Are food colour clashes worth the worry?

Food colourings are a class of chemicals that quite neatly encapsulates many cultural clashes over the nature and safety of substances. Is a ‘natural’ colour safer or better than a synthetic one? Does the fact that a compound poses some hazard at massive exposure (such as when fed to rats at high doses) translate to a real risk of harm to humans at low levels found in food? Where should regulators draw the line?