How Are We Exposed to Chemicals When Drugs Are Smoked Indoors?

Indoor smoking of psychoactive substances exposes not only users through "firsthand smoke" (FHS) but also bystanders through pathways of "secondhand smoke" (SHS; exhaled or side-stream smoke) and "thirdhand smoke" (THS; residual contamination that persists indoors) via different routes of inhalation, mouthing-mediated ingestion, and dermal absorption. Here, we explore how chemical properties, smoking behaviors, and features of exposed individuals together shape exposure pathways and routes, using a mechanistic indoor chemical fate and exposure model with scenarios varying by retention rate (the fraction of smoke-generated chemicals absorbed by the smoker) and smoking frequency. We estimate adult and child exposure to seven representative compounds spanning orders-of-magnitude differences in volatility and hydrophobicity. We find that dominant exposure pathways and routes are strongly chemical-specific and scenario-dependent. FHS is consistently the dominant exposure pathway for substance users, whereas among nonsmoking exposed individuals, the relative importance of SHS and THS is determined jointly by chemical partitioning properties and the relative durations of active-smoking and postsmoking periods. Exposure to volatile chemicals (e.g., nicotine) is dominated by inhalation, exposure to compounds with intermediate hydrophobicity by dermal absorption, while highly hydrophobic, lowly volatile compounds (e.g., Δ9-tetrahydrocannabinol) receive meaningful contributions from all three routes. These findings highlight that broad generalizations about exposure dominance can misrepresent risks, particularly for nonusers and children.