With the 2C's, my understanding is that the thioalkyls are worse than the alkyls which are worse than the halogens.
Incidentally DET in particular of the tryptamines can get very intense very fast and there might be some concerns there and with its cousins DPT and DiPT. DMT itself has high 5ht2b activity, which is bad; it's just hard to get that much DMT into your system under ordinary conditions. Nicotine overdoses are rare for a similar reason. As a class the tryptamines don't end up looking too safe, but the 4-subs are among the most innocuous compounds around. Presumably hydroxylation at 4 decreases affinity for a certain anti target-- better yet, it may alter the ways the drug is distributed in the brain.
The nbome's don't look too bad; except for some idiosyncratic hypersensitivity, which is weird for such selective ligands. The only overdose on an nbome was just a crazy high dose; it's probably unrelated to the hypersensitivity some people experience. I don't think anyone is sure what the problem is, but I'd still guess them to have a higher therapeutic index than most 2c's or tryptamines. At the potency of nbome's, though, the therapeutic index doesn't absolve these compounds from the simple and very real handling concerns associated with such potent compounds. Most people who have accesss to lots of 25i powder are not of the sort that traditionally would have been able to mess around with lots of acid.
