Nontargeted analysis of the urine nonpolar sulfateome: a pathway to the nonpolar xenobiotic exposome.

RATIONALE: Testing the urine nonpolar sulfateome can enable discovery of xenobiotics that are most likely to be bioactive. This is based on the fact that nonpolar xenobiotics are more likely to enter cells where they tend to undergo metabolism, in part, to sulfates that are then largely excreted into the urine. METHODS: The following sequence of steps, with conditions that achieve high reproducibility, was applied to large human urine samples: (1) competitive nonpolar extraction with a porous extraction paddle; (2) weak anion-exchange extraction with strong organic washing; and (3) ultrahigh-performance liquid chromatography (UHPLC)/negative ion matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometery (MALDI-TOF/TOF-MS) with recording of ions with signal-to-noise (S/N) ≥ 20 that yielded M-1-80 (loss of SO3 ) or m/z 97 (HSO4- ) upon fragmentation. RESULTS: From a collection of urine samples from six pregnant women, the masses of 1129 putative sulfates were measured. Three lists of candidate compounds (preliminary hits) from these masses were formed by searching METLIN, especially via MATLAB, yielding putative xenobiotic contaminants (35 compounds), steroids (122), and flavonoids (1582). CONCLUSIONS: A new way to reveal some of the nonpolar xenobiotic exposome has been developed that applies to urine samples. The value of the method is to suggest xenobiotics for subsequent targeted analysis in the population of people under study, in order to relate the environment to health and disease. Copyright © 2016 John Wiley & Sons, Ltd.

Urinary phthalate metabolites in relation to maternal serum thyroid and sex hormone levels during pregnancy: a longitudinal analysis.

BACKGROUND: Increasing scientific evidence suggests that exposure to phthalates during pregnancy may be associated with an elevated risk of adverse reproductive outcomes such as preterm birth. Maternal endocrine disruption across pregnancy may be one pathway mediating some of these relationships. We investigated whether urinary phthalate metabolites were associated with maternal serum thyroid (free thyroxine [FT4], free triiodothyronine [FT3], and thyroid-stimulating hormone [TSH]), and sex (estradiol, progesterone, and sex hormone-binding globulin [SHBG]) hormone levels at multiple time points during pregnancy. METHODS: Preliminary data (n = 106) were obtained from an ongoing prospective birth cohort in Northern Puerto Rico. We collected urine and serum sample at the first and third study visits that occurred at 18 +/- 2 and 26 +/- 2 weeks of gestation, respectively. To explore the longitudinal relationships between urinary phthalate metabolites and serum thyroid and sex hormone concentrations, we used linear mixed models (LMMs) adjusted for prepregnancy body mass index (BMI) and maternal age. An interaction term was added to each LMM to test whether the effect of urinary phthalate metabolites on serum thyroid and sex hormone levels varied by study visit. In cross-sectional analyses, we stratified BMI- and age-adjusted linear regression models by study visit. RESULTS: In adjusted LMMs, we observed significant inverse associations between mono-3-carboxypropyl phthalate (MCPP) and FT3 and between mono-ethyl phthalate (MEP) and progesterone. In cross-sectional analyses by study visit, we detected stronger and statistically significant inverse associations at the third study visit between FT3 and MCPP as well as mono-carboxyisooctyl phthalate (MCOP); also at the third study visit, significant inverse associations were observed between FT4 and metabolites of di-(2-ethylhexyl) phthalate (DEHP). The inverse association between MEP and progesterone was consistent across study visits. CONCLUSIONS: In this group of pregnant women, urinary phthalate metabolites may be associated with altered maternal serum thyroid and sex hormone levels, and the magnitude of these effects may depend on the timing of exposure during gestation.