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.
Examples:
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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.
Comic Books
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.
Film
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 sucker 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.
Tabletop Games
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.
In Forgotten Realms the Shadow Weave is an alternative arcane magic Power Source, mostly incompatible with normal magic which in itself brings some advantages. Its use involves either a pact with one of evil deities or taking mental/spiritual damage.
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).
Video Games
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.
The Phazon Suit seems to have a lot in common with the Omega Pirate, which the Space Pirate research notes pointed out led to insanity and a much shorter lifespan. Fortunately, Samus kills Metroid Prime, who tries to kill Samus, but instead removes the Phazon before this happens.
Unfortunately, Metroid Prime somehow merges with the suit, gains Samus's intellect, and spends the next two games spreading Phazon across the galaxy.
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.
Armored Core 4/For Answer has Kojima particles, which aren't dissimilar from GM or Minovsky particles, but turns the NEXTs into Walking Wastelands
Cleria in Ys I and II. It bolstered the titular civilization's rise to prosperity, but also caused its downfall. Said to be a corrupt form of Emelas.
The ancient civilization in Chrono Trigger was doing well using the powers of the sun and the elements. Then they discovered a certain sleeping Eldritch Abomination and decided to tap its power instead... Well, let's just say it did not end well.
Data Draining from .hack is a form of this, as normal use inflicts status effects on the main character, but overuse is much worse. For one, side effects occur more often when you Data Drain more often (due to increased spread of the virus). However, the worst effect you can experience is your character being randomly, unavoidably, and irretrievably corrupted. That's an instant Game Over.
The Lutece Fields (aka Tears) in Bioshock Infinite allow its users to peek or to travel into other timelines. Prolonged exposure to them causes cancer, sterility and rapid aging.
The G1 series had an episode where they created anti-matter for Megatron to absorb and pelt the Autobots with. He subsequently had to eject it later in fear of DEATH.
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.
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.
Real Life
Uranium. Sure, it does produce huge amounts of power and can create the most destructive weapons known at the cost of radiation, sickness, cancer not to mention the fallout that results when it blows up.
That's the 235 isotope. The one element that would fit the above description to the T would be plutonium which is medically toxic and doesn't even have a benevolent use; slugging a full rod of weapons-grade plutonium into a reactor and NOT sending a few extra control rods into the active zone after it doesn't really sound like a good idea. And yes, I know that reactors can't really explode like a nuke but steam explosions/pressure damage due to enhanced heat generation due to more fissile material in the active zone could occur, no?
Uranium is also a poisonous heavy metal.
Fissionables aside, pretty much every fuel, its ingredients, and its byproducts, count to some degree. The search for clean options is currently an issue of some disagreement.
Explosives. Counterintuitively, much of the technological research in explosives has been concentrated on making them not explode, progressing from extremely unstable ones like black powder and guncotton to virtually inert ones like plastique.
Oxygen is incredibly volatile, and can be toxic in concentration. Yet aerobic based life-forms are much more successful than anaerobic ones.
