What series of instructions provides comprehensive guidelines on safety issues?

The correct answer is OPNAV 5100, as it is specifically a series of instructions that addresses safety issues within the Navy. OPNAV, or the Office of the Chief of Naval Operations, publishes these instructions to ensure that safety protocols are established and followed across various activities and operations within the Navy. This series sets forth comprehensive guidelines aimed at preventing accidents and ensuring the safety and health of personnel and operations.

While SECNAV 3500 relates to operational risk management and is important for overall Navy operations, it does not focus exclusively on safety issues. CNO 3000 typically encompasses broader strategic and policy directions rather than detailed safety guidelines. JAG 4000 is more aligned with legal matters and regulations rather than direct safety instructions. Therefore, OPNAV 5100 stands out as the most relevant source for comprehensive safety guidelines in the context of naval operations.