When I debug similar issues, I do the following with Adobe Acrobat's Output Preview > Object Inspector tool :
1) Verify the object is not a bitmap object.
2) Verify the color space if not a bitmap object.
3) Verify if a transparency is visible.
If there is an active transparency, be sure to use the APPE interpreter - this interpreter is better for handling transparencies.
Can you let me know if APPE resolves the issue you are encountering.
BTW, there are no PDF/Fiery Substitute Color restrictions that I am aware of.
-victor
Victor Ibarra
Fiery Lead QA Engineer - Color & Imaging