Firefox does not obey "Audio MIDI Setup" in Apple macOS at all! It overwrites to whatever selected device master out preventing the audio from being properly routed according to the "Audio MIDI Setup" standard Apple macOS Audio Setup. If you need to route to a Quadraphonic, or anything other than Stereo you won't be able to do it. If you need to route the audio through a special set of virtual audio channels where you can add compressors, EQ, filters, it will not let you. Google Chrome and Safari do this right without any need to change any settings or configurations on the browser side, all you need to do is configure the System-Wide Audio Settings in "Audio MIDI Setup", which is the only way and standard to the audio configuration on any macOS systems. I am a Linux/Unix System Administrator/Engineer, and I also work with Music Production using special professional interfaces from UA United Audio Apollo x8p and Focusrite. Those interfaces are connected to different sets of speakers, and they also have virtual audio channels where you can add a chain of plugins to treat the audio signal passing through them. This behavior should be considered a bug, although it is probably by design, which needs to be changed to adhere to the macOS system configuration standards for audio routing. I tested this with the latest and greatest stable Firefox version, Google Chrome, and Safari. The only browser misbehaving is the Mozilla Firefox.