Determination of Thresholds of Radioactive Iodine Uptake Response With Clinical Exposure to Perchlorate: A Pooled Analysis.

OBJECTIVE: To conduct a more robust examination of perchlorate exposure on iodide uptake inhibition (IUI) using pooled data from four clinical studies of perchlorate exposure. METHODS: To establish a response threshold for IUI, data were analyzed using segmented linear regression and benchmark dose (BMD) analysis. RESULTS: Segmented linear regression applied to data for 69 subjects representing nine doses identified a breakpoint corresponding to a change in the slope of the dose-response relationship of 3.0 mg/d perchlorate. The estimated BMD for a 20% decrease in iodine uptake was 2.3 mg/d, with a lower 95% confidence interval limit of 1.6 mg/d. CONCLUSIONS: A threshold dose for IUI from perchlorate exposure of 1.6 to 3.0 mg/d (0.021 to 0.038 mg/kg d) was estimated using two modeling approaches. These estimates are slightly higher than the lowest observed effect level of 0.02 mg/kg d from the Greer Study.

Urinary nitrate, thiocyanate, and perchlorate and serum thyroid endpoints based on NHANES 2001 to 2002.

OBJECTIVE: To determine, on the basis of iodide uptake inhibition (IUI), whether associations between urinary concentrations of IUI agents (perchlorate, nitrate, and thiocyanate), as total perchlorate equivalent concentration (PEC), and serum thyroid parameters suggest functional thyroid abnormalities. Additional thyroid hormone measures were released to augment the National Health and Examination Survey (NHANES) 2001 to 2002 data set, which we used in this study. METHODS: Enhanced thyroid hormone measures released to augment the National Health and Examination Survey (NHANES) 2001-2002 data set were used in this study. Multiple regression was used to assess the relationships among total thyroxine (TT4), free thyroxine, total triiodothyronine (TT3), free triiodothyronine, and thyroid- stimulating hormone (TSH) and PEC. RESULTS: PEC was weakly and negatively associated with TT4, but not with TSH, TT3, or free hormone. This association with TT4 appears to be dominated by nitrate and thiocyanate. CONCLUSION: No evidence of functional thyroid abnormality (eg., low thyroid hormone coupled with high TSH) was seen with exposure to the combined IUI agents and enhanced estimates of thyroid function.

Toxicological relevance of pharmaceuticals in drinking water.

Interest in the public health significance of trace levels of pharmaceuticals in potable water is increasing, particularly with regard to the effects of long-term, low-dose exposures. To assess health risks and establish target concentrations for water treatment, human health risk-based screening levels for 15 pharmaceutically active ingredients and four metabolites were compared to concentrations detected at 19 drinking water treatment plants across the United States. Compounds were selected based on rate of use, likelihood of occurrence, and potential for toxicity. Screening levels were established based on animal toxicity data and adverse effects at therapeutic doses, focusing largely on reproductive and developmental toxicity and carcinogenicity. Calculated drinking water equivalent levels (DWELs) ranged from 0.49 microg/L (risperidone) to 20,000 microg/L (naproxen). None of the 10 detected compounds exceeded their DWEL. Ratios of DWELs to maximum detected concentrations ranged from 110 (phenytoin) to 6,000,000 (sulfamethoxazole). Based on this evaluation, adverse health effects from targeted pharmaceuticals occurring in U.S. drinking water are not expected.