Trivalent chromium (Cr(III) or Cr3+) is required in trace amounts for sugar and lipid metabolism in humans, and its deficiency may cause a disease called chromium deficiency. In contrast, hexavalent chromium (Cr(VI) or Cr6+) is very toxic and mutagenic when inhaled. Cr(VI) has not been established as a carcinogen when in solution, though it may cause allergic contact dermatitis (ACD). The use of chromium-containing dietary supplements is controversial due to the complex effects of the used supplements. The popular dietary supplement chromium picolinate complex generates chromosome damage in hamster cells. In the United States the dietary guidelines for daily chromium uptake were lowered from 50-200 µg for an adult to 35 µg (adult male) and to 25 µg (adult female). In a review of trials it was again concluded that chromium supplements had no effect on healthy people, but that there might be an improvement in glucose metabolism in diabetics, although the authors stated that the evidence for this effect remains weak. However, opinions differ on this conclusion, a review published in 2006 argued that these data instead supported the clinical efficacy of chromium picolinate for the treatment of diabetes. In 2006, the U.S. Food and Drug Administration stated that the "relationship between chromium picolinate intake and insulin resistance is highly uncertain".