Gatseva and Argirova found that consuming water with high-nitrate levels increases risk for thyroid dysfunction in vulnerable populations. Nitrate intake commonly occurs through diet and drinking water. The main objective of this pilot study is to characterize exposure to thiocyanate, nitrate and perchlorate in areas of Turkey with differing iodine intakes and potentially elevated levels of iodide uptake inhibitors. We chose non-lactating women because lactation complicates exposure assessment for 
these analytes: secretion into milk is a major pathway by which anions are cleared from a lactating woman’s body. Perchlorate exposure is likely driven by diet, and thus non-lactating and non-pregnant women are likely to have the same exposure KRX-0401 sources and exposure magnitudes as lactating and pregnant women. The scatter plot matrix illustrates correlations among analytes. Perchlorate, nitrate and iodine were more tightly correlated with each other than with thiocyanate, likely because of differences in exposure sources. Perchlorate, nitrate and iodine exposures are likely from the same sources. Conversely, tobacco smoke was the primary source of urinary thiocyanate as a metabolite of the cyanide in the tobacco smoke. We further explored second hand smoke exposure at home or at work as a potential source of thiocyanate, but did not find secondhand smoke categorization to be significantly related to increased urinary thiocyanate levels. Detailed distributions of tobacco smoke exposure results are shown in Figure S4a, Figure S4b and Figure S4c in File S1. This pilot study provides novel data indicating that study participants had low iodine intake and high intake of some iodide uptake inhibitors compared with reference populations. However, the study also is weak in that it draws these conclusions based on a relatively small number of participants and possibly biased selection between study sites. Thus, our findings need to be confirmed in larger groups of participants, especially in pregnant and lactating women. While the study does use rigorous 24-hr urine collection, multiple 24-hr samples would have resulted in more precise exposure estimates. Additionally, the study would have been strengthened by full assessment of current thyroid function of study participants. In addition to DGAT1’s role in these tissues, DGAT1 and DGAT2 have also been demonstrated to be expressed in the skin of mice and human. Mice with a deletion of the DGAT1 enzyme are protected from diet induced obesity and show increased sensitivities to insulin and leptin and increased energy expenditure. However, in addition to these metabolic phenotypes, DGAT1-/- mice develop leptin-dependent abnormal skin phenotypes, characterized by sebaceous gland atrophy and hair loss. The metabolic effects and the skin phenotype were shown to be recapitulated with pharmacological inhibition of DGAT1. Skin composition between human and preclinical species varies; wax diester is the major sebum lipid in mouse while TG is the major form in human. Although the exact role of sebum in human is not fully understood, sebum production could be decreased with pharmacological inhibition of skin DGAT1 activity. Since the identification and the characterization of DGAT1 -/mice, multiple pharmaceutical companies have been actively pursuing the discovery of small molecule DGAT1 inhibitors to reproduce the beneficial metabolic phenotypes of these mice. Recent early clinical data with DGAT1 inhibitors have uncovered gastrointestinal adverse effects as a major issue with no report of adverse skin effects. However, considering the role of DGAT1 in the skin, such inhibitors represent potential liabilities related to skin AEs as well. To that end one of our goals was to develop small molecule DGAT1 inhibitors with differential exposures at the site of Fulvestrant action vs. skin.