Health-based emissions limits: Integrating evidence for threshold vs. non-threshold health effects using HCl as an...

The US Environmental Protection Agency (EPA) may set emissions standards according to a threshold for maximum exposure that accounts for a substantial safety margin if exposure to a substance is expected to operate according to a non-linear, threshold model. The consideration of health-based thresholds for hazardous air pollutants (HAPs) that are being considered for carcinogenicity is relatively novel and reflects the fact that EPA now recognizes that some HAPs (both carcinogens and non-carcinogens) can be either non-threshold or threshold pollutants, or both, depending on the health outcome of interest. If a threshold model is accepted for carcinogenicity, EPA may set a health-based emission limit (HBEL), in addition to existing technology-based requirements, using the estimated threshold, plus an ample margin of safety. EPA is currently considering thresholds for several substances, including hydrochloric acid (HCl). To demonstrate the type of analysis that might address this issue, we conducted a targeted literature review of the evidence regarding the carcinogenicity of HCl based on available epidemiologic and toxicological studies, including genotoxicity studies. We discuss when regulations could be based on threshold vs. non-threshold models, using HCl as a case study. We found no evidence to support the use of a linear, no-threshold model and limited, inconsistent evidence to suggest that HCl is likely to be carcinogenic or a DNA-reactive mutagen. The evidence summarized here is intended to aid EPA in its risk evaluation and clearly supports the setting of an HBEL for HCl and other chemicals where the biological mechanism supports the existence of a threshold.Implications: Section 112(d)(4) of the Clean Air Act permits EPA to consider health-based emission limits for hazardous air pollutants when the available scientific evidence supports the existence of a threshold for adverse effects and an ample margin of safety can be established. Using hydrochloric acid as a case study, this review integrates epidemiologic, toxicologic, and mechanistic evidence relevant to evaluating threshold versus non-threshold modes of action. The evidence is more consistent with threshold-mediated effects than with a direct mutagenic carcinogenic mechanism and may inform future scientific evaluations conducted under Section 112(d)(4).