What precautions should I take when editing Exim's run time configuration file?

Edit the file and save the result in a new file. Test the syntax of the new file by running a command like this:

exim -bV -C exim.conf.new

That will check for syntax errors without disturbing your running configuration. If you are paranoid enough, run, as root,

exim -C exim.conf.new <some address>
<some message>
.

and see if it delivers it. Carry on testing until happy. When happy,

mv exim.conf.new exim.conf
kill -HUP `cat /var/spool/exim/exim-daemon.pid`

Then check the Exim log to be sure the daemon restarted OK. Watch the log for a bit to see that mail is flowing.