You've got a nice form of Applied Phlebotinum, and it's pretty powerful. But sometimes it's just not enough. You need more power. So what do you do?
Fortunately, you've somehow stumbled upon a shiny, new Power Source, stronger and easier to use than your current model. What Could Possibly Go Wrong?
Quite a bit, actually. See, your "new-and-improved" power source isn't near as safe as your old one. Sure, it'll get you the power you need, but at a very high price. Explosions, crippling injury, and sometimes even mutations can result if you overuse it. Better hope you can finish the job quickly or Zorlak the Planet Wedgier will be the least of your health concerns.
Unlike most dangerous forms of Applied Phlebotinum, this one is more likely to be used by the heroes, probably because unlike most other forms, this type's danger lies not in corruption but in simple explosions which would endanger the user more than the environment, making the risk heroic. See also Psycho Serum. Sometimes overlaps with Sentient Phlebotinum, in which case it's liable to become The Corruption or The Virus.
No real life examples please!
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Anime & Manga
Inverted in GaoGaiGar FINAL. The villains' power source is the "Loud G-Stone", which has a constant power output which is higher than the G-Stones the heroes are using. Of course, the Loud G-Stone isn't powered by courage. Sure enough, Guy's G-Stone power goes through the roof when he gets pissed off enough, and the rest of the robots follow suit. The Sol 11's "non-toxic" Loud G-Stones can't keep up. Guy points this out in his heroic Breaking Lecture: "Everything is because you were afraid! Afraid the G-Stone's power would transcend the Loud G-Stone! The power born from courage!"
In Busou Renkin, it is revealed that Kazuki's Kakugane is actually an unstable black version. The Black Kakugane (which had replaced his heart) causes his body to transform and grants him enormous power as a result. Unfortunately, being in this transformed state causes him to drain the life force of everyone and everything around him nonstop, and while the transformed state can be suppressed at first, it eventually becomes permanent.
Shinsoo, the absolute baseline of power inside the Tower of God is not always agreeable with the human body. Without a certain resistance, people can die in the denser higher levels.
Sakuradite from Code Geass is this, basically. Rumored to be the Philosopher's Stone of old, significant amounts of it were found in Japan (duh) under mount Fuji. While not used as a power source per se, the primarily electricity-based alternate world that Code Geass universe is based in (as opposed to steam and fossil-fuel based) makes Sakuradite very valuable as a room-to-high temperature superconductor. It is basically the phlebotinum that makes Game Breakers such as the Lancelot Knightmare Frame. The "toxic" part comes in that Sakuradite, especially in liquid form, is very volatile. How volatile? Volatile enough to make it viable as a booster in a nuke-slash-antimatter bomb.
The imperfect philosopher's stones and red water they're made from in Fullmetal Alchemist, which are extremely poisonous in and of themselves, and have an increased risk of alchemical rebound.
The prototype GN Tau drives in Gundam 00 have power only slightly below that of the "true" GN drives but their crimson red particles cause cellular abnormalities in humans that prevent tissue regeneration (just look at what happened to poor Louise) and eventually kill the subject (almost happened to Lasse and maybe Graham) in exchange for being far faster and easier to mass-produce. The final mass-production version fixes this issue which also incidentally changes the particles' color to orange.
Starting with Post-Crisis version of The DCU, Lex Luthor was able to harness kryptonite in a variety of means of bedeviling Superman. Unfortunately, Luthor learns the hard way that kryptonite radiation is also harmful to humans with sufficient exposure.
In the Marvel Universe, attempts to weaponize adamantium in Super Soldiers met problems because adamantium is toxic. One of their first successful subjects was Wolverine, who had a Healing Factor that kept the adamantium from killing him. The tradeoff for him is that his Healing Factor lost some of its potency.
In the Iron Man online Infinite Comics story "Fatal Frontier", the discovery of phlogistone, moonrocks that gained special powers after being exposed to various kinds of Phlebotinum (the Power Infinite, the Phoenix Force, etc.) kicks off a wave of colonization and industry on the moon. Tony eventually finds evidence that phlogistone also corrupts souls. After discovering this Tony puts all of his efforts into keeping phlogistone out of anyone's hands while looking for a way to depower it.
Iron Man 2: The palladium components of Tony's chest-mounted arc reactor decay over time and emit toxins into his blood, slowly killing him. At least, until he perfects the technology using a hidden schematic from his dead father to make a new atomic element to replace the Palladium.
This is really an inversion, since it's the original reactor that is killing him, and the shiny new one that is actually safe.
That it worked at all is a minor miracle.
Live Action TV
Naquadriah is the variant unstable form of Naqadah in Stargate SG-1. It's the basic form of this trope; more power can be taken from it, but it's unstable.
In fact, naquadriah's instability depends on how much energy you are trying to get from it. Higher energy means exponentially higher instability to the point where the X-302 attempted a hyperjump via its naquadriah-powered hyperdrive but the guidance computer automatically and intentionally missed the hyperspace window to avoid the craft being blown to pieces upon entry, and he Prometheus experienced a misjump while using its much bigger hyperdrive. After these incidents and the acquisition of some serious Asgard tech, naquadriah was never used for anything aside from boosting the yield of nuclear warheads - something the stuff is very good at.
In Stargate Atlantis they try extracting energy from an alternate reality, which will destroy the reality in question. No one has a problem with it at first since the chances of the reality being inhabited are astronomically small. Predictably, the alternate reality is inhabited and they have to deplete the ZPM (their usual power source) to stop the energy transfer before it is destroyed.
Trilithium, the dangerous form of dilithium in the Star Trek universe.
The Omega Molecule. The most powerful and dangerous thing in the universe. So much so that the Federation has a strict policy to destroy them at all costs (ordinary destructive things just destroys things. Omega Molecules can screw up subspace, meaning warp travel becomes impossible in the area).
Ghost rock from Deadlands was bad enough, what with miners and scientists using it contracting "rock fever" and spontaneously combusting, and the mineral itself highly explosive. If you want more power (and you're in one of the series' far-future settings) make irradiated ghost rock. Trope Co. not responsible for mutations, cancers, and death.
Warpstone from Warhammer Fantasy is not merely the setting's local Green Rocks, it can be used to boost magic workings and the skaven use it not only as the basis of their economy, but to power their Magitek... everything. As a downside, it's a magical, madness-inducing mutagen. Oh, and if it's used to "enhance" gunpowder, it makes it more powerful, and far more unstable (with a toxic cloud of powder smoke when ignited).
Phazon, pictured above, from the Metroid Prime series. Although there is no "safe" form of Phazon: it comes in "unstable and uber-deadly" blue and "even more unstable and uber-deadly" orange, unless you have the Phazon Suit from the original Prime, in which case you take no damage from the blue Phazon. Orange Phazon still hurts, though.
Tiberium in Command & Conquer. A virulent crystalline "plant", it leaches minerals from the soil and forms them into easily-harvested crystals on the surface, which is a hell of a lot easier than mining. The downside is that tiberium fields emit extremely toxic gases, mutates local flora, kills local fauna and is unstoppably spreading across the world.
In later games, blue form of tiberium gives double the resources, but also explodes when you shoot it. And let's not get into the liquid form, which creates explosions visible from space.
The Scrin don't suffer from these effects. On the contrary, they actually need regular infusions of Tiberium to survive. This is reflected in gameplay by Scrin units regenerating health while on Tiberium.
Makes sense, as tiberium is a Scrin xenoforming agent.
Dragon Age has the magical ore lyrium. The raw substance is toxic and can only be safely mined by dwarves, who then process it into a useful state. "Safe" lyrium can make mana potions for mages, enchant weapons and armor, and help Templars develop their Anti-Magic abilities. Too bad long-term use can lead to addiction, mental instability and, in extreme cases, mutation - the codex claims that Tevinter Magisters who overused the stuff stopped looking human. The sequels introduce red lyrium, which works faster and eventually turns you into a lyrium statue or monster.
Also in G1, The Matrix Of Leadership is usually a powerup for any 'bot lucky enough to have a high affinity for it. Its also Unicron's kryptonite, so when Scourge (a Unicron-made bot with Matrix affinity) picked it up, he simultaneously got a lot stronger and started melting.
Transformers Animated uses transwarp energy to fuse organic and machine elements, turning Wasp into Waspinator. Unfortunately, it's unstable, and he later fully explodes, teleporting at the same time. (He gets better.)
A somewhat less toxic variant was Nucleon. Created pretty much as an excuse for the Action Masters, it was more efficient and more powerful than Energon, but for some reason prevented them from actually transforming - supposedly forever. This, of course, became the excuse for the Powermasters, who could cleanse their partners of the Nucleon, regain their transformation ability, AND help boost their power levels to the point they were under the Nucleon.
Ore-13, aka Ultra Energon from IDW comics. It greatly enhances a transformers abilites, but burns out very quickly and leaves the user in a very vulnerable state.
Batman: The Animated Series once featured a crook who used a bodysuit made of a material that both granted invisibility and became toxic under an electric current. Through his spree of small-time robberies, the man was slowly killing himself. His invisible car, however, was probably harmless.
In Beast Wars raw Energon is extremely powerful but also very volatile. The reason the Transformers needed beast forms in the first place was to protect themselves from all of the raw Energon on the planet.
In Transformers Prime Dark Energon is extremely powerful and dangerous since it's the blood of Unicron. Megatron's abuse of it has dire consequences for him in the long run: he can never join the Allspark (the Transformers' afterlife) thanks to his contact with Unicron's Anti-spark.