I recommend going through design guide 2, which you appear to be doing. It is common to see holes in wide flanges for mech ducts, pipes etc.., my preference is to locate as close to the midspan as possible, where moment is highest and shear is lowest and to locate centered in the web. I especially try to avoid holes near ends due to shear being highest and as we know web plays a more important role in shear versus moment.
There are calculations out there that are done for holes in members, I believe AISC publishes these (maybe in the design guide), haven't looked in a long time as I use spreadsheets now for it, however it calculates if you need to reinforce the member around the hole, typically a moment check and a shear check. I have seen calc shortcuts for smaller openings and lighter loaded members of just adding the amount of steel taken out back around the opening as an angle top and bottom of the hole as well and welding it in place.
My gut tells me chances are if the holes are located at the center and are that tiny and located near midspan that if you calculate this you will find it's fairly easy to do. A beam with holes in it just acts like a joist/truss from a statics standpoint.
I have designed a few 36" deep beams years ago with 10' wide openings and maybe 4" left at top and bottom and it required significant reinforcing with angles around the opening, the contractor was scared and even took measurements as the equipment was placed on them to check deflection and stresses for their own piece of mind, it didn't move and has been there for 7 or 8 years now.
