Mammalian toxicology and human exposures to the flame retardant 2,2′,6,6′-tetrabromo-4,4′-isopropylidenediphenol (TBBPA): implications for risk assessment

Abstract

The compound 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol (tetrabromobisphenol A, TBBPA) is used as a reactive and additive flame retardant. This review evaluates the mammalian toxicology of TBBPA and summarizes recent human exposure and risk assessments. TBBPA has a low potential for systemic or reproductive toxicity, and no-observed-adverse-effect-levels were greater than 1,000 mg/kg body weight (bw)/day in a 90-day oral toxicity study, a developmental toxicity study and a two-generation reproductive and developmental toxicity study. Some interactions of TBBPA with hormone-mediated pathways were noted in vitro; however, when studied in vivo, TBBPA did not produce adverse effects that might be considered to be related to disturbances in the endocrine system. Therefore, in accordance with internationally accepted definitions, TBBPA should not be considered an "endocrine disruptor." Furthermore, TBBPA is rapidly excreted in mammals and therefore does not have a potential for bioaccumulation. Measured concentrations of TBBPA in house dust, human diet and human serum samples are very low. Daily intakes of TBBPA in humans were estimated to not exceed a few ng/kg bw/day. Due to the low exposures and the low potential for toxicity, margins of exposures for TBBPA in the human population were between 6 × 10(4) (infants) to 6 × 10(7) (adults). Exposures of the general population are also well below the derived-no-effect-levels derived for endpoints of potential concern in REACH.

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells

“…4,4 0 -(hexafluoroisopropylidene) diphenyl (BPAF, 98%) was purchased from Alfa Aesar (Ward Hill, Massachusetts). The chemical structures of these compounds are shown in Figure 1 Colnot et al, 2014). 5-Bromo-2 0 -deoxyuridine (BrdU, 99%) was purchased from Thermo Scientific (Waltham, Massachusetts).…”

“…HCA-based cell cycle analysis was conducted as recently reported by Roukos et al (Roukos et al, 2015). The frequency distributions of total DNA intensity of all individual nuclei were calculated and plotted for each experimental condition in a Colnot et al, 2014).…”

Flame Retardants and Environmental Issues

“…As a result of higher performance e ciency and lower costs, brominated compounds have been of greater practical importance than chlorinated compounds. ere are four main groups of commercially produced brominated FRs: hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBPA), polybrominated biphenyl (PBB) and polybrominated diphenyl ethers (PBDEs), i.e., decabromodiphenyl ether (decaBDE), octabromodiphenyl ether (octaBDE) and pentabromodiphenyl ether (pentaBDE) (Figure 1) [3,11,[16][17][18][19]. e activities of these FRs are based on the gas-phase action by a radical trap mechanism [1,2].…”

Perinatal exposure to tetrabromobisphenol A (TBBPA), a brominated flame retardant, exacerbated the pneumonia in respiratory syncytial virus (RSV)-infected offspring mice

“…TBBPA is considered to be a chemical of high concern in children by the Washington State Department of Health in the Children's Safe Product Act (Saegusa et al, 2012). Although the toxicity of TBBPA has been reported using several administration routes in animal models, and further, low acute toxicity has been shown (Colnot et al, 2014), its effects on the developmental immune system have not been studied definitively (Teshima et al, 2008).…”