Association between urinary organophosphate flame retardant diesters and steroid hormones: A metabolomic study on type 2 diabetes mellitus cases and controls

Metabolomic analysis was conducted by collecting urine samples from 128 participants in diagnose of type 2 diabetes mellitus (T2DM) and 105 volunteers in healthy condition, in order to identify biomarkers of experimental populations. The urinary concentrations of organophosphate flame retardant (OPFR) diesters were determined and linear regression model was used to find associations between OPFR diesters and the identified biomarkers. The urinary concentrations of OPFR diesters ranged from 0.17–779 μg/g creatinine. Diphenyl phosphate (DPHP) was detected with the highest frequency of 97% at a median level of 1.21 μg/g, and bis(1-chloro-2-propyl) phosphate (BCIPP) dominated the highest median level at 4.24 μg/g with a detection frequency of 94.4%. As compared with the control, the urinary median concentrations of bis(2-butoxyethyl) phosphate (BBOEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and DPHP were 2.76, 2.48, and 1.46 times higher in people with T2DM, respectively. Urinary metabolomic data revealed that steroid synthesis was the most significantly altered metabolic pathway between the case and control population. Two biomarkers of cortisol and cortisone that play an important role in steroid hormone regulation were quantified. The linear regression model indicated that per-quartile range increase in the concentrations of each OPFR diester was associated 18%–41% increase in the concentrations of cortisol and cortisone, which may impact energy metabolism linked with T2DM. To our knowledge, this study for the first time reported the altered levels of steroid hormones associated with urinary OPFR diesters.