Associations between urinary diphenyl phosphate and thyroid function

Abstract

Triphenyl phosphate (TPHP) is a commonly used organophosphate flame retardant and plasticizer with widespread human exposure. Data on health effects of TPHP are limited. Recent toxicological studies suggest TPHP may alter thyroid function. We used repeated measures to assess the temporal variability in urinary concentrations of the TPHP metabolite, diphenyl phosphate (DPHP), and to examine relationships between DPHP concentrations and thyroid hormones. We sampled 51 adults at months 1, 6, and 12 from 2010-2011. Urine samples were analyzed for DPHP. Serum samples were analyzed for free and total thyroxine (fT4, TT4), total triiodothyronine (TT3), and thyroid stimulating hormone (TSH). We assessed variability in DPHP using intraclass correlation coefficients (ICCs) and kappa statistics. We used linear mixed-effects models to examine associations between DPHP and thyroid hormones. DPHP was detected in 95% of urine samples. Mean DPHP concentrations were 43% higher in women than men. DPHP showed high within-subject variability (ICC range, 0.13-0.39; Kappa range, 0.16-0.39). High versus low (≥2.65 vs. <2.65 ng/mL) DPHP in all participants was associated with a 0.43 μg/dL (95% confidence interval: 0.15, 0.72) increase in mean TT4 levels. In sex-stratified analyses, high versus low DPHP was associated with a 0.91 μg/dL (95% CI: 0.47, 1.36) increase in mean TT4 in women. The association was attenuated in men (βeta= 0.19; 95% CI: -0.15, 0.52). We found no significant associations between DPHP and fT4, TT3, or TSH. We found evidence that TPHP exposure may be associated with increased TT4 levels, especially in women.

Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States

“…6,11,14−24,29 Descriptive studies were reported previously and are not discussed in detail here. Briefly, urine samples were collected in 2002–2015 and analyzed in 2009–2016.…”

Evaluation of exposure to metals, flame retardants, and nanomaterials at an electronics recycling company.

“…Specific gravity corrected urinary DPHP ranged from nondetectable (< 0.06 µg/L) to 9.84 (median 0.27 µg/L, 95th percentile 2.65 µg/L) in the study from which these men were a subset [Meeker et al 2013b]. Another study found a significant 0.43 µg/dL increase in mean total T4 serum concentrations in individuals with specific gravity corrected urine DPHP concentrations greater than or equal to 2.65 µg/L compared to those with concentrations below 2.65 µg/L [Preston et al 2017].…”

Structure-related interactions of brominated and organophosphate flame retardants and degradation products with thyroxine and human thyroid hormone transport proteins in vitro

“…Increasing evidence suggests that some OP triester FRs may have an impact on the thyroid system, and known metabolite products have been identified for several congeners including e.g. diester and para-OH triester conjugates in the case of TPHP (Farhat et al, 2013;Meeker and Stapleton, 2010;Preston et al, 2017;Su et al, 2015a). For this thesis project, a study set of four OP triester FRs was selected, including TDCIPP, TEP, TBOEP, TPHP, as well as two known metabolites of TPHP, diphenyl phosphate (DPHP) and para-OH-TPHP.…”

“…Increasing evidence suggests OP esters may impact the thyroid system, including recent studies on zebrafish (Kim et al, 2015;Wang et al, 2013;Xu et al, 2015) and chicken (Crump et al, 2012;Egloff et al, 2014;Farhat et al, 2014Farhat et al, , 2013. Additionally, biomonitoring studies of human urine and serum thyroid hormone (TH) levels have identified positive associations between triphenyl phosphate (TPHP) exposure and total thyroxine (T4) levels in women (Preston et al, 2017), as well as triiodothyronine (T3) levels in men (Meeker et al, 2013), based on urinary levels of the diester metabolite diphenyl phosphate (DPHP).…”