TCE Risk Assessment and Cancer Risk

1. Methodology Overview

RoseyFields conducts TCE risk assessments using the following methodology: we identify the exposure pathways and populations relevant to the scenario under evaluation — occupational inhalation and dermal exposure to workers and occupational non-users (ONUs), and consumer and bystander inhalation and dermal exposure; we reconstruct or adopt exposure estimates (central tendency and high-end, or low/moderate/high intensity for consumer products) appropriate to each pathway; we calculate non-cancer margins of exposure (MOEs) against EPA’s benchmark MOEs, with and without assumed personal protective equipment (PPE), and extra cancer risk against EPA’s inhalation unit risk (IUR) or oral slope factor (OSF); and we interpret the resulting risk estimates in light of the confidence and uncertainty EPA has documented for each exposure pathway and condition of use. The summary below documents EPA’s exposure assessment approach, risk characterization methodology, and scenario-specific risk results for TCE, and explains how RoseyFields applies this same framework in practice.

2. Endpoints Used for Risk Estimation

EPA’s risk characterization for TCE draws on the best-overall non-cancer endpoints identified in the hazard assessment: acute immunosuppression (Selgrade and Gilmour, 2010) as the representative acute endpoint, and chronic autoimmunity (Keil et al., 2009) as the representative chronic endpoint, both selected for being robust, sensitive, and having comparatively lower extrapolation uncertainty than alternative endpoints with numerically lower PODs (developmental neurotoxicity from Fredriksson et al., 1993; congenital heart malformations from Johnson et al., 2003). For cancer, risk is evaluated using the combined kidney/liver/non-Hodgkin lymphoma cancer potency values (IUR and OSF) described in RoseyFields’ companion TCE Hazard Characterization page. EPA notes that for the majority of occupational and consumer exposure scenarios, risk was actually identified for multiple endpoints simultaneously (not just the single best-overall endpoint used in its summary risk tables) — meaning the published summary risk tables likely understate the full breadth of non-cancer risk domains implicated in any given high-exposure scenario.

3. Risk Characterization Methodology

Non-Cancer Risk: Margin of Exposure (MOE)

Non-cancer risk is expressed as a margin of exposure, calculated separately for acute and chronic exposure durations:

MOE (acute or chronic) = Non-Cancer Hazard Value (POD, as HEC or HED) ÷ Human Exposure

Acute concentrations (ACs) and acute average daily doses (ADDs) are used for occupational non-cancer risk following acute inhalation or dermal exposure, respectively; average daily concentrations (ADCs) and chronic ADDs are used for chronic inhalation or dermal exposure. Consumer inhalation risk is calculated from maximum 24-hour time-weighted average (TWA) concentrations, and consumer dermal risk from acute dose rate (ADR). The resulting MOE is compared against a benchmark MOE equal to the total composite uncertainty factor used to derive that POD (10 for the acute immunosuppression endpoint; 30 for the chronic autoimmunity endpoint). An MOE below the benchmark MOE indicates a human health risk; an MOE at or above the benchmark MOE indicates negligible concern for the associated adverse effect.

Cancer Risk: Extra Lifetime Cancer Risk

Cancer risk is expressed as the incremental (extra) probability of an individual developing cancer over a lifetime as a result of chronic exposure:

Risk = Human Exposure (LADC) × POD (IUR = 0.022 per ppm, or OSF = 0.0464 per mg/kg-day)

EPA considers an extra cancer risk of 1 × 10⁻⁴ to be the benchmark for occupational risk estimation. Cancer risk was evaluated only for chronic occupational exposure scenarios (via lifetime average daily concentration or dose, LADC/LADD); EPA did not estimate cancer risk for consumer exposure scenarios, consistent with its conclusion (described in the companion hazard page) that the relationship between a single short-term exposure and cancer induction has not been established.

Route-to-Route Extrapolation and PPE

Because TCE’s underlying PBPK model does not include a dermal compartment, dermal PODs used in risk estimation were derived by route-to-route extrapolation from oral human-equivalent dose (HED) values, assuming 100% absorption across all routes based on available toxicokinetic data. As with PCE, EPA calculated occupational risk estimates both without PPE and with PPE (respirators, characterized by assigned protection factor, APF, up to APF 50; gloves, characterized by protection factor, PF, up to PF 10 or 20), presenting both the no-PPE and with-PPE risk estimates side by side and identifying, where risk was eliminated, the lowest protection factor sufficient to do so.

4. Occupational Exposure and Risk

EPA characterized occupational risk for workers and occupational non-users (ONUs) across the conditions of use evaluated in the TCE Risk Evaluation — including domestic manufacture, import/repackaging, processing as a reactant/intermediate, and numerous downstream industrial and commercial uses. Because reliable statistical distributions of actual workplace air concentrations were often unavailable, EPA generally used dataset means/medians as substitutes for 50th-percentile (central tendency) exposure and high-end reported values as substitutes for 95th-percentile (high-end) exposure — substitutes EPA explicitly flags as less reliable than true percentile data and, where checked, prone to overestimating exposure. ONU-specific exposure data were frequently unavailable, so EPA applied worker exposure estimates directly to ONUs as a conservative (likely overestimating) proxy in those cases.

Representative Occupational Risk Estimates (No PPE)

Findings across the full set of occupational conditions of use: without PPE, high-end exposure produced risk (MOE below benchmark, or cancer risk above 1 × 10⁻⁴) relative to at least one benchmark for every condition of use evaluated, for both acute and chronic non-cancer effects and for cancer. At central-tendency exposure, however, no risk was identified for any endpoint for three specific conditions of use — formulation of aerosol and non-aerosol products, repackaging, and process solvent recycling/worker handling of wastes — indicating that for these particular activities, risk is driven primarily by high-end (rather than typical) exposure scenarios. Wearing respirators (APF 10 or 50) eliminated risk for those same three central-tendency scenarios, but risk persisted with respirator use for the majority of other conditions of use at high-end exposure, and for essentially all conditions of use following chronic exposure regardless of PPE.

Dermal Exposure Findings

Dermal risk presents a materially different pattern than inhalation risk: without gloves, risk was identified for both non-cancer effects and cancer for workers across all conditions of use, at both high-end and central-tendency exposure levels — meaning, unlike inhalation exposure, there was no condition of use for which central-tendency dermal exposure was risk-free. Risk persisted for all conditions of use even with gloves worn at the maximum applicable protection factor (PF 10 or 20) for high-end acute exposure and for both exposure levels following chronic exposure. RoseyFields treats this as a key practical finding: for TCE, dermal protective equipment alone — even at maximum assumed effectiveness — does not eliminate chronic dermal risk under EPA’s exposure assumptions, unlike the inhalation pathway, where respirators were sufficient to eliminate risk for several conditions of use.

5. Consumer and Bystander Exposure and Risk

EPA evaluated consumer and bystander risk for a range of TCE-containing consumer products, assessed only for acute exposure scenarios (given the generally low frequency of consumer product use), using the same best-overall acute non-cancer endpoint (immunosuppression) as the primary basis for its consumer risk summary table.

Representative Consumer Product Risk Estimates (Acute Non-Cancer MOE, benchmark = 10)

Across nearly all consumer conditions of use, both users and bystanders show MOEs well below the benchmark of 10 at high- and moderate-intensity use, and frequently at low-intensity use as well — for inhalation exposure, risk was identified for every consumer condition of use except pepper spray, for both users and bystanders, at medium and high-intensity exposure levels; for dermal exposure, risk was identified for every consumer condition of use except pepper spray, across all three age groups evaluated (11–15, 16–20, and 21+), at medium and high-intensity use, and for most conditions of use at low-intensity use as well. Pepper spray is the sole consumer product category for which EPA’s best-overall acute endpoint did not indicate risk at any evaluated exposure level.

6. Interpreting TCE Risk Estimates

Several cross-cutting points inform how RoseyFields interprets the risk estimates summarized above:

• Consumer product risk is pervasive, not exceptional: unlike PCE, where low-intensity consumer use often falls near or above benchmark MOEs, TCE consumer risk is identified across nearly every evaluated product category at medium and high-intensity use (and often at low-intensity use too), with pepper spray as the sole notable exception. RoseyFields treats a TCE-containing consumer product as presumptively risk-flagged absent a specific low-intensity, low-frequency use pattern shown to fall above the acute benchmark MOE.
• PPE meaningfully reduces but does not eliminate occupational risk, and its effectiveness differs sharply by route: for inhalation, respirators eliminate risk for three specific lower-exposure conditions of use at central tendency, but leave risk in place for most others, especially at high-end exposure and for chronic duration. For dermal exposure, gloves at maximum assumed protection do not eliminate risk for any condition of use evaluated — a materially different (and more concerning) finding than for inhalation.
• Central-tendency vs. high-end distinctions matter more for some conditions of use than others: for domestic manufacture and processing as a reactant/intermediate, central-tendency inhalation MOEs are well above benchmark (203.5 acute; tens to hundreds chronic) while high-end MOEs fall below benchmark — meaning risk conclusions for these particular COUs are highly sensitive to which exposure percentile is assumed representative of the actual exposed population, and RoseyFields treats the underlying exposure data quality (monitoring-based vs. modeled, sample size, age of data) as directly relevant to how much weight to place on either bound.
• Cancer risk applies only to chronic occupational exposure: because EPA did not extend its cancer risk methodology to consumer or acute exposure scenarios, a TCE consumer product risk assessment should rely on the acute non-cancer MOE framework only, while an occupational TCE risk assessment should evaluate both the non-cancer MOE and the extra cancer risk in parallel, since a given scenario can pass one benchmark while failing the other.
• ONU risk estimates carry more uncertainty than worker risk estimates: because ONU-specific exposure data were frequently unavailable, many ONU risk values in EPA’s summary tables are actually worker-based proxies, which EPA itself flags as likely to overestimate ONU exposure in most (but not necessarily all) cases, given that ONUs are a heterogeneous population whose true exposure depends heavily on individual work activity and proximity to the TCE source.

7. Application in RoseyFields Risk Assessments

For a given site- or scenario-specific TCE risk assessment, RoseyFields follows the same sequence EPA uses in its risk evaluation:

• 1. Identify the relevant population(s) — worker, ONU, consumer user, or bystander — and the applicable exposure duration (acute only for consumer/bystander scenarios; acute and/or chronic for occupational scenarios).
• 2. Reconstruct or adopt exposure estimates specific to the condition of use, distinguishing central tendency from high-end (or low/moderate/high intensity for consumer products), and specifically noting whether the exposure estimate is based on true percentile monitoring data or on mean/median-as-percentile substitutes, since EPA itself flags the latter as less reliable and prone to overestimation.
• 3. Calculate non-cancer MOEs against the applicable acute (10) or chronic (30) benchmark MOE, and extra cancer risk against the IUR or OSF for any chronic occupational scenario.
• 4. For occupational inhalation scenarios, calculate risk both without and with the minimum respirator APF that EPA identifies as sufficient to eliminate risk (where such a level exists); for occupational dermal scenarios, calculate risk with gloves at the maximum applicable protection factor but do not assume this eliminates risk without confirming it against the specific condition of use, given how frequently EPA’s own data show persistent dermal risk even with maximum glove protection.
• 5. For any consumer or bystander scenario, apply the acute non-cancer MOE framework only (not a cancer risk calculation), and treat risk as the default expectation for TCE-containing consumer products other than pepper spray absent site-specific, low-intensity use data supporting an MOE above benchmark.

This sequence mirrors the risk characterization structure EPA itself uses in its TCE Risk Evaluation, and allows RoseyFields to present both the point estimate and the underlying exposure-data-quality, PPE, and route-specific context needed for an informed risk management decision, rather than a bare numerical risk value alone.

8. Conclusion

EPA’s TCE Risk Evaluation produces a risk picture in which non-cancer and cancer risk are identified across nearly all evaluated occupational conditions of use under high-end, no-PPE assumptions, and across nearly all evaluated consumer product categories (with pepper spray the sole clear exception) — a broader pattern of identified risk than either PCE or 1,4-dioxane show in RoseyFields’ companion risk-assessment pages for those chemicals. PPE materially reduces occupational inhalation risk for lower-exposure conditions of use but leaves risk in place for most higher-exposure conditions of use and for chronic duration generally, and — notably — does not eliminate dermal risk for any occupational condition of use evaluated, even at maximum assumed glove protection. RoseyFields applies this same exposure assessment and risk characterization framework — non-cancer MOE calculations (with and without PPE) and extra lifetime cancer risk, informed by scenario-specific dose reconstruction and close attention to exposure-data quality, route, and PPE assumptions — to characterize TCE risk for the workers, occupational non-users, consumers, and bystanders relevant to each site-specific assessment.

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