Publications : 2015

Wikoff D, White MC, Borghoff SJ, Haws LC. 2015. Evaluation of tetrabromobisphenol A (TBBPA)-induced endocrine-related target gene activity using high-throughput screening data from ToxCast. Presented at the Society of Toxicology’s 54th Annual Meeting, March 22-26, San Diego, CA.

Abstract

TBBPA is a widely used brominated flame retardant, commonly incorporated into printed circuit boards found in consumer and industrial products. TBBPA was shown to cause uterine tumors in female rats, thus leading to interest in characterizing potential endocrine activity. The objective of the current assessment was to mine the ToxCast Phase II data for information regarding the in vitro activity of TBBPA on endocrine-related gene targets. Using the EPA Dashboard interface, assays were selected based on the intended target gene symbol for: ESR1 (estrogen receptor α), ESR2 (estrogen receptor β), AR (androgen receptor), THRA (thyroid hormone receptor α), THRB (thyroid hormone receptor β), and CYP19A1 (aromatase). TBBPA was classified as active in 1 out of 19 ESR1 and ESR2 assays (AC50 = 53.2 μM), 2 out of 10 AR assays (AC50 = 9.79 – 41.5 μM), and 1 out of 3 aromatase assays (AC50 = 51.4 μM). TBBPA was not active in THRA or THRB assays (n=4). These activity profiles were compared to those of substances known to interact with the respective endocrine-related gene targets. The natural phytoestrogen genistein was classified as active in 17 out of 19 ESR1 and ESR2 assays (AC­50 = 0.0167 – 7.77 μM), demonstrating a comparatively low capacity of TBBPA to interact with or stimulate these receptors. Likewise, the anti-androgen hydroxyflutamide was active in 8 out of 10 (AC50 = 0.00763 – 13.7 μM) AR assays, respectively, demonstrating relatively low TBBPA-induced AR activity. Raloxifene hydrochloride, a selective estrogen receptor modulator, was similar to TBBPA in that it was active in the same 1 of 3 aromatase assays, though the potency (AC50 = 0.00342 μM) was significantly greater than TBBPA. Collectively, these data from a diverse panel of in vitro assays in the ToxCast database suggest a low level of interaction between TBBPA and estrogen, androgen, or thyroid receptors, and between TBBPA and aromatase.