Adverse Outcome Pathways Applied to Space Radiation Research.

Area of Science:

• Space biology and toxicology
• Radiation health effects
• Risk assessment modeling

Background:

• Long-duration spaceflight presents significant physiological stressors for astronauts.
• These stressors can lead to immediate and long-term health issues, including cellular and organ damage.
• Understanding radiation exposure effects is critical for astronaut safety and future space missions.

Purpose of the Study:

• To develop an adverse outcome pathway (AOP) network for radiation exposure relevant to spaceflight.
• To identify key events (KEs) linking molecular initiating events to non-cancer health outcomes.
• To guide research priorities and inform risk assessments for space exploration.

Main Methods:

• Expert consultation to develop the AOP network.
• A novel scoping review methodology for evidence evaluation.
• Identification of 18 key events (KEs) and four non-cancer outcomes.

Main Results:

• The AOP network links energy deposition (MIE) to oxidative stress, DNA damage, and potential mutations.
• Chronic inflammation, mitochondrial dysfunction, and immune cell activation are identified as key pathways.
• The network connects these events to learning/memory impairment, bone loss, vascular remodeling, and cataracts.

Conclusions:

• The AOP network consolidates knowledge on radiation-induced damage across biological levels.
• It identifies gaps in understanding causal relationships for radiation effects.
• This framework aids in developing space traveler risk models and is applicable to terrestrial radiation exposures.