Attn: Perchlorate_Comments_for OIG@epa

Objective: A significant negative association between serum thyroxine and urine perchlorate levels had been reported from NHANES 2001-2002 by Blount et al. (2006) for women age 12-85 with low iodine nutrition expressed as urine iodine (UI) less than 100 ug/l. We have reanalyzed the data using creatinine-adjusted urine iodine (UICr) as the measure of iodine nutrition and focused on women of childbearing age (age 15-44). UICr (creatinine-adjusted urine iodine) may better reflect 24-hour urine iodine excretion than does the UI (Manz, 2000; Thomson, 2001). Additionally, we have included urinary measures of the other two major iodine uptake inhibitors, nitrate and thiocyanate. Design: Of 2091 women of child-bearing age [WCBA], 625 had serum measurements for thyroxine and urinary measurements for iodine, creatinine, and the three iodineuptake inhibitors. Additional exclusions were made for thyroid history and extreme values. Multiple regression analyses on the thyroxine level were performed for each tercile of the UI distribution and of the UICr distribution, both with and without population-weighting, and including the three iodine-uptake inhibitors. Main Outcome: With iodine nutrition expressed as creatinine-adjusted urinary iodine, a significant negative association with serum thyroxine was found at high iodine levels rather than at low iodine levels for both urine perchlorate and urine thiocyanate levels.. Additionally, urinary thiocyanate levels were consistently found to have a significant negative association with serum thyroxine level at high iodine level, whether creatinineadjusted or not, whether population-adjusted or not. Conclusion: A variety of analytic methods, including Sudaan-weighting, consistently revealed that the negative association of serum thyroxine and urine perchlorate found for WCBA with low iodine defined by UI was not found for those with low iodine defined by UICr (creatinine-adjusted). March 10, 2009 CEOH Page 1 of 11 Perchlorate and Thyroxine: Creatinine and Population Adjustment