two chapters describe the scoping exercise 

EPA used and background information on TCE that sets the stage for the information 

available and used in the risk assessment. Chapter 3 includes the exposure, hazard

assessment and risk characterization and a section on uncertainties for each of the

three uses of TCE which are the focus of this risk assessment. The risk assessment is

intended to provide a clear and transparent summary of the Agency’s analysis.

Question 1-1: Please comment on whether the characterization provides a clear and logical 

summary of EPA’s analysis. Please provide specific suggestions for improving the 

document.

Question 1-2: Please comment on whether appropriate background information is provided 

and accurately characterized. Please provide any other significant literature, reports, or data 

that would be useful to complete this characterization.

Questions on the Exposure Assessment

Issue 2. Workplace exposure estimates were developed for adults using spray degreasers in 

small commercial settings. These scenarios represent small businesses that use degreaser 

products on equipment regularly, but not all day during the course of their job. An

example would be a garage/car mechanic business. Readily available data from sources

such as the National Emissions Inventory (NEI), Toxics Release Inventory (TRI), and

National Occupational Exposure Survey (NOES), other literature sources and

assumptions were used to develop the workplace exposure assessment. 

Question 2-1: Please comment on the approach used, and provide any specific 

suggestions or recommendations for alternative approaches, models or information that 

should be considered by the Agency for improving the workplace exposure assessment,

including estimations for bystander/non-users (e.g., women of childbearing age).
Page 2 of 3

Issue 3. Exposure estimates were developed for two different consumer uses: a degreasing 

product and a clear protective coating spray product. Both products are aerosol sprays

and appear to be available for sale and use by consumers/hobbyists in the US. There were 

no reliable data regarding the hobbyist scenarios, so OPPT estimated hobbyist exposures 

using a standard exposure assessment modeling approach (the Consumer Exposure 

Module [CEM] of the Exposure and Fate Assessment Screening Tool, or E-FAST).

Question 3-1: Please comment on the approach used and provide any specific 

suggestions or recommendations for alternative approaches, models, or information (e.g., 

information on duration and number of user events) that could be considered by the 

agency in developing the exposure assumptions and estimates for the hobbyist degreaser 

and clear protective coating spray uses, and for the bystander/non-users (e.g., children, 

women of childbearing age).

Questions on the Hazard Assessment

Issue 4. Information on the inherent hazards of TCE has been well-characterized. There 

are six major domains of adverse effects (primarily in animal models) following exposure 

to TCE: non-cancer effects on the liver, kidney, nervous system, immune system, 

reproductive (predominantly male) toxicity, and developmental toxicity; as well as cancer 

effects on the liver, kidney and the immune system (Non-Hodgkins Lymphoma, or NHL). 

TCE metabolism is extensive in mammalian systems and different metabolites are likely to

be responsible for different toxicity. The 2011 US EPA Integrated Risk Information System 

(IRIS) assessment for TCE reviewed many human and animal studies. There were 32 

endpoints/27studies identified as “candidates” for developing the reference concentration 

(called the RfC) - these included both inhalation and oral studies. Physiologically-based

pharmacokinetic (PBPK) modeling was used by the IRIS program to derive different HEC

(i.e., human equivalent concentration) values. OPPT reports all of these values, but

focused on using only the 12 inhalation studies. Rather than use a single value to represent

hazard, OPPT used the lowest lower bound HEC99 – the 99thpercentile predicted HEC

concentration -- for the effect of concern for each target organ. Furthermore, OPPT

distinguished between effects that may occur following acute exposure (i.e., neurotoxicity

and developmental toxicity) versus those that may occur following chronic exposures (i.e.,

liver, kidney, immunotoxicity, and male reproductive toxicity and cancer).

Question 4-1: Please comment on the strengths and weaknesses of evaluating different 

endpoints based on exposure durations (i.e., acute versus chronic).

Question 4-2: Please comment on the strengths and weaknesses of using multiple values 

for each type of adverse effect.

Question 4-3: PBPK modeling was employed in the 2011 IRIS assessment for route-toroute extrapolation to develop a corresponding inhalation value from oral studies, some 

of which involved endpoints not studied or reported in inhalation studies. OPPT supports 

the approach used in the IRIS assessment. However, OPPT did not use PBPK-derived 

human-equivalent concentrations from oral studies in the current draft risk assessment, 
Page 3 of 3

because OPPT focused on a narrow set of TCE consumer uses (e.g., degreasing and 

arts/crafts uses) that are subject to TSCA and therefore, OPPT’s draft risk assessment 

relied only on inhalation exposure studies that directly mimicked inhalation exposure use 

scenarios for both adults and developmental lifestages. Please comment on whether the 

2011 IRIS assessment's PBPK-derived inhalation values from oral studies should be used 

in the final OPPT risk assessment.

Questions on the Risk Assessment

Issue 5. A margin of exposure (MOE) approach was used to evaluate potential non-cancer 

risk and the IRIS inhalation unit risk (IUR) was used to evaluate potential cancer risk.

The small commercial degreaser workplace risk estimate assumed chronic (daily) inhalation

exposures to TCE. The consumer use of both the degreaser spray and the clear protective

coating spray used in the arts/crafts field risk estimates assumed only intermittent (acute)

inhalation exposures to TCE. As part of the risk characterization, there is a discussion of

the uncertainties surrounding the risk calculations.

Question 5-1: Please comment on the strengths and weaknesses of the MOE approach 

used to estimate the chronic, non-cancer risk for the workplace exposures; including nonusers.

Question 5-2: Please comment on the strengths and weaknesses of the MOE approach 

used to estimate the acute risk to consumers; including non-users (e.g., children, women 

of childbearing age). Specifically, please comment on the decision to limit the analysis

to acute exposures without residual concern between events (i.e., once/week for users of

the clear protective coating spray, and twice/month for degreaser users).

Question 5-3: Please comment on the use of a uniform benchmark MOE of 30 rather 

than a benchmark MOE equal to the composite Uncertainty Factors for each study as 

identified in the 2011 US EPA IRIS assessment for TCE.

Question 5-4: Please comment on whether the document has adequately described the 

uncertainties and data limitations in the methodology used to assess risks to allow the 

EPA to reduce risks to human health from TCE. Please comment on whether this 

information is presented in a transparent manner.