Impact of mean and instantaneous dose rates on hydrogen peroxide (H₂O₂) production in water radiolysis under varying pH and initial oxygen: a modeling 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 modeling. Approach: MCTS simulations (TOPAS-nBio v2.0) were used to model the physical and heterogeneous chemical stages up to 1 µs 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 (HO_2^•/O_2^(•-)) acid-base equilibrium and extending simulations up to 10³ s. Simulations covered doses from 0.2 to 60 Gy, Instantaneous dose rates up 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 O_2^(•-) formation and reduced steady-state H₂O₂ by ~12% compared to independent tracks approach, due to intertrack effects between radicals (OH^•,e_aq^-,H₃O⁺), an effect diminished at 21% pO₂. In contrast, mean dose rate (500 Gy s⁻¹) enhanced H₂O₂ production (~0.17 µM Gy⁻¹), representing a ~30% increase compared with 0.28 Gy s⁻¹ (~0.12 µM 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 10^3 Gy s^(-1), a behavior linked to OH^• lifetime effects in the homogeneous stage. The combined framework supports extension to biologically relevant media to advance our understanding of the FLASH effect mechanism. .