Well, what is your purpose? If it is to keep this box indefinately, 300-400K might be a good point to open it up, replace bearings, replace any chipped gears, synchro rings etc. However, M46 are cheap and plentyful, so you could run it until it dies, then determine if it's just bearings and a few synchro rings or if perhaps more structural damage has been done by its demise and a replacement is warranted. In that second scenario it might go past half a million, possibly more. Of course it depends on the application, a turbo or V6 will put more stress on it than a low compression B21.

Bram