Tetrabromobisphenol A (TBBPA) is currently the most commonly employed type of the brominated flame retardant (BFR), used to treat plastics and furnishings in order to reduce their flammability. BFRs including TBBPA and their metabolites have been shown to bio-accumulate to relatively high levels within humans as result of repeated environmental exposure [1]. Recent studies have also shown that low concentrations of TBBPA can modulate a number of cell signalling processes [2]. Using Ca,²⁺ATPase activity measurements as described in [3], the data in table 1 shows that TBBPA is a very potent inhibitor of both SERCA1a and SERCA2b Ca²⁺ATPases (IC₅₀ values of 1.7 and 2.3μM, respectively). Subsequent studies have indicated that Ca²⁺ pump inhibition is due to TBBPA decreasing its affinity for Ca²⁺. Thus TBBPA could potentially affect Ca²⁺ homeostasis processes leading to cellular dysfunction. In order to assess whether other commonly found intracellular Ca²⁺ transporters were also affected by TBBPA, its effects on both the inositol-1,4,5-trisphosphate receptor (IP₃R) and Ryanodine receptor (RyR) was also investigated. The effects of TBBPA on the function of the RyR was explored by assessing whether TBBPA could affect the opening of the channel by 2-Hydroxycarbazole (2HC), a potent caffeine-like agonist [4]. Ca²⁺ release via RyR was observed from muscle SR vesicles using suboptimal concentrations of 2HC (400μM). In Table 1 the data shows that pre-incubation of the vesicles with TBBPA at concentrations between 1-4μM greatly enhanced 2HC-induced Ca²⁺ release through the RyR. This result therefore indicates that TBBPA sensitizes the RyR to release more Ca²⁺ upon stimulation with 2HC. It is yet to be determined whether this increased Ca²⁺ release is due to an increase in the duration of the open state of the channel or due to a higher conductance state. The activation of the IP₃R was monitored by the addition of IP₃ to cerebellar microsomes pre-accumulated with Ca²⁺ and the changes in calcium measured using Fluo-3[5]. As shown in the table the extent of Ca²⁺ release in cerebella microsomes induced by IP₃ was not significantly affected, in the presence of up to 4μM TBBPA. The results presented here would indicate that low concentrations of TBBPA could have dramatic affects upon Ca²⁺ signalling processes within cells by abnormally elevating intracellular Ca²⁺ levels, which could ultimately lead to cell dysregulation and death. Our studies would indicate that TBBPA should be treated as a potential environmental ‘endocrine disrupter’.