Beyond the WHO Priority Toxicants: A Systematic Review of Harmful and Potentially Harmful Constituents in IQOS Aerosols.

Heated tobacco products (HTPs) generate an inhalable aerosol by heating tobacco instead of burning it as conventional cigarettes do. Although several harmful and potentially harmful constituents (HPHCs) are generally reduced compared with conventional cigarette smoke, the World Health Organization's list of nine priority toxicants (WHO 9) may not fully reflect the chemical complexity of HTP aerosols. The main goal of this review is to evaluate the occurrence, quantitative levels, and toxicological relevance of HPHCs identified in IQOS aerosols and to propose an expanded toxicant panel for aerosol characterization. The review was conducted according to PRISMA 2020 recommendations using literature retrieved from the Web of Science Core Collection database. The studies included in the present review consistently report lower levels of many combustion-related toxicants in IQOS aerosols, compared with conventional cigarette smoke, particularly for carbon monoxide, volatile organic compounds, and polycyclic aromatic hydrocarbons. However, several toxicologically relevant compounds, including carbonyls, tobacco-specific nitrosamines, phenolics, and trace metals, remained detectable in several studies. An expanded panel of twenty priority toxicants was proposed, based on toxicological relevance, frequency of detection, regulatory significance, and analytical feasibility. The proposed panel extends beyond the WHO 9 framework while preserving regulatory applicability and analytical practicality. The findings support the need for harmonized methodologies and broader toxicant monitoring strategies for the comparative assessment of heated tobacco products.