Impact of mean and instantaneous dose rates on hydrogen peroxide (H₂O₂) production in water radiolysis under varying pH and initial oxygen: A modelling study

Objective. Hydrogen peroxide (H2O2), a long-lived product of water radiolysis implicated in oxidative stress, has been proposed as a potential mediator of the FLASH effect. This work investigates how Mean and Instantaneous FLASH dose rates, alongside varying pH and initial oxygen levels, influence H2O2 yields using Monte Carlo track-structure (MCTS) simulations coupled with homogeneous chemistry modelling. Approach. MCTS simulations (TOPAS-nBio v2.0) were used to model the physical and heterogeneous chemical stages up to 1 & micro;s under both an independent-track approach (low dose-rate limit, 60Co reference) and pulsed irradiation to account for intertrack effects. Escape yields were propagated into a deterministic reaction module (GillesPy2/ODE) incorporating the (HO2 center dot/ O2 center dot-) acid-base equilibrium and extending simulations up to 103 s. Simulations covered doses from 0.2 to 60 Gy, Instantaneous dose rates up to similar to 108 Gy s-1 (10 ns FWHM pulse), and Mean dose rates from 0.28 to 105 Gy s-1 were investigated, across initial oxygen of 1%, 4%, and 21% pO2 and pH (0.4-7). Main results. The simulations reproduced experimental H2O2 yields, including variations in initial oxygen, single-pulse irradiation, and pH dependence (0.4-7), within 1 +/- 0.5%. An instantaneous dose rate of 108 Gy s-1 suppressed early O2 center dot- formation and reduced steady-state H2O2 by similar to 12% compared to independent tracks approach, due to intertrack effects between radicals ( OH center dot,eaq-,H3O + ), an effect diminished at 21% pO2. In contrast, mean dose rate (500 Gy s-1) enhanced H2O2 production (similar to 0.17 & micro;M Gy-1), representing a similar to 30% increase compared with 0.28 Gy s-1 (similar to 0.12 & micro;M Gy-1), consistently across oxygen levels at neutral pH. Significance. Dose-rate effects on H2O2 are jointly influenced by pH and initial oxygen. The model predicts an increase in H2O2 with mean dose rate around 103Gy s-1, a behaviour linked to OH center dot lifetime effects in the homogeneous stage. The combined framework supports extension to biologically relevant media to advance our understanding of the FLASH effect mechanism.