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OPPT Trichloroethylene (TCE) Draft Risk Assessment 

Final Comments of 9 Member Peer Review Panel 

September 5, 2013 

Penny Fenner-Crisp (Panel Chair) 

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. 

The draft document fails to articulate satisfactorily that the analysis described within should be 

characterized as a screening level assessment. Unless one was already familiar with the E-FAST exposure 

model, one has to dig into the details of the E-FAST model manual to discover that E-FAST V2.0 is 

described by EPA as a “screening model.” “Screening model results are intended to be conservative, 

meaning that predicted concentrations and exposures are likely to be at the high end of or higher than 

concentrations that might actually be occurring in a real-world setting. If an exposure estimated by a 

screening model results in an unacceptably high health risk, then an appropriate next step in the 

assessment process would be to refine the parameter input or perform the assessment with different and 

perhaps more complex models. Another response might be to consider monitoring to gather actual 

emissions data that can be used to estimate exposure” (EPA, 2007, page 1-1). Furthermore, the E-FAST 

webpage states that E-FAST “provides screening-level estimates of the concentrations of chemicals 

released to air, surface water, landfills, and from consumer products. .....Estimates provided are potential 

inhalation, dermal and ingestion dose rates resulting from these releases. Modeled estimates of 

concentrations and doses are designed to reasonably overestimate exposures, for use in screening level 

assessment” (EPA, 2013) (http://www.epa.gov/opptintr/exposure/pubs/efast.htm) 

Especially since nearly every exposure scenario examined in this document yielded a conclusion of 

“potential risk of concern,” inclusion of some discussion of what a “screening level assessment” is, and 

what should/could be done in the way of communicating and responding to the results of that assessment 

becomes very important. A “possible next steps” section also should be included in the Executive 

Summary, if the document were to be revised. 

However, I believe that the Agency acted prematurely in issuing this (screening level) assessment for 

public comment and in convening a formal scientific expert peer review, given the conclusions reached in 

it. If all of the conclusions had indicated “no problem, then that assessment should have been peer 

reviewed externally, to determine if there were outside expert agreement. Presumably, if so, then no 

further risk assessments would be needed. However, most (and, perhaps, all, if the Agency reverses its 

decision not to include an assessment of dermal exposure) of the exposure scenarios assessed in the 

present draft resulted in the conclusion of “indicates potential risks of concern.” This begs for refinement 

of the assessments, on both the exposure and hazard side of the equation. This is essential for any 

defensible regulatory actions to be undertaken. 

Prior to the July 17 meeting, I was inclined to suggest that some revision to the current document would 

be productive. Revision would be minimal and limited to embellishment with the necessary contextual 

information I recommended above and in my comments below on Question 1-2. 

After listening carefully to the comments and contributions from the other members of the Panel, I have 

concluded that there would little benefit in revising this draft screening assessment. Rather, I would 
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suggest that the effort be put into a higher tier, more refined assessment which would include empirical 

data gathered during the course of real-world uses, e.g., as OPP regularly asks be done for occupational 

exposures and sometimes for residential exposures, consumer use survey data, evaluation of exposure 

using additional modeling tools and a revisiting and reanalysis of the choices of toxicity and 

epidemiologic studies used to describe the health benchmark at the MEC99 level and the rationale for 

selecting the singular MOE of 30 to apply to the selected studies, each of which have varying degrees of 

credibility. This current draft screening level assessment could then be attached as an appendix to the new 

second-generation assessment, and described, in summary form, in the early chapter(s) of the new 

assessment. I would have saved the resources expended for the current external peer review and spent 

them on the next-generation assessment. 

References 

US EPA. 2007. 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. 

(available at http://www.epa.gov/opptintr/exposure/pubs/efast2man.pdf) (accessed July 10, 2013 

US EPA. 2013. Exposure and Fate Assessment Screening Tool Version 2.0 (E-FAST V2.0). (available at 

http://www.epa.gov/opptintr/exposure/pubs/efast.htm) (accessed July 12, 2013). 

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. 

An important question was posed by one of the peer review panelists following the Agency’s overview 

presentation at the July 7 pre-meeting. To paraphrase: “What is the purpose of this document?” To those 

who are very familiar with Agency legislative mandates and regulatory and communication practices, it 

may be easy to answer that question. But, for those with only minimal or sporadic contact or interaction 

with Agency activities and outputs, it may seem a mystery. This document was created to serve as one of 

several information sources in a complex and potentially lengthy decision-making risk management 

process. The Agency decided that it was important enough to warrant a review by outside experts. Given 

that status, it becomes incumbent upon the Agency to include in the document a more substantive 

discussion of where and how it fits into the decision-making process related to the Existing Chemicals 

Management Program-including a ‘what’s next?’ module. 

The current document was written primarily for “insiders,” that is, those Agency risk assessors and risk 

managers involved in TSCA’s Existing Chemicals Program. However, by virtue of the decision to make 

this assessment available for review and comment, the Agency becomes obligated to write it with 

“outsiders” in mind as an audience as well—“outsiders” being what EPA describes as the stakeholder 

community. OPPT’s stakeholder community comes to the table with varying degrees of prior knowledge, 

scientific expertise and sophistication. While not expecting to see a document pitched at an 8th gradereading level, as are many of the Agency’s communications vehicles targeted for the general public, I 

would expect it to include more context than it currently contains. 

Questions on the Exposure Assessment 

I have some general comments about the E-FAST model that apply to both Questions 2-1 and 3-1. I am 

concerned that some of the information used in the model that comes from EPA’s Exposure Factors 

Handbook is out of date or incorrect. The version of E-FAST currently used is dated 2007, and cites 
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information from the original 1997 version of the Handbook. EPA issued an update of the Exposure 

Factors Handbook in 2011. Needless to say, I didn’t take the time to look for specific mismatches, but I 

suspect there may be some, some of which will make a difference. One major error that could have been 

avoided is the age groupings used in the model vs. those recommended in the 2011 Handbook. E-FAST 

uses groupings presented in the 1997 Handbook. However, these were updated in 2005 (EPA, 2005), 

before the 2007 version of E-FAST was issued. 

E-FAST age groups: Infant (<1), Infant (1-2), Small child (3-5), Child (6-12), Youth (13-19), Adult 

[Table 3-3, p. 3-74], but less than age 1; ages 1 to 2; ages 3 to 5; ages 6 to 10; ages 11 to 15; ages 16 to 

20; and ages 21 to 78 were used in the degreaser and clear protective coating spray use assessments. 

2011 Handbook age groups: Birth to <1 month, 1 to <3 months, 3 to <6 months, 6 to <12 months,1 to <2 

years,2 to <3 years, 3 to <6 years,6 to <11 years,11 to <16 years,16 to <21 years, >21 years. 

Reference 

U.S. EPA. (2005) Guidance on selecting age groups for monitoring and assessing childhood exposures to 

environmental contaminants. Risk Assessment Forum, Washington, DC; EPA/630/P-03/003F. Available online at 

http://www.epa.gov/raf/publications/pdfs/AGEGROUPS.PDF. 

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). 

This question brings to mind the old adage attributed to George Box and often quoted: “Models: All are 

wrong. Some are useful.” And, further, a comment made by Dr. John Adgate, currently the Chair of the 

Department of Environmental & Occupational Health at the Colorado School of Public Health, during a 

2002 meeting of the FIFRA Scientific Advisory Panel charged with reviewing one of the several dietary 

exposure models that the Office of Pesticide Programs employs when conducting its tolerance assessment 

activities. He said something to the effect that, in his opinion, more than one model should be developed, 

validated and used for a particular purpose, given our understanding that, at this time, no one model is 

“the only right one,” nor can it precisely characterize the scenario under evaluation. 

So I agree wholeheartedly with the exposure experts on the panel that, if the Agency decides to move 

forward with additional assessments, it should also run the exposure assessments, using different 

model(s), perhaps, SHEDS-multimedia and some other screening models not developed by EPA, but 

considered to be credible. Some of these other models were specifically described by these experts (e.g., 

Dr. Driver mentioned CCEM and he and Dr. Jaycock both mentioned the Nica model. 

Just prior to the final meeting of the Peer Review Panel on August 21, the Agency presented a series of 

Clarifying Questions for the Panel’s consideration. One of them was directed to the statements I had made 

above regarding the use of additional models in the occupational (and, below, the consumer) assessments: 

“Dr. Fenner-Crisp recommended that the agency consider using an alternate model such as SHEDS for its 

occupational release and exposure assessment. Please clarify why the SHEDS model is applicable to the 

agency’s occupational release and exposure assessment; why is SHEDS a viable and/or preferred choice 

for facilities using TCE in degreasing operations compared to the near-field/far-field model that the 

agency used? Where possible, please provide the supporting reference(s).” 
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The point I was trying to make when advocating for the use of additional models was that no one model is 

perfect and fully predictive, and there is great value in employing additional relevant models when 

conducting an assessment. Yes, one may (will) get different answers, but it does provide an opportunity to 

better understand the driving factors in an assessment and a clarification of the uncertainties. I was not 

advocating for a replacing E-FAST, but, rather, using others in addition to. I was not advocating for the 

use of SHEDS, specifically, but suggesting that an exploration of its components, with or without 

modifications, and those of other models should be incorporated into any refinement of this initial 

screening assessment. 

During the July 7 pre-meeting, several of the Panel members raised a concern about the decision to 

exclude dermal exposure from this assessment. I share this concern and recommend that any revised 

assessment include this route of exposure in it. To support this recommendation, I examined the 

directions for use for several of the products listed in the Supplemental Product Information document 

provided to us. For many of the spray formulations, I discovered something like the following on the 

label: 

“Eye/face Protection: For normal conditions, wear safety glasses. Where there is 

reasonable probability of liquid contact, wear splash-proof goggles. 

Skin Protection: Use protective gloves such as nitrile or neoprene. Also, use full 

protective clothing if there is prolonged or repeated contact of liquid with skin.” 

Users, both in the commercial and consumer population, often don’t follow the label directions, in fact, 

never even bother to read them. It’s clear to me that dermal exposure will be occurring in the course of 

use in all of the scenarios being evaluated. Often the object being treated is held in a bare hand. The 

object may then be wiped dry with a shop cloth, which in turn, with repeated use, gets wet and soaks 

through to the skin of the holder. Furthermore, there is the question of enforceability of label directions 

for these products. There are mechanisms to do it for pesticide products, but TSCA doesn’t afford that 

authority and I’m unsure if the other federal agencies involved in worker and consume authority are 

effective in this matter. 

See my comment below about including children ages 11-15 as users in all of the user scenarios. In the 

commercial scenario, they should be assessed as bystanders as well. In some states, children as young as 

10 are allowed to work, although they may be required to get a work permit if they are under 16-18, 

depending upon state labor law. 

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). 

As mentioned earlier, determine if additional, useful, exposure assessments can be developed using 

SHEDS-multimedia or other credible non-EPA models. 

Use empirical monitoring data, generated in studies conducted either by requirement imposed upon the 

manufacturers or by EPA alone or in collaboration with other relevant agencies such as NIOSH or CPSC. 

Ditto for requiring or conducting consumer use surveys. 
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The two E-FAST model outputs (degreaser and protective coating uses) do not include children in the 11-

15 age group as users. I believe that there are many kids in that age group who are “users” under both 

scenarios; the assessment should include them as well. [For example, both my son and his son and their 

buddies from their respective generations started rebuilding automobiles, engines included, when they 

were 14 and my son started working in a gas station repair garage when he was 15]. 

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

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

It is perfectly appropriate, and quite commonplace, to match endpoints with durations of exposure, and, 

then, apply this information to specific subpopulations in addition to, or instead of, the general 

population. 

The body of historical data generally supports the observation that repeated exposures are required to 

elicit persistent adverse effects in the liver and kidney, although these might occur following less-thanlifetime exposures. As for effects on the immune system, it is clear that long-term effects can be produced 

following extended exposure. However, I cannot speak for inclusion/exclusion of immune system effects 

in the assessment of acute exposure, given that there are very few studies on acute exposures and I have 

little technical expertise with this particular system. 

While data are less precise for determining whether or not (and, as importantly, when) a single acute 

exposure to TCE can lead to developmental effects postnatally, the default health-protective assumption 

that one dose on any one day of gestation may do so is widely embraced in the risk assessment 

community. This principle applies when examining the data related to potential cardiac abnormalities in 

the fetus, but it does not apply to other kinds of observed effects such as fetal weight depression or others 

that are observed in the presence of maternal toxicity. 

Acute effects on the nervous system following acute exposures to TCE have been observed in many 

studies. Thus, it is appropriate to include an acute exposure scenario in this assessment. But, I believe that 

neurotoxicity also should be included in the chronic scenario assessment as well. While I did not examine 

closely the dose-response characteristics for effects observed in specific studies following extended 

exposure, they have been observed both in humans and animals. Perhaps, their NOAELs/ LOAELs/ 

BMDXs/HECs would be high enough to yield MOEs of no concern. I didn’t do that analysis, but simply 

would note some excerpts from the 2011 IRIS document that support evaluation of extended exposure. 

These include 1) “Four epidemiologic studies of chronic exposure to TCE observed disruption of auditory 

function. Further evidence for these effects is provided by numerous laboratory animal studies 

demonstrating that high-dose subacute and subchronic TCE exposures in rats disrupt the auditory system, 

leading to permanent functional impairments and histopathology,” 2) Overall, the human and laboratory 

animal data together suggest that TCE exposure can cause impairment of visual function, and some 

animal studies suggest that some of these effects may be reversible with termination of exposure, “ and 3) 

“Two studies of TCE exposure, one chamber study of acute exposure duration and one occupational study 

of chronic duration, reported changes in psychomotor responses” (US EPA 2011). 

Reference 

US EPA . (2011). Toxicological Review of Trichloroethylene (CAS No. 79-01-6). In Support of Summary 

Information on the Integrated Risk Information System (IRIS) EPA/635/R-09/011F. 
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Question 4-2: Please comment on the strengths and weaknesses of using multiple values for each 

type of adverse effect. 

One might argue that having and using more than one value for each endpoint is a strength in that it does 

demonstrate that one can get a variety of results, using different data sets. On the other hand, it doesn’t 

necessarily lessen any uncertainties in the hazard assessment, and it does take more effort and resources. 

One might be better off selecting a value from the study deemed “best,” that is, most representative of the 

database for each “-icity,” based upon an assessment of study integrity/quality, and using just that one in 

this screening assessment. 

Question 4-3: PBPK modeling was employed in the 2011 IRIS assessment for route-to-route 

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, 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 life stages. 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. 

I would hesitate to summarily dismiss all oral studies out of hand from this assessment. To me, the 

principal criterion for inclusion/exclusion would be the credibility/integrity of the study rather than 

simply the route of exposure. IF the Agency had conducted a systematic review of the literature and each 

study as it was developing the IRIS document, it would be a relatively easy task to identify the one best 

data set to represent the endpoint/duration of exposure/(sub)population to be evaluated. But, there is no 

documentation to show that this exercise was carried out and I doubt that it occurred. 

Therefore, I would recommend that OPPT take another look at the oral studies, make their own 

determination of their value and include the “good ones” in a refined assessment along with, or instead of, 

all of the inhalation studies in the current assessment. If OPPT didn’t do its own systematic review of 

those inhalation studies before using them in the screening level assessment, it should do it before 

keeping them in a refined assessment. 

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 non-users. 

I’ve always viewed the MOE approach as the RfD/RfC approach lying on its side. The MOE is a unitless 

number, derived by determining the ratio of the NOAEL/LOAEL/BMDX or HECto the estimated 

exposure. Embedded in the part-risk assessment/part-risk management determination of the 

“acceptability” of a specific MOE is a consideration of what uncertainty factors would be appropriate to 

apply if an RfD or RfC were being calculated for the same example. A strength of the MOE approach is 

that it is simpler and less time-consuming to calculate and describe than deriving an RfD or RfC because 

one doesn’t have to list and justify each uncertainty factor used. A weakness would be if the application 

of the MOE approach is not accompanied by a discussion of the rationale/practice/policy by which the 

judgment of acceptability is made. 

In this assessment, it does state what MOE value constitutes the point separating a potential risk concern 

from one of no concern (“When the hazard value (HEC) is divided by the exposure value, the resulting 
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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,” page 11). 

Some analysis/justification is offered on page 61 for this choice: 

“ 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 inadequacy of the argument is two-fold: 1) There’s no articulation for what the HEC99 is more 

conservative than, or 2) for why would/wouldn’t an MOE of 30 be satisfactory for a different HEC. In 

other words, why is this pairing (HEC99 and 30) the best choice, in this case? 

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). 

In my mind, the two sentences in the question are unrelated. I do not see the application of the MOE 

approach as dependent upon what parameters ( exposure duration and (sub)populations) are selected to 

assess an exposure scenario. As far as the strengths and weaknesses of using the MOE approach for 

estimating acute risks, they are the same as for estimating chronic, non-cancer risks. [See comments on 

question 5-1]. 

As for the second statement, I find it difficult to support the assumptions applied in the two acute 

scenarios, given that there appear to be no empirical data or even credible surrogate information or 

consumer survey data available to support them. 

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. 
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Although more convenient for making comparisons across studies, I do not agree with the use of a 

uniform benchmark MOE for all studies or endpoints. Each study should be judged on its own merits and 

deficiencies, and that judgment should be reflected in a study-specific composite uncertainty factor and 

benchmark MOE. 

Another aspect of the exercise as currently implemented is the lack of consideration of the adequacy of 

the database for characterizing both the qualitative and dose-response elements of each endpoint. I am 

aware that EPA, in the 2011 IRIS document, stated that there was no need for a database uncertainty 

factor (other than 1X) to be incorporated into any composite uncertainty factor for studies which 

contribute overall to the derivation of the RfD or RfC for TCE because the toxicity database, considered 

in its entirety, was adequate for that purpose. However, in this TCE assessment, adverse endpoints are 

being evaluated in isolation from one another. Therefore, I recommend that OPPT revisit this issue, 

asking the question “Is the data set available on Endpoint X adequate for describing this endpoint’s 

qualitative and dose-response elements?” And, if the answer is “No,” a database uncertainty factor >1X 

should be incorporated into the equation and the benchmark MOE increased to accommodate it. 

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. 

Chapter 3.D. presents a discussion of the key sources of uncertainty and data limitations in the risk 

assessment. I would generally agree with the arguments made as to which components of the exposure 

assessment reflect the greatest uncertainty and which ones are lesser contributors. I would differ with 

some of the statements made regarding the hazard assessment. I would not say that “uncertainty is 

captured by the use of uncertainty factors.” Use of uncertainty factors, particularly default factors, does 

not necessarily lessen the uncertainties. In fact, it may mask them. Only if chemical-specific factors are 

employed is the uncertainty reduced. They were not employed in this assessment. 

I also do not agree that developing multiple PODs/HECs from different studies for effects on the same 

system necessarily reduces uncertainty. In this case, it depends on the quality/integrity of each individual 

study and whether or not each study is evaluating the same set of parameters. This is not the case for 

TCE. 

By selecting the HEC99 and very conservative assumptions about exposure, one ends up with a very 

conservative (that is, health-protective) risk assessment, which assures only the certainty that the potential 

risk has not been under-estimated. It does little to resolve the uncertainty of the true estimate of risk. 

Odds and Ends 

1. Clarify that the statement on page 12: “ The method EPA used calculated extra cancer risk from 

benchmarks of concern based on no more than one excess cancer in a population of 100,000 

workers (i.e., 1 x 10-5) ....” is actually an OPPT policy, not a universal EPA policy. OPP’s target 

risk for cancer in the occupational setting (i.e., mixers, loaders, applicators) is no more than one 

excess cancer in population of 10,000 workers (i.e., 1 x 10-4). 

2. Correct the Agency’s cancer classification from “probable human carcinogen” to “likely 

carcinogenic in humans” as per Dr. Melnick’s observation. 
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3. Conduct an internal review of the Forand et al (2012) paper, and incorporate a summary and 

conclusions in a revise/refined assessment, when conducted. 

4. Run SpellCheck 

 
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Jeffrey H. Driver

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. 

The draft document and “characterization” contained therein represents a screening-level assessment and 

the report should be revised so that the assessment is described accordingly. Screening model (and 

assessment) results are intended to be conservative, i.e., predicted concentrations and exposures are likely 

to be at the “high end” of the distribution that might occur in real-world settings. If an exposure estimated 

by a screening model results in an unacceptably high health risk estimates, then an appropriate next step 

in the assessment process would be to identify sensitive input parameters and then refine them, and 

perform the assessment with different and perhaps more complex models. Another response might be to 

consider monitoring to gather actual product use information (e.g., worker and consumer application 

methods, amount used, micro-environmental setting, frequency of use, bystander time-activity patterns), 

emissions data, air monitoring data, etc., that can be used to estimate exposure. This above tiered, stepwise process is an EPA-accepted approach to risk analysis and should be implemented in the case of TCE. 

The clarity of the hazard characterization, specifically the HEC modeling requires additional discussion 

and consideration. The uncertainty around the HEC modeling is difficult to understand and is a critical to 

deciding on the appropriateness of lower bound 99th percentile across the various dose-response 

relationships considered. I would be informative to also provide a presentation of risks for each 

toxicological endpoint using traditional MOE derivation (with uncertainty factors documented). Given the 

early, screening-level nature of the TCE assessment, is not ready for peer review, but rather should be 

refined by EPA and via stakeholder input. Extending the peer review to colleagues in other EPA offices, 

such as the Office of Pesticide Programs, could also be helpful, given their experience with workplace 

and residential settings. 

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.

The draft document should expand presentation of other relevant TCE-related health protection standards 

and assessments. Workplace and residential environments where TCE products could be used should be 

further described/characterized. This is critical to realistic modeling of worker and consumer potential 

inhalation exposures. Existing exposure monitoring data (e.g., indoor air monitoring) should be discussed 

further. Alternative exposure modeling (e.g., EPA’s MCCEM model using probabilistic simulation 

options) should be considered, particularly of some of the toxicological endpoints should be compared to 

time-weighted average daily inhalation exposure/dose estimates, rather than near-field, peak exposures. 

Comparison of model predictions air concentrations and absorbed doses via inhalation to actual 

monitoring data (e.g., indoor air concentrations), biological monitoring (e.g., blood levels – see 

NHANES) should be considered. Background documentation should include reference to and summary of 

these existing data (e.g., indoor air monitoring, biological monitoring). 

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).
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1. EPA should refine the risk assessment for workers (and for consumers). While a two-zone, near 

field model is an appropriate choice for initial modeling and exposure evaluation, the resulting 

assessment as presented is not appropriate for informing risk management decisions. Areas of 

refinement for workers for example, include recognizing that OSHA has guidelines in place 

controls (NESHAP) that functionally limit the upper bound exposures to the current OSHA PEL 

of 100 ppm (the ACGIH TLV is 25 ppm – EPA 2012 TSCA Workplan Chemical Risk 

Assessment for TCE). EPA’s assessment of workers assumed that the degreasing operations 

occur during work hours. If the degreasing in fact occurs at the end of the day, there is virtually 

no exposure; apparently EPA assumed that the degreasing operation occurred in the same room 

occupied by workers, i.e., the “near field”. If, in fact, the degreasing operation occurs in a 

dedicated room devoid of workers, there is no “near field” exposure. An understanding of the 

actual work place practices (including ventilation conditions and the use of personal protective 

equipment) and the proportion of workers experiencing near field exposures is imperative. 

Distributions for parameters could be used, e.g., ventilation rates) to inform sensitivity evaluation. 

2. EPA should refine the screening-level exposure modeling presented and present the full range of 

exposure factors and risk estimates, e.g., exposure and risk estimates reflecting alternative 

percentiles for comparisons of exposure distributions to alternative, non-cancer HEC percentiles 

values. The refined modeling (probabilistic) should include a sensitivity analysis. Further, EPA 

should justify why an HEC99 is being applied to exposure estimates other than acute exposures. 

Even in the case of acute exposures, if an HEC99 is used, the uncertainty factors associated with 

the PBPK-derived value must be revised. In this context, over the course of 2 weeks to a lifetime, 

exposures experienced by any given individual will be an average, not an upper bound. 

3. The amount of product used for the consumer exposure aerosol application scenario should be 

informed by actual (or a simulated experiment) product use information. Aerosol products are the 

most common consumer product form used. A request for relevant data should be issued to the 

public and the regulated community. Product use studies (e.g., gravimetric measurements before 

and after use) are often available (or can be developed) to inform this highly sensitive input 

parameter for indoor air/exposure monitoring. Other sensitive input variables are the microenvironment where the applicator (and bystander) are located, e.g., outdoors or in a garage with 

an open door, and the associated air exchange range; also, the time spent applying and being colocated with the treated article/surface (currently assumed to be 1⁄2 hr, but actual spraying requires 

seconds). These factors can be addressed by consumer time-activity surveys, or at least can be 

informed by using ranges or distributions of values consistent with EPA’s current exposure 

factors guidance. 

4. The evaporation rate is estimated from equation (3–42 in the E-FAST manual) that provides an 

estimate of the time for 90% evaporation of a "pure chemical film" based on the vapor pressure 

and molecular weight. This results in a conservative estimate for consumer products which are 

mixtures released under non-steady state, intermittent conditions. EPA should also consider 

comparison of model predictions to any available actual air monitoring for chemicals with 

comparable uses, methods of application and vapor pressures. Toluene or xylene monitoring 

following aerosol use might be an excellent surrogate. The model used did not include provision 

for “sink effects”. The lipophilicity of TCE will drive the vapor to adsorb to organics in the room 

including floor coverings, wall coverings and furniture coverings, and reducing its concentration 

in air much more rapidly than air exchange alone. 

5. The exposure assessment for aerosol application assumes that the same maximum percentage 

product is used each time, and that no change in formulation occurs over a 57 year duration. It is 

unlikely the product will exist in 57 years, let alone that it will have the same composition, or that 
12 of 73 

the individual will use the same product all that time. It also assumes this individual will continue 

to lacquer-coat objects over their entire adult lifetime. The probability of all of these assumptions 

co-occurring is extremely low. EPA might be estimating the risk for a single individual in the 

US. 

6. A useful method for evaluating model predictions such as those presented in EPA’s TCE 

assessment is comparison to indoor air monitoring data (e.g., Bakke et al. 2007; Shah and Singh, 

1988; Sexton et al., 2005; Santodonato, 1985) during and following an aerosol application 

relevant to the TCE aerosol products of interest. While these data do not always reflect the same 

circumstances/scenario as being modeled, they are useful for characterizing potential inhalation 

exposures to TCE. Thus, while EPA acknowledged reviewing indoor air monitoring data, 

presenting available TCE and surrogate chemical data can still be useful to “ground truth” model 

predictions and inform data development recommendations (e.g., chamber studies). When 

screening-level assessments suggest issues of concern, the cost/risk benefit of collecting 

additional scientific data (e.g., NIOSH, CPSC) should be considered. 

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). 

Comments to Question 2-1 are relevant to this question. The consumer/hobbyist model should be 

refined/revised using alternative methods. The Nicas 2 zone model or MCCEM 

(http://www.epa.gov/opptintr/exposure/pubs/mccem.htm) are options to consider. The Nicas model can 

accommodate dynamic, non-steady state emission rates and can predict point-in-time and time-weighted 

average (TWA) exposures for relevant exposure periods. These can be expressed as 24 hr TWA 

exposures or longer-term, chronic exposures given the number of days per year in which the activity is 

engaged. Exposures to applicators could also be estimated generically using the EPA’s Pesticide Handlers 

Exposure Database unit exposure values for hand-held aerosol cans. This could provide a conservative 

estimate of dermal exposure in particular, given that PHED data are largely based on chemicals with 

lower vapor pressures than TCE. The inhalation exposure estimates based on PHED aerosol spray could 

be underestimates for this reason. 

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

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

1. A systematic evaluation of the quality (including relevance and reliability) of each key toxicology 

endpoint study is necessary. Further, selection of the appropriate time-averaging period, relevant 

to each endpoint selected from reliable studies is critically important for deciding what exposure 

(absorbed dose) metric should be used for risk estimate derivation. Neurotoxicity and 

developmental toxicity endpoints may, or may not be appropriate for comparison to acute / peak 

potential inhalation exposure/dose estimates, depending on the time to effect (e.g., trigeminal 

nerve response, development effects related to exposure on a critical period of gestation versus 

body weight gain decrease over a period of weeks). 

2. HECs derived in the IRIS document from the PBPK model are a daily average computed for 

continuous exposure (USEPA 2011). However the exposures considered for degreasers and 
13 of 73 

hobbyists reported in the TSCA work plan is not continuous, but rather is an 8-hour timeweighted average for the worker and a 24-hour average exposure for hobbyist. 

3. Just as inhalation toxicity testing results are amortized or adjusted for exposure frequency and 

duration, so should the exposure of the persons for whom the assessment is being conducted. In 

other words, toxicity testing results are adjusted from the 4 to 6 hour test animal / subject 

duration, and 5 to 6 days per week exposure frequency. Likewise the individual’s exposure 

estimates should be amortized over the duration of the toxicity testing, i.e., if an effect was 

observed on the 13th day of toxicity testing, the consumer exposure should be averaged over 

13 days. This was done for “chronic” effects, but not for the “acute” effects. In fact there were no 

true acute effects utilized in EPA’s assessment. The neurotoxicity study duration was 6 weeks, 

and although neurotoxicity can be observed in humans after a single exposure, it occurs at much 

higher dosages. Similarly, the developmental toxicity study duration was 13 days, but the some of 

the effects observed (e.g., decreased fetal weight and increased resorptions) are not consistent 

with a single dose exposure. 

 

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

type of adverse effect.

The HEC99 are from 2 to 10,000-fold lower than the corresponding POD value. When the difference 

between the benchmark from an animal study and the HEC99 is >100 it suggests that additional 

uncertainty factors (either within or between species) are not necessary. Moreover, differences of 1000-

fold or more call into question the underlying assumptions that produced these hypothetical differences. 

For example, when endpoints are similar (neurotoxicity or reproductive toxicity) for animals and humans, 

the ratio of POD to HEC are < 100-fold between species. So what underlying assumptions make the ratio 

of BMDL to HEC99 > 10,000 for kidney effects? 

Question 4-3: PBPK modeling was employed in the 2011 IRIS assessment for route-to-route 

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, 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.

Using oral toxicology studies with the same toxicological endpoints would be reasonable provided the 

oral and inhalation toxicokinetics (metabolites) can be appropriately modeled, and systemic absorbed 

dose is of interest. Comparison of benchmarks derived from relevant and acceptable oral and inhalation 

route studies could provide useful weight of evidence insight across animals and human data sources. 

However, the nature of the study designs and endpoint of interest should be considered, e.g., routespecific / route of entry dose-response. The PBPK model applied in the development of the HECs is 

apparently not intended to model pregnancy or gestation and as such application of this PBPK model to 

estimate dose-metrics for developmental effects should be reconsidered / evaluated. Typically the 

placenta will lower exposure to the fetus by 2 to 10-fold. Since a key concern is developmental toxicity, 

that should be considered. Comparison of benchmarks derived from oral and inhalation routes can 

provide useful insight. 
14 of 73 

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 non- users. 

The most significant issue associated with the TCE MOE-based risk assessment approach is the HEC 

derivation and use of the 99th percentile value. The HEC50 values derived by EPA are 1.5 to 1,000-fold 

lower than the lowest concentration tested in the toxicity tests from which they were derived. 

Interpolations of magnitudes >10-fold are so far removed from measurements as to be meaningless. When 

those interpolated dosages are than applied as acute endpoints, it implies that a single dose at these levels 

of exposure can have an effect. There is no rational scientific support for such estimates when toxicology 

study durations were a minimum of 13 days. For example, if the HEC50 predicted for human kidney 

effects is correct, there should be clear evidence of adverse effects in human users of TCE at EPA’s 

calculated levels of exposure. Since that effect does not seem to be in evidence, it suggests that both the 

exposure and HEC50 are in question. 

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). 

See comments regarding Question 5-1. The comparison of acute exposure estimates to repeat dose-based 

PODs is not appropriate. The specific time domain of “acute exposures” for MOE derivation to the 

endpoints of interest should be more clearly defined, e.g., 24-hour average inhalation exposures to 

provide a daily mg/kg/day absorbed dose estimate. Applicators and bystanders time-location patterns are 

documented in E-FAST supplemental information, however, only acute dose rate (based on peak 

concentration) and lifetime average daily dose are provided. 

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.

The use of the factor of 30 for the MOE is apparently composed of 10 for intraspecies variability and 

uncertainty and a factor of 3 for the pharmacodynamic portion of the interspecies extrapolation factor. 

The factor of 3 may not be appropriate for the HEC 99th percentile. The document should address this 

issue in the context of different toxicological endpoints (and their underlying studies) of interest. 

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. 

Data limitations and uncertainties are not adequately or transparently described for exposure estimates 

and associated parameters (e.g., how long, how much and the size of the exposed subpopulations using 

TCE-containing products within residences) or hazard benchmarks to support risk management decisionmaking. Also, the toxicological benchmark modeling used requires additional consideration and 

evaluation (e.g., consideration of oral data; consideration of endpoint relevance to humans; endpoint-byendpoint risk estimation). The risk estimates for TCE need to be careful considered and informed by 

additional context/information. For example, consideration of existing TCE exposure and biological 
15 of 73 

monitoring data (Wu and Schaum 2000). Reducing risks that are unacceptable is the obvious public and 

environmental health goal, but interpreting the results of the TCE assessment for risk mitigation purposes 

is premature. 

References 

Bakke, B., P.A. Stewart and M.A. Waters. 2007. Uses of and exposure to Trichloroethylene in U.S. 

industry: A systematic literature review. J. Occup and Environ Hygiene. Vol 4, Issue 5, pp. 375-390. 

Charles B. Keil, C.B. and Mark Nicas: Predicting Room Vapor Concentrations Due to Spills of 

Organic Solvents, AIHA Journal 64:445–454 (2003) 

Santodonato, J. 1985. Monograph on human exposure to chemicals in the workplace: trichloroethylene. 

NTIS PB86-134574/GAR (cited in ATSDR, 1997). 

Sexton, K., Adgate, J.L., Church, T.R. et al. 2005. Children’s exposure to volatile organic compounds as 

determined in longitudinal measurements in blood. Environ Health Perspectives 113(3): 342-349. 

Shah, J.J. and Singh, H.B. 1988. Distribution of volatile organic chemicals in outdoor air and indoor air: 

A national VOCs data base. Environmental Science and Technology 22(12): 1381-1388. 

Wu and Schaum. 2000. Exposure Assessment of Trichloroethylene. Environ Health Perspectives. 

108:359-363. 

 
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Montserrat Fuentes 

Question 5.2 

The margin of exposure (MOE) is the ratio of a toxicologic potency value to an estimated dose or 

exposure level. The application of the MOE-approach requires reliable animal carcinogenicity data or 

reliable epidemiological data including very good quality exposure assessment. A concern of using the 

MOE is that his procedure does not take into account differences that occur in susceptibility between 

humans and animals nor within animals or humans. The MOE would not determine casual relationships, 

but associations. For the TCE risk assessment, EPA is using the MOE to estimate non-cancer risk. EPA is 

using a very conservative value for the hazard, so the risk would not under-estimated. In the MOE, the 

exposure needs to be carefully characterized (duration of exposure, time in between...). 

The use by EPA of the MOE to estimate acute effects could be questionable, due to two important issues. 

For acute effects, there is less information on the hazard value that is being used, the adopted HEC99 

value is obtained using repeated exposure on consecutive days and calculating a 24-hour average. When, 

in practice, the exposure would likely last just few minutes, with potentially long times in between 

without exposure allowing for time to recover from the impact of the short time exposure, so using a 

24-hour average would potentially overestimate the risk. The other issue is to limit analysis to acute 

exposures without residual concern between events. In the case of once/week for users of the clear 

protective coating spray, and twice/month for degreaser users, the risk of residual would be relatively 

small, so this potentially would be less of a concern. 

The overall main issue with the use of the single MOE value is the lack of characterization of the 

uncertainty in the estimated risk. The fact that the MOE is reduced to the use of two numbers, the hazard 

value and the exposure value, regardless of how they were obtained, does not provide a quantitative 

assessment of how much we can rely on that estimated risk. Even if potentially a Bayesian statistical 

framework is used to obtain the hazard value. As long as just a number is used for the hazard value in the 

MOE calculations, there is no characterization of uncertainty. This issue could be addressed, by 

incorporating in the MOE a metric to characterize the uncertainty in the hazard value and/or the exposure 

value, for instance calculating the MOE with different possible values of both, the hazard and the 

exposure, under different scenarios to understand the impact in the obtained MOE. An empirical variance 

of the MOE would explain how variable the MOE would be, and sensitivity analysis would explain how 

sensitive the MOE is to how the exposure and the hazard are obtained under different scenarios of 

interest. Comparing the MOE to just a benchmark number, 30 in this case, is questionable, in particular 

when there is no assessment of the variability and uncertainty in the MOE. 

 
17 of 73 

Kathleen Gilbert 

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.

General comment: In general the characterization represented a reasonably clear and logical presentation 

of a lot of complex data. However, as raised in the panel discussion, it would be helpful to have a better 

idea of how this assessment is going to be used. Its purpose and expected readership would help define 

the style and content of the document. 

Specific comments include: 

Chapter 1. Scope of Assessment for TCE 

This chapter was, for the most part, satisfactory as it provided useful if basic background information on 

TCE, and most importantly provided the rationales used to decide the focus of the assessment. The 

rationale for confining the assessment to inhalation exposure and for using multiple endpoints was welldescribed and logical. The non-cancer endpoints selected, including neurotoxicity and developmental 

toxicity, made sense based on the human health effects of TCE that have been identified. 

On the other hand, the choice of hobbyists as the other population to be included in the assessment was 

less compelling. The assessment did suggest that this population may face some health risks as a result of 

their exposure. However, focusing on hobbyists instead of another population at risk from occupational 

exposure seemed odd. It is true that in the dry cleaning industry use of TCE as a bulk textile cleaner has 

largely been replaced by PERC or more recently by hydrocarbon or silicone-based cleaners. However, as 

pointed out in a 2007 document prepared for the California EPA’s Department of Toxic Substances 

Control and the US EPA TCE-containing spot/stain removers (e.g. Picrin, Volatile Dry Spotter, Semi Wet 

Spotter, ADCO Puro Spot Remover, Caled Fast P-R) are still used as paint, oil and grease spotting agents 

in the textile cleaning industry. 

According to a 2013 book entitled Chlorinated Solvents. A Forensic Evaluation published by the Royal 

Society of Chemistry: “In 2009, TCE was still widely used as a dry-side pre-cleaning or spotting agent 

and in water repellent agents. TCE is the principle ingredient in Fast PR, 2-1 Formula, Picrin, Puro, 

SemiWet Spotter, Spra-Dri and Volatile Dry Spotter”. 

Recent MSDS documents list TCE as the main ingredient for all of these spotters. There are currently in 

the US about 41,500 dry cleaning facilities employing approximately 4 people/facility (according to 

IBISWorld). That represents a substantial number of people who could presumably be exposed to TCE on 

a routine basis. It would be useful for the EPA to clarify why personnel in the dry cleaning industry were 

omitted from this assessment. Is there information that the TCE-containing spot removers are not widely 

used or have been discontinued? Alternatively, do the ventilation requirements in dry cleaning facilities 

make significant TCE exposure unlikely? 

Chapter 2. Sources and Environmental Fate of TCE 

This is the first time I have been asked to review such a document. So, perhaps there are historical or legal 

reason to include all of the information in this chapter. The basic physical and chemical properties 

described in Section A. Physical and Chemical Properties of TCE seemed appropriate, as did the Section 

C. Production Volume and General Information on Uses. However, from a driving the narrative 
18 of 73 

perspective the information in Section B. Environmental Fate did not seem to be necessary. Why is the 

fate of TCE in soil, sediment and groundwater needed for an assessment focused on inhalation of TCE 

from industrial or consumer products? 

Some other clarification would be appreciated. The chapter concludes with: 

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

have low bioaccumulation potential and moderate persistence.” 

Everything is relative. Some people consider the human half-life of TCE (around 51 hours) to be long 

while others consider it short. Is there an official definition of what constitutes “low bioaccumulation” 

and “moderate persistence”? If not, the use of these terms without qualifiers is less than satisfactory and 

leaves things up to interpretation. 

Chapter 3. Human Health Risk Assessment 

There was a good explanation of how TCE is released by small commercial degreasing operations and a 

comparison of the types of line and batch degreasing machines. The finding that most (66%) of TCE 

emissions in 2008 were from nonpoint sources (including small industrial/commercial operations) 

bolstered the choice of personnel at these facilities as assessment targets. However, the discussion 

regarding difference in fugitive aim emissions of TCE as reported by NEI and TRI was somewhat 

confusing. Especially unclear was the statement that 

“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).” 

What does “based on the comparison” mean? This should be clarified. 

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

accurately characterized. 

 As mentioned there are documents describing the role of TCE-containing spot/stain removers in 

the dry cleaning industry. These reports suggest that this form of TCE exposure may be worthy of 

inclusion in this assessment, and have been sent with these comments. 

 In Chapter 3 the description of the toxicity endpoints was based largely on the extensive 2011 

IRIS Toxicological Review of Trichloroethylene. The authors provided a useful summary of the 

basic findings and associated data points from selected manuscripts. In describing the TCE hazard 

database the assessment says: 

“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.” 

However, even in the IRIS document is was not easy to find the criteria used to select particular 

papers for inclusion. A brief statement explaining selection criteria would be appreciated. Since 
19 of 73 

many of the metrics used in the assessments were based on a limited number of studies it is 

important to understand how those studies were selected. 

Question 2-1 and 3-1 on Exposure Assessment 

 The authors seemed to make logical assumptions about possible exposures based on the limited 

information available. For example, the rationale for selecting the assessment target population 

consisting of employees of small commercial shops that perform relatively routine degreasing 

seemed logical. The assumption that the TCE exposure of the employees of these small shops 

would be less controlled than employees of a larger facility seems likely. The estimated duration 

and frequency of the exposure also seemed logical. 

 The nonpoint sources were assumed to be batch vapor or batch cold units. Based on the 

assumptions concerning differences in TRI and NEI emissions the estimate of TCE emissions to 

air from small commercial decreasing facilities seemed sound, as did the assumption of potential 

emissions per minute (average release per facility/260 days x 2 hours/day at those facilities) and 

the estimates of worker exposure taking into account typical and worst-case estimates of room 

ventilation volumes. 

 Their choice of TCE-containing household products based on the NIH Database seemed 

appropriate. The assumptions used to estimate hobbyist exposure based on duration and number 

of events seemed reasonable. Estimating exposure for the hobbyists was more problematic. 

However, it seemed like the E-FAST approach was a logical one. 

 The assessment applies the 1.2 decreasing units/facility found at the larger point source facilities 

based on the Emission Inventory System to estimate the number of smaller degreasing facilities 

(1,799 nonpoint sources divided by 1.2 machines to equal 1,483 small industrial facilities. It is 

not intuitive why the number of machines found at a large facility (which logically might be 

expected to have more than one machine) can be translated to small nonpoint sources (which 

logically might be expected to have only one machine/facility). Clarification on this point would 

be appreciated. 

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

based on exposure durations. 

 It is clear that the impact of TCE on different systems varies according to the duration of 

exposure. Neurotoxicity can be induced after a brief exposure, while immunotoxicity usually 

requires chronic exposure. Therefore, although it may be more complicated than evaluating a 

single cadre of endpoints, a comprehensible and precise hazard assessment requires evaluating 

different endpoints based on exposure duration. 

 Bioaccumulation of TCE, described as low, was dismissed from the exposure calculations. The 

following text described TCE half-life: 

“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 
20 of 73 

200 hours (i.e., about eight days) with nearly complete clearance by approximately 

350 hours (i.e., a little over two weeks).” 

While TCE bioaccumulation is definitely low compared to certain toxicants such as mercury, it is 

not clear from the half-life description that it can be completely dismissed, especially in the case 

of the personnel in the small degreasing facilities whose estimated exposure frequency is 260 

days per year for 2 hours per day. 

Question 4-2: Please comment on the strengths and weakness of using multiple values for each type 

of adverse effect. 

The OPPT seems to have done a good job deriving PODs and HEC99 from the existing data. Human data 

sets are often insufficient for quantitative risk assessment so the inclusion of animal studies was crucial. It 

is only to be expected that these will vary according to the target organ system. As described in the 

assessment there is an approximate 1000-fold difference between the lowest and highest lower-end HEC99

based on the organ system. Using all six endpoints provides the more comprehensive and precise risk 

assessment. However, a better justification of using HEC99 as opposed to another benchmark would be 

helpful. 

Question 4-3: 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. 

This question can be argued from both points of view. Since the assessment is focused on inhalation 

exposure it makes sense to derive their risk assessment from the data of inhalation studies. On the other 

hand, including data extrapolated from oral exposure studies would provide a richer data base and 

presumably increase the confidence of the metrics. The only caveat would be that in some cases, such as 

certain immunotoxicity endpoints (e.g. lung inflammation) oral and inhalation exposure would be 

expected to yield different results. In those cases, inhalation only exposure studies seem more appropriate. 

Questions 5: Please comment on the strengths and weakness of the MOE approach, and whether 

the document has adequately described the uncertainties and data limitations in the methodology 

used. 

 Depending on the approach used to determine the POD and to estimate exposure it is possible to 

derive very different values for the MOE. However, it can be a very useful risk assessment tool 

if the endpoint is carefully selected and the derivation of the values carefully justified. Especially 

important is the shape of the dose-response curve at human relevant doses. This information in 

the current setting requires a lot of assumptions, especially for the non-users. However, it seems 

like the best approach to use even with the limited quantitative data available. THE OPPT has 

fairly described the uncertainties regarding consumer TCE exposure. 

 Since benchmark MOE values usually range from 10 and 100, the selection of 30 as the 

benchmark for the TCE assessment seemed logical, especially in view of the factors used to 

account for intraspecies variability and the pharmacodynamic portion of the interspecies 

extrapolation factor. However, it would be helpful to include a better discussion of the 

uncertainty factors that were used (or omitted) to derive the particular benchmark. 
21 of 73 

 The OPPT described the uncertainties with both “typical” and “worst-case” scenarios. They 

pointed out the greatest uncertainties in the hobbyist groups and consumer use in general. This 

was useful, but as pointed out above, could have been more in-depth. 

Public comments 

I thought some of the public comments raised interesting points. I would appreciate clarification on these 

specific comments: 

 The point was made that TCE is already adequately regulated under the Clean Air Act. Does that 

pertain to the exposure scenarios described in the assessment? 

 It was stated that the assessment was based on exposure data that predated regulations on vapor 

degreasing. Is that true, and if so, would it expect to alter the risk assessment? 

Some other comments seemed more disingenuous and self-serving. Complaints that the EPA used worstcase rather than more likely estimates of exposure and risk seemed unwarranted, as did the suggestion 

that possible TCE substitutes used as a result of the assessment could turn out to be more harmful for the 

environment. The view that the assessment needed to use measured rather than modeled data of exposure 

was impractical. 

General comment 

The assessment represented a good attempt to devise reasonable risk assessment predictions based on a 

large, if somewhat disparate, body of literature. In an ideal world this assessment would be based on 

measurements of internal TCE levels following different types of human inhalation exposure scenarios. It 

would also include more definitive epidemiological data of human health responses to these scenarios. 

However, in many cases this data is not available, and unlikely to become available, at least in the 

foreseeable future. This means that exposure modeling and data extrapolation is required for risk 

assessment. This seems appropriate. Having said that, additional data including descriptions of TCE air 

levels following experimental releases, a better justification for the studies used to derive the metrics, 

possible sensitivity analyses, and more detail about the uncertainty factors used to determine the 

benchmarks would bolster the assessment. Yes, the assessment document can and should be improved. 

However, in my opinion, this important risk assessment should not be sidelined by the need to reach a 

complete consensus by all interested parties. 

Supplementary comments in response to EPA clarifying questions presented at August 21, 2013, 

TCE post-meeting 

See ‘TCE_Gilbert Supplemental Material.pdf’ for: 

1. Spotting Chemical Fact Sheet; 

2. DTSC Spotting Chemical for Web; 

3. Material Safety Data Sheet: Fast – PR; and 

4. Material Safety Data Sheet: Picrin. 
22 of 73 

Mike Jayjock 

General Comment: 

It is my opinion that uncertainty ultimately determines whether an assessment is considered to be 

definitive and ready to be used for regulatory control decisions or a screening level evaluation begging for 

and identifying more certain data to render a definitive evaluation. 

One never has complete information and this requires those doing the assessment at every level to trade 

conservatism for the missing and more confident knowledge. This need drives up the uncertainty and 

ultimately determines the utility of the effort. 

The exposure assessment in this document is primarily driven by airborne concentration modeling and the 

models are in turn driven by their primary predictor variables; namely, emission rates and fresh air 

ventilation rates. For the most part, these are first principle models and given good inputs will render 

reasonably accurate predictions of exposure. Some of the primary model inputs used in the current 

assessment and in suggested modeling approaches would benefit greatly from relatively little additional 

work and this work should be considered. 

A high level of uncertainty in both the estimation of exposure and hazard can be tolerated if the prediction 

of overexposure vis-à-vis an MOE approach is high enough that even considering the uncertainty bands 

around exposure and hazard the putative risk is clearly significant and in need of regulation. Thus even a 

highly uncertain risk assessment could be considered definitive given this condition. 

My read of the uncertainty in the exposure assessment portion of this assessment is that it is significant 

but that it can be narrowed with relatively little effort. My sense is that the exposure assessment of TCE 

can be improved especially in the realm of consumer exposure via the use of better models, better 

experimental estimates of the emission potential and a better understanding of the size of the exposed 

populations; however, whether this effort is worth this effort and expense ultimately depends on the 

overall uncertainty analysis and the distance between bounded predicted exposure and bounded predicted 

hazard potential. If these error bands significantly overlap then my sense is that this is a screening 

assessment in need of further refinement. If not, it should be considered complete enough for regulatory 

action assuming the exposed subpopulations are large enough to be of concern. 

I have a much better feel for the relative potential error bands around the assessment of TCE exposure in 

the various scenarios under consideration than I do for the hazard assessment. Indeed, what I did not get 

from this assessment is a reasonable sense or understanding of the uncertainty around the hazard 

assessment. Before the meeting with my colleagues, I thought that this likely is as much a result of my 

lack of understanding of these complex measures and descriptions as it is of the presentation within the 

report. I thought that the complexity of the approach is simply too high to allow for a presentation of the 

uncertainty around hazard that I, or technologists with a similar background, would understand. 

During the meeting I heard comments from colleagues with strong backgrounds in hazard assessment 

express essentially the same opinion relative to the hazard assessment. That is, that did not think that such 

high putative hazard as was ascribed to TCE in this report is reasonable or, at the least, it was not 

reasonably supported within the document. For me this translates into a very large error band around the 

ascribed hazard level used in the report; namely, the lowest HEC99 values. 

 
23 of 73 

Clearly, more work is needed on both the exposure and hazard side of this evaluation to tighten up the 

exposure assessment and to provide further justification or explanation of the exceedingly low HEC99

values used in the MOE 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. [Lead 

Discussant: Gilbert] 

I found the report to be generally well organized even though it is obviously very complicated and 

challenging to understand. In a summary document one always has to balance the need for sensible 

brevity with the requirement that there is enough information provided that it is understandable. My 

expertise is in exposure assessment and I generally found these aspects of the report to be quite clear and 

logical with two notable exceptions covered herein. 

Appendix D cites Keil et al. (2009) as the source of information for the 2 zone model outlined in this 

section. The only Keil et al. (2009) reference in the document is a toxicology study: 

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). 

This is not the Keil, et al. (2009) publication that outlines the Nicas 2 zone model. That reference is 

available from the American Industrial Hygiene Pressi

: 

It is clear to see where the confusion came from with two Keil et al 2009 references; however, the second 

one should be included in the assessment and distinguished from the first. 

Another area of confusion for the reader in Appendix D is the missing notation in the following paragraph 

cut and pasted from the report: 

“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:” 

Of course FSA should be inserted in the blanks but it does give the reader pause and someone not familiar 

with the model even more pause. 

As stated above and repeated through this review, my expertise is primarily in exposure assessment; 

however, in order to do risk assessment I have, of course, had to become reasonably knowledgeable in the 

realm of hazard assessment and toxicology. I found the presentation of this aspect to be particularly 

difficult to follow requiring considerable review of the referenced materials in order to make any 

reasonable sense of the approach. For example we are told in the assessment: 

“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 
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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.” [Emphasis added.] 

From my perspective as a reader attempting to understand what was done, more explanation should have 

been provided regarding the specifics of the modeling and the HECs. I will have more to say about this 

aspect in my later comments. 

Finally, the explicit estimation of the size of the population(s) at risk in the various exposure 

categories/scenarios and the uncertainty around these estimates should be included within the assessment. 

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. [Lead Discussant: Ryan] 

The assessment appears to me to be reasonably well documented in the realm of exposure assessment for 

the models being considered with one notable exception, indoor air monitoring. The report mentions that 

indoor air concentrations of TCE are expected to be higher than ambient levels (which are summarized in 

the document). It also acknowledges the existence of indoor air studies that included TCE but it does not 

summarize them. Even though these studies did not focus on the exposure from the use of TCE in 

consumer products, their summary could provide valuable information on the levels extant in indoor air 

and give some insight or clues as to the magnitude of chronic exposure potential and the size of the 

subpopulation for this exposure within residences. 

As discussed below there are additional exposure models that should have been considered and used in 

the assessment. I will outline these in detail later in my responses. 

I am not qualified to comment on the completeness of the available toxicological studies of TCE but my 

colleagues on the panel cover this area in their comments. Given my experience, however, it does appear 

to be a significant amount of information, covering many important end points. 

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). [Lead Discussant: Driver] 

The first subject I wish to discuss is the dermal exposure potential from this compound. Given the 

volatility of the TCE, I understand the Agency’s tendency to dismiss dermal out hand. Indeed, for every 

risk assessment I have seen or done over the years on compounds with a relatively high vapor pressure, 

the risk has been dominated by inhalation exposure. 

Clearly there will be some dermal exposure to TCE especially during the industrial and consumer use of 

degreasers and other consumer products. Thus, it is understandable that not doing an explicit quantitative 

dermal exposure/risk assessment has been an area for criticism. Having said this, my sense is that a 

reasonable worst case dermal scenario should be outlined and conducted to demonstrate that the dermal 

route is minor in this case and by analogy for all other scenarios under consideration. Useful models for 

dermal exposure assessment include the dermal modules in Consexpo 4.1ii or the IH Perm model offered 
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by the AIHA (reference vi). The option in E-FAST2 to estimate absorbed dose from dermal exposure can 

also be used given a permeability coefficient for TCE which should be available from the literature. 

I found the inhalation model choice, model inputs and treatment of the industrial inhalation scenario to be 

well done with the possible exception of the “typical ventilation” rate. The pieces of this scenario and 

model that appear to be adequately supported based on my experience: 

 The critical parameter of evaporation emission rate of 16.7 grams/min is well documented from 

different sources. 

 Using a default factor of 90% for capture efficiency of local exhaust ventilation (LEV). 

 The size of the model near field volume leading to potential breathing zone concentration for the 

workers around the degreaser. 

 The use of the steady-state 2 zone model for an industrial facility that is running continuously. 

 The use of a random air flow rate of 10 cm/sec from the Maynard study. 

The only questionable variable in my opinion is the use of 3000 cfm as the “typical value” for general 

ventilation in an industrial room. Consider an industrial room 20’ x 20’ x 20’ or 8000 ft3

 ventilated at 

180,000 ft3

/hour (3000 cfm) is equivalent to over 20 air changes per hour. A room twice this volume 

would have 10 air changes per hour at this rate. Hot industries, clean rooms, laboratories or industrial 

space with a lot of LEV can get to these levels or higher; however, my experience has been that industrial 

rooms without special exhaust will be ventilated in a range of 2-5 air changes per hour. I would expect 

degreasing operations without local exhaust to be in this range. Perhaps reviewing some of the previous 

work in these facilities would reveal this level of ventilation. In any event, 3000 cfm may not be “typical” 

case but more likely the best case for general ventilation. 

Lowering the presummed general ventilation rate in industrial rooms will increase the predicted exposure 

for bystanders but will do little for the predicted exposure to workers in the near field which is dominated 

by the inter-zonal ventilation. 

An important area of uncertainty relative to this exposure assessment occurs in the determination of the 

actual subpopulation of workers who might be exposed to the model-predicted values. Of course, the 

actual exposure to TCE of this population will be a function of the amount of time they spend in the near 

field and far field within the degreaser room and their actual use of person protective equipment. 

 

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). [Lead Discussant: Jayjock] 

I believe that E-Fast2 CEM is not the appropriate model to use for the primary person exposed in these 

scenarios. It could be useful for residential bystander exposure estimation, however. 

The E-Fast2 CEM inhalation exposure model is based on a dual zone model with the entire room where 

the source is located acting as the primary zone for predicting user exposure and the rest of the house as 

the remaining zone. Both zones are considered to be well mixed —as such, this model does not estimate 
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exposures that are near to the user (near field). Instead it estimates the average concentration within the 

room which is always significantly (sometimes dramatically) lower than the breathing zone concentration 

of someone performing a VOC spraying operation literately at arm’s length. 

The Nicas 2 zone model was specifically designed for these types of exposures. In its dynamic form, it 

can predict point-in-time and time-weighted average (TWA) exposures for operations of any length. 

These can then be readily converted into 24 hr TWA exposure or chronic exposures given the number of 

days per year in which the activity is engaged. A suggested near field volume would be a hemisphere 

1.5 meter in diameter which would include the source and the breathing zone of the person doing the 

spraying on a flat horizontal surface. 

For average random air velocity used by this model, a National Academy of Science publicationiii lists 

average residential indoor air speeds as occurring in the range of 0.05 to 0.3 m/s (3 to 18 m/min). 

Assuming that this range is log-normally distributed with the majority of values on the low end of the 

distribution, 0.07-0.1 m/sec would appear to be a reasonable estimated range. This range is also in line 

with some very limited field testing of residential volumes done by this reviewer. 

The evaporation rate of the TCE could be estimated by taking the amount used per session, assuming 

complete evaporation of the TCE during the session and thus dividing this mass by the time of the activity 

to render an average emission rate. Another approach would be to determine a first-order decreasing 

emission rate using the relationships outlined in the E-FAST2 documentation copied below: 

An alternative manner of determining k is a relatively simple experimental approach presented by Keil 

and Nicas.iv

Both of these methods (the E-FAST documentation shown above and the Keil/Nicas method) assume a 

bolus of TCE at time equal zero. In reality the TCE could, and mostly likely would, be applied over the 

entire time of use. The E-FAST2 documentation presents a more detailed algorithm which considers this 

situation by combining constant application and exponentially declining emissions: 
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It is suggested that all three modeling methods be used; namely, an assumed constant emission rate, a 

first-order decreasing emission rate after a bolus release and an emission rate combining constant 

application and exponentially declining emissions. The results of these three modeling approaches should 

be analyzed and compared. 

Unfortunately, this reviewer is not aware of any software modeling code that includes this algorithmic 

description of time varying emission rate and the Nicas 2 zone model or the eddy diffusivity model 

discussed below. This can be readily done by programmers, however. 

Another general model specifically designed for estimating the inhalation exposure potential from small 

sources near to the user is the Eddy Diffusivity model. This model provides a gradient of 

concentration/exposure from a point emission source for any point-in-space. It can predict point-in-time 

and integrated TWA concentrations for the point-in-space that would represent the nose/mouth of the 

user. 

One of the challenges previously with this model was the required input of the eddy diffusivity coefficient 

(D). These values have been historically difficult to measure and very few were available. This issue has 

been recently addressed by experimental work reported out of Stanford Universityv

 in which it is now 

possible to estimate D from information on the ventilation rate within the residence and the dimensions of 

the room in which the activity is occurring. 

It is further suggested that E-Fast2 be used for by-stander exposure in residences as it is currently done in 

the report. 

The complete form (point-in-time and time-weighted average concentration) Nicas 2 zone and eddy 

diffusivity models are provided in a thoroughly reviewed and vetted freeware spreadsheet (IH MOD) 

available from American Industrial Hygiene Association (AIHA)vi. Available models include assumed 

constant sources or bolus sources (e.g., spills) declining via first order kinetics. All of these models are 

thoroughly documented in a companion publication by the AIHA (reference i). As mentioned above IH 

MOD does not handle the input of combining constant application and exponentially declining emissions 

and this would have to be subsequently coded, possibly in the next revision of IH MOD. 

Please note that much of the uncertainty in this modeling is related to specifically how much product is 

sprayed during the degreasing (or coating) operations and exactly how much TCE is in the product. 

Simple experiments simulating the products’ use while measuring the weight loss of the containers will 

provide the analysis with very confident data on this important variable. Gas Chromatographic analysis of 
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the products would settle the issue of percentage TCE. It appears to this reviewer that these data represent 

a significant amount of confident knowledge for a relatively small investment. 

Finally, any modeling analysis would benefit from the application of a sensitivity analysis to determine 

which variable are driving the estimations of exposure. This would in turn inform which type of future 

work would provide the biggest returns on the reduction of uncertainty. 

 

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

based on exposure durations (i.e., acute versus chronic). [Lead Discussant: Driver] 

Looking at different endpoints is strength in that one gains a clearer perspective on which organ systems 

are affected and which one(s) might comprise the critical health hazard from exposure to TCE. If one 

accepts that more information is better than less, this approach has no weakness. 

Studies of chronic endpoints are appropriated identified and used in comparison with occupational 

exposure which can occur daily for a working lifetime. This is strength of this analysis. 

To the extent that acute end-points are appropriately determined in toxicological tests their comparison to 

the acute exposures extant in the human consumer exposure to TCE is a strength; however, this situation 

does not appear to be at work in this analysis. 

In the area of consumer exposure it is an acute event lasting perhaps tens of minutes or a few hours at 

most. Thus for members of the general public using these products there is a bolus of exposure in a 

relatively short time frame and any testing and understanding of the physiological risk associated with 

this brief and relatively intense exposure is appropriate. This is especially true for adverse endpoint events 

that are “timing critical” such as the acute or daily exposure on the most susceptible day of gestation. 

To the extent that the risk of adverse response as it relates to dose rate is known then the estimation short 

(or long) term exposures matched to a toxicological benchmark applicable over the same time interval has 

obvious value. To the extent that the effect of dose rate for acute exposure is either unknown or very 

uncertain, this approach has limited utility. This subject will be discussed in more detail below but suffice 

it to say that essentially all of the “acute” hazard studies come from dosing the subjects repeatedly over a 

number of days and may not provide a good hazard benchmark for comparison to exposures that happen 

during a single day and are not repeated for a long time. 

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

type of adverse effect. [Lead Discussant: Portier] 

From my reading of the document I note a few reports of multiple values for each type of adverse effect 

but I also do see a range of adverse effects reported within different target organs. For example, within 

neurotoxicity the following studies/adverse effects are noted and reviewed: Trigeminal nerve effects in 

humans, Changes in wakefulness in rats and Decreased regeneration of sciatic nerve in mice. Clearly the 

advantage of doing both is to show the width and depth of available data and the range of responses 

leading to different HEC50 and HEC99 values. This reported range also helps to feed the evaluation of the 

uncertainty associated with these effects and the predicted effect values for humans. 

Question 4-3: PBPK modeling was employed in the 2011 IRIS assessment for route-to-route 

extrapolation to develop a corresponding inhalation value from oral studies, some of which 
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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, 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. [Lead Discussant: Willhite] 

This is clearly not in my area of expertise; however, it strikes me that if there are sufficient inhalation 

studies to render a competent analysis then the approach used by the OPPT seems reasonable and 

appropriate to me. The obvious strength is that the inhalation studies use the same route of exposure as 

the dominant route predicted for human exposure. If the oral studies provide much more and better data 

and there is a high degree of confidence in their quality then it would seem that they should be used. 

In examining the report, I found two comparisons of oral versus inhalation studies that stand out. It is 

reported in Table F-1 and shows very small HEC99 values for decreased thymus weight and increased 

anti-dsDNA in the mouse. Presumably these are important effects that were either not noted or not looked 

for in the reported inhalation studies of the mouse. The same situation is true of the very low HEC99

reported for heart malformations in oral developmental studies in female rats dosed throughout gestation. 

The difference is striking and should be addressed and seems to argue for using the oral data. 

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 non- users. [Lead 

Discussant: Jayjock] 

From my perspective the largest strength of the MOE approach lies in its apparent simplicity. That is, it is 

a simple unitless ratio of exposure to hazard with large MOE values providing some confidence of 

relative lack of risk and small number indicating significant risk. The other strength is that we are dealing 

with potentially true chronic exposure in that workers can typically receive a daily exposure every day for 

many years and thus comparisons of this chronic exposure to output of extended repeat dose toxicological 

studies makes sense. 

The predominant weakness of this MOE approach, in my opinion, lies in the complexity of the hazard 

benchmark, namely, the HEC99. This complexity presents a challenge to just about anyone who is not a 

PBPK modeler/toxicologist in trying to understand it. It is my understanding that the MOE approach in 

this assessment is a ratio of the estimated exposure and the hazard expressed as the HEC99. The HEC99 is 

the lower-end of the range of hazard values for the “sensitive” human (the 99th percentile, or HEC99) for 

each target organ/endpoint. The flow-chart copied below from the EPA 2011 Toxicological review of 

trichloroethylenevii provides what I found to be the best explanation of this important value; however, any 

benchmark requiring a 15 component flow chart in 2 streams is clearly quite complex. 

There is a significant amount of uncertainty in this treatment when one compares the HEC99 values for 

ostensively the same effect in different species and large differences emerge as a result of this 

comparison. For example, comparison of sperm effects in human males (mean years on the job = 

5.1 years) indicates an HEC99 of 0.5 ppm while a study in male mice exposed 6 weeks at 1,000 ppm has 

an HEC99 that is 134 fold higher at 67 ppm. Indeed, an average of 5.1 years of exposure is more chronic 

than 6 weeks which may have accounted for at least some of the difference. 

 
30 of 73 

An advantage of this HEC99 approach is that one can gain a quantitative appreciation for the more 

sensitive non-cancer end-points. Adverse effects to the kidney really stand out showing very low HEC99

values and subsequently low MOEs. 

The biggest disadvantage for me is that the HEC99 this is a deterministic number. It is provided as a value 

in the tail of a distribution but the elements of any epistemological uncertainty feeding this distribution 

and value have not been made obvious. Indeed, because of my lack of knowledge about the details of the 

PBPK modeling and these uncertainties, I have little sense for the error bands around it relative to what 

might be the “actual” HEC99. During our meeting, most my colleagues who have a much better 

understanding of these hazard assessment techniques voiced serious concerns about the level of 

uncertainty extant in the HEC99 values driving the characterization of risk in this assessment. 
31 of 73 
32 of 73 

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). [Lead Discussant: Fuentes] 

Essentially of the same strengths and weaknesses I outlined in Q 5-1 are operational here with one notable 

exception; namely, the use of repeat dose toxicity data in an MOE along with acute exposure data 

represent a significant weakness in the approach. In this instance we are dealing with acute exposures 

lasting tens of minutes or, at most, hours and calculating a 24 hour average exposure for that one day of 

exposure. This exposure in the real world is followed by long periods of time with no exposure. During 

these periods of no exposure there is almost certainly effective elimination/detoxification of the TCE and 

the opportunity to repair any physiological damage done from that brief exposure. 

As best as I can tell, there is only one set of HEC99 values and these were developed from repeat dose 

studies in which the subjects were exposed on consecutive days. My sense is that this comparison of one 

day acute exposure with many day chronic (or repeat dose) hazard benchmarks is very conservative 

perhaps to the point of being not valid. I understand that the toxicology data do not exist for the most part 

to support it but technically what is needed is an acute HEC99 developed from single day acute dosing 

protocols. 

At the least, this inherent weakness should be highlighted in the assessment and the conservative nature of 

this comparison noted. 

Relative to 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), my 

advice is that that the daily exposure should be put into an annual (chronic) average exposure and 

compared to the chronic hazard benchmark. It is a relatively simple and straightforward task that is 

anticipated to show a relatively high MOE for consumer chronic exposure and risk to TCE. 

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. [Lead Discussant: Melnick] 

The use of the factor of 30 for the MOE is reportedly composed of 10 for intraspecies variability and 

uncertainty and a factor of 3 for the pharmacodynamics portion of the interspecies extrapolation factor. 

On its face it seems to make sense to me; however, please see my other comments about the MOE. 

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. [Lead Discussant: Portier] 

Some of my comments above touch on this question. Indeed, I believe that some of the data limitations 

are not adequately described especially in the realm of comparing repeat dose hazard benchmarks with 

acute exposure dosing. 

In general, I have not been able to determine from the assessment if there is overlap between the 

uncertainty associated with the hazard with that of the predicted exposure. I have a reasonable 
33 of 73 

understanding of the level of uncertainty within the estimation of the exposure potential. For me the 

largest uncertainty in the exposure piece occurs within the specific inputs of how long, how much and the 

size of the exposed subpopulations especially for those using TCE-containing products within residences. 

Uncertainties within the exposure assessment notwithstanding, the largest gap in the report’s transparency 

for me after reading it and referring to some of the references occurs in the magnitude of the range of 

uncertainty around hazard. My initial sense was that perhaps much of this inability on my part is caused 

by my lack of in-depth expertise in the realm of PBPK modeling and the complexity of the analysis; 

however, my colleagues on the panel who are skilled in the assessment of hazard seemed to have the 

same issue. 

Supplementary comments in response to EPA clarifying questions presented at August 21, 2013, 

TCE post-meeting 

1. Dr. Jayjock commented that the ventilation rate of 3000 cfm is likely to be a best-case scenario 

and not typical. The agency used room ventilation rates of 500 cfm and 3000 cfm to represent 

worst-case and typical ventilation scenarios, respectively. Please provide the agency with values 

that are representative of worst-case, typical and best-case scenarios for ventilation rates at 

facilities using TCE in degreasing operations? Regarding facility size (e.g., room volume), please 

provide the agency with values that are representative of facilities using TCE in degreasing 

operations. Where possible, please provide the supporting reference(s). 

My primary reasons for stating that 3000 cfm is likely a best-case scenario are presented in my original 

report. During my tenure as an industrial hygienist and risk assessor for a major chemical company I had 

the opportunity to study and sometimes measure mixing air changes in large and small industrial rooms. 

My experience and recollection is that these room had rates in the range of 2 to 6 air changes per hour IF 

they were not situated in hot industries (e.g., steel mill) or volumes with a purposely high level of local 

exhaust ventilation (e.g., laboratories). Some of these were measured rates and some were based on 

review of ventilation design. I do not have access to these data and indeed they probably no longer exist. 

I have searched the literature for many years and have not been able to locate good comprehensive data 

on levels of ventilation extant within industrial rooms. When data are lacking one must rely on their 

judgment and experience. This is what I did for these particular comments. 

2. Dr. Jayjock commented that the subpopulation of workers potentially exposed to TCE needed to 

be quantified. Please refer to a) Table 3-8 and the preceding paragraphs in the TCE risk 

assessment and b) slides 30 and 31 of the presentation that EPA presented during the July 9, 

2013 peer review meeting. Based on your experiences, please provide the agency with alternative 

estimates for the number of workers potentially exposed. Where possible, please provide the 

supporting reference(s). 

Upon further review of the items mentioned above it would appear that 5 workers per facility in about 

23,000 facilities is a reasonable estimation of the subpopulation. I apologize for the oversight. 

3. Dr. Jayjock recommended that the agency substantiate that dermal exposure is indeed negligible 

compared to potential exposures via the inhalation route. Based on your professional judgement, 

please provide the agency with recommended values for the diffusion/permeability coefficient of 

pure TCE through human skin. Where possible, please provide the supporting reference(s). 
34 of 73 

In the EPA Toxicological Review of Trichloroethylene Chapter 3 for IRIS (2011) (EPA/635/R-09/011F) 

there is the following passage: 

“With respect to dermal penetration of liquid TCE, Nakai et al. (1999) used surgically 

removed skin samples exposed to TCE in aqueous solution in a chamber designed to 

measure the difference between incoming and outgoing [14C]-TCE. The in vitro 

permeability constant calculated by these researchers averaged 0.12 cm/hour.” 

The book: Water Contamination and Health, Rhoda G.M. Wang, ISBN: 0-8247-8922-9, 1994, p 343 

found in a Google book search indicates an experimental value in hairless live Guinea Pigs of 0.23 

cm/hr. 

(http://books.google.com/books?id=xCruHfytXZYC&pg=PA324&lpg=PA324&dq=dermal+permeability

+constant+tce&source=bl&ots=wdqH97ai4u&sig=W5apk22NlxWovWIS5_iWKa1awow&hl=en&sa=X

&ei=ebsUUomvOYSdyQGr3oGoCQ&sqi=2&ved=0CGUQ6AEwBw#v=onepage&q=dermal%20permea

bility%20constant%20tce&f=false) 

Given these result my opinion is that the in-vitro human data would provide the best value to use 

because of known interspecies differences in dermal penetration. 

The above results were the result of a rather brief search. A more extensive Google search would 

possibly render considerably more data on the dermal penetration rate of TCE. 

Clarifying Questions for the Consumer Exposure Assessment 

The first two questions are based on comments from Dr. Jayjock: 

1. Please provide references for assessments on highly volatile chemicals that developed and 

compared estimates for the dermal and inhalation exposure pathways. 

A primary example of an assessment of a VOC that included and compared inhalation and dermal 

exposure assessment is presented in the EPA’s Voluntary Children’s Chemical Evaluation Program 

(VCCEP) Submission for methyl ethyl ketone (CAS NO. 78-93-3). Ref: 

http://www.tera.org/peer/VCCEP/MEK/MEK%20VCCEP%20Submission%20December%202003.pdf 

 

A more recent example is contained in Health Canada’s draft screening assessment for the even more 

highly volatile chemical: acetone. Ref: Draft Screening Assessment for Acetone, Chemical Abstracts 

Service Registry (CAS 67-64-1), Environment Canada, Health Canada, July 2013. 

http://www.ec.gc.ca/ese-ees/default.asp?lang=En&n=CB62CB1D-1#toc23 

Health Canada has performed scores of preliminary risk assessments on VOCs that include dermal and 

inhalation exposure. References for these should be available on the Internet. 

2. Please provide references for assessments that have implemented personal breathing zone 

calculations and/or eddy diffusivity modeling that could contribute to OPPT’s exposure 

assessment of TCE emissions from degreaser and arts/crafts products. 

I am not aware of any such references. Indeed, as mentioned in my comments, eddy diffusivity modeling 

has not been used much here-to-fore because of the difficulty in the estimation of the eddy diffusivity 

coefficient. The most highly vetted near-field model is the Nicas 2-zone model and the following 
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reference summarizes much of the work comparing breathing zone and model predictions. Ref: Jayjock, 

M.A., T.W. Armstrong, M. Taylor: The Daubert Standard as Applied to Exposure Assessment Modeling 

Using the Two-Zone (NF/FF) Model Estimation of Indoor Air Breathing Zone Concentration as an 

Example, Journal of Occupational and Environmental Hygiene, November 2011, 8: D114–D122 ISSN: 

1545-9624 print / 1545-9632 online. My suggestion is merely to include the eddy diffusivity modeling for 

comparison with the near-field Nicas two zone modeling. If it is determined to do only one type of model 

then my advice would be to use the Nicas model. 

References 

i

 Keil, C.B., C.E. Simmons, and T Renee Anthony (eds): Mathematical Models for Estimating Occupational 

Exposure to Chemicals, AIHA Press, 2009. 

ii National Institute for Health and Environment ()RIVM, Netherlands: http://www.rivm.nl/en/Topics/C/ConsExpo

Last accessed July 18 2013. 

iii National Academy of Science: Clearing the Air: Asthma and Indoor Air Exposures, Committee on the Assessment 

of Asthma and Indoor Air, Division of Health Promotion and Disease Prevention, p. 410, ISBN: 0-309-51861-X, 

456 pages, 6 x 9, (2000). 

iv Charles B. Keil, C.B. and Mark Nicas: Predicting Room Vapor Concentrations Due to Spills of 

Organic Solvents, AIHA Journal 64:445–454 (2003). 

v Kai-Chung Cheng, V. Acevedo-Bolton, Ruo-Ting Jiang, Neil E. Klepeis, Wayne R. Ott, Oliver B. Fringer, and 

Lynn M. Hildemann: Modeling Exposure Close to Air Pollution Sources in Naturally Ventilated Residences: 

Association of Turbulent Diffusion Coefficient with Air Change Rate, Environ. Sci. Technol. 2011, 45, 4016-4022. 

vi AIHA Exposure Strategies Committee: http://www.aiha.org/get-involved/VolunteerGroups/Pages/ExposureAssessment-Strategies-Committee.aspx, last accessed July 10 2013. 

vii 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. 

 
36 of 73 

Kenneth Portier 

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

type of adverse effect. 

I struggled with how to answer this question. 

Page 56 in the report states: 

“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.” 

Appendix F contains a detailed table of all 32 different candidate PODs/HECs developed by the IRIS 

program, with the 17 inhalation studies used in the assessment listed in Table 3-17. Of these 17, 9 are 

from studies with multiple doses, 8 from single dose studies. Table 3-19 contains summarizes the 

inhalation study values from Appendix F by target organ and exposure duration. 

If I have understood this section correctly, there is actually much less data available that it would seem at 

first glance of Table 3-19. For any one combination of target organ there are at most four separate values, 

and these values may not all relate to the same actual effect. For example, the chronic/liver adverse effect 

data, from Appendix F, actually comes from only two studies. Hence the range is defined by these two 

studies. Note that one of these studies in in mice and the other in rats. 

So, how has this assessment actually used multiple values to introduce “flexibility”. Primarily, the 

multiple POD values have allowed EPA to examine MOE across a set of “scenarios” other than just the 

“worst case”. These scenarios are generated by using different combinations of value from the range of 

HEC50 and HEC99 values for each exposure category. Results of this assessment is given in Table 3-26 

and discussed on pages 67-68. Note that Table 3-26 can be confusing unless one reads the footnotes 

carefully. A YES in this table indicates a change from “potential risk” to “no risk”, a very different 

interpretation than a YES in Table 3-25. 

How have these multiple scenarios been used? The whole alternate scenario effort is summarized on 

page 72. 

“As shown in Table 3-26, using different HEC50 

and HEC

99 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.” 

This statement leads me conjecture that regardless of the alternate scenario results, the worst case results 

will tend to drive conclusions, suggesting that there may be little benefit to this alternate scenario. 

In conclusion, the strength of using multiple POD values lies in allowing the assessment to explore in 

more detail multiple outcomes under different exposure scenarios (Table 3.21). The weakness of using 

multiple POD values is that time and effort is spent on generating results that may not really impact the 
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final conclusions beyond what was obtained by looking at the worst case scenario. This is not to say that 

this exercise is not without merit. Clearly keeping multiple effects in the discussion throughout the 

document increases the perception that these assessment did not focus down on one health effect too early 

in the process. In addition, it is possible that the results of a sensitivity analysis (for either or both of 

exposure and hazard) could point to more than one health effect having to be accounted for in the final 

conclusions. 

Transparency and readability of the report would be improved by combining Table F-1 with Table 3-19. 

This will reduce the burden on the reader to constantly shift between the two tables during reading. 

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.

This questions asks whether the uncertainty and data limitation discussion in the report is both adequate 

and transparent (readily understood). 

I felt that the section of the report where uncertainties are discussed was well written. The authors are 

attempting to point out limitations of data and assumptions that could bias results. There are a couple of 

areas where a little more discussion will improve transparency. 

Statistician typically have difficulty with phrases such as “medium to high degree of confidence” because 

these are qualitative assessments rather than quantitative likelihood estimates. It would help if these 

assessment levels were better defined. What generates “high degree of confidence” in an estimate or 

model input or output? 

On page 71 we are informed that “Virtually all of the information on TCE hazard for this risk assessment 

was taken from the recent IRIS publication...” I did not see any hazard information that did not originate 

from this publication. 

The discussion on page 71 which talks about why EPA chose to not use the RfC or RfD values generated 

for the inhalation studies is not adequate. 

“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.” 

A lot of time and effort went into generating RfC/RfD values for each study by effect combination in the 

IRIS assessment. In particular, a lot of thought went into what was the appropriate UF for each case. Why 

exactly does this assessment revert back to PODs and utilize an MOE? 

At the end of page 71 we have the statement: “By focusing only on inhalation studies and using lower-end 

HEC99 values, OPPT has increased the likelihood that risks are not under-estimated.” So, just how 

conservative are these estimates? My own personal preference in a data-rich environment is to utilize 

probabilistic risk assessment methodologies where we can address quantitatively the issue of degree of 

conservativeness. Could probabilistic risk assessment be used for this assessment and why not? 
38 of 73 

 I am not sure what to conclude from the discussion in the section titled “Uncertainties in the Risk 

Assessment”. The point of this discussion seems to be the conclusion that exposure estimates express 

small variation but may be biased high or low, while at the same time the hazard values are very variable. 

As a result, the overall risk assessment conclusions may be more dependent on which specific hazard 

value is used. 

As I re-read this section, I wondered if it would help to separate the concepts of variability and 

uncertainty in the discussion. Exposure and hazard estimates can be both uncertain and variable. 

Uncertainty relates to precision of estimation. Variability typically relates to how the true value changes 

within a population. The uncertainty sections seem to jump between these two concepts. 

Finally, there was much discussion before the Panel about the need to include a sensitivity analysis for 

both the exposure and hazard parts of the risk value estimation. On the hazard side, the SAB panel that 

reviewed the IRIS assessment and in particular the PBPK model recommended more sensitivity analysis 

of the model parameters be performed. The analysis that was performed indicated that model results 

(estimates) were not particularly sensitive to small perturbations of parameters. This suggests, as was 

pointed out in the Panel discussions, that more effort be placed on decreasing uncertainty on the exposure 

side of the equation. 

 
39 of 73 

Ron Melnick 

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. 

This document relies heavily on toxicity information from EPA’s 2011 IRIS review of trichloroethylene. 

Although it is appropriate to apply results from the IRIS review of TCE in this risk assessment, it is 

important that justification for use of those results is clearly communicated in the OPPT document—some 

examples of where further clarification would be helpful are noted in subsequent parts of this review. 

The TCE risk assessment for non-cancer endpoints is based solely on results from inhalation studies. In 

contrast, the IRIS review derived an RfC based on findings from oral studies using a PBPK model to 

perform route-to-route extrapolation of results. The estimated RfC is 0.0004 ppm. The current TCE risk 

assessment should note that the IRIS RfC for TCE (0.0004 ppm) is similar to the most sensitive hazard 

value from inhalation studies (HEC99 of 0.013 ppm for kidney effects) divided by an MOE of 30. This 

comparison adds confidence to the current assessment, but does not justify excluding results from oral 

studies in this assessment. This assessment would benefit if hazards of TCE from the oral route of 

exposure were also included (see response to Question 4-3 below). 

By not including dermal exposure in the exposure assessment, internal doses are likely to be 

underestimated. The document recognizes this deficiency (page 71) and notes that TCE is rapidly 

absorbed in humans following dermal exposure (page 35), but claims that the use of the lower-end 

HEC99 values provides a counterweight to not considering dermal exposure. That is a poor excuse for 

excluding this potentially relevant route of exposure. The assessment does not provide data to justify the 

claim that dermal exposure is “less significant” (page 14) and ignore this exposure pathway in the risk 

assessment. To justify excluding the dermal route of exposure in this assessment, some attempt must be 

made to estimate the extent of dermal exposure compared to inhalation exposure among degreasers and 

hobbyists using products containing TCE (e.g., the model used to estimate inhalation exposure by the 

hobbyist degreaser or clear protective coating spray provides a means to estimate dermal exposure). 

The TCE risk assessment refers to the HEC99 value as the human equivalent exposure concentration for 

the “sensitive” human; however, in EPA’s IRIS document, the HEC99 is defined as an exposure for 

which there is 99% likelihood that a randomly selected individual will have an internal dose less than 

rodent internal dose at the POD for each critical effect. Thus, the HEC99 value does not represent the 

“sensitive” human because it does not account for pharmacodynamic variability in the human population. 

Furthermore, the HEC99 is based only the range of human parameters entered into the PBPK model that 

provided this value, and may not represent the lower 99th percentile of human pharmacokinetic variability. 

Qustion 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. 

In the inhalation studies that provided the lowest HEC99 for the kidney (Woolhiser et al., 2006) and 

reproductive system (Chia et al., 1996), EPA’s 2011 IRIS review provided statements of concern. Kidney: 

Woolhiser et al. (2006). “the small number of animals and the variation in initial animal weight limit the 

ability of this study to determine statistically significant increases.” Reproductive system: Chia et al. 

(1996). “Mean exposure estimates for the exposure groups were limited because they were defined in 

terms of ranges and because they were based on mean urinary TCA” and “there is substantial uncertainty 
40 of 73 

in the conversion of urinary TCA to TCE exposure level”. “In addition, there was uncertainty about the 

adversity of the effect [hyperzoospermia] being measured”. The TCE assessment needs to provide 

justification for why these studies were selected for the MOE analysis in light of these 

uncertainties/limitations. 

EPA identifies TCE as “carcinogenic to humans by all routes of exposure.” The designation “probable 

human carcinogen” on pages 10 and 13 is outdated and needs to be corrected. On page 12 (second bullet), 

the statement that cancer risks were all “below” the benchmark values should be changed to “above.” 

References 

For completeness, the following references should be noted in this assessment: 

Hosgood HD III, Zhang L, Tang X, Vermeulen R, Qiu C, Shen M, et al. 2011. Decreased numbers of CD4+ naive 

and effector memory T cells, and CD8+ naive T cells, are associated with trichloroethylene exposure. Front Oncol

1:53; doi:10.3389/fonc.2011.00053 [Online 10 January 2012]. 

Karami S, Lan Q, Rothman N, Stewart PA, Lee KM, Vermeulen R, et al. 2012. Occupational trichloroethylene 

exposure and kidney cancer risk: a meta-analysis. Occup Environ Med 69:858–867. 

Karami S, Bassig B, Stewart PA, Lee KM, Rothman N, et al. 2013. Occupational trichloroethylene exposure and 

risk of lymphatic and haematopoietic cancers:a meta-analysis. Occup Environ Med [ONLINE MAY 30, 2013]. 

Vermeulen R, Zhang L, Spierenburg A, Tang X, Bonventre JV, Reiss B, et al. 2012. Elevated urinary levels of 

kidney injury molecule-1 among Chinese factory workers exposed to trichloroethylene. Carcinogenesis 33:1538–

1541. 

Zhang L, Bassig BA, Mora JL, Vermeulen R, Ge Y, et al. 2013. Alterations in serum immunoglobulin levels in 

workers occupationally exposed to trichloroethylene. Carcinogenesis 34:799-802. 

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).

In estimating inhalation exposures for workers and bystanders (Appendix D), a two-zone air model was 

used that includes discrete compartments for near field and far field exposures. Because bystanders may 

be present in the same room as the TCE emitting source, alternative models (e.g., 1-compartment 

evaporation and diffusion model) should also be considered for estimating concentrations of TCE in farfield locations. Does the model predict uniform concentrations of TCE in the far field or do gradients 

exist in this compartment? This is important because gradients would impact exposures for bystanders 

based on their distance from the generating source. 

Describe how the local exhaust ventilation (LEV) affects the generation rate. Discuss the reliability of the 

assumption that LEV reduces TCE emissions by 90%. Wadden et al. (1989) estimated the emission rate 

for TCE from commercial degreasers fitted with a local exhaust hood to be 2.6 g/min for an open-top 

degreaser and 0.67 g/min for an enclosed degreaser. Why was a single value of 1.67 g/min used as the 

emission rate for TCE with LEV? 

A weakness of the OPPT document is that it provides no information on attempts to validate model 

predictions with experimental data. The reference to ATSDR (1997) for support of the estimated 
41 of 73 

workplace exposure concentrations is inadequate, since that document contains no more information on 

the TCE worker exposure data than the one sentence given in Appendix D. The EU Risk Assessment for 

TCE (EC, 2004), which is also cited in Appendix D, only provides a claimed “reasonable worst-case 

exposure levels” (50 ppm for metal degreasing expressed as a 8-hour TWA). Both of these references are 

inadequate to validate model-based estimates of TCE exposure TCE by workers and bystanders, e.g., 

neither reference specifies whether or not the exposures were based on local exhaust ventilation. 

Validation of model predictions of near-field and far-field exposure concentrations for TCE or other 

volatile solvents would significantly reduce uncertainties in the exposure assessment. Jayjock et al. (J Occ 

Environ Hyg 8:D114-22, 2011) have shown that the performance of the two-zone near field/far field 

indoor air model used in the TCE risk assessment is remarkable in simulating near field air concentrations 

for several volatile contaminants and is therefore reasonably reliable in predicting workplace exposure 

levels. This type of information must be highlighted in the TCE risk assessment because it supports the 

use of the OPPT document as more than a screening level assessment. 

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). 

Similar to my comments above for model-based estimates of workplace exposure to TCE, I am concerned 

that there was no mention of any attempts to validate hypothetical exposure estimates for users (and 

bystanders) of aerosol spray products containing TCE or of other volatile solvents with physical/chemical 

properties similar to TCE. Any validation of model predictions should be noted in this assessment 

because it would add confidence to the model-based exposure estimates and would allow reasonable 

exposure estimates for other circumstances, e.g., larger house, different air flow rates between rooms, etc. 

Thus, while the approach used in the TCE assessment seems reasonable, there is no way to evaluate the 

reliability of the model-based exposure estimates. 

The approach for estimating air concentrations of TCE from aerosol spray products seems to be a bit 

convoluted – a model is used to estimate the potential acute dose rate (ADRpot), which is then used to 

calculate the air concentration of TCE that led to that parameter. Since the model allows estimation of 

dermal exposure, that calculation should be included in the estimation of the ADRpot. All model 

assumptions need to be explicit, e.g., ventilation in the room of use. Were other models considered (e.g., 

evaporation and diffusion model) and if so did they provide similar results as the model used in this 

assessment? Why aren’t air concentrations estimated from parameters that affect levels of TCE in the 

breathing zone of the user (e.g., vapor pressure, air exchange rate) and then validated with experimental 

data? A serious weakness of this exposure assessment is the lack of any validation of the hypothetical 

exposure estimates. 

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

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

Evaluating different endpoints based on acute versus chronic exposures is appropriate if the development 

of the adverse effect is a consequence of that exposure duration. A strength of evaluating an endpoint 

based on comparable exposure duration is that an additional adjustment factor would not be needed if 

only acute exposure data were available. However, if the progression or severity of an endpoint increases 

with chronic exposure, it would not be appropriate to assess the risk of that effect after only short-term 
42 of 73 

exposures. If only acute exposure data were available for a condition that worsens with chronic exposure, 

then an additional adjustment factor would be needed to account for the reduced exposure duration. 

A weakness of this approach in the OPPT risk assessment for TCE is that chemically induced 

neurotoxicity is not necessarily a result of only acute exposures. OPPT has not provided evidence 

showing that the development and progression of neurodegenerative diseases are limited to acute 

exposure conditions. As noted in the TCE risk assessment, neurotoxicity has been observed in animal 

studies and in humans after acute and chronic exposure conditions. Similarly, in target organs linked to 

chronic exposures (liver, kidney, reproductive toxicity, and immunotoxicity) adverse effects were 

identified after exposures of 4 weeks or less. For toxicological endpoints that can occur after acute or 

chronic exposures, health risks should be assessed for both short-term and chronic exposure durations. 

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

type of adverse effect. 

The strength of using multiple values for each type of effect is that the relationship between exposure and 

all identified potential target organ effects for workers and consumers exposed to TCE are presented in a 

transparent manner for the risk manager. The range of values for each target organ may reflect 

consistency or inconsistency in potency estimates for an evaluated effect between species or differences 

in sensitivity for specific target organ endpoints. 

The weakness of using multiple values for each target organ is that the underlying reasons for the range of 

values are not provided. This shortcoming might lead to a misinterpretation of the data and the analyses 

performed by OPPT. For example, the risk manager or others may interpret the selection of the lowest 

HEC99 value as EPA being overly conservative in its risk assessment, while the selected POD may 

actually represent the evaluation and detection of a more sensitive endpoint in the target organ. 

Question 4-3: PBPK modeling was employed in the 2011 IRIS assessment for route-to-route 

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, 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 life stages. 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. 

The only apparent criterion used to select PODs for the MOE analyses was that the studies involved 

inhalation exposures. Additional justification is needed for not including oral studies and conducting 

route-to-route extrapolations of results. In the IRIS review of TCE, EPA derived an RfC based on 

findings from oral studies using a PBPK model to perform route-to-route extrapolation of results. A 

comparison of the lowest HEC99 values, expressed in ppm, is shown below for the target organ effects 

observed in inhalation studies that were included in this assessment and values derived from oral studies 

using the PBPK model to provide route-to-route extrapolation. These comparisons support the inclusion 

of HEC values derived from oral studies in the OPPT risk assessment because: 

1. for liver, kidney, and neurotoxicity the HEC values are comparable reinforcing the 

inhalation derived values, 
43 of 73 

2. for immunotoxicity and developmental toxicity the inhalation derived values are 

substantially higher than the oral derived values indicating that risks for these target 

systems might be underestimated if based on the limited number of inhalation studies that 

evaluated health effects in these systems, and 

3. for reproductive toxicity the oral derived HEC was much higher than the inhalation 

derived value; however, because the inhalation study was based on sperm effects in men 

while the oral study is based on decreased in vitro fertilization for male rats, the lower 

value from the inhalation study may reflect the greater sensitivity of humans to 

reproductive effects of TCE. 

Target organ Route of exposure HEC99 (ppm) Reference 

Liver Inhalation 9.1 Kjellstrand et al, 1983 

Oral 11 Woolhiser et al, 2006 

Kidney Inhalation 0.013 Woolhiser et al, 2006 

Oral 0.0056 NTP, 1988 

Neurotoxicity Inhalation 4.8 Arito et al, 1994 

Oral 7.1 Isaacson et al, 1990 

Immunotoxicity Inhalation 11 Woolhiser et al, 2006 

Oral 0.033 

1.7 

Keil et al, 2009 

Sanders et al, 1982 

Reproductive toxicity Inhalation 0.5 Chia et al, 1996 

Oral 9.3 DuTeaux et al, 2004 

Developmental toxicity Inhalation 6.2 Healy et al, 1982 

Oral 0.0037 

3 

Johnson et al, 2003 

Fredriksson et al, 1993 

Some discussion is also needed on how PODs were determined, particularly for studies with a control 

group and a single TCE dosed group. For example, in the developmental study by Healy et al. (1982), the 

only concentration tested was 100 ppm, yet a LOAEL = 17 ppm was identified as the POD. What 

assumptions, beyond adjustment to continuous exposure, were made in estimating this POD? 

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 non- users. 

The MOE approach provides a meaningful signal of concern for several non-cancer health effects that 

might be caused by TCE in workers and bystanders exposed to this chemical. The approach relies on 

information of TCE’s hazards from EPA’s IRIS review and estimations of worker exposure in this TCE 

risk assessment. Aside from issues related to the assessment for workplace exposures (including nonusers) and estimations of hazard values discussed above, the MOE approach seems appropriate. The 

strengths and weaknesses of this approach are a function of the reliability of the two parameters that 

produce the MOE. The assumption of chronic exposure to TCE for the workplace degreaser is 

appropriate. The workplace TCE exposures are based on an 8-hour TWA, presumably for 5 days per 

week. However, the POD hazard values were adjusted in the IRIS program to continuous exposure. Thus, 

the worker exposure value should likewise be adjusted to continuous exposure. 
44 of 73 

Selecting a benchmark MOE of 30, as a unique value that can distinguish risk from “no potential risk of 

concern” requires that the uncertainties surrounding the exposure and hazard values have been accurately 

quantified. I don’t believe this to be the case. Thus, an MOE greater than 30 may indicate lesser concern 

than an MOE < 30, but does not establish “no potential risk of concern.” The exclusion of dermal 

exposure as a contributor to the internalized dose of TCE has not been adequately justified in this 

assessment. The assumptions used to support the conclusion that dermal exposure is not significant need 

to be tested with TCE or referenced to a validated exposure assessment of a solvent with similar 

physical/chemical properties. 

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). 

Similar to my response in 5-1, the MOE approach provides a meaningful signal of concern for several 

non-cancer health effects that might be caused by TCE in consumers and bystanders exposed to this 

chemical. I have no basis for commenting on several input parameters, e.g., whether consumer exposures 

are likely to occur once/week for users of clear protective coating spray and twice/month for degreaser 

users. Perhaps a distribution of frequencies and durations of use should be included in these model-based 

exposure estimates. The assumption that consumer use of degreaser sprays and clear protective coating 

spray is intermittent and that there is likely little residual concern for TCE or its metabolites between 

events seems reasonable. A weakness of the approach is the assumption that there is no chronic exposure 

concern for hobbyist degreasers and clear protective spray users (Table 3-20) because the use of 

consumer products is infrequent and that there would be insignificant residual TCE or its metabolites in 

users or bystanders between events. However, the supplemental information on E-FAST CEM outputs 

includes repeated exposures over a 57-year period for users in these scenarios and exposures may begin in 

utero and occur at a very early age for bystanders. Consequently, there may be may be a concern for 

potential chronic health effects, particularly cancer risk, among consumers who use products containing 

TCE. Thus, I recommend that assessments of potential cancer risk be conducted for hobbyist consumers, 

bystanders, and hobbyist consumers who had been exposed previously as bystanders (in utero and as 

children). Similar to my comment above for workplace exposures, the exclusion of dermal exposure as a 

contributor to the internalized dose of TCE has not been adequately justified in this assessment. Lastly, 

acute risks should also be assessed for adverse effects that were observed in the liver or kidney of 

experimental animals after 4 weeks or less of exposure. 

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. 

This risk assessment should provide a fuller description of what is uncertain in the exposure and hazard 

assessments. The use of a uniform benchmark MOE of 30 for all endpoints has not been justified. This 

value was based on a factor of 3 for extrapolating data from animal studies to humans and 10x for 

intraspecies differences within the human population. Because a model was used to extrapolate an 

internal dose in animals to a concentration that provides a human equivalent dose (HEC), the interspecies 

uncertainty factor of 3 was used to account for possible pharmacodynamics difference. EPA needs to 

explain why a factor of 10 was used for intraspecies variability in light of the fact that an HEC99 was 

used as the POD hazard value. The HEC99 is expected to account for the pharmacokinetic portion (3X) of 

the 10X factor that is typically applied for intraspecies variability. However, because the HEC99 value is 
45 of 73 

a function of the range of variability of human parameters entered into the PBPK model, it is not clear 

whether or not it truly captures the lower 99

th 

percentile of the human population for the concentration of 

TCE that leads to an internal dose in humans equivalent to the rodent internal dose. Based on the 

relatively narrow range of human metabolic parameters used in the PBPK model (obtained from only 

42 adults), it is likely that the model did not capture the full range of interindividual variability due to 

genetic polymorphisms in metabolizing genes, age, gender, and extrinsic factors that affect levels of gene 

expression. The selection of an appropriate uncertainty factor for intraspecies variability needs to be fully 

addressed in the OPPT risk assessment. 

For assessments of health effects that were based on LOAELS instead of BMDLs (neurotoxicity and 

developmental toxicity), an additional uncertainty factor may need to be applied. For assessments of 

chronic health effects that were based on studies of short duration (e.g., liver toxicity, immunotoxicity,), 

an additional adjustment factor needs to be applied for the reduced exposure duration. Thus, it is not 

appropriate to assess non-cancer risks with a benchmark MOE of 30 for all candidate effects. To justify a 

uniform MOE, the assessment would need to provide an adequate explanation on why this value is 

applicable to all critical studies regardless of differences in how the POD was estimated (LOAEL versus 

BMDL) and why an additional adjustment was not needed to assess chronic health risks from short 

duration studies. Lastly, no adjustment factor was applied for the uncertainties in the exposure 

assessments. The above issues reduce confidence in the use of a uniform benchmark MOE of 30. 

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.

A strength of this assessment that should be highlighted is that the inhalation unit cancer risk for TCE was 

based on human kidney cancer data. 

Possibly because this document relies so heavily on toxicity information from EPA’s 2011 IRIS review of 

trichloroethylene, it does not adequately communicate uncertainties in the non-cancer health hazard data 

in an adequately transparent manner. For example, as noted above, the TCE risk assessment does not 

address concerns raised in the IRIS review about the utility of the data by Woolhiser et al. (2006) and by 

Chia et al. (1996). My comments above concerning the exclusion of dermal exposure in this assessment 

are also noted in the section on uncertainty and data limitations. However, the document offers no 

solutions to address this issue other than to claim that the HEC99 “can provide a counterweight to not 

considering dermal exposure.” 

A metabolic scheme with indication of metabolites and/or pathways that were used in the dose-response 

analyses would be helpful. In addition, a strong justification for the selected dose metrics should be 

provided in the text. For example, I am not convinced that the amount of TCE oxidized in the liver is an 

appropriate dose metric for liver cancer and non-cancer liver effects because it does not include essential 

information on the clearance of metabolites that contribute to liver cancer or toxicity. Simply noting that 

this was done for the IRIS review is not a satisfactory explanation and does not reduce uncertainties in the 

estimated HEC99 values. 

BMDL needs to be defined. In the IRIS review, BMDL is the (one-sided) 95% lower confidence bound 

on the dose corresponding to the benchmark response for the effect (i.e., the lowest dose level that can be 

supported by modeling the data). The benchmark response rate(s) used in this assessment should be 
46 of 73 

specified. The reliability of BMDL values derived from single dose studies or studies of questionable 

quality should be addressed in the section on sources of uncertainty and data limitations. 

While recognizing that there are uncertainties in the exposure assessment and that “assumptions were not 

extensively evaluated,” no adjustment was made in the MOE analysis to account for this uncertainty. The 

fact that the exposure assessments for consumers were based on models that had not been validated raises 

uncertainty in the exposure values used in this assessment. This uncertainty could be reduced if evidence 

was provided showing that the exposure models had been validated with solvents having chemical and 

physical properties similar to TCE. 

Supplementary comments in response to EPA clarifying questions presented at August 21, 2013, 

TCE post-meeting 

Based on panel discussions on whether or not the TCE workplan assessment is adequate for regulatory 

purposes or should be considered simply as a screening-level assessment, the document should emphasize 

the fact that TCE has been shown to cause toxicity in multiple organs of humans and that both USEPA 

and IARC have classified TCE as a human carcinogen. Furthermore, the inhalation unit cancer risk 

reported in EPA’s 2011 IRIS review of TCE is based on human kidney cancer data. Thus, regulatory 

action is urgently needed to protect humans exposed to this agent in the workplace or in their residence. If 

OPPT anticipates significant delays in improving the exposure assessment for more accurate assessment 

of health risks for bystanders and hobbyists, then regulatory actions should be implemented with required 

workplace monitoring and consumer warnings based on both the IRIS RfC and the estimated inhalation 

cancer risk. The model-based estimates of workplace exposure for degreasers are reliable for regulatory 

purposes. 

 
47 of 73 

Barry Ryan 

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. 

In my opinion, EPA has performed a detailed analysis of the problem at hand but has failed to present it 

in a clear and concise fashion. As discussed under Question 1-2, many of the assumptions used are stated 

without reference and appear somewhat arbitrary or ad hoc. While it may be that neither of these is 

indeed the case, it is difficult for the reader to grasp the motivation for some of the parameter selections 

and hence transparency is lost. Further, the impact of alternative selections for modeling parameters is not 

clearly delineated through, for example, sensitivity analysis. It may well be that the ultimate outcome of 

the document, namely a screening risk analysis associated with various exposure scenarios, is not strongly 

affected by the choice of these parameters, but the reader is not privy to such information since it is not 

presented. 

I think the document would be substantially improved if a clear statement was made regarding the 

audience for the report. Is this, for example, a report that would be used by technically proficient risk 

modelers in the pursuit of their work? If so, perhaps it is sufficient. But, I believe, by its very nature it 

seems unlikely that such a document would be ignored by a more general audience. Under this scenario, 

much more detail into the reasoning must be present to ensure clarity of presentation and understanding 

by a less technical group of readers. This would begin with a clear and unambiguous statement of the 

content and expected utility of this document in the first few pages. This would be followed using 

essentially the same outline as is currently present but expanding each section to explain more fully what 

the selection criteria were for various modeling parameters, inclusion criteria for manuscripts and 

documents, and likely effects associated with alternative modeling strategies. At such a point, the 

document would be much more transparent. 

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. 

While the literature cited is useful, there does not seem to be an exhaustive effort made to find all existing 

appropriate literature for the various sections. Several statements are made to the effect that few if any 

data exist on the topics at hand- small-scale degreasing operations and hobbyist uses of TCE and TCEcontaining materials. Yet much of the “occupational” literature is directly applicable to the small-scale 

operations as it is to the large-scale degreasing facilities. Indeed, application of such data is used 

throughout. Emission characteristic are similar for both open and closed systems as well as for systems 

using local exhaust ventilation. Exposures to individuals are likely similar. It was interesting to note that 

the work of Wadden, et al., done in the late 1980s and EPA’s work were compared and found to give 

similar results for large facilities (See Table 3.7). The Wadden results are also compared for smaller 

facilities. EPA’s results suggest a three-fold decrease in emissions from smaller facilities. It is unclear 

what supports this decrease, which is, of course, crucial in determining the ultimate concentrations and 

thus exposures received by both workers in such facilities and by-standers. A more thorough discussion 

of this with appropriate references should be included. Further, scenarios common in the 1980s, which 

may have included ineffective ventilation systems, whole-building ventilation, or poor local exhaust 

ventilation (LEV) may result in different estimates in 2013. While the Wadden, et al., work was well 

done, it is now 25 years later. More literature is available and should be explored. 
48 of 73 

Little work has been done on hobbyists TCE exposure to my knowledge. However, exposure 

measurements on other hobbyist material, e.g., lead exposure among stained-glass hobbyists, or other 

VOC-related activities, has been done and could serve for as a better model. I saw no references to the 

literature that followed this approach. The utility of such work lies not only in the direct measurement of 

the exposures experienced by such individuals, but also in affording better parameterizations of the 

models (see Discussions below.) Use of such data, or at least the discussion of such, would support the 

approach used. If no such data are available, EPA could easily perform chamber experiments to evaluate, 

for example, the amount of TCE-containing spray used in a given application, and determine use patterns, 

e.g., is the 28 g per application and a 30-minute application once every two weeks at all associated with 

real-world use as discussed in the following paragraphs. 

Specific comment regarding the choice of modeling scenarios: 

The choice of modeling conditions and, in particular, the emission parameters and flow rates between 

compartments appear to be quite arbitrarily set and not well documented or referenced. Further, it is 

difficult to find the parameter used as they are scattered among several sections. A single table describing 

parameters for both the small-scale degreasing facilities and the hobbyist exposure scenarios would be 

well placed in Chapter 3 somewhere. Otherwise one has to examine both that Chapter and Supplemental 

materials to assess the quality of the model inputs. I would like to see EPA make a better effort in 

justifying the specific emission rates for hobbyist type crafts and for the emissions associated with the use 

of TCE-containing materials. For example, through a series of assumptions, e.g., one can of aerosol 

degreaser per year, etc. (See Supplemental Degreaser Document), EPA has come up with an emission rate 

for TCE in hobbyist activities To my mind, these emission rates, which strongly affect exposures and risk, 

are quite arbitrary and supported by very few data. Essentially all parameters used in these modelsemissions, durations, air flows etc., are poorly justified and have the appearance of ad hoc and arbitrary 

assumptions. Yet the values are critical in understanding the risk. Admittedly, few data are available, as 

has been pointed out by EPA, but in such circumstances, it become incumbent upon the modeler, and 

EPA in general, to produce full text describing the reasoning. Are there data to support the “one can a 

year” used at regular intervals? How does this really jibe with hobbyist use? How about the duration of 

the exposure- 30 minutes? Are there data to support this? I know of none, but perhaps EPA does and 

therefore must reference it. If no such data exit, justification of the scenario and what its utility might be 

is necessary. Do these represent typical, worst case, or some other percentile of the exposure distribution? 

Again, these are screening levels, but we need some context for our discussion. 

Characterization of Uncertainty in Modeling Scenarios: 

There is a specific question regarding uncertainties that will address details, but little in the way of 

literature or other reference materials was evident to support the characterization of uncertainties with 

regard to the modeling setup itself, i.e., Model Uncertainty. According to the diagram and equations 

presented, a simple two-compartment model was put forward where emissions were solely in the first 

compartment- where the primary user was- and the an outer compartment, for which concentrations were 

affected by flow out of the inner compartment. The bystanders were located in the outer compartment. 

Questions were raised in the preliminary conference call regarding these scenarios- first by Dr. Driver, 

then by others. I do not think that the emissions rates and exchanges rates between compartments were 

well documented. In fact, they seemed more ad hoc than anything else. Can we get some more clarity on 

that via literature reference or, barring that, the reasoning behind the value choices? 

In the inclusion of local exhaust ventilation (LEV), I think the models used make the untoward step of 

going from simple to simplistic. They make no real attempt to characterize the impact of LEV but rather 

they reference Wadden, Scheff, and Frank 1989. If memory serves me, Wadden, et al., make a more or 

less off-the-cuff statement that LEV can remove about 90% of airborne contamination when clearly many 
49 of 73 

factors are in operation for any given system. I do not believe that they ever intended this to be used in a 

quantitative sense. Many excellent scientists have spent their careers determining flow rates, capture 

efficiencies, and removal rates of LEV systems (See the works of, for example, Ellenbecker of UMassLowell, and Flynn of UNC.) Their application of this recommendation is also naïve; they simply reduce 

the emissions by a factor of 10. Such emissions would be markedly affected by the positioning of the 

LEV apparatus, the position of the degreaser/hobbyist in doing his/her work, capture efficiency of the 

LEV system, and the removal/exhaust of the captured air. If there is no removal or exhaust of the captured 

air, the LEV is completely ineffective. While this model may be used exclusively for scenario testing- and 

the scenarios themselves subject to great uncertainty in their utility- this just adds to the overall 

uncertainty of the risk estimates. 

During our discussion on 17 July 2013, Dr. Jayjock brought forward a paper done by him and other coworkers evaluating the accuracy of the two-compartment model. The bottom line is that such a model 

produces concentrations that are likely no more than a factor of 3 different from measured values. This 

adds strong support to the use of the modeling system outlined for both decreasing facilities and hobbyists 

use, albeit less so for the latter. Yet no reference was brought forward for this paper by EPA, despite the 

fact that it would have strongly strengthened their case for using such a model to infer exposures. 

The use of a steady-state assumption for concentrations is also problematic and perhaps simplistic for 

these scenarios. This is especially true of the hobbyist applications. As the name implies steady-state 

applications assume that all parameters in the model- emission rates, compartmental flow rates, sinks etc., 

are maintained for time periods “long” with respect to the characteristic time-scales of the overall system. 

If one is using TCE-containing materials in a semi-enclosed space it may take quite some time for steadystate to be established- perhaps longer than the scenario time, e.g., one hour, that is listed. Under such 

conditions, exposures maybe substantially different than those modeled for steady-state as the exponential 

approach to steady-state would afford lower concentrations than the steady-state values. Of course, one 

may argue that the models used here are screening tools and that estimates higher than what might be 

realistic are useful. If so, explicitly state this fact and indicate how large the impact of such might be on 

exposures, dose, and risks. 

The industrial hygiene and indoor air literature is replete with papers dealing with these type of effects. It 

would appear that little effort was made to make the model more realistic in its applicability to the 

scenarios at hand. 

While the above comments may appear to be excessively critical, they are given in the spirit of improving 

the transparency and readability of the document. EPA is to be commended for attacking a difficulty 

problem, especially in the case of the hobbyist exposure, for which few data are available to develop risk 

characterization. Nevertheless, EPA must address such issues and does best when taking on the problem 

as directly and clearly a possible. I stand ready to re-work my comments based on input from my 

colleagues, but these do represent my current thoughts. I look forward to further discussion at the full 

meeting. 

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). 

I have included many such comments under my response to Charge Question 1-2, and will not repeat 

those here. Instead, I will focus on improvements that might make the presentation clearer and more 

useful.
50 of 73 

I advocate the use of sensitivity analysis of some type to ascertain the important parameters in the model 

used for worker exposure. While Dr. Jayjock’s work suggests excellent accuracy for the twocompartment modeling system outlined in occupational applications, I believe that sensitivity analysis 

will aid in refining the model further. For the case of steady-state that might be approached in an 

industrial degreasing operation, there may still be some parameters of interest. For example, the 

ventilation rate for the room is fixed for this study. Concentrations, and thus exposures, are strongly (and 

almost linearly over narrow ranges) dependent on this parameter. This is true for both operator and 

bystander. Further, transfer rates from the source compartment to the “bystander” compartment strongly 

influence the concentrations experienced by both, and in the opposite sense, e.g., increased flow out of the 

source compartment lowers the exposure experienced by the source worker but increases the exposure 

experienced by the bystander. Since the risks shown at the end of the set of calculations are of interest if 

not for this group certainly for the home hobbyist, such an analysis is warranted. 

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). 

The approach used for the hobbyist scenarios suffers from many of the same shortcomings as the 

degreaser worker scenarios, but is likely more affected by parameter selection than is the industrial 

scenario. This is true because the exposures are intermittent and occur under much less controlled, and 

under poorly defined conditions. The hobbyist may well be a garage mechanic or other hobbyist with 

local ventilation determined by the garage opening, air “communication” from the house to the garage, 

open and closed windows, presence of sinks, and other variables poorly defined. Measurements on such 

systems are sparse for air contaminants in general and TCE contamination in particular. And, once again, 

these parameters strongly influence exposures. 

It is important to note that the bystanders in this case are not other workers in a manufacturing facility but 

rather women of child-bearing age, young children, infants, and developing fetuses- a much more 

vulnerable population. Use of a limited number of scenarios for such a diverse population subject to 

exposure is not especially useful. Focusing, for example, on neurodevelopment, during specific stages of 

gestation and during infancy up to about age 18 months, similar exposures can produce substantially 

different neurodevelopmental effects ranging from mental retardation, behavioral problems, learning 

disabilities, and other potential problems. The simple scenarios and assumptions regarding movement of 

contaminants and exposure do not take into account specific, short-term life stages where 

neurodevelopment is critically affected by exposure. 

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

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

...and... 

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

type of adverse effect. 

These two topics is quite far removed from my area of expertise other than the neurodevelopmental work 

discussed above. However I can make a few general points. 
51 of 73 

For the degreaser worker, exposures are more or less uniform during the working day for both the 

operator and bystanders. This leads to a cleaner analysis for the chronic case. Acute exposures are less 

likely- spills, catastrophic events, etc., notwithstanding. 

For the hobbyist, acute exposures are the principal operational effect. Indeed, exposures occur for a short 

duration and irregular intervals, although they are modeled as being more regular, e.g., 30 minutes every 

two weeks. Acute exposures are more difficult to assess both in terms of what the exposures would be as 

they are dependent upon conditions at the time, which may not afford a steady-state approximation, and 

what effects are likely to manifest given such exposures, as they are dependent upon life stage and other 

parameters. 

In general, I think it incumbent upon EPA to look at different endpoints and multiple values for endpoint 

effects, e.g., AEGLs, to assess this problem. 

Question 4-3: PBPK modeling was employed in the 2011 IRIS assessment for route-to-route 

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, 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. 

Again, this topic is outside my area of expertise. I only express concern for the large reliance on the 2011 

IRIS assessment, as thorough as it was, for the final answer. 

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 non- users. 

...and... 

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). 

I will address both 5-1 and 5-2 together. 

The calculations for Margin of Exposure (MOE) are outside my area of expertise. However, I have a few 

comments. 

MOE calculations are relatively simple once the point of departure is determined. In this case, the point of 

departure is HEC99, which is very complicated to get at. It includes calculations of exposure and then 

from exposure the calculation of HEC99. In each case- depending on the direction one is going, one 

assumes a perfect calculation of the “other” number. For example, HEC99 assumes a perfect calculation 

of the exposure. Yet we have seen in our discussion that the exposure numbers obtained can vary 
52 of 73 

substantially due to uncertain conditions used to generate them. This uncertainty is not propagated 

through to the HEC99; exposure is assumed to be some fixed number. Conversely, if one were to be 

interested in calculating an exposure that would lead to a given HEC99, then that would be fixed and one 

would back-calculate the exposure assuming a fixed value. Yet we saw multiple HEC99s depending on 

endpoint and influenced by within- and between-individual variability and uncertainty. 

This leads us to a full analysis of uncertainty in such models (See below). EPA has not presented an 

analysis of such even at the level of simple sensitivity analyses. The question of factors most strongly 

influencing the risk need to be addressed if not quantitatively, at least qualitatively in the text. 

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. 

The single, uniform MOE of 30 gives insufficient respect to the uncertainties of the various HEC99 

values used for multiple endpoints. The quality of data for various HEC99 values differ as does the 

quality of exposure data for the various scenarios. For example, occupation exposures for the small-scale 

degreasing operations may be, as reported in Dr. Jayjock’s paper, good to within a factor of 2-3 for both 

operator and bystander. Such is not likely to be the case for home hobbyist exposure. Further, calculation 

of HEC99 values based on these uncertain exposures themselves are not well calculated for various 

sensitive groups, e.g., pregnant women and young children. I should think that given such increased 

uncertainty for the sensitive populations that the MOE might be chosen differently- most likely larger- for 

these groups rather than relying on a single value. 

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. 

I have really addressed this question throughout my comments. I do not think that the uncertainties in the 

estimates have been addressed well at all. The combination of data limitations on the exposure side, 

multiple outcomes on the risk side, and fixed methodology of the MOE calls the values chosen into 

question. One positive aspect of this analysis is that a very conservative, i.e., protective, point of 

departure- HEC99- has been used. However, we have no clear delineation of what this number really 

represents in terms of real-world exposure. It is likely to be quite protective, but is very uncertain. And 

because the results for certain outcomes are at levels of concern, it becomes incumbent upon EPA to set 

some limits on this uncertainty. Further, a sensitivity analysis may give direction for continued work in 

this area. Perhaps one or more parameters, e.g., HEC99, exposure, etc., maybe selected for further 

scrutiny based on its influence on risk uncertainty and/or lack of quality data. 

Supplementary comments in response to EPA clarifying questions presented at August 21, 2013, 

TCE post-meeting 

1. Drs. Melnick and Ryan recommended that a sensitivity analysis be performed. Please provide 

specific suggestions on how the sensitivity analysis should be conducted. For instance, the agency 

performed a sensitivity analysis to characterize worst-case and typical exposure scenarios. This 

was done by varying parameters such as the room ventilation rate (from 500 cfm to 3000 cfm) 

and the effectiveness of local exhaust ventilation (from 0% to 95%); please provide the agency 

with alternative values for varying these parameters. Specifically, which other parameters should 
53 of 73 

the agency vary and what values should be used? Where possible, please provide the supporting 

reference(s). 

The process described here is not a sensitivity analysis but rather running a couple of different scenarios. 

A standard sensitivity analysis typically would vary each parameter or variable- generally one at a timeby a small amount, say 10% and evaluate the impact of that parameter on the model outcome. In the case 

of environmental concentrations, the variables may include emissions rates, application rates, volatility, 

etc. The impact of each is then rank-ordered and those giving the largest change in outcome are 

investigated further. It may be that some model variables have little effect on outcome over small ranges. 

Others may affect the outcome linearly or even super-linearly, e.g., a 20% change in outcome associated 

with a 10% change in input. Many modeling systems- even Crystal Ball- have such evaluations available 

as a single-step process. 

As to what variables, the answer is simple- all of them. The algorithm is straightforward; increase the 

value of the given variable or parameter by some amount and observe the effect on the outcome of 

interest. Such procedures not only identify the sensitivity of the model to such perturbations, they also 

identify area where increased scrutiny of the variables and parameters might be warranted. 

These questions are based on comments from Dr. Ryan: 

1. Please provide references containing available data relevant to sinks for TCE or chemicals 

comparable to TCE. 

A simple Google search “TCE sinks in indoor environments” yields a number of articles. The first to 

come up after the present work is a paper by An, Zhang, and Shaw published by the National Research 

Council of Canada entitled: “Sink Effect Study for Common Building Materials: A Literature Review and 

Research Plan.” Although published in 1997, this may be a good place to start. I also did a Web of 

Science Search using a similar criterion and recovered about 150 references. Inspection of the titles and 

abstracts led me to eliminate many of these. However 22 of these references are relevant to either one or 

the other of these questions or to questions on dermal exposure. They are given below. These include 

studies of TCE and other organic compounds in indoor environments modeling exercises, discussion of 

important factors influencing concentrations and exposure, and potential sources and sinks in residential 

environments. 

2. Please provide references for assessments that have varied parameters like compartmental flow 

or product composition with time, including currently available data that would permit such an 

analysis for TCE. 

See below: 

Bogen, K. T., B. W. Colston and L. K. Machicao (1992). "Dermal Absorption of Dilute Aqueous Chloroform, 

Trichloroethylene, and Tetrachloroethylene in Hairless Guinea-Pigs." Fundamental and Applied Toxicology 18(1): 

30-39. 

Borrazzo, J. E., C. I. Davidson and J. B. Andelman (1993). "Small Closed-Chamber Measurements for the Uptake of 

Trichloroethylene and Ethanol Vapor by Fibrous Surfaces." Modeling of Indoor Air Quality and Exposure 1205: 25-

41. 

Candura, S. M. and E. M. Faustman (1991). "Trichloroethylene: toxicology and health hazards." G Ital Med Lav 

13(1-6): 17-25. 
54 of 73 

Chao, C. Y. and G. Y. Chan (2001). "Quantification of indoor VOCs in twenty mechanically ventilated buildings in 

Hong Kong." Atmospheric Environment 35(34): 5895-5913. 

Cornejo, J. J., F. G. Munoz, C. Y. Ma and A. J. Stewart (1999). "Studies on the decontamination of air by plants." 

Ecotoxicology 8(4): 311-320. 

Davis, W. T., C. C. Hood and M. Dever (1995). "Analysis of a Thin Activated Carbon Loaded Adsorption 

Medium." Separation Science and Technology 30(7-9): 1309-1324. 

Demou, E., S. Hellweg, M. P. Wilson, S. K. Hammond and T. E. McKone (2009). "Evaluating Indoor Exposure 

Modeling Alternatives for LCA: A Case Study in the Vehicle Repair Industry." Environmental Science & 

Technology 43(15): 5804-5810. 

Geng, C. N., Q. S. Luo, M. F. Chen, Z. Y. Li and C. B. Zhang (2010). "Quantitative Risk Assessment of 

Trichloroethylene for a Former Chemical Works in Shanghai, China." Human and Ecological Risk Assessment 

16(2): 429-443. 

Heavner, D. L., W. T. Morgan and M. W. Ogden (1995). "Determination of Volatile Organic-Compounds and Ets 

Apportionment in 49 Homes." Environment International 21(1): 3-21. 

Hellweg, S., E. Demou, R. Bruzzi, A. Meijer, R. K. Rosenbaum, M. A. J. Huijbregts and T. E. McKone (2009). 

"Integrating Human Indoor Air Pollutant Exposure within Life Cycle Impact Assessment." Environmental Science 

& Technology 43(6): 1670-1679. 

Hughes, K., M. E. Meek and W. Windle (1994). "Trichloroethylene - Evaluation of Risks to Health from 

Environmental Exposure in Canada." Environmental Carcinogenesis & Ecotoxicology Reviews-Part C of Journal of 

Environmental Science and Health 12(2): 527-543. 

Lerner, J. E. C. and A. Porta (2011). "Study of air quality through passive diffusion samplers. Recovery of volatile 

organic compounds adsorbed." Afinidad 68(556): 406-411. 

Mendez-Roman, R. and N. Cardona-Martinez (1998). "Relationship between the formation of surface species and 

catalyst deactivation during the gas-phase photocatalytic oxidation of toluene." Catalysis Today 40(4): 353-365. 

Ohura, T., T. Amagai, Y. Senga and M. Fusaya (2006). "Organic air pollutants inside and outside residences in 

Shimizu, Japan: Levels, sources and risks." Science of the Total Environment 366(2-3): 485-499. 

Ondarts, M., C. Hort, V. Platel and S. Sochard (2010). "Indoor Air Purification by Compost Packed Biofilter." 

International Journal of Chemical Reactor Engineering 8. 

Pellizzari, E., P. Lioy, J. Quackenboss, R. Whitmore, A. Clayton, N. Freeman, J. Waldman, K. Thomas, C. Rodes 

and T. Wilcosky (1995). "Population-Based Exposure Measurements in Epa Region-5 - a Phase-I Field-Study in 

Support of the National Human Exposure Assessment Survey." Journal of Exposure Analysis and Environmental 

Epidemiology 5(3): 327-358. 

Sack, T. M., D. H. Steele, K. Hammerstrom and J. Remmers (1992). "A Survey of Household Products for Volatile 

Organic-Compounds." Atmospheric Environment Part a-General Topics 26(6): 1063-1070. 

Sexton, K., S. J. Mongin, J. L. Adgate, G. C. Pratt, G. Ramachandran, T. H. Stock and M. T. Morandi (2007). 

"Estimating volatile organic compound concentrations in selected microenvironments using time-activity and 

personal exposure data." Journal of Toxicology and Environmental Health-Part a-Current Issues 70(5-6): 465-476. 

Son, B., P. Breysse and W. Yang (2003). "Volatile organic compounds concentrations in residential indoor and 

outdoor and its personal exposure in Korea." Environment International 29(1): 79-85. 
55 of 73 

Wu, C. and J. Schaum (2000). "Exposure assessment of trichloroethylene." Environmental Health Perspectives 108: 

359-363. 

Yang, D. S., S. V. Pennisi, K. C. Son and S. J. Kays (2009). "Screening Indoor Plants for Volatile Organic Pollutant 

Removal Efficiency." Hortscience 44(5): 1377-1381. 

 
56 of 73 

Calvin Willhite 

General Comment 

Assuming 1 hr domestic cleaning or 0.5 hr spray during arts and crafts activities with trichloroethylene 

(TCE), the OPPT presented the following daily indoor air TCE concentrations (Tables 3-11 and E-1): 

 Solvent degreaser user (>16 years of age) 2.0 ppm (10.75 mg/m3

 ) 

 Solvent non-user (>16 years of age) 6-8 ppm (32-43 mg/m3

 ) 

 Clear protective coating user (> 16 years of age) 0.4 ppm (2.1 mg/m3

) 

 Coating non-user (> 1 year of age) 0.1 ppm (0.54 mg/m3

) 

The OPPT file Supplemental Information on E-FAST CEM Outputs (Degreaser Use) CEM Inhalation 

Exposure Estimates lists the following exposure concentrations for an assumed 1 hr use of TCE: 

 Degreaser User (>16 years of age) peak concentration 48 ppm (259 mg/m3) 

 Non-User (21 years of age) peak concentration 7 ppm (38 mg/m3) 

 Degreaser User (21 years of age) lifetime average 0.11 ppm (0.66 mg/m3

) 

 Non-User (21 years of age) lifetime average 0.04 ppm (0.21 mg/m3

) 

 Degreaser user (16-20 years of age) lifetime average 0.009 ppm (0.05 mg/m3) 

 Degreaser non-user (16-20 years of age) lifetime average 0.004 ppm (0.0187 mg/m3

) 

These values are said to equate to margins of exposure (MOE) of 2-8 for women of child-bearing age who 

use TCE degreasers and non-using females who live in the same home where hobbyist TCE activities 

occur. The OPPT considers these women at risk for adverse pregnancy outcome as a result of residential 

TCE use. 

The US EPA (2013) already released its residential indoor air TCE concentration levels for both cancer 

(0.43 μg/m3

) and non-cancer (0.21 μg/m3) endpoints. These US EPA (2013) residential indoor air 

concentrations are equivalent to a theoretical excess cancer risk of 1.0 x 10-6 and a hazard index (HI) of 

0.1, respectively. Increasing the US EPA (2013) non-cancer residential indoor air concentration to 2.1 

μg/m3

 equates to a HI of unity, somewhat less than the 18.7 μg/m3 value calculated above. The cancer 

risk value is based on USEPA conclusions that occupational TCE exposure causes human kidney and 

possibly other cancers and the HI indicates that ingested or inhaled TCE poses an increased risk for 

cardiovascular malformations. Comparing the above 0.1-8.0 ppm results shows that all OPPT values 

(including non-user residents of homes) are substantially greater (not less than 900x) than the published 

US EPA (2013) residential indoor air de minimus risk TCE level; should the residential indoor air TCE 

value be increased to a HI of unity, the OPPT values are not less than ~100x the published US EPA 

(2013) residential indoor air TCE level. 

 

For carcinogenesis, the US EPA adopted an inhalation potency factor (4.6 x 10-6 per mg/kg-day) based on 

human kidney cancer and an assumed mutagenic mechanism of action and released its residential air 

concentration (US EPA, 2013). Since the NRC (1993) has detailed methods for extrapolation of risks for 

long-term to short-term exposures for genotoxic carcinogens, why was it that method was not utilized to 

calculate the theoretical less than lifetime or short-term cancer risks associated with arts and crafts TCE 

exposure of concern to OPPT? 

 
57 of 73 

The non-cancer hazard index not only leads to calculation of the lowest equivalent ‘safe’ concentration of 

TCE in residential air, but those values are either less than or consistent with background TCE 

concentrations in United States urban or residential indoor air. As such, any domestic use of TCE in any 

amount for any use whatsoever will exceed the US EPA’s published residential indoor air TCE level 

(0.21 μg/m3

). As written, the previously published and current US EPA reports lead to the conclusion that 

current ambient TCE levels are associated with increased risk for human cardiovascular malformations - 

yet there are no suggestions from studies of occupational TCE exposures at concentrations 1-2 magnitude 

of orders greater than ambient pose excess non-cancer health risks to those workers. 

Given prior publication of US EPA (2013) guidance values for TCE in residential air, it is not clear why 

the current OPPT effort concerning domestic uses of TCE was deemed necessary? No empirical data are 

supplied and no literature reference was cited to support the assumed magnitude, frequency or duration of 

incidental TCE exposure during residential arts/crafts uses. While data for very high dose TCE-induced 

carcinogenesis in humans (Cherrie et al., 2001) can be considered convincing, fundamental biological 

problems with the OPPT non-cancer hazard indices and risk conclusions over concern for developmental 

toxicity render that aspect of the draft assessment unreliable. The draft document should be returned to 

the authors for major revision as there are substantial uncertainties in the domestic (hobby) exposure 

assessment and serious deficiencies in non-cancer hazard identification. 

Specific Comment 

Background 

The document submitted for review relies upon previous USEPA analyses of health risks posed by 

environmental exposure to TCE (Chiu et al., 2013) that declared: 

“TCE is carcinogenic to humans by all routes of exposure and poses a 

potential health hazard for noncancer toxicity to the central nervous 

system, kidney, liver, immune system, male reproductive system and 

the developing embryo/fetus. 

Recent avian and in vitro mechanistic studies provided biological 

plausibility that TCE plays a role in developmental cardiac toxicity, 

the subject of substantial debate due to mixed results from 

epidemiologic and rodent studies.” 

Based on the results of the Chiu et al. (2013) health risk assessment taken together with TCE calculated 

exposure for residential degreaser and arts/crafts uses (0.8-2 ppm as a 24 hr mean airborne concentration), 

the OPPT concludes that non-cancer risk estimates for women of childbearing age during use of two 

hobbyist products indoors at home using developmental toxicity as the endpoint of concern yields a 

margin-of-exposure of 2 (Table 3-24). Based on the OPPT exposure assumptions and calculations, the 

Agency states use of TCE degreasers in the home (by either the female applicator or non-user woman in 

the home) presents an acute risk for developmental toxicity and also found: “In terms of acute effects, 

neurotoxicity seems less of a concern than developmental toxicity.” Overall, the Agency concluded: 

“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).” 
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As conclusions on risk to human health are reflections of the intrinsic toxicity of TCE (e.g., ‘hazard 

value’) and the magnitude, frequency and duration of TCE exposure, the OPPT observed: 

“Thus, understanding that the exposure estimate may be an over- or underestimation, the choice in the hazard value used will likely have a greater 

outcome of the risk assessment for the uses discussed in this document.” 

Charge to the Reviewer 

Three key items formulated as Questions 1-1, 1-2 and 4-3 were requested of the present reviewer and 

these are addressed below. In order to place the answers to those questions into context, it is necessary to 

revisit the conclusions made by Chiu et al. (2013) and the data upon which those conclusions were based 

despite the specific charge to the OPPT review committee. Following that discussion, presentation of 

residential air concentrations associated with the Chiu et al. (2013) hazard value in relation to ambient 

and residential indoor air TCE concentrations are tabulated and conclusions on the wisdom of the Office 

of Chemical Safety and Pollution Prevention’s (OPPT) document are offered. Those conclusions are 

followed by two recommendations that if implemented should increase the accuracy and credibility of the 

current assessment. 

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. 

The answer to Question 1-1 has two components. The first concerns the assumptions and calculations of 

exposure estimates for small businesses and residential TCE uses. The second concerns the weight of 

evidence assessment used by and the conclusions reached by OPPT that environmental TCE exposure 

presents a serious risk for congenital heart malformations and increased intrauterine and neonatal death. 

A. Exposure 

The US EPA presents the results of calculations based on assumed quantities of TCE used during small 

business and home-based applications of the solvent in automotive parts cleaning and other recreational 

arts/crafts operations. No empirical area or personal monitoring data were collected to validate those 

exposure estimates; furthermore, there have apparently been no formal efforts to survey people who 

restore automobiles and other similar activities (e.g., home-based chain saw, lawnmower or other small 

engine service and repair) to ascertain duration and frequency of domestic TCE exposure. Most 

automobile hobbyists this reviewer queried at a local auto show did not use organic solvents at all, but 

instead due to cost and the inconvenience with recycling prefer detergent-based products. Of those who 

did respond in the affirmative, they soaked (rather than sprayed) their metal parts in (unidentified) 

solvents contained in a bucket with a tight lid (to retard evaporation and loss of liquid cleaner) for several 

hours or days and then only momentarily (and with rubber gloves) opened and closed their parts bucket. 

The purpose of the rubber gloves appears to be to avoid direct contact with oily organic solutions that 

defat the skin. Thus, this informal survey suggests a 1 hour per day exposure to uncontrolled TCE fume 

(perhaps by spray, cloth or brush application) is perhaps unlikely; the OPPT assumption appears to stem 

from shop practices used in the 1970s and 1980s and duration and the OPPT duration and frequency of 

exposure were determined by convenience (‘expert judgment’) without supporting empirical data. 

At a minimum, the OPPT should expand Chapter 3 and Table 3-1 to include published indoor and 

occupational air TCE concentrations. The document should compare and contrast the results of the 

assumed exposure parameters and calculated lifetime average residential exposure concentrations with 

ambient levels of TCE in outdoor (0.1-18 ppb) (Bozzelli et al., 1980; Singh et al., 1982) and indoor 
59 of 73 

residential air where the US mean is 7.2 μg/m3 (Shah and Singh, 1988) and with the TCE concentrations 

found in area and personal samples of workplace air. For example, the IRIS (2011) document tabulates 

the range of recent rural (0.005 – 1.9 μg/m3

) and urban (0.1 – 97 μg/m3) ambient TCE concentrations and 

points to the mean personal 24 hr (breathing zone passive sampling) of Minneapolis residents (1.0 μg/m3

) 

(Sexton et al., 2005). 

The magnitude of small business employee TCE exposure depends upon the nature of the operations and 

vapor controls (if any). A 1985 NIOSH survey of 23,225 industrial facilities where TCE was used found 

personal breathing zone concentrations of 1.2-5.1 ppm (6.7-27.3 mg/m3

) (Santodonato, 1985). Peak (15 

min) exposures during industrial vapor degreasing can reach upwards of 200 ppm, but smaller 

(uncontrolled) benchtop TCE cleaning during repair of small metal components (as might occur in home 

automotive TCE use) occurred as 5-10 min events of 15 per day and 5 min events at 4 per day; those 

exposures rarely exceeded 10 to 15 ppm (Stewart et al., 1991). As to small business TCE exposures, 

perhaps the most recent robust data come from a 2010 study by the National Cancer Institute of 80 

Chinese workers who used TCE in cleaning operations and their breathing zones were measured by fullshift personal sampling (22.19 ± 35.94 ppm) (Lan et al., 2010). Were the US EPA authors to query the 

NCI authors on the nature of those measurements and to survey small business operations it may be 

possible to place the exposure assumptions and resultant calculated levels into perspective in contrast to 

reliance upon assumed work practice. 

B. Hazard Identification 

Although the Agency stated it utilized a weight-of-evidence to conclude that environmental exposure to 

TCE “plays a role in developmental cardiac toxicity”, in fact the Agency relied upon strength-of-evidence 

and selected the report by Johnson et al. 2003) to the exclusion of all other bioassays as the key study 

upon which its 2011 TCE Non-Cancer Reference Concentration (0.21 μg/m3

) is based. The current OPPT 

non-cancer risk conclusions are based on the same endpoint as those used to formulate the US EPA 

(2013) residential air guidance value. There is no evidence that NCEA applied a formal systematic 

method (e.g., Klimisch et al., 1997) to analysis of the published developmental toxicity studies with TCE; 

instead, the default hazard analysis and the most conservative BMDL01 (as contrast to the conventional 

BMDL10) treatment of the non-cancer toxicity data rests with the Johnson et al. (2003) drinking water 

study in rats. The Agency justified selection of the 1% risk (as contrast to the customary 10% value) as 

“due to the severity of defects, some of which could have been fatal”, then applied a total toxicodynamic 

uncertainty factor of 10 resulting in an unusually low TCE Reference Dose. 

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. 

The information provided to substantiate the proposed hazard identification and potency for 

developmental toxicology of TCE has not been properly presented. 

Chiu et al. (2013) point to TCE data in avian eggs to support their conclusion that TCE is teratogenic. 

There is no question that chick embryo data can show remarkable similarities with what has been seen in 

some rare instances with human beings and that chick embryo data can provide mechanistic insights for 

certain known human teratogens (e.g., Eichele et al., 1985; Lee and Tickle, 1985); however, chick embryo 

data alone are poor predictors of mammalian teratogens despite similarities in vertebrate morphogenesis. 

Concordance in response between species in teratology is the rare exception, rather than the rule. One of 

the fundamental difficulties with avian embryos in developmental toxicity is the inability to distinguish 

generalized toxicity from specific effects on development; increased concentrations of chemicals injected 
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into the egg increase embryonic death and the numbers of survivors may not at all reflect the teratogenic 

potential of the test material in mammals. In the case of TCE, the data cited by Chiu et al. (2013) have 

been extended to explore 8 and 800 μg/L injected into fertilized chicken eggs (Makawana et al., 2010; 

2013) and the genomic data taken together with the stage-specific developmental data after injection of 

0.4 to 400 μg/L (Drake et al., 2006) confirm vulnerability of the chick embryo when TCE exposure 

occurs during valvuloseptal morphogenesis. 

 Chiu et al. (2013) failed to qualify their conclusion that although no one species can uniformly predict 

human teratogens, the chick embryo is regarded by teratologists as a system that can only provide a basic 

but not definitive data for comparative toxicity. Haschek and Rousseaux (1997) summarized the 

experience as: 

“Although the chicken is useful in studying the progression of 

abnormal development, its relatively high sensitivity to exogenous 

agents and the significant differences in embryogenesis among 

avian and mammalian species preclude the use of chickens 

in standard teratogenicity testing.” 

Kimmel et al. (2009) [Attachment 1] described in detail some of the technical issues faced in 

determination of reasons for the discrepancies between the Johnson results and results in rodents from 

other laboratories. The US EPA would never accept submission of a non-guideline bioassay that has not 

been subject to the strict audit requirements of Good Laboratory Practices in support of regulatory 

decisions for new products submitted for registration, yet in the present case this is exactly what has 

occurred. While the Agency could require manufacturers and suppliers to submit the results of additional 

TCE developmental toxicity GLP bioassays in rodents and/or rabbits designed and conducted in accord 

with international test guidelines, it is unlikely this will resolve the fundamental scientific question 

whether TCE exposure (by any route or at any dose) presents a risk for human congenital cardiac defects 

as questions on the Johnson et al. (2003) and Collier et al. (2003) data remain. 

Question 2-1. Please comment on the approach used and provide any specific recommendations for 

alternative approaches, models or information that should be considered by the Agency for 

improving the workplace assessment. 

The Agency should cooperate with the Consumer Product Safety Commission and NIOSH to gather 

empirical TCE concentrations in area samples and personal breathing zone of people engaged in the 

activites involving TCE that are of concern to OPPT. Exposure assumptions and models are no substitute 

for empirical exposure data. At a minimum, the OPPT should solicit and welcome peer review of the 

current work product from NIOSH and the CPSC. 

Question 3-1. Please comment on the approach used and provide any specific suggestions or 

recommendation for alternative approaches, models or information (e.g., information on duration 

and number of user events). 

While the indoor air dispersion model used is common, it assumes solvent input from a constant source 

and justification of that constant source based on rare or intermittent hobbyist use of a TCE-containing 

aerosol spray can is needed. Since residential hobby exposures (e.g., automobile repair) ordinarily occur 

either outside (e.g., on the driveway) in good weather or likely in the garage during inclement weather, it 

is incumbent upon the authors to explain the exact conditions under which these activities are assumed to 

occur (e.g., in a two-car garage with the garage door open or closed, in a basement with little ventilation) 
61 of 73 

and provide the full range of TCE concentrations both in the operator’s breathing zone as well in the 

immediate work area and then distributed throughout the other rooms of the residence taking into 

consideration single level and two story homes or apartments. 

The Agency should cooperate with the CPSC and NIOSH to gather empirical TCE concentrations in area 

samples and personal breathing zone of people engaged in the activities involving TCE that are of 

concern to OPPT. Exposure assumptions and models are no substitute for empirical exposure data. At a 

minimum, the OPPT should solicit and welcome peer review of the current work product from NIOSH 

and the CPSC. 

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

based on exposure duration. 

While it is commendable to evaluate risk for different health endpoints and exposure durations, it is only 

the lowest value in practice that is important to the regulatory agency risk manager (often a civil engineer, 

an attorney and/or a political appointee). Assuming the carcinogenic potency of TCE is accurate, indoor 

air or workplace air TCE concentrations controlled so as not to exceed the risk range considered safe and 

protective of the public health (US EPA (Federal Register 56(20): 3526-3614, 1991) should also be 

protective for non-cancer health endpoints. Assuming the OPPT agrees with the IRIS conclusions on the 

human carcinogenicity of TCE exposure, it is not necessary to complicate risk communication to the 

project manager and to the public by presenting a menu of candidate values that are difficult to explain to 

an audience not familiar with exposure modeling, weight of evidence and statistical analyses when it is 

the highest potency and lowest exposure concentration that generally drive regulatory risk management. 

Question 4-2. Please comment on the strengths and weaknesses of using multiple values for each 

type of adverse effect. 

Ordinarily providing multiple oral Reference Doses or inhalation Reference Concentrations is useful since 

it provides the risk manager with a full range of candidate values, but in practice the risk manager 

generally selects only the lowest value. Generally the lowest values are associated with carcinogenicity 

and the theoretical risk range 10-6 to 10-4 as given by the USEPA (Federal Register 56(20): 3526-3614, 

1991) in its statement that those risk values are safe and protective of public health. In the present case, of 

course, the lowest value is not related to carcinogenicity but to developmental toxicity. 

During the July 9 presentation by OPPT of the draft health risk assessment for TCE the USEPA stated 

they relied not upon the Johnson et al. (2003) drinking water study where the cardiac defects were 

reported, but utilized the Healy et al. (1982) results. The ATSDR review of trichloroethylene concluded 

(page 43): 

“No statistically significant increases in skeletal, visceral or external 

malformations have been found in pups of rat dams exposed to 100- 

500 ppm of trichloroethylene.” (Beliles et al., 1980; Hardin et al., 1981; 

Healy et al., 1982; Schwetz et al., 1975). 

 

The ATSDR Toxicological Profile on Trichloroethylene (page 173) continued: 

“Following inhalation exposure, the effects noted at concentrations that 

were not overtly maternally toxic were decreased fetal body weight 

and incomplete ossification.” (Dorfmueller et al., 1979; Healy et al., 1982). 
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Healy et al. (1982) allowed 32 pregnant Wistar rats to inhale 100 ppm TCE 4 hr/day on days 8-21 of 

gestation and compared the results with 31 control rats subject to the same conditions, but inhaled clear 

air. All of the rats were sacrificed on day 21 and the fetal hearts, ovaries, uterus, liver and lungs were 

dissected. There was no evidence of cardiac or other malformations in any of the offspring, but consistent 

with other publications found reduced fetal body weights and associated retarded skeletal ossification. 

Therefore, since “All studies investigating exposure to TCE vapors failed to detect any negative impact 

on the developing heart” (Watson et al., 2005) [Attachment 2], it is not accurate the OPPT took the 

position they used only the Healy et al. (1982) report since USEPA based the current assessment on 

increased risk for cardiovascular terata and no such effect was seen in the Healy et al. (1982) study. 

For the current effort, it is not clear why USEPA selected Healy et al. (1982) as the key inhalation study 

for calculation of “safe” workplace and residential indoor air TCE concentrations? The Healy et al. (1982) 

protocol examined only a single 100 ppm concentration and, as such, there is no opportunity to evaluate 

concentration-response or determine a NOAEL or BMD. If in fact, the OPPT developmental toxicity risk 

estimate is based on the inhalation data, then why is it that the Careny et al. (2001) inhalation bioassay 

conducted in accord with OPPT’s Guideline 870.3700 under Good Laboratory Practice was not utilized as 

the key study? In contrast to the Healy et al. (1982) protocol that examined only a single concentration, 

the guideline-compliant Carney et al. (2001) bioassay examined three concentrations (50, 150 and 600 

ppm) and included dissection of fetal hearts and the great vessels. While there was some indication of 

maternal intoxication (reduced body weight gain) at the highest dose, there were no signs of treatmentrelated congenital defects (including cardiovascular malformations) at any concentration. 

Question 4-3. PBPK modeling was employed in the 2011 IRIS assessment for route-to-route 

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 because OPPT focused on a 

narrow set of TCE consumer issues that are subject to TSCA and, therefore, OPPT’s draft risk 

assessment relied only on 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. 

Physiologically-based pharmacokinetic models (PBPK) differ from classical multicompartment 

pharmacokinetic models that fit blood (the central compartment) data to concentration-time profiles for 

parent drug and metabolites to predict distribution and elimination rates and half-times to one or two 

peripheral compartments (of unstated anatomical location). Classical compartment models facilitate 

calculations of clearance as well as understanding dose-dependency (Inchinosa and Inchinosa, 2009). 

Contemporary PBPK models identify exact physiologic compartments and take into account speciesdependent organ blood flows, tissue solubilities (e.g., partition coefficients), ventilation rates, parent 

compound uptake by different routes, metabolite generation and elimination (Leung, 2009). A rather large 

number of PBPK models have been developed for TCE and these were intended to address different 

endpoints ranging from neurotoxicity (e.g., Simmons et al., 2002) to carcinogenesis (e.g., Bogen, 1988). 

There is a long history in development of physiologically-based pharmacokinetic models for TCE in 

pregnancy beginning with the Fisher et al. (1999) effort. The current USEPA entry for TCE in IRIS 

system includes the following: 

“The estimates for kidney effects, thymus effect and developmental heart 

malformations are based on PBPK model estimates of internal dose for 

interspecies and intraspecies extrapolation and there is sufficient confidence
63 of 73 

in the PBPK model and support from mechanistic data for one of the dose 

metrics (total oxidative metabolism for the heart malformations).” 

The IRIS (2011) evaluation developed candidate RfDs from oral studies as well as inhalation studies via 

route-to-route extrapolation using the “harmonized” PBPK model referenced in Chiu et al. (2013). The 

present PBPK work used the parameters listed in Table 3-18 and at page 56 the authors state: “This model 

was reviewed by the Science Advisory Board (US EPA, 2011a) and found to be both useful and robust.” 

The present OPPT document provides neither clear rationale nor compelling reasons for deviation from 

the extensive US EPA PBPK-based interspecies scaling of rodent TCE data to human equivalent internal 

metabolized dose. Whether the lowest internal metabolized dose is associated with one or another route of 

exposure is actually of only minimal importance provided the PBPK scaling is robust and the results 

verified. 

The suggestion that OPPT utilized only the Healy et al. (1982) inhalation developmental toxicity data is 

not accurate when in fact the OPPT relies upon the Johnson et al. (2003) rat drinking water data 

[Attachment 3] for its hazard identification of increased risk for cardiovascular malformations (see 

answer to Question 1-2 above). The suggestion that OPPT relied only upon the Healy et al. (1982) 

inhalation data is not consistent with how the data are used by other USEPA programs (USEPA, 2013). 

As the OPPT endorsed the IRIS data evaluations and no compelling reasons are offered to reject the 

Regional Screening Levels for TCE in indoor air of residences derived using conventional PBPK 

interspecies metabolized dose scaling in developmental toxicity (USEPA, 2013), the OPPT should (for 

sake of consistency with Agency-wide IRIS policy) utilize the identical endpoints and PBPK-based 

methods and assumptions as have been used to calculate the US EPA Regional Screening Levels (RSLs) 

for TCE in indoor air (USEPA, 2013). 

Question 5-1. Please comment on the strengths and weaknesses of the MOE approach to estimate 

chronic noncancer risk for workplace exposures. 

The question here concerns risk characterization. Published USEPA guidance (1989) calculates ambient 

and residential air concentrations based on threshold endpoints and presents those results as a Hazard 

Quotient (“The ratio of a single substance exposure level over a specified time period (e.g., subchronic) to 

a reference dose for that substance derived from a similar exposure period.”) The noncancer Hazard 

Quotient is expressed as E/RfD where E= exposure level (or intake) and RfD = reference dose and E and 

RfD are expressed in the same units and represent the same exposure period. The Agency states: 

“The noncancer hazard quotient assumes that there is a level 

of exposure (i.e., RfD) below which it is unlikely for even 

sensitive populations to experience adverse health effects. If 

the exposure level (E) exceeds this threshold (i.e., if E/RfD 

exceeds unity), then there may be a concern for potential 

noncancer effects. As a rule, the greater the value of E/RfD 

above unity, the greater the level of concern.” 

Why it is the OPPT insisted on a MOE comparisons when the Hazard Quotient and Hazard Index 

methods are standard practice at federal and state agencies charged with environmental and consumer 

health protection? Does the OPPT advocate the Agency abandon the HQ and HI methodology in favor of 

a MOE approach? 
64 of 73 

Question 5-2. Please comment on the strengths and weaknesses of the MOE approach used to 

estimate the acute risk to consumers. Please comment on the decision to limit the analyses to acute 

exposures without residual concern between events. 

The question here again concerns risk characterization. Published USEPA guidance (1989) calculates 

ambient and residential air concentrations based on threshold endpoints and presents those results 

presented as a Hazard Quotient (“The ratio of a single substance exposure level over a specified time 

period (e.g., subchronic) to a reference dose for that substance derived from a similar exposure period.”) 

The noncancer Hazard Quotient is expressed as E/RfD where E= exposure level (or intake) and RfD = 

reference dose and E and RfD are expressed in the same units and represent the same exposure period. 

The Agency states: 

“The noncancer hazard quotient assumes that there is a level 

of exposure (i.e., RfD) below which it is unlikely for even 

sensitive populations to experience adverse health effects. If 

the exposure level (E) exceeds this threshold (i.e., if E/RfD 

exceeds unity), then there may be a concern for potential 

noncancer effects. As a rule, the greater the value of E/RfD 

above unity, the greater the level of concern.” 

Why it is the OPPT insisted on a MOE comparisons when the Hazard Quotient and Hazard Index 

methods are standard practice at federal and state agencies charged with environmental and consumer 

health protection? Does the OPPT advocate the Agency abandon the HQ and HI methodology in favor of 

a MOE approach? If so, the document should explain why the MOE is a superior method compared to the 

standard HQ and HI methods. 

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 identified in the 2011 

USEPA IRIS assessment for TCE. 

As written, it is not clear why a MOE was used in the present OPPT analysis leading to beg the question 

which MOE is safe and protective of public health? If the OPPT rejects the non-cancer Hazard Quotient 

and instead adopts MOE comparison (as used in USEPA regulation of dietary pesticide residues), the 

application and rationale for the MOE approach and values used by the Agency in other regulatory 

actions should be referenced and the values used should be similar. If data or discrepancies are noted that 

dictate alternative MOE values, those should be articulated. 

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

and data limitations. Please comment on whether this information is presented in a transparent 

manner. 

The general comments concerning the OPPT and IRIS conclusions on risk for cardiovascular 

malformations above illustrate the poor weight of evidence assessment carried out in this regard for TCE. 

The uncertainty attendant to the IRIS hazard identification for cardiovascular terata is so great that it leads 

to the present OPPT conclusion that all TCE exposures (including background concentrations in US 

urban ambient and indoor residential air) present increased risk for congenital malformation of the heart 

and great vessels. 
65 of 73 

 It is not clear why OPPT relied on the results of the Johnson et al. (2003) study to the exclusion of all 

other inhalation and oral developmental toxicity studies in rodents and rabbits. If in fact the OPPT is 

reliant upon only the inhalation data, why is it the Carney et al. (2001), the Schwetz et al. (1975), the 

Hardin et al. (1981), the Beliles et al. (1980) or the Dorfmueller et al. (1979) study was not used? Why is 

there no discussion of all of the available developmental toxicity inhalation bioassays in the present 

analysis? 

Since there are no empirical indoor air TCE concentration measures for either the small shop or 

residential use of spray cleaners that contain TCE and the assessment relies upon model estimates 

including assumptions on duration and frequency of these operations that have not been validated, 

confidence in the accuracy of the results of the OPPT assessment is called into question. 

Summary 

As submitted, the exposure parameters appear arbitrary (e.g., 0.5 and 1 hr/day) and may have been 

selected for sake of convenience. The data upon which conclusions put forward by OPPT on risk for 

developmental toxicity associated with arts and crafts use of TCE are not reliable. Nearly all 

developmental toxicity studies with TCE in rodents find no sign of teratogenicity (e.g., Beliles et al., 

1980) or find only slight developmental delay (Dormueller et al., 1979). Chiu et al. (2013) cite the NRC 

(2006) report as verification of their risk assessment for TCE developmental toxicity, but actually the 

NRC (2006) concluded: 

“Additional studies evaluating the lowest-observed-adverseeffect-level and mode of action for TCE-induced developmental 

effects are needed to determine the most appropriate species 

for human modeling.” 

In its present assessment, the OPPT ignored the serious deficiencies already identified in conduct of the 

Johnson et al. (2003) rat drinking water study upon which the BMD01 was based (Kimmel et al., 2009; 

Watson et al., 2006) [Attachments 1 and 2]. In their weight-of-evidence assessment, Watson et al. (2006) 

concluded: 

“...application of Hill’s causality guidelines to the collective body of data 

revealed no indication of a causal link between gestational TCE exposure 

at environmentally relevant concentrations and congenital heart defects.” 

Those conclusions were consistent with Hardin et al. (2005). Perhaps most disturbing of all in US EPA’s 

reliance upon Johnson et al. (2003) as the key study (which for the basis for their lowest non-cancer TCE 

hazard index and margin of exposure) is the observation by Hardin and associates (2004): 

“Conventional developmental and reproductive toxicology assays in mice, 

rats and rabbits consistently fail to find adverse effects of TCE on 

fertility or embryonic development aside from embryo- or fetotoxicity 

associated with maternal toxicity. Johnson and Dawson, with their 

collaborators, are alone in reporting that TCE is a “specific” cardiac 

teratogen.” 
66 of 73 

One of the fundamental tenants in science is the reliability and reproducibility of results of scientific 

investigations. In this regard, one of the most damning of the TCE developmental toxicity studies in rats 

is that by Fisher et al. (2005) who stated: 

“The objective of this study was to orally treat pregnant CDR(CD) 

Sprague-Dawley rats with large bolus doses of either TCE (500 mg/kg), 

TCA (300 mg/kg) or DCA (300 mg/kg) once per day on days 6 

through 15 of gestation to determine the effectiveness of these 

materials to induce cardiac defects in the fetus. All-trans-retinoic 

acid (RA) dissolved in soybean oil was used as a positive control. 

The heart malformation incidence for fetuses in the TCE-, TCA- and 

DCA-treated dams did not differ from control values on a per fetus 

or per litter basis. The RA treatment group was significantly higher 

with 33% of the fetuses displaying heart defects.” 

Unfortunately, Johnson et al. (2005) failed to report the source or age of their animals, their husbandry or 

provide comprehensive historical control data for spontaneous cardiovascular malformations in their 

colony. The Johnson study with 55 control litters compared to 4 affected litters of 9 treated was 

apparently conducted over a prolonged period of time (perhaps years); it is possible this was due to the 

time required to dissect and inspect fresh rodent fetuses by a small academic research group. However, 

rodent background rates for malformations, anomalies and variants show temporal fluctuations (WHO, 

1984) and it is not clear whether the changes reported by Johnson et al. (2005) were due to those 

fluctuations or to other factors. Surveys of spontaneous rates of terata in rats and other laboratory animals 

are common particularly in pharmaceutical and contract laboratory safety assessment (e.g., Fritz et al., 

1978; Grauwiler, 1969; Palmer, 1972; Perraud, 1976). The World Health Organization (1984) advised: 

“Control values should be collected and permanently recorded. 

They provide qualitative assurance of the nature of spontaneous 

malformations that occur in control populations. Such records 

also monitor the ability of the investigator to detect various 

subtle structural changes that occur in a variety of organ 

systems.” 

Rates of spontaneous congenital defects in rodents can vary with temperature and housing conditions. For 

example, depending on the laboratory levocardia and cardiac hypertrophy occur in rats at background 

rates between 0.8-1.25% (Perraud, 1976). Laboratory conditions can also influence study outcome; for 

instance, maternal hyperthermia (as a result of ambient elevated temperature or infection) can induce 

congenital defects (including cardiovascular malformations) in rodents and it acts synergistically with 

other agents (Aoyama et al., 2002; Edwards, 1986; Zinskin and Morrissey, 2011). Thus while the 

anatomical observations made by Johnson et al. (2003) may be accurate, in the absence of data on 

maternal well-being (including body weight gain), study details (including investigator blind evaluations), 

laboratory conditions, positive controls and historical rates of cardiac terata in the colony it is not possible 

to discern the reason(s) for the unconventional protocol, the odd dose-response and marked differences 

between the Johnson et al. (2003) results and those of other groups. 

As noted by previous investigators, the rat fetus is “clearly at risk both to parent TCE and its TCA 

metabolite” given sufficiently high prenatal TCE exposures that can induce neurobehavioral deficits 

(Fisher et al., 1999; Taylor et al., 1985), but to focus on cardiac terata limited to studies in one laboratory 

that have not been reproduced in other (higher dose) studies and apply the BMD01 with additional default 

toxicodynamic uncertainty factors appears misleading. 
67 of 73 

There was some suggestion during the July 9 USEPA oral presentation of the TCE arts and crafts risk 

assessment that data from Forand et al. (2012) may be taken as support for the very low developmental 

toxicity margin of exposure (2) presented in the OPPT assessment. Forand et al. (2012) concluded: 

“The study’s strongest finding is for an association of 

TCE and PCE exposures with cardiac birth defects...” 

 (specifically conotruncal cardiac malformations). 

This association was seen with a median Endicott, New York, indoor ambient TCE concentration of 16 

μg/m3

 (a value 8x greater than the US EPA 2013 residential indoor air RSL and equivalent to the current 

proposed OPPT lifetime average TCE concentration of 18.7 μg/m3

 for excess non-cancer risk for the 16-

20 year old residential non-user of TCE products). Forand et al. (2012) made an effort to account for 

tobacco use by their mothers, but admitted, “...the inability to control for smoking is also an important 

limitation in this study.” Forand et al. (2012) did qualify their association and noted the wide confidence 

intervals on relative risk. 

Unfortunately, congenital heart disease is the single most common birth defect affecting ~1% (some 

40,000) of all live births each year in the United States. While an apparent association between indoor air 

TCE and adverse pregnancy outcome could be interpreted in some circles, the Forand et al. (2012) study 

has a number of important deficiencies. While Forand et al. (2012) did attempt to account for smoking, 

their protocol failed to account for common known risk factors for cardiovascular terata. Maternal obesity 

increases risk for atrial septal defects, pulmonary stenosis, tetraology of Fallot, aortic stenosis and 

hypoplastic left heart (Mills et al., 2010), maternal diabetes mellitus presents a 5x increase risk for 

transposition of the great vessels, persistent truncus arteriosus, triscupid atresia and single ventricle (Wren 

et al., 2003; Lipowski et al., 2010; Fahed et al., 2013), maternal alcohol consumption increases 

atrioventricular septal and other defects (Burd et al., 2007; Smith et al., 1981), maternal disease (rubella, 

lupus) and inherited conditions including Down’s syndrome that increase the incidence of aberrant 

subclavian artery, patent ductus arteriosus, atrioventricular septal defect and tetralogy of Fallot (Chang et 

al., 2013; Fahed et al., 2013; Gelb, 2000; Lo et al., 1989; Stallmeyer et al., 2010) were not included. 

Moreover, Forand et al. (2012) made no effort to determine whether the mothers in their study used any 

of the common pharmaceuticals known to cause human cardiovascular malformations including those 

used to control epilepsy (Samrén et al., 1997), to treat dermatologic conditions (Lammer et al., 1985), to 

treat depression (Källén and Olausson, 2006; Bérard et al., 2007; Oberlander et al., 2008) or whether they 

were afflicted with maternal conditions like phenylketonuria or had reduced folate, protein deficiency or 

used dietary supplements (Yano et al., 2013) that increase risk for cardiovascular terata. 

Therefore, prior to any suggestion the Forand et al. (2012) observations be entered into a developmental 

toxicity weight-of-evidence for TCE exposure and risk of cardiovascular terata, the Forand et al. (2012) 

study should be subjected to independent critical review by epidemiologists and experts in teratology who 

have experience with these types of studies. 

Conclusion 

These sorts of situations in toxicology are neither novel nor new and history demonstrates mistakes by the 

US government in chemical hazard identification. Two brief examples illustrate the problem. For many 

years the US EPA considered the solvent 1,1,-dichloroethylene (also known as 1,1,-DCE or vinylidene 

chloride) to be a probable human carcinogen, a conclusion based on rat data reported by a single 

laboratory in spite of the fact 16 other cancer bioassays found no such effect. The 1,1-DCE cancer risk 

assessment was ultimately withdrawn by USEPA after many years of contentious debate. A second 

example concerns the US Consumer Product Safety Commission that concluded certain hobby spray 
68 of 73 

adhesives were responsible for human birth defects and instituted a nationwide ban. This ban was 

subsequently withdrawn after the data upon which the action was based were found without merit - but 

retraction of that CPSC regulatory activity occurred only after concerned mothers elected to abort their 

pregnancies (Hook and Healy, 1976). 

Taking at face value the lifetime mean concentrations calculated by OPPT for the present exercise, this 

reader comes to the conclusion that sexually active fertile women of child-bearing age who live in homes 

with the mean US indoor air TCE concentration (7.37 μg/m3

) are at increased risk of adverse pregnancy 

outcome. As written, the OPPT analysis leads one to the conclusion that to exposure to “background” 

urban ambient and/or indoor air concentrations of TCE presents increased risk for cardiac malformations 

whether or not the mothers themselves use TCE or live in a home where TCE is utilized during arts and 

crafts activities. 

Recommendations 

The debate over TCE non-cancer hazard identification and potential risk of congenital malformations 

illustrates the difficulty in identification of human teratogens based on avian and rodent data. There are at 

least two pathways forward to resolution of this problem. 

First, historical concentrations of TCE in US workplace air averaged 38.2 ppm (210 mg/m3

) (with the 

highest levels 44.6 ppm during vapor degreasing) across all industries (Bakke et al., 2007). While TCE 

consumption has declined since the 1970s when some 200,000 US workers (many of whom were females 

employed in dry cleaning) were exposed (NIOSH, 1973) or in the 1990s when ATSDR (1997) tabulated 

US facility air emissions (ATSDR Table 5-1) wherein daily occupational exposures amounted to 0.03-

13.6 mg/kg-day, there are hundreds of facilities that use TCE to this very day. The OPPT estimates 7,415 

employees currently work in small commercial degreasing operations in the US and that they experience 

8 hr TWA exposures of 2-6 ppm. In addition, the OPPT estimates that there are up to 17,796 (far field) 

workers exposed at 8 hr TWA values between 1-5 ppm with worst-case concentrations on the order of 17-

63 and 9-55 ppm (Tables 3-8, D-2 and D-3). It is not clear why either retrospective or preferably 

prospective epidemiologic pregnancy outcome data (adjusting for maternal age, parity, folate status, 

tobacco and alcohol use, exposures to known human cardiac teratogens and socioeconomic status) have 

not been collected from state (e.g., California Birth Defects Monitoring Program) and private (e.g., Kaiser 

Permanente) birth defects registries? If this is because no suitable US data are available, why has the US 

EPA in collaboration with other federal agencies not evaluated pregnancy outcome data for offshore TCE 

exposures as was done by Lan et al. (2010) in their evaluation of TCE immunotoxicity? A number of 

publications that describe robust studies of benzene exposure among Chinese occupational cohorts have 

been valuable in assessment of the shape of the benzene concentration-response relationship; it is not 

clear why similar studies could not be conducted with TCE to investigate reproductive failure? The 

reliance upon community-based (ecological) TCE studies with unreliable or no empirical exposure data in 

relation to pregnancy outcome is feeble. 

Second, the current TCE debate in developmental toxicity has historical parallels with the debate over the 

teratogenic activity of selenium (Se) and steps taken to resolve that matter. Selenium is an unequivocal 

teratogen in wild birds (Hoffman et al., 1988; Hoffman, 2002), injection of Se into chicken eggs causes 

cardiac malformations (Khan and Gilani, 1980) and mechanistic data implicate lipid peroxidation in the 

pathogenesis of Se-induced cardiac terata in avian species (Padmaja et al., 1993). Not only are there case 

reports of Se-associated congenital defects in humans, but consumption of high Se diets by ruminants and 

high doses of Se in hamsters can be teratogenic. Overall, the results in rodent studies with Se found 

reductions in the numbers of live births, increased fetal death and decreased fetal and pup body weights, 

but no such effects were seen in controlled dietary studies with pigs (reviewed in ATSDR, 2003). In order 
69 of 73 

to address the uncertainty over the potential developmental toxicity of ingested Se, controlled oral 

intubation studies in pregnant non-human primates were conducted at doses up to maternally maximum 

tolerated doses together with collection of maternal, transplacental and neonatal kinetic and disposition 

data (Tarantal et al., 1991; Hawkes et al., 1994). The advantage to the non-human primate, of course, is 

their comparatively large size and similar anatomy, physiology and general metabolic handling of 

xenobiotics. Those studies found that after repeated daily ingestion of up to near lethal doses of the most 

highly bioavailable dietary Se form during organogenesis there was no evidence whatsoever for 

manifestations of developmental toxicity. The debate over the potential developmental toxicity of 

ingested Se following publication of those reports ceased. 

 

Therefore, adoption of the 2011 US EPA hazard identification for TCE as a suspect or potential human 

teratogen is not supported by the weight of evidence of all of the available data (Hardin et al, 2005; 

Watson et al, 2006). This situation can be addressed either by study of pregnancy outcome among women 

currently employed in US or offshore industries who are exposed to much higher TCE levels in air than 

the OPPT considers represent increased teratogenic risk or by controlled study of TCE kinetics and 

pregnancy outcome in non-human primates. 

See ‘TCE_Post July 17_Willhite Attachments_3 of 3_FINAL.docx’ for additional material from Dr. 

Willhite. 

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International Journal of Hyperthermia 27(4): 374-387. 
Calvin Willhite (Attachment 1) 

Project: 0904539.000 

Comments on the EPA Toxicological Review of TCE: 

Developmental Effects 

Carole A. Kimmel, PhD 

Gary L. Kimmel, PhD 

John M. DeSesso, PhD 

Exponent 

1800 Diagonal Road, Suite 300 

Alexandria, Virginia 22314 

5 August 2009 

 
 The evidence used by the EPA to support the claim that TCE and/or its metabolites are specific 

cardiac teratogens comes from both human epidemiology investigations and studies in experimental 

animals. In both cases, the arguments are not persuasive of a causal linkage. Not only does the cited 

epidemiology literature fail to satisfy the Hill criteria for causation, it also fails to link the purported 

findings to TCE exposure. In addition, the EPA assessment is incomplete insofar as it does not consider 

the most recent and comprehensive animal studies (see below) regarding the effects of TCE and its major 

metabolites in pregnant mammals. The literature cited to support the contention that TCE and/or one of 

its metabolites is a cardiac teratogen is over interpreted. 

The Cited Human Data Do Not Support a Causal Association between TCE Exposure and Birth 

Defects 

 The studies that allegedly support the contention that TCE exposure of pregnant women resulted 

in births of infants with cardiac or other developmental defects find significance by combining many 

types of malformations into large categories that sound related, but are not. For example, the category of 

“cardiac malformations” is used loosely to include alterations in the structure of the heart as well as 

alterations in the arrangement of the large blood vessels. Not only are the subject organs different, but 

also they have very dissimilar embryological development. 

The human epidemiology studies used to support this contention are of two general types. The first 

includes investigations of births from regions that had contaminated water supplies. Goldberg et al. 

(1990) investigated births in a region of Arizona that had an aquifer contaminated with 6 – 239 ppb 

TCE. The authors reported the incidence for 33 types of malformation associated with the 

cardiovascular system, among which were 12 diagnoses that were predominantly malformations of 

the great vessels, such as transposition of the great vessels, coarctation of the aorta, interrupted aortic 

arch, and patent ductus arteriosus. A total of 44 non-cardiac malformation cases (18% of the total 

cases) was reported. What is remarkable about these studies is the low exposure concentrations of 

TCE. As will be discussed below, those animal studies that did report positive results had lowest 

observed effect levels (LOELs) that were four to six orders of magnitude higher than the highest 

reported contamination level in the Arizona aquifer. 

The “cardiac anomalies” reported in the contaminated Arizona aquifer studies contrast with the 

results of other epidemiology studies. For instance, Wilson et al. (1998) examined data from the 

Baltimore-Washington Infant Study and concluded that “solvents/degreasing agent exposure” 

(inclusive of TCE and many other substances) accounts for 4.6% of the attributable risk for 

hypoplastic left heart syndrome, but no attributable risk for anomalies including transposition of the 

great vessels and coarctation of the aorta. The findings in this study contrast with those of the 

Goldberg study mentioned above, where the individual malformations that together comprise 

hypoplastic left heart syndrome (aortic valve stenosis, mitral stenosis, hypoplastic left ventricle) 

accounted for only 15 cases (6% of the cases reported). Thus, there is poor concordance between 

these two study populations (i.e., three-fold difference in rate of occurrence and different types of 

“cardiac anomalies”). 

A study of births in 75 towns of New Jersey that experienced water supply contamination by a 

variety of agents, including TCE at an average of 55 ppb, reported significant associations between TCE 

contamination and “cardiac defects” and neural tube defects (Bove et al., 1995). Once again these 

categories were very broad and included multiple anomalies with very different modes of formation. It is 

peculiar that the reference population of >55,000 births in this study was stated to have experienced no 

birth defects. This is an incredible statement, because the background rate of major malformation in the 

United States is 1 – 3% (550 – 1650 expected cases in a population of 55,000), and neural tube defects 

and heart defects are among the most common, having an overall expected incidence of ~100/10,000 
(DeSesso et al., 1999; Hoffman and Kaplan, 2002). The authors reported as significant those effects that 

occurred with an odds ratio of 1.5 or greater, but they used relaxed 90% confidence intervals. In the case 

of the TCE-exposed population, for instance, the incidence of neural tube defects was reported as 

56/81,532 or 6.9/10,000, which is well within the expected number of cases based on the national 

incidence rate, although it is obviously higher than the “0” seen in the reference population. Notably, 

hypoplastic left heart syndrome (normal rate of occurrence ~2/10,000 births) was not associated with 

TCE contamination (see discussion below). 

A shortcoming that is common to all of the epidemiology studies is the lack of accurate exposure 

information and poor control of confounding factors. In the instance of the Arizona aquifer, the authors 

were clear to point out that their data showed “a significant association but not a cause and effect relation 

between parental exposure to the contaminated water area” and cardiac defects. By this they meant that 

the parents of affected children were present in the land area overlying the aquifer during early gestation– 

but not that they had necessarily drunk or used contaminated water. Thus, exposure was not quantified. 

With respect to the Baltimore-Washington Infant Study, interviews with parents identified activities and 

occupations that were likely to have involved organic solvents and degreasing substances. TCE is among 

the substances that could have been used, but it was not singled out as a causative agent and there is no 

information on levels of exposure. These data-sets fail to clearly identify a specific causative agent and 

do not quantify exposure levels, making the assessment of risk for a particular chemical (e.g., TCE) 

unfeasible. 

As detailed above, the human data cited by the assessment are inadequate for risk assessment. In 

the absence of clear-cut human data, strong evidence from animal studies in addition to good mechanistic 

information can help in the assessment of risk. 

Data from Early Animal Studies Have Been Used Without Critical Evaluation 

 Papers from the EPA laboratories in Cincinnati (Smith et al., 1989, 1992; Epstein et al., 1992) 

first reported cardiovascular anomalies in fetal rats whose mothers had received doses of the TCE 

metabolites TCA (up to 1,800 mg/kg/day) or DCA (up to 2,400 mg/kg/day) by gastric intubation during 

gestational days 6 – 15. The spectrum of cardiac malformations observed in these studies was unique. 

They included many cases of “levocardia” (displacement of the heart towards the left side of the thorax) 

and a defect that appears to have been very high in the membranous portion of the interventricular septum 

(the wall that separates the left and right ventricles and participates in the separation of the aorta from the 

right ventricle). As will be detailed later, other laboratories have not reproduced these malformations. 

The question arises as to the cause of the observations in these first studies. It should be noted 

that the doses used in these studies were six to seven orders of magnitude higher than the dose expected 

for a 65-kg pregnant woman who drinks water containing TCE at the concentration resulting from 

application of the proposed reference dose (RfD)(13μg/L). Further, the pregnant rats in the groups with 

anomalous fetal hearts experienced severe maternal toxicity, evidenced by diminished body weights at 

study termination, decreased weight gains during gestation, and total litter resorptions. The offspring 

from the affected litters had mean fetal weights that were approximately 33% lower than control values, 

as well as concomitant decreases in fetal size (e.g., decreased crown-rump lengths). In rats, the last 48 

hours of gestation are a period of rapid growth; not only do the fetuses gain much weight in this period, 

but also the thorax grows quickly to accommodate the lungs, which develop largely after birth (Rakusan, 

1984; Burri et al., 1974). While it is possible to associate the cardiac effects with the aforementioned 

maternal and fetal toxicities, there may be another contributing factor. Some findings in developmental 

toxicity studies can be caused by too over-zealous dissection methods (Harris and DeSesso, 1994). Fresh 

dissection of rat fetuses for examination of thoracic contents and dissection of the heart to observe 

internal cardiac structure is a demanding procedure because of the small size of fetuses. In fetuses that 

are one-third smaller than normal, the effort is even more difficult. The delicate tissues of compromised 
heart (especially the diaphanous tissue of the membranous interventricular septum) can be easily 

disrupted during the incision and opening of the heart. 

In a subsequent paper that laid out a proposed general toxicity-neurotoxicity-developmental 

toxicity screening approach, Narotsky and Kavlock (1995) administered large doses of TCE (1,125 or 

1,500 mg/kg/day) by gastric intubation to pregnant Fisher 344 rats on gestational days 6 – 19 and allowed 

the animals to deliver their litters. The maternal animals experienced noticeable toxicity at both doses. 

Pup weights were significantly decreased in both treated groups, and the pups were reported to have 

experienced “increased incidences of micro/anophthalmia,” although the numbers associated with these 

lesions were not reported. In the absence of data it is not possible to independently evaluate the latter 

conclusion. The thoracic contents (including hearts) were not examined. One notable design 

characteristic is the exaggerated dose of the material relative to the expected human exposure levels, as 

noted for the preceding studies. This brings into question the relevance of these findings for risk 

assessment purposes. 

In 1998, Johnson et al. studied a variety of TCE metabolites for potential effects on cardiac 

development in pregnant Sprague-Dawley rats by providing drinking water that contained one of the TCE 

metabolites (including TCA, MCA [monochloroacetic acid], DCVC, and others) from gestational day 1 

throughout pregnancy. They reported an increased incidence of cardiac anomalies only in pups from the 

eleven rats that had received water that contained 2,730 ppm of TCA. The defects included four cases of 

defects in the membranous interventricular septum. These findings are provocative, given the early 

reports by Smith and colleagues, but are in need of verification because of the small number of maternal 

animals in the TCA group, the lack of a dose-response design, and the low number of cases. As discussed 

in the next section, a robust follow-up study has been completed and was unable to reproduce the 

findings. 

In addition to the whole animal studies mentioned above, the EPA assessment reviews data from 

papers that have designs that are inappropriate for risk assessment. The papers include those of Dawson 

et al. (1990) wherein solutions of TCE (15 or 1,500 ppm in saline) were delivered directly to the uterine 

lumina of pregnant Sprague-Dawley rats by osmotic mini-pumps that had been surgically implanted in the 

abdominal cavities on gestational day 7. While alterations were observed in several fetuses, there were no 

cases of ventricular septal defects. Administration of compounds by such an irrelevant route provides 

little information about the potential risk due to environmental or occupational exposure to TCE. The 

other paper that deserves mention is that of Boyer et al. (2000) who explanted the atrioventricular canals 

from stage 16 chick embryos and cultured them in a collagen gel that contained 0 - 250 ppm TCE. The 

authors noted that mesenchymal cell formation was inhibited in cultures containing TCE. The findings of 

this study are not relevant to human health risk assessment for a variety of reasons. First, avian 

developmental models differ significantly from mammalian models due to the absence of a maternal 

influence and a placenta. Second, the dose at the exposed tissues in the culture system is static and is 

likely to be far higher than the target tissue dose in developing mammalian hearts. Third, the culture 

method is not widely used and there is little background data with which to compare the results of the 

experiments. 

Review of Johnson et al. (2003) Paper (Critical Study) and Associated Studies. 

The fact that Johnson et al. (2003) is actually a compilation of data from two or more studies, the 

first published ten years before the 2003 publication (Dawson et al., 1993), was not made clear in their 

paper. In fact, it appears that it took a letter to the editor (Hardin et al., 2004) to have the authors explain 

this situation (Johnson et al., 2004). This gives the appearance that the authors were unaware of how to 

design studies, analyze and present developmental toxicity data. 

There are a number of concerns regarding these studies: 
First, it is not clear where all of the data reported in Johnson et al. (2003) came from. Currently, 

we are aware of two papers: Johnson et al. (2003) and Dawson et al. (1993). These are the two papers 

that are referenced in their response to Hardin et al. (2004), but, there is no indication in the summary 

paper (Johnson et al., 2003) of which data came from Dawson et al. (1993) and which data came from 

later studies. 

Johnson et al. (2003) do not provide data on maternal and fetal parameters other than cardiac 

malformations, only mentioning that “maternal and fetal variables, including noncardiac congenital 

abnormalities, showed no significant differences between treated and control groups.” Dawson et al. 

(1993) did not provide any control data for maternal and fetal parameters, other than cardiac 

abnormalities. Consequently, there is no way to assess the impact of exposure on any parameter other 

than cardiac abnormalities, including such parameters as maternal body weight and body weight gain, 

fetal weight, and fetal viability. Johnson et al. (2004) note in their editorial reply that “Control values 

were consistent throughout our studies,” however, there is no way for the reader to determine that. 

Dawson et al. (1993) do not mention the number of pregnant dams that were assigned to each 

treatment group. There is no way to determine how much of the data in Johnson et al. (2003) is from the 

Dawson et al. (1993) study. 

It would be prudent to have a qualified statistician look at this data base and the statistical 

evaluations used. Given the pooling of discrete data and the unbalanced study design (55 dams in the 

control vs. 9-13 in the treatment groups), it would be interesting to know how a statistician would view 

the analysis. Moreover, can the analysis address the hypothesis? Johnson et al. (2003) indicate that their 

goal was to determine whether there was a threshold level of TCE in drinking water above which the 

incidence of congenital cardiac defects in the rodent increased significantly. Does their study design and 

statistical analysis permit the testing of a hypothesis derived from this goal? They do report that their data 

could indicate that a threshold effect exists at a level between 1.5 and 1,100 ppm. That is a range of three 

orders of magnitude, which is not very useful in establishing reference concentrations. 

In discussing the dose-response pattern in these studies, Johnson et al. (2003) specifically 

comment on the response of the highest exposure (1,100,000 ppb) relative to control, but they only 

mention that “Intermediate exposure levels produced intermediate response rates.” While this is true, the 

intermediate levels did not produce a clear dose-response relationship. The 2.5 ppb exposure level did not 

show any effects, even though 16.4% of the control litters had a cardiac defect. Moreover, there was a 

reduced (or at best an equivalent) response between 250 ppb and 1500 ppb. Johnson et al. (2003) provide 

a rationale for choosing the exposure levels that were used, but the extreme range makes it difficult to 

examine whether a continuous response pattern exists. To make the analysis more difficult to interpret, 

the fetus and not the dam (litter) was used as the experimental unit, or at least was the unit where 

statistically significant responses were noted. The dose-response pattern may be another area where the 

input of a qualified statistician/modeler would be prudent. 

Johnson et al. (2003) comment that TCE exposure using an in vitro chick model has been shown 

to have effects on several elements of epithelial–mesenchymal cell transformation at concentration ranges 

that correlate with their findings. They note a concentration range of 50-250 ppm (although it isn’t clear 

if this is the only concentration range used in the referenced studies). If the 50-250 ppm is correct, it does 

not correlate with the Johnson et al. (2003) concentration range. It is bounded by the Johnson et al. 

concentration range, but then, almost any range would be, given the extreme range that Johnson et al. 

used. More importantly, an application of any concentration of TCE in an in vitro chick embryo study is 

in no way comparable to an application of any other concentration of TCE in drinking water in an in vivo 
rat study. It is unclear why the authors even make this statement; are they suggesting that their drinking 

water dose range would produce similar inhibitions of the transcription factors? 

Johnson et al. (2003) do not reference Fisher et al. (2001), even though Johnson was one of the 

authors of the latter study and part of the cardiac examination team. Fisher et al. (2001), using techniques 

similar1

 to those reported in Johnson et al. (2003), did not find any cardiac defects following exposure to 

500 mg/kg/day TCE. They provide some possible explanations for the differences from the Dawson et al. 

(1993) study: TCE purity, rat strains (both used Sprague-Dawley, different sources?), and experimental 

design (see above footnote), and the use of a staining procedure in the Fisher study “to better visualize 

heart structure.” This last comment is surprising, since if the hearts were better visualized, one would 

expect that more, not zero, affected hearts would have been found. 

One additional note: In their conclusions, Fisher et al. (2001) comment: 

“The high background of fetal heart malformations on a per litter basis provides a 

challenge for using these data in regulatory decisions relating to risk characterization of 

TCE, TCA, and DCA. Also, the lack of clear dose-related effects (Dawson et al., 1993, 

and the present study) provide data of questionable utility for risk assessment 

applications.” 

Comments on Specific Types of Heart Defects Reported 

While there were similar methods used for examining fetuses in the Dawson/Johnson laboratories 

involved and Dr. Johnson collaborated on the Fisher et al (2001) study, there were several differences 

between the 3 studies as noted in the EPA review (see table 1). In addition, preparation of the heart for 

dissection also differed. Dawson et al (1993) and Johnson et al (2003) both removed the heart first, then 

flushed with a fixative, while Fisher et al (2001) flushed the heart in situ via the left ventricle with a 

staining solution for better visualization (1:3 hematoxylin-saline solution), perhaps a more 

physiologically normal situation, then removed the heart and immersion fixed it in 10% buffered 

formalin. 

Table 1. Comparison of Methods Used in the Dawson et al (1993), Johnson et al (2003), and 

Fisher et al (2001) 

Study Stock 

of 

animal

s 

Source of 

animals 

Route 

of 

exposu

re 

Dose Vehicl

e 

Treatmen

t days 

GD 

Day 

of 

sper

m 

GD 

Day of 

sacrific

e GD 

Heart preparation 

Dawso

n et al 

1993 

Spragu

e 

Dawle

y 

Harlan, 

Indianapoli

s? 

Drinki

ng 

water 

1.5 

and 

1100 

ppm 

Tap 

water 

1-22 1? 22? flushed with 2% 

glutaraldehyde after 

heart removal, fixed 

for 24 hrs in the same 

solution, transferred 

to 0.1 mol/L 

phosphate buffer 

                                                            

1 Fisher et al. (2001) used soybean oil as a vehicle for TCE and retinoic acid (positive control) and treated the

animals with a daily bolus gavage (GD 6‐15).  Johnson et al. (2003) used water as a vehicle for TCE, provided ad lib

in the drinking water, which was changed daily with fresh TCE.  The treatment period was over the entire 22‐day

pregnancy.  
Johnso

n et al 

2003 

Spragu

e 

Dawle

y 

Harlan? Drinki

ng 

water 

2.5 & 

250 

ppb, 

1.5 & 

1100 

ppm 

Distille

d water 

1-22 1? 22? flushed with 10% 

formalin, transferred 

to 10% formalin 

Fisher 

et al 

2001 

Spragu

e 

Dawle

y 

Charles 

River, 

Raleigh 

Gavage 500 

mg/k

g 

Soybea

n oil 

(TCE 

& RA); 

IERO* 

water 

(TCA, 

DCA) 

6-15 0 21 flushed in situ via the 

left ventricle with 

staining solution for 

better visualization 

(1:3 hematoxylinsaline solution), then 

removed and 

immersion fixed in 

10% buffered 

formalin 

* IERO = ion exchange/reverse osmosis 

The major difference in the data from the Dawson/Johnson laboratory vs. the Fisher laboratory 

appears to be the incidence of atrial septal defects (Table 2). The types of atrial septal defects are not 

detailed in any of the papers except for the statement that they are “secundum in type” (Dawson et al, 

1993). Since the septum primum and septum secundum both grow rapidly around the time of birth to 

close the foramen ovale (Momma et al, 1992), this may represent a variation in development like other 

structures that are developing around the time of birth in the rat, e.g., skeletal ossification of sternebrae, 

vertebrae centra, etc., and the renal papillae. Whether the different methods of flushing the hearts may 

have disturbed the position of the septum which would not be closed on the day of sacrifice is unclear. 

Even more disturbing, however, is that neither Dawson et al (1993) nor Johnson et al (2003) provide 

maternal or fetal weight data, so it is impossible to know whether there were differences in fetal weight 

that would suggest a delay in development. Also, data on other aspects of fetal development (e.g., 

skeletal ossification) were not presented to give any clues about developmental stage. Fisher et al (2001) 

report no significant difference from water controls in maternal weight, uterine weight, number of 

implantations or fetal weight for TCE at 500 mg/kg. In that study, the percent of fetuses with atrial septal 

defects was approximately the same in the two groups. Thus, there are many unanswered questions about 

the incompleteness of the data presented in the Dawson et al. (1993) and Johnson et al. (2003) papers, in 

addition to the obvious design flaws and protracted length of time over which the studies were conducted. 

Without concurrent control data, it is very difficult to evaluate small changes in heart development that 

may or may not be related to TCE exposure. 

Table 2. Comparison of Atrial Septal Defects in the Three Papers* 

Study/Data Treatment Groups 

Dawson et al 

1993 

Control 

Tap 

water 

TCE – 

Pre only 

1.5 ppm 

TCE – Pre 

only 

1100 ppm 

TCE – 

Preg only 

1.5 ppm 

TCE – 

Preg only 

1100 

ppm 

TCE – 

Pre & 

Preg 

1.5 ppm 

TCE – 

Pre & 

Preg 

1100 ppm 

No. of atrial 

septal 

defects/no 

hearts 

examined (%) 

1/232 

(0.4) 

3/130 

(2.3) 

7/147 

(4.8) 

4/181 

(2.2) 

7/105 

(6.7) 

5/256 

(2.0) 

19/435 

(4.4) 
Johnson et al 

2003 

Control 

Distilled 

water 

TCE – 

2.5 ppb 

TCE – 250 

ppb 

TCE – 

1.5 ppm 

TCE – 

1100 

ppm 

 

No. of atrial 

septal 

defects/no 

hearts 

examined (%) 

7/606 

(1.2) 

0/144 

(0) 

1/110 

(1.0) 

4/181 

(2.2) 

7/105 

(6.7) 

 

Fisher et al 

2001 

Control 

IERO** 

Water 

TCA 

300 

mg/kg in 

IERO 

water 

DCA 

300 mg/kg 

in IERO 

water 

Control 

Soybean 

oil 

TCE 

500 

mg/kg in 

soybean 

oil 

Retinoic 

acid – 15 

mg/kg in 

soybean 

oil 

No. of atrial 

septal 

defects/no 

hearts 

examined (%) 

2/273 

(1.0) 

2/269 

(1.0) 

3/298 

(1.0) 

6/367 

(1.6) 

4/290 

(1.4) 

3/155 

(1.9) 

*Highlighted boxes are the same data reported in both papers 

**IERO = ion exchange/reverse osmosis 

Later, Robustly-designed Studies in Animals Fail to Confirm Earlier Findings of Malformations in 

Rats 

A subsequent publication (Fisher et al., 2001) specifically investigated the cardiac teratogenic 

potential of TCE, TCA, and DCA in groups of 19 – 20 pregnant Sprague-Dawley rats. The rats received 

oral bolus doses of TCE (500 mg/kg/day, in soybean oil), TCA (300 mg/kg/day, in water) or DCA (300 

mg/kg/day, in water) on gestational days 6 –15. On gestational day 21, fetuses were removed by 

laparohysterectomy and hearts were examined and microdissected under a stereomicroscope by an 

investigator experienced in the procedure (Dr. Paula Johnson, author of the earlier report that TCA caused 

cardiac effects at 291 mg/kg/day). The rates of cardiac malformations among treated animals did not 

differ from control rates. 

Some early studies of TCA and DCA in pregnant Long-Evans rats (Smith et al., 1989, 1992) 

reported ocular malformations. In a study that reported findings after examination of the heads of the 

fetuses from the Fisher et al. 2001 study described above, Warren et al. (2006) reported that TCE, TCA, 

or DCA did not elicit gross ocular malformations. Morphometric analysis of the lens area, globe area and 

interocular distances revealed reductions of these parameters only in the TCA- and DCA-treated fetuses, 

but the overall smaller sizes of the fetuses in those groups were sufficient to explain the reductions. 

An inhalation study of TCE in pregnant Charles River CD IGS rats (Carney et al., 2001; 2006) 

exposed groups of 27 animals to filtered air or to atmospheric concentrations of TCE up to and including 

the limit dose (600 ppm) for 6 hours/day on each of gestational days 6 – 20. Although maternal toxicity 

(decreased body weight gain) was elicited at the highest dose, TCE exposure caused no increase in gross, 

skeletal, or visceral (including heart and eye) malformations. 

Assessment 

 Early findings of potential heart defects in rat pups associated with high doses of TCE 

metabolites during gestation prompted a series of investigations into the issue. The currently existing 

human data are deficient for risk assessment, but even so they do not support an association between TCE 

exposure and cardiac defects in babies. Data from GLP compliant animal studies that were carefully 
designed to probe the existence of potential links between TCE or its metabolites and heart or eye defects 

have shown no associations at exposure levels that are several orders of magnitude higher than those that 

are environmentally or occupationally relevant. 

The current EPA review of TCE toxicity focuses on several endpoints for establishing a reference 

concentration and a reference dose. These were considered the most sensitive effects in the current data 

base. Two of these are developmental endpoints: fetal heart malformations in rats and developmental 

immunotoxicity in mice. The current preliminary review focuses on the fetal heart malformations, since 

this appears to be an area with some controversy. 

The EPA has developed an RfC of 0.001 ppm and an RfD of 0.0004 mg/kg/day. The fetal heart 

malformation data reported in Johnson et al. (2003) is used to support both of these values (US EPA, 

2009; see Tables 5.1.23 and 5.1.24 and the associated text). 

Studies from the Dawson/Johnson laboratory are clearly compromised by a number of design 

weaknesses which are stated in the EPA review, but the weight of evidence discussion in section 

4.7.3.3.2.3 only considers those studies that reported cardiovascular defects and essentially ignores more 

carefully designed state-of-the art studies that do not report cardiovascular defects. This is not a “weight 

of evidence” evaluation but a “strength of evidence” evaluation. All the focus is on those studies that 

found an effect and none on the strengths and weaknesses of those that did not. There is nothing in the 

EPA weight of evidence about the studies that did not find cardiac defects but which used sound 

methodology, i.e., Fisher et al., 2001, and Carney et al., 2006. Weight of evidence clearly must consider 

all of the data, both positive and no effect data. When studies with clear flaws that use methods giving 

results not replicable in other laboratories constitute the majority of the positive data, it is difficult to see 

how the EPA can justify using these data as the basis for regulatory end-point(s). 

Final Comments 

The EPA Review Draft (pp 855-857) notes that potential limitations of the cardiac malformation 

data base have been raised. Nevertheless, EPA considers the animal data provide “strong, but not 

unequivocal, evidence” of TCE-induced cardiac malformations; and EPA’s final evaluation is that there is 

sufficient concern regarding the potential for TCE to lead to cardiac defects (p 861). 

EPA puts emphasis on the Johnson et al. (2003) and Dawson et al. (1993) studies and has noted 

that Johnson “has provided individual litter incidence data to the USEPA for independent statistical 

analysis (P. Johnson, personal communication, 2008) (see Section 6, dose-response)” (US EPA, 2009, p 

857). It is unclear why EPA refers to “Section 6, dose-response” regarding this additional data. Nothing 

in this section described these data or how they were used. Hopefully, EPA has examined these data, 

although it is unclear if this has ever been done or how it has been incorporated into EPA’s risk 

assessment. 

Finally, there has been too much focus on one set of studies that show a putative positive 

response to low-exposure levels of TCE, without considering the overall data base and the limitations of 

the focus studies. The Johnson et al. (2003) and Dawson et al. (1993) studies have significant limitations 

regarding the reporting of standard maternal and fetal parameters. Without evaluating all of the maternal 

and fetal parameters, it is not possible to get a clear idea of how the animals are responding to treatment 

and whether the endpoint values are within historical ranges. Studies where major components of the 

results are not reported or the missing data has not been evaluated by the risk assessors may be useful in 

supporting other, more complete, data sets, but are of questionable value as a primary study in 

establishing an exposure standard. 
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Teratology 1992; 46(3):217-23. 

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Warren, D.A., L.J. Graeter, S.R. Channel, J.S. Eggers, C.D. Goodyear, K.L. MacMahon, G.L. Sudberry, 

J.R. Latendresse, J.W. Fisher, and W.H. Baker. 2006. Trichloroethylene, trichloroacetic acid and 

dichloroacetic acid: Do they affect eye development in the Sprague-Dawley rat? International Journal of 

Toxicology 25:279-284. 

Wilson PD, Loffredo CA, Correa-Villaseñor A, Ferencz C. Attributable Fraction for Cardiac 

Malformations. Am J Epidemiol 1998; 148:414-23.
Supplement to Final Comments of Dr. Kathleen Gilbert, 

OPPT Draft Risk Assessment Peer Review Panel Member

September 5, 2013

1. Spotting Chemical Fact Sheet

2. DTSC Spotting Chemical for Web

3. Material Safety Data Sheet: Fast – PR

4. Material Safety Data Sheet: Picrin
Safer Spotting Chemicals

Best Practices for Textile Cleaning -- May 2007

Why and how are POG

spotting chemicals used?

Paint, Oil and Grease (POG) spotting

agents are used to remove spots

from garments by professional textile

cleaners. They are sprayed on spots

before and after garments are

processed through the garment

cleaning machine.

What are the commonly

used POG spotting

agents?

POG spotting agents containing

trichloroethylene (TCE) and perchloroethylene (PERC) are used

widely by the garment cleaning

industry.

What are the toxicity

problems with these

spotting agents?

TCE and PERC are carcinogens and

are heavily regulated in California.

Spotters and other employees in garment cleaning plants are exposed to

these dangerous chemicals.
How do these spotting

agents affect non-PERC

garment cleaning

processes?

Many cleaners have converted

away from PERC dry cleaning to

safer alternative processes. A number of them, however, continue to

use TCE and PERC spotting agents.

Use of these spotting agents will

make the waste streams generated

by the non-PERC garment cleaning

processes hazardous.

Is there a particular problem with these spotting agents 

for wet cleaning plants?

When cleaners pre-spot garments, the TCE and PERC residues are flushed into the sewer when

the water from the cleaning process is discharged. It is illegal for cleaners to discharge hazardous

waste to the sewer.
How do I know if my spotting agent contains TCE or PERC?

Ask your spotting chemical supplier for a Material Safety Data Sheet (MSDS) for the spotting agent.

If the spotting agent contains TCE or PERC, it should list the chemical under the second section of

the MSDS sometimes labeled "Composition / Information on Ingredients" or “Components.” The

Chemical Abstract Service (CAS) number should also be listed. This is important because suppliers

may call TCE and PERC by different names, but the CAS number stays the same. The CAS number for TCE is 79-01-6 and for PERC 127-18-4. The first page of an MSDS containing TCE is shown

below. The “Composition / Information on Ingredients” section is circled in blue.
Have safer alternative spotting

agents been tested?

The Institute for Research and Technical

Assistance (IRTA) is a technical nonprofit

organization. During a project sponsored by

California Environmental Protection Agency’s

Department of Toxic Substances Control

(DTSC) and U.S. EPA Region IX, IRTA tested

low-VOC safer alternatives with a number of

textile cleaning facilities using a range of different textile cleaning processes. IRTA and the

test facilities found that the alternative POG

spotting agents worked effectively.

Are the safer alternative POG

spotting agents available?

There are some alternative spotting agents on

the market. Many of these contain other ingredients that are toxic or are Volatile Organic

Compounds (VOCs) that contribute to smog.

The best alternatives from an overall health and

environmental standpoint are water-based and

soy based products.

Where can I get more 

information?

The IRTA report is on IRTA's website at

www.irta.us, the DTSC's website at

www.dtsc.ca.gov/PublicationsForms and the

Western Regional Pollution Prevention

Network website at www.wrppn.org.

You can contact IRTA at 

(818) 244-0300 with questions

on spotting agent alternatives.

Some Products Containing 

TCE or PERC

Picrin® -- R.R. Street & Co. Inc.

2-1 Formula® -- R.R. Street & Co Inc.

Volatile Dry Spotter (V.D.S.) -- Laidlaw Corp.

Wetspo -- Laidlaw Corp.

Fast P.R.® -- Caled Chemical

PURO® -- Adco Inc.

P.O.G. -- Pariser Industries Inc.

TarGo® -- A.L. Wilson Chemical Co.

Mention of trade names, products, or services does not convey, and should not be interpreted as conveying,

U.S. EPA, California Department of Toxic Substances Control (DTSC), the California Air Resources Board, or

any local government approval, endorsement, or recommendation. This document has not been subject to EPA’s

required peer and policy review. It does not necessarily reflect the views of the Agency, and no official endorsement should be inferred.
Spotting Chemicals: Alternatives to Perchloroethylene and Trichloroethylene in the

Textile Cleaning Industry

Prepared by:

Katy Wolf and Mike Morris

Institute for Research and Technical Assistance

Prepared for:

Cal/EPA’s Department of Toxic Substances Control and

U.S. Environmental Protection Agency Region IX

January 2007
DISCLAIMER

This report was prepared as a result of work sponsored and paid for by California

Environmental Protection Agency’s (Cal/EPA’s) Department of Toxic Substances

Control (DTSC) and the United States Environmental Protection Agency (U.S. EPA).

The opinions, findings, conclusions and recommendations are those of the authors and do

not necessarily represent the views of the sponsors. Mention of trade names, products or

services does not convey and should not be interpreted as conveying Cal/EPA, DTSC or

U.S. EPA approval, endorsement or recommendation. DTSC, U.S. EPA, their officers,

employees, contractors and subcontractors make no warranty, expressed or implied, and

assume no legal liability for the information in this report. The sponsors have not

approved or disapproved this report nor have the sponsors passed upon the accuracy or

adequacy of the information contained herein.
ii

ACKNOWLEDGMENTS

The analysis in this report benefited considerably from the efforts of many persons within

and outside the Institute for Research and Technical Assistance (IRTA). We would

particularly like to acknowledge the valuable contributions made by Robert Ludwig from

DTSC and John Katz from U.S. EPA. We are especially grateful to Dr. Julia Quint from

the Department of Health Services Hazard Evaluation System & Information Service for

her work in evaluating the toxicity of the materials. We would also like to give special

thanks to certain suppliers who provided the materials for spotting agent alternatives. We

are very thankful to the textile cleaning facilities who assisted us in testing the alternative

spotting agents. Finally, we are indebted to Amy Blume of IRTA for her assistance in

preparing the document.
iii

EXECUTIVE SUMMARY

Perchloroethylene (PERC) and trichloroethylene (TCE) are used in the textile cleaning

industry as Paint, Oil and Grease (POG) spotting agents. Spotting agents are used before

or after cleaning in equipment to remove spots on garments. PERC and TCE are

carcinogens. They are classified as Hazardous Air Pollutants by EPA and Toxic Air

Contaminants by the California Air Resources Board. Both chemicals are listed on

California’s Proposition 65 and are listed hazardous wastes under the Resource

Conservation and Recovery Act.

This project was sponsored by Cal/EPA’s Department of Toxic Substances Control and

the U.S. Environmental Protection Agency. It was conducted by the Institute for

Research and Technical Assistance (IRTA), a nonprofit organization. The purpose of the

project was to identify, test, develop and demonstrate low-VOC, low toxicity alternates to

PERC and TCE POG spotting agents.

IRTA tested safer alternative spotting agents with seven textile cleaning facilities that

have adopted alternatives to PERC dry cleaning. The alternative spotting agents were

used in facilities that have hydrocarbon, Green Earth, carbon dioxide and water-based

cleaning processes. The alternatives were used by each facility for one to five weeks on

the facility garments.

The alternative spotting agents that proved to be effective are shown in Table E-1. One

of the spotting agents, Cold Plus, is a commercial spotting product introduced to the

market in the last year or so. The other spotting agents are cleaners that IRTA has tested

successfully for other purposes.

Table E-1

Alternative Spotting Agents That Performed Effectively

Spotting Agent Type of Material 

Cold Plus Water-Based Cleaner

Mirachem NP 2520 Water-Based Cleaner

Soy Gold 2500 Methyl Ester and Surfactants

DPM Glycol Ether

90% Soy Gold 2500/10% Acetone Blend

90% Soy Gold 2500/10% DPM Blend

90% DPM/10% Acetone Blend 

IRTA conducted a cost analysis to compare the cost of using TCE spotting agents with

the cost of using the alternatives. The results indicated that the cost of using the

alternatives is lower than the cost of using TCE.

Waste streams from the textile cleaning process containing PERC or TCE are classified

as hazardous waste. One of the advantages of using the alternative spotting agents is that
iv

these waste streams may not be classified as hazardous waste. Another advantage is that

workers and consumers would not be exposed to PERC or TCE during spotting of or in

the wearing of the garments. The Department of Health Services Hazard Evaluation

System & Information Service assisted IRTA in evaluating the toxicity of the alternative

spotting agents based on their Material Safety Data Sheets. The findings indicate that the

alternatives are lower in toxicity than PERC or TCE spotting chemicals.

This project demonstrates that there are a variety of effective cleaners that could be used

as alternatives to PERC and TCE spotting agents in the textile cleaning industry. These

include water-based cleaners, soy based cleaners, glycol ethers, acetone and blends of

these cleaners.
v

TABLE OF CONTENTS

Disclaimer ................................................................................................................................ i

Acknowledgements.................................................................................................................ii

Executive Summary...............................................................................................................iii

Table of Contents.................................................................................................................... v

List of Figures .......................................................................................................................vii

List of Tables .......................................................................................................................viii

I. Introduction and Background ......................................................................................... 1

Previous Related Work ................................................................................................... 1

Project Approach............................................................................................................. 2

Structure of Document.................................................................................................... 2

II. Spotting Agent Characteristics ....................................................................................... 3

Waste and Effluent Generation and Results................................................................... 3

Waste and Effluent Analysis from CARB/U.S. EPA Project..................................... 3

Waste Analysis for DTSC Project............................................................................... 5

Summary of Analysis Results...................................................................................... 6

Spotting Procedures and Spotting Chemicals ................................................................ 6

Specific TCE and PERC Spotting Agents................................................................... 7

III. Alternatives Testing ........................................................................................................ 9

Screening Tests of Alternative Spotting Agents ............................................................ 9

Garments and Contaminants Used in Screening Tests ............................................... 9

Cleaners Used in Screening Tests ............................................................................. 13

Results of Screening Tests......................................................................................... 14

Field Tests of Alternative Spotting Agents .................................................................. 15

Approach to Field Testing ......................................................................................... 15

Results of Field Testing ............................................................................................. 16

Cost of Current and Alternative Spotting Agents ........................................................ 16
vi

IV. Health and Environmental Characteristics of Alternatives.......................................... 19

Air Regulations that Apply to Spotting Chemicals...................................................... 19

Waste Regulations that Apply to Spotting Chemicals................................................. 19

Toxicity of Spotting Agents.......................................................................................... 20

Toxicity of PERC and TCE ....................................................................................... 20

Toxicity of Alternative Spotting Agents ................................................................... 21

VI. Summary and Conclusions ........................................................................................... 22

Appendix A

MSDSs and Product Sheets for PERC and TCE Spotting Agents...................................... 24

Appendix B

MSDSs for Alternative Spotting Agents............................................................................. 62
vii

LIST OF FIGURES

Figure 3-1: White Shirt with Blue Screen Printing Ink ................................................... 10

Figure 3-2: Yellow Pants with Motor Oil ........................................................................ 10

Figure 3-3: Blue Shirt with Black Latex Paint................................................................. 11

Figure 3-4: Tan Dockers with Red Nail Polish................................................................ 11

Figure 3-5: Beige Pants with Mascara ............................................................................. 12

Figure 3-6: Gold Jacket with Black Sharpie Marker....................................................... 12

Figure 3-7: Beige Shirt with Lipstick............................................................................... 13
viii

LIST OF TABLES

Table E-1: Alternative Spotting Agents That Performed Effectively .............................iii

Table 2-1: Water-Based Cleaning Effluent Results – First Round Sampling ................. 4

Table 2-2: Water-Based Cleaning Effluent Results – Second Round Sampling............. 5

Table 2-3: PERC and TCE

Found in Waste Stream Analysis at Hydrocarbon Cleaners .......................... 5

Table 3-1: Spotting Agents That Were Used and

Performed Well in Scaled-Up Testing.......................................................... 16

Table 3-2: Price Estimates of Current and Alternative Spotting Agents

Based on One Gallon Quantities................................................................... 18

Table 5-1: Alternative Spotting Agents that Performed Effectively.............................. 23
9

I. INTRODUCTION AND BACKGROUND

According to the California Air Resources Board (CARB), there are about 5,000 textile

cleaning facilities in California. About two-thirds of these facilities use

perchloroethylene (PERC) for dry cleaning garments. Approximately one-third of the

cleaners in California have converted from PERC to various alternatives. The vast

majority of the cleaners have adopted hydrocarbon. However, other technologies,

including Green Earth which is a silicone based solvent, Rynex which is a glycol ether,

carbon dioxide and water-based technologies that rely on water and detergent are also

being adopted for textile cleaning.

Regardless of the technology that cleaners employ, they all perform spotting as part of

the garment cleaning process. Cleaners use spotting agents to remove spots prior to

cleaning the garments in the machine or after the garments have been cleaned in the

machine. Many of the spotting agents historically contained PERC and now contain

trichloroethylene (TCE). Both PERC and TCE are carcinogens, they are classified as

Hazardous Air Pollutants (HAPs) by EPA, they are classified as Toxic Air Contaminants

(TACs) in California, they are listed on Proposition 65 as substances known to cause

cancer to the state of California and they are listed hazardous wastes under the Resource

Conservation and Recovery Act (RCRA).

The Institute for Research and Technical Assistance (IRTA) is a nonprofit organization

established in 1989. IRTA works with companies and whole industries to identify, test,

develop and demonstrate low-VOC, low toxicity solvent alternatives. Under U.S. EPA’s

Pollution Prevention Grants program, Cal/EPA’s Department of Toxic Substances

Control contracted with IRTA to identify, develop, test and demonstrate safer spotting

agents for textile cleaning.

PREVIOUS RELATED WORK

Over the last three years, IRTA completed two projects related to the current spotting

chemical investigation. The first project, sponsored by CARB and U.S. EPA, was a

technology assessment of alternatives to PERC dry cleaning. Part of this project involved

sampling certain of the waste and effluent streams for some of the alternative cleaning

methods. In some of the streams, IRTA identified TCE and PERC. CARB is currently

proposing a phaseout of PERC dry cleaning in 2023 so cleaners in the state will be

converting to alternative technologies increasingly over the next 15 years.

The second project, sponsored by DTSC, involved examining the characteristics of the

hydrocarbon technology, the most widely used PERC alternative, in more detail. IRTA

sampled waste streams from the hydrocarbon process and, again, found PERC and TCE.

Although the PERC may have entered the waste streams from various sources, the

obvious source of the TCE was spotting chemicals.
10

Since PERC and TCE are listed hazardous wastes, if they are present in a waste stream,

the stream is classified as hazardous waste. Some waste and effluent streams generated

from the PERC cleaning alternatives would not be classified as hazardous waste if they

did not contain these substances. In addition, it could be less costly to dispose of these

wastes if they did not contain PERC or TCE. As cleaners convert away from PERC dry

cleaning over the next several years, it is important to eliminate PERC and TCE in

spotting chemicals as well.

PROJECT APPROACH

Virtually all cleaning facilities, regardless of the cleaning technology they have, use socalled Paint, Oil and Grease or POG spotting agents for spotting garments. These

spotting agents contain various solvents but the most widely used POGs contain TCE and

there are others that contain PERC.

The motivation for this project was to find effective alternative POG spotting agents that

do not contain PERC or TCE. One of the aims of the project was to find alternatives that

are low in VOC content and have low toxicity. There are alternative POG spotting agents

that do not contain PERC but cleaners do not believe they work effectively. IRTA

identified several existing POG spotting agents that do not contain PERC or TCE but, in

many cases, it is not clear what chemicals they do contain. Many of the suppliers claim

trade secrets on the Material Safety Data Sheets (MSDSs) and IRTA did not want to test

spotting agents that have unidentified components.

Because cleaners do not accept existing products and because it is not clear what

materials are in existing products, IRTA tested only one existing product, a water-based

cleaner. IRTA tested several other products and developed blends of other products used

in different industries for cleaning. IRTA tested these alternatives in screening tests and

selected the best seven cleaners for more extensive testing in cleaning facilities. IRTA

worked with seven cleaners to test the alternatives and the cleaners used a variety of

PERC dry cleaning alternative processes. IRTA wanted to make sure the alternative

spotting agents would be effective for all of the alternative technologies that cleaners will

adopt over the next several years.

STRUCTURE OF DOCUMENT

Section II of the document presents information on the waste stream analysis conducted

in the earlier two projects. It describes the spotting procedure in more detail and

identifies the POG spotting agents used today. Section III summarizes the alternatives

that were tested and the tests that were conducted. The health and environmental

characteristics of the current spotting agents and the alternatives are described in Section

IV of the document. The section presents information on the regulations, the VOC

content and the toxicity of the spotting agents used today and the alternatives. Finally,

Section V summarizes the results and conclusions of the analysis.
11

II. SPOTTING AGENT CHARACTERISTICS

This section presents information on the spotting agents found in the waste and effluent

streams in the textile cleaning industry. It focuses on relevant aspects of the analysis of

the waste and effluent streams from IRTA’s earlier CARB/U.S. EPA and DTSC projects.

It then discusses the procedures used in spotting. Finally, it presents information on some

of the current POG spotting agents used by cleaners throughout the industry.

WASTE AND EFFLUENT GENERATION AND RESULTS

The major alternatives to PERC dry cleaning are:

• Hydrocarbon dry cleaning;

• Green Earth, a silicone based dry cleaning process;

• Rynex, a glycol ether based dry cleaning process;

• Carbon dioxide cleaning; and

• Various water-based cleaning methods include traditional wet cleaning which

involves immersing garments in water and detergent, icy water cleaning which is

conducted with low temperature water and detergent and Green Jet which

involves spraying garments with a water mist and detergent.

The hydrocarbon, Green Earth and Rynex processes use filters to remove particulate

contaminants in the dry cleaning process. The filters or filter residue is disposed of as

waste. These processes also often use distillation to separate the oily contaminants from

the solvent; this results in a still bottom that is disposed of as waste. Finally, there is

water present in the systems from a variety of sources. The water and solvent are

physically separated and the solvent is reused in the process. The water, which still

contains some solvent, is a waste stream. Most cleaners use evaporation to dispose of

this separator water.

In the carbon dioxide process, there is no separator water but a still bottom containing a

high concentration of detergent is generated. In the water-based cleaning processes, the

wash and rinse effluents are discharged to the sewer.

Waste and Effluent Analysis From CARB/U.S. EPA Project

In the earlier project, IRTA worked with the Los Angeles County Sanitation Districts

(LACSD) to analyze the waste and effluent streams. IRTA collected samples from

facilities using alternative technologies and LACSD analyzed the samples in their lab.

IRTA and LACSD analyzed the samples for various components including toxic volatile

and semi-volatile organics. LACSD used EPA Test Methods 601/602 or 624 for the

volatile organics and EPA Test Method 625 for semi-volatile organics. PERC and TCE

are toxic volatile organics.
12

The analysis results for the still bottoms and separator water for the Green Earth,

hydrocarbon and Rynex processes and for the still bottoms for the carbon dioxide process

indicated that there were no toxic volatile and semi-volatile components found above

detection levels. This does not mean PERC and TCE were not present, however, because

the samples were very dirty. As a result, LACSD had to dilute them substantially to

analyze them and this may have reduced the concentration of volatiles to below detection

levels.

IRTA also sampled the wash and rinse effluents from four facilities using water-based

cleaning technologies in two rounds of sampling. In the first round of sampling, the

results indicated that PERC or TCE were found in the effluent at three of the facilities.

The results are shown in Table 2-1.

Table 2-1

Water-Based Cleaning Effluent Results--First Round Sampling

Facility Toxic Organics (micrograms per liter)

 PERC TCE 

Wash Rinse Wash Rinse

Wet Cleaner #1 5,300 1,100 <200 <40

Wet Cleaner #2 <40 <40 5,100 3,200

Wet Cleaner #3 <200 <40 <200 <40

Wet Cleaner #4 <1,000 140 <1,000 <40 

Note: Different dilutions were required for each facility so detection limits were also

different.

The values in Table 2-1 that have the “less than” (<) sign in front of them are below the

detection level. The values are different for different cleaners because different dilution

levels were required. Taking this into account, three of the wet cleaners had PERC or

TCE in the effluent streams that were above detection levels. Wet Cleaner #1 had high

concentrations of PERC in both the wash and rinse effluent. Wet Cleaner #2 had high

concentrations of TCE in both the wash and rinse effluent. Wet Cleaner #4 had PERC in

the rinse effluent.

IRTA investigated further to determine the origin of the PERC and TCE in the effluent

streams. Wet Cleaner #1 and Wet Cleaner #4 both had a wet cleaning machine and a

PERC dry cleaning machine. Wet Cleaner #2 and Wet Cleaner #3 had only wet cleaning

machines. Wet Cleaner #4 was using spotting chemicals containing PERC and Wet

Cleaner #2 was using spotting chemicals containing TCE.

Table 2-2 presents the results of the second round of sampling. Before the second round

of sampling, Wet Cleaner #1 removed the PERC machine and the spotting and finishing

supervisor was replaced. PERC and TCE were found in the wash effluent. The new

spotter may have begun using a TCE based spotting chemical. Wet Cleaner #2 stopped

using the TCE based spotting agent when IRTA reported the results. No TCE was found

in the second round of sampling at this facility. Wet Cleaner #4 removed the PERC
13

machine before the second round of sampling. Even so, PERC was still found in the

wash and rinse effluents and might be present in the spotting chemicals.

Table 2-2

Water-Based Cleaning Effluent Results--Second Round Sampling

Facility Toxic Organics (micrograms per liter)

 PERC TCE 

Wash Rinse Wash Rinse

Wet Cleaner #1 480 <100 510 <100

Wet Cleaner #2 <20 <20 <20 <20

Wet Cleaner #3 <200 <200 <100 <100

Wet Cleaner #4 83 82 <20 <20 

Note: Different dilutions were required for each facility so detection limits were also

different

Waste Analysis for DTSC Project

This project focused in more detail on the hydrocarbon alternative process which is being

adopted widely by cleaners. IRTA sampled the sludge/still bottom and the separator

water at eight hydrocarbon facilities. The DTSC Hazardous Materials Laboratory (HML)

analyzed the samples for the presence of VOCs. The method used by HML was EPA

Method 8260B “volatile organic compounds by GC/MS.”

A number of VOCs were present in the waste streams. Table 2-3 presents the results of

the analysis for PERC and TCE. The figures show that PERC and/or TCE were present

in at least one waste stream analyzed at each facility. In some cases, the concentrations

were very high.

Table 2-3

PERC and TCE Found in Waste Stream Analysis at Hydrocarbon Cleaners

Facility Separator Water Concentration Sludge Concentration

 (micrograms per liter) (milligrams per kilogram)

 PERC TCE PERC TCE 

#1 30,000 9,000 19 6

#2 230 2,400 1,900 400

#3 ND ND 3 ND

#4 6 ND 30 ND

#5 71 ND ND ND

#6 ND ND 130 ND

#7 17 2 2 ND

#8 16,000 ND 12 ND 

Note: ND is non-detectable.

Summary of Analysis Results
14

The analysis results indicate that PERC and/or TCE are present in most waste and

effluent streams in the textile cleaning industry. The PERC may come from a variety of

sources. First, it can come in as a residue on garments that were previously dry cleaned

using PERC. Second, cross contamination might occur in facilities with a PERC dry

cleaning machine and another technology. Third, the PERC may be present in the

spotting chemicals. The TCE comes from only one source, spotting chemicals. As

discussed below, many POG spotting agents contain TCE and they are widely used.

SPOTTING PROCEDURES AND SPOTTING CHEMICALS

Cleaners use POG spotting agents to remove several types of contaminants before and

sometimes after the garments have been cleaned in the machine. These spotting agents

are suitable for removing:

• tar;

• ink;

• shoe polish;

• mascara;

• lipstick;

• oil-based paints;

• nail polish; and

• crayon.

A number of different solvents are used in POG spotting agents. These include glycol

ethers, mineral spirits, methyl ethyl ketone, acetates and various alcohols. Cleaners often

find these solvents to be ineffective and many spotters prefer spotting agents that contain

PERC and/or TCE. As mentioned earlier, PERC was extensively used in spotting agents

in the past. Because cleaners were aware that PERC was under increasing scrutiny in the

dry cleaning industry, the spotting chemicals were reformulated with TCE. Although

TCE is also toxic, the industry perceived it as being less toxic than PERC.

There are a handful of suppliers that provide POG spotting agents to the industry. These

include R.R Street & Company, Laidlaw, Adco and Caled. These suppliers package the

POG spotting agents in quantities ranging from one gallon containers to 55-gallon drums.

Distributors purchase the spotting agents from the suppliers and sell them to cleaners.

Distributors in California include United Fabricare, HNS, McGregor and MDL.

IRTA worked with cleaners and suppliers to estimate the amount of TCE and PERC

containing spotting agents that are sold in California. About 42,000 gallons of the TCE

based spotting agents are sold in California annually. The concentration of TCE in the

spotting agents ranges from 10 percent to 100 percent. One of the most widely used

spotting agents containing TCE is called Picrin (see below); it contains 100 percent TCE.

Assuming that all of the spotting agents are TCE and not PERC, and assuming an average

concentration of TCE of 95 percent for all products, about 40,000 gallons of TCE are

used annually in spotting. The density of TCE is 12.11 pounds per gallon so this amounts

to 242 tons of TCE per year. A much smaller amount of PERC based spotting agents are
15

used annually, according to the suppliers. IRTA estimates the amount of PERC spotting

agents used annually in California at 150 gallons or about one ton per year.

Cleaners IRTA worked with to test the alternatives during this project described and

illustrated the proper process for spotting with POG agents. The garment is put on the

spotting board which is similar to an ironing board. The spotting agent is applied to the

spot on the garment using a squeeze bottle. It is rubbed in with a brush or bone used for

that purpose. The spot is flushed with water from the steam supply. It is then dried with

compressed air. The garment is placed aside for the next load in the machine. In some

cases, spotting is performed after the garments go through the machine when the cleaning

process does not successfully remove the spot. The procedure is the same as that

described above.

Specific TCE and PERC Spotting Agents

MSDSs for several spotting agents containing TCE and a few containing PERC are

shown in Appendix A. The most widely used POG spotting agent is Picrin which is

offered by R.R. Street & Company. A product sheet describing its use and an MSDS are

shown in appendix A. The MSDS indicates that Picrin contains about 100 percent TCE.

An MSDS for a product called Volatile Dry Spotter (V.D.S.) offered by Laidlaw is

shown in Appendix A. The MSDS indicates that the product contains approximately 98

percent TCE.

Another product, called Fast P-R, is offered by Caled. A product sheet and an MSDS for

this product are shown in Appendix A. The MSDS indicates that the concentration of

TCE in the product is approximately 95 percent.

Adco offers a product called PURO which apparently contains TCE. A product sheet and

a description of the contents of the product from the State Coalition for Remediation of

Drycleaners are shown in Appendix A. The contents sheet indicates that the

concentration of TCE is less than 100 percent. Another product offered by Adco called

Semi-Wet apparently contains 50 percent TCE. A product sheet and a content sheet

description are shown in Appendix A.

A contents sheet from the State Coalition for Remediation of Drycleaners for an R.R.

Street product called 2-1 Formula is shown in Appendix A. The contents sheet indicates

that the product contains less than 50 percent TCE.

A contents sheet from the State Coalition for Remediation of Drycleaners for a product

offered by Pariser Industries, Inc., is shown in Appendix A. According to the contents

sheet, the product, called P.O.G., contains 21.8 percent PERC.

An MSDS for a product offered by Fabritec International, called 6748 VOL Volatile

Spotter, is shown in Appendix A. According to the MSDS, the product contains between
16

30 and 60 percent of an unidentified halogenated hydrocarbon which is likely to be TCE

or PERC.

A contents sheet from the State Coalition for Remediation of Drycleaners for a product

offered by A.L. Wilson Chemical Co. called TarGo is shown in Appendix A. The

product contains 10 percent TCE.
17

III. ALTERNATIVES TESTING

During this project, IRTA tested one alternative spotting agent that is used as a spotting

agent commercially, some other cleaning agents used for cleaning in other industries and

blends of the other cleaning agents developed by IRTA specifically for the testing. IRTA

screen tested the alternative cleaners and then took them to cleaning facilities so they

could be tested by spotters. This section describes the tests of the alternative cleaning

agents in detail. It also presents a cost analysis and comparison of the current and

alternative spotting agents.

SCREENING TESTS OF ALTERNATIVE SPOTTING AGENTS

The screening tests were conducted to determine what types of cleaning agents used in

other industries might be suitable as alternatives to PERC and TCE based POG spotting

chemicals. The approach that was used was to obtain garments from Goodwill and select

garments for the screening tests that were made of a variety of different fabrics. Stains of

the type that are removed during spotting with POG spotting agents were put on the

garments. Baseline cleaners and a range of different cleaning agents were then tested to

see if they could effectively remove the spots. IRTA relied on two experienced textile

cleaners to conduct the spotting and to judge the comparative cleaning ability of the

cleaners.

Garments and Contaminants Used in Screening Tests

Some of the garments used in the screening tests and the contaminants that were put on

them were:

• white shirt that appears to be made of polyester with an Elite Security decal 

contaminated with blue screen printing ink;

• yellow men’s pants made of nylon and polyester contaminated with motor oil;

• blue men’s shirt made of 100 percent cotton contaminated with black latex

paint;

• tan men’s dockers made of 100 percent cotton contaminated with red nail

polish;

• beige women’s pants made of cotton and spandex contaminated with mascara;

• gold men’s jacket made of acetate contaminated with a black Sharpie marker;

• beige men’s shirt made of raw silk contaminated with lipstick;

• beige men’s pajama pants made of acetate and rayon contaminated with rubber 

cement; and

• beige men’s cargo pants made of 100 percent cotton contaminated with blue 

ballpoint pen ink.

Pictures of some of these garments with the stains from the contaminants are shown in

Figures 3-1 through 3-7.
18

Figure 3-1. White Shirt with Blue Screen Printing Ink.

Figure 3-2. Yellow Pants with Motor Oil.
19

Figure 3-3. Blue Shirt with Black Latex Paint.

Figure 3-4. Tan Dockers with Red Nail Polish.
20

Figure 3-5. Beige Pants with Mascara.

Figure 3-6. Gold Jacket with Black Sharpie Marker.
21

Figure 3-7. Beige Shirt with Lipstick.

Two owners of cleaning facilities who are experienced spotters tested the alternative

spotting agents on the Goodwill garments and on some of the garments in their cleaning

facilities. One spotter at one of these facilities also assisted in the screening tests. The

procedure that was used was to test the alternative cleaners on the spots and to use the

proper spotting techniques (rinse with steam and blow out with air) described earlier.

The baseline spotting agents were Picrin and Pyratex, two POG spotting agents

commonly used today.

Cleaners Used in Screening Tests

IRTA selected several different cleaning agents for the screening tests. IRTA wanted to

find alternative POG spotting agents that were low in VOC content and low in toxicity.

IRTA also wanted to select cleaning materials that would not lead to the classification of

the waste and effluent streams in textile cleaning as hazardous waste. Some of the

cleaning agents tested during screening did not meet these requirements but IRTA tested

them to see if they were effective enough cleaners to be used in smaller concentrations

with other cleaners. The cleaning agents selected for screening tests were:
22

• Cold Plus;

• Mirachem NP 2520;

• PWF-10;

• Soy Gold 1000;

• Soy Gold 2500;

• C-29;

• Acetone;

• 90 percent Soy Gold 2500/10 percent acetone;

• 90 percent C-29/10 percent acetone;

• VM&P;

• DB; and

• 90 percent DB/10 percent acetone.

Cold Plus is the only commercial spotting agent that was tested; it is a water-based

cleaner. Mirachem NP 2520 is a water-based cleaner developed for cleaning in the

screen printing industry. PWF-10 is a water-based cleaner used to clean oil and grease in

the auto repair industry. IRTA has tested Soy Gold 1000 and Soy Gold 2500 for cleaning

ink in the screen and lithographic printing industries and they are used in other cleaning

applications; they are based on methyl esters and they have low VOC content. C-29 is a

mineral spirit based cleaner used for cleaning ink in the lithographic printing industry;

like soy, it is low in VOC content. Acetone is used for cleaning in many applications and

it is not classified as a VOC. If it is present in a cleaning agent at or above 10 percent,

the spent cleaner would be classified as hazardous waste (see discussion in the next

section). IRTA tested it to see if it cleaned effectively and could be used as an ingredient

at 10 percent or less concentration in a spotting chemical. VM&P is a mineral spirits

based cleaner that is classified as a VOC. Again, it was investigated as a possible

ingredient in a spotting chemical. DB is a glycol ether that is considered to be a nonVOC in CARB’s consumer product regulations (see discussion of regulations in next

section).

Results of Screening Tests

The results of the screening tests showed that two of the three water-based cleaners

performed relatively well in the screening tests and one did not. The Soy Gold 1000 is

not water rinseable and it could not be rinsed with the steam; because it could leave a

ring, IRTA did not test the chemical further. The C-29 and VM&P mineral spirits based

cleaners did not perform well and IRTA did not use them further. Acetone at 100 percent

was a reasonably effective cleaner but dissolved part of an acetate garment; it did not

have a negative effect at 10 percent concentration. IRTA decided to test acetone, which

is a good cleaner, at only a 10 percent concentration in the alternative spotting agents.

Based on these conclusions, the cleaning agents that were selected for further testing as a

result of the screening tests are:

• Cold Plus;

• Mirachem NP 2520;

• Soy Gold 2500;
23

• DB;

• 90 percent Soy Gold 2500/10 percent DB;

• 90 percent Soy Gold 2500/10 percent acetone; and

• 90 percent DB/10 percent acetone.

MSDSs for these cleaners and the components of the cleaners are shown in Appendix B.

Part way through the project, IRTA became aware that DB which is called diethylene

glycol monobutyl ether, an ethylene glycol ether, has higher toxicity than the propylene

glycol ethers. IRTA decided to substitute DPM, a propylene glycol ether called

dipropylene glycol monomethyl ether, for DB. An MSDS for DPM is also shown in

Appendix B.

FIELD TESTS OF ALTERNATIVE SPOTTING AGENTS 

The field testing of the alternative spotting agents was conducted at seven facilities that

have a total of nine cleaning machines. The facilities and the cleaning technologies for

which the alternative spotting agents were tested are:

• Crown Cleaners--hydrocarbon machine;

• Porter Ranch Cleaners--hydrocarbon machine and wet cleaning machine;

• Flair Cleaners--hydrocarbon machine and wet cleaning machine;

• Larsen’s Cleaners--Green Earth machine;

• Village Cleaners--Green Jet machine;

• Royal Cleaners--carbon dioxide machine; and

• Imperial Cleaners--icy water machine.

As discussed earlier, most cleaners that are converting away from PERC are adopting

hydrocarbon so IRTA tested the alternative spotting agents at three facilities where

hydrocarbon is being used. IRTA also tested the spotting agents at one facility using

Green Earth and one facility using carbon dioxide. IRTA tested the alternative spotting

agents at four facilities that have water-based cleaning technologies. These included two

cleaners using the traditional wet cleaning technology, one cleaner that uses the Green Jet

technology and one cleaner that uses the icy water technology.

Approach to Field Testing

At each of the facilities, IRTA first tested the alternative spotting agents on Goodwill

garments and ran them through the machine. This was necessary to ensure that none of

the alternative spotting agents would leave a ring after they were cleaned with each of the

different technologies. IRTA selected alternative spotting agents originally with this in

mind. All of the alternatives that were selected as a result of the screening tests were

either water soluble or water rinseable. As discussed in Section II, if spotters use proper

procedures, they will flush the spot with steam (water) after the spotting agent is applied

and then dry it before cleaning it in the machine. Since all of the alternatives are water

soluble or rinseable, IRTA expected they would not leave a ring if the spotting were

performed properly. In all cases, with every technology, none of the alternative spotting
24

agents left a ring when spotting was performed properly. In some cases, when spotting

was not performed properly, the spotting agents did leave a ring.

After IRTA tested the selected alternatives initially on the Goodwill garments at some of

the facilities to ensure they would not leave spots, IRTA and the spotters tested them on

the cleaner’s garments. Generally one or more of the spotting agents performed better

than others. IRTA observed that there were strong personal preferences and the preferred

alternatives varied widely from facility to facility. IRTA provided larger quantities of the

alternatives the spotters preferred and the spotters tested them routinely in scaled-up

testing for one to five weeks on their garments in place of the POG spotting agent that are

currently used. IRTA staff visited the facilities at least once a week during the testing to

get feedback on the performance of the alternative spotting agents.

Results of Field Testing

Most of the owners or spotters who tested the alternatives thought that at least one of

them was as good as the current POG spotting agent. All of the alternatives had some

limitations but most owners and spotters indicated that even the POG spotting agents they

use currently have limitations. This is why cleaners often use more than one POG

spotting agent.

Table 3-1 shows the preferred spotting agents for the different facilities. One of the

facilities, Larsen’s, tested only one alternative in the scaled-up testing. Several of the

facilities tested most of the alternatives for at least a week. The facilities that tested DB

and DPM and blends containing the two chemicals generally thought DPM performed

better than DB.

Table 3-1

Spotting Agents That Were Used and Performed Well in Scaled-Up Testing

Facility Acceptable Alternative POG Spotting Agents 

Crown DB/acetone, soy/DB, Mirachem NP 2520

Porter Ranch DB/acetone, soy/DB, soy/acetone, DB

Flair DB/acetone, soy/DB, soy/acetone, DB, Mirachem NP 

2520, soy/DPM

Larsen’s Soy

Village Cold Plus, soy

Royal DPM, Cold Plus, soy

Imperial Cold Plus, soy/acetone, DPM 

COST OF CURRENT AND ALTERNATIVE SPOTTING AGENTS

IRTA performed a limited cost analysis of the current spotting agents and the alternative

spotting agents that were tested during this project. The baseline POG spotting agent

used for the analysis was TCE. IRTA collected price information from suppliers for the

price paid by cleaners for the spotting agent. The price ranged from about $42 to $50 per
25

gallon if the cleaner purchased the product in gallon quantities. The price of the

alternative spotting agents was compared with TCE at a mid range price of $46 per

gallon.

Cold Plus is the only alternative that was tested that is currently a commercial product

sold to the textile cleaning industry as a spotting agent. One local distributor indicates

that the price of the spotting agent purchased in one gallon quantities is $36 per gallon.

Three of the other alternative spotting agents, Soy Gold 2500, Mirachem NP 2520 and

DPM, are commercial products sold for other applications but not currently sold as

spotting agents to the textile cleaning industry. IRTA estimated the prices of these

materials if purchased in one gallon quantities as spotting agents based on discussions

with the suppliers of these chemicals and a company that would like to distribute them.

The Soy Gold 2500 can be purchased from the supplier at a price of $12.50 per gallon for

drum quantities. Assuming the markup by the distributor would double the price charged

to dry cleaners, the price of the Soy Gold 2500 for this industry would be $25 per gallon

The Mirachem NP 2520 supplier price is $10 per gallon for drum quantities. Again,

assuming the price would double from a distributor markup, the price of the Mirachem

NP 2520 to dry cleaners would be $20 per gallon. IRTA did not further evaluate DB as

an alternative spotting agent because it is more toxic than DPM. A supplier indicates that

the price of DPM is $12.56 per gallon if purchased in drum quantities. Again assuming

the distributor markeup would double the price, the price of DPM to the dry cleaner

would be $25 per gallon.

For the other blends containing Soy Gold 2500, acetone and DPM, IRTA assumed the

supplier would have to blend the chemicals before selling them in drum quantities to the

distributor. IRTA obtained prices for the blended materials from a supplier. The blend

of 90 percent Soy Gold 2500/10 percent acetone is priced at $12.57 per gallon based on

purchases of drum quantities. Assuming the distributor markup would double the price,

the cleaner would pay about $25 per gallon for the blend. For the blend of 90 percent

Soy Gold 2500/10 percent DPM, the supplier estimated a price of $12.91 per gallon

based on drum purchases. Again, assuming the distributor markup would double the

price, a cleaner would pay $26 per gallon. For the blend of 90 percent DPM/10 percent

acetone, the supplier would charge $11.76 per gallon based on drum purchases. The

distributor markup would double the price to $24 per gallon.

Table 3-2 shows the cost comparison for the TCE based spotting chemicals and the

alternatives tested in this project. Note that the analysis includes DPM rather than DB

because DPM is lower in toxicity.
26

Table 3-2

Price Estimates of Current and Alternative Spotting Agents

Based on One Gallon Quantities

Spotting Agent Price Per Gallon 

TCE $46

Cold Plus $36

Soy Gold 2500 $25

Mirachem NP 2520 $20

DPM $25

90% Soy Gold 2500/10% Acetone $25

90% Soy Gold 2500/10% DPM $26

90% DPM/10% Acetone $24 

The values of Table 3-2 show that the cost of the TCE based spotting chemicals is higher

than the cost of all of the alternative spotting chemicals. Even if the distributor markup

was substantially higher for the alternatives, they would still be less costly than TCE.
27

IV. HEALTH AND ENVIRONMENTAL CHARACTERISTICS OF

ALTERNATIVES

This section describes the regulations that affect the alternatives and the toxicity of the

alternatives. The DHS HESIS assisted IRTA in evaluating the toxicity of the alternatives

based on the information on the MSDSs.

AIR REGULATIONS THAT APPLY TO SPOTTING CHEMICALS

In California, four or five suppliers sell spotting agents in large quantities to distributors.

The distributors, in some cases, repackage the spotting agents in smaller quantities and

sell them to cleaners along with other supplies like filters, hangers and dry cleaning

agents. The local air districts have regulatory authority over spotting chemicals since they

regulate VOCs and toxic materials used in industrial facilities. Textile cleaning

operations are considered industrial facilities. CARB may also have regulatory authority

over spotting chemicals. CARB and local air districts do not currently have regulations

that affect spotting chemicals.

CARB and local air districts could regulate the VOC content of spotting chemicals. TCE

is classified as a VOC but PERC is not classified as a VOC. Other components of the

formulations containing TCE and PERC are classified as VOCs. These agencies could

also regulate the use of spotting agents containing TACs. Both TCE and PERC are listed

TACs; a few of the other components in some of the formulations are also classified as

TACs. The regulatory agencies might forbid the use of spotting agents that contain

chlorinated solvents like TCE or PERC, for example.

The alternatives that were tested during this project were selected to have low toxicity

and low VOC content. Cold Plus and Mirachem NP 2520 are water-based cleaners that

likely have low VOC content. Soy Gold 2500 alone and combined with glycol ethers and

acetone, also has low VOC content, at less than 25 grams per liter. Acetone, an

ingredient of the soy/acetone and DPM/acetone formulation, has a VOC content of zero

since it is exempt from VOC regulations. The glycol ethers, DB and DPM, have high

VOC content. In CARB’s consumer product regulations, however, both glycol ethers

would be classified as Low Vapor Pressure (LVP) materials. For purposes of the

consumer product regulation, LVPs are considered to be non-VOCs. Local air districts,

however, would regulate the glycol ethers as having very high VOC content.

WASTE REGULATIONS THAT APPLY TO SPOTTING CHEMICALS

TCE and PERC are listed hazardous wastes under RCRA. Both chemicals are listed in

RCRA under F001 and F002. F001 specifies TCE and PERC used “in degreasing.”

F002 specifies TCE and PERC when they are spent and “all spent solvent

mixtures/blends containing, before use, a total of ten percent or more (by volume) of one

or more of the above halogenated solvents or those listed in F001, F004, or F005; and

still bottoms from the recovery of these spent solvents and spent solvent mixtures.” The
28

MSDSs discussed in the last section all contained TCE or PERC in concentrations of 10

percent or more. Thus the spent materials would make the waste streams hazardous

waste.

This means that any waste stream from one of the alternative technologies that contains

these materials from spotting chemicals is classified as hazardous waste simply because

of the presence of TCE or PERC. This applies to sludge generated from spin-disk filters,

still bottoms generated from distillation, separator water and the effluent from waterbased technologies. Since spotting chemicals may be the origin of the PERC and TCE

that appear in the waste streams, textile cleaning facilities should use alternatives that do

not contain these materials.

Under RCRA, F003 specifies several other non-halogenated spent solvents including

acetone, one of the ingredients used in the alternative spotting chemicals tested by IRTA.

It includes “all spent solvent mixtures/blends containing, before use, only the above spent

non-halogenated solvents; and all spent solvent mixtures/blends containing, before use,

one or more of the above non-halogenated solvents, and, a total of 10 percent or more (by

volume) of one or more of those solvents listed in F001, F002, F004, and F005; and still

bottoms from the recovery of these spent solvents and spent solvent mixtures.” IRTA

used blends of acetone containing 10 percent acetone. To avoid having the waste streams

from use of the alternative cleaning technologies classified as hazardous waste,

commercial spotting chemical blends should contain no more than nine percent acetone.

TOXICITY OF SPOTTING AGENTS

As mentioned above, HESIS evaluated the MSDSs of some of the alternative spotting

agents that were tested during this project. Today PERC and TCE are the POG spotting

agents most widely used by cleaners, even those using alternative technologies for textile

cleaning. PERC and TCE are both carcinogens. Several years ago, because PERC, the

major dry cleaning agent, received negative publicity because it is a carcinogen, the

suppliers and distributors converted away from the chemical in POG spotting agents.

Although some of the POG spotting agents still contain PERC, the industry largely

adopted TCE as an alternative. This was a poor choice since TCE is also a carcinogen

and, unlike PERC, is classified as a VOC. It is not clear why the industry believed that

TCE was a better choice than PERC.

Toxicity of PERC and TCE

PERC is a probable human carcinogen and several studies conducted recently link PERC

exposure to leukemia and esophageal, bladder, colorectal and breast cancers. PERC

exposure also can harm the digestive and nervous systems, blood, liver and urinary tract.

Animal data also indicate that PERC can cause cancer and developmental damage.

Some occupational studies have shown that TCE produces central nervous system effects,

as well as membrane, skin and gastrointestinal irritation and decreased appetite.

Hepatotoxicity (liver cancer) has been associated primarily with TCE inhalation. Renal
29

failure has also been reported in concert with hepatic damage. Cardiac dysrhythmias may

be induced by heavy TCE use in susceptible persons.

Toxicity of Alternative Spotting Agents

The alternative POG spotting agents evaluated during this project included two waterbased cleaners, Cold Plus and Mirachem NP 2520. They also included Soy Gold 2500,

acetone, DB, DPM and blends of these three materials.

The MSDSs for the two water-based cleaners indicate the materials contain no hazardous

ingredients. Generally, water-based cleaners contain an appreciable amount of water.

The toxicity of these two cleaners appears to be low.

The MSDS for Soy Gold 2500 indicates the material contains no hazardous ingredients.

The soy cleaner is a fatty acid ester with added surfactants that make it water rinseable.

HESIS indicates that, although there were no toxicity data on fatty acid esters in Toxnet,

Scorecard and other chemical databases, they are not volatile, do not pose an inhalation

hazard and are of low toxicity compared to organic solvents. The European Union, in

conjunction with the U.S., is sponsoring research on vegetable oils and their fatty acid

esters as substitutes for organic solvents in industrial processes.

Consistent with general solvent toxicity, overexposure to acetone affects the nervous

system and causes skin and respiratory irritation. In the case of acetone, however, the

threshold for producing these health effects is higher (the Permissible Exposure Limit or

PEL of the acetone is 750 ppm) than for most other organic solvents. Thus, acetone is

lower in toxicity than many other organic solvents.

The HESIS review indicates that ethylene based glycol ethers, including DB, can damage

red blood cells and cause anemia. The propylene glycol ethers, including DPM, do not

cause this problem and they are less volatile than the ethylene glycol ethers. However,

they can produce neurotoxic effects through skin absorption as well as inhalation. As

described earlier, IRTA stopped testing DB and, instead, used DPM part way through the

project because DPM is lower in toxicity than DB.
30

V. SUMMARY AND CONCLUSIONS

The textile cleaning industry is undergoing a substantial change. The industry is

converting away from PERC dry cleaning to a variety of solvent, carbon dioxide and

water-based alternative processes. Cleaners rely heavily on spotting agents to remove the

spots from garments before or after they are cleaned in the machines. Some of these

materials, called POG spotting agents, are used for removing paint, oil and grease stains

from garments. The major POG spotting agent used by cleaners contains TCE; other less

widely used POG spotting agents contain PERC. Even many cleaners that have already

converted to alternatives to PERC dry cleaning still use the POG spotting agents based on

TCE and PERC.

PERC and TCE are carcinogens. They are classified as HAPs by EPA and TACs in

California. Both solvents are listed on Proposition 65 and wastes from processes where

PERC and TCE have been used for cleaning are classified as hazardous wastes. IRTA

estimates that about 40,000 gallons per year of TCE is used in spotting chemicals and 150

gallons per year of PERC are used for that purpose.

There is a need to find effective POG spotting agents that could replace PERC and TCE.

Although some POG spotting agents that do not contain PERC and TCE are on the

market, cleaners have indicated that most do not work well. During this project, IRTA

identified one new commercial product, Cold Plus, and developed several other materials

that could be tested as safer alternatives. IRTA performed screening tests of several

different types of cleaners to identify those that would be most effective. The screening

tests were conducted on typical POG stains that were put on Goodwill garments made of

a range of different fabrics. The screening tests helped IRTA to decide on which

cleaning agents would be most effective to test in textile cleaning facilities.

The scaled-up testing was conducted at seven textile cleaning facilities that used a variety

of PERC dry cleaning alternative technologies. The alternative spotting agents were

tested for hydrocarbon, Green Earth, carbon dioxide and three water-based technologies.

At each of the facilities, the spotting agents were tested on Goodwill garments and put

through the machine. This was necessary to determine whether the spotting agent would

leave a ring. In the proper spotting process, after the spotting agent is applied, it is rinsed

with steam and dried with compressed air. IRTA deliberately selected alternatives that

were water soluble or water rinseable. The results of the field tests indicated that none of

the alternative spotting agents left a ring if spotting was performed properly. The

spotting agents were then tested on each facility’s garments. Those the spotters preferred

were left for testing for one to five weeks. IRTA visited the facilities regularly to obtain

feedback on whether the spotting agents were effective.

The spotters at the seven test facilities had personal preferences but all of the alternatives

that were tested were judged to be effective by at least one of the facilities. Two waterbased cleaners were tested and one of these is already a commercial product. Two glycol

ethers, DB and DPM, were tested and found to be effective. One soy based cleaner was
31

tested and it performed well according to the spotters at some facilities. Various blends

of soy, acetone, and the glycol ethers were also tested and judged to be effective.

Because DB is a more toxic glycol ether than DPM, in the later testing, IRTA switched to

this material. Table 5-1 shows the spotting agents that were successfully tested during

the project.

Table 5-1

Alternative Spotting Agents That Performed Effectively

Spotting Agent Type of Material 

Cold Plus Water-Based Cleaner

Mirachem NP 2520 Water-Based Cleaner

Soy Gold 2500 Methyl Ester and Surfactants

DPM Glycol Ether

90% Soy Gold 2500/10% Acetone Blend

90% Soy Gold 2500/10% DPM Blend

90% DPM/10% Acetone Blend 

IRTA conducted a cost analysis which compared the cost of a TCE spotting agent with

the cost of the alternative safer spotting agents. The results indicate that the cost of using

the alternative spotting agents is lower than the cost of using TCE.

IRTA analyzed the regulations that affect spotting agents. When PERC and TCE from

spotting agents are present in waste streams generated by textile cleaners, those streams

are hazardous waste. Wastes from PERC dry cleaning alternative processes might not be

considered to be hazardous wastes if PERC and TCE were not present. As a result,

disposal of the wastes could be less costly. Both CARB and the local air districts in

California may have jurisdiction over regulating the VOC and toxic content of spotting

chemicals. The alternatives tested by IRTA were selected to have low VOC content and

low toxicity.

HESIS assisted IRTA in evaluating the toxicity of the alternative spotting agents. The

results of the analysis indicate that the alternative spotting agents tested during the project

are lower in toxicity than PERC and TCE.

This project demonstrates that there are a variety of other safer materials that can be used

in place of TCE and PERC spotting chemicals. These alternative materials were found to

be effective for a variety of different textile cleaning processes. The alternatives are also

less costly than TCE spotting chemicals used widely today.
 

 Material Safety Data Sheet 

Fast –PR 

 

1. Identification of the Substance/Preparation and the Company/Undertaking

Substance or preparation trade name: FAST – PR 

 Unique reference numbers(s): 052001 

Company/undertaking name & address: Caled Industries, 26 Hanes Drive, Wayne, NJ 07470 

 

Telephone: 1-800-652-2533 

Emergency telephone number: 1-800-424-9300 Chemtrec

2. Hazardous Ingredients

Substance: Aprox. % CAS # 

Trichloroethylene 95 000079-01 

 50 ppm OSHA 8 HOUR TWA 

 200ppm OSHA 15 MIN STEL 

 

3. Hazards Identification

Health: 2 Flammability: 1 Reactivity: 0 

4. First aid measures

Skin contact: Flush area with water. When irritation persists get medical attention. 

 Eyes contact: Flush eyes with large amount of water. Get medical attention. 

 Inhalation: Remove to fresh air. Get medical attention. 

 Ingestion: Not normal route of entry. Give water and induce vomiting. Get medical attention. 

5. Fire fighting measures

Suitable extinguishing media: Water, dry chemicals 

Unsuitable extinguishing media: None known 

Special hazards in fire: Use protective clothing and self contained breathing apparatus.

Not 

 Consider flammable under normal use 

Required special protective equipment . 

for fire-fighters: Wear Protective clothing and self contained breathing apparatus 

 in confined areas 

 

6. Accidental release measures

- 1 - 
 

 Material Safety Data Sheet 

Fast –PR 

 

Personal precautions: Wear safety glosses and gloves 

Environmental precautions: None known 

Methods for cleaning: Flush area with water if locally permitted. 

 Dispose of in accordance with federal, state and local regulations. 

7. Handling and storage

Handling: Keep container closed. Avoid contact with skin. 

 

Storage: Keep container closed away from open flame, heat and sparks. 

 

8. Exposure Controls

Engineering measures: Foam / Water / Fog 

 Control Parameters: 

Personal protection equipment:

Eye protection: Safety glasses or safety shield. Eye wash station. 

 Hand protection: Neoprene gloves 

 Hygiene measures: 

9. Physical and chemical properties

 Appearance: clear to slightly hazy liquid 

 Odor: none 

 pH: 6.5-7.2

 Boiling point: 1286-190

 Melting point: F 

 Flashpoint: closed cup 

Explosive properties: 

 Vapor pressure: 100 

 Relative density: 1.465 

 Solubility: insoluble 

10. Stability and reactivity

Conditions to avoid: None known 

Materials to avoid: water will lead to slow hydrolysis to form acid products. 

Hazardous decomposition products: Hydrogen chloride and possible traces of phosgene. 

 

- 2 - 
 

 Material Safety Data Sheet 

Fast –PR 

 

11. Toxicological information

 Acute toxicity: -Local effects: - required at of application Excessive exposure may affect human health as 

follows: Skin contact: May cause irritation and dermatitis.

Eye contact: Direct contact may cause irritation. 

Inhalation: Mists may cause irritation to mucous linings.

 Ingestion: Some as inhalation, including gastric disturbances. 

12. Ecological information

None known 

13. Disposal Considerations

 

Solvent can be reclaimed. Dispose of in Accordance With federal, state and local regulations. 

14. Transport information

Classification data: 

 DOT: Trichloroethylene CLS. 1Nu 1710, PG LII 

 UN: CLS 6.1, UN 1710 ,PG III IMDG PAGE 6273 

15. Regulatory information

Toxics Release Inventory SARA TITLE III, Section 313: 

Trichloroethylene 200ppm OSHA 15 Min. STEL 

 50 ppm OSHA 8 hour TWA 

Trichloroethylene is listed by SARA TITLE III Section 313 not regulated for water and ground transportation 

unless equal or exceeds 100lbs. per package. regulated for air transport per above dot info. 

16. Other Information

 Recommendations/restrictions: 

Sources of key data used to compile: 

 NA= Not applicable ND= No data available NE= No establish <=Less than >= Greater than 

We believe that the statements, Technical information and recommendation contained herein are reliable, but

Without warrantee or guarantee of any kind, express or implied and we assume no responsibility for any loss, 

Damage, or expense, direct or consequential arising from their use. 

This MSDS should be properly routed to all individuals who use or may come contact with this product,

Understand and follow all pertinent employee and Community Right To Known Regulation. 

Revision date: 01-04-07 

- 3 - 
Page 1 of 6 Picrin® UNITED STATES

MATERIAL SAFETY DATA SHEET

Date Issued: 11-05-2012

Picrin

1. PRODUCT AND COMPANY IDENTIFICATION 

PRODUCT NAME: Picrin

GENERAL USE: For professional drycleaning use only. 

PRODUCT DESCRIPTION: Stain Removal Agent 

MANUFACTURER

R. R. Street & Co. Inc.

215 Shuman Boulevard/Suite 403

Naperville, IL 60563

Product Stewardship: 800-323-7206 (USA

& Canada only) or 630-416-4244

24 HR. EMERGENCY TELEPHONE NUMBERS

Medical Emergency: 866-303-6947 (USA & Canada 

only) or 651-632-9272

Transportation Emergency: 800-424-9300 (USA & 

Canada only) or 703-527-3887

2. COMPOSITION / INFORMATION ON INGREDIENTS

Chemical Name Wt.% CAS#

Trichloroethylene >75 79-01-6 

3. HAZARDS IDENTIFICATION

POTENTIAL HEALTH EFFECTS

EYES: Substance may cause substantial eye irritation. 

SKIN: May cause skin irritation. Prolonged or repeated contact may cause dermatitis.

SKIN ABSORPTION: Absorption through skin is possible but not a likely route of significant 

exposure. 

INGESTION: Low to moderate toxicity. 

Can cause adverse health effects as described under INHALATION. In the case of vomiting 

after ingestion, product may be aspirated into lungs causing chemical pneumonia, which in 

extreme cases could lead to death. See section 4, First Aid Measures, for more 

information.

INHALATION: High concentrations can cause central nervous system depression, irregular 

heartbeat, cardiac arrest, unconsciousness or death. 

SIGNS AND SYMPTOMS OF OVEREXPOSURE

EYES: Irritation and pain. 

SKIN: Irritation. 

SKIN ABSORPTION: No data available. 

INGESTION: Irritation of mouth, nausea. 

INHALATION: Headache, nausea, dizziness, vertigo, fatigue, lightheadedness and coughing. 

MEDICAL CONDITIONS AGGRAVATED: Skin contact may aggravate pre-existing dermatitis. 

Prolonged overexposure may complicate liver and kidney disease.

ROUTES OF ENTRY: Inhalation and skin. 
Page 2 of 6 Picrin UNITED STATES

4. FIRST AID MEASURES

EYES: Immediately flush eyes with plenty of water for at least 15 minutes. Get immediate medical 

attention. 

SKIN: Remove contaminated clothing. Wash with soap and water. If irritation persists, call a physician.

INGESTION: Get immediate medical attention. Do not induce vomiting unless instructed to do so by 

poison center or physician. 

INHALATION: Remove affected person to fresh air. If not breathing, give artificial respiration. Get 

immediate medical attention. 

NOTES TO PHYSICIAN: Chlorinated hydrocarbons may sensitize the heart to epinephrine and 

adrenaline so that arrhythmias may occur. 

ADDITIONAL INFORMATION: After emergency actions, call the emergency medical information 

number on page 1 or a physician immediately. 

5. FIRE FIGHTING MEASURES

FLASHPOINT AND METHOD: None (TCC).

FLAMMABLE LIMITS: 8% to 45%

AUTOIGNITION TEMPERATURE: 420°C (788°F).

FLAMMABLE CLASS: Not applicable. 

EXTINGUISHING MEDIA: Not applicable. 

HAZARDOUS COMBUSTION PRODUCTS: Hydrogen chloride, phosgene.

OTHER CONSIDERATIONS: Concentrated vapor can be ignited by high-intensity ignition source. 

FIRE FIGHTING EQUIPMENT: As in any fire, wear self-contained breathing apparatus pressuredemand, (MSHA/NIOSH approved or equivalent) and full protective gear. 

6. ACCIDENTAL RELEASE MEASURES

SMALL SPILL: Clean up spill with absorbent material. 

LARGE SPILL: Provide plenty of fresh air. Contain spill. Avoid breathing vapor. Clean up spills 

immediately with absorbent material, observing precautions in the Personal Protective Equipment section. 

Place absorbed material in closed containers for disposal (see section 13). Do not flush to sewer. Avoid 

contamination of ground and surface waters. 

7. HANDLING AND STORAGE

GENERAL PROCEDURES: Not applicable.

HANDLING: Follow all MSDS/label precautions even after container is emptied because it may retain 

product residues. 

STORAGE: Store in labeled, tightly sealed containers in a cool, dry, well ventilated area. 

ELECTROSTATIC ACCUMULATION HAZARD: Not applicable.
Page 3 of 6 Picrin UNITED STATES

8. EXPOSURE CONTROLS / PERSONAL PROTECTION

EXPOSURE GUIDELINES:

OSHA HAZARDOUS COMPONENTS (29 CFR 1910.1200)

EXPOSURE LIMITS

OSHA PEL ACGIH TLV Supplier OEL

ppm mg/m3ppm mg/m3ppm mg/m3

Trichloroethylene TWA 100 10

[1]

STEL 200[2] 25

TABLE FOOTNOTES:

1. A2: Suspected human carcinogen. 

2. Ceiling concentration. A 300 ppm peak concentration is allowed for 5 minutes in any 2-hour 

period.

ENGINEERING CONTROLS: Local exhaust may be required to control vapor concentration. 

PERSONAL PROTECTIVE EQUIPMENT

EYES AND FACE: Safety glasses with side shields, or goggles.

SKIN: Viton®, PVA, or BarrierTM gloves. 

RESPIRATORY: NIOSH/MSHA approved air purifying respirator with an organic vapor 

cartridge or canister may be permissible under certain circumstances where airborne concentrations 

are expected to exceed exposure limits. Protection provided by air purifying respirators is limited. 

Use a positive pressure air supplied respirator if there is any potential for an uncontrolled release, 

exposure levels are not known, or any other circumstances where air purifying respirators may not 

provide adequate protection. 

PROTECTIVE CLOTHING: Where contact is likely, wear the appropriate chemical resistant 

equipment, which depending on circumstances may include, chemical resistant gloves, a chemical 

suit, rubber boots, and chemical safety goggles plus a face shield. 

WORK HYGIENIC PRACTICES: Wash thoroughly after handling. Do not smoke in presence of vapor. 

Do not eat or drink in work area. 

OTHER USE PRECAUTIONS: Have eye wash station available. Do not wear contact lenses without eye 

protection. 

9. PHYSICAL AND CHEMICAL PROPERTIES

PHYSICAL STATE: Liquid. 

ODOR: Ethereal. 

APPEARANCE: Clear. 

COLOR: Colorless. 

pH: Not applicable. 

PERCENT VOLATILE: 100 

VAPOR PRESSURE: 58 mm Hg at 20°C 

VAPOR DENSITY: 4.5 (air = 1) 

BOILING POINT: 87°C (188°F) 

FREEZING POINT: -85°C (-121°F) 

SOLUBILITY IN WATER: Negligible. 

EVAPORATION RATE: 4.5 (butyl acetate = 1)

SPECIFIC GRAVITY: 1.45

VISCOSITY: No data available.

COEFF. OIL/WATER: 2.42 

ODOR THRESHOLD: 20 ppm 
Page 4 of 6 Picrin UNITED STATES

10. STABILITY AND REACTIVITY

STABLE: Yes.

HAZARDOUS POLYMERIZATION: No.

CONDITIONS TO AVOID: Contact with open flame, electric arcs, other hot surfaces which can cause 

thermal decomposition. 

HAZARDOUS DECOMPOSITION PRODUCTS: Hydrogen chloride, phosgene.

INCOMPATIBLE MATERIALS: Strong alkalies, oxidizers, sodium, potassium, lithium, aluminum, 

barium, magnesium, titanium. 

11. TOXICOLOGICAL INFORMATION

ACUTE

DERMAL LD50: >2,000 mg/kg (rabbit) 

ORAL LD50: >5000 mg/kg (rat) 

INHALATION LC50: 12,500 ppm (rat) 

CHRONIC

TARGET ORGANS: Chronic overexposure to trichloroethylene has caused toxic effects in the 

liver, kidney, hearing, and central nervous system of experimental animals. 

SENSITIZATION: Has produced allergic effects in laboratory animals. 

CARCINOGENICITY

IARC: Trichloroethylene is classified as 2A (Probably carcinogenic to humans). 

NTP: Trichloroethylene is on the NTP list of substances reasonably anticipated to be 

human carcinogens. 

OSHA: Not listed as a carcinogen.

OTHER: ACGIH: A2. Limited epidemiology data have shown a weak association 

between trichloroethylene exposure and renal cancer.

OTHER: No data available.

REPRODUCTIVE EFFECTS: Not applicable.

MUTAGENICITY: Evidence for trichloroethylene is equivocal. 

SYNERGISTIC MATERIALS: Alcohol. 

GENERAL COMMENTS: Refer to Section 3 for additional information on potential health effects. 

12. ECOLOGICAL INFORMATION

ENVIRONMENTAL DATA: Trichloroethylene has moderate persistence in the environment. 

13. DISPOSAL CONSIDERATIONS

DISPOSAL METHOD: Recovered liquids may be sent to a licensed reclaimer or incineration facility. 

Contaminated material must be disposed of in a permitted waste management facility. Consult federal, state 

and local authorities for approved procedures. 

EMPTY CONTAINER: Do not cut or weld empty drums. 

RCRA/EPA WASTE INFORMATION: Contains material(s) listed by RCRA as a hazardous waste. 
Page 5 of 6 Picrin UNITED STATES

14. TRANSPORT INFORMATION

DOT (DEPARTMENT OF TRANSPORTATION)

PROPER SHIPPING NAME: Trichloroethylene 

PRIMARY HAZARD CLASS/DIVISION: 6.1 

UN/NA NUMBER: UN1710 

PACKING GROUP: III 

LABEL: Toxic, PG III

REPORTABLE QUANTITY (RQ) UNDER CERCLA: 8 gal 

OTHER SHIPPING INFORMATION: Original 4x1-gallon packaging is approved for ground 

shipments only. Drums of this product contain a Reportable Quantity of trichloroethylene. 

CANADA TRANSPORT OF DANGEROUS GOODS

PROPER SHIPPING NAME: Trichloroethylene 

PRIMARY HAZARD CLASS/DIVISION: 6.1 

UN/NA NUMBER: UN1710 

PACKING GROUP: III

LABEL: Toxic

OTHER SHIPPING INFORMATION: Original 4x1-gallon packaging is approved for ground 

shipments only.

AIR (ICAO/IATA)

PROPER SHIPPING NAME: Trichloroethylene 

PRIMARY HAZARD CLASS/DIVISION: 6.1 

UN/NA NUMBER: UN1710 

LABEL: Toxic

PACKING GROUP: III 

PLACARDS: Consult applicable regulations governing air shipments. 

IATA NOTE: Original 4x1-gallon packaging is not approved for air shipment. Consult applicable 

regulations for packaging requirements and quantity limitations. 

15. REGULATORY INFORMATION

UNITED STATES

SARA TITLE III (SUPERFUND AMENDMENTS AND REAUTHORIZATION ACT)

311/312 HAZARD CATEGORIES:

FIRE: No. PRESSURE GENERATING: No. REACTIVITY: No. ACUTE: Yes.

CHRONIC: Yes.

313 REPORTABLE INGREDIENTS: Trichloroethylene is reportable. 

CERCLA (COMPREHENSIVE RESPONSE, COMPENSATION, AND LIABILITY ACT)

CERCLA RQ: Trichloroethylene has an RQ of 100 lbs. 

REPORTABLE SPILL QUANTITY: 8 gals 

RCRA STATUS: See section 13. 

CANADA

WHMIS CLASS: Class D, Divisions 1 & 2 

MEXICO

Regulated for transportation. 
Page 6 of 6 Picrin UNITED STATES

STATE REGULATIONS

MASSACHUSETTS

Contains one or more substances regulated by the Massachusetts Substance List.

CALIFORNIA 

PROPOSITION 65 STATEMENT: Trichloroethylene is on the Proposition 65 list known 

to the State of California to cause cancer. 

16. OTHER INFORMATION

HMIS RATINGS

HEALTH 3

FLAMMABILITY 1

REACTIVITY 0

PERSONAL PROTECTION H

1

2 0

NFPA RATINGS