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Say I'm an Ursaring and the first thing I do is set up a Substitute after someone hits me. However, I'm holding a Toxic Orb. Would the Toxic Orb take effect?

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Of course it would!
Substitute only protects you from an enemy using Toxic on you; if you self inflict it, your Substitute will not block it.

Think of it as having the PSN status already, and than using Substitute; you already have it!

- 04.13.2012 4:46p

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One more thing: Do you still get hurt by poison when behind the substitute?
Yes, you would.
^ Yep, with the exception of Poison Heal, where you heal.