Top flange I really wouldn't worry. Top flange is compressing not pulling. Bottom flange I wouldn't like at all.
I don't like to admit this but probably 15 years ago I drilled 4 holes in my top flange between cab and fifth wheel. Ran that way for a few years then I put a bolt in the hole cut off the head and welded it in. Ground it smooth and you'd never know it's there. Still running truck today
I'm no frame shop. I'm a shadetree fabricator. So my opinion is worth the full price you're paying for it.
This rule applies to the web as well as the flanges, compression and tension. Use a reamer to get an exact fit to the bolt of choice. Preferably a bolt with a short shank at the head. Tighten the bolt to spec.
As the frame rail flexes an unfilled hole or one with a loose fit filler, will elongate and misshape. As it does this over and over 10s of thousands of times, the metal surrounding the hole will "work harden" and/or "cycle fatigue" and become brittle. Cracks will follow and eventual failure will happen.
If you fill the hole with a fastener tight enough that does not allow the hole to misshape or elongate etc. It can not cycle.
That rule was passed down to my from highly experienced old fabricators that also dabbled in blacksmithing. So.....for what's it's worth, that's my opinion.