Perchloroethylene (PCE) Risk Assessment and Neurotoxicity

1. Methodology

RoseyFields conducts PCE 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), consumer and bystander inhalation and dermal exposure, and, where relevant, the specific case of children present at dry cleaning facilities; 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 added cancer risk against EPA’s inhalation unit risk (IUR); 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 PCE, and explains how RoseyFields applies this same framework in practice.

2. Health Effects and Endpoints Used for Risk Estimation

EPA’s risk characterization for PCE draws on the weight-of-evidence hazard assessment to select the most sensitive and robust endpoints for quantitative risk estimation. For acute exposures, the risk-driving non-cancer endpoint is neurotoxicity — specifically, increased latencies for pattern-reversal visual-evoked potentials. For chronic exposures, the risk-driving non-cancer endpoints span multiple domains: central nervous system (CNS) effects, kidney toxicity (urinary markers of nephrotoxicity), liver toxicity, immune/hematological toxicity, and developmental toxicity. For cancer, risk is evaluated based on liver tumors, consistent with the inhalation unit risk and oral/dermal cancer slope factor described in RoseyFields’ companion PCE Hazard Characterization page. EPA notes that for the majority of occupational exposure scenarios where chronic neurotoxicity risk was identified, risk was also identified concurrently for kidney and immune-system toxicity — meaning that in practice, non-cancer risk for PCE tends to present across multiple organ systems simultaneously rather than in a single isolated domain.

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 in ppm) ÷ Human Exposure

For occupational inhalation exposure, the 8-hour or 12-hour time-weighted average (TWA) exposure is used for acute MOE calculations, and the chronic average daily concentration (ADC) is used for chronic MOE calculations; for dermal exposure, acute and chronic retained dermal doses are used. The resulting MOE is compared against a benchmark MOE equal to the total composite uncertainty factor used to derive that POD. An MOE below the benchmark MOE indicates human health risk; an MOE at or above the benchmark MOE indicates negligible concern for the associated adverse effect. As a general principle, the larger the MOE relative to the benchmark, the less likely a non-cancer adverse effect is to occur.

Cancer Risk: Added Lifetime Cancer Risk

Cancer risk is expressed as the incremental (added) probability of an individual developing cancer over a lifetime as a result of repeated exposure, calculated using the inhalation unit risk:

Risk = Human Exposure (LADC, mg/m³) × IUR (2 × 10⁻³ per mg/m³)

Cancer risk was evaluated only for chronic (repeated) exposure scenarios; EPA did not estimate cancer risk for single, acute PCE exposures because the relationship between a single short-term exposure and cancer induction in humans has not been established. As described in RoseyFields’ companion hazard page, this IUR should not be applied to exposure concentrations exceeding 60 ppm (400 mg/m³), above which the underlying dose-response relationship becomes non-linear.

Route-to-Route Extrapolation and Dermal Risk

Because PCE lacks a dermal compartment in its underlying PBPK model, dermal PODs used in risk estimation were derived by route-to-route extrapolation from either the inhalation or oral POD for each endpoint, using human data or PBPK-derived human-equivalent values as the starting point. Where dermal human-equivalent doses (HEDs) could be derived from both the inhalation and oral POD for the same endpoint, EPA selected the more sensitive (lower) of the two resulting HEDs for use in risk estimation, in order to be health-protective.

Role of Personal Protective Equipment (PPE)

A distinguishing feature of PCE’s occupational risk characterization is that EPA calculated risk estimates both with and without assumed PPE — respirators (characterized by an assigned protection factor, APF) for inhalation exposure, and gloves (characterized by a protection factor, PF) for dermal exposure. For each occupational exposure scenario where a risk was identified without PPE, EPA identified the minimum level of PPE (up to APF 50 for respirators; glove PF 20 industrial / PF 10 commercial) that would eliminate that risk, and presented both the no-PPE and with-PPE risk estimates side by side. EPA notes that respirator use was assumed implausible for certain small commercial settings (e.g., aerosol degreasing, dry cleaning, metalworking fluids, wipe/spot cleaning) where a respiratory protection program is unlikely to be in place, meaning the no-PPE risk estimate is the operative one for those scenarios regardless of the theoretical with-PPE value.

4. Occupational Exposure and Risk

EPA characterized occupational risk separately for workers (who directly handle PCE-containing materials) and occupational non-users (ONUs, who are present in the same facility but do not directly handle PCE), across the full range of conditions of use — including domestic manufacture, import/repackaging, use as a chemical intermediate/reactant, incorporation into other products, vapor degreasing (batch open-top, batch closed-loop, conveyorized, and web degreasing), cold cleaning, aerosol degreasing and lubricants, and dry cleaning and spot cleaning.

Representative Occupational Risk Estimates (No PPE)

The table below illustrates the pattern of risk estimates EPA calculated across representative conditions of use, expressed as MOEs for acute and chronic non-cancer risk (compared against benchmark MOEs of 10 for acute and 100 for chronic in these examples) and as added cancer risk (compared against a benchmark of 1 × 10⁻⁴), for high-end and central-tendency 8-hour inhalation exposure without PPE:

Across the full set of occupational conditions of use, MOEs below the acute (10) or chronic (100) benchmark, and cancer risks above 1 × 10⁻⁴, occur in numerous scenarios under high-end, no-PPE assumptions — indicating that, absent PPE, several occupational conditions of use present both non-cancer and cancer risk of potential concern at EPA’s stated benchmarks. Applying the minimum PPE EPA identifies as sufficient (e.g., APF 10 respirator, PF 10–20 gloves) brings most of these same scenarios to MOEs and cancer risks below their respective benchmarks, illustrating how central PPE assumptions are to the ultimate risk conclusion for occupational PCE exposure.

Special Analysis: Children Present at Dry Cleaning Facilities

EPA conducted a dedicated risk analysis for children who may be present at dry cleaning facilities — for example, children of employees who accompany a parent to work — using lifestage-adjusted acute HECs for CNS effects specific to the most sensitive lifestage (infants under 1 year old), and treating this population’s exposure as equivalent to that of occupational non-users, without assuming any PPE use (since PPE would not be fitted to or used by a child bystander).

These results show that risk to children present at dry cleaning facilities is highly sensitive to the generation of dry cleaning technology in use: MOEs based on the modeling-based scenario for facilities using older (“post-2006”) technology fall below the benchmark MOE of 10 under high-end assumptions, while facilities using only newer 4th/5th-generation (fully enclosed, more efficient) dry cleaning machines produce MOEs well above the benchmark under both exposure levels evaluated. EPA also concluded, based on the 2012 EPA IRIS PCE assessment, that children who live, attend daycare, or attend school above or adjacent to (rather than physically inside) dry cleaning facilities would have lower exposure than children present inside the facility itself, and that this dedicated in-facility analysis is therefore expected to be protective of those nearby-residence scenarios as well.

5. Consumer and Bystander Exposure and Risk

EPA evaluated consumer and bystander risk for a wide range of PCE-containing products, all assessed only for acute (not chronic) exposure scenarios, since consumer product use patterns for PCE were judged not to constitute chronic exposure. For each product category, EPA calculated separate MOEs for the product user (across low, moderate, and high use-intensity scenarios) and for bystanders in the vicinity, for both inhalation (typically 24-hour averaging) and dermal exposure routes where applicable.

Representative Consumer Product Risk Estimates

This pattern — acceptable or near-acceptable MOEs for low-intensity use, but MOEs one to three orders of magnitude below the benchmark for moderate- and especially high-intensity use — recurs across nearly all aerosol PCE consumer products EPA evaluated, and is the central finding driving consumer-product risk conclusions for PCE. By contrast, exposure from wearing or being near dry-cleaned clothing itself (as opposed to directly using an aerosol PCE product) produced MOEs well above benchmark for both the user and bystander, reflecting the much lower residual PCE levels in finished dry-cleaned garments compared with direct product use.

For dermal exposure to consumer products, EPA calculated risk separately for three consumer age groups (11–15 years, 16–20 years, and adults 21 and older), finding that differences in MOE across age groups were generally 10% or less and that no exposure scenario had a dermal MOE close enough to its benchmark for the age-group selection to change the risk conclusion; EPA’s summary tables therefore present dermal results for the most sensitive age group (11–15 years) as representative of all three.

6. Interpreting PCE Risk Estimates

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

• PPE assumptions materially change the risk conclusion for most occupational scenarios: many occupational conditions of use that show MOEs below benchmark or cancer risk above 1 × 10⁻⁴ under no-PPE, high-end assumptions fall to acceptable levels once EPA’s identified minimum respirator/glove protection factor is applied — meaning the practical risk-management question for many PCE occupational scenarios is less “is this activity hazardous” and more “is adequate PPE actually being used,” particularly in small commercial settings where EPA itself judges a respiratory protection program unlikely to be in place.
• Consumer product risk is strongly use-intensity dependent: low-intensity users of most PCE-containing aerosol products fall close to or above benchmark MOEs, while moderate- and high-intensity users fall one to three orders of magnitude below benchmark — meaning use frequency and duration, not just the product itself, are central determinants of consumer risk.
• Bystander risk generally tracks user risk but is not simply proportional to it: bystander MOEs are sometimes several-fold higher than user MOEs for the same scenario (reflecting lower incidental exposure) but follow the same intensity-dependent pattern, meaning a product flagged as high-risk for the primary user should not be assumed low-risk for bystanders without checking the specific bystander MOE.
• Children present at dry cleaning facilities are a distinct, EPA-flagged sensitive population whose risk depends heavily on the generation of dry cleaning equipment in use at that specific facility — RoseyFields treats the type of dry cleaning machine present (older transfer/vented systems versus modern 4th/5th-generation fully enclosed systems) as a first-order input to any risk assessment involving this population, not a secondary detail.
• Non-cancer risk for PCE tends to co-occur across organ systems: because CNS, kidney, and immune-system risk are frequently identified together in the same chronic occupational scenarios, RoseyFields does not treat a single-domain non-cancer risk finding (e.g., neurotoxicity alone) as capturing the full non-cancer risk picture for a chronic PCE exposure scenario.

7. Application in RoseyFields Risk Assessments

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

• 1. Identify the relevant population(s) — worker, ONU, consumer user, bystander, or the specific case of children present at a dry cleaning facility — and the applicable exposure duration (acute for consumer scenarios and for the children-at-dry-cleaners analysis; 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 identifying whether the exposure estimate is monitoring-based or model-based, since EPA’s own confidence ratings differ materially between the two.
• 3. Calculate non-cancer MOEs against the applicable acute or chronic benchmark MOE (equal to the total uncertainty factor for the relevant endpoint), and added cancer risk against the IUR for any chronic occupational scenario, confirming the exposure estimate falls within the IUR’s valid range (below 60 ppm / 400 mg/m³).
• 4. For occupational scenarios, calculate risk both without and with the minimum PPE (respirator APF, glove PF) that EPA identifies as sufficient to eliminate risk for that scenario, and clearly report which of the two is actually applicable given real-world PPE use in the setting under evaluation — RoseyFields does not default to the with-PPE estimate without evidence that adequate PPE is in fact used.
• 5. For any scenario involving children present at or near a dry cleaning facility, apply the lifestage-adjusted infant HEC and treat exposure as ONU-equivalent (no PPE assumed), and specifically identify the generation of dry cleaning technology in use at the facility as a key determinant of the resulting risk estimate.

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

8. Conclusion

EPA’s PCE Risk Evaluation produces a risk picture in which both non-cancer and cancer risk are of potential concern across a substantial share of occupational and consumer conditions of use, with the practical outcome for any given scenario depending heavily on three factors: the exposure intensity (central tendency versus high-end, or use-intensity tier for consumer products), whether adequate PPE is actually used in occupational settings, and — for the specific case of children present at dry cleaning facilities — the generation of dry cleaning technology in operation at that facility. RoseyFields applies this same exposure assessment and risk characterization framework — non-cancer MOE calculations (with and without PPE) and added lifetime cancer risk, informed by scenario-specific dose reconstruction and close attention to use-intensity and PPE assumptions — to characterize PCE risk for the workers, occupational non-users, consumers, bystanders, and children relevant to each site-specific assessment.

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