Safe mode only disables front-end code and will leave some server-side things in place, so it may still be a plugin even if it occurs in safe mode. There’s a recent post with more info in here Safe-mode failed with a plugin - #4 by david
I can’t replicate this issue on my test site. Do you have any plugins/extra settings/anything unusual that could be having an impact? Is there any more information in the /logs about the error?