Molecular Insights into Ocular Exposure Risk of Indoor Smoke Components on the Tear Film

Indoor smoke is a recognized respiratory hazard, yet its impact on the ocular surface remains unresolved. The tear film lipid layer (TFLL) constitutes the first physiologic barrier against airborne insults. Here, we construct an atomistic TFLL model to quantify interactions with six priority indoor smoke constituents under indoor-relevant conditions. These molecules cover the full hydrophobicity spectrum from smoking-relevant polycyclic aromatics and nicotine to cooking-emitted glycerol and succinic acid. Molecules with log P < 1 spontaneously nucleate into tighter and H-bond-rich agglomerates that exhibit 3-4 orders of magnitude higher trans-TFLL permeability than their hydrophobic counterparts. Polar agglomerates locally fluidize the wax-ester matrix, nucleating hydrophilic nanodomains that boost water-evaporation flux. Upon reaching the polar interface, carbonyl- and hydroxyl-bearing species form lipid-headgroup chelates to reduce film compressibility by 0.13-0.26 m/mN, accelerating mechanical rupture. Based on these findings, we propose a three-variable phase diagram that predicts whether a given smoke component will (i) penetrate TFLL, (ii) induce antievaporation loss, and/or (iii) accelerate film rupture. The work translates chemical concentration into trans-TFLL flux, identifies polar cooking and biomass markers as the highest ocular-bioavailable fraction, and provides quantitative thresholds for "ocular hazard" classification. These data complement respiratory-centric risk models and inform the rational design of pollutant-scavenging artificial tears.