Microbial transformations of tetrabromobisphenol a and its metabolites, and their impact on toxicity to the developing zebrafish ( Danio rerio) embryo

Anthropogenic chemicals are of concern because they are resistant to biodegradation, can accumulate in aquatic environments and sediments, and biomagnify in the food chain. One such compound, tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardant worldwide. TBBPA contamination has been detected in dust, sediments, and aquatic environments as well as in human serum, breast milk and other tissues of aquatic and terrestrial animals. Microorganisms utilize these chemicals by many mechanisms for degradation or transformation resulting in metabolites with different environmental fates. Microorganisms in the environment can transform TBBPA either by anaerobic dehalogenation to bisphenol A (BPA) or aerobic O-methylation to TBBPA dimethyl ether (TBBPA DME). Mycobacterium spp. were able to O-methylate TBBPA at a faster rate than BPA. Additionally, these data demonstrate that TBBPA O-methylation is a ubiquitous reaction in the environment. However, O-methylating organisms comprise only a minor portion of the total heterotrophic population. To determine whether microbial metabolism alters the toxicity of TBBPA, zebrafish embryos were exposed to TBBPA and its metabolites. These data show that BPA and TBBPA DME exhibit lower potency that TBBPA, demonstrating that microbial metabolism results in products with reduced toxicity. In addition, while all three caused edema and hemorrhage, only TBBPA caused decreased heart rate, edema of the trunk, and tail malformations. Matrix metalloproteinase (MMP) expression was examined due to the role of these enzymes in the remodeling of the extracellular matrix during tissue morphogenesis, wound healing and cell migration. The trunk and tail phenotypes seen after TBBPA exposure could in part be due to alteration of proper MMP expression/activity. Unlike the O-methylation of TBBPA, transformation of BPA to BPA monomethyl and BPA dimethyl ether results in increased toxicity to the developing zebrafish embryo causing increased mortality at 5 and 28 days post fertilization and lower LC50 values than for TBBPA DME. Taken together, the data presented in this thesis indicate that microbial metabolism of brominated flame retardants results in compounds with differing toxicity. Further, these data illustrate a new mechanism for microbial transformation of BPA, producing metabolites warranting further study to understand their prevalence in the environment.