alt Hacker NewsHypothetically, a train could derail, the train was carrying nuclear waste, the derailment occurred in a highly populated area, near a Virology Lab. The lab was damaged, which released a deadly form of Smallpox, which spread to every corner of the Earth, killing every single human. That would be pretty bad, but not sure if it would be the absolute worst.
You don't need the nuclear waste in that, the train could derail, be carrying a lazy courier transporting a deadly bio-hazard, and unleash a deadly virus and kill literally everyone. From a human-centred perspective that is probably the worst case.
If we're talking non-human it is a bit harder.