1,4-Dioxane Toxicology and Cancer Toxicity

1. Methodology Overview

RoseyFields conducts 1,4-dioxane risk assessments using the following methodology: we characterize hazard by relying on the peer-reviewed points of departure (PODs) that EPA has established for 1,4-dioxane’s most sensitive non-cancer endpoints and its cancer endpoints, each grounded in specific animal toxicology studies; we apply standard uncertainty-factor methodology within a margin-of-exposure (MOE) framework to derive health-protective non-cancer reference values, adjusted where necessary for the averaging time of the exposure scenario under evaluation; we evaluate carcinogenic potential using EPA’s inhalation unit risk (IUR) and cancer slope factor (CSF), each derived from multi-tumor-site dose-response modeling of chronic rodent bioassays; and we combine these hazard values with site- or scenario-specific exposure estimates to calculate margins of exposure and excess lifetime cancer risk for the populations of concern. The summary below documents the hazard evidence base for 1,4-dioxane as reflected in EPA’s most recent (2024) supplemental risk evaluation and explains how RoseyFields applies the resulting reference values in practice.

2. Chemical Identity and Background

1,4-Dioxane (CASRN 123-91-1, molecular formula C4H8O2, molecular weight 88.1 g/mol) is a cyclic ether that is fully miscible with water and most organic solvents. It is a colorless liquid at room temperature with a faint, pleasant odor. 1,4-Dioxane is used industrially as a solvent and solvent stabilizer, and it also occurs as an unintentional byproduct of the ethoxylation process used to manufacture surfactants, emulsifiers, and other ethoxylated compounds — meaning it is frequently present as a trace contaminant in a wide range of personal care products, detergents, and other consumer goods rather than being intentionally added to them.

Because 1,4-dioxane is highly water-soluble and resistant to biodegradation, it is a persistent and mobile groundwater contaminant, and general population exposure occurs predominantly through contaminated drinking water, along with lower-level exposure through ambient and indoor air and consumer products containing residual 1,4-dioxane. Occupational exposure occurs primarily via inhalation and dermal contact where 1,4-dioxane is manufactured, processed, or used as a solvent or solvent stabilizer, including in settings generating 1,4-dioxane as an unintentional byproduct.

EPA’s 2024 supplement evaluates a wide range of release and exposure scenarios beyond those addressed in the original 2020 Risk Evaluation, reflecting 1,4-dioxane’s presence across multiple environmental media and life-cycle stages. These include down-the-drain releases from products containing 1,4-dioxane as a byproduct, releases in hydraulic fracturing wastewater disposed of via underground injection or discharged to surface water, 1,4-dioxane migration to groundwater from landfill leachate, fugitive and point-source air emissions reported to the Toxics Release Inventory (TRI), and emissions from industrial and institutional laundries. This breadth of exposure pathways reflects both 1,4-dioxane’s use as an intentional solvent/stabilizer and its unintentional generation as an ethoxylation byproduct across a wide range of manufacturing and consumer product supply chains, meaning that communities and workers can be exposed through pathways not obviously tied to a facility’s primary product line.

3. Toxicokinetics (ADME)

The 2024 supplement does not restate a full toxicokinetic (ADME) narrative, deferring instead to the toxicokinetic discussion in EPA’s original 2020 Risk Evaluation; RoseyFields therefore summarizes here only what the supplement itself establishes about 1,4-dioxane disposition, which is directly relevant to how its hazard values were derived and applied.

Human inhalation studies indicate that 1,4-dioxane is readily and rapidly absorbed via the lungs (Young et al., 1976; Young et al., 1977), though the available data are qualitative rather than quantitative with respect to the fraction absorbed; EPA therefore conservatively assumes 100% inhalation absorption when extrapolating inhalation PODs to oral and dermal human-equivalent doses. For dermal exposure, EPA estimates a fraction absorbed (fabs) of approximately 0.86 in commercial/occupational settings, reflecting the portion of an applied dermal dose not lost to evaporation or retained in the stratum corneum before systemic absorption. Metabolism of 1,4-dioxane is understood to proceed substantially via cytochrome P450 2E1 (CYP2E1), a pathway relevant to potential lifestage differences in internal dose, since ventilation rate, anatomy, and CYP2E1 activity all differ between children and adults (U.S. EPA, 2012). EPA notes, however, that the physiologically based pharmacokinetic (PBPK) models currently available for 1,4-dioxane are not considered adequate for quantifying these lifestage toxicokinetic differences, and no generally accepted default method exists to do so outside a chemical-specific PBPK model; as a result, air concentration (rather than a PBPK-modeled internal dose) is used as the exposure metric across all lifestages, with the standard 10-fold human-variability uncertainty factor applied to account for this and other sources of toxicokinetic and toxicodynamic variability.

4. Toxicological Evidence Base (Animal Studies)

The quantitative non-cancer and cancer hazard values for 1,4-dioxane are each anchored in specific, high-quality animal bioassays. As with the toxicokinetics discussion above, the 2024 supplement presents these studies primarily through the lens of their role in POD derivation rather than as a comprehensive organ-system-by-organ-system toxicological review; RoseyFields summarizes the studies as EPA describes them below.

Acute/Short-Term Non-Cancer Toxicity — Liver

The acute/short-term non-cancer POD for 1,4-dioxane is based on the lowest-observed-adverse-effect concentration (LOAEC) for systemic liver toxicity identified in a short-term inhalation study in rats exposed 6 hours/day, 5 days/week (Putz et al., 1979; Mattie et al., 2012). EPA derived a general-population LOAEC-based HEC of 26.2 ppm (94.5 mg/m³) for continuous 24-hour exposure and an occupational HEC of 78.7 ppm (284 mg/m³) for an 8-hour occupational exposure, applying a dosimetric adjustment factor of 1 (the EPA default when the animal-to-human blood:air partition coefficient ratio exceeds 1). In the absence of acute oral or dermal toxicity studies specific to 1,4-dioxane, the corresponding oral and dermal human-equivalent doses (17.4 mg/kg-day) were derived from the inhalation HEC by route-to-route extrapolation, assuming 100% inhalation absorption, a general-population inhalation rate of 14.7 m³/day, and a body weight of 80 kg. A composite uncertainty factor of 300 was applied to this endpoint.

Chronic Non-Cancer Toxicity — Olfactory Epithelium and Liver

The chronic non-cancer PODs for 1,4-dioxane are based on two companion 2-year bioassays in rats: Kasai et al. (2009), a 2-year inhalation study (6 hours/day, 5 days/week) that identified effects in the nasal olfactory epithelium at a benchmark concentration lower confidence limit (BMCL10) — effects that EPA concluded, based on their uniform (rather than airflow-pattern-consistent) distribution within the nasal cavity, likely reflect systemic delivery rather than a direct portal-of-entry effect — and Kano et al. (2009), a 2-year drinking-water carcinogenicity/chronic toxicity study in rats and mice that identified liver toxicity at a benchmark dose lower confidence limit (BMDL) in male rats, corroborated by a nearly identical no-observed-adverse-effect level (NOAEL) for liver toxicity from a similar chronic study. The chronic inhalation HEC is 0.846 ppm (3 mg/m³) for continuous general-population exposure and 3.6 ppm (12.8 mg/m³) for 8-hour occupational exposure; the chronic oral HED (applicable to both occupational and general-population scenarios, since it is expressed as a daily dose rate) is 2.6 mg/kg-day; and the chronic dermal HED, derived from the chronic HEC by route-to-route extrapolation, is 0.56 mg/kg-day. A composite uncertainty factor of 30 was applied to these chronic endpoints.

Carcinogenicity Bioassays

The cancer hazard values for 1,4-dioxane are derived from the same two companion chronic bioassays that anchor the non-cancer chronic PODs. Kasai et al. (2009) identified statistically elevated incidences of multiple tumor types in male rats following 2-year inhalation exposure, including nasal cavity squamous cell carcinoma, Zymbal gland adenoma, hepatocellular adenoma or carcinoma, renal cell carcinoma, peritoneal mesothelioma, mammary gland fibroadenoma, and subcutis fibroma; EPA modeled the combined risk across all of these tumor sites using the MS-Combo model to derive the inhalation unit risk. Kano et al. (2009) identified liver tumors in female mice following continuous drinking-water exposure over 2 years; EPA modeled these data using the Multistage Weibull model to derive the oral (and, by route-to-route extrapolation, dermal) cancer slope factor. EPA describes a robust, high-quality set of chronic and subchronic inhalation and oral studies underlying both the non-cancer and cancer hazard values, with consistent findings of systemic toxicity and tumor formation across rats exposed by inhalation and rats and mice exposed via drinking water.

5. Epidemiological Evidence Base (Human Studies)

The quantitative non-cancer and cancer hazard values for 1,4-dioxane described in this supplement are derived entirely from animal bioassay data; no human epidemiological dataset is identified in the 2024 supplement as adequate for quantitative dose-response modeling of either non-cancer or cancer endpoints. The available human data cited in this supplement are limited to controlled human inhalation exposure and pharmacokinetic studies (Young et al., 1976; Young et al., 1977) confirming that 1,4-dioxane is readily absorbed via the lungs and providing qualitative support for the assumption of essentially complete inhalation absorption used in route-to-route extrapolation; these studies were not designed to and do not provide dose-response information for toxic or carcinogenic effects. RoseyFields notes this as an important distinction from TCE and PCE, where at least some quantitative human epidemiological evidence (for TCE, in particular) contributes to the cancer risk values; for 1,4-dioxane, human cancer risk is estimated entirely by interspecies extrapolation from the rodent bioassay evidence described in Section 4.

6. Health Outcomes Associated with 1,4-Dioxane Exposure, by Body System

The following overview organizes the illnesses and health outcomes associated with 1,4-dioxane exposure by body system, distinguishing findings with strong, quantitatively modeled dose-response support from those with suggestive or less consistent evidence, based on the evidence base presented in the 2024 supplement.

Liver

Strong, quantitatively modeled: Systemic liver toxicity is the basis of the acute/short-term non-cancer POD following short-term inhalation exposure in rats (Putz et al., 1979; Mattie et al., 2012), and liver toxicity following chronic oral exposure is one of the two chronic non-cancer PODs (Kano et al., 2009). Hepatocellular adenoma and carcinoma are also among the tumor types incorporated into the combined-tumor-site inhalation cancer POD (Kasai et al., 2009), and liver tumors in female mice following chronic drinking-water exposure are the sole quantitative basis for the oral and dermal cancer slope factor (Kano et al., 2009).

Nasal Cavity / Olfactory Epithelium

Strong, quantitatively modeled: Effects on the nasal olfactory epithelium following chronic inhalation exposure form one of the two chronic non-cancer PODs (Kasai et al., 2009); EPA’s assessment concluded these effects likely reflect systemic (rather than purely local portal-of-entry) delivery. Nasal cavity squamous cell carcinoma is also among the tumor types incorporated into the combined inhalation cancer POD (Kasai et al., 2009).

Kidney

Moderate, incorporated via combined cancer estimate: Renal cell carcinoma is among the tumor types observed in the chronic rat inhalation bioassay and incorporated into the combined-tumor-site MS-Combo cancer model (Kasai et al., 2009), though it is not independently modeled or presented as a standalone quantitative cancer risk value.

Reproductive and Peritoneal/Other Systemic Tumor Sites

Moderate, incorporated via combined cancer estimate: Zymbal gland adenoma, peritoneal mesothelioma, mammary gland fibroadenoma, and subcutis fibroma were each observed in the chronic rat inhalation bioassay and incorporated into the combined MS-Combo inhalation cancer risk estimate (Kasai et al., 2009), reflecting a multisite carcinogenic hazard profile rather than site-specific quantitative risk values for each individual tumor type.

Reproductive and Developmental Effects

Suggestive/data gap: EPA explicitly identifies limited data on some sensitive reproductive and developmental endpoints as a key source of uncertainty in the current hazard database for 1,4-dioxane; no quantitative reproductive or developmental POD is presented in this supplement, and EPA has not identified quantitative evidence of lifestage-specific susceptibility, though it qualitatively describes the potential for developmental toxicity and lifestage-related biological susceptibility, addressed through the standard 10-fold human-variability uncertainty factor rather than a chemical-specific quantitative adjustment.

Cancer (Systemic)

Strong, quantitatively modeled: Combined multisite tumor risk following inhalation exposure (nasal cavity squamous cell carcinoma, Zymbal gland adenoma, hepatocellular adenoma/carcinoma, renal cell carcinoma, peritoneal mesothelioma, mammary gland fibroadenoma, and subcutis fibroma in male rats) anchors the inhalation unit risk (Kasai et al., 2009); liver tumors in female mice following chronic oral exposure anchor the oral and dermal cancer slope factor (Kano et al., 2009). EPA expresses high confidence in the inhalation unit risk and medium-to-high confidence in the oral/dermal cancer slope factor.

Uncertain: The mode of action for 1,4-dioxane carcinogenicity is not fully characterized, which EPA identifies as a specific source of uncertainty in the cancer hazard assessment notwithstanding the robust dose-response dataset underlying the quantitative cancer values.

7. Derivation of Non-Cancer Reference Values (Points of Departure and Uncertainty Factors)

As with EPA’s parallel TSCA evaluations for TCE and PCE, the 1,4-dioxane hazard assessment derives PODs on an endpoint-specific basis (rather than a single classical oral reference dose) and characterizes non-cancer risk using a margin-of-exposure (MOE) framework: the MOE is the ratio of the non-cancer hazard value (HEC or HED) to the estimated human exposure, compared against a benchmark MOE equal to the total composite uncertainty factor used to derive that POD. An MOE at or above the benchmark indicates the exposure is not expected to result in the associated adverse effect with an adequate margin of safety; an MOE below the benchmark indicates the margin of safety is inadequate.

Uncertainty Factors Applied

EPA applied a composite uncertainty factor of 300 to the acute/short-term liver toxicity POD and a composite uncertainty factor of 30 to the chronic olfactory epithelium/liver toxicity PODs. Across both, EPA applied a 10-fold uncertainty factor for human variability specifically to account for potentially susceptible subpopulations (lifestage, genetic variability, and pre-existing disease, including liver disease) for which quantitative dose-response data are not available — this 10-fold factor functions as the primary quantitative safeguard for sensitive populations in the current 1,4-dioxane hazard assessment, in the absence of a validated 1,4-dioxane-specific PBPK model capable of quantifying lifestage-specific internal dose differences.

Duration and Route Adjustments Applied in This Supplement

The 2024 supplement did not re-derive the underlying 2020 PODs from the primary study data, but it did apply two categories of adjustment to align the previously peer-reviewed hazard values with new exposure scenarios (particularly continuous, 24-hour/7-day general-population exposure near fenceline communities, which was not evaluated in the 2020 Risk Evaluation):

• Duration adjustments: the original occupational HECs and IUR (developed for 8 hours/day, 5 days/week exposure) were adjusted to derive corresponding values for continuous (24 hours/day, 7 days/week) general-population exposure.
• Breathing-rate corrections: per a 2023 EPA correction memorandum, occupational oral and dermal HEDs that had been incorrectly extrapolated from occupational HECs using elevated (worker-specific) breathing-rate assumptions were corrected to apply the same general-population breathing-rate assumptions used to derive the underlying HEC in the first place; as a result, the acute and chronic occupational HEDs are now equal to the corresponding general-population HEDs.

Summary of Non-Cancer Reference Values

RoseyFields uses these HEC and HED values directly as the working non-cancer reference values for 1,4-dioxane, selecting the general-population or occupational, and acute or chronic, value appropriate to the exposure scenario and population under evaluation, and applying the corresponding benchmark MOE (300 for acute, 30 for chronic) as the acceptability threshold.

8. Carcinogenicity Classification and Cancer Slope Factor

The 1,4-dioxane cancer hazard values reflect a robust, high-confidence, multisite carcinogenicity dataset in animals; EPA’s dose-response assessment for 1,4-dioxane does not rely on a specific IARC or EPA weight-of-evidence cancer descriptor being restated in this supplement, but the derivation of both a linear inhalation unit risk and a linear cancer slope factor from chronic bioassay data reflects a conclusion that 1,4-dioxane carcinogenicity is appropriately evaluated using a low-dose linear (non-threshold) approach.

Inhalation Unit Risk (IUR)

The inhalation unit risk was derived using the MS-Combo model to evaluate combined cancer risk across multiple tumor sites (nasal cavity squamous cell carcinoma, Zymbal gland adenoma, hepatocellular adenoma/carcinoma, renal cell carcinoma, peritoneal mesothelioma, mammary gland fibroadenoma, and subcutis fibroma) observed in male rats following 2-year inhalation exposure (Kasai et al., 2009). The original occupational IUR (8 hours/day, 5 days/week), rounded to 1 × 10⁻⁶ per µg/m³, was further duration-adjusted in this supplement to derive values applicable to continuous, general-population exposure:

• Occupational IUR: 3.7 × 10⁻³ per ppm (1.0 × 10⁻⁶ per µg/m³), for 8 hours/day, 5 days/week exposure.
• General population IUR: 1.6 × 10⁻² per ppm (4.3 × 10⁻⁶ per µg/m³), duration-adjusted for continuous, 24 hours/day, 365 days/year exposure.

Oral and Dermal Cancer Slope Factor (CSF)

The oral and dermal cancer slope factor is 1.2 × 10⁻¹ per (mg/kg-day)⁻¹, derived using the Multistage Weibull model applied to liver tumor incidence in female mice following continuous chronic drinking-water exposure (Kano et al., 2009). EPA calculated a human-equivalent dose for each modeled tumor type by scaling rodent doses using body-weight-to-the-three-quarters-power (BWA/BWH)^0.25 allometric scaling, then derived the CSF by dividing the benchmark response rate (0.5) by the resulting human-equivalent dose. This single CSF value is applied to both occupational and general-population/consumer scenarios, using exposure estimates and risk benchmarks specific to each scenario; the dermal cancer slope factor used for dermal exposure pathways is extrapolated from this same oral CSF.

EPA expresses high confidence in the inhalation unit risk and medium-to-high confidence in the oral/dermal cancer slope factor, reflecting the robust, high-quality chronic and subchronic bioassay dataset underlying both values, tempered by residual uncertainty regarding the specific mode(s) of action for 1,4-dioxane carcinogenicity across the several tumor sites involved.

9. Uncertainties and Sensitive Populations

Key Uncertainties

• Entirely animal-based hazard values: because no human epidemiological dataset is adequate for quantitative modeling, both the non-cancer and cancer reference values for 1,4-dioxane depend entirely on interspecies extrapolation from rodent bioassay data.
• Incompletely characterized mode of action: the mode of action underlying 1,4-dioxane’s multisite carcinogenicity is not fully understood, adding uncertainty to the low-dose linear extrapolation approach even though the underlying dose-response data are considered high quality.
• Reliance on route-to-route extrapolation: in the absence of acute oral/dermal toxicity studies and chronic dermal toxicity studies specific to 1,4-dioxane, the corresponding oral and dermal PODs are derived by extrapolation from inhalation data (for acute and dermal endpoints) rather than from route-specific dose-response studies.
• Limited reproductive/developmental toxicity data: EPA identifies this as a specific data gap, meaning the current hazard database may not fully capture this domain of potential susceptibility.
• No adequate chemical-specific PBPK model: unlike TCE and PCE, for which validated PBPK models support internal-dose-based extrapolation, EPA concludes that available PBPK models for 1,4-dioxane are not adequate, so lifestage-specific internal dose differences (e.g., in children, whose ventilation, anatomy, and CYP2E1-mediated metabolism differ from adults) are addressed only qualitatively through the standard 10-fold human-variability uncertainty factor rather than quantitatively modeled.

Because 1,4-dioxane’s non-cancer and cancer hazard values were carried forward from the 2020 Risk Evaluation with only duration and breathing-rate adjustments — rather than re-derived from primary study data in this supplement — RoseyFields treats the confidence characterizations EPA assigned in 2020 (medium confidence in the acute non-cancer PODs; high confidence in the chronic non-cancer PODs; high confidence in the inhalation unit risk; medium-to-high confidence in the oral/dermal cancer slope factor) as still current and applicable. Any future primary re-analysis of the underlying Kano et al. (2009), Kasai et al. (2009), Putz et al. (1979), or Mattie et al. (2012) datasets, or the availability of a validated 1,4-dioxane-specific PBPK model, would be the most likely source of a material change to these reference values.

Sensitive and Susceptible Subpopulations

• Young children, given evidence that lifestage differences in ventilation rate, anatomy, and CYP2E1-mediated metabolism may result in higher inhaled internal doses relative to adults, even though this cannot currently be quantitatively modeled for 1,4-dioxane specifically.
• Formula-fed infants and other general-population lifestages, specifically incorporated into drinking-water exposure scenarios through lifestage-specific exposure factors.
• Individuals with pre-existing liver disease or other chronic conditions that may alter 1,4-dioxane metabolism or target-organ susceptibility, a qualitative concern EPA identifies but for which it did not find direct quantitative evidence.
• Individuals with genetic variability affecting CYP2E1 activity, given this pathway’s role in 1,4-dioxane metabolism and the potential for altered internal dose as a result.
• Populations relying on drinking water sources with elevated 1,4-dioxane concentrations (e.g., from down-the-drain industrial/consumer product releases, hydraulic fracturing wastewater, or landfill leachate) and communities near industrial facilities, hydraulic fracturing operations, or industrial/institutional laundries with fugitive or point-source air emissions.

10. Application of Reference Values in RoseyFields Risk Assessments

Non-Cancer Risk: Margin of Exposure

For each relevant 1,4-dioxane exposure pathway and averaging time, RoseyFields calculates a margin of exposure (MOE) as the ratio of the scenario-appropriate POD (HEC or HED) to the estimated human exposure:

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

The resulting MOE is compared against the benchmark MOE for that endpoint (300 for the acute liver toxicity POD; 30 for the chronic olfactory epithelium/liver toxicity POD). An MOE at or above the benchmark indicates the exposure is not expected to result in the associated adverse effect with an adequate margin of safety; an MOE below the benchmark indicates an inadequate margin of safety warranting further evaluation or risk mitigation. As with TCE and PCE, RoseyFields notes that calculated risk estimates are not treated as bright-line indicators of unreasonable risk on their own, consistent with EPA’s own framing, and are considered alongside other relevant risk-related factors specific to the scenario under evaluation.

Cancer Risk: Excess Lifetime Cancer Risk

For scenarios involving chronic or lifetime exposure, RoseyFields calculates extra (excess) lifetime cancer risk using the estimated human exposure (expressed as a lifetime average daily concentration or dose, LADC/LADD) and the applicable IUR or CSF:

Inhalation Cancer Risk = Human Exposure (LADC) × IUR

Dermal/Oral Cancer Risk = Human Exposure (LADD) × CSF

RoseyFields selects the occupational or general-population IUR value appropriate to the exposure duration pattern of the scenario under evaluation (8 hours/day, 5 days/week versus continuous 24/7 exposure) before applying this calculation, and compares the resulting extra cancer risk against applicable regulatory benchmarks (commonly in the 1 × 10⁻⁶ to 1 × 10⁻⁴ range depending on the regulatory and population context) to characterize whether the estimated risk falls within an acceptable range.

Dose Reconstruction

Where direct exposure monitoring data are unavailable, RoseyFields reconstructs 1,4-dioxane exposure using validated modeling approaches appropriate to the setting — occupational inhalation and dermal exposure modeling (including a fraction-absorbed adjustment of approximately 0.86 for commercial/occupational dermal contact), drinking-water exposure modeling incorporating lifestage-specific water intake factors for adults, children, and formula-fed infants, and fate-and-transport or air dispersion modeling for releases to surface water, groundwater, land, and ambient air (including fenceline, hydraulic-fracturing-related, and industrial/institutional-laundry-related air emission scenarios) — combined with population-specific behavioral parameters (exposure duration, frequency, body weight, and, for cancer risk, total years of lifetime exposure). Reconstructed exposure estimates are then evaluated against the appropriate scenario-specific MOE benchmark or cancer slope value described above.

11. Conclusion

1,4-Dioxane presents a hazard profile anchored in a robust, high-quality set of chronic and subchronic rodent bioassays, with liver toxicity and effects on the nasal olfactory epithelium as the primary quantitatively modeled non-cancer endpoints and a multisite carcinogenic hazard — spanning the nasal cavity, Zymbal gland, liver, kidney, peritoneum, mammary gland, and subcutis — anchoring EPA’s high-confidence inhalation unit risk and medium-to-high-confidence oral/dermal cancer slope factor. Unlike TCE, for which human epidemiological data anchor the cancer risk values, the 1,4-dioxane hazard values described in this supplement rely entirely on animal-to-human extrapolation, and EPA identifies limited reproductive/developmental data, an incompletely characterized carcinogenic mode of action, and the absence of an adequate chemical-specific PBPK model as continuing sources of uncertainty, particularly for lifestage-specific susceptibility. RoseyFields applies the resulting reference values — duration- and population-specific HEC/HED PODs evaluated through a margin-of-exposure framework, together with the inhalation unit risk and oral/dermal cancer slope factor for cancer risk — within a standard MOE and excess lifetime cancer risk framework, informed by scenario-specific dose reconstruction, to characterize risk for the populations and exposure pathways relevant to each site-specific assessment.

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