It's true that the overdose is at a lower threshold than other dewormers, at least for horses. It's still several times (4 or 5) the weight limit, so the risk is usually in very young foals when someone estimates weight incorrectly, or minis.
It's an extremely effective dewormer showing little, if any, resistance. The BIGGEST problem is just that... it works so well. It should never be used on a malnourished or heavily infested animal or bird. Many of the problems seen with it (not quite as widespread as many would have you think), is because it does it's job so well, if there is a heavy worm load, the sudden and large number of them dying off at once cause problems-- they give off toxicity themselves. It can be too much for a weakened or heavily infested animal to endure, not to mention cause impaction. For instance, I have a (bad) habit of 'rescuing' neglected, sickly horses. They are usually on their last leg, literally, and carry a heavy, heavy worm load. On these, I have to start with safeguard... and sometimes at HALF dose to just maybe get a *few* worms. Then, several weeks later, I can full dose them with safeguard. THEN, ivermectin a few weeks later, possibly at a reduced dose, too. THEN, I powerpack them with safeguard. THEN... and it depends on the individual case, I can use something that really packs a punch. The whole process can span several months before I get them to a point where they can go on a regular, less monitored deworming schedule. Too much, too soon, WILL kill them... even though you'd like to get every last one of them instantly. It's not the dewormer/drug that's the problem, it's the massive die off of worms that can cause all kinds of havoc.
The same could be said from many dewormers if used on heavily infested animals or birds or on ones that haven't been on a good deworming schedule. If you kill off EVERYTHING at once, it can cause problems. That's why it's best to use a milder, actually less effective dewormer in these cases FIRST. Quest targets (in horses) even more stages of the worms that other dewormers don't touch... so suddenly, there might be even more dying off.
There have been cases of invermetin type dewormers causing reaction (allergic and otherwise) in mammals (horses/dogs, Particularly certain breeds of dogs that carry a certain gene ), too. Sometimes after successfully using the drug many times before.
Done properly, dosed properly, there's rarely a bad effect or outcome from any of the dewormers.