What your saying does make sense, and I can definitely attest to the cleaner feeling experiences produced by plugging... just about every drug I've plugged as a matter of fact. I'm very pro-plugging and some substances I refuse to take any other way, aMT is one that comes to mind but I also strictly plug the lesser absorbed opioids like morphine derivatives, even heroin though I do smoke it occasionally as well.
I don't know if others have had a similar reaction, but every time I would plug the APB's, they were noticably less psychedelic... every time. Also, what's weird is that different ROA's tend to drastically affect aMT's "character". Vaped is almost pure stimulant and zapped of all magic, nasal was more stimmy than psycheddlic, oral is fantastic and reminds me of Mescaline a bit, though it also comes with the "purge" and full array of side-effects, though an overall mord complete experience.
Rectal, funnily enough, still takes me three hours to peak, but the experience is far far cleaner but also less of a journey so to speak, essentially over by the tenth hour as well, despite the three hour come-up. Of course this has just been my experience, but I would agree that different ROA's change the effects. I can think of many more examples, but i'd get into tl/dr territory.
Whether or not it makes the substance more or less toxic I would think it's entirely dependent on the drug... mephedrone, theoretically, being a good example. I'd imagine there are drugs that would be more toxic had they skipped first pass metabolism... but when we get into rectal use of RC's, that's sorta uncharted territory I guess. Would rectal MDMA affect the conversion to MDA or alpha methyl dopamine? Meh, guess I could find out if these are converted by first pass, just throwing some ideas around.
Interesting topic, I hope we get some knowledgeable people to chime in, as this is something that's been in the back of my mind for a while actually.