Thyroid Receptor Antagonism of Chemicals Extracted from Personal Silicone Wristbands within a Papillary Thyroid Cancer Pilot Study.

Research suggests that thyroid cancer incidence rates are increasing, and environmental exposures have been postulated to be playing a role. To explore this possibility, we conducted a pilot study to investigate the thyroid disrupting bioactivity of chemical mixtures isolated from personal silicone wristband samplers within a thyroid cancer cohort. Specifically, we evaluated TRß antagonism of chemical mixtures extracted from wristbands (n = 72) worn by adults in central North Carolina participating in a case-control study on papillary thyroid cancer. Sections of wristbands were solvent-extracted and analyzed via mass spectrometry to quantify a suite of semivolatile chemicals. A second extract from each wristband was used in a bioassay to quantify TRß antagonism in human embryonic kidney cells (HEK293/17) at concentrations ranging from 0.1 to 10% of the original extract (by volume). Approximately 70% of the sample extracts tested at a 1% extract concentration exhibited significant TRß antagonism, with a mean of 30% and a range of 0-100%. Inhibited cell viability was noted in >20% of samples that were tested at 5 and 10% concentrations. Antagonism was positively associated with wristband concentrations of several phthalates, organophosphate esters, and brominated flame retardants. These results suggest that personal passive samplers may be useful in evaluating the bioactivities of mixtures that people contact on a daily basis. We also report tentative associations between thyroid receptor antagonism, chemical concentrations, and papillary thyroid cancer case status. Future research utilizing larger sample sizes, prospective data collection, and measurement of serum thyroid hormone levels (which were not possible in this study) should be utilized to more comprehensively evaluate these associations.

Effects of personal air pollutant exposure on oxidative stress: Potential confounding by natural variation in melatonin levels.

Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) are commonly used biomarkers of oxidative stress. However, their associations with air pollutant exposure have not been consistent across studies. We hypothesize that the inconsistency is partly due to confounding of circulating melatonin. We analyzed urinary 6-sulfatoxymelatonin (aMT6s), a surrogate of circulating melatonin, along with 8-OHdG and MDA, in 159 healthy adults who had not taken melatonin supplementation. Within the natural range of endogenously-generated aMT6s (0.3-93.5 ng/mg creatinine) measured in this study, increasing aMT6s levels were significantly associated with increasing concentrations of 8-OHdG and MDA. Measurements of PM2.5, ozone (O3), and nitrogen dioxide (NO2), coupled with time-activity data, were used to calculate time-averaged personal exposures 12 -hour (12h) and 24-hour (24h) prior to urine collection. Without controlling for aMT6s, the relationships between pollutant exposure and 8-OHdG or MDA were not clear. After controlling for aMT6s, an interquartile range (IQR) increase in 12h PM2.5 and 12h NO2 exposure was associated with 6.1% [95%CI: 1.6%-10.8%] and 8.6% [1.3%-16.5%] increase in MDA, respectively. An IQR increase in 12h O3 exposure was associated with a 5.7% [1.9%-9.7%] in 8-OHdG. The findings suggest the need for controlling for aMT6s as a confounder in using urinary 8-OHdG and MDA as biomarkers of oxidative stress related to short-term air pollution exposure.