Human biomonitoring of novel brominated flame retardants: A review on invasive and non-invasive biomarkers

Novel brominated flame retardants (NBFRs) are a group of chemicals applied mainly as alternatives to the phased-out polybrominated diphenyl ethers (PBDEs). However, toxicological studies show that NBFRs may pose health risks similar to PBDEs.The present study reviews available information on the biomonitoring of NBFRs and their metabolites in humans through invasive and non-invasive biomarkers, as well as the toxicological effects of these chemicals both in vivo and in vitro. In general, higher concentrations of NBFRs were reported in tissues of occupationally exposed adults from NBFR production facilities, e-waste recycling facilities and inhabitants living close to these areas, compared to the general population. It is worth noting that NBFR human biomonitoring data are limited to few countries located in North America, Europe and Asia, while data from developing countries are scarce. Evidence from in vivo and in vitro toxicity studies show that several NBFRs can cause adverse health effects through various modes of action, mainly: hormone disruption, genotoxicity, endocrine disruption, and behavioural changes. Although few studies have investigated the biotransformation of NBFRs in humans, evidence suggests that the toxicity of some NBFRs may be augmented through their metabolites, as in the case of 2,3,4,5- tetrabromobenzoic acid (TBBA), which may exhibit higher toxicity than its parent compound 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB). More research is required to assess toxicity thresholds, toxic endpoints, and tolerable intakes for various NBFRs, and their metabolites in human. Comprehensive epidemiological studies are highly recommended to further understand the risk arising from human exposure to different NBFRs, particularly in occupational settings.