Novel brominated flame retardants (NBFRs) are chemical mixtures added to materials after manufacturing to increase the amount of time it would take a small open flame to ignite the item. These compounds are not chemically bound to the material they are applied to; therefore, NFBRs continuously leach out of materials into the environment. NBFRs are ubiquitously detected in indoor dust and on hands of people living or working in study areas. NBFRs have been detected in human serum, breast milk, and urine, demonstrating that they are taken up from the environment. Two NBFRs commonly applied to flexible polyurethane foam as part of the Firemaster (FM) 550 and BZ formulations (Chemtura) are 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP).Systematic literature review and meta-analysis were conducted on EH-TBB and BEH-TEBP in indoor dust. In the United States and Canada, the mean concentration of EH-TBB in indoor dust was 28- times higher (p-value < 0.001) than in countries in Africa, Asia, Australia, Europe, and South America. BEH-TEBP mean concentration was 4-times higher (p-value <0.0001) in North America compared to other continents. Not only does North America have higher concentrations of these two brominated flame retardants than elsewhere, the concentration of EH-TBB relative to BEH-TEBP is higher, 1:1 and 1:5 in North America and other continents, respectively. Estimated daily intakes of EH-TBB and BEH-TEBP in North America were 330 – 1015 and 219 – 552 pg/kg bw/day respectively (95% confidence interval for median ingestion rate from mean indoor dust concentration). The approximately 1.7-times higher ingestion rate of EH-TBB relative to BEH-TEBP, along with detection of its metabolite, TBBA, in urine of North Americans at a maximum concentration of 0.002 µM lead us to focus on the potential heal effects of EH-TBB. EH-TBB is reported as weakly antiandrogenic; however, the mechanism remains unknown. We hypothesized that EH-TBB directly inhibits androgen receptor (AR) function, causing disruption of androgen mediated processes, including gene expression and cell proliferation, in androgen dependent prostate cancer cells (PCa). EH-TBB inhibited proliferation of two PCa lines, LNCaP and LAPC4, in a dose dependent manner across a 10-fold curve from 0.0002 to 20 µM (p-value < 0.05) after four days of treatment. In the presence of 10 nM DHT, EH-TBB did not inhibit PCa proliferation. EH-TBB (20 µM) significantly inhibited (p-value < 0.05) androgen driven luciferase activity in LNCaP co-treated with DHT, but not LAPC4. EH-TBB inhibited expression of PSA (KLK3) and NKX3-1 in LNCaP after 48-hours of treatment. Co-treatment with DHT resulted in no change in NKX3-1 in LNCaP treated with EH-TBB. PSA was not significantly inhibited in LAPC4, with or without DHT. Androgen did not increase NKX3-1 expression. We speculate this is because of PTEN inhibition of AR activity through negative regulation of PI3K/Akt signaling. LNCaP were treated with EH-TBB at 0.0002, 0.02, and 20 µM, with or without DHT. Then RNA was isolated and used in high throughput sequencing (RNASeq). Pathway analysis of differentially expressed genes showed EH-TBB treatment effects PI3K/Akt signaling in LNCaP. EH-TBB possibly inhibits the interaction of AR and Src, which activates PI3K/Akt. Pathway analysis demonstrated that cross-talking hormone nuclear receptors, GR, PPAR/RXR, or ER, may also be involved in EH-TBB mechanism of action. All doses of EH-TBB impacted PI3K/Akt signaling. This suggests that environmentally relevant concentrations of EH-TBB may disrupt signaling pathways that are dysregulated in cancer, possibly leading to hormone independence, treatment resistance and poor prognosis. It is critical to further investigate the effects of NBFRs and their risk for prostate cancer disease progression.